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Alaska Blind Child Discovery

A cooperative, charitable research project to Eliminate Amblyopia Blindness in Alaska



BACKGROUND/AIMS: The effectiveness of occlusion therapy for the treatment of amblyopia is a research priority. The authors describe the design of the Monitored Occlusion Treatment for Amblyopia Study (MOTAS) and its methodology. MOTAS will determine the dose-response relation for occlusion therapy as a function of age and category of amblyopia. METHODS: Subjects progress through up to three study phases: (1) Assessment and baseline phase: On confirmation of eligibility, and after parental consent, baseline visual functions are determined, and spectacles prescribed as necessary; (2) Refractive adaptation phase: Subjects wear spectacles full time and return to clinic at 6 weekly intervals until 18 weeks, by which time all improvement due to refractive correction is complete; (3) Occlusion phase: All subjects are prescribed 6 hours of occlusion per day. Daily occlusion is objectively monitored using an occlusion dose monitor (ODM). Outcome variables: visual acuity (logMAR charts), log contrast sensitivity (Pelli-Robson chart), and stereoacuity (Frisby) are assessed at 2 weekly intervals until gains in visual acuity cease to be statistically verifiable. CONCLUSION: Four methodological issues have been addressed; firstly, baseline stability of visual function; secondly, differentiation of refractive adaptation from occlusion; thirdly, objective measurement of occlusion dose and concordance; fourthly, use of validated outcome measures.( Stewart CE, Fielder AR, Stephens DA, Moseley MJ. Design of the Monitored Occlusion Treatment of Amblyopia Study (MOTAS). Br J Ophthalmol 2002;86(8):915-9.)

PURPOSE: Amblyopia is the commonest visual disorder of childhood. Yet the contributions of the two principal treatments (spectacle wear and occlusion) to outcome are unknown. This study was undertaken to investigate the dose-response relationship of amblyopia therapy. METHODS: The study comprised three distinct phases: baseline, in which repeat measures of visual function were undertaken to confirm the initial visual deficit; refractive adaptation: an 18-week period of spectacle wear with six weekly measurements of logarithm of the minimum angle of resolution (logMAR) visual acuity; occlusion: in which participants were prescribed 6 hours of "patching" per day. In the latter phase, occlusion was objectively monitored and logMAR visual acuity recorded at 2-week intervals until any observed gains had ceased. RESULTS: Data were obtained from 94 participants (mean age, 5.1 +/- 1.4 years) with amblyopia associated with strabismus (n = 34), anisometropia (n = 23), and both anisometropia and strabismus (n = 37). Eighty-six underwent refractive adaptation[Spectacle treatment of amblyopia]. Average concordance with patching was 48%. The relationship between logMAR visual acuity gain and total occlusion dose was monotonic and linear. Increasing dose rate beyond 2 h/d hastened the response but did not improve outcome. More than 80% of the improvement during occlusion occurred within 6 weeks. Treatment outcome was significantly better for children younger than 4 years (n = 17) than in those older than 6 years (n = 24; P = 0.0014). CONCLUSIONS: Continuous objective monitoring of the amount of patching therapy received has provided insight into the dose-response relationship of occlusion therapy for amblyopia. Patching is most effective within the first few weeks of treatment, even for those in receipt of a relatively small dose. Further studies are needed to elucidate the neural basis for the dose-response functions.( Stewart CE, Moseley MJ, Stephens DA, Fielder AR. Treatment dose-response in amblyopia therapy: the Monitored Occlusion Treatment of Amblyopia Study (MOTAS). Invest Ophthalmol Vis Sci 2004;45(9):3048-54.)

PURPOSE: To identify factors that influence the outcome of treatment for unilateral amblyopia, as a part of the Monitored Occlusion Treatment of Amblyopia Study (MOTAS). METHODS: This was an intervention study consisting of three nonoverlapping phases: "Baseline", "refractive adaptation" (18 weeks of full-time spectacle wear), and "occlusion" (6 hours of patching per day, objectively monitored). Condition factors: type of amblyopia, age of participant, initial severity of amblyopia, fixation, and binocular vision status; treatment factors: refractive adaptation and occlusion (total dose [hours] and dose rate [hours per day]) were assessed for their influence on visual outcome. Visual outcome was expressed in three ways: logMAR (logarithm of the minimum angle of resolution) change, residual amblyopia, and proportion of the deficit corrected. RESULTS: The study included 85 participants (mean age, 5.1 +/- 1.4 years) with amblyopia associated with strabismus (n = 32) or anisometropia (n = 20) or associated with both anisometropia and strabismus (n = 33). Treatment factors: cumulative occlusion dose exceeding 50 hours, and dose rates >/=1 hour per day resulted in (P </= 0.01) lower residual amblyopia and a greater proportion of the deficit corrected. Condition factors associated with poor outcome (high residual amblyopia) were presence of eccentric fixation, severe initial amblyopia, and no binocular vision. CONCLUSIONS: Factors influencing outcome with treatment for amblyopia are occlusion dose (the rate of delivery and cumulative dose worn), the initial severity of the amblyopia, binocular vision status, fixation of the amblyopic eye, and the age of the subject at the start of treatment.( Stewart C, Fielder A, Stephens D, Moseley M. Treatment of unilateral amblyopia: factors influencing visual outcome. Invest Ophthalmol Vis Sci 2005;46(9):3152-3160.)

We examined the loss of letter contrast sensitivity (LCS) measured using the Pelli-Robson chart, and the extent to which any such loss was modulated by spectacle wear and occlusion therapy in children participating in an amblyopia treatment trial. Their initial mean interocular difference in logMAR acuity was approximately three times that of their LCS (0.45 vs 0.14 log units). Log LCS was weakly though significantly correlated with logMAR visual acuity (VA) for all VAs better than 0.90 (r = -0.19, 95% CI: -0.28 to -0.10) whereas for all VAs of 0.90 or poorer, log LCS was markedly and significantly correlated with VA (r = -0.72, 95% CI: -0.83 to -0.53). LCS in those children with a > or =0.1 log unit interocular difference on this test improved commensurately with VA during treatment. We conjecture that the spatial visual loss in all but the most severe amblyopes occurs in an area of resolution and contrast space that lies beyond that sampled by the Pelli-Robson chart.( Moseley MJ, Stewart CE, Fielder AR, Stephens DA. Intermediate spatial frequency letter contrast sensitivity: its relation to visual resolution before and during amblyopia treatment. Ophthalmic Physiol Opt 2006;26(1):1-4.)

PURPOSE: This article describes an empirically derived mathematical model of the treatment dose-response of occlusion therapy for amblyopia based on outcome data obtained from the Monitored Occlusion Treatment for Amblyopia Study (MOTAS). METHODS: The MOTAS protocol comprised three discrete phases: baseline, refractive adaptation, and occlusion. Only data from the occlusion phase were used in this dose-response model. Seventy-two participants, 3 to 8 years of age, mean +/- SD age 5.2 +/- 1.4 years (anisometropia [n = 18]); strabismus [n = 22]); both anisometropia and strabismus [n = 32]) completed the occlusion phase. All participants were prescribed 6-h/d patching, which was objectively monitored by an occlusion dose monitor (ODM). RESULTS: Simple normal linear regression modeling of the data on an interval-by-interval basis (interval between clinic visits) indicates that increasing cumulative dose within interval (hours) yields an increase in visual acuity (R(2) = 0.918; 684 data points). Most of the children achieved their best visual acuity with 150 to 250 hours' cumulative dose. Specific patient characteristics (especially age) modify the steepness of this function. For example, a 0.20-logMAR (2-line logarithm of the minimum angle of resolution) gain in visual acuity requires a cumulative dose of 170 hours for children at age 48 months and 236 hours at age 72 months. CONCLUSIONS: Mathematical modeling of amblyopia therapy is a novel approach that elucidates the kinetics of the therapeutic response in humans. This response is age-influenced so that older children require a greater dose to achieve the same outcome-evidence of altered plasticity of the visual system. Fine-tuning the dose-response in amblyopia therapy will facilitate the development of child-specific, evidence-based treatment plans.( Stewart CE, Stephens DA, Fielder AR, Moseley MJ. Modeling dose-response in amblyopia: toward a child-specific treatment plan. Invest Ophthalmol Vis Sci 2007;48(6):2589-94.)
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