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VOLUME 15 ISSUE 3 MARCH 2010 Featured Inside Post-LASIK Ectasia
VOLUME 15 ISSUE 3 MARCH 2010
Featured Inside Post-LASIK Ectasia
1
The Special Focus for this month’s issue of EuroTimes is Post-LASIK Ectasia and I am sure EuroTimes readers will welcome the opportunity to read a number of very interesting articles on this always hot topic.
In the first article on this theme we discuss how recent ISRS/AAO and ASCRS surveys of refractive surgeons suggest that the rate of new cases of post-LASIK ectasia is declining. However, even a low incidence of ectasia is worrying and therefore, researchers are continuing to study the aetiology of post-LASIK ectasia, identify additional risk factors and screening methods, as well as to define the safety of surgical alternatives in at-risk eyes.
We also feature a number of supporting stories on our theme, including a study that suggests that Collagen cross-linking with riboflavin may provide an effective and safe treatment for post-refractive-surgery ectasia by stabilising the biomechanical properties of the cornea and avoiding the need for a penetrating or lamellar keratoplasty in the majority of cases.
It has also been suggested that advances in femtosecond laser technology for the creation of thinner corneal flaps, as well as greater awareness of the full range of risk factors involved in the development of post-LASIK keratectasia, may reduce the incidence of this particular complication of refractive surgery.
EuroTimes Roundtable
This issue also features a report on the EuroTimes Roundtable which took place during the XXVII Congress of the ESCRS in Barcelona, Spain.
The roundtable has now become an annual event and last year the focus was on the multiple challenges posed by patients with co-existing macular cataract disease to both anterior and posterior segment specialists. Which patients should be considered for cataract surgery, and when? What are the best lens choices? What is the role of nutrition? These and other questions were debated in a roundtable
discussion convened during the XXVII Congress of the ESCRS in Barcelona. Jose Cunha-Vaz MD, PhD, University of Coimbra, Portugal, and past-president of the ESCRS, moderated the discussion.
The roundtable, which will also be posted as a Podcast on the EuroTimes website at www.eurotimes.org, generated a lively debate and no doubt this is a subject that we will be returning to in the future.
Young Ophthalmologists
There are a number of very interesting features in this month’s issue but I would definitely draw particular attention to the Young Ophthalmologists’ column, a new addition to the magazine under the direction of my colleague Oliver Findl.
This month’s column suggests that senior ophthalmologists have a responsibility to produce more open access content online to support young ophthalmologists in training who are increasingly using social media as their primary learning resource.
Dr Findl, chairman of the ESCRS Young Ophthalmologists’ Forum, says there is a need for a new approach to online education, but he also cautions that much of the new social media is entirely unedited.
This makes it fast and lively, but it may make it difficult to handle for the ophthalmologist in training. This is where a good teacher or established textbook still plays a major role.
Finally, as the new president of ESCRS, I would like to thank all ESCRS members and EuroTimes readers for the advice and support you have already given me in the early months of my presidency.
I look forward to hearing from you throughout the year and if you have any views or information you wish to actively share, do not hesitate to contact me. [email protected]
* José Güell is president of the ESCRS and a medical editor of EuroTimes.
From the Editor
José Güell MD
Noel Alpins ausTralia
Bekir Aslan TurKEY
Bill Aylward uK
Peter Barry irElaND
Roberto Bellucci iTalY
Hiroko Bissen-Miyajima JaPaN
John Chang CHiNa
Joseph Colin FraNCE
Alaa El Danasoury sauDi araBia
Oliver Findl ausTria
I Howard Fine usa
Jack Holladay usa
Vikentia Katsanevaki GrEECE
Thomas Kohnen GErMaNY
Anastasios Konstas GrEECE
Dennis Lam HONG KONG
Boris Malyugin russia
Marguerite McDonald usa
Cyres Mehta iNDia
Thomas Neuhann GErMaNY
Gisbert Richard GErMaNY
Robert Stegmann sOuTH aFriCa
Ulf Stenevi sWEDEN
Emrullah Tasindi TurKEY
Marie-Jose Tassignon BElGiuM
Manfred Tetz GErMaNY
Carlo Enrico Traverso iTalY
Roberto Zaldivar arGENTiNa
José Güell Ioannis Pallikaris
Clive Peckar Paul Rosen
Emanuel Rosen Chairman
ESCRS Publications Committee
Medical Editors
International Editorial Board
New challenges in diagnosis and treatment of post-LASIK ectasia
Ed
ito
rial
Mar
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paris 2010XXVIII Congressof the ESCRS
10TH EURETINA Congress
4–8 September Le Palais des Congrès
www.escrs.org
2–5 September Le Palais des Congrès
www.euretina.org
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8 Prevention and treatment of post-LASIK ectasia
10 Studies look at risk factors for ectasia
11 A look at alternative therapies for treating post-refractive-surgery ectasia
Special Focus – Post-LASIK Ectasia
6 Experts debate lens choice and the role of nutrition in cataract surgery
Roundtable
14 Phakic IOLs for refractive surgery
16 New technique delivers promising results in DALK procedures
18 Femtosecond laser advantageous for PK and DALK
Refractive Lens
Cornea Update
9Special
Focus>
10Cataract>
16Cornea>
22Cornea>
Co
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Cataract Update
12 Faster visual rehabilitation with biaxial microincision cataract surgery
13 Zeiss IOL mimics young crystalline lens in terms of spherical aberration
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Approved for irrigation during ophthalmic surgery only. Postoperative inflammatory reactions, as well as incidents of corneal edema and corneal decompensation have been reported. Their relationship to the use of BSS PLUS® sterile intraocular irrigating solution has not been established.
Maintains corneal detumescence1
Maintains corneal endothelial integrity1
Appropriate composition necessary for the maintenance of normal retinal electrical activity
denotes a registered trademark of Alcon Inc.© 2009 Alcon, Inc. BSS243 EU-1
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24 Study looks at congenital cataract surgery and low risk of glaucoma
Glaucoma Update
20 Methodical approach necessary to manage corneal infections
22 Promising treatment for conjunctival papilloma
Cornea Update
28 Understanding the pathology of diabetic retinopathy
Retina Update
30 Young ophthalmologists use social media sites as a learning resource
32 EUREQUO gets ready to go live in some European countries
33 Studies look at measuring quality of vision
ESCRS News
36 Practice Development
37 Outlook on Industry
38 EU Matters
40 Eye on Travel
43 In Your Good Books
Features
39 Industry News
41 JCRS Highlights
42 Journal Watch
44 Calendar
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Included with this issue:
Patients with co-existing macular cataract disease pose multiple challenges, presenting potential problems to both anterior and posterior segment specialists. Which patients should be considered for cataract surgery, and when? What are the best lens choices? What is the role of nutrition? These and other questions were debated in a roundtable discussion convened during the XXVII Congress of the ESCRS in Barcelona. Jose Cunha-Vaz MD, PhD, University of Coimbra, Portugal, and past-president of the ESCRS, moderated the discussion.
Dr Cunha-Vaz: There are so many controversies when it comes to the management of patients with macular disease who may require cataract surgery. Moreover, macular oedema after cataract surgery is an important cause of vision loss. Where do you start?
Dr Lobo: First, it is important to separate the normal patients and the high-risk patients. With the high-risk patients we have a different strategy. We recommend preoperative anti-inflammatory drugs, steroids and/or NSAIDs, depending on the patient. In a patient with uveitis we would consider using oral steroids. In diabetic patients we try to optimise metabolic control. If we have a normal patient we begin the anti-inflammatory treatment after the surgery using an association of steroids and NSAIDs.
Dr Cunha-Vaz: Yes, you really do have to look at each case and identify the higher risk patients. What is your current approach when you have a patient with cataract and concurrent macular disease?
Dr Tassignon: I’m fortunate to work in a centre with colleagues in the posterior
segment field. It is very difficult to do it all, and I would advise a surgeon in a small practice to refer these patients to a centre with appropriate facilities. The first thing is to determine if the macular disease is stable and dry, or if it shows signs of activity. This requires special tests. It is well known that patients with macular disease are at risk of reactivation of macular lesions following cataract surgery. Scanning laser ophthalmoscopy, combined with microperimetry, is very useful to determine if the patient has good fixation, and what the acuity is at the level of the retina, without presuming that the anterior segment is perfect. If there is not much reduction in the sensitivity of the retina, then the patient may recover very well after cataract surgery.
Personally I also like to talk with the patient, and tell them whether they will benefit, and how much. It is very important for me to be able to tell that to the patient. They will be better prepared for the surgery and have appropriate expectations.
Dr Schmidt-Erfurth: Cataract and AMD frequently occur in combination, as both are diseases that affect elderly patients. In general patients should undergo cataract surgery if their vision is compromised by the turbid lens, not other factors. This applies to both dry and wet AMD patients. We have to be sure that the vision decline is due to cataract formation, and not progression of macular disease. Only when we are sure this is the case do we schedule patients for surgery.
In dry AMD patients I’m more worried about the patient being unsatisfied after surgery because their central visual acuity may not improve as much as it does in patients without retinal disease, the patients’ expectations have to be realistic and they should only get surgery if they will experience some benefit and truly want to have something done. I discuss this
intensively with the patient. In some cases I have to tell the patient he may not have reading ability after cataract surgery. But there are other reasons the patient may still want the cataract surgery. They will end up with less photosensitivity, and may have a better peripheral field.
For wet AMD, the fluctuations in vision change depending on the acute phases of disease. You have to make sure you have a dry condition to really understand the effect of the cataract on vision, and then you have to make sure that the lesion remains dry throughout surgery. I only do surgery when the patient has shown a dry macula for at least three months. When I do surgery I usually add anti-VEGF therapy intraoperatively in patients with a history of exudative disease.
Dr Cunha-Vaz: Let’s consider diabetic retinopathy. What is the optimal approach to treatment?
Dr Richard: The decision matrix is to determine if you need to do cataract surgery only, or also do additional treatment, such as anti-VEGF treatment or pars plana vitrectomy. In cases of cataract surgery only, you do it in the normal fashion, but make it as atraumatic as possible. You need to look for the postoperative inflammatory reaction. It is sometimes necessary to give additional steroids postoperatively, and even to dilate the pupil for a period of time. This is usually necessary if you combine the cataract surgery with the pars plan vitrectomy. If we see very low visual acuity or macular traction on the OCT, this is an indication for combination surgery. In such cases we also usually add anti-VEGF treatment. It is then necessary to follow the patient very carefully, to determine if additional injections are required. We also need to remember to keep an eye on diabetes control in these patients.
You also have to look at the macula before cataract surgery, to determine the need for combination surgery. It is a very often overlooked problem that during cataract surgery you may expect a release of VEGF, which could lead to a thickening of the macula and decrease in visual acuity.
Dr Cunha-Vaz: When you have a patient with cataract and need to approach vitreoretinal disease simultaneously, what are the options?
Dr Schmidt-Erfurth: You need to check multiple criteria. First, the patient should be more than 50 years old, with some evidence of cataract formation. We would not take out a completely clear lens, even in an elderly patient. The prognosis for retinal function recovery has to be quite good, so that patient will benefit from cataract removal. It also depends what is happening in the posterior pole. If it is uncomplicated vitreomacular traction then I know that visual function in terms of retinal function will be excellent. Remember that it may take months before the patient can feel the difference. Not only will metamorphopsia be gone, but also essential visual acuity will be above the baseline presentation.
On the other hand if I see a patient with extensive submacular and intravitreal haemorrhage, then I would rather leave the lens in, for two reasons. One is that visual recovery will not be very good. Second, I don’t want blood causing synechiae and other changes in the anterior segment.
If there is extensive anterior traction in PVR, lens removal is mandatory for technical reasons, to be able to remove anterior tissue, patients may even remain aphakic for a while.
When a patient needs an endotamponade I make sure he is able to keep prone position postoperatively. Some patients may be too overweight to do this. In those cases I would rather not do combined surgery, because I don’t want an anteriorly dislocated lens with iris capture or other problems.
Dr Richard: The indication for combined surgery is not that problematic if you follow some basic rules. Firstly, the anterior segment surgery must be as atraumatic as possible. This means you have to take care that the cornea remains clear during the whole procedure. You use a long corneal scleral tunnel, you dilate the pupil during surgery, and implant the IOL into the capsular bag, so you are able to see the retina and the fundus and the vitreous afterwards. Secondly, you want to be able to solve problems intraoperatively in the right way. If you need an endotamponade it is sufficient to use 70 per cent gas or air. This is enough to solve problems you might
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Which patients should be considered for cataract surgery, and when?EuroTimes Roundtable also debates best lens choices and role of nutritionE
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have at the posterior pole, if you have to treat a macular hole, elevated retina, or macular pucker.
Postoperatively, if there is a problem related to haemorrhage in the eye, or if you expect a disturbance of the blood-retina barrier, you will want to give more steroids, and dilate the pupil for two to four weeks, depending on the disturbance. This makes the combined surgery safe, and makes sure the patient doesn’t need a second operation.
Dr Schmidt-Erfurth: A big issue in combined surgery is PCO, which occurs in a much higher percentage than in normal cataract surgery. Typically this PCO is of the proliferative type. Working with Dr Klaus Eckhardt in Germany, we have worked on the bag-in-the lens implantation approach. In combination surgery it is very important to maintain a visual axis that is very clear, in the event that you need to do more interventions later. Our initial clinical results have been very good.
Quality of vision is also an issue. These days, cataract surgeons are operating early, so we are seeing more patients who have already had cataract surgery, some of whom have received multifocal IOLs. We know that multifocality will decrease contrast sensitivity, which may be an issue in patients who develop macular disease. So sometimes we need to explant MIOLs.
Dr Cunha-Vaz: You have had some experience with the Lipshitz macular implant. Is it proving to be useful?
Dr Tassignon: The Lipshitz macular implant is a major improvement compared to the earlier miniaturised telescopic device. It has not been implanted in many eyes yet. We need more data to judge its merits. We particularly need to define the ideal candidates eligible for the device. While the lens requires a smaller incision size than the implantable telescope, the incision size is still relatively large. Also, the device may be difficult for some patients to adapt to. If the patient cannot cope with it, you will need to explant it. I’d like to see multicentre trials with the device.
Dr Cunha-Vaz: There is some debate on the use of blue-filtering IOLs, what are your views?
Dr Tassignon: It is important to know what the blue filtering effect of the lens is. Surgeons use many different lenses made of various biomaterials. Each biomaterial has different profile of transmission of the light spectrum. Blocking the blue part of the light spectrum is different for each biomaterial. The Alcon yellow IOL has a relatively good transmission profile in
terms of blue light. Other yellow and even orange lenses have been introduced since. You have to be concerned about filtering too much blue light. This could decrease comfort of patients in scotopic conditions. It therefore concerns me that lenses are being put on the market without giving the surgeon a complete transmission profile of the lens.
Dr Schmidt-Erfurth: The question of a defined transmission spectrum is very important. The spectrum of the blue-filtering lenses we are using is well known to us. We have measured the impact of this blue filtering on colour perception, and have done scotometric testing. We found no significant difference in quality of vision. I think they are useful in all elderly patients, not just those with AMD.
Dr Cunha-Vaz: Another interesting controversy is nutritional intervention in macular disease patients, especially with intermediate disease. Do you recommend special supplements to patients?
Dr Richard: I think that supplementation following the AREDS guidelines is something we always have to consider. Beyond this, we give our patients advice regarding general behaviour: avoiding smoking, eating colourful fruit, and so on. Diet and lifestyle counselling is part of our role as ophthalmologists.
Dr Schmidt-Erfurth: In general it is clear that balanced nutrition will cover all of the needs for vitamins and minerals. On the other hand it may be overly optimistic to try and change a person’s lifestyle after eating a certain diet for many many decades. Some studies show that in the elderly, you will get better compliance asking them to take one pill a day, rather than eat an apple a day if they haven’t done so during the last 90 years.
Dr Tassignon: I have the impression that at the time of AMD diagnosis it may be too late to change the attitude of the patient. I often think it would be
better to try and educate school children on the value of nutrition. I agree that it is part of the job of the ophthalmologist to play a role in patient lifestyle education.
[email protected]@[email protected] [email protected]@uke.uni-hamburg.de
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José Cunha-Vaz Conceição Lobo Marie-Jose Tassignon Ursula Schmidt-Erfurth Gisbert Richard Eur
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By Cheryl Guttman Krader
RECENT ISRS/AAO and ASCRS surveys of refractive surgeons suggest that the rate of new cases of post-LASIK ectasia is declining. However, even a low incidence of ectasia is worrying, considering the number of laser vision correction procedures performed each year and the devastating nature of this complication. Therefore, researchers continue to study the aetiology of post-LASIK ectasia, identify additional risk factors and screening methods, as well as to define the safety of surgical alternatives in at-risk eyes.
Theo Seiler MD, PhD, is credited with describing the first case of post-LASIK ectasia in 1996 and coined the term ‘iatrogenic keratectasia’. Since then, various investigators have tried to determine the incidence of this complication, and while the estimates vary between series, the best available data suggest the rate is about one in 2500 procedures, said José Güell MD, PhD, who spoke on preventing corneal ectasia after refractive surgery during the 17th Congress of the European Society of Ophthalmology (SOE). The symposium was cosponsored by the ESCRS.
Almost half of cases occur within one year after surgery, but the corollary is that development is delayed in the other half. Therefore, the possibility of late post-LASIK ectasia should not be overlooked, noted Dr Güell, Universidad Autonòma de Barcelona, Spain.
Prevention strategies – the Ectasia Risk Score System
“As is always the case, prevention is the best management for post-LASIK ectasia, and today, there are certain ‘laws’ that surgeons need to adhere to in order to prevent ectasia. One is to always perform intraoperative pachymetry and the other is to avoid LASIK in high-risk eyes,” Dr Güell said.
However, there is controversy regarding methods for identifying high-risk eyes. Using regression analyses to compare eyes with post-LASIK ectasia and those with a normal postoperative course, J Bradley Randleman MD, and colleagues at Emory Eye Centre, Atlanta, GA, developed the Ectasia Risk Score System (ERSS) as an easy-to-use tool for helping surgeons in their decision-making process. Age, manifest refraction SE, corneal thickness, placido disc topographic pattern, and residual stromal bed thickness are incorporated into the weighted scoring system, and the total score determines whether an individual is at low (score 0–2), moderate (3) or high risk (>4) for post-LASIK ectasia.
“In a follow-up study (am J Ophthalmol. 2008 May) using an independent dataset, these researchers validated the ERSS and
determined it has sensitivity of 92 per cent and specificity of 94 per cent, which is quite good, if finally it would be accepted by all of us, considering its simplicity,” Dr Güell said.
However, there are still eight per cent of the ectasia cases that were identified as a low risk based on the ERSS and there is no published data on the incidence of ectasia among eyes with different risk scores calculated using the ERSS, and its creators acknowledge the system is not perfect. Therefore, there is still a need for improvement in either sensitivity and specificity for screening refractive candidates, which will be refined and improved over time through the application of appropriate research and statistical methodology.
Other leading refractive surgeons also seem to agree the ERSS is an important step forward, but as expressed in “Letters to the Editor” [Ophthalmology 2008 115;849; Ophthalmology 2009;116:1014-5], some are waiting for further validation and raising questions about use of this theoretical tool as the sole screening method in clinical practice.
Perry S Binder MD, questions the appropriateness of applying the ERSS to today’s refractive surgery candidate considering that the method was developed using data from eyes that were mostly operated on prior to 2002. He also has concerns about using a number from the ERSS to “draw a line in the sand” dividing eyes that can undergo LASIK from those that should be excluded.
“The ERSS may fail to identify some eyes that are truly at higher risk and inadvertently exclude those that are not,” he said.
Improving safety with alternative techniques and technology
Research by John Marshall PhD, and others leading to improved understanding about the lamellar organisation of the corneal collagen fibrils, its relationship with corneal tensile strength and biomechanics, and how the latter is affected by LASIK flap creation and laser ablation has been the foundation for understanding why the risk of ectasia is lower after PRK versus LASIK as well as for the development of new LASIK techniques, eg, thin-flap LASIK and creation of flaps with an inverted side cut using the femtosecond laser, aiming to better preserve corneal biomechanical stability.
However, while iatrogenic ectasia appears to be far more common after LASIK than after PRK, the exact incidence of post-PRK ectasia is unknown, noted Dr Güell.
“The only published literature consists of relatively few case reports, and most of those cases had identifiable, but undiagnosed risk factors, particularly significant inferior corneal steepening or frank keratoconus. In
other eyes, preoperative topography was not available,” he explained.
“Therefore, for patients who are identified as a questionable candidate for LASIK, the safety of advanced surface ablation or sub-Bowman’s keratomileusis (SBK, ie, thin-flap LASIK) remains to be defined.”
In theory, use of the femtosecond laser for LASIK flap creation might reduce the risk for ectasia after refractive surgery via several mechanisms. Considering that residual stromal bed thickness is a risk factor for this complication a thin flap could afford biomechanical advantages; this suggests there is probably a benefit for using the femtosecond laser because it performs reliably in creating predictably thin flaps, said Rudy Nuijts MD, PhD.
The planar shape of the femtosecond laser flap versus the meniscus geometry of a mechanical microkeratome flap also contributes to less variation in flap thickness when using the former technique and is thought to be more beneficial for preserving corneal biomechanical stability. Moreover, the femtosecond laser enables creation of a flap with an inverted side cut that has been shown in animal and clinical studies to favour stronger flap adhesion due to increased healing.
In addition, results of a randomised, contralateral eye controlled study conducted by Drs Durrie and Slade and using the Ocular Response Analyzer (Reichert) to measure corneal hysteresis and corneal resistance factor provide evidence that the biomechanical properties of the cornea are similar after SBK compared with PRK.
“Still, while there are no published articles yet in the literature, it may be premature to conclude that SBK is immune from ectasia,” said Dr Nuijts, Maastricht University, The Netherlands.
Prevention with intervention – corneal collagen crosslinking
Growing evidence of the success of corneal collagen crosslinking (CXL) for treating progressive keratoconus and post-LASIK ectasia has prompted interest in its use as a prophylactic technique in eyes at risk for post-LASIK ectasia. Both Theo Seiler MD, PhD, and A John Kanellopoulos MD, have experience combining CXL with laser vision correction in at-risk eyes, but they have different opinions on which procedure should be performed first and whether the two surgeries should be done simultaneously or in a staged approach.
Dr Seiler, Institute for Refractive and Ophthalmic Surgery, Zurich, Switzerland, told EuroTimes he has performed CXL and customised PRK simultaneously and stage in more than 20 eyes of patients with forme fruste keratoconus who have a strong desire for refractive surgery. Taking into account the viscoelastic properties of the cornea, he believes the outcomes are more predictable if the CXL is done before the surface ablation.
“Any biomechanical reaction to an external change to the cornea, such as ablation, consists of an immediate, elastic component and a delayed, creeping viscous component. If the PRK is done first, it creates an immediate elastic bulging out-effect that is frozen by CXL. To optimise outcome predictability, it makes much more sense to do the CXL first and freeze the cornea, followed six months later by the PRK. Don’t forget some of these patients need more than a simple surface ablation but rather require a customised topography-guided treatment to correct the cone,” he explained.
Dr Seiler acknowledges there are advantages to same session surgery – it is more efficient than a staged approach and minimises patient exposure to
Figure 1: Thickness profile of a normal thin cornea with CCT 458 microns (A) and a Keratoconic cornea with CCT 548 microns (B)
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Progress is being made towards the prevention and treatment of post-LASIK ectasia
Sp
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postoperative morbidity. While he has done both simultaneous and sequential procedures, depending in part on patient preference, he favours waiting six months between procedures with the goal of enhancing predictability.
Over the last five years, Dr Kanellopoulos, Laservision Institute, Athens, Greece, has performed topography-guided PRK followed immediately by CXL to treat over 600 eyes with progressive keratoconus or post-LASIK ectasia. The simultaneous procedure affords the benefit of single session convenience and he believes there are multiple advantages for performing the surface ablation procedure prior to CXL.
Dr Kanellopoulos explained to EuroTimes, “By exposing cornea stroma, the partial PRK facilitates the diffusion of the topically applied, large riboflavin molecule, and so may increase the efficacy of the CXL. In addition, the PRK redistributes the strain from the cone apex in a larger area. This normalisation of the ectatic cornea prior to the CXL appears to create more biomechanical stability so that the tissue may better resist blinking and eye rubbing.”
“Furthermore, this protocol avoids removal of cross-linked tissue by the PRK and seems to reduce PRK-related scarring. The simultaneous combined technique also appears to have synergistic efficacy compared to when crosslinking is done first and the partial topo-guided PRK later.”
We have recently published a large comparison case series. In this study of about 400 cases we compared CXL first followed at least six months later with a partial PRK, to combining topo-guided PRK and CXL immediately after. In almost all the parameters studied the same day combined:
topo-guided PRK and CXL group did better, suggesting a synergistic effect. (Kanellopoulos aJ, Jrs sept 2009.)
About four years ago, Dr Kanellopoulos began performing CXL prophylactically at the completion of the laser vision correction procedure in eyes at risk for ectasia. He has combined it with both PRK and thin flap LASIK, choosing between these procedures primarily by considering patient age and thinnest cornea pachymetry – PRK is performed when the cornea is less than 480 microns and usually if the patient is less than 30 years old. Based on his experience, CXL prophylaxis appears to be safe and effective.
“I have observed no adverse effects on healing after surface ablation, refractive outcomes are as expected without any need for nomogram adjustment, and no eyes have developed ectasia with follow-up ranging up to four years,” Dr Kanellopoulos said.
He added, “I also feel this combined technique may have wider application in all LASIK cases in the future as it may not just reverse some of the negative corneal biomechanical changes induced by LASIK, but also provide a ‘suturing’ effect of the flap to the stroma through CXL-promoted interlinking of collagen fibres.”
Alternative screening criteria
While Placido disc-based corneal topography is one of the most important components of refractive surgery patient screening, limitations of this methodology are prompting investigation of alternative techniques. Some of these were presented at the 2009 annual meeting of the American Society of Cataract & Refractive Surgery.
For example, researchers at Emory Eye Centre evaluated the role of Orbscan II (Bausch & Lomb) slit beam-based indices, but found that this information did not improve the identification of abnormal corneas beyond use of Placido-based imaging alone, reported J Bradley Randleman MD, Emory Eye Centre.
However, novel methods for interpreting Corneal Tomography (CTm) should be considered, so that the more detailed 3D corneal architecture data would provide clues to identify ectasia risk. Methods for characterising pachymetric distribution have been developed by Renato Ambrósio Jr MD, PhD, and colleagues from the Rio de Janeiro Corneal Tomography and Biomechanics Study Group in Brazil since 2003, using different systems. The concept of corneal thickness spatial profile (CTSP) is based on the rate of increase in thickness from the thinnest point out to the periphery. The averages of values on circle lines centred on the thinnest point with increase in diameters are calculated along with the percentage thickness increase (PTI) at each diameter. This concept was implemented and further refined on the Pentacam software since 2004. Graphics are presented containing the mean and 95 per cent confidence interval of a normal population for the CTSP and the PTI, along with pachymetric indexes. The comprehensive analysis beyond central corneal thickness (CCT) enables characterisation of patients with very thin normal corneas without ectasia (Figure 1A), and cases with keratoconus and relatively normal CCT (Figure 1B).
The sensitivity of the thickness profile for screening ectasia risk or susceptibility has been demonstrated in a study comprising 53 patients with very asymmetric keratoconus, in which one eye had a normal topography that was presented by Marcella Salomão MD from the Rio de Janeiro Corneal Tomography and Biomechanics Study Group at the ESCRS in 2008. The combination of CTSP and PTI data along with enhanced elevation analysis with a new best-fit sphere to the peripheral cornea, as proposed by Michael W Belin MD, FACS (Tucson, Arizona), identified abnormalities in 94 per cent of cases despite a normal surface curvature map (Figure 2).
The improvement in sensitivity was also demonstrated in another study by Allan Luz MD from the Rio de Janeiro Corneal Tomography and Biomechanics Study Group. Data from four cases with ectasia after IntraLase-LASIK, despite having low-risk ERSS score and normal preoperative Orbscan interpretation was provided by Dr Colin Chan MD from Australia. The CTSP and PTI graphs were calculated from the numeric
pachymetric maps from the Orbscan. The vertical pachymetric asymmetry (VAP), another method described by Canrobert Oliveira MD from Brasilia’s Eye Hospital (HOB), was also applied. All cases have abnormalities identified on the comprehensive pachymetric analysis. “The opportunity to identify preoperative corneal abnormalities in eyes that had post-LASIK ectasia with unrecognised risk factors is a strong evidence of the enhanced sensitivity of this approach. In addition, we have also collected cases that had LASIK with stable outcomes, in which there was a retrospective identification of high-risk ERSS scores. Such cases have typically normal pachymetric distribution, which suggest this approach also enhances specificity. However, we still need to expand these studies to definitively validate this approach,” concludes Dr Ambrósio.
David Huang MD, PhD, and colleagues at University of Southern California, Los Angeles, are developing a method using optical coherence tomography-derived pachymetry maps to capture the focal thinning that is characteristic of keratoconus. Dr Huang’s group has developed a system to detect focal thinning and asymmetric thinning that he believes will complement topographic detection of keratoconus. An even newer approach based on fitting the data to a Gaussian waveform also shows promise.
Expanding the etiologic view
During the SOE symposium, Ioannis Pallikaris MD, PhD, University of Crete, suggested that researchers focusing entirely on the cornea may be pursuing the wrong path in trying to understand the aetiology of ectasia refractive surgery. Recognising the cornea as being only part of the “system”, it is important to consider the bigger picture that is the whole globe, he said.
Dr Pallikaris has been studying how corneal shape may be influenced by other ocular factors, including ocular rigidity (a parameter expressing the elastic properties of the globe) and intraocular hydrodynamics (blood circulation and aqueous flow). His research includes developing methods to measure these factors so that he can investigate their interactions.
[email protected]@terra.com.br
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Theo Seiler José Güell Perry S Binder Rudy Nuijts A John Kanellopoulos Renato Ambrósio Jr Ioannis Pallikaris
Post-LASIK Ectasia
Figure 2: BAD from the contralateral eye with normal front surface curvature map of a patient with very asymmetric (not unilateral) keratoconus. This eye, if evaluated independently from the right eye, would have been considered as a low risk for ectasia based on the ERSS
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Dermot McGrath in Barcelona
ADVANCES in femtosecond laser technology for the creation of thinner corneal flaps as well as greater awareness of the full range of risk factors involved in the development of post-LASIK kerectasia seem to be reducing the incidence of this particular complication of refractive surgery, Nader Robin MD told delegates attending the XXVII Congress of the ESCRS.
“It is still early days but it is our impression that thin-flap LASIK with the femtosecond laser seems to be safer than LASIK with a mechanical microkeratome concerning the risk of ectasia. If this is categorically proved to be the case then perhaps the indications of laser refractive surgery could safely be enlarged to include higher refractions and thinner corneas,” said Dr Robin.
He added that in his clinical experience, well-analysed standard topographies and pachymetry are sufficient for preoperative screening before refractive surgery. “Naturally these outcomes have to be confirmed in a larger series and with longer follow-up,” he said.
Dr Robin was presenting the results of a retrospective study of 2,000 patients who were treated at the Clinique Vision Laser Des Alpes, Grenoble, France, between May 2006 and July 2007.
Preoperative evaluations included corneal topography, pachymetry and aberrometry. Dr Robin noted that preoperative ametropia ranged between -12 D to +5.0 D with astigmatism up to 5.0 D. Exclusion criteria included the presence of suspect keratoconus and residual stromal thickness of less than 250 microns.
All patients were treated with thin flap femto-LASIK with the IntraLase femtosecond
laser (AMO) set at 90-microns depth and the ablations were performed with the Mel 80 excimer laser (Zeiss). Clinical evaluation and topographies were obtained at two months, one year and two years for 1,760 patients.
There were no intraoperative complications in this series of patients, reported Dr Robin. Postoperative complications included one patient who developed bacterial keratitis that responded well to medical treatment.
Of the 1,760 patients included in the follow-up period of two years, there was just one case of ectasia, which presented six months postoperatively.
“Careful review of the preoperative topography of the affected eye revealed the existence of sub-clinical keratoconus before the procedure. Even though the pachymetry was normal, the corneal regularity and the shape factor on the topography map were irregular,” he said.
Looking at the currently accepted LASIK contraindications, Dr Robin said that the list typically includes factors such as thin corneas of less than 500 or 520 microns, high myopes of greater than -8 D or -10 D, an ablation of more than 100 or 120 microns, residual stromal thickness of less than 250 or 300 microns, a history of eye rubbing, autoimmune disease or allergies, and young age of patient.
“Now the question we have to ask today is do these contraindications apply to thin-flap femto-LASIK or sub-Bowman’s keratectomy? We believe that the thin flap induces less weakening of the corneal resistance, and the perpendicular side cuts that are possible with the femtosecond laser contribute to a better fit of the flap and less shearing forces between the flap and the underlying stroma. Furthermore, the circular fibrous ring that appears in the weeks after femto-LASIK may
also contribute to resistance to ectasia. We are all aware that flap lifting after femto-LASIK is usually very difficult after a few months postoperatively, so the flap is more adherent to the stroma,” he said.
Bearing these factors in mind, Dr Robin said that thin-flap LASIK seems to be safer than mechanical LASIK in terms of the risk of ectasia and suggested that the indications of laser refractive surgery could safely be enlarged in the future to include higher refractions and thinner corneas.
Role of thicker flaps in post-LASIK ectasia
While there is still a lot of speculation about the pathogenesis of post-LASIK ectasia, there is little current evidence to suggest that excessively thick corneal flaps are primarily responsible for the development of the disease, according to J Bradley Randleman MD.
“Thicker than anticipated corneal flaps have been implicated in the development of post-LASIK ectasia. However, this is primarily based on case reports and anecdote. Our study showed that measured flap thickness in a post-LASIK ectasia population was comparable with the normal flap thickness range, and no excessively thick flaps occurred. The take-home message is that while unintended thick flaps remain a potential mechanism for post-LASIK ectasia, it does not appear to be the major mechanism underlying the development of ectasia,” he said.
In order to assess flap-thickness variability in post-LASIK ectasia eyes and determine the incidence of unexpectedly thick flaps, Dr Randleman and co-workers at the
Emory Eye Center, Atlanta, US, performed confocal microscopy analysis of 51 eyes from 29 patients and evaluated preoperative and intraoperative records to compare the intended versus the measured flap thickness.
The mean preoperative corneal thickness was 528 microns and the mean preoperative residual spherical equivalent was -4.1 D. While the mean intended flap thickness was 161 microns, the actual measured thickness averaged 138 microns, a statistically significant difference, noted Dr Randleman.
“Only 13 eyes (26 per cent) were more than 150 microns thick but this would be expected given that most of these flaps had been created with 160 or 180 micron plates. Only two eyes (four per cent) had flaps that were more than 180 microns and only five eyes (10 per cent) were 10 microns or more above the intended flap thickness,” he said.
Looking at the data in more detail, Dr Randleman noted that no firm trend emerged in the type of microkeratome responsible for creating the thicker flaps in the study.
“One flap was created with the ACS microkeratome, three with the Moria microkeratome and one with the IntraLase femtosecond laser. So while it is possible that thicker than anticipated flaps occur in post-LASIK ectasia eyes, they are rare. For the vast majority of these cases, the measured flap was less than the planned flap and so we have to conclude that while it may be a mechanism for rare cases of ectasia, unintended thick flaps are unlikely to be a major factor contributing to post-LASIK ectasia,” he concluded.
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Nader Robin
New studies shed light on risk factors for post-LASIK ectasia
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Dermot McGrath in Barcelona
COLLAGEN cross-linking with riboflavin may provide an effective and safe treatment for post-refractive-surgery ectasia by stabilising the biomechanical properties of the cornea and avoiding the need for a penetrating keratoplasty in the majority of cases, Paolo Vinciguerra MD told delegates attending the XXVII Congress of the ESCRS.
“We still need larger studies with longer follow-up but the evidence of this series suggests that cross-linking appears to stabilise eyes with post-refractive-surgery ectasia and improve their best spectacle-corrected visual acuity without any adverse events,” he said.
Dr Vinciguerra, director of the Ophthalmology Department of the Humanitas Clinic in Milan, Italy, said the incidence of post-LASIK ectasia is on the increase and there is therefore a need to find some alternative therapies to treat one of the most serious side effects of refractive surgery. He also urged surgeons to employ greater vigilance in carrying out thorough preoperative examination of patients using both topography and pachymetry readings.
“Almost 20 per cent of all keratoplasties performed in some months at the Humanitas Clinic are performed on eyes with post-LASIK ectasia, and we have seen the incidence increase significantly in recent years. Furthermore we have observed peripheral curvature changes in post-LASIK corneas which had previously shown no evidence of ectasia. So preoperative topography assessment is not sufficient to identify cases at risk for ectasia – detailed pachymetry maps are also essential. We need to connect the findings from the corneal curvature to the findings for the pachymetry to make a proper assessment of the risk,” he said.
While its incidence is rare, corneal ectasia remains a feared side effect of corneal refractive surgery. The disease is characterised by a progressive thinning and steepening of the central and inferior portions of the cornea.
Dr Vinciguerra noted that ectasia may become evident many years after the initial refractive procedure. He surmised that the increase of the condition in recent years may be due to a variety of factors, including incorrect interpretation of topography maps at early stages of ectasia, the rare use of pachymetry maps in preoperative assessment and the increased use of larger flaps and optical zones which sever more corneal collagen fibres and ablate more tissue.
Traditional treatments for ectasia after excimer laser refractive surgery include rigid gas permeable contact lenses,
intracorneal ring segments, or most frequently corneal transplantation. The latter option, however, is far from ideal, said Dr Vinciguerra.
“The surgery is difficult and a patient with full visual acuity who undergoes a -3 D LASIK procedure becomes totally crushed when later told that he needs a penetrating keratoplasty that is likely to result in high ametropia and poor visual acuity. Frequently patients appear at such a late stage of ectasia that cross-linking is no longer possible,” he said.
Against this background, collagen cross-linking provides a viable and repeatable alternative to corneal transplants for such patients, said Dr Vinciguerra.
His prospective, non-randomised, single-centre study included 13 eyes of 9 consecutive patients in whom postoperative excimer laser refractive surgery ectasia progression had been detected. Inclusion criteria were previous excimer laser refractive surgery, a documented ectasia progression in the previous six months, corneal thickness of at least 350 microns at the thinnest point, and being aged between 18 to 60 years.
Preoperative ectasia progression was confirmed by serial differential corneal topography and by differential optical pachymetry analysis in all eyes included in the study. Exclusion criteria were corneal thickness of 350 microns at the thinnest point, a history of herpetic keratitis, severe dry eye, concurrent corneal infections, corneal opacities, concomitant autoimmune diseases, and any previous non-excimer laser refractive ocular surgery. Pregnant or nursing women, patients with poor compliance, and patients wearing rigid gas permeable lenses for at least four weeks before baseline examination were also excluded.
All patients previously had excimer laser refractive surgery, either PRK (three eyes) or LASIK (10 eyes), and were referred from other centres. The reasons for biomechanical instability after excimer laser refractive surgery was due to formerly undiagnosed forme fruste keratoconus in five eyes and high correction with reduced residual corneal thickness in three eyes. The cause could not be identified in the remaining four eyes, said Dr Vinciguerra.
All eyes underwent corneal cross-linking with photosensitising riboflavin 0.1 per cent solution and subsequent exposure to an ultraviolet light source.
Turning to the results, Dr Vinciguerra said that best spectacle corrected visual acuity improvement was statistically significant beyond six months postoperatively, the mean refractive sphere reduction was also statistically
significant at six months and close to significant at 12 months’ postoperatively. The mean endothelial cell counts, keratometry as well as Klyce and Ambrosio indexes for corneal curvature showed no deterioration at the one-year follow-up point. Coma and spherical aberration did not change significantly. Mean pupil centre pachymetry and corneal thickness at 0 and 2.0mm decreased significantly, he said.
Putting the results into context, Dr Vinciguerra said that cross-linking appears to stabilise eyes with ectasia consequent to excimer laser refractive surgery and improve BSCVA.
“The limited invasiveness as well as the potential for repeatability of cross-linking make it an ideal treatment for these refractive surgery patients. There were no complications in this series. All patients displayed stability, the optical zone was apparently re-centred, there was a mild reduction of refractive error, and improvement could be seen long after cross-linking. It is also possible to treat corneas thinner that 400 microns with this approach,” he said.
Dr Vinciguerra added that
surgeons should perform regular topography and tomography examinations using differential maps and should always bear in mind that a LASIK patient may develop ectasia at some future point.
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Cross-linking effective at stabilising post-LASIK ectasia
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Post-LASIK Ectasia
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Roibeard O’hEineachain in Barcelona
BIAXIAL microincision cataract surgery appears to induce less trauma to the eye than
coaxial small incision surgery, which in turn results in faster visual rehabilitation and less endothelial cell loss, said Burkhard Dick MD, Ruhr University Eye Clinic, Bochum, Germany.
In a prospective randomised trial involving 78 cataract patients who underwent biaxial microincision surgery in one eye and conventional coaxial surgery in the other,
the coaxial surgery required less phaco time, resulted in less surgical astigmatism and better visual acuity in the early postoperative period, Dr Dick told the XXVII Congress of the ESCRS.
In the single-surgeon study, Dr Dick performed phacoemulsification with both the biaxial and coaxial procedures using Bausch and Lomb’s (B&L’s) Stellaris vision enhancement system, and implanted Akreos™ microincision IOLs. The Akreos microincision lens is a single-piece, biconvex, hydrophilic acrylic IOL consisting of a central optic and four flexible haptics and an aberration-free aspheric biconvex optic. It is designed specifically for implantation through a sub-2.0mm incision.
When performing the biaxial procedures, Dr Dick first made a clear corneal one-step tunnel incision 1.2mm wide and 1.5mm long at 10 o’clock. He then made a second, 1.0mm-wide incision at two o’clock. He performed the capsulorhexis with a 24–gauge bent needle. After performing hydrodissection and hydrodelineation, he broke up and emulsified the lens with the B&L phacoemulsification needle inserted through the 10 o’clock incision and the 19-gauge irrigating chopper through the 2 o’clock incision.
When carrying out the coaxial procedures he first made a corneal tunnel incision 2.75mm wide at 12 o’clock, and a second incision 1.0mm width at 10 o’clock, through which he preformed the 19-gauge sleeved phacoemulsification needle, and another 1.0mm incision at 2 o’clock, through which he inserted the chopper.
Less phaco time, faster visual recovery
Dr Dick noted that the mean surgical time for the biaxial microincision procedure, 7.8 minutes, was significantly longer than that of the coaxial procedure, 7.0 minutes (p =
0.0005). However, the average phaco time was significantly lower in the biaxial group than in the coaxial group (0.9 seconds vs. 14.7 seconds, P<0.0001), as was the effective phaco time (1.6 seconds vs. 2.8 seconds p<0.0001), he pointed out. The liquid turnover was also significantly lower in the biaxial group (p=0.05).
In terms of visual results, surgically induced astigmatism was higher by approximately 0.4 D in the coaxial group (p=0.01) at day 7-10, but the difference decreased to around 0.2 D (p=0.04) by week seven to nine, Dr Dick said. The biaxial group also performed slightly better with regard to the mean achieved MRSE on day one after surgery (-0.08 vs. -0.38, p =0.02), but that difference had disappeared by day three to four, he noted.
Similarly, the logMAR UCVA was significantly better during the first days of the first postoperative week, but as the weeks progressed there was less difference between the groups and at week seven to nine there was no significant difference between the groups, with values of 0.15 and 0.19 in the biaxial and coaxial respectively, he continued.
“There was an earlier improvement in UCVA and BCVA in the biaxial MICS group, with 31 per cent of eyes gaining more than three lines at day one compared to only six per cent for standard coaxial. I think this might be due to the reduction in corneal oedema, because the smaller the incision, the faster the visual rehabilitation,” he added.
An unexpected finding was that the amount of endothelial cell loss was also significantly lower in the biaxial group. By 12 months’ follow-up, there was only 1.4 per cent endothelial cell loss in the biaxial group, compared with 7.8 per cent endothelial cell loss in the coaxial group (p =0.05). Dr Dick noted that this is the first time that lower endothelial cell loss has been reported with microincision surgery.
“The results indicate 1.8mm biaxial MICS reduces surgical trauma and promotes faster healing with less induced astigmatism. Compared to coaxial small incision cataract surgery, biaxial MICS significantly reduced intraoperative parameters and resulted in less surgically induced astigmatism and endothelial cell loss, with the biaxial MICS technique providing an earlier improvement in UCVA and BCVA,” he added.
Dr Dick added that in his experience biaxial techniques have particular advantages when dealing with hard nuclei, floppy iris syndrome and certain other difficult scenarios. The separation of irrigation from aspiration means that aspiration remains on top of the iris. With coaxial techniques there is an increased chance of the iris being moved into the incision by fluidic forces, he said.
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Burkhard Dick
Micro lens and microsurgery result in less intraocular trauma and faster visual recovery
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Roibeard O’hEineachain in Barcelona
CATARACT patients implanted with the Zeiss Invent ZO aspheric IOL can achieve a similar quality of visual performance to that of healthy young adults without cataracts, said Fabrizio Camesasca MD, Istituto Clinico Humanitas, Milan, Italy.
In a multicentre study, there were no significant differences between the spherical aberrations of 55 eyes of 55 patients implanted with the Zeiss Invent ZO IOL and that of a control group of 97 healthy phakic eyes throughout one year’s follow-up, Dr Camesasca told the XXVII Congress of the ESCRS. “The Invent ZO IOL has been designed to provide the same Z(4.0) spherical aberrations than the natural crystalline lens. In patients having received an Invent ZO, the Z(4.0) MTF seems equivalent than in the control group, whatever the pupil size (3 and 4.5mm) is,” he added.
The patients in the study all underwent routine cataract surgery with intracapsular implantation of the IOL. The inclusion criteria of the study were for patients to be aged over 55 years, a required IOL power between 18 D and 26 D, astigmatism less than 1.50 D. Patients were excluded if they had other ocular pathologies, such as keratoconus or glaucoma, or if they had undergone previous ocular surgery or had a metabolic disease. Another requirement for inclusion in the study was a minimum pupil diameter of 4.0mm to 5.0mm in mesopic conditions after two minutes of dark adaptation.
The lens appeared to have good refractive predictability, Dr Camesasca noted. At 12 months’ follow-up the difference between the mean spherical equivalent and target refraction was only -0.12 D+/- 0.85. The mean sphere at 12 months was -0.8 D+/-0.95 and the mean cylinder was –0.7 D +/-0.48. In addition, the mean best-corrected distance vision was 0.086+/- 0.096 logMAR and the mean best corrected near vision was 0.096+/- 0.083 logMAR at 12 months.
“The Zeiss Invent ZO lens demonstrated good stability of visual acuity and refraction over time with good refractive stability,” Dr Camesasca said.
Evaluation as well as NIDEK OPD showed that the mean modulation transfer function of the whole eye of the patients in the study was slightly inferior to that of controls. However, the mean spherical aberration at 3.0mm and 4.5 pupil was roughly equal to that of the reference group throughout follow-up. The same was true regarding the higher order aberrations of the internal structure of the eye, which excluded the cornea.
“There was no clinically relevant difference regarding modulation transfer function. The Invent ZO optic is designed to provide the same amount of spherical aberrations as the natural lens in a young eye and since the internal spherical aberration of patients is not inferior to that of control group, the lens reached its intended performance,” Dr Camesasca said.
He noted there was a 7.69 per cent incidence of IOL decentration at 12 months’ follow-up, with a mean value of 1.75+/-0.5mm. There was a slight tilt of the IOL in 3.85 per cent of eyes. Although 96 per cent were free of visual symptoms, in the remaining eyes there was mild glare in one eye (1.92 per cent) and severe glare in another eye. One patient reported one halo, and two reported blurring, which in one case was moderate.
In addition, by 12 months’ follow-up eight patients (15.4 per cent) had a significant loss of BCVA due to PCO, and three eyes (5.77 per cent) required YAG laser capsulotomy. Among those who did not undergo capsulotomy, opacification was absent in 23 eyes (46.9 per cent), mild in 18 eyes (36.7 per cent), moderate in five (10.2 per cent) and severe in three (6.12 per cent).
Further analysis of the higher order aberrations showed that the MTF of corneal spherical aberration and corneal coma were not inferior to those of the healthy young eyes used as a reference group, but that was not true of corneal trefoil or internal trefoil or coma, said Damien Gatinel MD, PhD, Fondation Rothschild, Paris, France, who was one of the study’s investigators.
“This suggests that the Invent ZO aspheric IOL mimics the
young crystalline lens in terms of spherical aberration. However, the internal odd-order aberrations are increased in the Invent ZO group. Corneal incision size of 2.8mm is
neutral on corneal coma and SA but not on corneal trefoil,” he added.
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In addition, by 12 months’ follow-up eight patients (15.4 per cent) had a significant loss of BCVA due to PCO, and three eyes (5.77 per cent) required YAG laser capsulotomy
Aspheric IOL mimics performance of crystalline lens in young eyes
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Fabrizio Camesasca
ZEISS Optic aspheric lenses
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Roibeard O’hEineachain in Barcelona
PHAKIC IOLs continue to have a bright future in refractive surgery despite the withdrawal of some angle-supported phakic IOLs for safety concerns, says Beatrice Cochener MD, University of Brest and president of the French Society of Ophthalmology (SFO) France.
“There is definitely a place for phakic IOLs in patients with high ametropia, that is those with high myopia more than -9.0 D and hyperopia more than + 6.0 D, especially in patients younger than 50 years when you wish to retain the clear crystalline lens. It is also an option for refractive patients with thin corneas or abnormal topography,” Prof Cochener told the XXVII Congress of the ESCRS.
Phakic IOL implantation leaves the cornea largely unchanged, with the potential for a better quality of vision than photoablation procedures will provide, she said. Moreover, it can be used in conjunction with LASIK and related procedures, to lessen the depth of ablation required to achieve the target refraction, she added. For eyes
with high astigmatism, toric models are available and the non-toric models can be combined with incisional or photoablative techniques, she said.
However, eyes must meet certain anatomical criteria to be suitable for phakic IOLs. They must have an anterior chamber of at least 3.0mm for anterior chamber IOLs, and 2.8mm for posterior chamber IOLs. In addition, their endothelial cell counts must be 2000/mm2, with attention to cell morphology, especially in contact lens wearers.
There is also the general recommendation that white-to-white measurements be at least 11.0mm for anterior chamber angle-fixated IOLs, such as the Alcon AcrySof phakic IOL, although the white-to-white measurement is just a surrogate for the angle-to-angle diameter and is not very reliable, Prof Cochener said.
So far, intraocular measurements are not integrated into the nomograms of phakic IOLs, but they are nonetheless necessary to achieve good results with the lenses. Optical coherence tomography
and Scheimpflug cameras provide very accurate measurements of the angle-to angle diameter for angle-supported lenses. However, for posterior chamber IOLs, only high frequency ultrasound will provide reliable measurements of sulcus diameter.
Prof Cochener noted that intraocular measurements can identify eyes unsuitable for phakic IOL implantation and are also useful for postoperative follow-up. They can show the IOL’s position in relation to other intraocular structures such as the endothelium and the crystalline lens, and the lens also moves in response to dynamic changes in the iris and the ciliary muscle.
Avoiding endothelial cell loss
The anterior chamber lenses include the iris fixated Artisan/Verisyse and Artiflex/Veriflex lenses (Ophtec/AMO) and the angle supported AcrySof phakic IOL. The available posterior chamber lenses include the ICL and the PRL. All produce great visual results, but experience has shown that phakic IOLs have the potential for late anatomical complications.
“For each new generation we need a new evaluation and that takes at least 10 years to make sure that we will be perfectly safe regarding the endothelium and the lens. The retinal risk is less likely than might be expected with refractive lens exchange,” Prof Cochener said.
Because of the large incision required for their implantation there is a risk of induced astigmatism. There is a learning curve involved for the surgeon, and the lenses can also induce pupil ovalisation. As with all anterior chamber lenses, regular monitoring of the cornea is necessary. However, in 15 years of experience with the lens, the rate of endothelial cell loss has generally remained at acceptable levels.
More recently a foldable model of the lens has become available, the Artiflex/Veriflex (Ophtec/AMO). The lens has a silicone optic and PMMA haptics, allowing insertion through 3.2mm incision. However, safety has yet to be proved with respect to the endothelium and there is a small incidence of deposits forming on the IOLs.
New hydrophobic acrylic angle supported IOL
Prof Cochener noted that two angle-supported IOLs, the GBR (IOLtech) and the Icare (Corneal) were withdrawn from the Market in 2007, when the lenses were shown to cause high rates of catastrophic endothelial cell loss within three years of implantation.
Meanwhile, a new angle-supported IOL has become available in Europe, the AcrySof® phakic IOL, which received its CE mark in 2008 because of the favourable results achieved in FDA trials. The hydrophobic acrylic lens has an optic diameter of 6.0mm and an overall length 12.5 to 14.0mm in 0.5mm steps. It’s available in refractive powers ranging from -6.0 D to 16.5 D in 0.5 D steps.
Pooled outcomes for 360 subjects implanted with the AcrySof phakic IOL in prospective global clinical trials show very good visual results with a good safety profile at three years’ follow-up. In addition, refraction with the lens was very predictable with no endothelial cell loss or detectable damage to the cornea, angle or iris, she pointed out.
“Despite sizing based on white-to-white measurements, the lens has proved spectacularly innocuous at five years when the majority of other angle-supported implants have to be removed after three years. That may be because of the high refractive index of the hydrophobic material, which makes the lens thinner, or the softness of the haptics which may adjust to the angle more gently,” Prof Cochener added.
Posterior chamber phakic IOLs largely eliminate the dangers of the endothelium and do not cause pupil ovalisation. In addition, because of the lens’s position in the eye, the optical zone can be less than 6.0mm and the quality of vision achieved is less affected by pupil size than is the case with anterior chamber IOLs.
The main drawback of posterior chamber phakic IOLs is that they can cause cataracts and may also accelerate the development of cataracts, especially in older patients. Among her own patients implanted with the ICL there was six per cent incidence of cataracts overall and a 40 per cent incidence of cataracts among patients over 45 years of age.
Prof Cochener was a clinical investigator for icare (Corneal lab.) GBr (ioltech lab.) iCl (staar lab.) and acrysof Cachet (alcon lab.).
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“Despite sizing based on white-to-white measurements, the lens has proved spectacularly innocuous at five years...”
Beatrice Cochener
Phakic IOLs remain the best surgical option for some refractive indications
Ref
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3/10
Dermot McGrath in Barcelona
A VARIATION of the big-bubble technique in deep anterior lamellar keratoplasty (DALK) procedures assisted by femtosecond laser has delivered promising early results with excellent graft adhesion and good refractive outcomes, according to Luca Buzzonetti MD.
“IntraBubble, linking all the advantages of femtosecond technology and big bubble DALK, represents a new possible application of IntraLase that could partially standardise big-bubble DALK and make the intraoperative conversion to penetrating keratoplasty (PK) easier, resulting in a better fit of the donor cornea and very good refractive outcomes,” Dr Buzzonetti MD told delegates attending the XXVII Congress of the ESCRS.
Dr Buzzonetti, chief of the Ophthalmology Department of the Bambino Gesù Hospital, Rome, Italy, presented the results of 15 eyes of 15 patients with keratoconus that had been treated with the IntraBubble technique.
Describing the technique in more detail, Dr Buzzonetti said that the first step is to create the donor lamella. For this, the cut is performed on the corneoscleral rim, analysed and then processed by an ocular tissue bank before being mounted on an artificial anterior chamber (Coronet Patient Artificial Anterior Chamber, Network Medical Products Ltd).
The femtosecond laser then makes a full lamellar cut of 8.2mm diameter, 100 microns above the thinnest corneal point as measured by Oculus Pentacam and creates a mushroom lamella with an anterior diameter of 9.0mm and posterior diameter of 8.0mm at the same depth. An original model was applied to calculate the donor thickness for each patient, said Dr Buzzonetti.
Dr Buzzonetti explained that the big-bubble approach, created by Dr
Mohammad Anwar, offers surgeons a safe and efficient means of baring Descemet’s membrane.
Using this approach, a 27-gauge bent needle is inserted deep into the corneal stroma and air is then forced into the pre-Descemet’s plane creating a bubble between the stroma and Descemet’s membrane.
After big-bubble formation, debulking of the anterior two-thirds of the corneal stroma is performed and the corneal stromal tissue excised. The donor lamella is then fitted into place using interrupted sutures.
In this series of patients, Descemet’s separation using the bubble technique was successfully achieved in 13 out of 15 eyes. In one patient, the surgical procedure was intraoperatively converted to full thickness PK because of a large tear in Descemet’s membrane, said Dr Buzzonetti.
Six months after surgery, the mean best-corrected visual acuity was 0.5 and the mean spherical equivalent was -2.75 D. The mean refractive astigmatism was approximately -2.50 D while the topographic astigmatism was approximately +2.0 D.
While these results were largely positive, Dr Buzzonetti and co-workers decided to explore ways of standardising, at least partially, the big-bubble technique, and thereby removing some of the unpredictability associated with this approach.
“After our initial experiences, we think that IntraLase can really help us to make this goal achievable because of the level of accuracy and precision that the laser delivers,” he said.
Dr Buzzonetti explained that the enhanced version of the IntraBubble technique entails using the femtosecond
laser to create an intrastromal channel using a lamellar cut 0.6mm in diameter, with a side cut at a 45-degree angle and a 12-degree arc length positioned 50 microns above the thinnest corneal site measured by Pentacam.
He noted that the IntraLase laser can be reliably programmed to cut much closer to Descemet’s membrane than is possible with a metal or mechanical trephine, where it might lead to unplanned perforation and necessitate conversion to PK.
Another benefit of this approach, as described by Frank Price MD, is that a deep femtosecond laser incision close to Descemet’s membrane minimises air escape into the peripheral cornea and prevents peripheral opacification that may impair big-bubble visualisation.
After the intrastromal channel has been created, Dr Buzzonetti said that the laser then generates a full lamellar cut 9.5mm in diameter, 100 microns above the thinnest corneal site.
On the donor cornea, a zigzag incision, sized to match the recipient incision, is created with the femtosecond laser. The zigzag-shaped incision, popularised by Roger Steinert MD, helps to provide a smoother transition between host and donor and a hermetic wound seal. This particular cut profile results in
an excellent anterior apposition and extremely smooth graft interface, he said.
“After the lamella is removed we can insert the cannula for air injection using the channel created by the IntraLase. We then inject the air and create the bubble and perform a bubble test to verify the baring of Descemet’s membrane,” he said.
Of the four eyes that have been treated using this technique, the results have been very promising, said Dr Buzzonetti.
“The big bubble was achieved in all cases. The mean best-corrected visual acuity was 0.5, with a mean spherical equivalent of +2.0 D and a mean topographic astigmatism of +3.7 D. Although we do need further long-term study of this approach, we believe that it could help to standardise the big bubble technique in DALK, reducing the risk of intraoperative complications, especially perforation which is the real risk with this procedure, and allowing good refractive outcomes.”
The big-bubble has been achieved and the bubble test has been performed
One month after the standardised big-bubble technique in DALK assisted by IntraLase femtosecond laser
A smooth Fogla 27-gauge air injection cannula (Bausch & Lomb Storz Ophthalmic), flat with a hole facing down at the tip site, connected to a 5ml syringe filled with air is inserted into the channel
created by IntraLase in the posterior residual stroma
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‘IntraBubble’ technique delivers promising results in DALK procedures
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“After our initial experiences, we think that IntraLase can really help us to make this goal achievable because of the level of accuracy and precision that the laser delivers”
Dermot McGrath in Barcelona
THE ability to create complex incisions combined with a high degree of safety and accuracy gives the femtosecond laser a definite advantage over mechanical trephines in penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) procedures, according to Francis W Price MD.
“The IntraLase (AMO) femtosecond laser allows complex interlocking incision patterns, which would be difficult, or even impossible, to create accurately with mechanical methods. It works very well for anterior lamellar procedures and allows us to get close to Descemet’s membrane without compromising safety,” he told delegates attending the XXVII Congress of the ESCRS.
Reviewing his three-plus years’ experience working with the IntraLase laser, Dr Price, in private practice in Indianapolis, US, said that the latest software version of the laser gives surgeons the option to generate complex customised incisions with advanced edge profiles, helping to establish secure grafts that require less suture tension.
“In my experience, it is very hard to be precise with a deep cut with mechanical methods and trephines and we are much more accurate with the femtosecond laser going down to within 70 microns of Descemet’s membrane. We perform these incisions in our laser centre and then move the patient to the operating room for the actual surgery, so they are initially done with topical anaesthesia. It is very important that we do not perforate with these incisions so it is vital to carry out careful preoperative
and intraoperative planning,” he said.Dr Price noted the importance of
obtaining accurate corneal thickness measurements in order to ensure that the programmed laser incisions do not penetrate the recipient anterior chamber. For this, he uses optical coherence tomography pachymetry mapping (Visante, Carl Zeiss, Inc.) for preoperative assessment and then verifies those readings at the time of surgery using ultrasonic pachymetry (Palm Scan AP2000, Micro Medical Devices).
Focusing on the IntraLase cut profiles in more detail, Dr Price said that configurations such as mushroom, top hat and zigzag are all possible using the femtosecond device. The mushroom-shaped incision preserves more host endothelium than the traditional trephine approach, while the top-hat-shaped incision allows for the transplantation of large endothelial surfaces, as well as a lamellar step for stronger healing and a reduced anterior surface area that is further from the limbus, possibly reducing rejection risk.
The zigzag incision profile, popularised by Roger Steinert MD, provides a smooth transition between host and donor tissue and allows for a hermetic wound seal. This type of incision provides oblique planes of contact and may potentially improve the strength of wound healing, said Dr Price.
“Over the last three years we started out doing top hat incisions as well as mushroom incisions for keratoconus cases. More recently, we have switched to zigzag for almost all of our cases and most of these are for deep anterior lamellar keratoplasty,” he said.
Dr Price emphasised the importance of precise graft centration and of avoiding getting too close to the limbus when using such complex incision patterns with wider diameter grafts. To achieve this, the centre of the cornea is located first using a 12.0mm ring marker with central crosshairs and the centre of the cornea is marked with gentian violet on a Sinskey hook. An unstained 8.0mm ring with crosshairs is then centred on the gentian violet mark and used to indent the cornea. This second ring mark identifies the area of the incisions.
After the laser suction ring is placed on the eye, a crosshair marker is placed inside the suction ring to help centre the ring on the previously made gentian-violet mark on the cornea. Once good suction is achieved and the ring is centred appropriately, the crosshair is removed, the cornea is applanated and the laser incision created.
Dr Price noted the utility of using incomplete incision patterns on the recipient eye to ensure that the incisions do not spontaneously rupture.
“In our early cases, we found that not fully completing the anterior or posterior side cut provided excellent wound stability, whereas an incomplete lamellar ring cut did not. Leaving only 70 microns incomplete on one of the transverse/vertical side cut incisions was sufficient to provide a stable eye, which could successfully undergo retrobulbar injection and pressure application with a device such as a Honan Balloon, without wound rupture,” he said.
Dr Price added that the zigzag pattern, with an incomplete posterior side cut which does not penetrate into the anterior chamber, is also ideal for DALK procedures.
The angled incision edge facilitates final stromal excision with scissors and compared with standard vertical incisions the zigzag incisions provide an interlocking wound configuration and facilitate matching the donor and recipient anterior surfaces.
The safety of the DALK procedure is also enhanced by using the femtosecond laser. Unlike mechanical trephines, the femtosecond laser allows the surgeon to safely cut within 70 microns of Descemet’s membrane, he said.
“Cutting that deep with a mechanical trephine may lead to an unplanned perforation and make it necessary to convert to a PK, whereas the precision of the IntraLase laser allows us to successfully make these deep incisions.”
Dr Price noted that the deep incisions created by the laser facilitates the use of either Anwar’s big-bubble technique by minimising escape of the injected air to the limbus, or hand dissection by providing a reference point 70 microns above Descemet’s membrane.
While the zigzag pattern is Dr Price’s current incision of choice in DALK procedures, he said that there are still some instances when the top-hat incision might be preferable, such as in patients with severe scarring or corneal thinning.
Dr Price said that femtosecond-assisted DALK was part of an ongoing trend towards more targeted and customised keratoplasty surgery. While noting that DALK is more difficult than standard PKP, the zigzag DALK technique may ultimately result in better outcomes with fewer complications.
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Francis W Price
Complex incision patterns give femtosecond laser the edge in keratoplasty procedures
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Roibeard O’hEineachain in Dublin
A STANDARDISED and methodical approach will yield optimum results in the management of corneal infections, said Harminder Singh Dua FRCS, FRCOphth, MD, PhD, University Hospital, Queens Medical Centre, Nottingham, UK, in his Dermot Pierse memorial lecture which he delivered at the 6th International Refractive Meeting, held in Croke Park, Dublin, Ireland.
Dermot Pierse (1922-1994) was a consultant ophthalmologist at the Croydon Eye Unit, Surrey UK. He was a pioneer of ocular microsurgery and was an inventor of microsurgical instrumentation.
“Microbial keratitis is the most common cause of unilateral blindness worldwide. Meticulous clinical and laboratory assessment, constant review of symptoms and signs, and establishing and working to protocols helps,” said Prof Dua.
Prof Dua said that in his initial patient work-up he investigates the patient’s history with particular regard for those factors that may influence the ocular infection’s pathology. Those factors include a history of contact lens wear, previous ocular surgery, ocular surface disease, nasolacrimal obstruction and cold sores. In trauma cases he also tries to get as much information from the patient as possible about how the injury occurred and what types of material were involved.
He noted that examining the cornea and eye layer by layer, from the outside inwards provides a more complete picture of the disease processes involved and the treatment strategies to be undertaken. It is a good idea to first examine the eyelids and lashes and the conjunctiva for signs of blepharitis, he said.
“Untreated blepharitis provides a reservoir of bacteria for colonisation of the cornea. In addition the associated conjunctival lesions, such as papillae, follicles and ulcers may impose a mechanical stress on the corneal surface which can, in turn, delay corneal healing.”
It is also important not to overlook nasolacrimal sac obstructions, the simple syringing of which can reveal blockage, which may need to be overcome to successfully treat bacterial keratitis. Examination of the limbus with fluorescein staining can reveal inflammation (limbitis), which can be a sign of infections like herpes simplex or Acanthamoeba.
In the early stages of infection, the best clinical clues can be obtained with fluorescein staining by first instilling an anaesthetic, then the fluorescein, and allowing the patient to blink and waiting about 30 seconds before examining the cornea. When examining the corneal surface, fluorescein staining will reveal pseudodendritic patterns on the epithelium
that are a frequent feature of Acanthamoeba infections in their early stages. Prof Dua noted that viewing the ulcers and infiltrates separately will allow a more accurate tracking of the infection’s pathology since the one will exceed the other depending on the disease’s progress and its response to therapy.
Assessing the stroma is possible either with lower-tech approaches like slit-beam or higher-tech approaches like the Pentacam and OCT. Stromal features found in active infections include stromal thickening, melts, and perforation. In cases of perforation, the leak will become more clearly visible when stained with 2.0 per cent fluorescein.
Vascularisation in both the deep and superficial layers of the stroma are sometimes related to active inflammation, although they don’t generally occur until the very late stages with Acanthamoeba infection, Prof Dua said. “Immune rings” sometimes occur on the stromal surface. Those manifestations respond well to sterilisation with antimicrobials followed by topical steroids.
Intraocular signs and symptoms
Examination of internal structures such as the anterior chamber, the iris and the pupil, will reveal features such as hypopyon and hyphaema, dilated iris vessels and synechiae. In cases of corneal infection, hypopyon is generally sterile and results from toxins percolating through the stroma.
Therefore tapping the anterior chamber for culture samples is generally unwise, since it will raise the chance of microbes entering the eye, he cautioned. The pupil may be secluded, when ring synechiae occur or occluded with exudate or fibrin. Rigorous dilation is necessary in such cases to break the adhesions, he added.
Scleral infection is often overlooked in examination of eyes for keratitis. It can be mistaken for an inflammatory response to the corneal infection. Such infections require special attention and a different treatment strategy, which will generally include systemic antibiotics and at time immunosuppression, he stressed.
Examination of the corneas with Acanthamoeba infection by in vivo confocal microscopy can reveal the presence of cysts, which will present in three forms, depending on the level at which the cyst is scanned. The surface view gives a bright spot appearance to the cyst, further into the cyst the classic double-walled image is seen and when imaged obliquely or towards the margins a signet ring image is seen, he explained.
Infections by fungi such as Aspergillus will often have the appearance of bright intrastromal interlocking filaments when viewed by confocal microscopy. However, dendritic cells can have a similar appearance.
Immediate treatment essentialProf Dua said that his department ensures that antibiotic drops are commenced at the earliest opportunity even whilst the patient is waiting in the eye casualty prior to admission. The regimen he recommends is cefuroxime 10 per cent every five minutes for 30 minutes, alternating with gentamicin 1.5 per cent every five minutes for 30 minutes. This is followed by hourly administration of the drugs, alternating on the hour and the half hour or 24 to 48 hours and tapered according to clinical response.
He added that while some advocate sub-conjunctival or intracorneal injections, he has not administered one in the past 10 years because intensive topical therapy will achieve the same results.
Once Acanthamoeba has been definitively diagnosed, patients undergo an intensive regimen of treatment with topical anti-Acanthamoeba agents, tapering treatment over two to four months. In the case of mild non-sight threatening infections, monotherapy with topical ciloxan, ofloxacin, or levofloxacin is often adequate. In the case of atypical mycobacteria, amikacin is the drug of choice.
Steroids can be helpful in reducing inflammation of corneal infections, but are best used after there has been a definitive
response to treatment. The agents are particularly beneficial in the treatment of infectious keratitis in eyes that have undergone keratoplasty. In such cases, the eye’s immune response to the infection can trigger graft rejection.
Indicators of a good response to therapy include a reduction in pain, discharge and oedema. There will also be a blunting of the infiltrate edge and surrounding ‘fuzz,’ and a commencement of re-epithelialisation. If therapy has not been effective and the condition is worsening a cessation of therapy, repeated swabs and scrapes and reappraisal of treatment strategy is generally necessary. The causes for treatment failure include additional undiagnosed infectious agents, a low sensitivity of the microorganism to the agent used, or a toxic reaction to the agent.
Prof Dua is chair and professor of ophthalmology at the university Hospital, university of Nottingham. He is also current vice-president and president-elect of EuCornea. The 1st EuCornea Congress will be held in Venice, italy from June 17-19, 2010.
For further information see: www.eucornea.org
Acknowledgements: Dr Thaer Alomar and Dr Dalia G Said.
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Harminder Singh Dua
Standardised protocol is essential for the treatment of infectious keratitis
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Successfully treated contact lens-related psuedomonas keratitis
Post-LASIK interface candida keratitis, successfully treated. Residual scars remained and the patient needed a rigid gas permeable contact lens for full visual potential
ISTANBUL
15th ESCRS WintER MEEtingin conjunction with
tOS Cataract & Refractive Surgery Society
18 – 20 February 2011 hilton hotel, istanbul, turkey
www.escrs.org
EuropEan SociEty of cataract and rEfractivE SurgEonS
Cheryl Guttman Krader in Barcelona
SUBCONJUNCTIVAL injection of interferon alfa-2a (IFN alfa-2a; Roferon-A, Roche) shows promise as a safe, well-tolerated and effective treatment for conjunctival papilloma, according to the experience of ophthalmologists at Queen Victoria Hospital, East Grinstead, UK.
Radwan Almousa MD reported outcomes from a retrospective case series comprised of three adult patients with a conjunctival papilloma treated with subconjunctival injection of IFN alfa-2a three million IU/0.5ml as monotherapy or combined with topical IFN alfa-2a drops one million IU/ml (one patient). Two patients, one with a large papilloma and the other with a small lesion, achieved total resolution with biweekly injections. In the third patient, who had a large, recurrent conjunctival papilloma, only partial regression occurred with monthly injections.
One patient had a local allergic reaction to the injection with the development of localised oedema that lasted for just two hours. Otherwise, there were no local adverse events and no permanent injury to the ocular surface. The treatment was otherwise well tolerated. Systemic reactions included flu-like symptoms in two patients that were also transient and controlled with paracetamol, reported Dr Almousa, at the XXVII Congress of the ESCRS.
“Our limited experience suggests that subconjunctival IFN alfa-2a is a suitable treatment for conjunctival papilloma, although considering its cost, IFN alfa-2a may be best considered for the management of large or frequently recurring lesions. Our small series indicates that biweekly injection is more effective than once monthly treatment, also once weekly use has also been reported to be effective. We believe further study is needed in the form of a large prospective trial to establish the efficacy of this treatment, delineate the appropriate dosing frequency and length of treatment, and to better characterise its safety.”
The antiviral activity of IFN alfa-2a, the association of conjunctival papilloma with human papilloma virus subtypes 6 and 11, and the limitations of existing destructive intervention provides a rationale for using IFN alfa-2a as a treatment modality for these ocular lesions.
“Conjunctival papilloma can be treated by surgical excision, however surgery also destroys normal tissue, and so lesions that are very large or associated with a high recurrence rate may not be amenable to this intervention. CO2 laser ablation has also been used successfully
to eradicate these lesions, but it has been associated with a high recurrence rate. Topical mitomycin-C is another option that has been reported effective for achieving tumour resolution, but carries risks of causing corneal and conjunctival erosion. In fact, there was a report of scleral melt in a patient treated with mitomycin-C for a pterygium,” said Dr Almousa.
The duration of treatment with IFN alfa-2a in the British series varied. One of the three patients with a large conjunctival papilloma was treated with a total of 13 biweekly injections of IFN alfa-2a combined with topical drops four times daily. The lesion resolved completely within eight months and the topical treatment was continued for a total of 38 months. During follow-up of
three years, there was no recurrence of the conjunctival papilloma.
The second patient had a large lesion located in the anterior fornix that represented a recurrence; in this patient, the primary lesion occurred 20 years prior and was treated by surgical excision. IFN alfa-2a treatment was initiated with monthly injections. Over a period of seven months, only partial regression occurred.
“We are considering increasing the frequency of injection in this patient from monthly to biweekly or even weekly and adding topical drops to the regimen,” said Dr Almousa.
The third patient had a small lesion located in the medial canthus that was treated with biweekly injections. The lesion resolved after three injections
were administered, but the treatment was continued with monthly injections (two). After four months, the lesion recurred. Treatment with two subconjunctival injections administered two weeks apart resulted in lesion resolution, and the patient has been free of recurrence during 14 months of follow-up. “This patient was left with an area of raised conjunctiva after the papilloma resolved. The tissue was excised and histological evaluation demonstrated absence of the papilloma,” Dr Almousa said.
He noted that the diagnosis of conjunctival papilloma had not been confirmed by biopsy prior to treatment in any of the three patients. During the ensuing discussion of the paper, an audience member suggested that perhaps the large lesions might have been carcinoma rather than a papilloma. Dr Almousa observed that IFN alfa-2a also has anti-oncogenic properties, can prevent angiogenesis with longer term use, and has been used successfully at a frequency of three times a week to treat corneal/conjunctival intraepithelial neoplasia.
While topical IFN alfa-2a was used as an adjunct in one of the patients, Dr Almousa suggested that topical treatment might be more appropriate as a prophylactic versus a therapeutic modality since, according to the manufacturer, IFN alfa-2a is only chemically and physically stable for 24 hours after reconstitution.
“Longer term contact with the papilloma is probably needed to achieve resolution,” he said.
Questioned about treatment cost, Dr Almousa reported that each injection of IFN alfa-2a costs £16 (€18) and a one-month supply of the drops cost £840 (€937).
“This off-label treatment is not covered by the National Health Service and before we can ask the Primary Care Trust to pay for this use of IFN alfa-2a, we need to prove its efficacy,” he noted.
Although the paralesional injections of IFN alfa-2a were well tolerated in this small series, Dr Almousa mentioned that IFN treatment should be avoided in patients with renal or hepatic failure as well as in patients with cardiac arrhythmias or who are pregnant.
“The injections should also be delivered paralesionally to prevent regurgitation with possible loss of the desired therapeutic effect and increased risk for systemic reactions from drainage through the lacrimal puncta,” he added.
Left eye with large papilloma extending over the palpebral and bular conjunctiva
The same eye, eight months following paralesional treatment with IFN alfa-2a. The lesion resolved completely
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Paralesional Interferon injections show promise as alternative treatment for conjunctival papillomaRadwan AlmousaC
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Roibeard O’hEineachain in Barcelona
CONGENITAL cataract surgery during the first six weeks of life does not appear to increase the incidence of glaucoma compared to surgery performed later, according to a retrospective study reported by Andrew J Tatham MRCOphth, Leicester Royal Infirmary, UK at the first World Congress of Paediatric Ophthalmology and Strabismus, which took place in conjunction with the XXVII Congress of the ESCRS.
“Glaucoma is a serious complication which can develop at any time following surgery for congenital cataracts. Previous studies have suggested that surgery early in life is a risk factor but the children in our series had a low incidence of glaucoma even when surgery was performed at a very young age,” Dr Tatham said.
The case-note review study included data from 90 children who underwent surgery for congenital cataracts at an age of 14 years or less over a 20-year period from 1987 to 2007. Dr Tatham and his associates excluded patients with pre-existing glaucoma, those with secondary cataracts and those with a follow-up of less than six months. They based a diagnosis of glaucoma on the physician’s decision to initiate treat.
Low incidence of glaucoma
Dr Tatham’s review showed that over a follow-up period of 5.3 years only one patient developed glaucoma, and that the age of the patient at surgery appeared to have no significant bearing on the incidence of the condition. That is, among 18 eyes
of 13 children who underwent surgery at less than age 50 days, none had developed glaucoma after a mean follow-up period of 7.5 years. Among 28 children aged 51 days to one year at the time of surgery one patient developed glaucoma in both eyes, and among those aged one to 14 years none developed glaucoma.
“The incidence of glaucoma in our series was lower than in previous reports and significantly those children aged less than six weeks at the time of surgery did not appear to be at increased risk. Our study included 44 children who had surgery at less than one year of age and as yet just one has developed glaucoma. None of the 18 eyes undergoing surgery during the first six weeks of life has developed glaucoma”
“Previous series show that when aphakic glaucoma occurs the long term outcome is poor and unfortunately the child in our series was no exception. Also, glaucoma can occur at any time following surgery. Our patient had bilateral lens extractions at age five months and despite regular outpatient visits, intraocular pressure checks and optic disc examinations were not diagnosed with glaucoma until age 12,” Dr Tatham said. “It is possible that more of our patients will develop glaucoma with time”.
The median length of follow-up in the study was almost five years and there was no difference between the groups in the length of follow-up. Although this was a one surgeon study there was some variation in surgical technique over the study’s 20 year duration. The surgical technique also differed depending on the age of the child at the time of surgery, for example, in group one just one eye had
a primary intraocular lens implantation compared to 86 per cent in group three.
Dr Tatham noted that in 11 recent published series of glaucoma following congenital cataract surgery, the incidence of the complication ranged from 3.7 per cent to more than 50 per cent. The reason for such a large variation in the studies remains unclear, as was the reason for the low incidence in their own study.
“We can think of several possible reasons. We know that glaucoma can develop at any time following surgery so we would expect studies with longer follow up to report higher incidences of glaucoma, however this is not always the case and our own follow-up period compared favourably with other studies. Failure to diagnose glaucoma could be another possibility, but we were able to measure the intraocular pressure in 95 per cent of children and in the remaining five per cent there was a stable refractive error and normal optic disc appearance,” Dr Tatham said.
A possible factor may have been the surgical technique used. Children who suffer complications during surgery may be at increased risk of developing glaucoma. He said that in his approach to cataract surgery in very young children he tries to remove as much lens material as possible, without regard for the difficulties that this might create for secondary intraocular lens placement. The elimination of residual lens matter may reduce postoperative inflammation and subsequent glaucoma.
“The findings of our series suggest that factors other than age at surgery are important risk factors for aphakic glaucoma. A key part of the problem is that we don’t understand the reason why aphakic glaucoma occurs, perhaps when we have better understanding of the mechanism of the disease we will better understand the risk factors”, Dr Tatham concluded.
Possibilities for prevention
In a separate presentation Alex Levin MD, chief of pediatric ophthalmology and ocular genetics at Wills Eye Institute, Philadelphia, Pennsylvania, US, suggested that patient selection and individualised
treatment are key ingredients to reducing the incidence of glaucoma after paediatric cataract surgery.
“I don’t think we can prevent paediatric aphakic glaucoma completely, but there are things we can do to reduce the risk to a minimum,” he added.
For example, surgeons should be somewhat circumspect regarding the use of IOLs, particularly in cases with iritis, where failures can be disastrous. When a child achieves a satisfactory result with contact lenses, IOL implantation is likely to provide only a modest additional benefit of convenience and cost rather than vision while possibly increasing glaucoma risk.
In the case of persistent foetal circulation (previously PHPV), the lowest risk surgery can be achieved by using ultrasound biomicroscopy, for preoperative evaluation, and intraoperative endoscopy to insure that ciliary process tension is relieved. Moreover, if the posterior capsule is opacified throughout its entirety it may be best to refer the patient to a retinal surgeon.
The utility of peripheral iridectomy in eyes at risk of acute iritis is debatable, Dr Levin said. Where iritis is already present, performing the iridectomy may aggravate the condition, he pointed out. The posterior capsule is best left intact if the child has no contraindications for YAG laser capsulotomy, he advised. He added that he always leaves the capsule intact in iritis cases and they rarely require subsequent capsulotomy.
When despite all precautions glaucoma occurs following paediatric cataract surgery, early detection provides the best means of harm reduction. Patients carry a lifetime risk of the condition and should undergo, at minimum, yearly eye exams, he stressed. The examinations should include IOP measurements (even if sedation or anaesthesia are required), over-refracting patients to detect myopic shifts, and assessment of the cornea for signs of oedema.
“I have seen far too many cases in which the problem was not so much the glaucoma, as the late diagnosis of the disease,” Dr Levin said.
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“Previous studies have suggested that surgery early in life is a risk factor but the children in our series had a low incidence of glaucoma even when surgery was performed at a very young age”Andrew J Tatham, MRCOphth
Andrew J Tatham
Study shows congenital cataract surgery at a young age does not appear to increase glaucoma risk
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Gearoid Tuohy PhD in Vienna
DEATH and remodelling of retinal ganglion cells may explain a number of early anomalies in visual function brought about by diabetes, suggests new research presented at the Winter EURETINA conference.
Alistair Barber PhD, associate professor of ophthalmology at Penn State College of Medicine, reported many years of work by the Penn State Retina Research Group into neuronal damage associated with diabetic retinopathy (DR). While the disorder has clear vascular and neuronal abnormalities assumed to be intimately connected, Dr Barber told delegates that separate vascular and neuronal mechanisms may be occurring within the retina.
DR affects more than 90 per cent of people with diabetes and, despite significant advances in clinical management, it remains a leading cause of new cases of adult blindness worldwide. It has been well established that the best predictor of DR is the duration of diabetes – for Type 1 diabetes the risk is low over the first five years however, the risk climbs to 27 per cent for those diagnosed for 5-10 years and 71-90 per cent for those with diabetes for 10 years or longer. The incidence rises to 95 per cent for those diagnosed with diabetes for 20-30 years.
Optimal management of DR is achieved through a combination of glucose control, laser therapy and vitrectomy. Regular fundus examination, in addition to adherence to the ETDRS recommendations, greatly reduces vision loss, however the vast majority of lost vision arises from delays in seeking medical attention. Consequently there is significant interest in understanding the complex pathology of DR and the mechanics of molecular pathology in the early stages.
Dr Barber and his research team have been investigating the cell biology of DR attempting to obtain an improved knowledge of the molecular events that might ultimately open diagnostic or therapeutic opportunities. When the Penn State University group initiated their studies into DR one of the big questions posed by the research team was what happens to the neuronal cells? Although there was some data in existence, for example a number of researchers had recognised apoptotic neurons in the retinas of diabetic animals, there was relatively little information on what was occurring at the cellular level.
Textbook schematics of the neural retina illustrate a complex tissue. Photoreceptor cells synapse or connect with bipolar cells and horizontal cells, bipolar cells synapse with retinal ganglion cells (RGCs) which in turn lead to the brain while amacrine
cells are thought to regulate many of these connections. This delicate intricacy illustrates the experimental challenge of teasing out which cells are doing what.
In initial studies Dr Barber’s team looked at cross sections of retina from rats with diabetes and over a period of eight months made detailed morphological measurements. Analysis of such measurements showed a clear reduction in the thickness of some of the retinal layers over a period of streptozotocin (STZ) induced diabetes, a well established model for mimicking diabetes. Of all the retinal layers, the inner plexiform layer (IPL) of such animals appeared to be changed the most with almost a 22 per cent reduction in the thickness. Interestingly, the IPL is mostly comprised of synapses, so the loss of thickness hinted at a reduction in neuronal function. The inner nuclear layer (INL) was also reduced in thickness, however there was no observation of thinning seen in the outer layers.
Such histological data showed that something was lost from the retina but it was unclear what specific cells were being removed by the pathology. Measuring apoptosis across the whole retina and counting TUNEL (TdT-mediated dUTP nick end labelling) positive cells revealed that there was significant increases of apoptosis in diabetic animals across all time points studied, which suggested there was something happening quite early on in the retinas of these diabetic animals. Identifying which cells were dying has been a difficult question to answer, explained Dr Barber. Some of the cells appear to be vascular in origin while others are clearly inter-vascular. Detecting active forms of caspase 3, a key molecular player in apoptotic cell death, showed that apoptotic cells were found some distance from the vasculature, implying that these cells were more likely to be neural than vascular.
Transgenic detective work
To understand more of the cellular biology, Dr Barber and colleagues carried out some transgenic crosses (Ins2Akita/+ X Thy1-CFP or Thy1-YFP [reporter genes]) which allowed researchers to visually track the impact of diabetes on retinal ganglion cells. The “Akita” mice are spontaneously diabetic carrying a point mutation on one of the insulin genes and, while born normal, within four or five weeks of birth they develop diabetes, which persists for the rest of their lives. The Thy 1 promoter is specifically expressed within the retinal ganglion cells and by tagging on –CFP (cyan fluorescent protein) and –YFP (yellow fluorescent protein) markers one can observe and count the number of surviving retinal ganglion cells in the retina.
CFP is expressed in the cell bodies of the RGCs while YFP appears to be expressed throughout the entire neuronal structure. The use of both allows for the detection of morphological events in distinct parts of the cell and crossing the animals then allowed the researchers to track the fate of these cells in a diabetic retina.
Quantifying the RGCs in eight different regions of the retina (four central, four peripherally) the team found that there was a significant loss of RGCs in the peripheral region but not in the central region. The YFP mice were especially interesting (YFP is expressed throughout the entire structure of the RGC cell) as they showed that swellings occurred along the axons of these cells. Approximately 30 per cent showed swellings that appeared to be associated with narrowing and often the cell bodies appeared to be larger, similar to Wallerian degeneration observed when axons are severed. Dr Barber hypothesised that such swellings might be due to a “train wreck scenario” in which transport of proteins along the axon is blocked, leading to their accumulation, but why this might occur in DR remains unclear. Certainly the morphological data suggested that there might be transport issues in the axons and such interruption may be linked to apoptotic triggers.
Another set of observations included the dendrite structures, axon lengths, branch points and terminals. In diabetic animals there were more terminals, branch points and lengths in the ON cells but not the OFF cells suggesting something specific to functional activity. Such observations gave rise to further studies built around the synapses. As previously established, the inner plexiform layer (IPL) was significantly thinned in the diabetic models and as the IPL is comprised of many synapses it was logical to take a look at pre-synaptic markers such as synapsin 1 and others. Many such markers appeared to be depleted in the diabetic model and depletion would suggest there
may be some functional consequence for neurotransmission in this cell layer, which might explain some of the changes widely observed in electrophysiology recordings both in humans and in animals.
To drill a little deeper the research team isolated synaptic terminals or “synaptosomes”, using a standard technique well established in experimental neurophysiology. Pinching off the synaptosome allows for measurement of the levels of a number of synaptic proteins inside – synaptophysin, synapsin 1, VAMP2 and SNAP25 – all involved in different functions of regulating neurotransmission vesicle movement. Remarkably, all such measurements showed significant depletion of synaptic proteins in rat retinas, even after one month of diabetes.
According to Dr Barber, such observations might explain some of the functional effects seen in neuronal cells in the diabetic retina. Synapsin 1 is phosphorylated and when the synaptosomes are isolated and stimulated by depolarisation with KCl (a classic experiment in neuroscience) phosphorylation of synapsin 1 occurs within about a minute of depolarisation. This is exactly what is observed in synaptosomes from control animals, however in animals that have been diabetic for only one month the KCl stimulation does not give rise to the same amount of phosphorylation of synapsin 1, indicating that there may be some manner of loss of functional activity caused by diabetes.
It is difficult to envision a model in which vascular events influence a reduction in phosphorylation of synapsin. Therefore, it may be time to consider distinct neuronal and vascular mechanisms at play. Identifying such mechanisms represents the first step in devising some strategy to modify the decrease in phosphorylation that might ultimately benefit neuronal function in the diabetic retina.
Dr Barber and his team have built a body of evidence showing that diabetes increases the rate of apoptosis in the retina, that some of the dying cells are neurons; that there is a loss of synapsin 1 phosphorylation and that this may explain some of the loss in function seen in the early stages of DR.
Dr Barber suggested that it may be time to consider a more unusual possibility, which is that early on in the course of DR there may be separate mechanisms going on in the retinal tissue – vascular events and neuronal events with distinct molecular mechanisms, however difficult it might be to imagine given the general belief that vascular and neuronal pathologies are intimately connected.
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DR affects more than 90 per cent of people with diabetes and, despite significant advances in clinical management, it remains a leading cause of new cases of adult blindness worldwide
Dual mechanisms may contribute to the pathology of diabetic retinopathy
Alistair BarberRet
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Colin Kerr in Dublin
SENIOR ophthalmologists have a responsibility to produce more open access content online to support ophthalmologists in training who are increasingly using social media as their primary learning resource.
That is the view of Andrew Doan MD, PhD, assistant professor of surgery, Naval Medical Center, San Diego, US who told the recent American Academy of Ophthalmology annual meeting in San Francisco, US that social media is becoming increasingly important for ophthalmologists in their daily work.
It can be a source of patient referrals, he said, allowing doctors to promote their practices, 24 hours a day. It can also facilitate debates and discussions among doctors, said Prof Doan.
Facebook, said Prof Doan, is being used by some doctors to allow them to discuss clinical cases.
Another useful resource is LinkedIn, a website which allows ophthalmologists and other professionals to post information about their activities and to connect with their colleagues. It can also be accessed by patients who may want to find out more about an ophthalmologist’s practice.
LinkedIn, like Facebook, can also offer a link back to an ophthalmologist’s personal website which can provide more information for patients and other doctors.
The latest buzz word in social media is Twitter where ophthalmologists can post up-to-the-minute comments, usually no more than 20 or 30 words, on news that affects them.
On a simple level, this could mean that a young ophthalmologist attending the ESCRS Congress in Paris in September
2010 will be able to communicate with colleagues about symposia, case studies or free papers which may be of particular interest to them.
YouTube is another valuable outlet for ophthalmologists, said Prof Doan. “Uday Devgan (associate clinical professor at the Jules Stein Eye Institute at the UCLA School of Medicine) uses YouTube very effectively,” said Prof Doan. “He has a cataract and refractive surgery channel on YouTube which allows him to demonstrate his surgical techniques. His YouTube channel is also linked back to his practice website udaydevgan.com.”
A survey carried out by Prof Doan at the University of Iowa showed that Internet resources were preferred by the majority of students over textbooks, medical journals and lecture notes.
“Young ophthalmologists want information that is rapidly accessible,” said Prof Doan. “They want the information on their iPhone and on their BlackBerry. “
Dr Oliver Findl, chairman of the ESCRS Young Ophthalmologists’ Forum, says Prof Doan’s research on social media shows there is a need for a new approach to online education.
“I believe that social media is interesting for quick exchanges of information or
informal telemedicine. It may also be a good tool for trainees preparing for exams. The exchange of information is becoming faster and new technologies allow instant access to images of cases and allow essentially online discussion of these – telemedicine from the mobile phone,” said Dr Findl. “However, this exchange of information is also short-lived and the content found is of varying quality. A good example is many of the surgical videos shown on YouTube, some of which are low in both video quality as well as surgical technique,” he said.
“The new social media is entirely
unedited – this makes it fast and lively, however, may make it difficult to handle for the ophthalmologist in training. In the early phases of learning, especially the first few years of training, the trainee may find it difficult to separate commercial interests from actual evidence-based. This is where a good teacher or established textbook still plays a major role - they need to stand the test of time.”
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Social media may be used to complement existing training methods for ophthalmologists
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design alliance Büro Roman Lorenz MünchenFebruary 2010
WOC® 2010 Honorary PresidentProfessor Dr. Bruce E. Spivey, ICO President
WOC® 2010 Scientific Program Committee Chair:Professor Stephen J. RyanCo-Chairs:Professor Bernd BertramProfessor Gabriele E. Lang
Professional Congress OrganizerMonika PorstmannPorstmann Kongresse [email protected]
WOC® 2010 Congress President:Professor Gerhard K. LangDOG President
WOC® 2010 Executive Committee:PresidentProfessor Gerhard K. Lang
Secretary General Professor Anselm Kampik
TreasurerProfessor Jochen Kammann
Program DirectorProfessor Gabriele E. Lang
Executive Director of the DOGDr. Philip Gass
World Ophthalmology Congress® 2010Berlin, Germany
XXXII International Congress of Ophthalmology 108th DOG Congress5 - 9 June 2010
AAD Congress 20103 - 6 June 2010
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Dermot McGrath in Paris
After a successful pilot programme in Scandinavia, the Netherlands and Spain last
year, preparations are now well advanced for the launch of the online European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO) in a number
of European countries in 2010.The EUREQUO system, which is designed
to improve standards of care as well as develop evidence-based guidelines for
cataract and refractive surgery across Europe, is scheduled to go live this year in Austria, Belgium, Germany, Hungary, Ireland, Turkey, Slovakia, Italy and the UK.
Creating such a Europe-wide network of national registries requires considerable administrative, technical and logistical planning. As lead partner for the EU-funded project, the ESCRS is working closely with the various national ophthalmological societies to create effective registries to ensure maximum adoption of the EUREQUO system and the efficient implementation of the data collection.
However, while the ESCRS is responsible for coordinating the overall project, it is the national registry manager in each participating country who will play the vital frontline role in recruitment and implementing the EUREQUO initiative.
Their job is to solicit the support of relevant national health agencies, ophthalmolgical societies and medical organisations with a final objective that the national registries (or datasets) are smoothly integrated into the overall EUREQUO network.
Gill Topp, EUREQUO registry manager for the UK and Ireland, says that her initial task has been to build support for the initiative through active networking with relevant organisations.
“Since my appointment in November 2009, I have developed direct relationships with key medical societies and government agencies including the Royal College of Ophthalmologists, the Care Quality Commission and the Department of Health. I hope this strategy will ensure the support of the organisations and allow collaboration with establishing information pathways. I have also identified both NHS Trusts and Independent Clinics to approach regarding gaining their participation for the first roll-out of data collection in March 2010. This trial run will involve recording data from pre-op through to post-op for all patients operated on in March,” she said.
While it is still early days, the initial feedback from ophthalmologists in the UK and Ireland has been largely positive, she says.
“Many of the surgeons have already pre-registered their interest on the website following EUREQUO
exposure at conferences and meetings in 2009. And the feedback from surgeons I have spoken to has been positive, although naturally questions regarding administration and organisation arise. These concerns are alleviated by explanation of the web-based IT system and the support role of the registry manager,” she said.
One of the major advantages of EUREQUO is that the data collection is conducted via a secure Internet server, which allows all participants to compare the accuracy of their outcomes with those of colleagues in their own regions and other countries as well as the entire database.
Although new initiatives always have to be ‘sold’ to some degree to their target users, in the case of EUREQUO the majority of ophthalmologists need little convincing that the project will prove beneficial to them, their patients and the profession as a whole, said Ms Topp.
“I found that it is not hard to get ‘buy-in’ to the registry as many surgeons have been recording their own data for some time. They are also now quite used to data collection for audit/research/NICE purposes. The main challenge is highlighting to them that project involvement will not cost them or their teams too much time and that the IT software process for data input is effective and efficient,” she said.
Once the go-ahead has been given by all the respective national partners concerned, the next step for EUREQUO will be to start the process of inputting and validating real data from the surgical centres.
“The first data collection roll-out is very important as it is crucial to input real data into the system. This will then allow us to access and compare real results. It will also allow us to identify any further project needs in terms of IT, administration requirements and so forth. This initial collection of data will be taken from a small cohort of NHS Trusts and private practices who have a good geographical and case mix with high surgical volumes. It will also derive from surgeons who have requested user information and highlighted their interest via the website,” she said.
With the UK and Ireland roll-out very much on schedule, the battle to win hearts and minds will continue in earnest throughout 2010, with EUREQUO promotions scheduled at the 14th ESCRS Winter meeting in Budapest, as well as the United Kingdom and Ireland Society of Cataract and Refractive Surgeons (UKISCRS) satellite meeting in Liverpool and the UKISCRS annual meeting in Brighton.
Surgeons wishing to register their interest in EUREQUO can do so at www.eurequo.org/join.asp.
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EUREQUO
EUREQUO gathers momentum for UK and Ireland roll-out with assistance of key organisations
European Registry of Quality Outcomes for Cataract & Refractive Surgery
EUREQUO
What is EUREQUO?
Improve treatment and standards of care for cataract and refractive surgery
Develop evidence-based guidelines for cataract and refractive surgery across Europe
Make significant impact on the exchange of best practice between practitioners in relation to patient safety
1
2
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The project aims to:
EUREQUO is a European Quality Registry for visual outcomes of cataract
and refractive surgery
Join the network
EUREQUO gives a unique opportunity to monitor and compare results
Quality registries create a sufficient basis for studying rare diseases, treatments and complications
Collecting data will support you to make an audit report
The collection of your data will facilitate the analysis of surgical outcomes and the development of evidence-based European Quality Guidelines
See www.eurequo.org for more information
Gill Topp
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The ideal refractive and lens surgery would allow patients to detect and recognise large and small objects, of
high and low contrast, at all distances and under all lighting conditions.
Numerous scientific studies regarding quality of vision after refractive surgery or intraocular lens implantation (multifocal, aspheric, phakic, etc) have been published in recent years. However, what is the meaning of the term quality of vision and, more importantly, how can it be accurately measured? Because image degradations involve a subjective interpretation of an image, detailed questionnaires (psychometric testing) have been developed; in a recent world literature review of quality of life and patient satisfaction after LASIK surgery, it was demonstrated that it has a higher satisfaction rate (95.4 per cent) compared with several other elective procedures and it has influenced the quality of life of these patients.1
However, visual acuity, wavefront measurement, contrast sensitivity evaluation and subjective and objective perception of unwanted visual effects such as haloes, glare, shadows and starburst provide a more complete measure of the patient’s quality of functional vision. As Rosen wrote “we are now able to measure all these parameters to convince ourselves what one technique or one lens is better than another, which almost assumes a universality of the human response in both sexes and all ages”.2
Visual acuity remains important to determine the quantity of vision in relation to the optical impact of low-order aberrations. Waterfront measurements are also crucial to determine the optical impact of high-order aberrations giving the optical quality of the eye in terms of spatial distortion but contrast sensitivity measures the total performance of the visual system.
Multiple scientific studies have demonstrated that contrast sensitivity, which declines with age even in the absence of ocular pathology, represents a robust indicator of functional vision. The contrast sensitivity function measured under varying conditions of luminance and glare, establishes the limits of visual perception across the spectrum of spatial frequencies and determines the relationship between the optical efficiency of the eye and the minimum retinal threshold for pattern detection. Therefore, contrast sensitivity testing effectively describes the function of the physiologic visual system as a whole.
Quantitative computerised psychophysical approaches offer substantial advantages over previously used classical clinical semi-quantitative tests that have been used to assess CS after refractive surgery. These conventional tests including the Pelli-Robson test charts, CSV 1000 and Vistech tables,
probe mainly central vision and in photopic conditions. There is a lack of published studies using more accurate CS methods, in particular under background luminance in the scotopic–mesopic range which may be more sensitive to optical changes than photopic conditions. Furthermore, patients frequently report symptoms such as glare disability only in the scotopic–mesopic range. Most of these clinical tests lack standardisation of lighting conditions, of correlation with symptoms and full scientific validity being therefore hard to interpret by the physician and the patient. They provide limited quantification power and do not allow for the extraction of participants’ reliability parameters, due to lack of stimulus randomisation and poor calibration3 while quantitative psychophysical computerised methods are much more sensitive and reproducible. This is due to the fact that testing steps can be calibrated and dynamically changed in a random manner, in a way that is unpredictable for the observer, allowing for the extraction of confidence parameters concerning subjects’ performance and reliability. This computerised testing approach uses interleaved staircases keeping attention homogeneously distributed over the visual field, being less prone to artefacts than classical methods.
In a recent study, we adopted a novel method, the Intermediate Spatial Frequency (ISF), to assess spatial vision at an intermediate spatial frequency (3.5 cpd) under mesopic CS testing conditions.4 This test strategy measures simultaneously visual
performance in the central and peripheral regions (central 20°) and makes the best compromise to measure visual sensitivity across multiple regions in visual space, in particular in myopic eyes (Figure 1). The rationale for the choice of Intermediate Spatial Frequency (ISF) testing conditions is based on the fact that this spatial frequency is near the acuity limit for peripheral vision, thereby best isolating the parvocellular (high resolution system) in that part of the visual field. That same spatial frequency is near peak sensitivity in central vision in spite of less specifically isolating the parvocellular system near the fovea. Indeed, under these conditions CS performance decays steadily from the centre to the visual periphery, as is typical for the parvocellular pathway, and unlike conditions that isolate the low resolution magnocellular pathway. It has been shown that these parvocellular test conditions are better to test loss of retinal sampling, due to photoreceptor damage, rather than magnocellular testing approaches.5 In the former case there is less photoreceptor convergence which enables testing of subtle losses in retinal sensitivity.
These new and comprehensive quantitative methodologies to evaluate CS under mesopic conditions have several advantages: quantitative calibration, presence of reliability criteria, reproducibility and multifocality (since it gathers data from many locations). In fact, its sensitivity is sufficient to detect even physiological asymmetries. CS perimetry is performed in central locations and in
more peripheral regions (up to 20º), while previously studies exclusively tested central regions of the visual field (Figure 2).
The development of precise, reproducible and accurate methodologies to obtain objective measurements of quality of vision, namely night vision, are mandatory in order to create surgical techniques that maximise the quality and function of vision, preventing or surgically correcting high order aberrations and decreasing or eliminating post-refractive vision disturbances.
Joaquim Neto Murta MD, PhD is director of the Department of Ophthalmology, University Hospital Coimbra, EPE, Portugal.
1. Solomon K , Castro LF, Sandoval HP et al. LASIK World literature review. Quality of life and patient satisfaction. Ophthalmology 2009;116:691-7012. Rosen E. Quality will always distinguish itself. J Cataract Refract Surg 2007;33:173-1743. Fan_Paul NI, Li J, Miller JS, Florakis GJ. Night vision disturbances after corneal refractive Surgery. Surv Ophthalmol 2002;47:533-46.4. Murta JN, Caixinha M, Silva MF et al. Twelve months evaluation of quality of vision after LASIK (Planoscan vs Zyoptix). Comparison of different new methodologies (submitted for publication)5. Maia-Lopes S, Silva ED, Silva MF et al. Evidence of widespread retinal dysfunction in patients with stargardt disease and morphologically unaffected carrier relatives. Invest Ophthalmol Vis Sci 2008;49:1191-9.
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Methods to evaluate quality of visionby Joaquim Neto Murta
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Figure 2. CS in the emmetropic control group, in all myopic patients (pre-op) and in the post-op three months and 12 monthsFigure 1- Contrast sensitivity (Intermediate Spatial Frequency, ISF) examination. Basic scheme of the Visual Field locations. Sinusoidal gratings were used as
detection target stimuli
Binkhorst Lecture: Looking Back, Looking Ahead
ASCRS Lecture on Science and Medicine: Managing Medical Errors:How to Talk with Your Patient and Live with Yourself
ASCRS Government Relations Committee Panel Discussion: What in the World is Going on with Health Care?
Charles D. Kelman’s Innovator’s Lecture: Evolution of Surgical Pharmacology: Reviewing the Past and Looking to the Future
Fea
ture
Many patients are willing to pay more for the refractive benefits promised by premium intraocular
lenses. This has made presbyopia-correcting and toric IOLs among the most profitable items for ophthalmic device manufacturers and surgeons alike.
When the indication for implanting premium lenses is primarily refractive, it’s expected that the patient will pay the entire cost out of their own pocket, just as they do for LASIK and other refractive procedures. This practice is generally considered ethical and appropriate in part because most patients have other choices, including spectacles or contact lenses, to avoid significant disability due to refractive error.
The risk-benefit calculation is fairly straightforward – patient and surgeon weigh the potential refractive and lifestyle improvements against the costs and risks
of surgery. There is no necessity to treat an underlying disease state to complicate the question. If anything, the presence of an ocular disease, particularly corneal or retinal defects, often gravitates against refractive surgery.
More often, though, premium IOLs are implanted in patients with cataracts. And volume goes up dramatically when state-sponsored insurance plans cover the cost of standard cataract surgery, but allow surgeons to bill patients directly for the extra cost of the lenses and additional services needed to implant them. This practice also is justified on the grounds that patients are receiving a premium product and a premium service with the expectation of a premium outcome. But the fact that the primary indication for surgery generally is to treat cataracts creates the potential for a conflict of interest.
“Multifocals do give a benefit, but they also have drawbacks,” notes Oliver Findl MD, who heads the ophthalmology service at Hanusch Hospital, Vienna, and is a consultant at Moorfields Eye Hospital, London. Reduced contrast sensitivity, poor night vision, glare and haloes are among them. Indeed, dysphotopsias of various types are by far the leading cause of multifocal lens explants, according to explants reports collected by researchers at the University of Utah, US. “Used conservatively, they have a place in the surgical armamentarium. But many patients would be satisfied with standard lenses, and many cannot tolerate multifocals.”
The problem with allowing surgeons to charge extra for premium lenses is that it creates pressure, conscious or not, to push patients who may not be good candidates to select premium lenses, Dr Findl believes. He notes that in addition to markups on the lens, the fees charged for the extra services that go along with refractive cataract surgery often are out of proportion for the actual work done. “It is sometimes €600 or €700 more than the lens costs. This has become an incentive to put in the premium lens.”
Moreover, peer pressure can be intense to both offer premium services and keep the fees high, Dr Findl observes. “Your colleagues are doing the premium lenses and advertising them, and patients are starting to demand that they be offered. The doctor is in a situation where you not only need to offer the technology, but you also need to push it as much as possible to stay competitive.” He has spoken to several surgeons in the US, where patient copayments for multifocal lenses began with a special
dispensation from the state-run Medicare program in 2005, who are uncomfortable with this situation, but feel they will be ostracised if they speak out.
“My biggest concern is that the indication for using the technology is possibly not the same as if you had less incentive financially,” Dr Findl says. “You may not intend it, but in the real world there is the pressure of the market, the financial pressure of having a large office and lots of staff, and that pressure can be resolved as a change in clinical behaviour. You want to avoid the incentive to go down that road.”
Dr Findl believes surgeons have an ethical duty to resist. “At this point we are getting further away from what we would call delivering healthcare for a disease called cataract. The companies are pushing for copayments in Europe because their profit margins are high. We have to make sure we don’t get dominated by these pressures.”
Standardising extra fees
Still, multifocal, toric and other premium lenses do offer many patients significant benefit. And they do require additional services to implant. Dr Findl believes that these technologies should be available. He also believes that potential financial conflicts could and should be minimised by standardising copayments for premium services.
To establish reasonable copayment rates, Dr Findl suggests a cost study to determine the actual value of the extra services needed for premium lenses. Multifocal lenses require more chair time for informed consent and possibly more exact biometry. Toric lenses require corneal topography as well as additional time for calculations and to mark the lens axis on the patient’s eye before surgery. Dr Findl suspects that the total added time for implanting a premium lens might be 15 to 20 minutes for the doctor. The cost of additional equipment,
administrative time to order custom lenses and the cost of touch-ups might also be factored in.
Once these costs are known, fees should be established that compensate the surgeon at rates comparable to other services, Dr Findl says. “Then the incentive to implant a premium lens is not my own financial gain, it is for the patient’s benefit. I can make the decision without a conflict.” Regulating allowable fees for these extra services in state systems also would reduce market pressures to push premium lenses, he believes.
Kevin Corcoran of the Corcoran Consulting Group, San Jose California, US, recommends creating a fee based on a bundle of services. He suggests listing all the possible services you might provide before and after surgery for a refractive cataract case, establishing a fee for each and then multiplying each by the likelihood that you will need to deliver the service.
For example, if you do a personality and lifestyle inventory to screen patients, it costs €30 and you do it for 100 per cent of patients, add €30 to the bundled fee. If you do LASIK or other touch-ups, they cost €800, and you do them 10 per cent of the time, add €80. A package fee makes it easier to market presbyopia-correcting lenses to patients, while giving you the flexibility to determine which services are appropriate for each patient, Mr Corcoran notes. He also recommends clearly stating to patients which services are covered by insurance and which are the patients’ responsibility. A package fee helps make this clear.
The bottom line is that patients’ welfare should drive treatment decisions, Dr Findl says. “We are doctors and the Hippocratic Oath is what medicine believes. We have to be calm and think about the ultimate goal and not get distracted by financial incentives.”
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Practice Development
Standardising out-of-pocket fees for premium IOLs may help avoid financial conflict of interest
by Howard Larkin
“We are doctors and the Hippocratic Oath is what medicine believes. We have to be calm and think about the ultimate goal and not get distracted by financial incentives”Oliver Findl MD
Don’t MissIn Your Good Books
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The problem with allowing surgeons to charge extra for premium lenses is that it creates pressure, conscious or not, to push patients who may not be good candidates to select premium lenses, Dr Findl believes
37
Toric intraocular lenses are a good example of a new technology that offers huge potential clinical benefits
for patients. That same technology, however, also
poses significant challenges for surgeons. Among those challenges are the
complex calculations to determine lens power and axis, accurately aligning the lens with the desired axis during surgery, and keeping incisions small to minimise surgically induced astigmatism.
By combining its broad expertise in ophthalmic systems, including surgical microscopes and diagnostic equipment, with advanced software integration and surgical products including microincision and multifocal toric lenses, Carl Zeiss Meditec provides solutions that both improve patient care and make surgeons’ lives easier, says Michael Kaschke PhD.
Dr Kaschke’s 20-month tenure as the firm’s president and CEO, in which he plotted a new course for growth known as “RACE 2010”, is set to end this month as Ludwin Monz PhD will take the executive reins. Shareholders are expected to return Dr Kaschke to his former position as chairman of Carl Zeiss Meditec AG’s supervisory board.
A customer-focused, solution-based approach to specifically identified clinical and practice management challenges is at the heart of Dr Kaschke’s market strategy.
“Too often, technology is developed in search of a problem,” he says. “We do not start from the technology. We start from the ‘pain points’ in our customers’ lives and ask ‘what are the solutions?’ You have to understand and define the problem first before you can solve it.”
For toric lenses, IOL calculations are one such “pain point.” To relieve it, Carl Zeiss Meditec developed Z CALC, an online calculator for ZEISS toric IOLs based on a sophisticated and highly reliable algorithm. Based on biometric data and the refractive target, the calculator generates appropriate sphere and cylinder powers along with an axis alignment screen transparency that can be printed out to guide lens alignment during surgery.
With Carl Zeiss, surgeons could eliminate another “pain point”: aligning the toric lens during surgery – with Z ALIGN. Part of the CALLISTO eye OR Cockpit, this video tool projects reference and cylinder alignment axes on a video image of the surgical field during surgery. This eliminates the need to refer to paper diagrams during surgery, making lens alignment easier and faster. Sophisticated eye tracker technology keeps the projected transparency centred, helping ensure that the accurate axis alignment
that is so critical to a successful astigmatism correction is achieved.
To minimise the chances that all that precision work will be spoiled by the unpredictable astigmatism induced by a large incision, Carl Zeiss Meditec offers aspheric monofocal bitoric and multifocal toric IOLs that can be injected through a sub 2.0mm incision. Because it is toric on both surfaces, the monofocal AT TORBI provides better imaging quality far beyond the range of monotoric designs. The AT LISA toric is the only microincision lens on the market that can correct sphere, cylinder and presbyopia.
“All of our technologies work together for a better clinical outcome,” Dr Kaschke says. “This is a new approach and we can demonstrate already that it is widely accepted by our customers.”
It’s an approach that Dr Monz, who previously headed the Ophthalmic Systems and Microsurgery divisions of CZ Meditec, intends to embrace. “I am looking forward to my new role and will continue to pursue the path oriented to sustainable growth that has already been adopted,” Dr Monz says.
Better care through data sharing
Accurate ophthalmic diagnoses often rely on combining information from multiple diagnostic modalities. Traditionally, this has been done manually using printouts of various instruments. This paper-based approach is not only cumbersome – it can only be done when the doctor has access to the entire paper record – it also carries the risk that data will be overlooked or lost in the shuffle. It is also expensive and difficult to administer paper records, and it complicates billing for services.
Carl Zeiss Meditec’s solution is two-fold: first, develop instruments using the DICOM data standard, which enables different devices to communicate with each other. This also makes ZEISS instruments compatible with those made by other manufacturers adhering to the DICOM standard, which Dr Monz says is emerging as the accepted industry standard.
Second, Carl Zeiss has created FORUM, an eye care data management system that includes a central data archive supporting
a variety of clinical and administrative functions. Fully compatible with electronic health record standards, FORUM greatly improves administrative efficiency by eliminating the need to re-enter patient data for every visit or on the different instruments. Patient data are entered once and electronically transferred to the instruments by a so-called ‘worklist’. The exam data are sent into the central archive. This makes office personnel more productive, reduces data entry errors and improves charge capture for services rendered, Dr Monz says.
FORUM also makes it possible for physicians to view a patient’s entire record, including test data, at any time from any location. This allows better evaluations and consultations with patients.
Even more important, FORUM creates a powerful tool for combining clinical test results, Dr Monz adds. “It is not just easy and efficient, there is a clinical value.” One example is the retinal workstation. “Fundus camera images and OCT data are brought together for the doctor on one screen. Having the diagnostic data next to each other makes it easier to make a diagnosis.”
In the field of refractive laser surgery, Carl Zeiss Meditec is developing a completely new treatment modality that could revolutionise laser vision correction by enabling surgeons to perform minimal invasive procedures using the VisuMax femtosecond (fs) laser only. The so-called SMILE procedure uses the fs-laser to cut an intrastromal lenticule which is then removed through a small incision without cutting a flap. This method aims at preserved biomechanics and a reduced incidence of dry eye because Bowman’s layer remains intact. Safety and efficacy outcomes in more than 250 cases are very promising, Dr Kaschke says.
Already close to market is the FLEx procedure, set to launch in April 2010. FLEx also uses the VisuMax femtosecond
laser to cut an intrastromal lenticule. However, this lenticule is removed after opening a conventional corneal flap. FLEx offers distinct advantages, specifically for correction of high refractive errors as the accuracy of the procedure is not affected by ambient room conditions, corneal hydration or other factors typically affecting excimer laser ablations. Refractive outcomes in more than 600 eyes are comparable to LASIK, Dr Kaschke says. It’s also easier and much faster for the surgeon because it’s a single step procedure using just one laser. Both procedures can be performed using the existing VisuMax laser with upgrades. “This is our idea of a step-wise solution. The doctor takes the first step today while yet another procedure is currently in development which he will get as an upgrade; so he does not have to spend a half-million dollars for a new machine every three years.”
The success of this approach is reflected in Carl Zeiss Meditec’s 2009 results. For the fiscal year ending September 30, 2009, revenues were @640m, up from @600m the previous year. Regionally, the company achieved its highest growth rates in the “Asia/Pacific” region, where growth was 21.1 per cent. The “Americas” region continues to account for the largest share of revenue, generating 35.6 per cent. Sales in Germany were up 2.9 per cent, though revenues for Europe/Middle East/Africa were down 3.0 per cent. Ophthalmic systems, including diagnostic and OR instruments, saw 9.0 per cent growth, while surgical ophthalmology, including lenses and consumables, grew 6.8 per cent.
“Our professed aim is to achieve sustainable, profitable growth,” Dr Kaschke says. “We are continuously working towards this goal with our RACE 2010 programme. We expect revenue growth in financial year 2009/2010 to again be at least on a par with market growth.”
Fea
ture
Outlook on Industry
Carl Zeiss Meditec feels your ‘pain point’ – and offers solutionsby Howard Larkin
FORUM eye care data management VisuMax
Fea
ture
State-controlled health insurers can enforce a mandatory retirement age for ophthalmologists under a new
ruling from the European Court of Justice.In the case, the EU’s highest court ruled
that a German regulation that required a dentist to retire from the country’s health insurance system at the age of 68 years did not infringe the EU’s ban on age discrimination.
The court based its decision on the finding that such a retirement age is legal if it protects the finances of public health services or promotes employment opportunities for younger dentists.
The court’s decision, which applies equally to ophthalmologists and all other health practitioners who work for the state or a state-sponsored health insurer, is a blow for older practitioners who want to remain in public practice beyond their statutory retirement age.
Although the court decision affects public service work, it does not affect the right of ophthalmologists or any other health practitioners to engage in private practice. Whether an older ophthalmologist can continue in private practice will remain a matter for the individual ophthalmologist.
The German case arose over Dr Domnica Petersen, who joined the dental panel of the German statutory health insurance scheme in the District of Westphalia and Lippe in 1974. In June of 2007, after Dr Petersen had reached the mandatory retirement age of 68 years, the Admissions Board that determined who could practise on the public dental panel removed her from the district’s panel according to the scheme’s retirement rule.
Outside the public panel system, Dr Petersen – like any other German dentist or doctor – could practise the profession privately until infirmity or death if she chose. Engaging in private practice outside the state health insurance scheme, however, is no easy matter. Some 90 per cent of German patients are covered by the public statutory scheme.
In light of such difficulties, Dr Petersen appealed her forced retirement, ultimately bringing a lawsuit against the Admissions Board for Dentists for the District of
Westphalia and Lippe in the Social Court in the city of Dortmund.
Before that court, Dr Petersen challenged the panel’s retirement age as contrary to the EU Directive on Equal Treatment in Employment and Occupation. The directive generally prohibits an employer from discriminating against an employee on the basis of religion or belief, disability, age or sexual orientation.
The directive, however, provides that the general prohibition does not preclude an employer from enforcing age limits on hiring or retiring if “by reason of the nature of the particular occupational activities concerned or of the context in which they are carried out, such a characteristic constitutes a genuine and determining occupational requirement, provided that the objective is legitimate and the requirement is proportionate.”
In particular, the directive provides that an EU country “may provide that differences of treatment on grounds of age shall not constitute discrimination, if, within the context of national law, they are objectively and reasonably justified by a legitimate aim, including legitimate employment policy, labour market, and vocational training objectives, and if the means of achieving that aim are appropriate and necessary”.
In interpreting the directive in Dr Petersen’s case, the Dortmund Social Court was also faced with conflicting rulings in previous German cases involving doctors. In one case, a German court had ruled that the mandatory retirement age was necessary to protect patients from doctors whose abilities may have declined because of their
age. In a second case, another German court had ruled that doctors could be forced to retire at a certain age to allow young doctors to have an opportunity to enter and practise medicine.
Faced with such conflicting reasons, the Dortmund court asked the European Court of Justice to determine whether the mandatory retirement age could be justified by either of the two reasons:
1. “To protect patients insured under the statutory health insurance scheme against the risks presented by older panel dentists whose work is no longer the best.”
2. “To ensure a balanced sharing of burdens between the generations and remains of use for preserving the employment opportunities of young panel dentists.”
In its decision, handed down in Luxembourg on January 12, the Court of Justice rejected the first reason for a mandatory retirement age – to protect the health of individual patients. In doing so, it pointed out that there was no mandatory retirement age for dentists in private practice.
“A measure to which there is so broad an exception as that for dentists practising outside the panel system cannot be regarded as essential for the protection of public health,” the court ruled. “If the aim of the age limit at issue in the main proceedings is the protection of patients’ health, from the point of view of the competence of the practitioners concerned, clearly patients are not protected where the exception applies.
The exception thus appears to run counter to the objective pursued. Moreover, it is not limited temporally and, although no figures have been supplied, it potentially applies to all dentists and appears liable to concern a not inconsiderable number of patients.”
Although the Court of Justice rejected a reason based on the potential risk that an older dentist might pose to the health of an individual patient, the court did accept that an EU country could enforce a mandatory retirement age if it could show that the regulation benefited health generally by preserving “the financial balance of the public healthcare system”.
“The introduction of an age limit which applies only to panel dentists, in order to control public health sector expenditure, is compatible with the objective pursued,” the court observed. “The fact that dentists practising outside the statutory health insurance scheme are not concerned does not therefore interfere with the consistency of the legislation in question. Insofar, therefore, as the measure maintaining that age limit is intended to prevent a risk of serious harm to the financial balance of the social security system in order to achieve a high level of protection of health, which is for the national court to ascertain, the measure may be regarded as compatible with the directive.”
The EU court also accepted the second reason for a mandatory retirement age – to preserve opportunities for young panel dentists. In coming to that finding the court held that “the encouragement of recruitment undeniably constitutes a legitimate social policy or employment policy objective of the Member States, and that that assessment must evidently apply to instruments of national employment policy designed to improve opportunities for entering the labour market for certain categories of workers.
“Similarly, a measure intended to promote the access of young people to the profession of dentist in the panel system may be regarded as an employment policy measure,” the court added.
“In this respect, in view of developments in the employment situation in the sector concerned, it does not appear unreasonable for the authorities of a Member State to consider that the application of an age limit, leading to the withdrawal from the labour market of older practitioners, may make it possible to promote the employment of younger ones.”
For details about the case, Domnica Petersen –v- Berufungsausschuss für Zahnärzte für den Bezirk Westfalen-Lippe (C-341/08), please visit the website of the EU Court of Justice at www.curia.eu.
38
EU Matters
by Paul McGinn
Mandatory retirement age does not discriminate against ophthalmologists in public practice
Whether an older ophthalmologist can continue in private practice will remain a matter for the individual ophthalmologist
Ind
ust
ry N
ews
Alcon to purchase US rights for topical eye care products from Sirion Therapeutics, Inc
Alcon has announced that it will purchase the US rights for two FDA-approved topical eye care products from Sirion Therapeutics, Inc. The first is Durezol™ (difluprednate ophthalmic emulsion) 0.05 per cent, an ophthalmic corticosteroid approved for the treatment of inflammation and pain associated with eye surgery. The other is Zirgan™ (ganciclovir ophthalmic gel) 0.15 per cent, a recently approved antiviral for the treatment of acute herpetic keratitis. Alcon also acquired the global rights, excluding Latin America, for Zyclorin™ (cyclosporine), which is currently in clinical development to treat dry eye and other ocular surface diseases.
New company to offer specialised training courses for ophthalmologists
Advanced Ophthalmic Trainings is a new company founded with the goal of offering highly specialised advanced training courses for ophthalmologists. The company has announced that its first international advanced training course is now fixed and ready for registrations – a comprehensive training course on ophthalmic and oculoplastic reconstruction and trauma surgery in which the participants will be trained directly on human specimens. This hands-on advanced training course is hosted by Prof Ursula Schmidt-Erfurth MD, and directed by Prof Franz-Josef Steinkogler MD, and Asst Prof Stephan Kaminski MD. It will take place in April 2010 in Vienna.
www.ophthalmictrainings.com/en
Presbia announces new appointments to Medical Advisory Board
Jorge L Alio MD, PhD, of Madrid, Spain, and Kerry K Assil MD of Beverly Hills, Calif., are the latest high-profile surgeons to join the Medical Advisory Board of start-up company Presbia. The company recently announced that its Flexivue™ micro-lens received CE certification for its products sold within the European Economic Area (http://en.wikipedia.org/wiki/European_Economic_Area). The Flexivue is a three-millimetre-diameter optical lens that is implanted in the cornea, by the creation of a pocket using a femtosecond laser. The developers believe the product will provide a safe, effective, permanent yet reversible correction of presbyopia.
www.presbia.com
New CEO is appointed at Carl Zeiss Meditec
Dr Ludwin Monz is the new chief executive officer at Carl Zeiss Meditec. Former CEO Dr Michael Kaschke will return to the company’s Supervisory Board. The US subsidiary Carl Zeiss Meditec Inc., Dublin, CA will be headed by Dr Ralf Kuschnereit, president & CEO.
www.meditec.zeiss.com/
BV Group has increased its stake to 19.3% in Ziemer
Swiss investment company BV Group has increased its stake to 19.3 per cent in Ziemer, a company known for its innovations in ocular diagnostics and refractive ocular surgery products. The Ziemer family will remain the majority shareholder. The move should allow the company to expand product development and international marketing.
www.ziemergroup.com
Biotech company announces launch of its ENVISION Clarity Trial
US biotech company Acucela has announced the launch of its ENVISION Clarity Trial, a Phase 2 clinical trial of ACU-4429, an investigational oral treatment for dry age-related macular degeneration. The company says ACU-4429 is one of the only treatments in development that works to slow the eye’s visual cycle for processing light. By slowing this cycle, ACU-4429 has demonstrated the ability to decrease the levels of toxic by-products in the eye and thereby potentially stop the advance of dry AMD.
www.acucela.com
pSivida Corp report promising results from study of Iluvien®
The pSivida Corp reported promising 24-month results from the Phase III FAME™ study of Iluvien® (sustained release fluocinolone acetonide) for the treatment of diabetic macular oedema being conducted by pSivida’s collaborative partner Alimera Sciences. The FAME study was designed as two Phase 3 pivotal clinical trials (Trial A and Trial B). 956 patients with DME were enrolled and randomised to receive either a high dose Iluvien (0.45 µg/day), a
low dose Iluvien (0.23 µg/day) or a sham insertion. The primary efficacy endpoint was met with statistical significance for both doses of Iluvien in each of Trial A and Trial B, as well as on a combined basis. Based on these and other data, Alimera plans to file for approval of the low dose of Iluvien for the treatment of DME in the second quarter of 2010, followed by registration filings in
various European countries and Canada. Submission of the NDA will be based on the month 24 safety and efficacy data while the FAME Study will continue to month 36.
www.psivida.comwww.alimerasciences.com
39
Recent developments in the vision care industryIndustry News
BD launches expanded line of instruments
BD Medical – Ophthalmic Systems, a unit of BD (Becton, Dickinson and Company), recently announced the worldwide launch of its expanded line of the BD Visitec™ stainless steel single-use instruments at the XXVII Congress of the ESCRS in Barcelona, Spain.
With the addition of 30 new instruments and customised trays, healthcare facilities have the potential to increase efficiency by eliminating the need for costly and time-consuming re-sterilisation of each product.
“BD is pleased to expand our offering of single-use microsurgical instruments to meet the challenges of infection transmission prevention and help facilities around the world comply with strict safety requirements,” said Doug Lawrence, vice-president and general manager, BD Medical - Ophthalmic Systems. “This launch reflects BD’s continued commitment to developing safety-engineered, single-use medical devices to protect patients and healthcare workers against the threat of cross contamination and bloodborne diseases.”
www.bd.com/ophthalmology
Haag-Streit introduces LED powered slit lamp
Haag-Streit says the new LED powered slit lamp delivers its sharpest, brightest and most homogeneous slit ever. “The light spectrum is specially designed for Haag-Streit to fulfil the high quality standard and matches the well established tungsten light. This ensures best details in diagnosis from the cornea to the retina,” said a company spokesman. “In terms of economic efficiency, the new LED technology brings significant improvements. Due to the high lifetime of the LED illumination, no more bulbs must be exchanged in future. Combined slit and background illumination control results in best ergonomics,” he said.
New ProductsCompany News
Clinical Trials
What can be more humdrum than taking a taxi from an airport into a city? Unless, that is, the
taxi is a luxurious motor launch and the city is Venice – then it’s hard not to feel some kind of thrill when the captain hands you aboard, you settle into the leather-seated interior and the boat takes off like a flightless bird, slicing through the water of the Adriatic.
In his Companion Guide to Venice, the British art historian Hugh Honour wrote that to approach Venice in any way but by sea “is like entering a palace through the back door”. You will understand what he means when, from the lagoon, your first view of the city is the majestic white dome of the Church of Santa Maria della Salute. Punctuating the low skyline of Venice, as indistinct in its envelope of mist as a painting by Turner or Monet, it is the iconic symbol of Venice.
In Venetian terms, the church is not old; it dates from the mid-17th century when it was built in thanksgiving to “Our Lady of Good Health”, whose intercession was credited with halting a plague that had raged for two years and killed more than one-third of the population of Venice. The competition for the design of the church was won by an unknown, 26-year-old architect, Baldassare Longhena. He promised a building that would be “strange, worthy, and beautiful”. And that does describe Longhena’s octagonal Venetian Baroque building which, though supported by over one million wooden piles, seems to float near the tip of the Dorsoduro, the west bank of the Grand Canal.
One of the six sestieri or areas of Venice, the Dorsoduro (Italian for “hard ridge”) has always been considered less fashionable than the facing bank which is home to St Mark’s Basilica and the Doge’s Palace. But from the tourist’s point of view that works in Dorsoduro’s favour. Far less congested and in many ways more atmospheric than the sestieri across the Grand Canal, the area is mysterious and misty in the winter and in summer cooler and more tranquil. With its narrow streets and hidden alleys, Dorsoduro yields up its treasures one by one as if it were turning over playing cards.
Although it’s linked with the opposite shore by the Accademia Bridge and the number one waterbus, you can make crossing the Grand Canal an authentic Venetian experience in itself; take the traghetto that runs during daylight hours
from a “campo del traghetti” near the Guglie waterbus stop. (Yellow signs on house walls point you to it.) Traghetti are old gondolas, their seats stripped out to make room for passengers who stand on the short crossing, contriving to keep their balance even when the traghetto crosses the wake of a motorboat. You pay your 50 cent fare to the oarsman on arrival at a little wooden pier convenient to La Salute, the new Punta del Dogana art gallery and the Peggy Guggenheim collection of modern art.
If this very Venetian ride across the Grand Canal isn’t excuse enough to make the excursion, here are six more good reasons to visit Dorsoduro:
1. Experience La Salute The No 1 waterbus brings you right to the steps of the church; if you come by traghetto, turn left from the landing and a short walk will bring you there. Enter this Baroque masterpiece to admire the ceiling panels by Titian and Tinteretto’s famous painting, the Marriage at Cana. On the feast day of Santa Maria della Salute, November 21, a temporary pontoon bridge links La Salute with the San Marco district. Venetians carrying candles walk across to pay their respects and gondoliers bring their oars for a blessing.
2. Visit the Punta della Dogana The only building further out to sea than La Salute, is the low-lying Dogana, a 17th century maritime Customs House recently remodelled by the Japanese architect, Tadao Ando into a chic contemporary art gallery; it opened in June 2009 to house one-half of the ongoing ‘Mapping the Studio’ exhibition made up of art works belonging to the French billionaire Francois Pinault. The other half of the exhibition can be seen in the Palazzo Grassi which also belongs to Mr Pinault. The two museums share a website: www.palazzograssi.it. Opening hours are 10:00 to 19:00, with the last entrance at 18:00. Closed Tuesdays and from December 24 to January 2.
3. Stroll down the Zattere quay If you follow around the tip of the Dorsoduro you find yourself on the Zattere, a picturesque promenade lined with 15th and 16th century palazzi and churches which front on the Giudecca Canal. Zattere means ‘raft of logs’, and it was here that the wood that floated down river from the Dolomites was landed to be made into ships’ masts and pilings for the city of Venice. Today the Zattere is popular with Venetians for its restaurants (including one whose dining tables are set out on a platform in the water) and Gilette Nico, which serves what many claim to be the city’s best ice cream.
4. See a gondola repair shop Turn left off the Zattere at the fondamento that runs along the Rio San Treviso. From here you have the best view of the boatyard, the squero. New gondolas are rarely made here (there are three other boatyards in the city) but when they are, they are built traditionally from seven kinds of wood in a process that takes up to two months to complete. The principal work in this boatyard is the repairing and maintaining of the 350 gondolas still in service in Venice. The picturesque Tyrolian-looking wooden buildings that surround the squero have been home to the same owners for generations and are the original workshops, dating from the 17th century.
5. Visit the Accademia Gallery This museum covering five centuries of Venetian painting up to the 19th century is so huge – 24 rooms – you should plan your visit in advance, it’s also a good idea to buy
your ticket online and save queueing. The Accademia was founded in 1750 as an art school, but had several homes before its move in 1807, under Napoleonic edict, to the present location at the foot of the bridge of the same name. It benefitted from Napoleon’s suppression of religious schools and convents, acquiring many extraordinary works of art. The gallery is open every day from 8:15, closes at 19h every day but Monday when it closes at 14h. You can find descriptions of the exhibitions – to help you decide which rooms to visit – as well as online ticket purchase at www.tickitaly.com.
6. Relax at the Peggy Guggenheim museum: This small palazzo, with its breathtaking view of the Grand Canal, was where the American millionaire collector lived. The rooms in which her sensational assemblage of modern art is shown still feel ‘domestic’. You can easily imagine the parties, the drinks on the terrace, the lifestyle she led here surrounded by her treasured collection. At the back of the garden is a café where you can enjoy a coffee or a light lunch. Open every day from 10:00 to 18:00. Closed on Tuesdays and on Christmas Day. For further details, visit: www.guggenheim-venice.it
For further information on the 1st EuCornea Congress, June 17-19, 2010 in Venice, in conjunction with Societa Italiana Cellulle Staminali e Superficie Oculare (S.I.C.S.S.O), [email protected] and Societa’ Oftalmologica Universitaria (S.O.U.), visit http://www.eucornea.org.
40
Head for the sights and atmosphere on Venice’s other side – Dorsoduro
Eye on TravelF
eatu
re
by Maryalicia Post
The Grand Canal and Santa Maria della Salute church in Venice, Italy
Take the taxi!Book your water taxi on arrival in the airport – there’s a desk in the arrivals’ hall – or, pre-book at www.venicewelcome.com or www.venicewatertaxi.com.
Fare from Marco Polo to most destinations is under ç100 for up to four people.
41
Endophthalmitis - more support for intracameral prophylaxis
Endophthalmitis continues to be a rare but serious complication of cataract surgery. The ESCRS endophthalmitis study published preliminary results in 2006 showing a near five-fold decrease in the rates of postoperative endophthalmitis with the use of intracameral cefuroxime. Nonetheless, a significant percentage of surgeons, particularly in the United States, have been slow to adopt this approach to prophylaxis. A new study by Dr García-Sáenz and colleagues provides further support for intracameral cefuroxime. They report an infectious endophthalmitis rate of 0.043 per cent (95 per cent confidence interval [CI], 0.02 per cent to 0.06 per cent) from October 2005 to December 2008 with intracameral cefuroxime compared with a rate of 0.59 per cent without cefuroxime, in line with the ESCRS multicentre study findings. As Dr Emanuel Rosen notes in an editorial, the efficacy of intracameral cefuroxime as a prophylactic measure against infectious endophthalmitis is now well established. However, it is not perfect. It has limited efficacy against
Gram-negative bacteria. Practical issues continue to limit its use – it is not available in prepackaged form for intracameral use; and it has to be diluted from concentrate in the operating room, giving scope for errors in dilution and contamination.
E Rosen, JCRS, “Endophthalmitis”, Volume 36, Issue 2, Pages 191-192.M García-Sáenz et al., JCRS, “Effectiveness of intracameral cefuroxime in preventing endophthalmitis after cataract surgery: Ten-year comparative study”, Volume 36, Issue 2, Pages 203-207
Safety of manual small-incision cataract surgery
Manual small-incision cataract surgery (SICS) is gaining adherents in areas where the cost or availability of phacoemulsification cataract surgery may be problematic. Is manual SICS more harmful to the endothelium than phacoemulsification? Researchers in India compared the effects of both procedures on endothelial cell counts. Their randomised study evaluated 200 patients, 100 in each group. The mean preoperative ECC by the
manual counting method was 2950.7 cells/mm2 in the phacoemulsification group and 2852.5 cells/mm2 in the SICS group and by the automated counting method, 3053.7 cells/mm2 and 2975.3 cells/mm2, respectively. The difference at six weeks was 543.4 cells/mm2 and 505.9 cells/mm2, respectively, by the manual method (P = .44) and 474.2 cells/mm2 and 456.1 cells/mm2, respectively, by the automated method (P = .98). The corrected distance visual acuity at six weeks was better than 6/18 in 98.5 per cent of eyes in the phacoemulsification group and 97.3 per cent of eyes in the SICS group. These results indicate that manual SICS is as safe for the corneal endothelium as phacoemulsification, is almost as effective, and is much more economical. This confirms that SICS can be an alternative to phacoemulsification in areas in which phacoemulsification is not available.
P Gogate et al., JCRS, “Comparison of endothelial cell loss after cataract surgery: Phacoemulsification versus manual small-incision cataract surgery: Six-week results of a randomized control trial”, Volume 36, Issue 2, Pages 247-253.
Paediatric LASEK
Once a taboo, refractive laser surgery is finding a place in the treatment of paediatric patients. Canadian researchers reviewed a series of cases to assess the refractive, visual acuity, and binocular results of laser-assisted subepithelial keratectomy (LASEK) in children with bilateral hyperopia or hyperopic anisometropic amblyopia. The review included 72 eyes of 47 hyperopic patients (0.00 to +12.50 D), ranging in age from 10 months to 17 years. One year after treatment, 41.7 per cent of eyes had improved corrected distance visual acuity. The mean anisometropic difference in the hyperopic anisometropic amblyopia subgroup (18 eyes) improved from 4.39 D preoperatively to +0.51 D at one year.
W Astle et al., JCRS, “Laser-assisted subepithelial keratectomy for bilateral hyperopia and hyperopic anisometropic amblyopia in children: One-year outcomes”, Volume 36, Issue 2, Pages 260-267.
JCR
S H
ighl
ight
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by Thomas Kohnen
Journal of Cataract and Refractive Surgery jointly published by the ESCRS and ASCRS
JCRS Highlights
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Bifocals may delay paediatric myopic progression
Bifocal glasses may be effective in slowing the progression of myopia in children with high rates of progression. Researchers conducted a randomised controlled clinical trial among 135 Chinese Canadian children with progressive myopia. Participating children were assigned to one of three treatment groups: 41 wore single-vision lenses, 48 wore bifocals and 46 wore bifocals with prism. Progression of myopia was most rapid among those who wore single-focus lenses, slower among those who wore bifocals and slowest among those who wore prismatic bifocals. Because the fundamental characteristics of myopia likely do not vary by ethnic group, the results would likely apply to other children with rapidly progressing forms of the condition, the authors note.
D Cheng et al, Arch Ophthalmol., “Randomized Trial of Effect of Bifocal and
Prismatic Bifocal Spectacles on Myopic Progression”, 2010;128[1]:12-19.
Smoking gun
Smoking continues to increase the risk for age-related macular degeneration (AMD) even among patients more than 65 years old. After age, smoking is the second most common risk factor for AMD. Investigators sought to determine whether age influences the effects of smoking on AMD risk. They followed a group of 1,958 women who underwent retinal photographs at five-year intervals, starting with a baseline exam at age 78. Four per cent of the women smoked. Overall, women who smoked had 11 per cent higher rates of AMD than other women their same age. In women over 80, however, those who smoked were 5.5 times more likely to develop AMD than women their age that did not smoke. In addition, after confounder adjustment, alcohol consumption was significantly associated with an elevated risk of incident early AMD.
A Coleman et al., American Journal of Ophthalmology, “The Association of Smoking and Alcohol Use With Age-related Macular Degeneration in the Oldest Old: The Study of Osteoporotic Fractures”, Vol. 149, Issue 1, 160-169.
Lead-based eye makeup to treat infection?
Some 4,000 years ago, the ancient Egyptians used lead to make eyeliners with purported medical properties. Chemistry researchers attempted to evaluate the impact of very small amounts of lead on skin cells. Results showed that, at low dosages, lead does not kill skin cells. Instead, it leads to the production of nitrogen monoxide, which is known to activate the immune system. The researchers looked into laurionite, a lead chlorate among the salts synthesised by the ancient Egyptians, and at its action on an isolated skin cell. Laurionite can trigger the presence of Pb2+ lead ions in the eye or on the skin, at sub-micromolar concentrations.
After depositing very small quantities of laurionite solution on a keratinocyte, the scientists were able to observe the overproduction of tens of thousands of NO° nitrogen monoxide molecules. This plays a major role in the regulation of blood pressure. It stimulates the arrival of macrophages, which ingest bacteria, and favours their passing through capillary and blood vessel walls. These findings appear to support the claims in ancient medical texts, the researchers report.
I. Tapsoba et al., Analytical Chemistry, “Finding out Egyptian Gods’ secret using analytical chemistry: biomedical properties of Egyptian black makeup revealed by amperometry at single cells”, 15 January 2010, Volume 82, Issue 2, 457-762.
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by Sean Henahan
Vision science highlights from the world’s leading journals of medicine and scienceJournal Watch
June 17-19In conjunction with Società Italiana Cellulle Staminali e Superficie Oculare (S.I.C.S.S.O.), [email protected] and Societa’ Oftalmologica Universitaria (S.O.U.)
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Surgical Techniques in Ophthalmology - Oculoplasty and Reconstructive SurgeryEditors in Chief – Ashok Garg and Jorge L AlioPublished by Jaypee - Highlights Medical Publishers Inc. 2010
One of the most unjust
aspects of the public perception of medical specialties is the automatic response of most laypersons to the words “plastic surgeon”. The plastic surgeon has become a caricature figure of show business excess, inflating lips and bosoms and sucking away fat to try and satisfy an insatiable vanity. A surgical discipline that was forged in the wars of the 20th Century, as new ways of killing brought new ways of disfiguring, is reduced too often in the public imagination to another tawdry aspect of modern celebrity culture.
Plastic surgery is not only one of those areas where art most directly meets medical science – it is one of those specialties that can transform a life. To adapt the words of Lady Macbeth, our faces are like books, and only in recent times have we developed the ability to write out some of the misery written there.
Juan Murube MD, professor of ophthalmology in Madrid, contributes one of the most thorough and thoughtful prefaces I have ever read in a medical book. Eschewing the usual rather clichéd
approach of these introductory remarks, he embarks on a meditation on the evolutionary importance of eye lids and facial musculature. He discusses his hypothesis that eyelids developed not to protect the eye, but to provide a smooth tear film for the cornea for creatures that had moved from the seas to land – in
the time span of evolution, of course. He goes on to chart the evolution of facial muscles which developed later in the evolu-tionary story, and allowed the possibility of facial expression.
One of Darwin’s late works was The Expression of the Emotions in Man
and Animals, which looked at the whole range of emotional expression in the animal kingdom. This work influenced the psychologist Paul Ekman, whose exhaustive Facial Action Coding System was described by Malcolm Gladwell in his book Blink. Even if you don’t necessarily appreciate Gladwell’s more dramatic claims, it is undoubtedly true that facial expression constitutes a huge part of how humans communicate. Newspapers and magazines very often feature pictures of their contributors (including this one), a seeming irrelevance that perhaps indicates how universal the desire to see the faces of those communicating with us is.
Murube’s foreword goes on to discuss the volume he is introducing. It “didactically treats the two most important divisions of lid and orbital surgery – the functional and the aesthetic,” he writes. The functional relates to the lubricating and cleansing function Murube relates to those evolutionary innovations that accompanied the move to dry land. The aesthetic relate to the later changes associated with expression. Murube brings
in such concepts as the development of the “closed and monoparental family” and the beginnings of agriculture at this point. It is truly a remarkably interesting and thought-provoking foreword.
After all that, what of the book itself? It is an excellent production, full of colour photographs and illustration. The photographs are taken from clinical settings and well illustrate the pathology being discussed. It is a clinical text practical in tone. It is divided into three sections – the first on external eye disorders, the second on orbital disease, and the third on recent advances in oculoplasty. As may be clear from the words of Dr Murube, this surgical field is one where outcomes are more than simple functional or therapeutic ones, and this is a distinction many authors echo in their own words.
For instance, Arturo Perez-Arteaga and two other collaborators from Mexico, in their chapter on “Free Conjunctival Autograft for Primary and Recurrent Pterygia,” observe that pterygium surgery does not have a “defined technique.” The reason for this is that the rate of recurrence varies from one technique to the next, and no one technique can lay claim to completely preventing this complication. Techniques in reconstructive surgeries, in general, are always open to revision and refinement
Ophthalmology is known as a highly technological, innovation-heavy discipline. So is plastic and reconstructive surgery. When these worlds overlap or combine, any consideration of future trends is likely to be particularly rich. This is certainly
the case in this book, with interesting discussions of stem cell transplants and applying periocular botulinum toxin.
The book is another in this series on surgical techniques which Jaypee Brothers have been publishing. It is of a good production standard, with clear text and illustrations. It is a good reference text for practitioners in this field, or for trainees. I was impressed with the overall level of the contributions which are from contributors in India, Egypt, Turkey, Mexico, Brazil, the US, Italy and Belgium. There is an Indian predominance of contributors, but the other nations are well represented.
Overall, this book is one of the most interesting and well-produced volumes in the series; it provides much food for thought as well as supporting and guiding practice.
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Transforming vision – and lives – with ‘plastic’ surgery F
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In Your Good Books
by Seamus Sweeney
Juan Murube MD, professor of ophthalmology in Madrid, contributes one of the most thorough and thoughtful prefaces I have ever read
March 20104-7 PRAGUE, CZECH REPUBLIC 1st World Congress on Controversies in Ophthalmology (COPHy) Web: www.comtecmed.com/cophy/2010
5-6 LJUBLIANA, SLOVENIA 4th Ljubliana Refractive Surgery Meeting Web: www.lj-refractive.com
8-9 COMO, ITALY International Congress on Imaging and New Treatments in Retinal Diseases Web: www.mcaevents.org
22-26 COLORADO, USA Snowmass Glaucoma Conference Web: www.snowmasscme.com
April 20107-9 BOSTON, MA, USA World Cornea Congress VI Web: www.corneacongress.org
9-14 BOSTON, MA, USA ASCRS/ASOA Symposium and Congress Web: www.ascrs.org
May 201019-22 NATAL, BRAZIL XI International Congress of Cataract and Refractive Surgery Web: www.catarata-refrativa.com.br/2010
June 20105-9 BERLIN, GERMANY World Ophthalmology Congress Web: www.woc2010.de
17-19 VENICE, ITALY 1st EuCornea Congress Web: www.eucornea.org
July 20102 BRIGHTON, EAST SUSSEX, UK Contact Lens Basics and Laser Refractive Surgery Complications Course Email: [email protected]
9-11 CRETE, GREECE Aegean Cornea X Web: www.aegeancornea.gr
18-23 MONTREAL, CANADA ISER 2010 XIX Biennial Meeting of the International Society for Eye Research Web: www.kenes.com/iser
August 20107 GENEVA, SWITZERLAND PRESBYMANIA 2010 Web: www.presbymania.com
20-22 VILNIUS, LITHUANIA XIII Baltic Ophthalmologicum Balticum Web: www.fob2010.com
September 2010 PARIS, FRANCE2-5 10th EURETINA Congress Web: www.euretina.org
4-8 XXVIII Congress of the ESCRS Web: www.escrs.org
9-11 MUNICH, GERMANY 28th Annual ESOPRS Meeting Web: www.esoprs2010.org
16-20 BEIJING, CHINA 25th Congress of the Asia-Pacific Academy of Ophthalmology (APAO) in combination with the 15th National Congress of the Chinese Ophthalmological Society (COS) Website: www.apao2010beijing.org
October 20106-9 CRETE, GREECE European Assocation for Vision and Eye Research 2010 Web: www.ever.be
16-19 CHICAGO, IL, USA American Academy of Ophthalmology Web: www.aao.org/annual_meeting
21-24 HAMBURG, GERMANY 23rd International Congress of German Ophthalmic Surgeons Web: www.doc-nuernberg.de
December 20109-12 MACAU, CHINA The International Symposium on Ocular Pharmacology and Therapeutics – ISOPT ASIA Web: www.isopt.net
April 201126-30 SAN DIEGO, CA, USA ASCRS/ASOA Symposium and Congress Web: www.ascrs.org
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