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

Thankyou