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Engin Akyol, Andrew Lotery Clinical Neurosciences Research Group, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UKCorrespondence: Andrew LoteryClinical Neurosciences Research Group, Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 806, South Lab & Path Block, Tremona Road, Southampton SO16 6YD, UKTel +44 23 8120 5049Email a.j.lotery@soton.ac.ukAbstract: Here we discuss antibody, cell and gene-based therapies that are currently available and under investigation for both wet and dry age-related macular degeneration (AMD). We initially discuss ocular anatomy, AMD modelling as well as the underlying pathophysiology of AMD. The antibody-based trials which have revolutionised the management of wet AMD are reviewed. The latest concepts in antibody therapy for wet AMD such as the port delivery systems, bispecific antibodies, designed ankyrin repeat protein (DARPINs) and brolucizumab are explored. Furthermore, the antibody-based trials targeting the complement pathway to reduce progression of geographic atrophy (GA) in dry AMD are discussed. Stem cell therapy and gene therapy are novel treatment modalities with no established clinical use in wet or dry AMD. Here, we discuss their efficacy so far in clinical trials. Their benefits and risk in the treatment of both wet and dry AMD are evaluated.Keywords: choroidal neovascularisation, geographic atrophy, gene therapy, macular degeneration, stem cell therapy, monoclonal antibodies

Praveen J Patel,1 Helen Devonport,2 Sobha Sivaprasad,1 Adam H Ross,3 Gavin Walters,4 Richard P Gale,5 Andrew J Lotery,6 Sajjad Mahmood,7 James S Talks,8 Jackie Napier9 1National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK; 2The Ophthalmology Department, Bradford Royal Infirmary, Bradford, UK; 3The Ophthalmology Department, Bristol Eye Hospital, Bristol, UK; 4Department of Ophthalmology, Harrogate District Hospital, Harrogate, UK; 5The Ophthalmology Department, The York Hospital and Department of Health Sciences, University of York, York, UK; 6Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 7Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 8Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK; 9Medical Affairs, Bayer plc, Reading, Berkshire, UK Abstract: National recommendations on continued administration of aflibercept solution for injection after the first year of treatment for neovascular age-related macular degeneration (nAMD) have been developed by an expert panel of UK retina specialists, based on clinician experience and treatment outcomes seen in year 2. The 2017 update reiterates that the treatment goal is to maintain or improve the macular structural and functional gains achieved in year 1 while attempting to reduce or minimize the treatment burden, recognizing the need for ongoing treatment. At the end of year 1 (ie, the decision visit at month 11), two treatment options should be considered: do not extend the treatment interval and maintain fixed 8-weekly dosing, or extend the treatment interval using a treat-and-extend regimen up to a maximum 12 weeks. Criteria for considering not extending the treatment interval are persistent macular fluid with stable vision, recurrent fluid, decrease in vision in the presence of fluid, macular hemorrhage, new choroidal neovascularization or any other sign(s) of exudative disease activity considered vision threatening in the opinion of the treating clinician. Treatment extension is recommended for eyes with a dry macula (ie, without macular fluid) and stable vision. Under both options, the treatment interval may be shortened if visual and/or anatomic outcomes deteriorate. Monitoring without treatment may be considered for eyes with a fluid-free macula for a minimum duration of 48 weeks. A patient completing one full year of monitoring without requiring injections may be considered for discharge from clinic. The treatment algorithm incorporates return to fixed 8-weekly dosing for disease reactivation during treatment extension and reinstatement of treatment for disease recurrence following discontinuation or discharge. For bilateral nAMD, either the eye requiring the more intensive treatment or the eye with the better vision, guided by local clinical practice, should determine the retreatment schedule overall. Keywords: anti-vascular endothelial growth factor, maintenance therapy, treatment algorithm, treat-and-extend, visual acuity

Philip Hykin,1 Usha Chakravarthy,2 Andrew Lotery,3 Martin McKibbin,4 Jackie Napier,5 Sobha Sivaprasad1,6 On behalf of the AURA Study Group 1National Institute for Health Research Biomedical Research Centre in Ophthalmology, Moorfields Eye Hospital, London, UK; 2Institute of Clinical Science, The Queen’s University of Belfast, Belfast, UK; 3Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 4Eye Clinic, St James’s University Hospital, Leeds, UK; 5Bayer HealthCare Pharmaceuticals AG, Newbury, Berkshire, UK; 6Ophthalmology Department, King’s College Hospital, London, UK Purpose: AURA was an international, retrospective, observational study that monitored the real-life use and effectiveness of ranibizumab injections in patients with neovascular age-related macular degeneration (nAMD). This paper reports the findings from the UK. Methods: Patients who started treatment with ranibizumab between January 1, 2009, and August 31, 2009, and had documented follow-up to the end of their treatment and/or monitoring or until August 31, 2011, were retrospectively monitored; the diagnosis and subsequent decision to treat was made by the patient’s own physician. Assessments included the change in visual acuity (standardized letter count) during the first and second years after start of ranibizumab therapy and resource utilization. Results: Four hundred and ten patients from 13 UK centers were analyzed. The mean (standard deviation [SD]) letter score at baseline was 55.0 (17.8). The mean (SD) change in visual acuity from baseline was +6.0 (15.4) letters at year 1 and +4.1 (16.9) at year 2. Most of the patients (86.6%) completed a 3-month loading phase; the visual improvements were numerically higher in these patients. Over 2 years, the mean (SD) number of clinic visits and injections was 18.4 (5.0) and 9.0 (4.7), respectively. Resource use and visual acuity gains were greater than those observed in the global population, which included other countries enrolled in AURA (Canada, France, Germany, Ireland, Italy, the Netherlands, and Venezuela). When patients were stratified according to severity of nAMD (based on letter count at baseline), the mean change in visual acuity score at years 1 and 2 was also higher for the UK than for the global population across all subgroups. Conclusion: Monitoring and treatment rates were high in the UK, resulting in better visual acuity outcomes compared with other included countries. This suggests that translation of clinical study outcomes into real-life settings is achievable, but at the expense of higher resource utilization than is currently the norm in most developed countries. Keywords: neovascular or wet age-related macular degeneration, anti-vascular endothelial growth factor

Background Most neovascular age-related macular degeneration treatments involve long-term follow-up of disease activity. Home monitoring would reduce the burden on patients and those they depend on for transport, and release clinic appointments for other patients. The study aimed to evaluate three home-monitoring tests for patients to use to detect active neovascular age-related macular degeneration compared with diagnosing active neovascular age-related macular degeneration by hospital follow-up. Objectives There were five objectives: Estimate the accuracy of three home-monitoring tests to detect active neovascular age-related macular degeneration. Determine the acceptability of home monitoring to patients and carers and adherence to home monitoring. Explore whether inequalities exist in recruitment, participants’ ability to self-test and their adherence to weekly testing during follow-up. Provide pilot data about the accuracy of home monitoring to detect conversion to neovascular age-related macular degeneration in fellow eyes of patients with unilateral neovascular age-related macular degeneration. Describe challenges experienced when implementing home-monitoring tests. Design Diagnostic test accuracy cohort study, stratified by time since starting treatment. Setting Six United Kingdom Hospital Eye Service macular clinics (Belfast, Liverpool, Moorfields, James Paget, Southampton, Gloucester). Participants Patients with at least one study eye being monitored by hospital follow-up. Reference standard Detection of active neovascular age-related macular degeneration by an ophthalmologist at hospital follow-up. Index tests KeepSight Journal: paper-based near-vision tests presented as word puzzles. MyVisionTrack®: electronic test, viewed on a tablet device. MultiBit: electronic test, viewed on a tablet device. Participants provided test scores weekly. Raw scores between hospital follow-ups were summarised as averages. Results Two hundred and ninety-seven patients (mean age 74.9 years) took part. At least one hospital follow-up was available for 317 study eyes, including 9 second eyes that became eligible during follow-up, in 261 participants (1549 complete visits). Median testing frequency was three times/month. Estimated areas under receiver operating curves were < 0.6 for all index tests, and only KeepSight Journal summary score was significantly associated with the lesion activity (odds ratio = 3.48, 95% confidence interval 1.09 to 11.13, p = 0.036). Older age and worse deprivation for home address were associated with lower participation (χ2 = 50.5 and 24.3, respectively, p 6 and < 42 months earlier. We tried to recruit equal numbers by time since starting treatment in the first-treated study eye (6–17 months; 18–29 months; 30–41 months) to ensure test performance was estimated across this range of duration of nAMD. Patients were followed for at least 6 months. Reference standard The reference standard was the reviewing ophthalmologist’s decision about the activity status of a study eye at a HES monitoring visit, recorded as active, inactive or uncertain. There were no additional hospital visits for the study. Such decisions are usually based on clinical examination and the results of hospital-based retinal imaging investigations, for example, colour fundus photographs and ocular coherence tomograms (OCTs). The reference standard grouped uncertain with inactive judgements for analyses. Index tests Three home-monitoring (‘index’) tests were evaluated, spanning low to moderate cost and complexity. These were: KeepSight Journal (KSJ): a paper-based booklet of near-vision tests presented as word puzzles developed in the United States and adapted by the study team for use in the study. MyVisionTrack® (mVT®): electronic vision test, intended to be viewed on a tablet device. MultiBit (MBT): electronic vision test, intended to be viewed on a tablet device. Specific thresholds indicating a significant clinical change were not provided for any of index tests in advance by their developers. Outcomes The primary outcome was classification of a study eye at a monitoring visit as having active or inactive disease (active, inactive, uncertain), that is, the reviewing ophthalmologist’s decision. A secondary outcome (new reference standard) for Objective A was a change from inactive to active status from one management visit to the next. This was considered better to represent how home monitoring might be implemented. For Objective C, outcomes investigated were willingness in principle to participate; ability to carry out index tests; adherence to weekly testing. For Objective D, the outcome was conversion of a fellow eye to active nAMD as judged by an ophthalmologist, that is, same reference standard. For Objective E, the following outcomes were described as measures of the technical and logistical challenges identified during the study: Frequency and reason for incoming calls made to the helpline and outgoing calls made to participants. Frequency and duration of events leading to the digital tests being unavailable for testing. Other technical and logistical challenges. Objective B study recruitment and data collection Recruitment to the qualitative component began 3 months after the monitoring for neovascular age-related macular degeneration reactivation at home (MONARCH) study began recruiting. During the consent process for participation in the study, patients could consent to further contact from the qualitative research team to discuss participation in the qualitative study. Maximum variation sampling ensured a range of perspectives were captured in relation to: age (young-old 50–69 years and older-old > 70 years), gender, one or both eyes with nAMD, time since first treatment (defined as above) and adherence to home monitoring (test data from the two electronic tests were used to categorise participants into ‘regular’ testers and ‘irregular’ testers). Patients who declined to participate in MONARCH but provided consent to be contacted about the qualitative study, informal ‘carers’, supporters or significant others in the lives of patients and healthcare professionals who interacted with participants at study sites visits were also approached to gather their perspectives about the acceptability of home monitoring. Statistical analysis Objective A: The test accuracy of index tests was estimated by fitting a logistic regression model to predict the reference standard from summary test scores for the interval between monitoring visits, adjusting for participants’ baseline data. Accuracy was estimated for the primary outcome using all index test data, data only for the 4 weeks preceding the monitoring visit, the reference standard based on reading centre decisions made from OCT images and for the secondary outcome. Test scores were summarised as: means (MBT and mVT); median (KSJ reported near visual acuity (VA), ordinal six-point scale); proportions (KSJ reported VA, Amsler grid and household object appearance reported worse than baseline vs. same or better). All four scores were fitted in the KSJ model and a single area under the receiving operator curve (AUROC) was estimated. Separate models were fitted for each test for the primary outcome, the two sensitivity analyses and the secondary outcome. Model performance was quantified by the odds ratio (OR) for the index test summary score(s) and the estimate of the AUROC and their respective confidence intervals (CIs). AUROCs were based on predicted probabilities calculated using only the fixed effects in the models. Sensitivity, specificity, positive and negative predictive values and 95% CIs were calculated using cut-off thresholds corresponding to Youden’s index for each model, which minimises overall misclassifications. Average test scores above and below the thresholds were also calculated. Analyses took account of the structure within the data, that is, the nesting of visits and eyes within patients. Objective B: All interviews were audio-recorded and transcribed. A directed content analysis approach based on deductive and inductive coding was used. NVivo version 12 was used to manage data and facilitate the analysis process, which, in summary, included the following stages: (1) independent transcription, (2) data familiarisation, (3) independent coding, (4) development of an analytical framework, (5) indexing, (6) charting and (7) interpreting data. Objective C: Willingness in principle to participate was defined as an approached eligible patient agreeing to attend a research visit for training. Ability to perform an index test was defined as the proportion of monitoring visits for which some valid index test data were available. Adherence was defined as the proportion of weeks between monitoring visits for which some valid data for an index test were available. The ability and adherence models were performed for each test separately at the level of the patient. Regression models estimated associations of age, sex, Index of Multiple Deprivation (IMD), stratum of time since first diagnosis and baseline visual acuity at diagnosis on the outcomes of willingness to participate, ability to perform tests and adherence to weekly testing; models for the latter two outcomes were fitted for each index test. Associations were reported with 95% CIs. Analyses of adherence and ability took account of nesting of visits within participants. Objective D: The test accuracy of the index tests for the reference standard of an ophthalmologist’s classification of a fellow eye as having active disease at a monitoring visit, that is, conversion to active nAMD, was estimated by the same methods as described for Objective A. Two sensitivity analyses were carried out: (1) the same reference standard but using test data only for the 4 weeks preceding the management visit and (2) the alternative reference standard of classification of a fellow eye having active disease based on reading centre grading of OCTs carried out during the monitoring visits. Objective E: This objective used descriptive summary descriptive statistics only. Results The study recruited 297 patients (consented participants) between 21 August 2018 and 31 March 2020. Half of recruited participants were first treated for nAMD 6–17 months before consenting, 28% 18–29 months before consenting and 22% 30–41 months before consenting. At the end of the study, data for at least one monitoring visit after starting to use the index monitoring tests were available for 357 study eyes in 297 patients. Data were available for at least one complete monitoring visit after starting to use the index monitoring tests for 317 study eyes of 261 patients. More participants were women (58.6%). Participants’ mean age was 74.9 (6.6) years [standard deviation (SD)]. The mean visual acuity of study eyes (better seeing eyes if participants had two study eyes) was 0.2 (0.2) Logarithm of the minimum angle of resolution (LogMAR) (SD). Objective A: Median testing frequency was three times per month. In the primary analysis, estimated AUROCs were < 0.6 for all index tests, and only KSJ summary score was significantly associated with the lesion activity (OR = 3.48, 95% CI 1.09 to 11.13; p = 0.036). Estimated AUROCs were < 0.6 for all tests in both sensitivity analyses and for the secondary outcome of change from inactive to active status between adjacent management visits. Objective B: Two overarching meta-themes emerged from the qualitative studies related to acceptance or non-acceptance of home monitoring. Meta-theme 1 encompassed four main themes: (1) the role of home monitoring; (2) suitability of procedures and instruments; (3) experience of home monitoring; and (4) feasibility of home monitoring in usual practice. Meta-theme 2 consisted of one main theme covering key inhibitors to acceptability. The main factors influencing acceptability included a participant’s understanding about the purpose of home monitoring and their experience of using it. While home monitoring was generally seen as a relatively straightforward exercise to undertake and non-burdensome, training and ongoing support were regarded as essential to its success. Home monitoring was acceptable to patients and its potential to reduce clinic visits during non-active treatment phases was recognised. Objective C: A minority of patients who were approached were willing in principle to participate. Increasing age and worse deprivation index for home address were associated with being unwilling in principle to participate (χ2 = 50.5 and 24.3, respectively, both p ≤ 0.001). Recruiting site was also associated with willingness in principle to participate, believed to be due to sites adopting different strategies for approaching and recruiting patients. Increasing age and worse deprivation were not consistently associated with either being able to self-monitor with the index tests or adherence to weekly testing (χ2 for all tests 0.08 for ability and adherence, except for worse IMD being associated with better adherence for the KSJ, χ2 = 12.15, p = 0.016). Recruiting site was also associated with being able to test and adhering to weekly testing. Objective D: There were 132 fellow eyes with data from 544 monitoring visits, 17 of which (12.9%) had nAMD recorded at one or more management visits over about 100 participant-years. This rate of conversion was higher than expected based on epidemiological studies of conversion rates in unaffected fellow eyes, potentially due to study eyes having had nAMD longer ago. Some predictors could not be fitted in models and estimates of associations were imprecise. The no-test model predicted conversion better than for Objective A (AUROC = 0.73) and electronic tests did not increase this (AUROCs = 0.73 and 0.76 for MBT and mVT, respectively). The estimated AUROC for the KSJ was 0.85, due to a strong positive association of the household object summary score with conversion (OR 15.3, p = 0.036). Objective E: Despite two-thirds of the population having previously used a smartphone, there were still a variety of challenges experienced with the electronic devices while testing at home that contributed to both reduced adherence and ultimately withdrawals from the study. Strengths and limitations The study had several strengths. Estimates of the diagnostic test accuracy of index tests were at low risk of bias: the study population was appropriate for the intended use of the tests, and summary test scores were not available to ophthalmologists providing the reference standard, which was judged after the index test data were collected. Limitations A smaller-than-planned sample size (less than half the target number of monitoring visits); nonetheless, 95% CIs for AUROCs were narrow (± 0.04) and estimates were able to rule out tests providing adequate accuracy for diagnosing active nAMD to enable patients to be monitored without hospital review. Tests were sometimes not available for technical reasons that were beyond the control of the research team. The study had no control over monitoring visits and participants are likely to have reported their subjective visual experience to their consultants, which might have influenced the reference standard. We could not define test thresholds a priori, and instead estimated AUROCs. We did not compare AUROCs for tests due to their poor accuracy. The ways in which patients were approached and screened varied across sites, generating a site effect in analyses of potential inequalities; variations may have reflected the pre-conceptions of research staff regarding the capabilities of patients to use the electronic tests. Conclusions Based on the detection of lesion activity assessed by clinicians in the clinic, we have shown that none of the index tests provides acceptable test accuracy for home monitoring in this context. Associations of increasing age and deprivation index for home address with unwillingness in principle to participate despite provision of hardware highlight the potential for inequality with interventions of the kind evaluated. While a proportion of nAMD patients are willing and interested in the potential for home monitoring, substantial practical and technological issues are encountered in the implementation of such, requiring a significant support infrastructure, including a study helpline. Future work Future research should focus on the methodological challenge of efficiently evaluating mobile health technologies which deal with constantly emerging new technology. The clear evidence of inequalities in participation and retention should prompt future research on ways to encourage participant and adoption of mobile health technologies by underserved populations. Focus should also be placed on methods to improve adherence and retention in longitudinal studies involving electronic testing, particularly around the nature of feedback to participants. Trial registration This trial is registered as ISRCTN79058224. Funding This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/97/02) and is published in full in Health Technology Assessment; Vol. 28, No. 32. See the NIHR Funding and Awards website for further award information.

PurposeUveal coloboma is a congenital eye malformation caused by failure of the optic fissure to close in early human development. Despite significant progress in identifying genes whose regulation is important for executing this closure, mutations are detected in a minority of cases using known gene panels, implying additional genetic complexity. We have previously shown knockdown of znf503 (the ortholog of mouse Zfp503) in zebrafish causes coloboma. Here we characterize Zfp503 knockout (KO) mice and evaluate transcriptomic profiling of mutant versus wild-type (WT) retinal pigment epithelium (RPE)/choroid.MethodsZfp503 KO mice were generated by gene targeting using homologous recombination. Embryos were characterized grossly and histologically. Patterns and level of developmentally relevant proteins/genes were examined with immunostaining/in situ hybridization. The transcriptomic profile of E11.5 KO RPE/choroid was compared to that of WT.ResultsZfp503 is dynamically expressed in developing mouse eyes, and loss of its expression results in uveal coloboma. KO embryos exhibit altered mRNA levels and expression patterns of several key transcription factors involved in eye development, including Otx2, Mitf, Pax6, Pax2, Vax1, and Vax2, resulting in a failure to maintain the presumptive RPE, as evidenced by reduced melanin pigmentation and its differentiation into a neural retina-like lineage. Comparison of RNA sequencing data from WT and KO E11.5 embryos demonstrated reduced expression of melanin-related genes and significant overlap with genes known to be dynamically regulated at the optic fissure.ConclusionsThese results demonstrate a critical role of Zfp503 in maintaining RPE fate and optic fissure closure.

Objectives Remote monitoring of health has the potential to reduce the burden to patients of face-to-face appointments and make healthcare more efficient. Apps are available for patients to self-monitor vision at home, for example, to detect reactivation of age-related macular degeneration (AMD). Describing the challenges when implementing apps for self-monitoring of vision at home was an objective of the MONARCH study to evaluate two vision-monitoring apps on an iPod Touch (Multibit and MyVisionTrack).Design Diagnostic Test Accuracy study.Setting Six UK hospitals.Methods The study provides an example of the real-world implementation of such apps across health sectors in an older population. Challenges described include the following: (1) frequency and reason for incoming calls made to a helpline and outgoing calls made to participants; (2) frequency and duration of events responsible for the tests being unavailable; and (3) other technical and logistical challenges.Results Patients (n=297) in the study were familiar with technology; 252/296 (85%) had internet at home and 197/296 (67%) had used a smartphone. Nevertheless, 141 (46%) called the study helpline, more often than anticipated. Of 435 reasons for calling, all but 42 (10%) related to testing with the apps or hardware, which contributed to reduced adherence. The team made at least one call to 133 patients (44%) to investigate why data had not been transmitted. Multibit and MyVisionTrack apps were unavailable for 15 and 30 of 1318 testing days for reasons which were the responsibility of the app providers. Researchers also experienced technical challenges with a multiple device management system. Logistical challenges included regulations for transporting lithium-ion batteries and malfunctioning chargers.Conclusions Implementation of similar technologies should incorporate a well-resourced helpline and build in additional training time for participants and troubleshooting time for staff. There should also be robust evidence that chosen technologies are fit for the intended purpose.Trial registration number ISRCTN79058224.

Abstract Real-world retinal optical coherence tomography (OCT) scans are available in abundance in primary and secondary eye care centres. They contain a wealth of information to be analyzed in retrospective studies. The associated electronic health records alone are often not enough to generate a high-quality dataset for clinical, statistical, and machine learning analysis. We have developed a deep learning-based age-related macular degeneration (AMD) stage classifier, to efficiently identify the first onset of early/intermediate (iAMD), atrophic (GA), and neovascular (nAMD) stage of AMD in retrospective data. We trained a two-stage convolutional neural network to classify macula-centered 3D volumes from Topcon OCT images into 4 classes: Normal, iAMD, GA and nAMD. In the first stage, a 2D ResNet50 is trained to identify the disease categories on the individual OCT B-scans while in the second stage, four smaller models (ResNets) use the concatenated B-scan-wise output from the first stage to classify the entire OCT volume. Classification uncertainty estimates are generated with Monte-Carlo dropout at inference time. The model was trained on a real-world OCT dataset, 3765 scans of 1849 eyes, and extensively evaluated, where it reached an average ROC-AUC of 0.94 in a real-world test set.

Abstract l-DOPA is deficient in the developing albino eye, resulting in abnormalities of retinal development and visual impairment. Ongoing retinal development after birth has also been demonstrated in the developing albino eye offering a potential therapeutic window in humans. To study whether human equivalent doses of l-DOPA/Carbidopa administered during the crucial postnatal period of neuroplasticity can rescue visual function, OCA C57BL/6 J-c2J OCA1 mice were treated with a 28-day course of oral l-DOPA/Carbidopa at 3 different doses from 15 to 43 days postnatal age (PNA) and for 3 different lengths of treatment, to identify optimum dosage and treatment length. Visual electrophysiology, acuity, and retinal morphology were measured at 4, 5, 6, 12 and 16 weeks PNA and compared to untreated C57BL/6 J (WT) and OCA1 mice. Quantification of PEDF, βIII-tubulin and syntaxin-3 expression was also performed. Our data showed impaired retinal morphology, decreased retinal function and lower visual acuity in untreated OCA1 mice compared to WT mice. These changes were diminished or eliminated when treated with higher doses of l-DOPA/Carbidopa. Our results demonstrate that oral l-DOPA/Carbidopa supplementation at human equivalent doses during the postnatal critical period of retinal neuroplasticity can rescue visual retinal morphology and retinal function, via PEDF upregulation and modulation of retinal synaptogenesis, providing a further step towards developing an effective treatment for albinism patients.