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Winfried Amoaku,1 Konstantinos Balaskas,2,3 Tomas Cudrnak,4 Louise Downey,5 Markus Groppe,6 Sajjad Mahmood,7 Hemal Mehta,8 Quresh Mohamed,9 Bushra Mushtaq,10 Philip Severn,11 Athanasios Vardarinos,12 Yit Yang,13 Saad Younis14 1Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK; 2NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College of London Institute of Ophthalmology, London, UK; 3University of Manchester, Manchester, UK; 4Royal Eye Infirmary, University Hospitals Plymouth NHS Trust, Plymouth, UK; 5Hull and East Yorkshire Eye Hospital, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK; 6Ophthalmology, Stoke Mandeville, Buckinghamshire Healthcare NHS Trust, Aylesbury, UK; 7Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 8Royal Free London NHS Foundation Trust, London, UK; 9Gloucestershire Eye Unit, Cheltenham General Hospital, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK; 10Birmingham and Midland Eye Centre, Sandwell and West Birmingham NHS Trust, Birmingham, UK; 11South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK; 12Eye Treatment Centre, West Suffolk Hospital, West Suffolk NHS Foundation Trust, Bury St Edmunds, UK; 13Wolverhampton Eye Infirmary, The Royal Wolverhampton NHS Trust, Wolverhampton, UK; 14Ophthalmology, Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK Abstract: The treatment of neovascular (wet) age-related macular degeneration (AMD) with ranibizumab is now very well established in terms of efficacy and safety. Recent clinical trials and real-world studies have demonstrated the advantages of a Treat-and-Extend (T&E) regimen, and many hospital departments are now in the process of adopting this new regimen in favor of the pro re nata regimen for initiating and continuing ranibizumab therapy for patients with wet AMD. The comprehensive spectrum of issues related to implementation of the regimen is covered qualitatively in ten didactic topics provided by a group of clinicians with direct experience of this regimen in their department. The topics include definition, new and previously treated eyes, management of high-frequency injections, maximum extensions, discontinuing T&E, bilateral cases, clerical, audit, and patient counseling. This article aims to provide a useful resource for the implementation of the T&E regimen. A quantitative summary of the visual outcomes in key publications is also provided in this article. This article should be a valuable resource for staff training. Keywords: ranibizumab, age-related macular degeneration, nAMD, Treat and Extend, anti-VEGF treatment

This review is intended to recall the diagnosis and treatment of deep-vein thrombosis, which is along with pulmonary embolism, a manifestation of the same disorder of venous thrombosis. The importance of using updated algorithms for the evaluation and cure of the patients with suspected disease, It is obvious. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case study of 41-year-old patient with fundus dystrophy and treated with Ranibizumab.

Oestrogen and progesterone fluctuate cyclically in women throughout their adult lives. Although these hormones cross the blood-retinal barrier and bind to intraocular receptors, their effects remain unclear. We present the first review to date on associations between posterior pole structures-specifically the macula, choroid, and optic disc-and both the menstrual cycle and post-menopausal period, utilising multimodal imaging techniques in healthy adult non-pregnant women. We excluded studies on contraception and hormonal replacement therapy, focusing solely on physiological associations. Despite the comprehensive scope of our review, limited data and inconsistent reporting among studies prevented the establishment of meaningful trends. Across menstrual cycle phases, choroidal thickness (CHT) was the most consistently reported parameter, with thinning during the luteal phase compared to the follicular phase. Conversely, no significant differences were observed in macular or disc morphology across the cycle, likely reflecting a preserved structure despite potential fluctuations in blood flow and perfusion. Studies comparing pre- and post-menopausal associations, after adjusting for age or body mass index (BMI), failed to reveal meaningful trends, highlighting the difficulty in separating the effect of age from hormonal declines in older women. Understanding how hormonal cycles impact the posterior pole in women is crucial for addressing sex differences in various ocular pathologies. Research on female-specific factors is still sparse, and interestingly, the majority of affiliations in the reviewed articles did not originate from regions with the highest biomedical research funding and publication rates. We encourage further studies focusing on female-specific variables and provide recommendations for future designs., Competing Interests: Competing interests: The authors declare no conflicts of interest related to the content of this manuscript. Specifically, S. Sivaprasad and A. P. Khawaja, who are members of the Eye editorial board. Their editorial roles have not influenced the peer review or decision-making process for this article., (© 2025. The Author(s).)

Importance: Predicting undesirable outcomes following anti-VEGF initiation in macular oedema is critical for effective clinical decision-making and optimised care., Objective: To estimate the time to undesirable events in diabetic macular oedema (DMO), central and branch vein occlusions (CRVO and BRVO) after appropriate loading doses with either ranibizumab or aflibercept and identified baseline predictors of negative outcome., Design, Setting, Participants: A retrospective cohort study of 3277 patients (N = 2107 in DMO, N = 413 in CRVO and N = 757 in BRVO) collected over a 10-year period, in a large UK tertiary centre. Only one eye was included per patient. Inclusion criteria pre-specified a minimum of two clinic visits with one being at least 6 months post treatment., Main Outcome and Measures: The main outcome measure was absence of visual acuity (VA) improvement due to macular oedema failure of anti-VEGF therapy (defined as VA gain <5 ETDRS letters and CST increase of 50 µm or CST > 325 µm) modelled using time-event analyzes of appropriately loaded patients. Secondary outcomes included survival curves by individual condition (DMO, CRVO, BRVO) and factors associated with negative outcomes., Results: After starting anti-VEGF, there was a 50% chance of undesirable outcomes at 2.3, 5.24 and 6.16 years for DMO, CRVO and BRVO, respectively. Cox proportional hazards modelling identified presenting age, intraretinal (IRF) volume, presence of DMO and VA as predictors of negative outcomes, whilst South East Asian ethnicity conferred an independent protective effect., Conclusion: Real-world data suggest that undesirable events following anti-VEGF injections is likely to in 50% of patients by the third year of treatment in spite of appropriate loading. The definition of undesirable treatment events captured nearly all patients who were escalated to another therapy, but this proportion represented a small percentage of our definition of failed response., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Although it is well known that photoreceptor damage and color vision loss occur in patients with diabetic retinopathy (DR), the relationship between structural and functional changes in diabetes mellitus (DM) remains unclear. Using highly sensitive measures of photoreceptor structure and function, we aim to determine whether early loss of color sensitivity in DM is also accompanied by decreased cone density., Methods: Monocular data from 26 patients with DM and 25 healthy controls were examined to assess cone photoreceptor metrics, using confocal adaptive optics scanning light ophthalmoscopy, and red/green (RG) and yellow/blue (YB) color vision thresholds, using the Colour Assessment and Diagnosis test., Results: Both RG and YB thresholds were significantly greater in patients with DM than in the healthy controls (RG and YB = P < 0.001), and there were statistically significant differences between the 2 groups in confocal cone density at 1 degree (P = 0.024), and intercell regularity at both 1 (P = 0.013) and 2 degrees (P = 0.012). In patients with DM, cone density was inversely correlated with YB (at 0.5, 1 and 2 degrees, all P values < 0.041), but not for RG color vision thresholds., Conclusions: This is the first study to investigate the relationship between cone metrics and color vision in patients with DM. The results reveal a significant inverse relationship between confocal cone density and color vision thresholds at the locations assessed within the foveal region. These findings represent a significant advancement in oculomics research.

Age-related macular degeneration (AMD) is a multifactorial retinal disease with a large genetic risk contribution. Reticular pseudodrusen (RPD) is a sub-phenotype of AMD with a high risk of progression to late vision threatening AMD. In a genome-wide association study of 2,165 AMD+/RPD+ and 4,181 AMD+/RPD-compared to 7,660 control participants, both chromosomes 1 ( CFH ) and 10 ( ARMS2/HTRA1 ) major AMD risk loci were reidentified. However association was only detected for the chromosome 10 locus when comparing AMD+/RPD+ to AMD+/RPD-cases. The chromosome 1 locus was notably absent. The chromosome 10 RPD risk region contains a long non-coding RNA (ENSG00000285955/BX842242.1) which colocalizes with genetic markers of retinal thickness. BX842242.1 has a strong retinal eQTL signal, pinpointing the parafoveal photoreceptor outer segment layer. Whole genome sequencing of phenotypically extreme RPD cases identified even stronger enrichment for the chromosome 10 risk genotype.

Background: Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased healthspan. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity, and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand, and meet the healthcare, workforce, wellbeing, and socioeconomic needs of ageing populations, while supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies., Methods: The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19 th , 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥70% for approval., Results: The accepted criteria for an ageing-related pathology, disease or syndrome were: Develops and/or progresses with increasing chronological age.Should be associated with, or contribute to, functional decline, or an increased susceptibility to functional decline.Evidenced by studies in humans., Conclusions: Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.

Purpose: To quantify relevant fundus autofluorescence (FAF) image features cross-sectionally and longitudinally in a large cohort of inherited retinal diseases (IRDs) patients., Design: Retrospective study of imaging data (55-degree blue-FAF on Heidelberg Spectralis) from patients., Participants: Patients with a clinical and molecularly confirmed diagnosis of IRD who have undergone FAF 55-degree imaging at Moorfields Eye Hospital (MEH) and the Royal Liverpool Hospital (RLH) between 2004 and 2019., Methods: Five FAF features of interest were defined: vessels, optic disc, perimacular ring of increased signal (ring), relative hypo-autofluorescence (hypo-AF) and hyper-autofluorescence (hyper-AF). Features were manually annotated by six graders in a subset of patients based on a defined grading protocol to produce segmentation masks to train an AI model, AIRDetect, which was then applied to the entire MEH imaging dataset., Main Outcome Measures: Quantitative FAF imaging features including area in mm 2 and vessel metrics, were analysed cross-sectionally by gene and age, and longitudinally to determine rate of progression. AIRDetect feature segmentation and detection were validated with Dice score and precision/recall, respectively., Results: A total of 45,749 FAF images from 3,606 IRD patients from MEH covering 170 genes were automatically segmented using AIRDetect. Model-grader Dice scores for disc, hypo-AF, hyper-AF, ring and vessels were respectively 0.86, 0.72, 0.69, 0.68 and 0.65. The five genes with the largest hypo-AF areas were CHM , ABCC6 , ABCA4 , RDH12 , and RPE65 , with mean per-patient areas of 41.5, 30.0, 21.9, 21.4, and 15.1 mm 2 . The five genes with the largest hyper-AF areas were BEST1 , CDH23 , RDH12 , MYO7A , and NR2E3 , with mean areas of 0.49, 0.45, 0.44, 0.39, and 0.34 mm 2 respectively. The five genes with largest ring areas were CDH23 , NR2E3 , CRX , EYS and MYO7A, with mean areas of 3.63, 3.32, 2.84, 2.39, and 2.16 mm 2 . Vessel density was found to be highest in EFEMP1 , BEST1 , TIMP3 , RS1 , and PRPH2 (10.6%, 10.3%, 9.8%, 9.7%, 8.9%) and was lower in Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis genes. Longitudinal analysis of decreasing ring area in four RP genes ( RPGR, USH2A, RHO, EYS ) found EYS to be the fastest progressor at -0.18 mm 2 /year., Conclusions: We have conducted the first large-scale cross-sectional and longitudinal quantitative analysis of FAF features across a diverse range of IRDs using a novel AI approach.

Purpose: Application of artificial intelligence (AI) to macular OCT scans to segment and quantify volumetric change in anatomical and pathological features during intravitreal treatment for neovascular age-related macular degeneration (AMD)., Design: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database., Participants: A total of 2115 eyes from 1801 patients starting anti-VEGF treatment between June 1, 2012, and June 30, 2017., Methods: The Moorfields Eye Hospital neovascular AMD database was queried for first and second eyes receiving anti-VEGF treatment and had an OCT scan at baseline and 12 months. Follow-up scans were input into the AI system and volumes of OCT variables were studied at different time points and compared with baseline volume groups. Cross-sectional comparisons between time points were conducted using Mann-Whitney U test., Main Outcome Measures: Volume outputs of the following variables were studied: intraretinal fluid, subretinal fluid, pigment epithelial detachment (PED), subretinal hyperreflective material (SHRM), hyperreflective foci, neurosensory retina, and retinal pigment epithelium., Results: Mean volumes of analyzed features decreased significantly from baseline to both 4 and 12 months, in both first-treated and second-treated eyes. Pathological features that reflect exudation, including pure fluid components (intraretinal fluid and subretinal fluid) and those with fluid and fibrovascular tissue (PED and SHRM), displayed similar responses to treatment over 12 months. Mean PED and SHRM volumes showed less pronounced but also substantial decreases over the first 2 months, reaching a plateau postloading phase, and minimal change to 12 months. Both neurosensory retina and retinal pigment epithelium volumes showed gradual reductions over time, and were not as substantial as exudative features., Conclusions: We report the results of a quantitative analysis of change in retinal segmented features over time, enabled by an AI segmentation system. Cross-sectional analysis at multiple time points demonstrated significant associations between baseline OCT-derived segmented features and the volume of biomarkers at follow-up. Demonstrating how certain OCT biomarkers progress with treatment and the impact of pretreatment retinal morphology on different structural volumes may provide novel insights into disease mechanisms and aid the personalization of care. Data will be made public for future studies., 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.)

Importance: Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials., Objective: To analyze the association between pegcetacoplan and consensus GA SD-OCT end points., Design, Setting, and Participants: This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023., Interventions: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month., Main Outcomes and Measures: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal)., Results: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month., Conclusions and Relevance: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors., Trial Registration: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

Introduction: The diagnosis of neovascular age-related macular degeneration (nAMD), the leading cause of visual impairment in the developed world, relies on the interpretation of various imaging tests of the retina. These include invasive angiographic methods, such as Fundus Fluorescein Angiography (FFA) and, on occasion, Indocyanine-Green Angiography (ICGA). Newer, non-invasive imaging modalities, predominately Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA), have drastically transformed the diagnostic approach to nAMD. The aim of this study is to undertake a comprehensive diagnostic accuracy assessment of the various imaging modalities used in clinical practice for the diagnosis of nAMD (OCT, OCTA, FFA and, when a variant of nAMD called Polypoidal Choroidal Vasculopathy is suspected, ICGA) both alone and in various combinations., Methods and Analysis: This is a non-inferiority, prospective, randomised diagnostic accuracy study of 1067 participants. Participants are patients with clinical features consistent with nAMD who present to a National Health Service secondary care ophthalmology unit in the UK. Patients will undergo OCT as per standard practice and those with suspicious features of nAMD on OCT will be approached for participation in the study. Patients who agree to take part will also undergo both OCTA and FFA (and ICGA if indicated). Interpretation of the imaging tests will be undertaken by clinicians at recruitment sites. A randomised design was selected to avoid bias from consecutive review of all imaging tests by the same clinician. The primary outcome of the study will be the difference in sensitivity and specificity between OCT+OCTA and OCT+FFA (±ICGA) for nAMD detection as interpreted by clinicians at recruitment sites., Ethics and Dissemination: The study has been approved by the South Central-Oxford B Research Ethics Committee with reference number 21/SC/0412.Dissemination of study results will involve peer-review publications, presentations at major national and international scientific conferences., Trial Registration Number: ISRCTN18313457., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: Implementing teleophthalmology into the optometric referral pathway may ease the current pressures on hospital eye services caused by over-referrals from some optometrists. This study aimed to understand the practical implications of implementing teleophthalmology by analysing lived experiences and perceptions of teleophthalmology in the optometric referral pathway for suspected retinal conditions., Design: Qualitative in-depth interview study SETTING: Fourteen primary care optometry practices and four secondary care hospital eye services from four NHS Foundation Trusts across the UK., Participants: We interviewed 41 participants: patients (17), optometrists (18), and ophthalmologists (6) who were involved in the HERMES study. Through thematic analysis, we collated and present their experiences of implementing teleophthalmology., Results: All participants interviewed were positive towards teleophthalmology as it could enable efficiencies in the referral pathway and improve feedback and communication between patients and healthcare professionals. Concerns included setup costs for optometrists and anxieties from patients about not seeing an ophthalmologist face to face. However, reducing unnecessary visits and increasing the availability of resources and capacity were seen as significant benefits., Conclusions: Overall, we report positive experiences of implementing teleophthalmology into the optometric referral pathway for suspected retinal conditions. Successful implementation will require appropriate investment to set up and integrate new technology and remunerate services, and continued evaluation to ensure timely feedback to patients and between healthcare professionals is received., Trial Registration Number: ISRCTN18106677., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Data are limited pertaining to the long-term benefits of aflibercept treatment for neovascular age-related macular degeneration (nAMD). The aim of this study was to provide outcomes, safety, durability and quality-of-life data with aflibercept using a modified treat, extend and fixed regime over 4 years., Methods: Prospective, multicentre, single cohort observational study of treatment-naïve nAMD participants treated with aflibercept as 2-year extension of the MATE-trial that compared early and late Treat-and-Extend for 2 years. Refracted ETDRS best corrected visual acuity (BCVA), central retinal thickness (CRT), treatment interval and adverse events were assessed. Quality-of-life was measured using the Macular Disease Dependent Quality of Life (MacDQoL) and Macular Disease Treatment Satisfaction Questionnaires (MacTSQ)., Results: Twenty-six of 40 participants completing the MATE-trial were enrolled with 20 completing the total 4-year study. Mean BCVA was 60.7 at Month 0 and 64.8 ETDRS letters at Month 48 while CRT decreased from 423.7 μm to 292.2 μm. Five participants discontinued treatment due to inactivity. The mean number of treatments and visits for the remaining participants was 27 and 30.0, respectively, with treatment intervals extended to 12 weeks in four participants at Month 48. Both AMD-specific QoL and treatment satisfaction remained stable between Months 0 and 48 and mean BCVA significantly correlated with AMD-specific QoL scores at Months 12, 24 and 48., Conclusions: Results suggest that BCVA can be maintained over 48 months when following a treat-extend-and-fix regimen of aflibercept with intervals out to 12 weeks, while maintaining AMD-specific QoL and treatment satisfaction., (© 2023 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)