Background and objectives Over the years, several treatment options have been developed for neovascular age-related macular degeneration (AMD), the most notable being intravitreal injections of anti-vascular endothelial growth factor drugs. The rationale for treating neovascular AMD is to preserve and improve central vision, enhance the quality of life for affected individuals, stabilize or improve vision, and prevent further structural damage to the macula. The objective of the present study was to evaluate the clinical course of different disease types of neovascular age-related macular degeneration and their treatment response to anti-vascular endothelial growth factor (anti-VEGF) injections. Methods This prospective observational study was conducted at a tertiary care referral hospital in Eastern India during October 2019 and September 2021. Patients diagnosed with neovascular AMD attending our Outpatient department and retina clinic were recruited for the study. An experienced ophthalmologist examined all patients, meeting the inclusion criteria. The clinical profile, including initial best corrected visual acuity (BCVA), ophthalmoscopic, fluorescein angiographic, and optical coherence tomography (OCT) findings of different patterns of neovascular AMD, were collected and analyzed. Patients were subjected to intravitreal Ranibizumab every month for three months and then on a when-required basis. Visual outcomes were recorded at each follow-up, and a comparison was done between initial and final visual acuity. Descriptive statistics were used for analysis, with p< 0.05 taken as statistically significant. Results A total of 72 patients were included in the study. Fundus fluorescein angiography revealed that 52.78% were classic, 15.28% were minimally classic, and 31.94% were of occult variety. 41.66% of lesions were subfoveal in location, 47.22% were juxtafoveal, and 11.11% lesions were extrafoveal in location. The mean BCVA was Log MAR (Logarithm of the Minimum Angle of Resolution) 1.061±0.25. The average number of intravitreal Ranibizumab injections given to each eye was five. BCVA of patients after the third injection was log MAR 0.818±0.296. There was a significant improvement in mean BCVA from baseline 1.061±0.254 to 0.787±0.317 after the study (p-valve: p<0.05). After the first injection, 49 patients (68.05%) experienced an initial improvement of at least one line, 20 patients (27.77%) did not exhibit any improvement, and 3 patients (4.16%) had a decline of one line in Snellen\'s visual acuity chart. Over the follow-up period,10 showed improvement in 1 line in the Snellen chart after subsequent injection. At the end of the study, six patients showed no change, and four patients showed deterioration after the completion of injections. No adverse events were noted during the study period. Conclusions Intravitreal Ranibizumab is effective in improving visual outcomes in treatment-naïve individuals with neovascular age-related macular degeneration. The decision for repeat intravitreal anti-VEGF injection should be based on OCT findings of subretinal fluid, pigment epithelial detachment, and cystoid macular edema as an indicator of disease activity. This can also lessen the number of intravitreal injections and morbidity in these patients.

The goal of this study was to evaluate the role of texture-based baseline radiomic features (Fr) and dynamic radiomics alterations (delta, FΔr) within multiple targeted compartments on optical coherence tomography (OCT) scans to predict response to anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (nAMD).
HAWK is a phase 3 clinical trial data set of active nAMD patients (N = 1082) comparing brolucizumab and aflibercept. This analysis included patients receiving 6 mg brolucizumab or 2 mg aflibercept and categorized as complete responders (n = 280) and incomplete responders (n = 239) based on whether or not the eyes achieved/maintained fluid resolution on OCT. A total of 481 Fr were extracted from each of the fluid, subretinal hyperreflective material (SHRM), retinal tissue, and sub-retinal pigment epithelium (RPE) compartments. Most discriminating eight baseline features, selected by the minimum redundancy, maximum relevance feature selection, were evaluated using a quadratic discriminant analysis (QDA) classifier on the training set (Str, n = 363) to differentiate between the two patient groups. Classifier performance was subsequently validated on independent test set (St, n = 156).
In total, 519 participants were included in this analysis from the HAWK phase 3 study. There were 280 complete responders and 219 incomplete responders. Compartmental analysis of radiomics featured identified the sub-RPE and SHRM compartments as the most distinguishing between the two response groups. The QDA classifier yielded areas under the curve of 0.78, 0.79, and 0.84, respectively, using Fr, FΔr, and combined Fr, FΔr, and Fc on St.
Utilizing compartmental static and dynamic radiomics features, unique differences were identified between eyes that respond differently to anti-VEGF therapy in a large phase 3 trial that may provide important predictive value.
Imaging biomarkers, such as radiomics features identified in this analysis, for predicting treatment response are needed to enhanced precision medicine in the management of nAMD.

OBJECTIVE: To report long-term results from a phase 1/2a clinical trial assessment of a scaffold-based human embryonic stem cell-derived retinal pigmented epithelium (RPE) implant in patients with advanced geographic atrophy (GA).
METHODS: A single-arm, open-label phase 1/2a clinical trial approved by the United States Food and Drug Administration.
METHODS: Patients were 69-85 years of age at the time of enrollment and were legally blind in the treated eye (best-corrected visual acuity [BCVA], ≤ 20/200) as a result of GA involving the fovea.
METHODS: The clinical trial enrolled 16 patients, 15 of whom underwent implantation successfully. The implant was administered to the worse-seeing eye with the use of a custom subretinal insertion device. The companion nonimplanted eye served as the control. The primary endpoint was at 1 year; thereafter, patients were followed up at least yearly.
METHODS: Safety was the primary endpoint of the study. The occurrence and frequency of adverse events (AEs) were determined by scheduled eye examinations, including measurement of BCVA and intraocular pressure and multimodal imaging. Serum antibody titers were collected to monitor systemic humoral immune responses to the implanted cells.
RESULTS: At a median follow-up of 3 years, fundus photography revealed no migration of the implant. No unanticipated, severe, implant-related AEs occurred, and the most common anticipated severe AE (severe retinal hemorrhage) was eliminated in the second cohort (9 patients) through improved intraoperative hemostasis. Nonsevere, transient retinal hemorrhages were noted either during or after surgery in all patients as anticipated for a subretinal surgical procedure. Throughout the median 3-year follow-up, results show that implanted eyes were more likely to improve by > 5 letters of BCVA and were less likely to worsen by > 5 letters compared with nonimplanted eyes.
CONCLUSIONS: This report details the long-term follow-up of patients with GA to receive a scaffold-based stem cell-derived bioengineered RPE implant. Results show that the implant, at a median 3-year follow-up, is safe and well tolerated in patients with advanced dry age-related macular degeneration. The safety profile, along with the early indication of efficacy, warrants further clinical evaluation of this novel approach for the treatment of GA.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

UNASSIGNED: The aim of this retrospective cohort study was to obtain three-dimensional (3D) photoreceptor outer segment (OS) metrics measurements with the assistance of a deep learning model (DLM) and to evaluate the longitudinal change in OS metrics and associated factors in retinitis pigmentosa GTPase regulator (RPGR) X-linked retinitis pigmentosa (XLRP).
UNASSIGNED: The study included 34 male patients with RPGR-associated XLRP who had preserved ellipsoid zone (EZ) within their spectral-domain optical coherence tomography volume scans and an approximate 2-year or longer follow-up. Volume scans were segmented using a DLM with manual correction for EZ and apical retinal pigment epithelium (RPE). OS metrics were measured from 3D EZ-RPE layers of volume scans. Linear mixed-effects models were used to calculate the rate of change in OS metrics and the associated factors, including baseline age, baseline OS metrics, and follow-up duration.
UNASSIGNED: The mean (standard deviation) of progression rates were -0.28 (0.43) µm/y, -0.73 (0.61) mm2/y, and -0.014 (0.012) mm3/y for OS thickness, EZ area, and OS volume, respectively. In multivariable analysis, the progression rates of EZ area and OS volume were strongly associated with their baseline values, with faster decline in eyes with larger baseline values (P ≤ 0.003), and nonlinearly associated with the baseline age (P ≤ 0.003). OS thickness decline was not associated with its baseline value (P = 0.32).
UNASSIGNED: These results provide evidence to support using OS metrics as biomarkers to assess the progression of XLRP and as the outcome measures of clinical trials. Given that their progression rates are dependent on their baseline values, the baseline EZ area and OS volume should be considered in the design and statistical analysis of future clinical trials. Deep learning may provide a useful tool to reduce the burden of human graders to analyze OCT scan images and to facilitate the assessment of disease progression and treatment trials for retinitis pigmentosa.

Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration.
Two eyes of a White woman in her 90\'s with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes.
Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells.
Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch\'s membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.

OBJECTIVE: To report and document a case of torpedo maculopathy found in a patient affected by keratoconus.Case report: An healthy 16-year-old male patient, affected by keratoconus in both eyes, was referred to the cornea service of our hospital for a follow-up visit.During the dilated fundus examination of the left eye, an oval, well-demarcated, hypopigmented lesion was observed in the juxtafoveal temporal region, pointing towards the center of the macula. Multimodal imaging of the lesion was performed, and the diagnosis of Torpedo Maculopathy was established based on the clinical picture.
CONCLUSIONS: This is the first case of torpedo maculopathy described in a patient affected by keratoconus. This association may be merely fortuitous or the result of developmental abnormalities affecting both corneal and retinal structures.

This study aimed to determine the retest variability of quantitative fundus autofluorescence (QAF) in patients with and without age-related macular degeneration (AMD) and evaluate the predictive value of patient reliability indices on retest reliability. A total of 132 eyes from 68 patients were examined, including healthy individuals and those with various stages of AMD. Duplicate QAF imaging was conducted at baseline and 2 weeks later across six study sites. Intraclass correlation (ICC) analysis was used to evaluate the consistency of imaging, and mean opinion scores (MOS) of image quality were generated by two researchers. The contribution of MOS and other factors to retest variation was assessed using mixed-effect linear models. Additionally, a Random Forest Regressor was trained to evaluate the extent to which manual image grading of image quality could be replaced by automated assessment (inferred MOS). The results showed that ICC values were high for all QAF images, with slightly lower values in AMD-affected eyes. The average inter-day ICC was found to be 0.77 for QAF segments within the QAF8 ring and 0.74 for peripheral segments. Image quality was predicted with a mean absolute error of 0.27 on a 5-point scale, and of all evaluated reliability indices, MOS/inferred MOS proved most important. The findings suggest that QAF allows for reliable testing of autofluorescence levels at the posterior pole in patients with AMD in a multicenter, multioperator setting. Patient reliability indices could serve as eligibility criteria for clinical trials, helping identify patients with adequate retest reliability.

OBJECTIVE: To report the emergence and progress of four late-stage characteristics: incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA), drusen ooze and drusen collapse in eyes with dry age-related macular degeneration (AMD) using Spectral Domain Optical Coherence Tomography (SD-OCT).
METHODS: This was a retrospective analysis of eyes with non-exudative AMD. Multimodal imaging was done at follow up visits ≤ 12 months. OCT volume scan was used to assess and identify the 4 characteristics. Univariate analysis was done for the various demographic and clinical characteristics.Patients with a mean age of 76.7 ± 10 years were followed up for 69.9 ± 20.6 months. iRORA, cRORA, drusen ooze was present in 15.6%, 15.6% and 15.6% of patients at baseline, respectively, and 25.0%, 40.6% and 53.1% of patients at the final follow-up, respectively. At baseline 9.1%, 0% and 9.1% of patients had bilateral drusen ooze, iRORA and cRORA, respectively. By the final follow-up, drusen collapse occurred in 46.9% and 18.8% patients in unilateral and bilateral eyes, respectively.For bilateral cases, the mean interval of time between emergence inthe two eyes for drusen ooze, drusen collapse, iRORA, and cRORA was 5 ± 1.4 years, 2.2 ± 2.2 years, 3.5 ± 0.7 and 1.7 ± 0.6 years, respectively.
CONCLUSIONS: Late-stage OCT biomarkers are seen bilaterally at 21.9% at baseline and at 56.3% at 5.8 years follow-up. Once present in one eye, cRORA had the shortest mean interval before appearance in the other eye.

OBJECTIVE: To identify the baseline predictors of anti-VEGF treatment response at 3 years in patients affected by choroidal neovascularization (CNV) secondary to central serous chorioretinopathy (CSCR).
METHODS: In this retrospective longitudinal study, medical records of patients diagnosed with CNV secondary to CSCR and treated using anti-VEGF injections between April 2015 and May 2020 were reviewed. The potential qualitative and quantitative predictors of treatment response were identified or measured based on the multimodal imaging examination available for each patient at the baseline, including structural OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT-angiography (OCT-A). Univariate and multivariate analyses were performed.
RESULTS: Twenty-nine eyes from 29 patients affected by CNV complicating CSCR were included in the study. At the end of the 3-year follow-up, the mean BCVA was 20/50 Snellen equivalent (0.38 ± 0.36 LogMAR), and no significant difference with baseline BCVA (0.37 ± 0.29 LogMAR) was found (p = 0.9). Twenty out of 29 eyes (69%) had active lesions at the end of the follow-up. At multivariate analysis, none of the included features was independently associated with the 3-year BCVA outcome. Pigment epithelium detachment (PED) height (ß = 0.017, p = 0.028) and outer limiting membrane (OLM) preservation at the fovea (ß = -5.637, p = 0.026) were independently associated with the CNV activity at 3 years.
CONCLUSIONS: PED height and OLM obliteration at the fovea might be considered baseline predictors of lesion activity at 3-year follow-up in patients with CNV secondary to CSCR treated with anti-VEGF therapy.

Trace elements play crucial roles in cellular biology. Their improper homeostasis may contribute to the progress of eye diseases, exacerbated during ageing. The retinal pigment epithelium (RPE) is progressively deteriorated during age-related neurodegeneration and metal homeostasis may be compromised. In this study, elemental mass spectrometry (MS) was combined with cellular and molecular biology techniques to identify changes in trace elements during the in vitro degeneration of human RPE cells. Cells were collected at 21, 91, and 133 days and processed for RNA sequencing; Ca, Na, P, Mg, and Cu quantification by flow injection analysis and inductively coupled plasma-MS; and protein analysis by immunocytochemistry. Four-month-old RPE cultures showed depigmentation, impaired barrier function, and antioxidant protection, manifesting signs of epithelial-to-mesenchymal transition. Na and P significantly increased in the cytosol of degenerated RPE cells (from 15 ± 20 to 13495 ± 638 ng·µg-1 and from 30.6 ± 9.5 to 116.8 ± 16.8 ng·µg-1, respectively). Mg decreased in both the cytosol and insoluble fraction of cells (from 2.83 ± 0.40 to 1.58 ± 0.56 ng·µg-1 and from 247.57 ± 11.06 to 30 ± 8 ng·g-1, respectively), while P and Cu decreased in the insoluble fraction after 133 days in culture (from 9471 ± 1249 to 4555 ± 985 ng·µg-1 and from 2251 ± 79 to 1054 ± 235 ng·g-1, respectively), along with changes in metal-dependent antioxidant enzymes and Cu transporters. This RPE model reflected metal homeostatic changes, providing additional perspectives on effects of metal regulation during ageing.