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Current Trend in Management of Amblyopia
Maharajgunj Medical Campus, IOM, Nepal
Bikash SapkotaB. Optometry
AMBLYOPIA
Old Definition: Reduction in visual form perception withoutany structural deficits of the visual system, not correctable byoptical means
Current Definition: A unilateral or bilateral decrease of visualacuity caused by pattern vision deprivation or abnormalbinocular interaction for which no obvious causes can bedetected by physical examination of the eye and cannot becorrected by optical or surgical means but in appropriatecases is reversible by therapeutic measures
Difference of > 2 lines between two eyes
< 6/9 VA
Amblyopia originated from Greek word:
Amblyos - dullness / blunt, Ops – vision
Condition in which the observer sees nothing & patient very little
Prevalence
o Globally 1-5% (WHO 2015)
o In Nepal around 0.9 to 1.8%
o 4 times more frequent in premature children
o 6 times more frequent in children with delayed mile stones
o Smoking and use of drugs and alcohol during pregnancy have been associated with risk of amblyopia
CLASSIFICATION OF AMBLYOPIA
Prognostic Factors in Amblyopia
Positive factor Negative factor
functional organic
Central fixation Eccentric fixation
Random dot stereopsis No random dot stereopsis
Short duration Long duration
Young patient, motivated Older patient, un-motivated
Type Prognosis Treatment
OrganicTobacco
Toxic
Congenital
Good
Poor–fair
Poor
Abstinence
Medical attention
Functional vision therapy
FunctionalHysterical
Light deprivation Refractive
Strabismic
Good
Poor
Good
Good
Psychotherapy
Remove obstacles
Refractive correction
Functional vision therapy
CURRENT TREND OF MANAGEMENT
IMPORTANCE OF TREATMENT
If left untreated, amblyopia produces a range of functional deficits
Binocular function is also compromised
The presence of amblyopia (or its treatment) impact on educational attainment, future career opportunities, self-esteem & quality of life
The studies reveal the practical and emotional impact of amblyopia and provide additional evidence in support of the need to develop effective treatment
Goal of TreatmentTo restore and improve visual acuity by two strategies:
I. Present clear retinal image to the amblyopic eye
o Eliminate causes of visual deprivation
o Correcting visually significant refractive errors
II. Make the child use the amblyopic eye
Recommended treatment should be based on
o Pt.’s age, VA, compliance with previous treatment &
physical, social and psychological status
What would be the perfect amblyopia therapy?
Effective Good compliance Acceptable to pts. and parent Quick Safe Easy to administer Cost effective Well maintained
Choices of TreatmentThe choices of treatment of amblyopia are used alone or in combination to achieve goal of treatment
1. Passive Therapy
The patient experiences a change in visual stimulation without any conscious effort
i. Proper refractive correction
ii. Occlusion
iii. Penalization
2. Active Therapy
It is designed to improve visual performance by the patient’s
conscious involvement in a sequence of a specific, controlled
visual task that provide feedback
i. Pleoptics
ii. Near activities
iii. Active stimulation therapy using CAM vision stimulator
iv. Syntonic phototherapy
v. Role of perceptual learning
vi. Binocular stimulation
vii. Software-based active treatments
viii. Exposure to dark
ix. Pharmacological Therapy
Passive Therapy
Refractive Correction
OcclusionPenalization
Proper Refractive CorrectionPurpose
To provide sharp images and providing optimal environment for amblyopia therapy
Give pt. proper optical correction alone
- Short period of time (6-8 weeks) before initiation of
other therapy
- In case of refractive amblyopia, a progressive improvement in
acuity for up to 16 - 22 weeks has been shown in some pts.
after refractive correction (Stewart C. et al 2004)
When to Prescribe
REFRACTIVE ERROR CORRECTION
Improves VA in 25-33% of patients with anisometropicamblyopia and also in strabismic amblyopia
ATS-5 (PEDIG) 2006 concluded that amblyopia improved with optical correction in 77% and resolved in 27%
Chen et al (AJO 2007) concluded that amblyopia improved with optical correction in 93% and resolved in 45%
Penalisation and occlusion is required only if the VA doesn’t improve with glasses for 4 months
Occlusion Therapy
The most powerful and effective means of treating amblyopia
Mainstay of treatment since 18th century to till now
Highly effective until 8 years of age
New studies have shown improvements upto 24 yrs of age
Cover good eye to stimulate amblyopic eye
Success rate 30-92%
o When fixation is central: simple & effective
o When fixation is eccentric: <7yrs central fixation recover
o Older the child harder to regain central fixation
Mode of Action
Prevent fixating eye taking part in act of vision and removes inhibitory stimulus that arises from stimulation from fixating eye (non-amblyopic eye)
TYPES OF OCCLUSION
Occlusion
Total or Partial
Conventional or Inverse
Full Time or Part Time
Total VS Partial Occlusion
Total Partial
•All light is prevented fromentering eye•Employed in amblyopic eyes
with acuity less than 6/24•Occlusion using elastoplast, gauze pad, tape, doynesrubber occluder
•Does not cut off the total lightentering eye•Degrades the vision of normaleye such that amblyopic eyegets better vision andpreference•Occlusion using cellophane,transparent nail polish, or ahigher plus lens
Conventional VS Inverse
Conventional Inverse
•Occlusion of sound eye •Occlusion of amblyopiceye so that eccentricfixation becomes less fixed
Full Time VS Part Time
Full time Part time
Removed only while going to bed at night
Short time each day during close work or watching television
Choice of initial Rx In relapses after Rx and also for maintenance
PatchesMicropore tape with soft tissue paper
Spectacle patch / frost glass Doyne’s occluder Opaque Contact Lens
How to go about Occlusion?
Motivation of child and parents
Active vision exercises by amblyopic while non-amblyopic eye is occluded
Occlusion is continued till amblyopic eye has developed equal vision and equal preference of fixation
May take 3-6 months
If there is no improvement, then treatment is stopped
Maintenance treatment is continued at least up to 9 yrs of age with part time occlusion and exercises
Follow up-depending on age, severity of amblyopia and compliance-to look for VA, fixation pattern and occlusion amblyopia
When to stop occlusion
- VA equals in both eyes
- Alternation of fixation (Repka 2008)
When VA is stable patching may be decreased slowly
Because amblyopia recurs in large no. of pts. maintenance therapy or tapering of therapy should be strongly considered
Disadvantages of occlusion
Prolonged treatment
Occlusion amblyopia
Non compliance
Psychological distress
Allergic skin rash
Cosmetically inacceptable
Prognostic considerations
Younger the age better the prognosis
Type of amblyopia myopic anisometropia> hyperopic anisometropia> strabismic amblyopia> stimulus deprivation
Pre-treatment VA
Type of occlusion
Type of fixation
Near exercises
Pt. compliance and parent education
Presence of astigmatism
Previous treatment
Refractive correction
Treatment of Anisometropic Amblyopia
Treatment of Strabismic Amblyopia
Penalization
Therapeutic technique performed by optically defocusing the eye with better vision by using cycloplegia or altering the eye glass lens
Indications
o No compliance for occlusion
o Mild degrees of amblyopia
o Maintainence after occlusion
o Anisometropic amblyopia
Advantages: Cheap, better compliance
Disadvantages: Side effects of drugs
- Risk of occlusion amblyopia
- Systemic absorption
Unless penalisation decreases the VA of dominant eye below the amblyopic eye this form of treatment is not adviced
Methods of penalisation
a. Near penalization: fixing eye is atropinized & fullycorrected for distance, amblyopic eye is overcorrectedwith +2.00 to +3.00 D
b. Distance penalization: fixing eye is atropinized & overcorrected, amblyopic eye is fully corrected
c. Total: fixing eye is atropinized & undercorrected by 4.00 to 5.00 D, amblyopic eye is fully corrected
Summary of the PEDIG studies
Short title
Ages (Yrs)
Baseline amblyopic eye acuity
Primary outcome measure
Initial treatment prescribed
Results (Improvement)
Primary conclusion
ATS 1 (35)
3 to <7
20/40-20/100
Lines improvement after 26 weeks
Daily atropineAt least 6 hrs daily patching
2.8 lines
3.2 lines
Atropine and patching are equally effective as primary treatment for moderate amblyopia
ATS 2A (37)
3 to <7
20/100-20/400
Lines improvement after 17 weeks
6 hrs daily patching Full time patching
4.8 lines
4.7 lines
6 hrs daily patching produces improvement similar to full time patching for severe amblyopia
ATS 2B (36)
3 to <7
20/40-20/80
Lines improvement after 17 weeks
2 hrs daily patching6 hrs daily patching
2.4 lines
2.4 lines
2 or 6 hrs of prescribed daily patching produce similar improvement for moderate amblyopia
Summary of the PEDIG studiesShort title
Ages (Yrs)
Baseline amblyopic eye acuity
Primary outcome measure
Initial treatment prescribed
Results (Improvement)
Primary conclusion
ATS3 (39)
7 to <18
20/40-20/400
Proportion of responders (improvement >2 lines) after 24 weeks
2-6 hrs daily patching (+ atropine if <12 yrs)
Spectacles alone if needed
Response rates:Age≤12 yrs: 53%Age≥13 yrs: 25%Age≤12yrs: 25%Age≥13 yrs: 23%
ATS 4 (34)
3 to <7
20/40-20/80
Lines improvement after 17 weeks
Weekend atropineDaily atropine
2.3 lines
2.3 lines
Weekend and daily atropine produce similar improvement for moderate amblyopia
ATS 5 (38)
3 to <8
20/40-20/400
Lines improvement after 5 weeks
2 hrs daily patchingSpectacles alone if needed
1.1 lines
0.5 lines
After a period of spectacle wear, 2 hrs daily patching is superior to continuing spectacles alone
Practical Implications of the PEDIG studies
Children < 7 yrs and VA between 6/12 to 6/24
- 2 hrs and 6 hrs patching - same effect
Children < 7 yrs and VA 6/30 - 6/120
- 6 hrs and full time patching - same effect
Children < 7 yrs and VA 6/12 - 6/30
- Daily atropine produces similar effect as 6 hrs patching
Practical Implications of the PEDIG studies
Children 7 to 18 yrs and VA 6/12 to 6/120
- 2 - 6 hrs patching leads to at least 2 lines improvement
(if no previous treatment) but
- the compliance rate is poor in age >13 yrs
Children < 8 yrs and VA 6/12 - 6/120
- Patching 2 hrs is better than spectacles alone
ACTIVE THERAPY
Pleoptics
Pleoptics: Gr. meaning full vision
Used for active stimulation of the fovea to overcome eccentric fixation and improves the visual acuity
In this technique
- the peripheral retina is dazzled with an intense light protecting
foveal area
- after the light source is turned off, the fovea functions better
as the surrounding retinal area is in a state of hypofunction
- this can be followed by direct stimulation of fovea
by pleoptophore (Bangerter’s method)
or indirectly by producing after image (Cupper’s method)
Demerits
The technique is complex and requires an absolute co-operation of the pt. and intelligence to appreciate after-images
Daily sitting for a longer period of time is required
Since occlusion of the dominant eye is a very successful simple and inexpensive method of treating eccentric fixation, so the use of pleoptics methods is abandoned
Only indication is co-operative and intelligent child older than6yrs having eccentric fixation
Pleoptics VS Occlusion of sound eye
Visual acuity outcomes in children who have had conventional occlusion are found to be better than in those who have gone through pleoptic treatment (VerleeDL, Iacobucci 1967)
Visual acuity improvements are significantly greater in the direct occlusion group than in the group undergoing pleoptic therapy and inverse occlusion(Veronneau T.S. et al 1974)
Treatment using grating stimuli(Active stimulation therapy using CAM
vision stimulator)
Method
Non amblyopic eye is occluded
Amblyopic eye is stimulated for 7 mins by slowly rotating (at about 1 revolution per min) high contrast square wave grating of different spatial frequencies
The treatment is carried out once in a week for 3 to 4 weeks
Advantages over the conventional occlusion therapy
o The sound eye remains open between the weekly treatment sessions
Principle
Assumption that rotating grating provides specific stimulation for cortical neurons
Present status of CAM vision stimulator
This technique is not as effective as conventional occlusion therapy
So it has failed to replace time tested conventional occlusion therapy for the treatment of amblyopia
Some workers use this technique as supplementary to occlusion therapy in co-operative pts. with supportive who can carry out the treatment at home
Recently a new treatment has been described based on a similar principle, namely, the use of grating stimuli to activate certain cortical cells (Angelika Shanshinova et al, 2008)
The treatment is computer-based and is intended to supplement occlusion treatment, particularly in patients beyond childhood
The treatment comprises a computer game viewed on a monitor against the background of a low spatial frequency drifting sine wave grating
The stimulus is a drifting sinusoidal grating of a spatial frequency of 0.3 cyc/deg and a temporal frequency of 1 cyc/sec, reciprocally coordinated with each other to a drift of 0.33 deg/sec
Based on the idea that stimulation of motion-sensitive cells might help to improve function of form-sensitive cells by synchronisation of responses
Efficacy of treatment is higher for the computer based method combined with occlusion than for occlusion only
Syntonic phototherapy in the treatment of amblyopia
Syntonics is the branch of ocular science dealing with the application of selected visible light frequencies through the eyes
For the purposes of treatment, syntonic optometrists define four syndromes as follows: acute, chronic, emotional fatigue and lazy eye
In lazy eye syndrome, amblyopia, strabismus, vergenceanomalies, suppression, ARC or visual field constrictions are treated using red/orange filters
It is based on work by Spitler, in which 2,791 of 3,067 individuals responded positively to syntonic phototherapy
However, there is no published studies on the effectiveness of this technique in amblyopia therapy
In the absence of studies providing good quality evidence that amblyopic patients will be helped by syntonic phototherapy, there seems to be no basis for prescribing this treatment
Wallace LB. The theory and practice of syntonic phototherapy 2009
Spitler HR. The Syntonic Principle. Pennsylvania: Science Press Printing Company, 1941.
Role of perceptual learning in amblyopia treatment
Perceptual Learning Any relatively permanent and consistent change in the
perception of stimulus array following practice or experience with this array- Gibson (1963)
No. of studies suggest that perceptual learning (PL) may provide an important new method for treating amblyopia
Principle
PL is reported to operate via a reduction of internal neural noise and/ or through more efficient use of stimulus information by returning weighting of the information
PL employs repeatedly practicing a visual discrimination
task, e.g: positional acuity, contrast sensitivity,
stereo-acuity, etc
Recommended period for PL: 2hrs/ day, 5 days/ week, for a period of 9 months
Significant improvements found in VA and CS (Chen P. et al 2008, Huang C. et al 2006)
Role of PL is still controversial, but utility is reported in adult amblyopes
Video Game Play & Brain Plasticity
The intense sensory-motor interactions are immersed video-game play
This might push brain functions to the limit
Enables the amblyopic visual system to learn, on the fly, to recalibrate and adjust, providing the basis for functional plasticity
Video Game Play & Brain Plasticity
Game playing requires the allocation of spatial detection, and localization of low contrast, fast moving targets, and aiming
Video games may include several essential elements for active vision training to boost visual performance
According to C. S. Green and co workers (2003) action video game modifies visual selective attention
Thus, it could potentially be useful in improving amblyopic vision
Video-Game Play Induces Plasticity in the Visual System of Adults with Amblyopia(Roger W. Li1 et al, August 30 2011)
o 10 amblyopic adults: Action Video Game, 40 hrs, 2hrs/day
o 3 amblyopic adult: Non-action Video Game, 40 hrs, 2 hrs/ day
o Non-amblyopic eye: Occlusiono Control Group 7 adults: Only patching
Action Game: Medal of Honor: Pacific AssaultNon-Action Game: SimCity Societies
PL is an area with clear potential for treating amblyopia
Significant improvements in vision can result from training periods that are relatively short using tasks that are relatively engaging, compared to conventional occlusion
It is important to be aware that the way in which these improvements arise is not yet fully understood
Further research is needed before optimal training strategies can be devised and before the way in which those strategies modify visual function can be fully understood
Binocular stimulation in thetreatment of amblyopia
During occlusion therapy, the non-amblyopic eye is occluded i.e. binocular vision is not encouraged during these periods
It has been recognized that binocular stimulation may be important in the treatment of amblyopia
Animal research (Mitchell DE 2008) and recent studies (Baker DH et al 2007, Mansauri et al 2007) indicate that binocular stimulation encourages binocular cortical connections during recovery from deprivation amblyopia
Offers support for binocular stimulation when treating amblyopia
One existing approach to treating amblyopia that allows binocular stimulation is the use of Bangerter foils (Baker and colleagues 2007)
Another long-standing and widely used approach is atropine penalization
In both cases, the image at the fovea of the non-amblyopic eye is degraded (for near vision in the case of atropine), while input to the amblyopic eye is not affected
In these therapeutic scenarios, vision is binocular in the sense that both eyes receive light stimulation and peripheral resolution is not significantly impeded (Wang YZ et.al 1997)
Comparisons between occlusion and atropine (LI T et al 2009)
or between occlusion and Bangerter foils (PEDIG 2010) as treatments for amblyopia show no significant difference in outcome
Suggests that this type of binocular stimulation does not offer significant advantages over the combination of binocular and monocular vision allowed by periods of occlusion
The ‘monocular fixation in a binocular field’ (MFBF) technique
Introduced with the intention of training the amblyopic visual system to integrate information from both eyes (Cohen AH. Monocular fixation in a binocular field. J Am Optom Assoc 1981)
This technique involves the presentation of peripheral stimuli to both eyes, while only the amblyopic eye is stimulated at the fovea
The ‘monocular fixation in a binocular field’ (MFBF) technique
Applied in a range of paper-based formats.
E.g, pt. may be instructed to complete tasks such as crossword
puzzles or placing dots in the ‘o’ letters in a text, using a
pen and wearing red-green glasses, with the red lens in
of the non-amblyopic eye (Wick B. et al 1992)
I-BiT™ Interactive Binocular Treatment for Amblyopia
Concept Present separate images to each eye Dynamic visual scene Preferentially stimulating amblyopic eye
Patient motivation Interactive games and videos Encourage patient compliance
Shutter Glasses Technologyo Shutter glasses o High definition screens o Faster processing speeds
Adaptations for use with the I-BiT system Shutter glasses with I-BiT software is to change the ratio
of information presented to each eye in order to stimulate one eye more than the other
This creates a 2D view rather than the intended 3D stereoscopic view
DVD Player
o Border with controls common to both eyes
o Only amblyopic eye sees the DVD
NUX Game
Evidence Six children treated with prototype and gained 2 lines of
vision (Waddingham et al Eye 2006)
10 treated with I-BiT and improvement of 0.189 logMAR,
almost 2 lines (Herbison et al Eye 2013)
Other groups: e.g. Hess’s group with the game Tetris in adults (required a minimum of 6 hrs play before any effect is discernible)
Fig: Visual acuity in LogMAR units for all patients from baseline to week 10.
Herbison et al Eye 2013
Software-based active treatments for amblyopia for use at home or in office
The AmbP iNet program for the treatment of Amblyopia
Marketed by Home Therapy Solutions
System features 12 treatment programs, 6 of which are randomly assigned for completion by the patient each 5 days per week
Involve activities like ‘letter jump’, among others
The treatment involves visual search of certain target
The AmbP iNet program for the treatment of Amblyopia
Treatment system is designed to improve hand eye co-ordination, VA, crowding effect and visual memory
No published reports of clinical trials of this method, so it is not possible to know whether the design is effective as part of a treatment for amblyopia
Thus, controlled trials of this treatment are needed
(Cooper J. et al 2007)
Not a "lazy" eye, but a "lazy" brain
Amblyopia therapy is:
o Completed at home on a computer
o 2-3 times per week
o Each of the 40 sessions takes an average of 40 minutes
Precise visual tasks consisting of patterned images with subtle differences in orientation, size and contrast
Through repetitive practice the brain is trained to be efficient and to improve visual processing
Specialized RevitalVision™ algorithms analyze
Binocular iPad Game VS Part-Time Patching
2 studies (PEDIG 2016), (K.R. Kelly et al 2016) were done to compare VA improvement in children with amblyopia treated with a binocular iPad game vs part-time patching
Effect of a Binocular iPad Game vs Part-time Patching in Children Aged 5 to 12 Years With Amblyopia A: Randomized Clinical Trial;Jonathan M. Holmes et; for the Pediatric Eye Disease Investigator Group, JAMA Ophthalmology, November-3, 2016
Binocular iPad Game vs Patching for Treatment of Amblyopia in Children:ARandomized Clinical Trial; Krista R. Kelly, PhD; Reed M. Jost, MS; Lori Dao, MD; Cynthia L. Beauchamp, MD; Joel N. Leffler, MD; Eileen E. Birch, PhD, JAMA Ophthalmology, December 2016
Fig: Visual Acuity (VA) in Amblyopic Eyes From Baseline to 16Weeks
(PEDIG 2016)
VA improves with binocular game play and with patching, particularly in younger children (age 5 to <7 years)
VA improvement with this particular binocular iPad treatment is not as good as with 2 hrs of prescribed daily patching
• High-contrast red elements (miners and fireball) are seen by the
amblyopic eye
• Low-contrast blue elements (gold and cart) are seen by the fellow
eye
• Gray elements (rocks and ground) are seen by both eyes• Both eyes must see the game for successful play
Fig: Dig Rush Game
(K.R. Kelly et al 2016)
Fig: Best-Corrected Visual Acuity (BCVA) at Baseline, the 2-Week Visit, and the 4-Week Visit
(K.R. Kelly et al 2016)
Binocular iPad game is a successful treatment for childhood
amblyopia and is more effective than patching at the 2-week visit
Exposure to Darkness
Dark exposure promotes recovery from amblyopia
It is based on Duffy and Mitchell (2013, current biology) animal (kittens) experiments
Three key parameters will have to be established first
o What is the minimum period of dark exposure needed to trigger restoration of visual cortex plasticity?
o What is the age dependence of this effect?
o How absolute does the darkness have to be?
The answers to these questions will ultimately determine the utility of this approach to treating amblyopia
Pharmacological Therapy
Levodopa & citicoline are the most extensively studied drugs
Plasticity of visual system during the sensitive period is dependent on input from non-adrenergic neurons and thus can be subjected to pharmacological manipulation
Precursor for the catecholamine dopamine, a neurotransmitter, known to influence visual system at retina and cortical level
It either extends or reactivates the visual system’s sensitive period of neural plasticity
Catecholamine based medical treatment has been demonstrated to improve vision in amblyopic eyes.
Leguire and co-workers (1993) found that 1 hr after levodopa ingestion,VA, CS and PVEP temporarily improve but starts to decrease 5 hrs after drug ingestion
They concluded that combination of levodopa and occlusion improves visual function more than levodopa-carbidopa alone in amblyopic children
Dadeya et al (2009) concluded that there is more than two lines improvement in visual acuity, especially in children younger than eight years of age
Citicoline (cytidine 5’-diphosphocholine) used in a dose of 1,000 mg I.M. for 15 days to patients aged 9–37 yrs causes a temporary improvement in visual acuity without any side effects (Campos et al 1995)
Use of oral levodopa while continuing to patch 2 hrsdaily does not produce a clinically or statistically meaningful improvement in VA compared with patching (PEDIG 2015)
Advantages
o Augments conventional occlusion
o Speeds up recovery of visual functions
o Improves compliance
o Possibility for adult amblyopes
o Reduces cost and duration of treatment
Near activities used in thetreatment of amblyopia
Active vision therapies for amblyopia involve paper-based near activities such as reading, writing and word puzzles
Von Noorden and associates (1970) found that minimal (1 hrper day) occlusion combined with these exercises is beneficial in the treatment of amblyopia for older children
The latter studies (PEDIG 2005, 2008) provide high level evidence that the use of near activities is not helpful in the treatment of amblyopia
In the absence of reliable evidence to the contrary, there is not yet a sound basis for prescribing these tasks for pts. undergoing treatment for amblyopia
Summary
Amblyopia occurs due to abnormal visual experience early in life
Proper optical correction alone is necessary for short period of time (6-8 weeks) before initiation of other therapy
Part time occlusion of better eye is mainstay of treatment since 18th century to till now
For severe and moderate amblyopia, 6 hrs and 2 hrs of patching is advised respectively
Atropine is also used in children with poor compliance
Trial of patching can be given in patients as old as 17 yrsof age
Perceptual learning and pharmacological manipulation have shown areas of amblyopia treatment beyond the critical period of visual development
Binocular stimulation, software based treatments and other methods do not have promising result to replace the patching therapy till date
Most of the active therapy methods have good results when used together with patching therapy
Summary
Amblyopia is still an unsolved problem, the best modality of treatment is still to be explored in
future
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