Occlusion dose monitoring in amblyopia therapy: status, insights, and future directions.

Occlusion therapy remains the mainstay treatment of amblyopia, but its outcome is not assured or universally excellent. Many factors are known to influence treatment outcome, among which compliance is foremost. The occlusion dose monitor (ODM) removes one variable from the treatment equation, because it records the occlusion actually received by-rather than prescribed for-the child. Improvement observed can thus be quantitatively related to the patching received. This review summarizes the insights the ODM has provided to date particularly in elucidating the dose-response relationship. We are entering the era of personalized ophthalmology in which treatments will be tailored to the needs of the individual child and facilitated by the use of wearable monitors.

Treatment of Amblyopia Using Personalized Dosing Strategies: Statistical Modelling and Clinical Implementation.

PURPOSE: To generate a statistical model for personalizing a patient's occlusion therapy regimen. METHODS: Statistical modelling was undertaken on a combined data set of the Monitored Occlusion Treatment of Amblyopia Study (MOTAS) and the Randomized Occlusion Treatment of Amblyopia Study (ROTAS). This exercise permits the calculation of future patients' total effective dose (TED)-that predicted to achieve their best attainable visual acuity. Daily patching regimens (hours/day) can be calculated from the TED. RESULTS: Occlusion data for 149 study participants with amblyopia (anisometropic in 50, strabismic in 43, and mixed in 56) were analyzed. Median time to best observed visual acuity was 63 days (25% and 75% quartiles; 28 and 91 days). Median visual acuity in the amblyopic eye at start of occlusion was 0.40 logMAR (quartiles 0.22 and 0.68 logMAR) and at end of occlusion was 0.12 (quartiles 0.025 and 0.32 logMAR). Median lower and upper estimates of TED were 120 hours (quartiles 34 and 242 hours), and 176 hours (quartiles 84 and 316 hours). The data suggest a piecewise linear relationship (P = 0.008) between patching dose-rate (hours/day) and TED with a single breakpoint estimated at 2.16 (standard error 0.51) hours/day, suggesting doses below 2.16 hours/day are less effective. CONCLUSION: We introduce the concept of TED of occlusion. Predictors for TED are visual acuity deficit, amblyopia type, and age at start of occlusion therapy. Dose-rates prescribed within the model range from 2.5 to 12 hours/day and can be revised dynamically throughout treatment in response to recorded patient compliance: a personalized dosing strategy.

Personalized versus standardized dosing strategies for the treatment of childhood amblyopia: study protocol for a randomized controlled trial.

BACKGROUND: Amblyopia is the commonest visual disorder of childhood in Western societies, affecting, predominantly, spatial visual function. Treatment typically requires a period of refractive correction ('optical treatment') followed by occlusion: covering the nonamblyopic eye with a fabric patch for varying daily durations. Recent studies have provided insight into the optimal amount of patching ('dose'), leading to the adoption of standardized dosing strategies, which, though an advance on previous ad-hoc regimens, take little account of individual patient characteristics. This trial compares the effectiveness of a standardized dosing strategy (that is, a fixed daily occlusion dose based on disease severity) with a personalized dosing strategy (derived from known treatment dose-response functions), in which an initially prescribed occlusion dose is modulated, in a systematic manner, dependent on treatment compliance. METHODS/DESIGN: A total of 120 children aged between 3 and 8 years of age diagnosed with amblyopia in association with either anisometropia or strabismus, or both, will be randomized to receive either a standardized or a personalized occlusion dose regimen. To avoid confounding by the known benefits of refractive correction, participants will not be randomized until they have completed an optical treatment phase. The primary study objective is to determine whether, at trial endpoint, participants receiving a personalized dosing strategy require fewer hours of occlusion than those in receipt of a standardized dosing strategy. Secondary objectives are to quantify the relationship between observed changes in visual acuity (logMAR, logarithm of the Minimum Angle of Resolution) with age, amblyopia type, and severity of amblyopic visual acuity deficit. DISCUSSION: This is the first randomized controlled trial of occlusion therapy for amblyopia to compare a treatment arm representative of current best practice with an arm representative of an entirely novel treatment regimen based on statistical modelling of previous trial outcome data. Should the personalized dosing strategy demonstrate superiority over the standardized dosing strategy, then its adoption into routine practice could bring practical benefits in reducing the duration of treatment needed to achieve an optimal outcome. TRIAL REGISTRATION: ISRCTN ISRCTN12292232.

Compliance with occlusion therapy for childhood amblyopia.

PURPOSE: Explore compliance with occlusion treatment of amblyopia in the Monitored and Randomized Occlusion Treatment of Amblyopia Studies (MOTAS and ROTAS), using objective monitoring. METHODS: Both studies had a three-phase protocol: initial assessment, refractive adaptation, and occlusion. In the occlusion phase, participants were instructed to dose for 6 hours/day (MOTAS) or randomized to 6 or 12 hour/day (ROTAS). Dose was monitored continuously using an occlusion dose monitor (ODM). RESULTS: One hundred and fifty-two patients (71 male, 81 female; 122 Caucasian, 30 non-Caucasian) of mean ± SD age 68 ± 18 months participated. Amblyopia was defined as an interocular acuity difference of at least 0.1 logMAR and was associated with anisometropia in 50, strabismus in 44, and both (mixed) in 58. Median duration of occlusion was 99 days (interquartile range 72 days). Mean compliance was 44%, mean proportion of days with no patch worn was 42%. Compliance was lower (39%) on weekends compared with weekdays (46%, P = 0.04), as was the likelihood of dosing at all (52% vs. 60%, P = 0.028). Compliance was lower when attendance was less frequent (P < 0.001) and with prolonged treatment duration (P < 0.001). Age, sex, amblyopia type, and severity were not associated with compliance. Mixture modeling suggested three subpopulations of patch day doses: less than 30 minutes; doses that achieve 30% to 80% compliance; and doses that achieve around 100% compliance. CONCLUSIONS: This study shows that compliance with patching treatment averages less than 50% and is influenced by several factors. A greater understanding of these influences should improve treatment outcome. (ClinicalTrials.gov number, NCT00274664).

The effect of amblyopia treatment on stereoacuity.

PURPOSE: To explore how stereoacuity changes in patients while they are being treated for amblyopia. METHODS: The Monitored Occlusion Treatment for Amblyopia Study (MOTAS) comprised 3 distinct phases. In the first phase, baseline, assessments of visual function were made to confirm the initial visual and binocular visual deficit. The second phase, refractive adaptation, now commonly termed "optical treatment," was an 18-week period of spectacle wear with measurements of logMAR visual acuity and stereoacuity with the Frisby test at weeks 0, 6, 12, and 18. In the third phase, occlusion, participants were prescribed 6 hours of patching per day. RESULTS: A total of 85 children were enrolled (mean age, 5.1 ± 1.5 years). In 21 children amblyopia was associated with anisometropia; in 29, with strabismus; and in 35, with both. At study entry, poor stereoacuity was associated with poor visual acuity (P < 0.001) in the amblyopic eye and greater angle of strabismus (P < 0.001). Of 66 participants, 25 (38%) who received refractive adaptation and 19 (29%) who received occlusion improved by at least one octave in stereoacuity, exceeding test-retest variability. Overall, 38 (45%) improved one or more octaves across both treatment phases. Unmeasureable stereoacuity was observed in 56 participants (66%) at study entry and in 37 (43%) at study exit. CONCLUSIONS: Stereoacuity improved for almost one half of the study participants. Improvement was observed in both treatment phases. Factors associated with poor or nil stereoacuity at study entry and exit were poor visual acuity of the amblyopic eye and large-angle strabismus.

Amblyopia therapy: an update.

We review the findings of trials of mainstay amblyopia treatment conducted within the last 5 years. These have confirmed that an initial period of full-time refractive correction is beneficial in all types of amblyopia. Adopting this practice may allow up to 30% of children to avoid any further treatment. Studies that have investigated the role of atropine occlusion as a first-line treatment for amblyopia have shown "weekend atropine" to be as effective as patching for children with both moderate and severe amblyopia. Where patching is prescribed, 2-4 hours/day of occlusion appears sufficient to provide an optimum outcome for the majority of children, although those over 6 years tend to require a larger dose to achieve best outcome, their amblyopia being more resistant to treatment. Educational interventions such as cartoons and written and video explanations of treatment aimed at improving compliance appear to raise it to a therapeutic level in those who may otherwise have poor compliance or drop out from treatment. Formal, evidence-based practice guidelines for the management of amblyopia have emerged although their adoption by practitioners, at least in the United Kingdom, has been questioned.

Amblyopia and real-world visuomotor tasks.

A question of increasing interest to the basic science and clinical management communities during the past decade is whether children and adults with amblyopia and associated binocular visual abnormalities experience difficulties in executing real-world actions, to which vision normally makes an important functional contribution. Here we provide objective evidence that they do, by reviewing quantitative data from a number of studies comparing their performance with that of matched normally sighted subjects on a range of everyday visuomotor tasks. Because in real life, these tasks (grasping objects, walking, driving, reading) are habitually performed with both eyes open, our focus is on their binocular skill deficits, rather than those with their amblyopic eye alone. General findings are that individuals with abnormal binocularity show impairments in critical aspects of motor control--movement speed, accuracy or both--on every one of these activities, the extent of which correlates with their loss of stereoacuity, but not the severity of their amblyopia. Impairments were especially marked when the task was time-limited or novel. Implications are that children and adults with severely reduced or absent binocularity may be accident-prone when required to respond rapidly to unexpected situations and that amblyopia management should focus more attention on evaluating and restoring stereoacuity and stereomotion processing.

Optimizing microsurgical skills with EEG neurofeedback.

BACKGROUND: By enabling individuals to self-regulate their brainwave activity in the field of optimal performance in healthy individuals, neurofeedback has been found to improve cognitive and artistic performance. Here we assessed whether two distinct EEG neurofeedback protocols could develop surgical skill, given the important role this skill plays in medicine. RESULTS: National Health Service trainee ophthalmic microsurgeons (N = 20) were randomly assigned to either Sensory Motor Rhythm-Theta (SMR) or Alpha-Theta (AT) groups, a randomized subset of which were also part of a wait-list 'no-treatment' control group (N = 8). Neurofeedback groups received eight 30-minute sessions of EEG training. Pre-post assessment included a skills lab surgical procedure with timed measures and expert ratings from video-recordings by consultant surgeons, together with state/trait anxiety self-reports. SMR training demonstrated advantages absent in the control group, with improvements in surgical skill according to 1) the expert ratings: overall technique (d = 0.6, p < 0.03) and suture task (d = 0.9, p < 0.02) (judges' intraclass correlation coefficient = 0.85); and 2) with overall time on task (d = 0.5, p = 0.02), while everyday anxiety (trait) decreased (d = 0.5, p < 0.02). Importantly the decrease in surgical task time was strongly associated with SMR EEG training changes (p < 0.01), especially with continued reduction of theta (4-7 Hz) power. AT training produced marginal improvements in technique and overall performance time, which were accompanied by a standard error indicative of large individual differences. Notwithstanding, successful within session elevation of the theta-alpha ratio correlated positively with improvements in overall technique (r = 0.64, p = 0.047). CONCLUSION: SMR-Theta neurofeedback training provided significant improvement in surgical technique whilst considerably reducing time on task by 26%. There was also evidence that AT training marginally reduced total surgery time, despite suboptimal training efficacies. Overall, the data set provides encouraging evidence of optimised learning of a complex medical specialty via neurofeedback training.

The optical treatment of amblyopia.

The role of refractive correction has been underestimated as a distinct component of amblyopia therapy. Until relatively recently, the extent to which it could ameliorate the amblyopic acuity deficit remained unquantified and the time course of its effect unknown. Improvement of vision after refractive correction appears to occur in all the major types of amblyopia, including, somewhat surprisingly, in the presence of strabismus. Although the neurophysiological basis of the remediative effect of such "optical treatment" is unknown, some insight is now available from animal models and psychophysical investigations in humans. An appreciation of the role that refractive correction can play in the overall management of amblyopia has led to the formulation of new treatment guidelines, whereby a defined period of spectacle or contact lens wear always precedes traditional therapies, such as occlusion or penalization.

Computerized analysis of retinal vessel width and tortuosity in premature infants.

PURPOSE: To determine, with novel software, the feasibility of measuring the tortuosity and width of retinal veins and arteries from digital retinal images of infants at risk of retinopathy of prematurity (ROP). METHODS: The Computer-Aided Image Analysis of the Retina (CAIAR) program was developed to enable semiautomatic detection of retinal vasculature and measurement of vessel tortuosity and width from digital images. CAIAR was tested for accuracy and reproducibility of tortuosity and width measurements by using computer-generated vessel-like lines of known frequency, amplitude, and width. CAIAR was then tested by using clinical digital retinal images for correlation of vessel tortuosity and width readings compared with expert ophthalmologist grading. RESULTS: When applied to 16 computer-generated sinusoidal vessels, the tortuosity measured by CAIAR correlated very well with the known values. Width measures also increased as expected. When the CAIAR readings were compared with five expert ophthalmologists' grading of 75 vessels on 10 retinal images, moderate correlation was found in 10 of the 14 tortuosity output calculations (Spearman rho = 0.618-0.673). Width was less well correlated (rho = 0.415). CONCLUSIONS: The measures of tortuosity and width in CAIAR were validated using sequential model vessel analysis. On comparison of CAIAR output with assessments made by expert ophthalmologists, CAIAR correlates moderately with tortuosity grades, but less well with width grades. CAIAR offers the opportunity to develop an automated image analysis system for detecting the vascular changes at the posterior pole, which are becoming increasingly important in diagnosing treatable ROP.

Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina.

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found that short-wavelength light preferentially suppressed melatonin, reset the circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of the photopic visual system. In an action spectrum for pupillary constriction, the female subject exhibited a peak spectral sensitivity (lambda(max)) of 480 nm, matching that of the pRGCs but not that of the rods and cones. This subject was also able to correctly report a threshold short-wavelength stimulus ( approximately 480 nm) but not other wavelengths. Collectively these data show that pRGCs contribute to both circadian physiology and rudimentary visual awareness in humans and challenge the assumption that rod- and cone-based photoreception mediate all "visual" responses to light.

Objectively monitored patching regimens for treatment of amblyopia: randomised trial.

OBJECTIVES: To compare visual outcome in response to two prescribed rates of occlusion (six hours a day and 12 hours a day). DESIGN: Unmasked randomised trial. SETTING: Research clinics in two London hospitals. PARTICIPANTS: 97 children with a confirmed diagnosis of amblyopia associated with strabismus, anisometropia, or both. INTERVENTIONS: 18 week period of wearing glasses (refractive adaptation) followed by occlusion prescribed ("patching") for six or 12 hours a day. MAIN OUTCOME MEASURES: Visual acuity measured by logMAR letter recognition; objectively monitored rate of occlusion (hours a day). RESULTS: The mean age of children at study entry was 5.6 (SD 1.5) years. Ninety were eligible for occlusion but 10 dropped out in this phase, leaving 80 children who were randomised to a prescribed dose rate of six (n=40) or 12 (n=40) hours a day. The mean change in visual acuity of the amblyopic eye was not significantly different (P=0.64) between the two groups (0.26 (95% confidence interval 0.21 to 0.31) log units in six hour group; 0.24 (0.19 to 0.29) log units in 12 hour group). The mean dose rates (hours a day) actually received, however, were also not significantly different (4.2 (3.7 to 4.7) in six hour group v 6.2 (5.1 to 7.3) in 12 hour group; P=0.06). The visual outcome was similar for those children who received three to six hours a day or more than six to 12 hours a day, but significantly better than that in children who received less than three hours a day. Children aged under 4 required significantly less occlusion than older children. Visual outcome was not influenced by type of amblyopia. CONCLUSIONS: Substantial (six hours a day) and maximal (12 hours a day) prescribed occlusion results in similar visual outcome. On average, the occlusion dose received in the maximal group was only 50% more than in the substantial group and in both groups was much less than that prescribed. Younger children required the least occlusion. TRIALS REGISTRATION: Clinical Trials NCT00274664.

Modeling dose-response in amblyopia: toward a child-specific treatment plan.

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 (R2 = 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.

Factors affecting the stability of visual function following cessation of occlusion therapy for amblyopia.

AIM: To identify factors that predict which children with amblyopia are at greatest risk of regression of visual acuity (VA) following the cessation of occlusion therapy. METHOD: A retrospective analysis was performed of 182 children (mean age at cessation of treatment; 5.9+/-1.6 years) who had undergone occlusion therapy for unilateral amblyopia, and had been followed up at least once within 15 months of cessation. Statistical analysis was used to identify whether change in VA following treatment cessation had any association with various factors, including the child's age, type of amblyopia, degree of anisometropia, initial severity of amblyopia, binocular vision status, length and dose of occlusion therapy, and VA response to treatment. RESULTS: At 1 year, follow-up from treatment cessation, children with "mixed" amblyopia (both anisometropia and strabismus) demonstrated significantly (p=0.03) greater deterioration in VA (0.11+/-0.11 log units) than children with only anisometropia (0.02+/-0.08 log units) or only strabismus (0.05+/-0.10 log units). However, none of the other factors investigated were found to be significant predictors. CONCLUSION: This study supports previous research that it is possible to identify those children most at risk of deterioration in VA following cessation of occlusion therapy. The presence of mixed amblyopia was the only risk factor identified in this study. Management of amblyopia should take this into account, with a more intensive follow-up recommended for those with both anisometropia and strabismus (mixed) amblyopia.

Optic disk size and optic disk-to-fovea distance in preterm and full-term infants.

PURPOSE: Few studies have assessed optic disk and retinal morphology in infants. Here the optic disk and optic disk-to-fovea distance were measured in preterm and full-term infants in vivo. METHODS: Optic disk (OD) dimensions and the center-to-center distance between the OD and the macula were measured using digital imaging in infants undergoing routine ophthalmic examinations. Postmenstrual age of the mother at the time of examination ranged from 32 to 50 weeks. From each image, the OD-to-fovea distance (ODF) and the OD height (ODH) and OD width (ODW) were measured. RESULTS: In 51 retinal images from 51 infants, mean +/- SD values obtained were 4.4 +/- 0.4 mm (ODF), 1.41 +/- 0.1 9 mm (ODH), and 1.05 +/- 0.13 mm (ODW). These dimensions did not change significantly over the age range studied. The mean value for the ratio between ODF and mean OD diameter (ODF/DD) was 3.76. CONCLUSIONS: Results of this in vivo study suggest that though the optic nerve head diameter increases by more than 50%, only limited growth occurs at the highly organized area of the posterior pole from birth to adulthood. This study discusses the finding of a large-angle kappa in infants and the use of a disk macula/disk diameter ratio in the diagnosis of optic nerve hypoplasia.

Comparison of logMAR ETDRS chart and a new computerised staircased procedure for assessment of the visual acuity of children.

The validity and repeatability of visual acuity measures are particularly important in the detection and monitoring of childhood visual anomalies such as amblyopia. The repeatability and sensitivity of a new computerised visual acuity test, 'Staircased Procedure' is compared with the now gold standard visual acuity test, the early treatment of diabetic retinopathy study (ETDRS). Twenty-seven visually normal children (mean age: 6.7 +/- 1.1 years) and 27 children with amblyopia (mean age: 6.1 +/- 0.7 years) were tested with the ETDRS and Staircased Procedure. A retest was administered 4-5 weeks later and 30 min later for the visually normal and the amblyopic children, respectively. The staircased procedure produced significantly better visual acuity than the ETDRS for visually normal and amblyopic children. Repeatability was similar for both tests (ETDRS: 0.11 log units; staircased procedure: 0.13 log units). In conclusion, the Staircased Procedure was an acceptable test with high repeatability and validity.

Intermediate spatial frequency letter contrast sensitivity: its relation to visual resolution before and during amblyopia treatment.

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.

Treatment of unilateral amblyopia: factors influencing visual outcome.

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 > or =1 hour per day resulted in (P < or = 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.

Treatment dose-response in amblyopia therapy: the Monitored Occlusion Treatment of Amblyopia Study (MOTAS).

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. 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.