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Age-related macular degeneration associated with glucagon-like peptide-1 receptor agonist use: a systematic review.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for diabetes, obesity, and cardiovascular risk reduction. However, their ocular safety profile, particularly regarding age-related macular degeneration (AMD), remains uncertain. This systematic review evaluates the association between GLP-1 RA use and the incidence or progression of AMD including both nonexudative and neovascular subtypes. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD420251183938). MEDLINE, Embase, CENTRAL, Web of Science, and PubMed were searched from inception through 2025 for observational studies and randomized trials evaluating AMD outcomes among adults exposed to GLP-1 RAs. Comparators included nonuse, placebo, or alternative metabolic therapies. Risk of bias was assessed using Risk of Bias in Non-Randomized Studies of Interventions and certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Due to heterogeneity of outcome definitions, results were synthesized qualitatively. RESULTS: Eight observational studies encompassing 91 408 to 600 816 participants were included. GLP-1 RA use was associated with a reduced incidence of nonexudative AMD across diabetic and nondiabetic populations, with relative risk reductions varying substantially by population, comparator, and follow-up duration. Findings for neovascular AMD were heterogeneous: most studies reported neutral or protective associations, whereas one population-based cohort of older adults with diabetes observed an increased risk (adjusted hazard ratio 2.21, 95% CI 1.65-2.96), with low absolute event rates. Overall risk of bias was moderate to high, and certainty of evidence for all outcomes was very low. CONCLUSIONS: Current evidence does not demonstrate a consistent increase in AMD risk associated with GLP-1 RA therapy and may be associated with a lower incidence of nonexudative AMD, although the certainty of evidence is very low and noncausal explanations cannot be excluded. Prospective studies with standardized endpoints are needed to clarify causal relationships.

Humans

The role of adjunctive aqueous suppressants for anti-vascular endothelial growth factor therapy: A systematic review.

Our goal is to determine whether adjunctive aqueous suppressants (topical β-blockers, carbonic anhydrase inhibitors, or oral acetazolamide) enhance outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), focusing on retinal thickness, visual acuity, injection burden, intraocular pressure (IOP), and safety. DME, RVO, and nAMD are leading causes of vision loss treated with repeated intravitreal injections, yet many eyes show persistent fluid. Aqueous suppressants are inexpensive and widely available, with potential to prolong intravitreal drug residence and improve outcomes, but their clinical value remains uncertain. Following a registered protocol, we searched 4 databases (January, 2000 toMay, 2025) for randomized and comparative studies evaluating adjunct aqueous suppressants with anti-VEGF therapy. Primary outcome was change in retinal thickness; secondary outcomes included visual acuity, injection burden, IOP, and adverse events. Risk of bias was assessed and findings synthesized narratively. Twelve studies (7 randomized trials; 495 eyes) met inclusion criteria. In DME, 3 of 4 trials showed greater thickness reduction with adjunctive dorzolamide (±timolol), although visual gains were inconsistent. In RVO, 1 trial suggested transient anatomical benefit, whereas oral acetazolamide showed no added effect. In nAMD, adjunctive dorzolamide-timolol reduced residual fluid in refractory cases without visual or treatment-sparing benefit. Topical therapy produced modest IOP reductions without serious adverse events. Adjunct aqueous suppressants may provide limited short-term anatomical benefit, particularly in DME and refractory nAMD, but consistent functional or durability effects are not found in this study. Larger, longer-term randomized studies are needed.

Humans

Transcriptome analysis of the pectoral fin degeneration in half-smooth tongue sole (Cynoglossus semilaevis).

Appendage degeneration is a notable morphological feature of some teleosts with specialized benthic lifestyles. The half-smooth tongue sole (Cynoglossus semilaevis) undergoes severe pectoral fin regression during metamorphosis. However, the molecular basis underlying rapid pectoral fin degeneration remains unclear. Here, we performed time-series transcriptome sequencing on pectoral fins at pre-metamorphosis, metamorphosis peak and post-metamorphosis to characterize the molecular changes associated with pectoral fin degeneration. Transcriptional dynamics and functional enrichment showed that no significant enrichment of classical apoptosis-related transcriptional pathways was detected during pectoral fin degeneration. Instead, sustained downregulation of twist1b, identified as a transcriptomic candidate, together with significant upregulation of ssh1, coupled with enrichment of lysosome and ubiquitin-proteasome system (UPS) pathways, suggested enhanced tissue remodeling during pectoral fin degeneration. Temporal expression clustering revealed heterochronic misalignment in the developmental gene expression: upstream initiator tbx5 was upregulated at early metamorphosis, while downstream maintenance signal fgf10 decreased synchronously. Distal patterning gene hoxd12a exhibited premature expression and rapid decay, losing sustained late-phase expression. Moreover, transient elevation of gli3 during metamorphosis may contribute to restricted distal fin growth. We conclude that pectoral fin degeneration in C. semilaevis is associated with heterochronic disruption of developmental signaling and extensive tissue remodeling. This study provides transcriptomic insights into pectoral fin degeneration in tongue soles and establishes a basis for future functional studies of appendage reduction in teleosts.

Animals

Diabetic macular edema and GLP-1 receptor agonist use: a systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type II diabetes and obesity because of their cardiometabolic benefits. However, concerns regarding potential ocular adverse effects, particularly diabetic macular edema (DME), have prompted the need to clarify their retinal safety. METHODS: A systematic review and meta-analysis study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements (PROSPERO registration: CRD420251176164). MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid), Web of Science, and PubMed were searched from inception to October 24, 2025. Randomized trials and observational cohort or case-control studies, including individuals with diabetes without baseline DME and exposed to GLP-1RAs were eligible. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Random-effects models were used to pool incidence proportions and hazard ratios (HRs). RESULTS: Thirteen retrospective cohort studies (2021-2025) using large real-world databases were included. Across 6 studies, the pooled proportion of incident DME among GLP-1RA users was 0.14 (95% CI: 0.07-0.23; I² = 99.8%). Compared with mixed antihyperglycemic therapies, GLP-1RA use was not associated with increased DME risk (pooled HR: 0.81, 95% CI: 0.52-1.26). GLP-1RAs were associated with a higher relative risk of DME compared with sodium-glucose cotransporter-2 inhibitors (HR: 1.50, 95% CI: 1.17-1.94) but not compared with dipeptidyl peptidase-4 inhibitors (HR: 0.90, 95% CI: 0.69-1.19). Evidence certainty was very low. CONCLUSION: Current low-certainty observational evidence does not support an overall increased risk of DME with GLP-1RA use. Prospective studies are needed to clarify comparative retinal safety.

Humans

Association of the Charlson Comorbidity Index With 1-Year Outcomes in Patients With Macular Edema Secondary to Retinal Vein Occlusion.

OBJECTIVE: To determine the predictive value of the Charlson Comorbidity Index (CCI) for outcomes in patients with macular edema secondary to retinal vein occlusion (RVO). DESIGN: Retrospective clinical cohort study. SUBJECTS: Patients seen between 2013 and 2023 at the Cole Eye Institute, Cleveland Clinic, were included. All patients were >18, diagnosed with RVO (International Classification of Diseases (ICD)-9 and 10 codes), had a complete CCI score, and had at least 1 year of ophthalmic follow-up data after their first intravitreal injection (baseline). Patients with ocular surgery, trauma, or panretinal photocoagulation were excluded. METHODS: Age-adjusted CCI scores were calculated for each patient from chart review. For patients with bilateral RVO, one eye was selected randomly. Patients were stratified into tertiles by CCI distribution: tertile 1 (CCI 0-5; mean 3.4), tertile 2 (age-CCI 4.1-6; mean 4.9), and tertile 3 (CCI &#x2265; 8; mean 9.6). Multivariable linear regression was performed to determine the predictive value of CCI and other covariates on visual and anatomical outcomes. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 1-year follow-up. RESULTS: A total of 972 patients met all criteria, with an average age-adjusted CCI score of 6.2. Each one-point increase in CCI predicted 0.38 fewer letters in BCVA at follow-up (P < .001). Baseline BCVA was a significant predictor of follow-up BCVA in all tertiles (P < .001). In the third tertile, each one-point increase in CCI was associated with a 0.72 letter reduction in follow-up BCVA (P < .001). For CST, baseline CST was strongly predictive of final CST (P < .001), while CCI was only significant in the first tertile, where each point increase in CCI predicted a 13.7 &#xb5;m increase in CST (P = .02). In RVO subtype interaction models, the age-adjusted CCI &#xd7; CRVO interaction was not statistically significant for either 1-year BCVA (P = .269) or 1-year CST (P = .695). CONCLUSIONS: Higher CCI scores are significantly associated with worse visual outcomes in patients with RVO, particularly in the combined population and most comorbid patients (tertile 3). CCI was significantly associated with higher (thicker) CST only among the least comorbid patients (tertile 1).

Humans

Noncombustible Nicotine or Tobacco Product Use After Smoking Cessation and Major Vision-Impairing Diseases: A Nationwide Cohort Study.

OBJECTIVE: We assessed the risk of major vision-impairing eye diseases among smokers who quit combustible cigarettes (CC) and switch to noncombustible nicotine or tobacco products (NNTPs) compared with those who completely quit using tobacco. DESIGN: Retrospective cohort study. PARTICIPANTS: About 179 273 adults from the Korean National Health Insurance Service who smoked CC in 2011 to 2012 and reported cessation in 2018 to 2019, classified into complete quitters and NNTP switchers. METHODS: This nationwide longitudinal cohort study followed participants for up to 6 years and identified incident major vision-impairing eye diseases (cataract, glaucoma, age-related macular degeneration, diabetic retinopathy, and refractive and accommodation disorders) using standardized diagnostic codes. Propensity score matching was applied to emulate a pseudo-randomized comparison, balanced on key demographic, clinical, comorbidity, and lifestyle characteristics. Subdistribution hazard ratios (SHRs) were evaluated using the Fine-Gray subdistribution hazards model accounting for all-cause mortality as a competing risk. MAIN OUTCOME MEASURES: Adjusted SHRs for incident major vision-impairing eye diseases. RESULTS: Among 32 316 matched participants followed for a mean of 4.6 years, 6328 incident major vision-impairing eye disease events occurred. The incidence was 41.1 and 44.0 per 1000 person-years for complete quitters and NNTP switchers, respectively. Switching to NNTPs was associated with an increased risk of major vision-impairing eye disease (SHR, 1.07; 95% CI, 1.02-1.13). The risk elevation was most pronounced for diabetic retinopathy (SHR, 1.24; 95% CI, 1.00-1.53) and refractive and accommodation disorders (SHR, 1.07; 95% CI, 1.01-1.12). These findings were robust across inverse probability-weighted and Cox proportional hazards models. The association remained consistent in sensitivity analyses and across clinical subgroups. CONCLUSIONS: Transitioning from CC to NNTPs is associated with a modest but consistent increase in the risk of major vision-impairing eye diseases compared with complete nicotine abstinence. These findings challenge the assumption that substituting NNTPs for CCs is visually harmless and indicate that, from an ophthalmic perspective, complete cessation of all nicotine products should remain the preferred cessation goal.

Humans

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n&#x202f;=&#x202f;4), Leber hereditary optic neuropathy (n&#x202f;=&#x202f;13), and Wolfram syndrome (n&#x202f;=&#x202f;5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

Humans

Muscular fiber properties and multi-omics investigation of larval and adult locomotor muscle in Microhyla fissipes.

During metamorphosis, Microhyla fissipes undergoes a critical transition from an aquatic to a terrestrial lifestyle, accompanied by significant remodeling of skeletal muscle. Notably, larval tail muscle degenerates, while adult hindlimb muscle develops. However, the molecular mechanisms that orchestrate these muscle type-specific adaptations to the changing environment remain unclear. In this study, histological observation, transcriptomics, and metabolomics were integrated to compare locomotor muscles from two stages: larval muscle from tail versus adult muscle from hindlimb. Our results revealed that adult muscle fibers exhibited reduced diameter and shorter sarcomere length compared to those of tadpoles. Transcriptomic analysis identified 4103 differentially expressed genes (DEGs), including 2182 up-regulated and 1921 down-regulated genes. Up-regulated genes were mainly involved in energy metabolism and cellular homeostasis pathways, including PPAR signaling and oxidative phosphorylation, whereas down-regulated genes were associated with carbohydrate metabolism and cell proliferation pathways, such as glycolysis/gluconeogenesis and PI3K-Akt signaling. Metabolic profiling indicated a metabolic shift from anaerobic to aerobic energy production, with 57 differential metabolites identified, mainly involved in protein metabolism and insulin-related pathways. Integrated multi-omics analysis further highlighted the AMPK and FoxO signaling pathways play key roles in this process. In conclusion, our findings demonstrate that the metabolic and structural differences between larval and adult skeletal muscles are mediated by AMPK- and FoxO-dependent signaling pathways, providing novel insights into the molecular mechanisms underlying adaptive development and locomotor transition in anuran amphibians.

Animals

Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of auditory nerve output after threshold recovery.

BACKGROUND: Acoustic stress can alter cochlear function even in the absence of permanent threshold elevation; however, synaptic consequences of transient acoustic stimulation remain incompletely understood. OBJECTIVE: This study aimed to investigate whether transient acoustic stimulation induces changes in the auditory nerve output and cochlear ribbon synapse morphology following hearing threshold recovery. METHODS: Young adult CBA/CaJ mice were exposed to band-limited acoustic stimulation (45-2,000&#xa0;Hz, 95&#xa0;dB SPL, 2&#xa0;h). Auditory brainstem responses (ABRs), hair cell and spiral ganglion neuron survival, and synaptic morphology were evaluated before exposure and up to 2&#xa0;weeks post-exposure. RESULTS: ABR thresholds were transiently elevated immediately after exposure but largely recovered by 1&#xa0;day post-exposure. In contrast, ABR wave I amplitudes significantly increased after threshold recovery across multiple test frequencies. Ribbon-associated puncta in both inner and outer hair cell regions exhibited biphasic temporal changes, with an initial decrease immediately after exposure followed by an increase at 1&#xa0;day post-exposure. The ribbon-associated punctal area also increased after exposure and remained elevated at later post-exposure time points. No significant loss of hair cells or spiral ganglion neurons was observed. Exploratory genomic analysis suggested enrichment of pathways related to metabolic defense and cellular stress responses. CONCLUSIONS: Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of peripheral auditory nerve output without overt cellular degeneration. These findings support a model in which early cochlear responses to acoustic perturbation include adaptive synaptic plasticity and gain regulation, extending current concepts of noise-induced cochlear change beyond irreversible synaptic loss.

Animals

Ciliochoroidal Effusion and Regional Scleral Thickening in Peripapillary Pachychoroid Syndrome.

PURPOSE: To assess anterior scleral thickness and the presence of ciliochoroidal effusion (CE) in eyes with peripapillary pachychoroid syndrome (PPS), and to compare the results with a cohort of healthy age-matched controls. DESIGN: Retrospective cross-sectional study METHODS: A total of 20 eyes from 12 patients diagnosed with PPS and 30 eyes from 15 healthy control subjects. All participants underwent a comprehensive ophthalmic examination, including spectral-domain optical coherence tomography with enhanced depth imaging (EDI-OCT) and anterior segment OCT (AS-OCT). Choroidal thickness was measured at predefined macular and peripapillary locations, while anterior scleral thickness was assessed 6 mm posterior to the scleral spur in 4 quadrants. Ciliochoroidal effusion was evaluated qualitatively using AS-OCT. Comparisons between groups were performed using linear mixed models with Bonferroni correction (scleral thickness corrected P < .010) RESULTS: The mean age of PPS patients was 75.6 &#xb1; 9.8 years, and 16% were females. Anterior scleral thickness was significantly greater in the temporal quadrant in PPS eyes compared to controls (396.85 &#xb1; 74.97 &#xb5;m vs 331.13 &#xb1; 62.65 &#xb5;m: P = .007). Ciliochoroidal effusion was detected in 60% of PPS eyes, predominantly in the superior and temporal sectors, whereas no effusion was observed in healthy controls (P < .001). Eyes with CE exhibited a thicker mean scleral thickness and a thicker subfoveal choroidal thickness compared to eyes without effusion (P < .05). CONCLUSION: Eyes with PPS demonstrated increased temporal scleral thickness and a high prevalence of CE. These findings suggest that scleral characteristics may represent a predisposing anatomical factor in PPS, although the precise pathophysiological mechanisms remain to be elucidated.

Humans

Safety of insulin eye drops in the treatment of open angle glaucoma: a randomized phase I clinical trial.

OBJECTIVE: The progression of glaucoma despite adequate intraocular pressure (IOP) control highlights the need for neuroprotective and neuroregenerative therapies. Preclinical studies suggest insulin promotes retinal ganglion cell survival and regeneration, but its safety in higher concentrations (100 and 500 units/mL), administered topically, has been poorly characterized in humans. We aim to assess the safety and tolerability of these two concentrations of insulin eye drops in patients with open-angle glaucoma (OAG). DESIGN: A phase I, randomized, double-blind, placebo-controlled, single-centre clinical trial. PARTICIPANTS: Patients with mild to moderate OAG were randomized 2:2:1 to receive once-daily topical insulin U-100, U-500, or placebo in 1 eye for 5 days, with follow-up visits at 1, 3, and 6 months. The primary safety outcomes include glycemia, serum potassium, ocular adverse events (AEs), and ocular tolerability scores. Secondary outcomes included IOP, best-corrected visual acuity (BCVA), retinal nerve fibre layer thickness, ganglion cell complex, visual field, and OCT angiography. RESULTS: Eighteen open-angle glaucoma patients were enrolled (mean age: 66.2 &#xb1; 10.1 years). No serious AEs related to insulin were observed. One asymptomatic, transient near-hypoglycemia event occurred in a fasting participant (3.9 mmol/L), with no recurrence after dietary adjustment. No significant changes were found in serum potassium, IOP, BCVA, visual fields, or OCT. Ocular symptoms in the insulin groups were limited to transient, mild burning sensation upon application. One participant experienced cystoid macular edema at 3 months, which was attributed to pre-existing ocular pathology. CONCLUSION: Topical insulin at 100 and 500 units/mL concentrations was well tolerated in patients for short-term use and did not result in significant systemic or ocular toxicity.

Aged

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD&#xa0;=&#xa0;-0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD&#xa0;=&#xa0;-0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

Humans

Aflibercept With Versus Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: Optical Coherence Tomography Angiographic Changes From a Randomized Clinical Trial.

OBJECTIVES: To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fluence PDT. DESIGN: Image analysis of a double-masked, sham-controlled, randomized clinical trial. SUBJECTS: 55 eyes of 55 treatment-na&#xef;ve participants with symptomatic macular PCV completing 52 weeks of follow-up. METHODS: Participants underwent protocolized, multimodal imaging, including OCT, OCTA, fluorescein angiography, and indocyanine green angiography at baseline, week 12, and week 52. Quantitative OCTA parameters included total lesion area, branching neovascular network (BNN) area, and BNN vessel density (VD). Qualitative features included trunk vessel presence and OCTA signal within the polypoidal lesion (PL). Eyes were categorized by treatment arm and PL closure at week 52. MAIN OUTCOME MEASURES: Longitudinal OCTA changes and predictors of PL closure at week 52. RESULTS: We included 55 eyes (28 combination therapy and 27 monotherapy). Total lesion area decreased at week 12 but returned toward baseline at week 52 (combination: 3.72 &#xb1; 3.01mm2 at baseline, 2.86 &#xb1; 2.50mm2 at week 12, 3.59 &#xb1; 3.26mm2 at week 52; monotherapy: 3.77 &#xb1; 2.23mm2 at baseline, 3.27 &#xb1; 2.36mm2 at week 12, and 3.47 &#xb1; 2.58mm2 at week 52). BNN area decreased at week 12 and remained reduced at week 52 in both treatment arms (combination: 2.29 &#xb1; 2.08 mm2 at baseline, 1.46 &#xb1; 1.36mm2 at week 12, and 1.53 &#xb1; 1.32mm2 at week 52; monotherapy: 2.39 &#xb1; 1.85mm2 at baseline, 1.87 &#xb1; 1.68mm2 at week 12, and 1.82 &#xb1; 1.38mm2 at week 52). BNN VD reduction was greater in the combination arm at week 12 (-10 &#xb1; 15% vs - 3 &#xb1; 12%, P = .02). The proportion of eyes with trunk vessels increased over time in both arms (combination: 35.7% at baseline, 59.3% at week 12, and 67.8% at week 52; monotherapy: 25.9% at baseline, 44.4% at week 12, and 71.4% at week 52). In multivariable analysis, baseline BCVA predicted BCVA change at week 52 (&#x3b2;=-0.96 [-1.21 to -0.72], P < .01), and baseline CST predicted CST change (&#x3b2;=0.93 [0.75 to 1.10], P < .01). Greater reduction in BNN VD at week 12 was independently associated with PL closure at week 52 (OR 0.62 [0.39 to 0.97], P = .03). CONCLUSIONS: Early reduction in BNN vessel density, rather than reduction in lesion size, was associated with subsequent PL closure. OCTA-derived vascular changes may serve as noninvasive biomarkers for predicting treatment response in PCV.

Humans