Publication trends of vascular endothelial growth factor (VEGF) and anti-VEGF treatment in neovascular age-related macular degeneration during 2001-2020: a 20-year bibliometric study.

PURPOSE: This study sought to provide an overview of the current research and further analyze publication trends in the field of vascular endothelial growth factor (VEGF) and anti-VEGF treatment for neovascular age-related macular degeneration (NVAMD). METHODS: We downloaded all related publications from 2001 to 2020 from the Web of Science Core Collection and conducted a bibliometric analysis using the bibiometrix package in R programming software. RESULTS: A total of 3717 publications were included in the analysis. The USA contributed the largest number of publications (1443), and achieved the highest number of citations (74,946) and H-index value (28). Johns Hopkins University, USA, was the top institution with the most publications, and Peter A. Campochiaro was the most productive professor at The Wilmer Eye Institute, USA. 9.60% of the total publications were from the Journal of Retinal and Vitreous Diseases. Trend analysis demonstrated that anti-VEGF therapy was introduced in early 2000 after steroids, and the last 2 decades have witnessed the blossom of several anti-VEGF agents. "Treat-and-extend" and "resistance" were two popular trend topics in recent years. CONCLUSIONS: The USA occupies a dominant position in the research field of VEGF and anti-VEGF treatments in NVAMD. Steroid administration, photodynamic therapy, and anti-VEGF therapy have been pivotal advances in the treatment of NVAMD patients over the past 2 decades. Limited acting period and resistance are potential investigation directions in future studies.

Quantitative Optical Coherence Tomography Detection of New Neovascular Branches and Association With Exudation Recurrence in Neovascular Age-Related Macular Degeneration.

Purpose: The purpose of this study was to investigate the clinical role of multi-signal quantitative optical coherence tomography angiography (OCTA) perfusion sampling in neovascular age-related macular degeneration (AMD). Methods: The study was designed as a cross-sectional case series. We collected data from already treated macular neovascularization (MNV), characterized by (I) clinically relevant recurrent exudation, (II) nonclinically relevant recurrent exudation, and (III) inactive lesion. We proposed a new OCTA metric, calculating the gap between high-resolution (HR) and high-speed (HS) OCTA samplings, hypothesizing that this gap might improve the detection of new secondary MNV branches, being also associated with exudation recurrence. Main outcome measures were the HR-HS gap-based categorization of MNV lesions and the assessment of its association with exudative, minimally exudative, and inactive lesions. Results: Our cohort (which consisted of 32 MNV eyes; 32 patients; mean disease duration 5 years) was classified as type 1 (17; 53%), type 2 (11; 34%), or mixed type (4; 13%) MNV. Subretinal fibrosis was found in 17 out of 32 eyes (53%), whereas outer retinal atrophy involved 22 of 32 eyes (69%). HR-HS MNV gap was significantly different among MNV subgroups: 18% for the exudative subgroup, 12% for the minimally exudative subgroup, and 4% for the inactive subgroup. HR-HS gap significantly correlated with best corrected visual acuity (BCVA), disease duration, fibrosis, and outer retinal atrophy. Conclusions: HR-HS gap is a novel quantitative metric to detect the secondary novel branches of AMD-related MNV. This parameter is clinically relevant because it is associated with fluid recurrence. The integration of HR-HS gap in artificial intelligence models might help to predict MNV reactivation and to optimize treatment strategies.

Predictive factors of age-related macular degeneration with poor response to three loading doses of anti-vascular endothelial growth factor.

PURPOSE: To evaluate the predictive factors of neovascular age-related macular degeneration (nAMD) with poor response to three loading doses of intravitreal bevacizumab (IVB). METHODS: A retrospective cohort study was performed on nAMD patients three loading IVB initial treatment. The patients were divided into two groups, without residual fluid on optical coherence tomography (OCT) images (Group 1) and with residual fluid (Group 2). Demographic data, OCT findings, and morphological features of macular neovascularization (MNV) in optical coherence tomography angiography (OCTA) were recorded. RESULTS: The study included one hundred thirty-six eyes of 120 patients (Group 1: n = 66 eyes, Group 2: n = 70 eyes). Central macular thickness, presence of intraretinal fluid, subretinal fluid, hyperreflective foci-band, pigment epithelial detachment (PED), and prechoroidal cleft were similar between the two groups. Pre-injection central choroidal thickness (CCT) was 214.17 ± 50.28 µm in Group 1 and 247.40 ± 60.55 µm in Group 2 (p = 0.021). PED width (p = 0.028) and PED area (p = 0.042) were statistically significantly higher in Group 1. When the morphology of MNV in OCTA was examined, branching (p = 0.736), loops (p = 0.442), peripheral arcade (p = 0.600), hypointense halo (p = 0.779), sea fan (p = 0.250), medusa (p = 0.255), pruned vascular tree pattern (p = 0.148), capillary fringe (p = 0.683) were similar in both groups. The presence of a closed circuit pattern was significantly higher in Group 2 (p = 0.028). CONCLUSION: Initial CCT and closed circuit pattern MNV were higher in IVB-resistant cases. It was observed that PEDs with large bases and areas responded significantly better to loading therapy. The presence of a closed-circuit pattern was an independent risk factor for poor response to loading therapy. Retrospectively registered. REGISTRATION NUMBER: 2011-KAEK-25 2023/05-08.

Implications of Ocular Confounding Factors for Aqueous Humor Proteomic and Metabolomic Analyses in Retinal Diseases.

Purpose: To assess the impact of ocular confounding factors on aqueous humor (AH) proteomic and metabolomic analyses for retinal disease characterization. Methods: This study recruited 138 subjects (eyes): 102 with neovascular age-related macular degeneration (nAMD), 18 with diabetic macular edema (DME), and 18 with cataract (control group). AH samples underwent analysis using Olink Target 96 proteomics and Metabolon's metabolomics platform Data analysis included correlation, differential abundance, and gene-set analysis. Results: In total, 756 proteins and 408 metabolites were quantified in AH. Total AH protein concentration was notably higher in nAMD (3.2-fold) and DME (4.1-fold) compared to controls. Pseudophakic eyes showed higher total AH protein concentrations than phakic eyes (e.g., 1.6-fold in nAMD) and a specific protein signature indicative of matrix remodeling. Unexpectedly, pupil-dilating drugs containing phenylephrine/tropicamide increased several AH proteins, notably interleukin-6 (5.4-fold in nAMD). Correcting for these factors revealed functionally relevant protein correlation clusters and disease-relevant, differentially abundant proteins across the groups. Metabolomics analysis, for which the relevance of confounder adjustment was less apparent, suggested insufficiently controlled diabetes and chronic hyperglycemia in the DME group. Conclusions: AH protein concentration, pseudophakia, and pupil dilation with phenylephrine/tropicamide are important confounding factors for AH protein analyses. When these factors are considered, AH analyses can more clearly reveal disease-relevant factors. Translational Relevance: Considering AH protein concentration, lens status, and phenylephrine/tropicamide administration as confounders is crucial for accurate interpretation of AH protein data.

Study protocol: optical coherence tomography angiography for the detection of neovascular age-related macular degeneration: a comprehensive multicentre diagnostic accuracy study in the UK-the ATHENA study.

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.

Double-dose investigation of aflibercept in neovascular age-related macular degeneration (DIANA): a real-world study.

BACKGROUND: To investigate the clinical effects of double-dose (4 mg) aflibercept treatment in neovascular age-related macular degeneration (nAMD), compared with the standard-dose (2 mg) treatment. METHODS: A total of 108 eyes from 97 patients with nAMD and received intravitreal aflibercept 2 mg and/or 4 mg treatment were retrospectively reviewed. The changes of central macular thickness (CMT)/ pigmental epithelium detachment height and the recurrence rate of exudation during the 12-month follow-up were compared between the 2 mg group and the 4 mg group. Self-control comparisons (2 mg switch to 4 mg) were also made between two regimens. RESULTS: Compared with the 2 mg group, tendencies of lower intraretinal fluid incidence and more CMT reduction were observed in the 4 mg group. The later one was also observed when eyes switching from 2 mg to 4 mg regimen. The median remission interval was 5 months in the 4 mg group, 2 months longer than the 3 months in the 2 mg group (P = 0.452). Injections needed in the 4 mg group were 3.644 ± 1.670, less than the 4.286 ± 2.334 injections in the 2 mg group within 12 months as well (P = 0.151). However, no associated vision benefits were gained from the double-douse regimen. No markedly increased-intraocular pressure events, or other adverse events were found in two groups. CONCLUSIONS: Compared to the aflibercept 2 mg treatment in nAMD, tendencies of anatomic gains and relieving treatment burden were brought by the aflibercept 4 mg treatment. This study may have additional importance, given the further application of high-dose aflibercept in real-world settings.

Central retinal artery occlusion after intravitreal brolucizumab injection for treatment-naïve neovascular age-related macular degeneration; a case report.

BACKGROUND: To report a case of central retinal artery occlusion (CRAO) after intravitreal injection of brolucizumab for a treatment-naïve neovascular age-related macular degeneration (nAMD) patient without comorbid cardiovascular disease history. CASE PRESENTATION: A 79-year-old Asian male without a cardiovascular disease history such as diabetes or hypertension underwent three times of monthly consecutive intravitreal brolucizumab injections for treatment of progressed nAMD in his left eye. Two days after the third injection, the patient presented with acute painless visual loss. Typical retinal whitening with a cherry red spot was observed on the fundus photograph, and retinal swelling with hyper-reflectivity was also identified on the optical coherence tomography (OCT) scan. On the fundus fluorescein angiography, arm-to-retina time and arteriovenous transit time were remarkedly delayed, but clinical findings suggesting an intraocular inflammation (IOI) were not observed. Therefore, CRAO was diagnosed, and anterior chamber paracentesis was administrated immediately. However, there had been no improvement in visual acuity during the follow-up period of three months, despite prolonged oral steroid and anti-platelet agent medication. CONCLUSIONS: In rare cases, patients without cardiovascular comorbidities can develop CRAO after intravitreal brolucizumab injection without gross evidence of IOI. Therefore, CRAO should always be in consideration and careful observation is required after intravitreal brolucizumab injection for nAMD patients with old age, even if the patient does not have any other cardiovascular disease history.

Effect of intravitreal injections due to neovascular age-related macular degeneration on retinal nerve fiber layer thickness and minimum rim width: a cross sectional study.

PURPOSE: The present study tested the hypothesis that repeated anti-VEGF injections are associated with reduced retinal nerve fiber layer (RNFL) and minimum rim width (MRW) of the optic nerve head. PATIENTS AND METHODS: Sixty-six patients with a history of intravitreal injections due to neovascular age-related macular degeneration were included. RNFL and MRW were measured using optical coherence tomography (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). RESULTS: Mean global RNFL was 90.62 µm and both RNFL as well as MRW significantly decreased with advanced age (p = 0.005 and p = 0.019, respectively). Correlating for the number of injections, no significant impact on RNFL was found globally (p = 0.642) or in any of the sectors. In contrast, however, global MRW was significantly reduced with increasing numbers of intravitreal injections (p = 0.012). The same holds true when adjusted for the confounding factor age (RNFL p = 0.566 and MRW p = 0.023). CONCLUSION: Our study shows that repeated intravitreal injections due to choroidal neovascularization seem to have a deleterious effect on MRW but not on RNFL. This suggests that MRW is a more sensitive marker than RNFL for evaluating the effect of frequent intravitreal injections on the optic nerve head since it seems to be the first structure affected.

Examining the correlation of lymphangiogenesis biomarkers with clinical condition in Age-Related Macular Degeneration (AMD).

The aim of this study is to investigate the relationship between age-related macular degeneration (AMD) and lymphangiogenesis biomarkers, namely LYVE-1, Podoplanin, VEGF-C, VEGFR-2 and VEGFR-3. This prospective and interventional study includes 30 patients with AMD which may be dry or wet type and 30 controls for whom vitrectomy and phacoemulsification was indicated due to additional pathologies (epiretinal membrane, macular hole, retinal detachment, and cataract). 0.1-0,2 ml of aqueous humor and 0.5-1 ml of vitreous sample was taken during the operations. Before the operations 1 tube serum was also taken. All the lymphangiogenesis biomarkers in the study are examined by ELISA method. LYVE-1 (p = 0.001) and Podoplanin (p = 0.004) levels in the vitreous for the patient group are found to be significantly lower than the control group. Serum (p = 0.019), vitreous (p = 0.001), aqueous (p < 0.001) levels of VEGF-C for the patient group are significantly higher than the control group. VEGF-C/VEGFR-2 (p < 0.001), VEGF-C/VEGFR-3 (p < 0.001) ratios in the vitreous for the patient group are found to be significantly higher than the control group. Especially in wet AMD patients, LYVE-1 level is significantly lower in the vitreous (p = 0.002) and aqueous (p = 0.002) than the control group. In addition, Podoplanin level is observed as significantly lower in the vitreous (p = 0.014) and serum (p = 0.002) in comparison to control group. In the wet AMD group, VEGF-C level in the vitreous (p < 0.001), aqueous (p < 0.001) and serum (p = 0.001) is higher than the control group. The result of this study indicates a valid relationship between the weakening of lymphangiogenesis and the pathophysiology of AMD, especially for the wet type. It is observed that the levels of receptors that bind VEGF-C (VEGFR-2 and VEGFR-3) do not increase at the same rate as VEGF-C to compensate for the increase in VEGF-C. The absence of an increase in VEGFR-3, which is especially necessary for lymphangiogenesis, also suggests that lymphangiogenesis is weakened or decreased in AMD. In the future interventional studies with larger series, examination of lymphangiogenic biomarkers in inflammatory retinal diseases and glaucoma may reveal unexplored details.

Effect of Pro Re Nata Regimen with Anti-VEGF on Type 3 Macular Neovascularization: Long-Term Outcomes.

INTRODUCTION: The purpose of this study was to investigate long-term outcomes of intravitreal injections (IVI) of antivascular endothelial growth factor (VEGF) in neovascular age-related macular degeneration (nAMD) with type 3 macular neovascularization (MNV). METHODS: This retrospective study included 19 eyes of 17 patients with nAMD and type 3 MNV treated with anti-VEGF IVI with a loading dose and a PRN regimen. Best corrected visual acuity (BCVA), central macular thickness (CMT), presence of macular intraretinal fluid (IRF) and subretinal fluid (SRF), flow area (FA), subfoveal choroidal thickness (CT), and macular atrophy (MA) were assessed at baseline (T0) and during follow-up (T1, post-loading phase; T2, 1 year; T3, 2 years; T4 >2 years). The correlations between MA at the last follow-up and standard deviation (SD) values of CMT and CT during follow-up were assessed. The influence of the number of injections on the change in MA over time was also analyzed. MA differences at T4 were assessed for pseudodrusen presence. RESULTS: BCVA improved significantly during follow-up (p = 0.013) particularly increasing from baseline to post-loading phase and then did not modify significantly thereafter. CMT significantly reduced from T0 to T1 and remained stable during follow-up (p = <0.001). MNV flow area showed a trend toward an increase in the post-loading phase that was not statistically significant (p = 0.082) and CT decreased significantly during follow-up (p < 0.001). MA changed significantly during follow-up (p < 0.001) with a significant increase from T0 to T3 and from T0 to T4 (p < 0.010). A Cochran-Armitage test for trend showed a significant reduction (p = 0.001) of macular IRF and SRF during follow-up. MA at T4 showed a significant positive correlation with SD (standard deviation) values of CMT (p = 0.040) and CT (p = 0.020). Indeed, the number of injections did not influence the change over time of MA (p = 0.709). MA at T4 was not statistically significantly different between patients with pseudodrusen at baseline (p = 0.497). CONCLUSIONS: Intravitreal anti-VEGF injections with PRN regimen in MNV type 3 showed functional and anatomical benefits. Variations of retinal thickness and choroidal thickness during treatment were related to MA modification over time.

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.

Retinal and choroidal changes after anti-VEGF therapy in neovascular-AMD patients: A systematic review and meta-analysis of SD-OCT studies.

BACKGROUND: In recent years, the progress made in the field of optical coherence tomography has helped to understand the changes in eye layers in patients with exudative age-related macular degeneration (nAMD). Early diagnosis of nAMD, a leading cause of irreversible vision impairment, is helpful. Therefore, we performed a meta-analysis on OCT measurement alterations before and after anti-VEGF therapy in patients with nAMD and controls. METHOD: We systematically searched Scopus, PubMed, Cochrane, and Web of Science to find articles that measured choroidal and retinal layer changes after anti-VEGF therapy in nAMD Patients. We chose either a fixed-effects or random-effects model based on the assessed heterogeneity level to perform a meta-analysis. In addition, we conducted meta-regression, subgroup analyses, publication bias, and quality assessment for included studies. RESULTS: Thirteen studies were included in the meta-analysis, with 733 total participants. Foveal thickness and subfoveal choroidal thickness (CT) decreased significantly in the first 3 years after injections, except for subfoveal CT in the third year after injection. It also showed that CT at 1500 µm temporal and nasal to the fovea did not significantly change. CONCLUSION: Our results showed anti-VEGF treatment for nAMD patients was associated with a significant reduction in foveal thickness and subfoveal CT in the first 2 years after treatment. Our analysis did not reveal any correlation between changes in foveal thickness and subfoveal CT with best-corrected visual acuity or other factors.

Qualitative and quantitative comparisons of type 1 macular neovascularizations between pachychoroid neovasculopathy and neovascular age-related macular degeneration using optical coherence tomography angiography.

OBJECTIVES: To compare qualitative and quantitative features of type 1 macular neovascularizations (MNV) in pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD). METHODS: Forty-three treatment-naive eyes of 41 PNV patients and 40 treatment-naive eyes of 38 patients with nAMD were included. The patients were classified as PNV or nAMD according to the presence of pachychoroid features and soft/reticular drusen. Presence of central trunk and maturity of the MNV were evaluated on optical coherence tomography angiography (OCTA) images. MNV area, vessel density (VD), total vessel length (VL), number of intersection points (IPs), fractal dimension (FD), and lacunarity (LAC) were calculated using ImageJ software and FracLac plugin. RESULTS: The mean age was 56.8 ± 8.7 years in PNV and 70.4 ± 8.8 years in neovascular AMD groups (p < 0.001). Compared to nAMD, the presence of central trunk was less frequent in PNV (48.8% vs 77.5%, p = 0.007). Immature MNV pattern was observed more frequently in PNV eyes than nAMD (41.9% vs 20.0%, p = 0.009). PNV cases had significantly lower median MNV area [0.913(1.115) vs 2.542(3.273) mm²], total VL [14.84 (20.46) vs 36.34 (44.68) mm], number of IPs [104(140) vs 335(417.3)], and FD [1.56(0.10) vs 1.59(0.11)] comparing to nAMD cases (p < 0.001, p = 0.001, p < 0.001, p = 0.043 respectively). However, the mean VD (42.4 ± 6.8 vs 42.9 ± 9.0%) and the median LAC values [0.42 (0.09) vs 0.42 (0.09)] did not differ significantly between groups (p = 0.776, p = 0.526, respectively). CONCLUSION: Morphological and quantitative differences exist in type 1 neovascular lesions. Type 1 MNVs in the PNV group are characterized by a smaller and less complex structure.

Long-term Follow-Up and Regeneration of Retinal Pigment Epithelium (RPE) after Tears of the Epithelium in Exudative Age-Related Macular Degeneration (AMD).

BACKGROUND: The goals of this study are to evaluate potential long-term visual deterioration associated with retinal pigment epithelial (RPE) tears in patients with neovascular age-related macular degeneration (nAMD) and to find treatment-related and morphological factors that might influence the outcomes. PATIENTS AND METHODS: This retrospective study enrolled 21 eyes of 21 patients from the database of Vista Eye Clinic Binningen, Switzerland, diagnosed with RPE tears, as confirmed by spectral domain optical coherence tomography (SD-OCT), with a minimum follow-up period of 12 months. Treatment history before and after RPE rupture with anti-VEGF therapy, visual acuity, and imaging (SD-OCT) were analyzed and statistically evaluated for possible correlations. RESULTS: Mean patient age was 80.5 ± 6.2 years. The mean length of total follow-up was 39.7 ± 13.9 months. The mean pigment epithelial detachment (PED) height increased by 363.8 ± 355.5 µm from the first consultation to 562.8 ± 251.5 µm at the last consultation prior to rupture. Therefore, a higher risk of RPE rupture is implied as a result of an increase in PED height (p = 0.004, n = 14). The mean visual acuity before rupture was 66.2 ± 16.0 letters. Mean visual acuity deteriorated to 60.8 ± 18.6 letters at the first consultation after rupture (p = 0.052, n = 21). A statistically nonsignificant decrease in vision was noted in the follow-up period. After 2 years, the mean BCVA decreased by 10.5 ± 23.7 ETDRS letters (p = 0.23, n = 19). PED characteristics before rupture and amount of anti-VEGF injections after rupture did not affect the visual outcome. None of the 21 patients included in our study showed a visual improvement in the long-term follow-up. RPE atrophy increased significantly from 3.35 ± 2.94 mm2 (baseline) to 6.81 ± 6.25 mm2 over the course of 2 years (p = 0.000 013, n = 20). CONCLUSIONS: The overall mean vision decrease after rupture was without statistical significance. There was no significant change in BCVA at the 2-year follow-up, independent of the amount of anti-VEGF injections provided. In this study, there was a significant increase in RPE defect over a follow-up of 2 years, implying progression of contraction of RPE and/or macular atrophy.

Relative yield of retinal imaging versus clinical exam in following neovascular exudative age related macular degeneration.

PURPOSE: To compare therapeutic decisions between 3 diagnostic protocols and to assess the need for in-person physical doctor-patient encounter in follow up and treatment of neovascular exudative age-related macular degeneration (AMD). METHODS: Analysis of 88 eyes of 88 unique patients with neovascular AMD who were routinely followed at our medical retina clinic. A retinal specialist reviewed all images in advance and wrote his decisions. He later attended an in-person encounters with all patients and documented his decisions. Masking was done by not exposing any identifying information to the specialist and by randomizing patient's images order before the in-person encounter. Therapeutic decisions regarding intravitreal injections intervals and agent selection were made based on three protocols: (1) optic coherence tomography (OCT); (2) OCT/Ultra-widefield (UWF) color image; (3) OCT/UWF/full clinical exam. Visual acuity (VA) was incorporated into all protocols. RESULTS: We found an agreement of 93% between those protocols regarding the intervals of injections, and of 100% regarding injection agent selection. When comparing OCT, OCT/UWF and OCT/UWF/clinical exam guided decision making, there were no discrepancies between OCT and OCT/UWF. There were 6 out of 88 discrepancies (7%) between OCT/UWF and OCT/UWF/clinical exam. Of those 6 discrepancies, all were regarding intervals (Bland-Altman bias = - 0.2386). All discrepancies between OCT/UWF and OCT/UWF/Clinical exam were due to patients' preferences, socioeconomic issues and fellow eye considerations, addressed during the face-to-face encounter with patients. Physical examination itself did not affect decision making. CONCLUSIONS: Neovascular exudative AMD follow up and treatment decisions can be guided by VA and OCT, with UWF adding important information regarding macula and peripheral retina, but rarely affecting decision making. However, decision making may also be driven by patients' preferences and other considerations that are being made only during the face-to-face visit and discussion. Thus, every approach supporting imaging only decision making, must take these factors into account.

Assistance Burden Comparison Between Age-Related Macular Degeneration and Retinal Angiomatous Proliferation Over a Three-Year Follow-up.

BACKGROUND AND OBJECTIVE: We compared assistance burden between neovascular age-related macular degeneration (nAMD) and retinal angiomatous proliferation (RAP) under intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment on a treat-and-extend (T&E) regimen in a third-level hospital in a developed country. PATIENTS AND METHODS: This retrospective study using data from the Fight Retinal Blindness! Registry included patients treated between January 2016 and December 2020. Final event was established as best corrected visual acuity (BCVA) lower than 20 Early Treatment Diabetic Retinopathy Study letters. According to choroidal neovascularization (CNV), three different study groups were established: type 1, 2, and 3. RESULTS: A total of 285 eyes of 227 patients were included. Mean age was 80.1 ± 6.5, 79.1 ± 7.9, and 81.2 ± 7.2 years, for the three study groups, respectively. Mean injections were 16.0 ± 4.8, 16.5 ± 4.1, and 14.1 ± 5.7, respectively; and mean number of visits were 17.9 ± 4.3, 18.2 ± 3.1, and 16.8 ± 5.3, respectively. No differences were found (P > 0.05). Survival curves and log-rank analysis also showed no differences (P = 0.344). Cox proportional hazard models showed that a lower baseline BCVA, subfoveal geographic atrophy (GA), and subfoveal fibrosis (SF) were associated with a higher risk of reaching ≤ 20 letters. CONCLUSIONS: nAMD and RAP under a T&E regimen indicate a high assistance burden during the first three years. The presence of subfoveal GA or SF are associated with a BCVA lower than 20 letters. [Ophthalmic Surg Lasers Imaging Retina 2024;55:197-203.].

Fellow Eyes Conversion Rates in Patients With Unilateral Exudative Age-Related Macular Degeneration: An Academy IRIS® Registry Analysis.

BACKGROUND AND OBJECTIVE: This study aimed to examine conversion rates from non-exudative to exudative age-related macular degeneration (AMD) in the fellow eye of patients with unilateral exudative AMD using the Academy IRIS® Registry. PATIENTS AND METHODS: This study was a retrospective, cohort analysis from 2016 to 2019. Patient and disease characteristics including initial AMD stage were collected. Cox proportional-hazard (PH) and logistic regression modeling were performed. RESULTS: The risk of conversion was lower for men relative to women and for Asians and Blacks relative to Whites. Compared to never-smokers, active smokers were at increased risk of conversion, and compared to initially early non-exudative AMD eyes, intermediate and advanced non-exudative AMD eyes had higher rates of conversion. Compared to active choroidal neovascularization eyes, eyes with inactive choroidal neovascularization and inactive scars had lower rates of fellow eye conversion. CONCLUSIONS: In this cohort analysis of unilateral exudative AMD patients, women, Whites, and active smokers had higher rates of non-exudative to exudative AMD conversion in the fellow eye. [Ophthalmic Surg Lasers Imaging Retina 2024;55:220-226.].

MORPHOLOGICAL BIOMARKERS PREDICTING EXUDATIVE CONVERSION IN TYPE 1 NONEXUDATIVE MACULAR NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To investigate the incidence and morphological biomarkers to predict the exudative conversion in eyes with type 1 nonexudative macular neovascularization using swept-source optical coherence tomography angiography. METHODS: Macular neovascularizations were detected using the retinal pigment epithelium-to-retinal pigment epithelium-fit slab of swept-source optical coherence tomography angiography scan. Depending on whether exudation developed within a year, the eyes were divided into two groups: active and silent. Qualitative and quantitative optical coherence tomography angiography parameters of the two groups were evaluated to discriminate the biomarkers associated with exudative conversion. RESULTS: Of the 40 eyes, nine developed exudation within 1 year (incidence rate 22.5%). The active group exhibited a significantly higher "anastomosis and loops" pattern, greater "vessel density," increased "junction density," fewer "number of end points," and lower "lacunarity" compared with the silent group. "Anastomosis and loops" and higher "vessel density" were correlated with the active group in multivariate analyses. A predictive model combining these biomarkers achieved 95% accuracy in predicting exudative conversion. CONCLUSION: At 12 months, the risk of exudation was 22.5%, and "anastomosis and loops" and "vessel density" were useful optical coherence tomography angiography biomarkers for predicting exudative conversion in eyes with type 1 nonexudative macular neovascularization. For eyes with a high risk of exudative conversion, more frequent follow-up is recommended.

Advancements in the treatment of age-related macular degeneration: a comprehensive review.

Age-related macular degeneration (AMD) stands as a leading cause of irreversible blindness, particularly affecting central vision and impeding daily tasks. This paper provides a thorough exploration of AMD, distinguishing between its two main subtypes-Wet and Dry AMD-while shedding light on the prevalence and risk factors, including age, genetics, and smoking. The focus shifts to the current and future treatment landscape, examining both Dry and Wet AMD. Regarding Dry AMD, interventions such as antioxidant supplementation and ongoing clinical trials offer hope. Notable among these is Pegcetacoplan which is the only Food and Drug Administration (FDA)-approved medication, displaying promising results in reducing geographic atrophy lesions. For Wet AMD, anti-Vascular Endothelial Growth Factor therapies like Ranibizumab (Lucentis®) have been instrumental, and newer drugs like Faricimab and OPT-302 show comparable efficacy with extended dosing intervals. Additionally, gene therapies such as RGX-314 present a potential paradigm shift, reducing or eliminating the need for frequent injections. Biosimilars offer cost-effective alternatives. The paper also delves into the integration of technology and artificial intelligence in AMD management, highlighting the role of smartphone apps for patient monitoring and artificial intelligence algorithms for diagnosis and surveillance. Furthermore, patient perspectives on artificial intelligence demonstrate a positive correlation between understanding and trust. The narrative concludes with a glimpse into ground-breaking technologies, including retinal implants and bionic chips, offering hope for vision restoration. Overall, this paper underscores the multifaceted approach in addressing AMD, combining traditional and innovative strategies, paving the way for a more promising future in AMD treatment.