Amblyopia: Screening and Management

Amblyopia: definitions, screening, clinical evaluation and management. This ppt outlines the current management protocols as per studies.

1. Amblyopia : Screening and management Dr. Obaidur Rehman Junior Resident Government Medical College & Hospital Chandigarh

2. Definition and types Amblys = dull , ops = eye Decrease in visual acuity in one eye when caused by abnormal binocular interaction or occurring in one/both eyes as a result of patterned vision deprivation during immaturity, for which no cause can be detected during physical examination of the eyes and which is reversible by therapeutic measures at appropriate time Clinically, defined as difference in BCVA between the two eyes of atleast 0.20 logMAR or 2 lines on Snellen chart Noorden GK, Campos EC. Binocular Vision and Ocular Motility, 6 th edition

3. Bowling B. Kanski’s Clinical Ophthalmology 8 th edition.

4. Epidemiology 1-5% population affected in developed countries In India, 1-4% of children affected In an Indian study in school children, incidence found to be 1%. Higher in rural(0.7%) than urban(0.5%) Weber JL, Wood J. Amblyopia : Prevalence, Natural History, Functional Effects and Treatment. Clinical and Experimental Optometry. 2005; 88: 365-75. Vijaylakshmi P, Panadikar R. Classification of amblyopia . Strabisscope 1996; 3: 6-7. BS Goel . Strategy for early detection of amblyopia . Strabismology and Pediatric Ophthalmology 1999; 5: 9-11.

5. Pathophysiology Normal Retino - geniculo -cortical pathway Critical period 3 periods in development of visual acuity and ocular dominance i ) Development of acuity: birth to 3-5 yrs ii) Period during which deprivation causes amblyopia : birth to 7-8 yrs iii) Period during which recovery can occur: time of deprivation to teenage life Time of functional architecture development and maturation of visual cortex is the ‘ critical period ’. Imbalance/disruption in this period leads to alteration in neuronal signals to visual input.

6. Retinal changes Development of retinal cones depends on visual experience and maturation continues till adulthood Amblyopigenic factors hinder in maturation of cones and reduced sensitivity of foveal cones has been noted in Amblyopes Reduced bioelectric activity in retina, as shown using Electroretinogram studies by Slyshalova , has been noted in Amblyopes Stellwagen D, Shatz CJ. An instructive role for retinal waves in the development of retinogeniculate connectivity. Neuron 2002: 357-367. Slyshalova NN, Shamshinova AM. Retinal bioelectrical activity in amblyopia . Europe PMC 2008. 124:32-36

7. Cortical changes Hubel and Wiesel demonstrated that the axons carrying visual stimuli from the 2 eyes form ocular dominance columns(ODC) in the primary visual cortex, in which inputs from the 2 eyes alternate equally. Axonal arborization , forming multiple connections occurs in Lateral Geniculate Nucleus and Cortex. Cortical circuit is immature in postnatal life and ODCs amenable to alteration. Decreased stimuli from one eye during critical period leads to narrowing of ODCs in this eye and expansion in the fellow eye Le Vay S, Wiesel TN, Hubel DH. The development of ocular dominance columns in normal and visually deprived monkeys. J Comp Neurol 1980;191:1‑51.

8. Clinical evaluation Thorough clinical history- current age - age when low vision noted - duration - deviation noted or not, constant/intermittent - white reflex or any other abnormailty noted - family h/o low vision/squinting - prior treatment received Thorough clinical examination, including Acuity, pupillary reactions, extraocular movements, anterior segment and posterior segment examination.

9. Clinical signs Deceased visual acuity Decreased stereoacuity Fixation preference Crowding phenomenon Deviation in strabismic amblyopia

10. Diagnosis & Ancillary testing Key to successful treatment: Early detection Screening at young age: Cost effective and clinically effective American Academy of Ophthalmology recommends first screening by the age of 3 years and thereafter every 2 years Ideal treatment window: first decade of life Regular screening programs in schools have aided in early detection of low vision in children and timely referrals to hospitals

11. Visual Acuity Atleast a difference of 2 lines between the amblyopic eye and normal eye on Snellen chart For Bilateral disease: VA 6/12 or less in each eye Pre-verbal children - Fixation and following : Using bright attention grabbing objects - Comparison of two eyes : Reveals unilateral preference Child strongly objects to occlusion of normal eye - Fixation behaviour : Look for centration /steadiness/ maintainence - Preferential looking : Infants prefer patterns rather than simple stimulus. Teller cards(gratings) or Cardiff cards used.

12. Verbal children - Preferable to test at 4 meters distance than 6 meters (better compliance) - 2-3 years: Picture charts or crowded Kay chart or matching of optotypes charts - Older children: Crowded letter tests used

13. Crowding phenomenon Also called separation difficulty , it is the inability to discriminate optotypes that are crowded closely Amblyopes can discriminate optotypes when presented singly against a uniform background( angular acuity/single E acuity ) rather than when presented in a row( line acuity/ Snellen acuity ) Contour interaction and lateral inhibition suggested as underlying mechanism Single optotype acuity improves more than line acuity with treatment Thus, imperative to evaluate both Noorden GK, Campos EC. Binocular Vision and Ocular Motility, 6 th edition

14. Stereopsis Measured in seconds of arc Normal spatial resolution = 1 minute Normal stereoacuity = 60 seconds Lower value: better Titmus test : 3-D polarized vectograph with 2 plates, viewed with polarized spectacles. Right side has a large fly, Left side has series of circles and animals. Performed at 40 cm distance. - Fly: Gross stereopsis (3000 seconds), for younger children. Ask to hold wings between finger and thumb - Circles: Graded series 800 to 40 sec of arc. One circle stands out from the rest - Animals: 400 to 100 sec of arcs. One animal stands out

15. TNO test : Radomly distributed red & green dots viewed with red-green spectacles. In different plates, different shapes formed. Measures 480 to 15 seconds of arc. Lang test : Targets seen with one eye at a time through built-in cylindrical lens. Plates have dots that create disparity and a shape is seen. Does not require special spectacles.

16. Sensory Anomaly testing Worth 4 dot test : Patient wears red lens in front of right eye and green in front of left eye. Asked to view box with 4 lights: one white, one red, two green. - Normal BSV: All 4 seen - 2 reds seen: Left suppression - 3 greens: Right suppression - 2 red & 3 green: Diplopia - Alternating red and green: Alternate suppression

17. Bagolini striated glasses : Patient wears glasses with lens having striations, that converge point source of light into a line. The two lenses are placed at 45 and 135 degrees respectively, and fixated on a focal light source. - lines intersect at their centres in X pattern: Normal BSV - lines seen but no crossing: diplopia - only one streak seen: supression - small gap in one of the streaks: suppression scotoma

18. Deviation measurement Hirschberg test : Rough objective estimate of manifest strabismus Pen torch shone in patient’s eye at an arm’s length Corneal reflection in deviated eye is decentred , opposite to direction of squint. 1mm deviation ~ 7 degrees(15 dioptres ) - at temporal border of pupil ~ 15 degrees - at limbus ~ 45 degrees Krimsky test : Prisms placed in front of fixating eye until corneal reflections symmetrical Prism reflection test : Prisms placed in front of deviated eye until corneal reflections symmetrical

19. Cover-uncover test Cover test: detect heterotropia . - Patient looks straight, examiner covers fixing eye and notices movement of deviated eye - No movement: Orthotropia / heterotropia of fixing eye - Movement and Fixation of deviated eye: Heterotropia in deviated eye - Downward movement: Hypertropia - Upward movement: Hypotropia Uncover test: detect heterophoria - Patient looks straight, examiner covers the eye for 2-3 seconds and notes movement after uncovering - No movement: Orthophoria - Adduction: Exophoria - Abduction: Esophoria - Upward/downward: Vertical phoria

20. Alternate cover test : Induces dissociation to reveal deviation on fusion disruption - One eye covered for few seconds, occluder then shifted to other eye. - Back and forth shifting few times - Decompensation to manifest deviation seen in a patient with poor control. Prism cover test : Measure angle of deviation in near/distance fixation - prism bar with prisms of progressive strength used - prism placed in front of the eye, with base opposite to direction of deviation - amplitude of re-fixation noted with increasing strength - strength of prisms increased till no movement seen

21. Refraction Cycloplegic refraction should be carried out in all children Prevents underestimation of the refractive error and better visualization of retinoscopic reflex Cyclopentolate : 0.5% for infants, 1% for older children 1 drop, repeated after 5 minutes Retinoscopy performed 45 min after first drop Atropine ointment : 0.5% for infants, 1% for older Preferred in children <5 years Applied twice daily, for 3 days before refraction

22. Treatment Early diagnosis and initiation of therapy is the key. A study by Pediatric Eye Disease Investigator Group (PEDIG) on treatment of moderate strabismic and/or anisometropic amblyopia showed that the visual acuity of the amblyopic eye improved to 20/30 or better 6 months after initiating treatment in 75% children under 7 years of age Principles - Removal of cause of amblyopia - Correction of refractive error - Promotion of use of amblyopic eye over fellow eye

23. Cataract removal - Removal of congenital cataracts within 4-6 weeks of life - In B/L disease, interval between both eyes should be 1-2 weeks - Significant traumatic cataract should be removed withing few weeks Refractive error correction - initial treatment of choice - cycloplegic refraction f/b adequate correction - vision improvement in 1/3 rd patients observed in Amblyopia Treatment Study - full correction of astigmatism, myopia and anisometropia - undercorrection of hypermetropia by no more than +1.50DS

24. PEDIG has performed extensive research on amblyopia in the Amblyopia Treatment Study(ATS) Optimal refractive correction with frequent follow ups should be tried as first line of treatment ATS 5 Studied effect of refractive corrcction alone in anisometropic amblyopia . Total resolution noted in 27% patients ATS 7 Studied effect of refractive correction alone in bilateral refractive amblyopia . 74% achieved BCVA 20/25 ATS 13 Effect of refractive correction alone in strabismic amblyopia . Full resolution in 32% patients noted Pediatric Eye Disease Investigator Group. Optical Treatment of Strabismic and Combined Strabismic-Anisometropic Amblyopia . Ophthalmology 2011

25. Recommended refractive correction in children www.aao.org

26. Active treatment- Occlusion therapy Occlusion of the sound eye removes inhibitory stimulus, arising from it’s visual stimulation Initiated in children who are not improving with refractive correction alone Types of occluders - adhesive skin patches - commercially available opticludes - spectacle/contact lens occluder Constant motivation of child and parents needed Encourage active vision exercises

27. ATS studies These studies showed that patching was an effective treatment for treating amblyopia . Part time patching is the preferred modality. Optimal improvement occurs when BCVA is first stabilised with refractive correction, then patching initiated Pediatric Eye Disease Investigator Group. A randomized trial comparing Bangerter filters and patching for treatment of moderate amblyopia in children. Ophthalmology 2010; 117: 998-1004 ATS 2b Compared 2 hours vs 6 hours patching in moderate amblyopia . At 4 months, BCVA improvement of 2.4 lines in both with better compliance in 2 hour group ATS 2a Compared 6 hour patching vs full time patching in severe amblyopes . At 4 months, both groups had 4.8 lines BCVA improvement with better compliance in 6 hours group ATS 5 2 hours patching in mod. and severe amblyopia after BCVA stabilisation with spectacles. 2.2 lines improvement seen in patching group compared to control group

28. PEDIG studies now recommend 2 hours patching in moderate amblyopia (VA 20/40-20/100) and 6 hours patching in severe amblyopia (VA 20/100-20/400) Follow up depends on age, severity and compliance If no improvement seen despite compliance, look for other causes Pediatric Eye Disease Investigator Group. A randomized trial comparing Bangerter filters and patching for treatment of moderate amblyopia in children. Ophthalmology 2010; 117: 998-1004

29. Kapoor S. Update on Diagnosis and Management of Amblyopia .

30. Penalisation Optically defocusing the better eye with therapeutic means Cycloplegia with atropine or using glass lens Indicated in - non compliant patients - mild amblyopia Disadvantages - Systemic absorption of Atropine and side effects - Occlusion amblyopia

31. ATS study PEDIG studies have found atropinisation to be as effective as patching Pediatric Eye Disease Group. A randomized trial of atropine vs patching for treatment of amblyopia in children. Arch Ophthalmol 2002. 120:268-78. ATS 1 Studied 1% daily Atropine vs 6 hours patching in mod amblyopia . At 2 yrs, 20/32 vision in 86% patching and 83% atropine group ATS 4 Daily atropine use compared to weekend only use. Both groups improved by 2.3 lines ATS 8 Compared refractive correction alone with correction plus atropinisation . Treatment group imrpoved to 2.8 lines vs 2.4 lines in control group

32. Surgery Stabismus surgery should always be performed after adequate treatment for and reversal of amblyopia Refractive surgeries for refractive amblyopia in non-compliant patients - enhance binocular vision - improve spectacle tolerance

33. Pharmacologic adjuncts Levodopa : Some investigators reported low levels of retinal Dopamine in deprivation amblyopia - a PEDIG trial with levodopa and 2 hours patching found no significant gain in visual acuity - another trial by Sofia et al , utilising 3 times more dosage than PEDIG trial found significant vision gain at 1 year follow up Citicholine : Confers cholinergic and neuroprotective properties. - earlier studies were promising - no concrete evidence to support use Sofi IA, Gupta SK, Bharti A, Tantry TG. Efficiency of the occlusion therapy with and without levodopa‑carbidopa in amblyopic children‑A tertiary care centre experience. Int J Health Sci 2016;10:249‑57.

34. Upcoming modalities Binocular visual stimulation: through the use of dichoptic glasses while playing video games is the newest treatment regimen under investigation - patients wearing red-green 3D glasses asked to play games on iPad - amblyopic eye receives higher contrast than fellow eye - as binocular function develops, contrast gradually reduced upto a potential point where no difference in contrast is required

35. PEDIG conducted a large-scale trial comparing the effectiveness of 1 hour/day, 7 days/week binocular game play to 2 hours/day patching in children<13 and found no statistically significant difference between the groups at 16 weeks. Holmes JM, Manh VM, Lazar EL, et al. . Effect of a Binocular iPad Game vs Part-time Patching in Children Aged 5 to 12 Years With Amblyopia : A Randomized Clinical Trial. JAMA Ophthalmol 2016;134:1391–400.

36. AmbP iNet program for the treatment of amblyopia Can be assessed at http://www.visiontherapysolutions.net 12 treatment programs, five days per week Designed to improve hand eye co‐ordination, visual acuity, crowding effect and visual memory Improvement in acuity as well contras sensitivity seen Avr am E, Stanila A . Treating anisometric amblyopia with HTS Amblyopia iNet Software--preliminary results. Oftalmologia 2013; 57:32-7

37. Interactive binocular treatment (I- BiT ) system Dichoptic stimuli presented via virtual reality game play or movie watching Shutter glasses used, where the glasses lighten and darken in synchrony with the monitor, allowing an enriched image to be presented to the amblyopic eye only Treatment well tolerated and imrovement in visual acuity seen in studies   Herbison  N,  MacKeith  D , Vivian A ,  et al  .  Randomised controlled trial of video clips and interactive games to improve vision in children with amblyopia using the I- BiT system. Br J Ophthalmol  2016; 100 :1511–6 .

38. Liquid crystal display eyeglasses : eyeglasses alternate between a clear and opaque lens before the fellow eye - an electronic shutter controlled by a pre-programmed microchip - improvement in near and distance visual acuity noted - compliance found to be better than patching Spierer , A., Raz , J., BenEzra , O., Herzog, R., Cohen, E., Karshai , I., & BenEzra , D. (2010).  Treating Amblyopia with Liquid Crystal Glasses: A Pilot Study. Investigative Opthalmology & Visual Science, 51(7), 3395.  doi:10.1167/iovs.09-4568

39. Take home message Amblyopia is a common childhood problem With early screening and treatment, economic as well as social burden of the disease can be reduced Appropriate and early therapy can help achieve good visual outcomes Motivated , compliant child and parents are an ally to the therapist in treatment Goal of therapy should also include attainment of good binocular function, apart from visual acuity

40. Thank you