Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, IndiaDepartment of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
r t i c l e i n f o
rticle history:eceived 15 March 2013eceived in revised form 23 July 2013ccepted 28 August 2013
eywords:orneal transplantationraft registryye Bank
a b s t r a c t
Purpose: To describe and analyze the Corneal Transplant Registry of National Eye Bank and also evaluategraft outcomes in India.Methods: All patients who underwent corneal transplant at our center within six months of setting up ofCorneal Transplant Registry and installation of database at National Eye Bank were included in the study.The established database was analyzed for utilization, donor and recipient details and graft outcomes.Outcome was assessed at the end of one year follow up. The influence of various donor and recipient fac-tors affecting outcome were evaluated. Visual outcome was analyzed in terms of shift in visual handicapcategory. Statistical tests like analysis of variance, Kruskal–Wallis test and Chi square tests were appliedfor determination of clinical significance wherever required.Results: 326 corneas were received from 168 donors; of these, 234 (71.7%) were utilized for transplanta-tion. Out of 177 patients with adequate (one year) follow up (75.6% patients), optical corneal replacementwas performed in106 patients and therapeutic keratoplasty in71. 78% (82/106) patients in the opticalgroup retained clear grafts at the end of follow up. 59.7% (49 of 82) of patients who attained clear graftsbelonged to visual disability category 3 or worse pre-operatively. 59.1% of these achieved BCVA of ≥6/60at the end of follow up; thus shifting up their visual handicap category. Primary graft failure was found tobe associated with full thickness keratoplasty and not with lamellar procedures (p < 0.05) and occurred in4.2% patients (5) with optical corneal replacement whereas 7.5% patients (8) developed secondary graft
failure. Age of donor (p = 0.54), death enucleation time (p > 0.05), cause of donor death (p = 0.15), type ofsurgical procedures (p = 0.538) and indication for surgery did not have any significant effect on outcome.76% patients who underwent therapeutic graft achieved elimination of corneal infection.Conclusions: The development of corneal graft registry established an effective means to evaluate ourcorneal transplantation services. Outcomes of sight restoring corneal transplants performed were com-
According to the data released by the World Health OrganizationWHO) in 2000, approximately 50 million blind people inhabit theorld and nearly 150 million people suffer from ‘low vision’ [1]. The
lobal data identified three major causes of blindness in the world,amely cataract, trachoma, and glaucoma [2,3]. Corneal diseaseshould primarily be prevented as the overall success rates remain
� Authors have full control of all primary data and they agree to allow Graefesrchive for Clinical and Experimental Ophthalmology to review their data uponequest.∗ Corresponding author at: Dr. Rajendra Prasad Centre for Ophthalmic Sciences,ll India Institute of Medical sciences, Ansari Nagar, New Delhi 110029, India.el.: +91 11 26593145.
tries from developed nations.h Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
poor when visual rehabilitation is offered with corneal transplan-tation [4–15]. In order to appropriately address the problem faceddue to corneal blindness, there is a long felt need for individu-alization of blindness control programs to suit different regionsand for optimum utilization of available resources. Therefore, weconducted this study to understand the nature and prevalence ofcorneal diseases in this part of the world, donor’s personal and tis-sue characteristics, and the structural and functional outcomes ofcorneal replacement. To aid us in this endeavor, the National EyeBank Corneal Transplant Registry was established with the aim ofestimating the efficiency of the corneal services being provided.
2. Materials and methods
All consecutive patients presenting to our cornea clinic, Dr.Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute
f Medical Sciences (AIIMS), New Delhi, who underwent kerato-lasty over six months from the date of establishment of the graftegistry were included in the study. AIIMS is a public funded teach-ng hospital and tertiary care referral center in Northern India. Its representative of the population of India as a whole. Apart from
residency training program, it offers higher specialist training inornea and all other subspecialty areas of expertise such as retina,ediatric ophthalmology and ophthalmoplasty. The National Eyeank at the Dr Rajendra Prasad Centre for Ophthalmic Sciences
s run by the central government dedicated to the procurementnd distribution of corneal tissue for transplantation. It is the apexody of the National Program for Control of Blindness adminis-ered by the Chief of Dr. Rajendra Prasad Centre for Ophthalmicciences and the day-to-day activities and protocols are super-ised by the Faculty-in-charge. The Eye Bank collects the eyes (i)f voluntary registered eye donors after their death, (ii) of thoseeceased persons when enlightened relatives agree to donate theyes as a service to humanity, (iii) from hospital deaths and fromost mortem cases, after motivating and obtaining the consent fromhe next of kin, and (iv) from the collection centers of the Institute.hese eyes are processed by the Eye Bank and are supplied to eyeurgeons for corneal grafting and other sight restoring operations.
Donor’s personal and tissue details which included corneal pro-urement source, donor age, socio-demographic data, date andime of death, cause of death, death enucleation time (DET),erology details, and culture were recorded in the database. Therocured corneas were clinically graded based on slit lamp biomi-roscopy and endothelial count on specular microscope [16].Annexure 1) The recipient details included socio-demographicata, preoperative diagnosis, visual disability category and type ofrocedure performed. Indications for surgery were classified intoa) Optical purpose i.e. corneal replacement performed primarilyo restore corneal clarity, (b) therapeutic purpose i.e. surgery per-ormed to eradicate corneal infection and (c) tectonic i.e. surgeryerformed primarily to restore the integrity of the globe. Type ofurgery performed was categorized as penetrating, triple (i.e. ker-toplasty in addition to lens extraction and IOL implantation) andamellar keratoplasty. Therapeutic keratoplasty is performed byaculty members specializing in cornea or Senior Residents whore qualified ophthalmologists with an MD or MS degree havinglready completed a three year residency program in ophthalmol-gy and are undergoing a further three years of senior residencyhich is a higher specialist training in cornea and refractive
urgery. Optical penetrating keratoplasty and lamellar keratoplastyre also performed by the cornea faculty and the Senior Residentsssisted or supervised by the faculty.
Supplementary material related to this article can be found, inhe online version, at http://dx.doi.org/10.1016/j.clae.2013.08.155.
.1. Acquisition of clinical data and analysis of outcome
Patients were reviewed in corneal transplant follow up clinict 1 week, 1 month, 3 months, 6 months and one year. At eachisit patients were examined for their best corrected visual acuitynd graft status. Adequate follow up was defined as at least 1 yearollow up after surgery, others were categorized as ‘lost to followp’ and the results of these patients were not analyzed. In relationo optical keratoplasty, success was defined as clear graft at the endf follow up, primary graft failure was defined as a graft which failso clear in the early postoperative period ≤ 4 weeks, and secondaryraft failure was development of corneal edema with or withoutrremediable loss of graft clarity in a previously thin and clear graft.
herapeutic keratoplasty was done in cases of active keratitis anderforated corneal ulcers and therefore usually require larger sizedrafts in an already inflamed eye. Success in these cases is thus notefined on the basis of graft clarity which is difficult to achieve; but
rior Eye 37 (2014) 111–115
on the basis of eradication of corneal infection with no episode ofrecurrence. Maintenance of globe integrity was considered as suc-cessful outcome for tectonic keratoplasty at the end of one year. Acomplication was defined as any development which has the poten-tial to compromise final graft outcome [17]. Visual outcome of thepatients was analyzed by change in preoperative visual categories(up or down shift) (Annexure 2) [18,19].
Supplementary material related to this article can be found, inthe online version, at http://dx.doi.org/10.1016/j.clae.2013.08.155.
The effect of various donor and recipient factors on the out-comes of optical keratoplasty were evaluated using univariateanalysis. Analysis of variance and Kruskal–Wallis tests were appliedto evaluate the effect of donor age and DET on outcome. Chisquare test was applied to know the effect of procurement sourceand type of surgery on graft outcome. Any difference with a pvalue of ≤0.05 in any of these variables was considered signifi-cant.
3. Results
3.1. Descriptive analysis of registry
Donor details: In the six-month period analyzed, 326 corneaswere received from 168 donors. 234 (71.7%) were utilized for trans-plantation and 92 (28.3%) could not be used. Of these unutilizedcorneas 45/92 (48.9%) were not suitable for transplantation dueto poor tissue quality. Other factors accounting for non utility ofthe tissue included serology positivity of donors, culture positiv-ity of the tissue and inadvertent damage during the surgery. Withrespect to donor corneal retrieval sources, the Institute and itscollection centers were the major providers of donor tissue con-stituting 73.8% of total cornea received. Contributions made byother Eye Banks and voluntary donors accounted for the rest of the15.1% and 10.7% cornea, respectively. Ischemic heart disease wasthe most frequent cause of mortality amongst the donors (35%).Other causes included death due to cardio-respiratory failure (30%),stroke (6%) and road traffic accidents (4%). Mean age of the donorswas 52.74 ± 22.7 years (range 15–95). Mean DET was 4.83 ± 2.91 h(range 45 min–14.5 h).
3.1.1. Recipient detailsThe average rate of performing keratoplasty at our institute was
found to be 1.3 per day and of the 234 patients who received cornealtransplants during the study period, only 177 (75.6%) patients com-pleted adequate follow up and the remaining 67 patients werelost to follow up including 19 patients who underwent tectonickeratoplasty as a globe salvage procedure. Amongst these 177patients, 106 patients had undergone elective sight restoration ker-atoplasty and the indication for surgery included post-infectiousscar (36, 33.9%), keratoconus (11, 10.3%), bullous keratopathy (19,17.9%), corneal dystrophy (12, 11.3%) regraft (12, 11.3%) and mis-cellaneous causes (16, 15.09%). Of these full thickness keratoplastywas done in 73, (68.8%) and lamellar surgery was performed in33 eyes (31.2%). Of the lamellar surgery, 7 globes were used fortwo patients i.e. DSAEK and DALK/LK were done from the samedonor cornea in 7 instances. The remaining 71 patients under-went emergency keratoplasty for active infectious keratitis whichwas relentlessly progressive and not responding to medical ther-apy leading to extensive corneal involvement and perforation orimpending perforation. Diagnosis of patients with adequate followup with respect to the type of surgeries performed is shown in
Table 1. Success in optical group was achieved in 82 of 106 (78%)patients as primary and secondary graft failure occurred in 5(4.2%) and 8 (7.5%) patients, respectively and non sight threateningcomplications developed in 11 eyes (10.3%) which included suture
corneal dermoids, post traumaticscars, post trabeculectomy cornealdecompensation)
18 10.1
Total 177 100
ig
pnr
3
dtcgts
1oatepoi(
ent and any condition causing impending perforation of the hostcornea [23]. Since the primary indication of surgery influences the
TE
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nfiltrates, loose sutures, raised intraocular pressure and improperraft host apposition.
Amongst patients who underwent grafting for therapeuticurposes, 54/71 (76%) achieved graft success in the form of elimi-ation of corneal infection whereas the remaining 24% developede-infection sometime during follow-up in the graft.
.1.2. Effect of donor and recipient factors on outcomeAge of donor (p = 0.54, Analysis of variance), cause of donor
eath (p = 0.15, Fischer exact test) and DET (p > 0.05, Kruskal–Wallisest) did not have any significant influence on final graft out-ome. Though clear grafts, had lowest mean DET of 4.5 h andrafts with primary failure had the highest mean DET of 6.52 h,he difference was not statistically significant to affect the grafturvival.
Optical outcomes were best for corneal dystrophies at the end of year, though it did not reach significance levels (p = 0.6). The ratef graft survival was similar for post-infectious scar, keratoconusnd bullous keratopathy at the end of one year (Table 2). None ofhe recipients with keratoconus or corneal dystrophy developedither primary or secondary graft failure. Also, the type of procedureerformed (penetrating, triple or lamellar) did not affect the overallutcome (p = 0.5, Fisher exact). Primary graft failure occurred only
n cases of penetrating keratoplasty and not in other proceduresTable 3).
able 2ffect of diagnosis on graft outcome.
Diagnosis Success (%) Primary graft failure (%)
Post-infectious keratitis 27 (75) 1 (2.78)
Keratoconus 8 (72.73) 0
Corneal dystrophy 11 (91.67) 0
Bullous keratopathy 14 (73.68) 2 (10.53)
Failed graft 9 (75) 1 (8.33)
Others 13 (81.25) 1 (6.25)
Total 82 5
able 3ffect of surgical procedure on graft outcome.
Procedure Success (%) Primary graft failure (%)
Penetrating keratoplasty 40 (75.47) 5 (9.43)
Triple procedure 16 (80) 0
ALTK 5 (83.33) 0
LK 5 (71.43) 0
DALK 8 (80) 0
DSAEK 8 (82) 0
Total 82 5
rior Eye 37 (2014) 111–115 113
3.2. Visual outcomes
Out of 82 recipients with successful sight restoration surgery,49 (59.7%) were socially blind preoperatively (category 3 or more)(Annexure 2); 29 (59.1%) of these patients achieved BCVA ≥ 6/60at the end of one year (category 1&2) and 15 patients fell in theseverely visually impaired category. 5 patients had no change intheir visual impairment category (Annexure 2). 22 (26.8%) patientspreoperatively belonged to severe visually impaired category andall these gained visual acuity of >6/60 with 7 patients achievingvision >6/18. 11 patients had mild visual impairment, of which 6(54.5%) patients were shifted to category with normal visual acuity(>6/18). (Annexure 2).
4. Discussion
Periodic monitoring of the corneal transplantation servicesbeing provided to the population is essential in order to understandthe changing trends of the indication for grafting, graft survival fac-tors and causes of graft failure. This helps implement the existingresources in a better way and bring about the necessary changefor the improvement of the results. For this purpose, we designeda corneal graft registry which takes into consideration the donorand recipient details as well as the postoperative outcome of theoperated patients. The different details of the patients enteredon separate sheets are interconnected with each other through aunique identification number of each donor cornea.
At the rate of 1.3 keratoplasties per day, the amount of cornealtransplantation being done in our setup is huge when compared tothe data from other registries [20–22]. Despite this rate, the annualrequirement figures for donor cornea in India is projected to be at20 times the current procurement rate which clearly indicates ahuge lacuna between the demand and supply of the donor cornealtissues [19]. The combination of paucity of good quality and quan-tity of donor tissue as well as failure to adequate utilization of theprocured tissue is a big deterrent in eliminating corneal blindnessin this part of the world. According to a recent study main riskfactors for graft failure include host factors only i.e. host cornealvascularization, any systemic auto immune disease in the recipi-
final outcome in graft survival [24], the judicious use of availabledonor tissue is necessary.
Secondary graft failure (%) Complication (%) P value [1]
In our series, we observed that approximately 28% of donorornea remained unutilized; mostly due to poor clinical grade orerology positivity of the donors. Utilization rate in our series wasomparable to other reports, however it could not match rates asigh as 88%, documented in New Zealand Eye Bank Study [25].
multitude of factors such as tropical Indian weather with aigher mean atmospheric temperature and moisture, late retrievalf donor cornea, damage caused during travel may partially accountor this high percentage of poor clinical grade corneas.
Majority of donor tissue was acquired from the National Eyeank. Nearly one third of total tissue was received from other
ocal eye banks as compared to other countries which also receiveornea from international eye banks [21]. Despite rising awarenessegarding eye donation, voluntary donations contributed the leastnlike reported by other studies [21].
Our donor population was younger at a mean age of 52.74 ± 22.7ears when compared to data from other registries [21]. Though inur series, donor age was not correlated to graft outcome simi-ar to the results quoted by Singapore graft registry, however inther long term follow up studies, donor age has been establisheds a significant variable affecting graft survival [15,26]. As expected,urviving grafts were found to have lower mean DET, though noteaching significance. Amongst donor mortality causes, cardiovas-ular event was major cause of mortality similar to other developedountries [18,21]. In contrast, to developed nations incidence oferebrovascular accidents was lower in donors of our series.
Perforated corneal ulcers and active keratitis (36.63%) consti-uted the most common indication of corneal transplant. Due toecreased awareness in a country where most of the populationesides in rural areas, people often seek treatment late in the diseaseourse and thus eventually require therapeutic corneal replace-ent for ocular salvage. Thus, emergency penetrating keratoplastyhich is performed in active keratitis was the most common indi-
ation of corneal surgery, followed by elective optical keratoplasty.his is in accordance with results from other series from develop-ng countries where active keratitis and post infectious scars remainhe major indication for corneal transplantation [8]. A reasonableuccess rate (76%) in these cases in our series calls for continuoussage of below optical quality donor tissue in cases with perfora-ion and imminent perforation; as infection is eliminated and globentegrity is maintained.
Large numbers of regrafts (10.9%) were also performed andhe number was comparable to 12.4% in Singapore registry [26].owever, regrafts constituted nearly one fifth of total indications
19%) in Australian corneal graft registry (ACGR) [15]. This might beecause in our series, success was defined as clear grafts at the endf follow up, while ACGR considered amount of astigmatism alongith graft clarity as success. Likewise, reflecting this trend, regraftsave emerged as the most common indication in the current decadeccording to Hungarian transplant registry [20].
Overall one year outcomes of optical corneal replacement in oureries were comparable to Australian (89%), Singaporean (86.6%)nd UK (86%) graft registries [26,24,27]. Unlike in other studies,ndication of transplantation did not affect the final outcome ofurgery in our study [15].
Lamellar surgeries accounted for one fourth of the overall sur-eries being performed which was much higher to that seen inCGR (5.5%) [24]. Anterior lamellar surgeries were being per-
ormed for indications like corneal dystrophy and keratoconusnd posterior lamellar for bullous keratopathy and Fuch’s dys-rophy. Furthermore, the structural and functional outcomes ofamellar and full thickness keratoplasty were similar. This rising
rend toward lamellar surgeries and the good clinical outcome is
marked leap forward in future direction because these surgeriesave an overall decreased rate of graft rejection, less astigmatism,ore wound strength, less sutures (posterior corneal replacement),
[
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rior Eye 37 (2014) 111–115
decreased intraocular inflammation as well as less chances of seri-ous complications like expulsive hemorrhage [28]. In addition theyhold great promise as a tissue acquired from a single donor can beused for at least two recipients thus simultaneously addressing theproblem of less good quality corneal tissue availability [29].
We found that the though patients achieved a significant changein visual acuity postoperatively, the visual outcomes were not asgood as quoted in other registries [15,30]. This may reflect the dif-fering trends of surgeries in other places [31] where most commonindications remain keratoconus, dystrophies and failed grafts. Con-trary to this, we found post-infectious scar (adherent leucoma),bullous keratopathy as other common causes for doing cornealtransplant at our setup attributing to poorer visual gain. Dandonaet al. found aphakic bullous keratopathy, previous transplant fail-ure, corneal clouding due to glaucoma, adherent leucoma and poorsocioeconomic status as major risk factors for graft failure in thispart of the country [19].
Limitations of our study include a high number of patients whowere lost to follow up and a short duration of follow up. Longerfollow up results in higher rate of graft failure secondary to chronicgraft rejection, endothelial cell loss and increased incidence ofhigh intraocular pressure. Nevertheless, despite these limitationsour study provides an indispensable glimpse into the status ofcorneal transplantation at a tertiary care center in India. Though ourresults do match the results from other registries, a lot is requiredto uplift the grim picture of corneal blindness in this part of theworld.
Funding
No financial support has been received by any author and noneof the authors have proprietary interest in the subject matter pre-sented.
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