Deep Learning-Based Clustering of OCT Images for Biomarker Discovery in Age-Related Macular Degeneration (PINNACLE Study Report 4).

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.

Metadata-enhanced contrastive learning from retinal optical coherence tomography images.

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.

Central retinal artery and Common Carotid artery occlusions following COVID-19 infection: A case report.

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.

Dual pathway inhibition with faricimab for previously treated neovascular age-related macular degeneration and diabetic macular oedema: guidance from a UK panel of retina specialists.

BACKGROUND/OBJECTIVES: Some eyes with neovascular age-related macular degeneration (nAMD) and centre-involving diabetic macular oedema (DMO) fail to respond sufficiently or lose response over time to standard of care intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. This paper explores clinical scenarios for switching to dual action angiopoietin-2 (Ang-2)/VEGF-A inhibitor faricimab (Vabysmo, Roche Products Limited) in previously anti-VEGF-treated patients. METHODS: A national steering group meeting of UK retina specialists was held in London on 27 October 2023. Clinician practice and experience were reviewed together with pivotal clinical trial data and early findings from real-world settings. Roche Products Limited facilitated and funded the meeting. RESULTS: While there is no standardised protocol for identifying suboptimal response, the authors review relevant clinical biomarkers of disease activity used in routine clinical practice to determine patient response and guide treatment decisions. Common reasons identified for considering a change of treatment were lack of efficacy demonstrated by suboptimal anatomic or visual improvement and insufficient durability of response. The panel outline strategies for switching to faricimab among eligible patients with a prior anti-VEGF treatment history, with initial monthly loading doses or maintaining the previous treatment interval before attempting to extend, that may be integrated into current treat-and-extend (T&E) clinical pathways for treating patients with nAMD and DMO. General considerations for switching between treatments are also reviewed. CONCLUSION: Clinicians may consider a treatment switch to faricimab in nAMD and DMO patients who have suboptimal disease control or insufficient durability of response on initial anti-VEGF therapy.

Genetic Testing of Patients with Inherited Retinal Diseases in the European Countries: An International Survey by the European Vision Institute.

INTRODUCTION: The purpose of this project was to explore the current standards of clinical care genetic testing and counseling for patients with inherited retinal diseases (IRDs) from the perspective of leading experts in selected European countries. Also, to gather opinions on current bottlenecks and future solutions to improve patient care. METHODS: On the initiative of the European Vision Institute, a survey questionnaire with 41 questions was designed and sent to experts in the field from ten European countries. Each participant was asked to answer with reference to the situation in their own country. RESULTS: Sixteen questionnaires were collected by November 2023. IRD genetic tests are performed in clinical care settings for 80% or more of tested patients in 9 countries, and the costs of genetic tests in clinical care are covered by the public health service to the extent of 90% or more in 8 countries. The median proportion of patients who are genetically tested, the median rate of genetically solved patients among those who are tested, and the median proportion of patients receiving counseling are 51-70%, 61-80%, and 61-80%, respectively. Improving the education of healthcare professionals who facilitate patient referrals to specialized centers, improving access of patients to more thorough genotyping, and increasing the number of available counselors were the most advocated solutions. CONCLUSION: There is a significant proportion of IRD patients who are not genetically tested, whose genetic testing is inconclusive, or who do not receive counseling. Educational programs, greater availability of state-of-the-art genotyping and genetic counselors could improve healthcare for IRD patients.

Home-monitoring for neovascular age-related macular degeneration in older adults within the UK: the MONARCH diagnostic accuracy study.

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 < 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.

Treatment for neovascular age-related macular degeneration, the most common cause of sight loss in those over 50 years, involves regular eye injections and frequent follow-up appointments. This is inconvenient for patients and causes capacity issues in the hospital eye service. Finding tests that could be undertaken at home that could detect if a further injection and hospital appointment was required or not would increase capacity to see those at highest risk of sight loss and also reduce the burden on patients and their carers. We investigated three different visual function tests, one paper-based and two applications on an iPod Touch_TM tablet (Apple, Cupertino, CA, USA). We wanted to see if they could detect an increase in disease activity that would require treatment, compared to the decision by a retinal specialist at a traditional hospital eye outpatient visit based on clinical examination and retinal imaging. To encourage those without a smartphone or home internet to participate, we provided both an iPod Touch and Mobile Wireless-Fidelity device with a mobile contract. None of the tests performed well enough to safely monitor patients at home. Those who were willing to participate tended to be younger, had previous experience of using smartphones, sending e-mail and internet access and were more well-off than those who chose not to participate. Some participants also experienced difficulties with the devices provided and successfully uploading the data which were not related to the extent of previous information technology experience. There were also significant technical challenges for the research team. The study helpline was used heavily, considerably more than we anticipated. These tests are not ready to be used in this context. Future studies involving mobile health technology need to carefully consider how to reach those unlikely to participate and provide sufficient technical support to support long-term follow-up.

Acceptability of Home Monitoring for Neovascular Age-Related Macular Degeneration Reactivation: A Qualitative Study.

This study formed part of a diagnostic test accuracy study to quantify the ability of three index home monitoring (HM) tests (one paper-based and two digital tests) to identify reactivation in Neovascular age-related macular degeneration (nAMD). The aim of the study was to investigate views about acceptability and explore adherence to weekly HM. Semi-structured interviews were held with 98 patients, family members, and healthcare professionals. A thematic approach was used which was informed by theories of technology acceptance. Various factors influenced acceptability including a patient's understanding about the purpose of monitoring. Training and ongoing support were regarded as essential for overcoming unfamiliarity with digital technology. Findings have implications for implementation of digital HM in the care of older people with nAMD and other long-term conditions.

Epiretinal membranes in patients with uveitis: an update on the current state of management.

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.

Comprehensive functional characterization of complement factor I rare variant genotypes identified in the SCOPE geographic atrophy cohort.

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.

Central Serous Chorioretinopathy: Epidemiology, Genetics and Clinical Features.

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.

Morph-SSL: Self-Supervision With Longitudinal Morphing for Forecasting AMD Progression From OCT Volumes.

The lack of reliable biomarkers makes predicting the conversion from intermediate to neovascular age-related macular degeneration (iAMD, nAMD) a challenging task. We develop a Deep Learning (DL) model to predict the future risk of conversion of an eye from iAMD to nAMD from its current OCT scan. Although eye clinics generate vast amounts of longitudinal OCT scans to monitor AMD progression, only a small subset can be manually labeled for supervised DL. To address this issue, we propose Morph-SSL, a novel Self-supervised Learning (SSL) method for longitudinal data. It uses pairs of unlabelled OCT scans from different visits and involves morphing the scan from the previous visit to the next. The Decoder predicts the transformation for morphing and ensures a smooth feature manifold that can generate intermediate scans between visits through linear interpolation. Next, the Morph-SSL trained features are input to a Classifier which is trained in a supervised manner to model the cumulative probability distribution of the time to conversion with a sigmoidal function. Morph-SSL was trained on unlabelled scans of 399 eyes (3570 visits). The Classifier was evaluated with a five-fold cross-validation on 2418 scans from 343 eyes with clinical labels of the conversion date. The Morph-SSL features achieved an AUC of 0.779 in predicting the conversion to nAMD within the next 6 months, outperforming the same network when trained end-to-end from scratch or pre-trained with popular SSL methods. Automated prediction of the future risk of nAMD onset can enable timely treatment and individualized AMD management.

3DTINC: Time-Equivariant Non-Contrastive Learning for Predicting Disease Progression From Longitudinal OCTs.

Self-supervised learning (SSL) has emerged as a powerful technique for improving the efficiency and effectiveness of deep learning models. Contrastive methods are a prominent family of SSL that extract similar representations of two augmented views of an image while pushing away others in the representation space as negatives. However, the state-of-the-art contrastive methods require large batch sizes and augmentations designed for natural images that are impractical for 3D medical images. To address these limitations, we propose a new longitudinal SSL method, 3DTINC, based on non-contrastive learning. It is designed to learn perturbation-invariant features for 3D optical coherence tomography (OCT) volumes, using augmentations specifically designed for OCT. We introduce a new non-contrastive similarity loss term that learns temporal information implicitly from intra-patient scans acquired at different times. Our experiments show that this temporal information is crucial for predicting progression of retinal diseases, such as age-related macular degeneration (AMD). After pretraining with 3DTINC, we evaluated the learned representations and the prognostic models on two large-scale longitudinal datasets of retinal OCTs where we predict the conversion to wet-AMD within a six-month interval. Our results demonstrate that each component of our contributions is crucial for learning meaningful representations useful in predicting disease progression from longitudinal volumetric scans.

Home-Monitoring Vision Tests to Detect Active Neovascular Age-Related Macular Degeneration.

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.

Inequalities in Uptake and Use of Digital Applications for Home-Monitoring of Neovascular Age-Related Macular Degeneration in an Elderly Visually Impaired Population: The MONARCH Study.

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.

Central retinal artery occlusion after cardioversion of atrial fibrillation.

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.

Diagnostic and therapeutic challenges in acute retinal necrosis; an update.

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.

Descriptive study of the challenges when implementing an app for patients with neovascular age-related macular degeneration to monitor their vision at home.

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.

Diagnostic and therapeutic considerations in patients with bilateral diffuse uveal melanocytic proliferation.

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.

Central serous chorioretinopathy: An evidence-based treatment guideline.

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.