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Contains fulltext : 292919.pdf (Publisher’s version ) (Open Access) BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

In coming decades, artificial intelligence (AI) platforms are expected to build on the profound achievements demonstrated in research papers towards implementation in real-world medicine. The implementation of AI systems is likely to be as an adjunct to clinicians rather than a replacement, but it still has the potential for a revolutionary impact on ophthalmology specifically and medicine in general in terms of addressing crucial scientific, socioeconomic and capacity challenges facing populations worldwide. In this paper we discuss the broad range of skills that clinicians should develop or refine to be able to fully embrace the opportunities that this technology will bring. We highlight the need for an awareness to identify AI systems that might already be in place and the need to be able to properly assess the utility of their outputs to correctly incorporate the AI system into clinical workflows. In a second section we discuss the need for clinicians to cultivate those human skills that are beyond the capabilities of the AI platforms and which should be just as important as ever. We describe the need for such an awareness by providing clinical examples of situations that might in the future arise in human interactions with machine algorithms. We also envisage a harmonious future in which an educated human and machine interaction can be optimised for the best possible patient experience and care.

The combined effects of fossil fuel combustion, mass agricultural production and deforestation, industrialisation and the evolution of modern transport systems have resulted in high levels of carbon emissions and accumulation of greenhouse gases, causing profound climate change and ozone layer depletion. The consequential depletion of Earth’s natural ecosystems and biodiversity is not only a devastating loss but a threat to human health. Sustainability—the ability to continue activities indefinitely—underpins the principal solutions to these problems. Globally, the healthcare sector is a major contributor to carbon emissions, with waste production and transport systems being amongst the highest contributing factors. The aim of this review is to explore modalities by which the healthcare sector, particularly ophthalmology, can reduce carbon emissions, related costs and overall environmental impact, whilst maintaining a high standard of patient care. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00404-8.

Visual impairment resulting from diseases such as neovascular age-related macular degeneration (nAMD) may cause behavioural, environmental, psychological, and logistical challenges that could act as barriers to effective uptake and sustainability of treatment with anti-vascular endothelial growth factor agents (anti-VEGFs). Understanding emotions and experiences of patients with nAMD may help inform the determinants of adherence, and could contribute to improvements in ophthalmic outcomes and quality of life.Seventeen patients with nAMD receiving anti-VEGF injections were enrolled from three clinics: one each in France (n = 5), Germany (n = 6), and the UK (n = 6). Patients' health information and treatment characteristics were collected. Individual phone interviews were conducted by experienced health care interviewers. Transcripts were analysed thematically.Patients (53% female) had a mean age of 77 years. Bilateral anti-VEGF injections were received by 24% (n = 4); and most (76%, n = 13) were adherent to their treatment. Patient emotions at diagnosis ranged from happiness at learning about the treatment for nAMD to being terrified of receiving an injection in the eye. Most patients mentioned feeling anxious and fearful before their first injection despite receiving reassurance. After the first injection, these feelings and apprehension abated for many, but not all. With the goal of maintaining the best possible vision, few (24%, n = 4) patients reported more than one missed appointment, and most had never considered stopping treatment. No patient reported additional assistance beyond family support; however, many had difficulties with recreational and domestic activities and had developed coping strategies.This study provides insights on patients' emotions related to their experience of nAMD and its management, highlighting the varying experiences between individuals. It shows the importance of the patient's voice when considering patient care and management, and how the nature and timing of interventions can improve the experience of living with and managing nAMD.Neovascular age-related macular degeneration (nAMD), also known as wet age-related macular degeneration (wAMD), is an eye condition that is a common cause of vision loss and worsens over time without treatment. This condition mainly occurs in people aged 70 years or older. The standard of care is an injection of anti-vascular endothelial growth factor (anti-VEGF) into the eye to minimise vision loss that continues over time without treatment. To maximise the benefits of treatment, injections are required at regular intervals over time. The purpose of this study was to understand the emotions and experiences of patients with nAMD about their disease, its consequences, and its management. Seventeen patients from three countries (France, Germany, and the UK) were interviewed over the telephone. Patients reported diverse feelings and responses to their disease and treatment. Many felt nervous and anxious at diagnosis and before their first injection (despite reassurances from their doctors); however, after the first injection, these feelings and apprehension abated for many, but not all. Most patients (76%) missed fewer than two appointments in the past year, and almost all (82%) did not consider stopping treatment. Patients learned to deal with their nAMD, but many had difficulties with daily activities. Patients developed ways to manage tasks such as cooking, cleaning, knitting, and driving. The insights from this study help understand how care for patients with nAMD can be improved by addressing patients’ concerns and feelings about their disease and treatment.

Purpose: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). Design: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. Participants: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009. Methods: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). Main Outcome Measures: Corneal-compensated IOP. Results: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06–0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08–0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05–0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07–0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03–0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06–0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (–0.05 mmHg; 95% CI, –0.08 to –0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30). Conclusions: Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.

Purpose The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR. Design Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom. Participants Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease. Methods A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists). Main Outcome Measures Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings. Results The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%–99%) and specificity of 31% (95% CI, 23%–40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%–91%] and 48% [95% CI, 41%–56%], respectively) or UWF images (83% [95% CI, 75%–89%] and 54% [95% CI, 46%–61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%–93%] and 49% [95% CI, 42%–56%], respectively, for UWF versus 80% [95% CI, 69–88%] and 40% [95% CI, 34%–47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists’ assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits. Conclusions The new pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementation.

Objectives There are few papers concerning ethnic differences in disease expression in PsA, which may be influenced by a number of genetic, lifestyle and cultural factors. This article aims to compare clinical and radiographic phenotypes in people of South Asian (SA) and North European (NE) origin with a diagnosis of PsA. Methods This was a cross-sectional observational study recruiting patients of SA and NE origin from two hospitals in a well-defined area in the North of England. Results A total of 58 SA and 48 NE patients were recruited. SA patients had a more severe clinical phenotype with more tender (median 5 vs 2) and swollen (median 1 vs 0) joints, more severe enthesitis (median 3 vs 1.5), more patients with dactylitis (24% vs 8%), more severe skin disease (median PASI 2.2 vs 1) and worse disease activity as measured by the composite Psoriatic Arthritis Disease Activity Score (mean 4.5 vs 3.6). With regards to patient-completed measures, SA patients had worse impact with poorer quality of life and function (mean HAQ 0.9 vs 0.6; mean PsAQoL 10.8 vs 6.2; mean 36-item short form physical component score 33.5 vs 38.9). No significant differences in current MTX and biologics use were found. Conclusions SA patients had a worse clinical phenotype and worse impact of disease than NE patients. Further studies are needed to confirm and explore the reasons behind these differences.

PURPOSE: To share a useful intervention to minimize risk of COVID-19 infection to both healthcare workers and patients in the eye clinic.METHODS: We present our experience of virtual, within-clinic remote visual acuity assessment to reduce the risk of infection with COVID-19.RESULTS: Along with standard recommendations for personal protective equipment and hand hygiene to contain viral spread and treating only urgent cases, remote within-clinic visual acuity testing and consultations can be undertaken with minimal specialist equipment and appears to provide useful information whilst being acceptable to patients.CONCLUSION: Ophthalmology practice must adapt in order to combat COVID-19. This measure can easily be incorporated into daily practice to reduce both patient footfall within the department and close contact between patient and healthcare practitioners.

PURPOSE: The aim of this systematic literature review was to describe patient-reported outcomes, mental health and caregiver burden in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents in routine clinical practice.METHODS: Electronic searches were conducted in Embase and MEDLINE according to pre-defined criteria.RESULTS: Of 856 records identified, 63 met inclusion criteria. Depression or depressive symptoms were reported in up to 42% of patients with nAMD. Of 25/63 (40%) studies evaluating quality of life (QoL) and using various tools, eight studies reported composite National Eye Institute Visual Functioning Questionnaire scores following anti-VEGF treatment. Of these, seven reported a statistically significant improvement at the earliest time point measured (Month 3-12) and approximately 50% reported sustained QoL benefits at 12 months. In studies comparing the attributed or different regimens, the most important factor from the patient's perspective was the likelihood that a particular regimen would maintain vision. There was a preference towards treat and extend, which was associated with a perceived reduction in patient and caregiver burden, compared to fixed dosing.CONCLUSIONS: A coordinated holistic approach to patient care is key to optimizing patient well-being as well as visual outcomes. Further research regarding the patient-reported impact of nAMD management outside the trial setting (particularly international longitudinal studies) is warranted. Standardization of QoL studies would assist in establishing whether sustained QoL improvement, rather than prevention of QoL decline, should be a realistic expectation of treatment of nAMD in the longer term.

To evaluate the effect of COVID-19 on retinal tissues by conducting a systematic review and meta-analysis of the current literature.The novel coronavirus disease is not yet well understood. The orbit provides a window into the body's microvasculature, and as such, it is a non-invasive opportunity to analyse the systemic circulation in vivo. By analysing the current literature, we test the hypothesis that non-invasive imaging of the retina could provide insight into the effect of COVID-19 on the retinal microvasculature.For this systematic review and meta-analysis, we screened PubMed databases and LitCOVID19 using the search criteria: (OCTA or Optical Coherence Tomography Angiography) AND (COVID-19 or corona or SARS-CoV-2) AND (retina or fundus). Databases were searched on 11 January 2022. The primary study outcomes were studies that utilised OCTA to analyse the retina; secondary outcomes involved studies that involved other imaging modalities such as OCT, fundus photography, and fundus autofluorescence.The total number of studies included in this review was 32. Optical coherence tomography angiography scans show reduced central retinal vascular density, a thinner ganglion cell layer, a thicker retinal nerve fibre layer, and an enlarged foveal avascular zone. Optical coherence tomography scans demonstrate a thicker central macular thickness and other changes to the macula, ganglion cell, and inner nuclear layers. Many fundus photographs depicted cotton wool spots, microhaemorrhages, and vascular occlusions. Non-invasive imaging technology has demonstrated that COVID-19 can profoundly affect the retina. Therefore, there is a requirement for long-term follow-up of COVID-19 patients to assess whether the retinal damage caused by COVID-19 is reversible.

Background: Early identification of AMD can lead to prompt and more effective treatment, better outcomes, and better final visual acuity, several risk scores have been devised to determine the individual level of risk for developing AMD. Herein, the Delphi method was used to provide recommendations for daily practice regarding preventive measures and follow-up required for subjects at low, moderate, and high risk of AMD evaluated with the Simplified Test AMD Risk-assessment Scale (STARS®) questionnaire. Methods: A steering committee of three experts drafted and refined 25 statements on the approach to be recommended in different clinical situations [general recommendations (n = 2), use of evaluation tools (n = 4), general lifestyle advice (n = 3), and AREDS-based nutritional supplementation (n = 5)] with the help of a group of international experts, all co-authors of this paper. Thirty retinal specialists from Europe and the US were chosen based on relevant publications, clinical expertise, and experience in AMD, who then provided their level of agreement with the statements. Statements for which consensus was not reached were modified and voted upon again. Results: In the first round of voting, consensus was reached for 24 statements. After modification, consensus was then reached for the remaining statement. Conclusion: An interprofessional guideline to support preventive measures in patients at risk of AMD based on STARS® scoring has been developed to aid clinicians in daily practice, which will help to optimize preventive care of patients at risk of AMD.

Purpose To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell–inner plexiform layer (GCIPL) thicknesses in a large cohort. Design Cross-sectional study. Participants We included 42 044 participants in the UK Biobank. The mean age was 56 years. Methods Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. Main Outcome Measures Thicknesses of mRNFL, GCC, and GCIPL. Results We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: –0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61–0.30]; P = 1.1×10–8), greater social deprivation (most significant for GCIPL: –0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, –0.42 to –0.14]; P = 6.6×10–5), lower educational attainment (most significant for mRNFL: –0.36 μm for less than O level compared with degree level [95% CI, –0.45 to 0.26]; P = 2.3×10–14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: –1.65 μm [95% CI, –1.86 to –1.43]; P = 2.4×10–50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (–0.04 μm/mmHg [95% CI, –0.05 to –0.03]; P = 4.0×10–10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, –0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). Conclusions The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.

Introduction: The purpose of this review was to explore the potential link between macular atrophy (MA) of the retinal pigment epithelium in patients with neovascular age-related macular degeneration (nAMD) with the disease characteristics and morphological features. Methods: To this end, we performed a search of peer-reviewed articles published on the PubMed database and included all relevant papers. We then examined these papers for possible risk factors for MA development in the context of nAMD treated with anti-vascular endothelial growth factor drugs, as well as possible protective factors. Results: Our review of the relevant publications revealed that areas of MA can be directly visualized through multiple imaging modalities. Associations have been identified between MA of the retinal pigment epithelium and choroidal neovascular membrane characteristics, intra- and subretinal fluid, pigment epithelial detachment, choroidal thickness, subretinal hyperreflective material, outer retinal tubulations, hemorrhage, subretinal drusenoid deposits, refractile drusen, hyperreflective foci, retinal angiomatous proliferation, polypoidal choroidal vasculopathy, geographic atrophy in the fellow eye, genetic factors, and age. Conclusion: The findings of this review indicate that a multimodal approach is recommended for the assessment of MA. The conclusions drawn to date on the correlation between MA development or progression of MA and specific risk factors and possible protective factors are mixed. More clinical research is needed to reach a better understanding of this association.

PURPOSE To explore the characteristics of choroidal tissue in patients with and without central serous chorioretinopathy (CSC) using an automated system of image analysis to determine known and novel metrics. METHODS This was a retrospective case-control analysis of optical coherence tomography (OCT) scans of patients seen at Manchester Royal Eye Hospital, UK, comparing patients with active CSC to an age and gender-matched group with no CSC using a purpose-built automated system of image analysis. The expert system segments and measures established and novel features of choroid using a combination of thresholding, noise removal and morphological techniques. RESULTS A total of 72 patients were included in this study, with 40 included in the group with CSC and 32 patient controls with no CSC. There were significant increases from normal to CSC of median choroidal vascular index, 54.7(Median absolute deviation=9.8) to 61.2(4.3) and all choroidal thickness indices including maximum depth, from 249.0(90.1) µm to 372.3(80.3) µm. For novel measures there was a significant increase in tissue entropy from 6.68(0.28) to 6.95(0.17) and area of the largest five vessels from 6.28(3.04) mm2 to 9.10(3.49) mm2. The ratio of vessel lumen to stromal tissue intensity was conversely significantly reduced from 0.674(0.11) in normal patients to 0.59(0.06) in CSC. CONCLUSIONS The automated system of choroidal analysis expands on the utility of known measures and introduces novel metrics. These findings contribute pathophysiological insights and metrics for further assessment and research on conditions affecting choroidal tissue.

Introduction The aim of this study was to develop a statistical model to determine the visual significance of subretinal fluid (SRF) in combination with other constructed optical coherence tomography (OCT) features in patients with wet age-related macular degeneration. Methods The project used labelled data from 1211 OCTs of patients with neovascular macular degeneration (nAMD) attending the macular treatment centre of Manchester Royal Eye Hospital to build a statistical model to determine vision for any virtual, constructed OCT. A four-dimensional plot was created to represent the visual impact of SRF in OCTs in the context of the associated OCT characteristics of atrophy and subretinal hyperreflective material (SHRM). Results The plot illustrates that at levels of SRF below 150 µm, the impact of SRF on vision is very low. Increasing the amount of fluid to 200 µm and beyond increases the impact on vision, but only if there is little atrophy or SHRM. Conclusions This study suggests that levels of SRF up to around 150 µm thickness on OCT have minimal impact on vision. Greater levels of SRF have greater impact on vision, unless associated with significant amounts of atrophy or SHRM, when the additional effect of the SRF on vision remains low. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-020-00327-w.

2020 will forever be marked as a year that brought with it an unprecedented number of challenges for the healthcare community. COVID-19 had monumental effects on all fields, including ophthalmology. Considering this we are truly thankful for all of the support we have received, despite the pressures brought about by the pandemic. We are very grateful to our Editorial and Advisory boards who have continued to offer their advice, to our authors for working with us to help publish their work, and to our readers for engaging with our content. The Editorial below has been authored by Ophthalmology and Therapy's EU Editor-in-Chief Professor Tariq Aslam. Professor Aslam writes about his aspirations for the healthcare and ophthalmology community in 2021, and how the journal hopes to play its part in facing these challenges.

Given that depression and anxiety can be comorbid to several treatable eye diseases, it is paramount to understand whether vitreous opacities are also associated with increased risk of well-being and mental health problems. The current systematic review summarises research examining psychological implications of vitreous opacities in adult patients.PubMed, Cochrane library, EMBASE, Global Health, Web of Science, EBSCO, and Science Direct were systematically searched for all articles published up to May 5th 2021. Inclusion criteria included studies that have assessed outcomes related to patients' mental health; well-being; quality of life; coping with the disease; studies exploring patients' experiences/perceptions/cognitions of illness and/or medical treatments related to vitreous opacities.5 studies were included in this review, with a total of 139 patients [278 eyes] assessed. Patients' age ranged from 32 to 78 years old. Compared with healthy controls, patients with vitreous opacities showed significantly higher levels of symptoms of depression, perceived stress, state anxiety, and trait anxiety. Studies also suggested that patients are more likely to show low vision-related quality of life, and social functioning. Studies also suggested a significant positive effect of medical treatments [e.g. pars plana victretomy] on patients' symptoms of depression and anxiety and on patients' vision-related quality of life.The topic of psychological implications of vitreous opacities is still relatively new in the literature with very preliminary evidence of mental health problems and reduced quality of life associated with this condition.

IMPORTANCE The study highlights the role of optical coherence angiography in the management of patients with neovascular age-related macular degeneration (nAMD) who have developed sub-retinal fibrosis. BACKGROUND Development of sub-retinal fibrosis in the context of nAMD is known to adversely affect visual function. The aim of this study is to assess structure and flow features obtained through swept-source optical coherence tomography angiography (OCTA) in patients with sub-retinal fibrosis and associate these with visual acuity (VA). DESIGN Institutional retrospective cohort study. PARTICIPANTS A total 39 eyes of 39 patients with nAMD with sub-retinal fibrosis imaged with OCTA were included in this study. METHODS Patients underwent swept-source OCTA. Thickness of sub-retinal hyper-reflective material (SHRM) and presence and configuration of a choroidal neovascular membrane were recorded in each case. MAIN OUTCOME MEASURES A univariate multiple regression was performed seeking associations between VA and structural and flow OCTA features. RESULTS Average VA on the date of OCTA was 53 ± 22 ETDRS letters. Average thickness of centre-involving SHRM was 157 ± 73 μm. A choroidal neovascular membrane was detectable in 26 cases and not detectable in 13. VA was independently influenced by thickness of SHRM (P = 0.034) and presence of a detectable choroidal neovascular membrane (P = 0.02) on OCTA. CONCLUSIONS AND RELEVANCE Poorer VA in patients with nAMD and sub-retinal fibrosis is associated with presence of a detectable neovascular membrane on OCTA. The role of OCTA to guide nuanced management decisions in this patient population may be significant.

PurposeMucopolysaccharidoses (MPSs) are a heterogeneous group of lysosomal storage disorders. Ocular complications (such as corneal clouding, retinopathy and optic neuropathy) are common. Notably, there is a paucity of data on the effect of genotype and systemic treatments (enzyme replacement therapy or haematopoietic stem cell transplantation) on the ocular phenotype in MPS. We prospectively studied the ocular features of patients with MPSI (Hurler/Hurler-Scheie/Scheie), MPSIV (Morquio) and MPSVI (Maroteaux-Lamy), to evaluate the effect of different therapeutic interventions and to correlate the findings with genetic and biomarker data.MethodsProspective observational cohort study. Study participants underwent detailed ocular examination including visual acuity; assessment of corneal clouding (Iris camera Corneal Opacification Measure score and Pentacam densitometry) and retinal and optic nerve imaging (optical coherence tomography and wide-field fundus imaging). Data on genotype, biomarkers and delivered therapies (type and length of treatment) were also collected for each patient where available.ResultsOverall, 21 patients with MPSI, 4 patients with MPSIV and 3 patients with MPSVI were recruited. Corneal clouding scores were higher in MPSI compared with MPSIV and MPSVI. Retinopathy was evident in patients with MPSI only. Association was observed between corneal clouding and biomarkers in MPSI, MPSIV and MPSVI. However, no clear association was seen between genotype or treatment type and ocular phenotype.ConclusionsThe ocular phenotype in MPS is variable, with corneal clouding occurring in MPSI, MPSIV and MPSVI, and retinopathy in MPSI only. There was an association between corneal clouding and efficacy of systemic treatment as measured by biomarkers.

PurposeTo develop a neural network for the estimation of visual acuity from optical coherence tomography (OCT) images of patients with neovascular age related macular degeneration and to demonstrate its use to model the impact of specific controlled OCT changes on vision.DesignArtificial Intelligence (neural network) study.MethodsWe assessed 1400 OCT scans of patients with neovascular age related macular degeneration (AMD). 15 physical features for each eligible OCT as well as patient age were used as input data and corresponding recorded visual acuity as the target data to train, validate and test a supervised neural network. We then applied this network to model the impact on acuity of defined OCT changes in subretinal fluid, subretinal hyperreflective material and loss of external limiting membrane integrity.Results1,210 eligible OCT scans were analysed resulting in 1210 data points which were each 16 dimensional. A ten layer feed-forward neural network with one hidden layer of 10 neurons was trained to predict acuity and demonstrated a root mean square error of 8.2 letters for predicted compared to actual visual acuity and a mean regression coefficient of 0.85. A virtual model using this network demonstrated the relationship of visual acuity to specific, programmed changes in OCT characteristics. When external limiting membrane (ELM) is intact, there is a shallow decline in acuity with increasing sub-retinal fluid but a much steeper decline with equivalent increasing sub-retinal hyperreflective material. When ELM is not intact, all visual acuities are reduced. Increasing subretinal hyperreflective material or subretinal fluid in this circumstance reduces vision further still, but with a smaller gradient than when ELM is intact.ConclusionsThe supervised machine learning neural network developed is able to generate an estimated visual acuity value from OCT images in a population of patients with AMD. These findings should be of clinical and research interest in macular degeneration, for example in estimating visual prognosis or highlighting the importance of developing treatments targeting more visually destructive pathologies.