o Georges-Louis LeClerc, Comte de Buffon,1743 o Comberg (1930 s) flashing letters o Bangerter (1940 s) the localiser, the corrector, the drill

Transcription

1 03/11/2014 Amblyopia What s all the fuss about? Basis for treatment Reduced visual acuity, despite full optical correction No observable pathology Most cases are believed to be caused by strabismus or anisometropia Prevalence is 1-3% Most common pediatric ophthalmic disorder in industrialized countries Professor Anita J Simmers In the UK, ~90% of UK children s hospital eye appointments are for amblyopia treatment or screening for it NES Annual Conference Glasgow 2014 Basis for treatment Intriguing history of treatment o Hippocrates, 480 BC used the term amblyopia Having amblyopia greatly increases the risk of blindness/ significant visual loss in later life Chua & Mitchell (2004): the chances of the better eye s visual acuity being reduced to 6/12 or worse are 2.7 times greater in amblyopes than visual normals [16x> as a child (Rahi et al., 2002)] Leeuwen et al. (BJO,2007) risk of socially significant visual Impairment in amblyopes is almost double (18%) compared to visual normals (10%) o Georges-Louis LeClerc, Comte de Buffon,1743 Dissertation sur les causes du Strabisme, he described the weak eye as regaining all its strength by occluding the good eye ( reprendre toutes ses forces ) o Comberg (1930 s) flashing letters o Bangerter (1940 s) the localiser, the corrector, the drill o Bangerter and Cuppers (1950 s) pleoptics o Campbell (1970 s) CAM visual stimulator 1

2 03/11/2014 strychnine arbidopa levodopa/c Downloaded from bjo.bmj.com on March 21, Published by group.bmj.com Corrector Localizer Preliminary results of a physiologically based treatment of amblyopia eyeball mas 749 patient to the grating disc was 57 cm, but almost all the children worked closer than this. If only 1 patient was being treated, the orthoptist acted as the opponent in the game for the duration of the treatment. The length of treatment was standardised so that the patient was observing the gratings for 7 minutes. The selected grating to be used was placed on the turntable; the Perspex plate was placed over this, and the patients were given drawing pens. The patients were then instructed, according to age and abilities, to play 'noughts and crosses', 'hangman', 'squares', or 'boxes', or to draw pictures, while the grating was rotating under the Perspex plate. This procedure forced the child to attend to the under- Drill lying stimulus. All patients had a full ophthalmological examination, cycloplegic refraction, and orthoptic assessment, although it was not possible to fully assess binocular functions in all of them. The majority of Fig. 1 The grating treatment device in use children tested (75 %) had previously undertaken partial or constant total occlusion, which had at The simplicity and low cost of the method has best been only partially effective. Before any treatencouraged us to publish these early results so that ment was administered, visual acuity was assessed the treatment can be assessed on a much greater by the Snellen or linear Sheridan Gardiner optonumber of children and adults. types and Sheridan single optotypes at 6 and 033 m. In those patients who had been recently accepted for Patients and methods treatment contrast thresholds for both a low and medium spatial frequency grating were assessed Treatment consists in viewing an apparatus on with simplified clinical plates. which any one of a selection of high-contrast These plates were circular and consisted of a sine square-wave gratings are rotated slowly at 1 revo- grating each at a different contrast level near lution per minute behind a transparent cover on threshold. Each plate was presented to the child which drawing games can be played. Occlusion was firstly at the highest contrast, and the child indicated used (only during the test) to limit vision to the its orientation. The contrast at which this task could amblyopic eye. If possible, 2 patients of equal age not be performed was taken as the threshold. and intelligence were seated side by side in front of Normal and amblyopic eyes were tested with this the apparatus with the non-amblyopic eye occluded technique for a low as well as a medium frequency (Fig. 1). The intended distance from the eye of the grating. CAM Fig. 2 Range ofgrating stimuli used plaster cast arm restraints sage acupunctur e diet of white wine and hypnosis removal of the adenoid s veal suturing eyelids I I I IiDiI FINhI"I I I I I 1I Ii" Can Amblyopia be Treated? Response to spectacle wear Refractive adaptation Improvement due to Correction of refractive error Distinct component of amblyopia treatment expect 2-3 lines gain Only 5% show no significant improvement Needs full differentiation from occlusion Effective in all types of amblyopia and/or Occlusion? Clinical impact Start occlusion with improved visual acuity May enhance concordance Occlusion avoided for some Moseley et al 2002 Stewart et al

3 03/11/ forces patient to use the amblyopic eye by preventing fellow eye from taking part in vision 0.10 log units LogMAR visual acuity 0.88 Occlusion 0.68 (0.60) (0.50) 0.78 Occlusion that excludes light and form: 0.66 (0.48) 4 weeks Amblyopic Eyes Occlusion that excludes form vision: 0.54 o Bangerter foils (various densities) o blenderm opaque sticky tape o frosted glass 0.28 (0.22) (0.04) 0.06 o patches such as plasters BEST (worn on face to avoid peeking) o hand made cloth to go over glasses (but may peek) o opaque contact lenses (dense amblyopia) Optical penalization o high plus contact lenses for milder amblyopia o manipulate spectacle correction to create blur in dominant eye" Moseley et al., 2002 Response to occlusion Difficult to assess effectiveness with dose-rates due to variable compliance with patching Thus dose-response has been limited Need for precise, objective Measurements of occlusion dose the occlusion dose monitor (ODM) Monitored Occlusion Treatment for Amblyopia Study (MOTAS) Randomized Occlusion Treatment of Amblyopia Studies (ROTAS) Model used for clinical trials Fielder, Stewart and Moseley

4 Methods of MOTAS Subjects 94 (mean age = 5.1 ± 1.4 years) Strabismus (n=34) Anisometropia (n=23) Mixed (n=37) Phases Initial assessment Refractive adaptation Occlusion Outcome variables LogMAR visual acuity Log letter contrast sensitivity (Pelli-Robson) Occlusion objectively recorded using an ODM (Fielder et al. 1994) Visual Acuity (logmar) Occlusion dose (hours per day) Dose monitoring occlusion hours per week (42) JO, Age 3 years 0.6 strabismic amblyopia 0.5 Amblyopic eye Fixing eye occlusion started Time (weeks) Conclusion MOTAS Positive dose-response linear up to 400 hours 75% of improvement with occlusion in the first 6 weeks No significant difference in response to occlusion between types of amblyopia What's the optimum occlusion dose-rate? ROTAS Occlusion phase 81 (mean age = 5.5 ± 1.5 years) with amblyopia Strabismus (n=19; age = 4.6 ± 1.2) Anisometropia (n=35; age = 6.2 ± 1.5) Anisometropia and strabismus (n=27; age = 5.1 ± 1.2) 81 randomised to be prescribed occlusion 6-hour group (n=39; age = 5.4 ± 1.7) 12 strabismic, 13 anisometropic, 14 mixed 12-hour group (n=42; age = 5.6 ± 1.4) 7 strabismic, 22 anisometropic, 13 mixed Stewart et al

5 Prescribed dose Outcome same for both prescribed groups 6 hrs/day (n=39) 12 hrs/day (n=42) Mann- Whitney VA start 0.45 ± ± 0.30 p = 0.87 VA best 0.19 ± ± 0.24 p = 0.71 Change in visual acuity 0.26 ± ± 0.19 p = 0.64 Residual amblyopia 0.17 ± ± 0.23 p = 0.25 Proportional improvement 0.67 ± ± 0.36 p = 0.34 Cumulative dose (hrs) 235 ± ± 251 p = 0.30 Dose-rate (hrs/day) 4.0 ± ± 3.90 p = 0.06 Time until best (days) 59± ± 33 p = 0.48 Conclusions from ROTAS Prescribed dose-rates of 6 hrs/day and 12 hrs/day provide equivalent visual outcome Concordance for 12 hrs/day was 3.6 x more variable than for 6 hrs/day Monitoring actual doses received reveals that moderate doses ( 4 hrs/day) are required to achieve optimum outcome Increasing doses above 4 hrs/day does no further benefit to outcome Currently Refractive adaptation is an important component of amblyopia treatment Monitoring actual dose worn has provided insight into dose-response function of occlusion treatment for amblyopia Someday these devices will be part of routine clinical practice 4 hours/day seems optimum regimen for most children Bangerter Filters alternative to a patch o PEDIG Ophthalmology (2010) o o 186 children (3-10yrs) with moderate amblyopia (6/12-6/24) RCT: patching 2 hrs v s Filters (.3 or.2) monitored every six weeks for 6 months. Glasses worn min. 16 weeks before intervention 5

6 Patching advantage less than 0.5 line Less adverse effects, social stigma with Bangerter Group No difference stereopsis, compliance Reasonable first choice option in moderate amblyopia Penalisation alternative to a patch o o o o o Long acting topical cycloplegic agent to fellow eye o Atropine ointment o Atropine drops o Repka et al (2004) reports that moderate amblyopia is as effectively treated by instilling once daily at the weekends. To prevent accommodation of fellow eye Encourages amblyopic eye to fixate at near Optical over correction used to achieve additional blurring of fellow eye (commonly by to +3.00) will blur for distance Side effects (lid/conjunctival irritation, light sensitivity, eye pain/ headache, facial flushing, skin irritation) Effectiveness of atropine penalisation Trial of 6-8 hours/ a day patching vs. atropine penalization Similar gains for moderate amblyopia Atropine has a higher degree of acceptance and concordance Reduced atropine scheduling (weekend) appears as effective as daily Not usually effective for children with severe amblyopia PEDIG 2004, 2009, 2010 What is the impact of active vs. passive treatment What is passive? Refractive correction with/without occlusion Requires no action on part of patient What is active? Specific tasks assigned in addition to passive treatment or sometimes in isolation Engage patient and encourage use of amblyopic eye 6

7 Active treatment: near activities What evidence exists? No high level evidence Previous research may be supportive but plagued by lack of control/compliance Recent evidence (PEDIG 2008) raises some questions 425 children (3-7 yrs) all types of amblyopia 6/12 6/120 2hrs occlusion - randomized into two groups- active vs. passive ~2.5 lines improvement both groups No difference in rate of improvement or compliance Things to watch out for If visual deficit progresses during treatment Investigate further Poorly controlled phorias do occlusion gingerly likely to regain control with improved VA Older strabismic amblyopes with weak suppression Assess likelihood of decompensation or intractable diplopia. May decide not to treat if either likely Follow up Reviewed regularly once treatment started in order to prevent occlusion amblyopia at least every 3 months (RCO guidelines) Younger children review more regularly What about the future? More occlusion review more regularly Once visual acuity stable for 2 consecutive visits consider stopping occlusion Slowly taper off occlusion maintenance occlusion 7

8 Aims of New Treatment o It would be a more effective treatment for amblyopic children o It might be applicable to those who treatment has been abandoned and the many adults left permanently visually disabled o It would not have the adverse psycho-social effects of the present approach o It might promote cooperation between the two eyes with the hope of establishing some rudimentary form of binocular function Aims of New Treatment o It would be a more effective treatment for amblyopic children o It might be applicable to those who treatment has been abandoned and the many adults left permanently visually disabled o It would not have the adverse psycho-social effects of the present approach o It might promote cooperation between the two eyes with the hope of establishing some rudimentary form of binocular function Is there plasticity beyond the sensitive period for amblyopia? our ideas of cortical plasticity in amblyopia are undergoing change Clinical trials provide some clues PEDIG randomised trials have shown in 7-13 year olds and years patching 2-6 hours with near activities can improve visual acuity even if the amblyopia has been previously treated No trials on adults 8

9 03/11/2014 Three blind mice Plasticity in adults cortex. Baroncelli et al Recent studies show 10 Is visual loss permanent? from El Mallah et al., 2000 remarkable plasticity in amblyopes with AMD in their fellow eye Incentive to manage co- Evolving plastic capacity across the lifespan (blue arrows) (E/I, Excitatory-inhibitory circuit balance) suggests possible mechanisms for enhancing learning and recovery of function in adulthood (red). Bavelier et al deterioration - Mallah at al (2000) reported 5 morbidity in patients with amblyopia more proactively -100 Amblyopic Eyes Fellow Eyes Change in logmar (%) spontaneous improvement after losing the fellow eye Change in logmar (lines) - Some amblyopes show 200 improvement remarkable plasticity in adult visual cortex Visit Perceptual Learning Perceptual Learning o concept that humans are capable of improving performance through repeated practice - human brain is malleable & plastic o concept that humans are capable of improving performance through repeated practice - human brain is malleable & plastic o à la mode in visual and cognitive rehabilitation o à la mode in visual and cognitive rehabilitation o practice on specific tasks (vernier acuity) can improve visual performance Snellen acuity o practice on specific tasks (vernier acuity) can improve visual performance Snellen acuity Bisection up/down Curvature left/right Interval wider/narrower 9

10 Perceptual Learning o concept that humans are capable of improving performance through repeated practice - human brain is malleable & plastic o à la mode in visual and cognitive rehabilitation o practice on specific tasks (vernier acuity) can improve visual performance Snellen acuity o there have been more than 20 studies of PL in amblyopia published to date, involving more than 300 amblyopic subjects (Levi, 2012) Perceptual Learning o neural plasticity in adult amblyopia o this suggests that perceptual learning protocols might be important in providing a possible alternative or supplement to traditional amblyopia therapy o Is it too specific? Is it too boring? o What about video game play? 90% school aged children 10

11 average gamer 33 years Increased resolution Increased contrast sensitivity ~43% 11

12 CHAIR TABLE BOAT HORSE YELLOW BLUE RED ORANGE GREEN ORANGE RED YELLOW GREEN ORANGE BLUE RED BLUE GREEN BLUE YELLOW RED Video Game Play o Action video game (Medal of Honor) average improvement 1.6 lines o Non-action game play (Sim city) average improvement 1 line o Cross over (Sim city then Medal of Honor) average improvement 1 line o Control group (patch only) no improvement after 20 hours after switching to VGP average improvement 1.7 lines Li and Levi 2012 Aims of New Treatment o It would be a more effective treatment for amblyopic children o It might be applicable to those who treatment has been abandoned and the many adults left permanently visually disabled o It would not have the adverse psycho-social effects of the present approach o It might promote cooperation between the two eyes with the hope of establishing some rudimentary form of binocular function 12

13 Aims of New Treatment o It would be a more effective treatment for amblyopic children o It might be applicable to those who treatment has been abandoned and the many adults left permanently visually disabled o It would not have the adverse psycho-social effects of the present approach our ideas on the binocular status of amblyopia are undergoing change o It might promote cooperation between the two eyes with the hope of establishing some rudimentary form of binocular function Normal 60 Number of Cells ipsilateral binocular contralateral Binocular Dominance Category 13

14 Strabismus 200 Number of Cells ipsilateral binocular contralateral Binocular Dominance Category o a reduced sensitivity of cells driven by amblyopic eye and a reduced number of cells that receive input from both eyes o loss of monocular and binocular cellular function o binocular connections to cells in the cortex lost o unlikely to recover after critical period o a reduced sensitivity of cells driven by amblyopic eye and a reduced number of cells that receive input from both eyes o loss of monocular and binocular cellular function o binocular connections to cells in the cortex lost o unlikely to recover after critical period ARE BINOCULAR MECHANISMS INTACT IN AMBLYOPIA BUT UNUSED? the loss of binocular responsiveness of cortical cells has been shown to be partly reversible by selective blockers of GABA A receptors animal models show that correlated binocular vision is essential for successful recovery/play a critical role in the development from experimentally induced amblyopia the vision in the poorer eye of amblyopic adults can be temporarily improved (rtms) to the visual cortex 14

15 converging evidence that amblyopes possess cortical cells with binocular connections BUT that under normal viewing conditions inhibitory mechanisms render the cortex functionally monocular Improvement in VA Improvement in Stereo 15

16 o The majority of children showed an increase in visual function although traditional treatment regimes had previously reached a plateau o A dichoptic based learning therapy was effective in improving monocular visual acuity in the AE as well as stereo function o Whether the gains over the short treatment (5hrs vs. 60/80hrs) time observed in the present study resulted from the binocular modality of the training paradigm warrants further investigation o It can be hypothesized that patients who do not respond to existing treatments and/or show regression in visual function, may obtain an improved and more stable visual outcome with a binocular approach to treatment Perceptual Learning/Video Game Play o In contrast to perceptual learning VGP is varied and may have a broader transfer to real life o Entertainment games may have an advantage - Readily available - Rich and varied environment - Designed to encourage success flow - Arousal and award may increase dopamine levels 16

17 Binocular video games currently in development that incorporate entertainment and perceptual learning tasks In the meantime, practice (and videogame play) makes, if not perfect, better 17