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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

Glaucoma is a common, complex, heterogenous disease and it constitutes the major cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG) is the most common type of glaucoma in all populations. Most of the molecular mechanisms leading to POAG development are still unknown. Gene mutations in various populations have been identified by genetic studies and a genetic basis for glaucoma pathogenesis has been established. Linkage analysis and association studies are genetic approaches in the investigation of the genetic basis of POAG. Genome-wide association studies (GWAS) are more powerful compared with linkage analysis in discovering genes of small effect that might contribute to the development of the disease. POAG links to at least 20 genetic loci, but only 2 genes identified in these loci, myocilin and optineurin, are considered as well-established glaucoma-causing genes, whereas the role of other loci, genes, and variants implicated in the development of POAG remains controversial. Gene mutations associated with POAG result in retinal ganglion cell death, which is the common outcome of pathogenetic mechanisms in glaucoma. In future, if the sensitivity and specificity of genotyping increases, it may be possible to screen individuals routinely for disease susceptibility. This review is an update on the latest progress of genetic studies associated with POAG. It emphasizes the correlation of recent achievements in genetics with glaucoma pathophysiology, glaucoma treatment perspectives, and the possibility of future prevention of irreversible visual loss caused by the disease. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world. The study of a rare mendelian form of macular degeneration implicated fibulin genes in the pathogenesis of more common forms of this disease. We evaluated five fibulin genes in a large series of patients with AMD.Methods: We studied 402 patients with AMD and 429 control subjects from the same clinic population. Patients were examined by means of indirect ophthalmoscopy, slit-lamp microscopy, and fundus photography to establish the presence and phenotypic pattern of AMD. DNA samples were screened for sequence variations in five members of the fibulin gene family.Results: Amino acid-altering sequence variations were found in all five fibulin genes, many of which were observed only in patients with AMD. Several of the altered residues have been conserved during evolution. Seven of the 402 patients with AMD had amino acid-altering sequence variations in the fibulin 5 gene, whereas none were observed among 429 control subjects (P<0.01). In addition, these seven patients all had small, circular drusen, which are commonly referred to as basal laminar or cuticular drusen.Conclusions: Missense mutations in the fibulin 5 gene were found in 1.7 percent of patients with AMD. Many variations in other fibulin genes were also found in these patients, and the evolutionary conservation of the affected residues suggests that several of these variations may also be involved in AMD. [ABSTRACT FROM AUTHOR]

Deep learning has potential to automate screening, monitoring and grading of disease in medical images. Pretraining with contrastive learning enables models to extract robust and generalisable features from natural image datasets, facilitating label-efficient downstream image analysis. However, the direct application of conventional contrastive methods to medical datasets introduces two domain-specific issues. Firstly, several image transformations which have been shown to be crucial for effective contrastive learning do not translate from the natural image to the medical image domain. Secondly, the assumption made by conventional methods, that any two images are dissimilar, is systematically misleading in medical datasets depicting the same anatomy and disease. This is exacerbated in longitudinal image datasets that repeatedly image the same patient cohort to monitor their disease progression over time. In this paper we tackle these issues by extending conventional contrastive frameworks with a novel metadata-enhanced strategy. Our approach employs widely available patient metadata to approximate the true set of inter-image contrastive relationships. To this end we employ records for patient identity, eye position (i.e. left or right) and time series information. In experiments using two large longitudinal datasets containing 170,427 retinal optical coherence tomography (OCT) images of 7912 patients with age-related macular degeneration (AMD), we evaluate the utility of using metadata to incorporate the temporal dynamics of disease progression into pretraining. Our metadata-enhanced approach outperforms both standard contrastive methods and a retinal image foundation model in five out of six image-level downstream tasks related to AMD. We find benefits in both a low-data and high-data regime across tasks ranging from AMD stage and type classification to prediction of visual acuity. Due to its modularity, our method can be quickly and cost-effectively tested to establish the potential benefits of including available metadata in contrastive pretraining., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To report a case of central retinal artery and common carotid artery occlusions following COVID-19 infection in a young female with no other risk factors., Methods: Retrospective analysis of the medical notes of a patient hospitalized with COVID 19 infection at University Hospital Southampton., Results: The patient was found to have dural venous sinus thrombosis and an acute infarct within the right parietal lobe. There was an occlusive thrombus within the right common carotid artery. Subsequently she was found to have a right central artery occlusion secondary to the right common carotid artery occlusion., Conclusion: COVID-19 infection can cause retinal artery occlusion via systemic thrombosis in previously healthy patients., Competing Interests: Conflict of interest: All authors declare that they have no conflict of interest in this study., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Competing Interests: The authors declare that they have no conflict of interest.

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 (χ 2  = 50.5 and 24.3, respectively, p  < 0.001) but not ability or adherence to self-testing. Areas under receiver operating curves appeared higher for conversion of fellow eyes to neovascular age-related macular degeneration (0.85 for KeepSight Journal) but were estimated with less precision. Almost half of participants called a study helpline, most often due to inability to test electronically., Limitations: Pre-specified sample size not met; participants' difficulties using the devices; electronic tests not always available., Conclusions: No index test provided adequate test accuracy to identify lesion diagnosed as active in follow-up clinics. If used to detect conversion, patients would still need to be monitored at hospital. Associations of older age and worse deprivation with study participation highlight the potential for inequities with such interventions. Provision of reliable electronic testing was challenging., Future Work: Future studies evaluating similar technologies should consider: Independent monitoring with clear stopping rules based on test performance. Deployment of apps on patients' own devices since providing devices did not reduce inequalities in participation and complicated home testing. Alternative methods to summarise multiple scores over the period preceding a follow-up., 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.

Acute retinal necrosis (ARN) is a rare but severe ophthalmic pathology defined by panuveitis, retinal necrosis, and high rates of retinal detachment. ARN may lead to poor visual outcomes even if promptly diagnosed and treated. ARN may present with a wide spectrum of clinical findings compatible with panuveitis including anterior uveitis, scleritis, vitritis, necrotizing retinitis, occlusive vasculitis, and optic disc edema. The American Uveitis Society introduced clinical criteria in 1994 for the diagnosis of ARN, while more recent criteria have been proposed by the Standardization of Uveitis Nomenclature (SUN) Working Group and the Japanese ARN Study Group. Multimodal imaging is a valuable tool in evaluating patients with ARN, particularly in unusual cases, while utilizing retinal imaging and applying AI algorithms in these areas of clinical research could be highly beneficial. Over the last few years, significant progress has been made in achieving timely diagnosis and treatment. The precise identification of the viral cause in suspected ARN cases has been greatly enhanced by the advancements in PCR techniques and flow cytometry used for intraocular fluids. systemic (intravenous or oral) antivirals with adjunctive intravitreal antiviral therapy are recommended as first-line therapy to reduce disease severity, the risk of vision loss, and retinal detachment incidence. Although aciclovir was the first existing antiviral agent, at present many clinicians prefer high-dose valaciclovir orally or intravenous aciclovir combined with intravitreal foscarnet. Despite significant progress in diagnosing and treating ARN, further research is needed to improve visual outcomes in this challenging clinical condition., (© 2024. The Author(s).)

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC., Competing Interests: Declaration of competing interest Bailey Freund is an consultant for Bayer, Genentech, Heidelberg Engineering, Nidek, Novartis, Regeneron, and Zeiss. The author authors declare not to have conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rare variants (RVs) in the gene encoding the regulatory enzyme complement factor I (CFI; FI) that reduce protein function or levels increase age-related macular degeneration risk. A total of 3357 subjects underwent screening in the SCOPE natural history study for geographic atrophy secondary to age-related macular degeneration, including CFI sequencing and serum FI measurement. Eleven CFI RV genotypes that were challenging to categorize as type I (low serum level) or type II (normal serum level, reduced enzymatic function) were characterized in the context of pure FI protein in C3b and C4b fluid phase cleavage assays and a novel bead-based functional assay (BBFA) of C3b cleavage. Four variants predicted or previously characterized as benign were analyzed by BBFA for comparison. In all, three variants (W51S, C67R, and I370T) resulted in low expression. Furthermore, four variants (P64L, R339Q, G527V, and P528T) were identified as being highly deleterious with IC50s for C3b breakdown >1 log increased versus the WT protein, while two variants (K476E and R474Q) were ∼1 log reduced in function. Meanwhile, six variants (P50A, T203I, K441R, E548Q, P553S, and S570T) had IC50s similar to WT. Odds ratios and BBFA IC50s were positively correlated (r = 0.76, p < 0.01), while odds ratios versus combined annotation dependent depletion (CADD) scores were not (r = 0.43, p = 0.16). Overall, 15 CFI RVs were functionally characterized which may aid future patient stratification for complement-targeted therapies. Pure protein in vitro analysis remains the gold standard for determining the functional consequence of CFI RVs., Competing Interests: Conflict of interest D. K.: Gyroscope Therapeutics (consultancy, equity, grant income), Novartis (consultancy), Alexion Pharmaceuticals (consultancy), Apellis (consultancy); Sarepta (consultancy), Chemocentryx (Consultancy), Sobi (consultancy), Samsung (consultancy), Purespring (consultancy), Roche (consultancy); C. L. H: Q32 Bio (consultancy), Gyroscope Therapeutics (Consultancy), Novartis (employee), Ra Pharmaceuticals (Grant income), Biocryst (consultancy); K. J. M: Qualasept (consultancy), Freeline Therapeutics (consultancy), Catalyst Biosciences (grant income, consultancy), Idorsia Pharmaceuticals (grant income), Gemini Therapeutics (grant income, consultancy), Alexion Pharmaceuticals (grant income, consultancy); T. M. H.: Gyroscope Therapeutics, Novartis (employee); S. J. S.: Gyroscope Therapeutics, Novartis (employee); E. G.: Gyroscope Therapeutics, Novartis (employee); A. D.: Gyroscope Therapeutics, Novartis, Beacon Therapeutics (employee); A. V. J.: Gyroscope Therapeutics, Novartis (employee); A. L.: Gyroscope Therapeutics (consultancy, equity), Roche (consultancy), Apellis (consultancy), Novartis (consultancy)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up, and therapeutic approach of uveitic epiretinal membranes (ERM)., Methods: A thorough investigation of the literature was conducted using the PubMed database. Additionally, a complementary search was carried out on Google Scholar to ensure the inclusion of all relevant items in the collection., Results: ERM is an abnormal layer at the vitreoretinal interface, resulting from myofibroblastic cell proliferation along the inner surface of the central retina, causing visual impairment. Known by various names, ERM has diverse causes, including idiopathic or secondary factors, with ophthalmic imaging techniques like OCT improving detection. In uveitis, ERM occurrence is common, and surgical intervention involves pars plana vitrectomy with ERM peeling, although debates persist on optimal approaches., Conclusions: Histopathological studies and OCT advancements improved ERM understanding, revealing a diverse group of diseases without a unified model. Consensus supports surgery for uveitic ERM in progressive cases, but variability requires careful consideration and effective inflammation management. OCT biomarkers, deep learning, and surgical advances may enhance outcomes, and medical interventions and robotics show promise for early ERM intervention., (© 2024. Crown.)

Importance: Most neovascular age-related macular degeneration (nAMD) treatments involve long-term follow-up of disease activity. Home-monitoring would reduce the burden on patients and their caregivers and release clinic capacity., Objective: To evaluate 3 vision home-monitoring tests for patients to use to detect active nAMD compared with diagnosing active nAMD at hospital follow-up during the after-treatment monitoring phase., Design, Setting, and Participants: This was a diagnostic test accuracy study wherein the reference standard was detection of active nAMD by an ophthalmologist at hospital follow-up. The 3 home-monitoring tests evaluated included the following: (1) the KeepSight Journal (KSJ [International Macular and Retinal Foundation]), which contains paper-based near-vision tests presented as word puzzles, (2) the MyVisionTrack (mVT [Genentech]) vision-monitoring mobile app, viewed on an Apple mobile operating system-based device, and (3) the MultiBit (MBT [Visumetrics]) app, viewed on an Apple mobile operating system-based device. Participants were asked to test weekly; mVT and MBT scores were transmitted automatically, and KSJ scores were returned to the research office every 6 months. Raw scores between hospital follow-ups were summarized as averages. Patients were recruited from 6 UK hospital eye clinics and were 50 years and older with at least 1 eye first treated for active nAMD for at least 6 months or longer to a maximum of 42 months before approach. Participants were stratified by time since starting treatment. Study data were analyzed from May to September 2021., Exposures: The KSJ, mVT, and MBT were compared with the reference standard (in-hospital ophthalmologist examination)., Main Outcomes and Measures: Estimated area under receiver operating characteristic curve (AUROC). The study had 90% power to detect a difference of 0.06, or 80% power to detect a difference of 0.05, if the AUROC for 2 tests was 0.75., Results: A total of 297 patients (mean [SD] age, 74.9 [6.6] years; 174 female [58.6%]) were included in the study. At least 1 hospital follow-up was available for 312 study eyes in 259 participants (1549 complete visits). Median (IQR) home-monitoring testing frequency was 3 (1-4) times per month. Estimated AUROC was less than 0.6 for all home-monitoring tests, and only the KSJ summary score was associated with lesion activity (odds ratio, 3.48; 95% CI, 1.09-11.13; P = .04)., Conclusions and Relevance: Results suggest that no home-monitoring vision test evaluated provided satisfactory diagnostic accuracy to identify active nAMD diagnosed in hospital eye service follow-up clinics. Implementing any of these evaluated tests, with ophthalmologists only reviewing test positives, would mean most active lesions were missed, risking unnecessary sight loss.

Purpose: We introduce a deep learning-based biomarker proposal system for the purpose of accelerating biomarker discovery in age-related macular degeneration (AMD)., Design: Retrospective analysis of a large data set of retinal OCT images., Participants: A total of 3456 adults aged between 51 and 102 years whose OCT images were collected under the PINNACLE project., Methods: Our system proposes candidates for novel AMD imaging biomarkers in OCT. It works by first training a neural network using self-supervised contrastive learning to discover, without any clinical annotations, features relating to both known and unknown AMD biomarkers present in 46 496 retinal OCT images. To interpret the learned biomarkers, we partition the images into 30 subsets, termed clusters, that contain similar features. We conduct 2 parallel 1.5-hour semistructured interviews with 2 independent teams of retinal specialists to assign descriptions in clinical language to each cluster. Descriptions of clusters achieving consensus can potentially inform new biomarker candidates., Main Outcome Measures: We checked if each cluster showed clear features comprehensible to retinal specialists, if they related to AMD, and how many described established biomarkers used in grading systems as opposed to recently proposed or potentially new biomarkers. We also compared their prognostic value for late-stage wet and dry AMD against an established clinical grading system and a demographic baseline model., Results: Overall, both teams independently identified clearly distinct characteristics in 27 of 30 clusters, of which 23 were related to AMD. Seven were recognized as known biomarkers used in established grading systems, and 16 depicted biomarker combinations or subtypes that are either not yet used in grading systems, were only recently proposed, or were unknown. Clusters separated incomplete from complete retinal atrophy, intraretinal from subretinal fluid, and thick from thin choroids, and, in simulation, outperformed clinically used grading systems in prognostic value., Conclusions: Using self-supervised deep learning, we were able to automatically propose AMD biomarkers going beyond the set used in clinically established grading systems. Without any clinical annotations, contrastive learning discovered subtle differences between fine-grained biomarkers. Ultimately, we envision that equipping clinicians with discovery-oriented deep learning tools can accelerate the discovery of novel prognostic biomarkers., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Central serous chorioretinopathy (CSCR) is the fourth most common medical retinal disease. Moderate vision loss occurs in approximately one-third of patients who have the chronic form of the disease. CSCR has a multifactorial etiology, with acquired risk factors and increasing evidence of genetic susceptibility factors. The detection of new gene variants in CSCR and association of these variants with age-related macular degeneration provide insights into possible disease mechanisms. The contribution of multimodal ocular imaging and associated research studies to the modern-day clinical investigation of CSCR has been significant. This review aims to provide an overview of the most significant epidemiological and genetic studies of CSCR, in addition to describing its clinical and multimodal imaging features. The review also provides an update of the latest evidence from studies investigating pathophysiological mechanisms in CSCR and current opinions on multimodal imaging to better classify this complex retinal disease.

Purpose: To analyze the choroidal parameters of patients with chronic central serous chorioretinopathy (cCSC) and the association with central serous chorioretinopathy susceptibility genes., Methods: The choroidal vascular index (CVI) was obtained by binarizing spectral domain optical coherence tomography enhanced depth images of patients with cCSC and healthy age-matched controls. Patients with cCSC were genotyped for three central serous chorioretinopathy susceptibility single-nucleotide polymorphisms: rs4844392 ( mir-29b-2/CD46 ), rs1329428 ( CFH ), and rs2379120 (upstream GATA5 )., Results: One hundred three eyes with cCSC and 53 control eyes were included. There was a significant increase in the subfoveal choroidal area in both the affected (2.4 ± 0.6 mm 2 ) and fellow (2.2 ± 0.6 mm 2 ) eyes of patients with cCSC compared with controls (1.8 ± 0.5 mm 2 , P < 0.0001 and P < 0.0001). The CVI was reduced in patients with cCSC 63.5% ± 3.1% compared with controls 65.4% ± 2.3% ( P < 0.001) and also in the affected compared with the fellow eyes 64.6% ± 2.9% ( P < 0.01). There was a significant association between CVI in the cCSC group and presence of the risk single-nucleotide polymorphisms rs2379120 at GATA5 ( P < 0.01)., Conclusion: The relative reduction of CVI in patients with cCSC may suggest a persistence of vessel hyperpermeability over dilation in chronic disease. GATA5 is associated with CVI in patients with cCSC and therefore may have a role in choroidal vascularity., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up, and therapeutic approach of bilateral diffuse uveal melanocytic proliferation (BDUMP)., Methods: A meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items. Our search strategy utilized the following keywords: "bilateral diffuse uveal melanocytic proliferation", "BDUMP", and "Paraneoplastic Syndrome". Articles were considered based on their relevance, with the search spanning publications up to 2023. Studies were excluded if they did not contribute pertinent information or lacked methodological rigor. A critical appraisal of included studies was conducted, assessing study design, sample size, methodology, and potential bias, ensuring a thorough and transparent review process., Results: BDUMP is a rare and potentially sight-threatening condition characterized by the bilateral proliferation of melanocytes within the uvea. BDUMP is typically observed in middle-aged or elderly individuals and is often associated with an underlying malignancy, most commonly of gastrointestinal origin. BDUMP is frequently misdiagnosed as a benign nevus or choroidal metastasis, leading to delayed diagnosis and treatment. The ophthalmic symptoms and signs typically precede the diagnosis of a systemic malignancy, emphasizing the crucial role of ophthalmologists in the recognition of BDUMP. Several diagnostic modalities can aid in the diagnosis of BDUMP, including ophthalmic examination, imaging studies such as optical coherence tomography, fluorescein angiography, and indocyanine green angiography, and biopsy of the uveal tissue. Treatment of BDUMP is directed towards the underlying malignancy and may include chemotherapy, radiotherapy, or surgical resection. Additionally, strict monitoring with regular follow-ups may contribute to the detection of new lesions and the reduction in the size of existing ones., Conclusions: BDUMP can be considered a potential biomarker in the management of malignancies, especially when the primary underlying tumor has not been detected. Further research is needed to better understand the pathogenesis of BDUMP and its association with malignancy., (© 2024. Crown.)

Central retinal artery occlusion (CRAO) is a vascular ophthalmic emergency. Often caused by a sudden interruption of blood flow to the eye, with profound and painless vision loss, resulting in irreversible cell damage. An impacted embolus at the narrowest part of the central retinal artery is the most common cause. Cardioversion is a medical procedure used to restore a normal heart rhythm in individuals with atrial fibrillation (AF). In some cases, cardioversion can lead to thromboembolic complications. If an embolus reaches the central retinal artery, it can block the blood flow to the retina, resulting in CRAO and subsequent vision loss., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To describe inequalities in the Monitoring for Neovascular Age-related Macular Degeneration Reactivation at Home (MONARCH) diagnostic test accuracy study for: recruitment; participants' ability to self-test; and adherence to testing using digital applications during follow-up., Methods: Home-monitoring vision tests included two tests implemented as software applications (apps: MyVisionTrack and MultiBit) on an iPod Touch device. Patients were provided with all hardware required to participate (iPod and MIFI device) and trained to use the apps. Regression models estimated associations of age, sex, Index of Multiple Deprivation, strata of time since first diagnosis, and baseline visual acuity at study entry on outcomes of willingness to participate, ability to perform tests, and adherence to weekly testing., Results: A minority of patients who were approached were willing-in-principle to participate. Increasing age was associated with being unwilling-in-principle to participate. Patients from the most deprived areas had a 47% decrease in odds of being willing compared to those from the middle quintile deprived areas (odds ratio, 0.53; 95% confidence interval = 0.32, 0.88). Increasing age and worse deprivation were not consistently associated either with ability to self-monitor with the index tests, or adherence to weekly testing., Conclusions: Associations of increasing age and worse deprivation index were associated with unwillingness-in-principle to participate despite the provision of hardware' highlighting the potential for inequality with interventions of the kind evaluated., Translational Relevance: The clear evidence of inequalities in participation should prompt future research on ways to encourage adoption of mobile health technologies by underserved populations.

Punctate inner choroidopathy (PIC) is an uncommon idiopathic inflammatory condition characterized by multifocal chorioretinopathy that primarily affects young adults, with a predilection for myopic females. Clinically, it manifests as small, yellowish-white lesions in the inner choroid and outer retina, often associated with inflammatory changes. Accurate diagnosis remains a challenge due to its resemblance to other posterior uveitic entities, necessitating an astute clinical eye and advanced imaging techniques for differentiation. Multimodal imaging plays a crucial role by offering valuable insights, as it enables the visualization of various abnormalities related to uveitis. The pathogenesis of PIC is still a subject of debate, with a complex interplay of genetic, immunological, and environmental factors proposed. Managing PIC presents multiple challenges for clinicians. Firstly, variable disease severity within and among patients requires diverse treatments, from observation to aggressive immunosuppression and/or anti-VEGF therapy. Secondly, treatment must distinguish between primary causes of vision loss. New or worsening PIC lesions suggest active inflammation, while new neovascular membranes may indicate secondary neovascular processes. Thirdly, deciding on maintenance therapy is complex, balancing PIC prognosis variability against immunosuppression risks. Some patients have long periods of inactivity and remission, while others face sudden, vision-threatening episodes during quiescent phases. Through a systematic review of the literature, this paper sheds light on the current understanding of PIC, its challenges, and the prospects for future research. By synthesizing existing knowledge, it aims to aid clinicians in accurate diagnosis and guide treatment decisions for improved visual outcomes in individuals affected by PIC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There is a need to identify accurately prognostic factors that determine the progression of intermediate to late-stage age-related macular degeneration (AMD). Currently, clinicians cannot provide individualised prognoses of disease progression. Moreover, enriching clinical trials with rapid progressors may facilitate delivery of shorter intervention trials aimed at delaying or preventing progression to late AMD. Thus, we performed a systematic review to outline and assess the accuracy of reporting prognostic factors for the progression of intermediate to late AMD. A meta-analysis was originally planned. Synonyms of AMD and disease progression were used to search Medline and EMBASE for articles investigating AMD progression published between 1991 and 2021. Initial search results included 3229 articles. Predetermined eligibility criteria were employed to systematically screen papers by two reviewers working independently and in duplicate. Quality appraisal and data extraction were performed by a team of reviewers. Only 6 studies met the eligibility criteria. Based on these articles, exploratory prognostic factors for progression of intermediate to late AMD included phenotypic features (e.g. location and size of drusen), age, smoking status, ocular and systemic co-morbidities, race, and genotype. Overall, study heterogeneity precluded reporting by forest plots and meta-analysis. The most commonly reported prognostic factors were baseline drusen volume/size, which was associated with progression to neovascular AMD, and outer retinal thinning linked to progression to geographic atrophy. In conclusion, poor methodological quality of included studies warrants cautious interpretation of our findings. Rigorous studies are warranted to provide robust evidence in the future., Competing Interests: Declaration of Competing Interest Philipp Anders is supported by the “Freiwillige Akademische Gesellschaft Basel” and “OPOS zugunsten von Wahrnehmungsbehinderten” foundations. Ursula Schmidt-Erfurth receives grant support from Genentech, Kodiak, Novartis, RetInSight and Roche and is a consultant for Apellis. Hendrick Scholl is a member of the Scientific Advisory Board of: Astellas, Boehringer Ingelheim, Gyroscope/Novartis, Janssen, Okuvision, and Third Rock Ventures. He is a consultant of Gerson Lehrman Group, Guidepoint Global, and Tenpoint Therapeutics. He is a member of a Data Monitoring and Safety Board/Committee for Belite Bio, ReNeuron Group Plc/Ora Inc., Roche, and member of a Steering Committee for Novo Nordisk. He is a co-director of the Institute of Molecular and Clinical Ophthalmology Basel (IOB) which receives funding from the University of Basel, the University Hospital Basel, Novartis, and the government of Basel-Stadt. Daniel Rueckert is a co-founder and shareholder of IXICO Plc. Sobha Sivaprasad has received funding/fees from Bayer, Novartis, AbbVie, Roche, Boehringer Ingelheim, Optos, EyeBiotech, Biogen, and Apellis. She is a member of a Data Monitoring and Safety Board/Committee for Bayer and a member of a Steering Committee for Novo Nordisk. Andrew Lotery is a consultant for Gyroscope/Novartis, Eyebio, Complement Therapeutics, Allergan, Apellis and Tarsus Pharmaceuticals. No other disclosures were reported. No conflicts related to this project., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)