Background and Objectives: Myopia is the most common refractive eye anomaly with a prevalence that is constantly increasing. High myopia is associated with numerous complications that can lead to permanent vision loss. It is believed that the basis of these complications lies in changes in the microvasculature of the retina caused by an increase in the longitudinal axis of the eye. Materials and Methods: Optical coherence tomography angiography (OCTA) was used to analyze differences in macular zone vascular and perfusion density and foveal avascular zone (FAZ) parameters in myopic subjects. The following OCTA parameters were analyzed: the vessel and perfusion density of retinal blood vessels in the superficial plexus; the area, perimeter, and index of circularity of the foveal avascular zone (FAZ); and foveal and ganglion cell complex (GCC) thickness. Results: Subjects with low myopia did not show statistically significant differences compared to the control for any of the analyzed parameters. Groups with moderate and high myopia showed a significant decrease in vessel and perfusion density in the parafoveal and the entire 3 × 3 mm analyzed field. Foveal vessel and perfusion densities in the myopic groups were similar to those of the control regardless of the degree of myopia. The area and perimeter of the FAZ, as well as foveal and mean GCC thickness, did not differ significantly no matter the degree of myopia, while the index of circularity was lower in highly myopic subjects. The minimal thickness of the GCC was also lower in the high myopia group. Conclusions: High and moderate myopia led to a loss of blood vessels in the macular region. Perfusion and vascular densities were preserved in the foveal region and were not affected by different degrees of myopia. The FAZ was not significantly larger in myopic subjects, but its circularity was lower in subjects with high myopia.

Purpose: The purpose of this study was to characterize the distribution and longitudinal evolution of intraretinal and subretinal hyperreflective foci (HF) in treatment-naive neovascular age-related macular degeneration (nAMD), and to examine associations between HF burden, hyperreflective material boundary remodeling (HRM-BR), and best-corrected visual acuity (BCVA) outcomes following bevacizumab treat-and-extend therapy. Methods: This was a retrospective observational study of 84 treatment-naive nAMD eyes receiving intravitreal bevacizumab via a treat-and-extend protocol. Spectral-domain OCT (Revo FC, Optopol) was performed at baseline (M0), month 3 (M3), and month 6 (M6). HF were quantified in the intraretinal and subretinal compartments using ImageJ software (version 1.54, National Institutes of Health, Bethesda, MD, USA) by two masked graders, with inter-rater agreement assessed by intraclass correlation coefficient (ICC). Eyes were classified into four HRM evolution patterns following the framework of Yu et al. Primary outcome was BCVA change from M0 to M6. Multivariable linear regression was performed to assess independent predictors of BCVA change. Results: Baseline intraretinal HF counts increased significantly across HRM Patterns 1 through 4 (median 0, 6, 4, and 8, respectively; Kruskal–Wallis p < 0.001; 95% CI for Spearman r = 0.471: [0.286, 0.623]). A higher baseline intraretinal HF count correlated with worse BCVA change at M6 (r = −0.300, 95% CI [−0.483, −0.092], p_adj = 0.010). In the primary multivariable model (n = 67), both intraretinal HF burden (β = −0.449, 95% CI [−0.879, −0.020], p = 0.041) and HRM width (β = −0.003, 95% CI [−0.005, −0.001], p = 0.014) were independent predictors of BCVA change. The transient M3 intraretinal HF peak in Pattern 3 eyes (median 4 → 12 → 4) was statistically confirmed by Wilcoxon signed-rank testing (M0 → M3: p = 0.004; M3 → M6: p = 0.001). Conclusions: Intraretinal HF burden is a graded marker of HRM pattern severity and an independent predictor of visual outcomes in nAMD, alongside HRM width. The statistically validated transient M3 HF peak in Pattern 3 may represent an early OCT signal of active boundary remodeling.

Background and Objectives: Faricimab, the first bispecific antibody targeting VEGF-A and angiopoietin-2, has demonstrated durable efficacy in pivotal phase 3 trials for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Real-world data on treatment-naïve patients managed with fixed-interval maintenance protocols, particularly from South-Eastern Europe, remain limited. This pilot study evaluated 24-month outcomes of intravitreal faricimab in treatment-naïve nAMD and DME, using a standardized four-injection loading phase followed by fixed every-16-week (Q16W) maintenance. Materials and Methods: This study conducted a retrospective, observational, single-center pilot cohort study of 20 consecutive treatment-naïve eyes (9 nAMD, 11 DME). All patients received four monthly loading injections followed by a fixed every-16-week (Q16W) maintenance schedule, supplemented by discretionary additional injections for residual or recurrent disease activity (215 injections total; mean 10.75 ± 0.79 per patient; range 9–12). Primary outcomes were changes in central foveal thickness (CFT) and best-corrected visual acuity (BCVA; Snellen lines with ETDRS letter equivalents) at months 4 and 24. Prespecified secondary analyses included bootstrap 95% confidence intervals, a linear mixed-effects model with a time × disease-group interaction, Bayesian credible intervals with weakly informative priors, false-discovery-rate (FDR) correction, and a minimum detectable effect-size analysis. Results: All 20 eyes completed 24-month follow-up. In nAMD, mean CFT decreased by 186.9 ± 71.9 µm (35.9%; bootstrap 95% CI 148.1–236.0; p < 0.001; d = 2.60), and BCVA improved by 3.89 ± 0.78 Snellen lines (~19 ETDRS letters; 95% CI 3.44–4.33; p < 0.001; d = 4.97). In DME, CFT decreased by 197.7 ± 65.7 µm (39.3%; 95% CI 162.5–237.3; p < 0.001; d = 3.01), and BCVA improved by 4.55 ± 1.04 lines (~23 ETDRS letters; 95% CI 4.00–5.09; p < 0.001; d = 4.39). All 20 eyes (100%) achieved ≥ 3 Snellen lines gain and ≥20% CFT reduction; 80% reached final BCVA ≥ 7 lines. A linear mixed-effects model showed a significant time effect (p < 0.001) but no time × group interaction (CFT p = 0.84; BCVA p = 0.51), indicating concordant trajectories across diseases. Bayesian analysis with weakly informative priors yielded posterior P(|d| > 0.8) ≥ 0.99 for all primary outcomes. After FDR correction, all pre-specified primary comparisons remained significant. The minimum detectable effect size with the realized sample sizes (Cohen’s d ≈ 0.66 combined, 1.07 nAMD, 0.94 DME at 80% power) was substantially below all observed effect sizes. No ocular or systemic adverse events were recorded. Conclusions: In this small, single-center, treatment-naïve pilot cohort, a fixed Q16W faricimab maintenance schedule with discretionary additional injections was associated with durable anatomical and functional improvements over 24 months in both nAMD and DME, with no adverse events recorded across 215 injections. Given the limited sample, these findings should be regarded as hypothesis-generating. The high responder rates likely reflect the cohort’s substantial baseline visual impairment (mean baseline BCVA ~20/120–20/200), which provides greater absolute capacity for measurable gain than in higher-acuity registration trial populations. These pilot data support fixed-interval faricimab as a logistically feasible candidate strategy in resource-constrained settings and should be confirmed in larger multicenter cohorts using standardized ETDRS acuity assessment.

Background and Objectives: Open-angle glaucoma subtypes share a structural phenotype but differ in pathophysiology: pseudoexfoliative glaucoma (PXG) involves vascular endothelial dysfunction associated with deposition of exfoliative material, whereas normal-tension glaucoma (NTG) reflects primary vascular dysregulation in the absence of elevated intraocular pressure. We characterized subtype-specific OCT angiography (OCTA) profiles obtained from a 3 × 3 mm macular scan and evaluated their discriminatory power for pairwise subtype classification. Materials and Methods: This was a single-center, cross-sectional study of 304 eyes: 198 glaucomatous eyes—primary open-angle glaucoma (POAG, glaucoma simplex in our clinical nomenclature), n = 102; PXG (glaucoma capsulare), n = 68; NTG (glaucoma sine tensio), n = 28—and 106 healthy controls. The Cirrus HD-OCT 5000 AngioPlex 3 × 3 mm OCTA protocol was used to assess vessel density (VD), perfusion density, foveal avascular zone (FAZ) morphology, ganglion cell complex (GCC), and retinal nerve fiber layer (RNFL) thickness. Analyses included Kruskal–Wallis tests with Bonferroni post hoc correction, ROC analysis with DeLong comparison of combined versus structural-only models, multivariate regression, and an exploratory XGBoost classifier with SHAP-based interpretation. Results: VD Inner and Perfusion Inner were lower in PXG (16.37 ± 3.33%; 0.31 ± 0.05) than in POAG (18.73 ± 3.41%; 0.34 ± 0.05; both p < 0.001); Perfusion Inner was also lower than in NTG (p < 0.05). FAZ Area was largest in NTG (0.27 ± 0.11 mm²) and greater than in PXG (0.19 ± 0.08; p < 0.01); FAZ Circularity differed across subtypes (p < 0.001). Combined OCTA–structural models outperformed structural-only models for POAG vs. PXG (DeLong p = 0.002) and for PXG vs. NTG (AUC = 0.770; p = 0.010). Sector-resolved Spearman analysis revealed subtype-specific coupling: in NTG, VD Inner and Perfusion Inner correlated with the inferior RNFL (r = 0.53 and r = 0.52; both p < 0.01); in PXG, coupling shifted nasally (r = 0.41 and r = 0.46; both p < 0.001). The exploratory XGBoost classifier separated glaucoma from controls with an internal cross-validated AUC of 0.975 ± 0.008 (5-fold CV; not externally validated); FAZ Circularity (mean |SHAP| = 0.418) and FAZ Area (0.411) were the top inter-subtype features, supported by case-level SHAP. RNFL avg and average GCC independently predicted MD across subtypes; in PXG, Perfusion Inner also predicted MD (β = −32.78; p = 0.032). Conclusions: In this single-center, cross-sectional cohort, OCTA revealed subtype-associated macular microvascular profiles that are complementary to structural OCT. Reduced vessel and perfusion density characterized PXG, whereas FAZ enlargement and reduced circularity distinguished NTG and PXG. Vascular–structural coupling was nasal-predominant in PXG and inferior-predominant in NTG. Combined multimodal models outperformed structural-only approaches. Macular perfusion additionally predicted MD in PXG. The XGBoost/SHAP analysis is exploratory; prospective and externally validated studies are required before clinical deployment.

Background and Objectives: Micropulse transscleral cyclophotocoagulation (MP-TSCPC) selectively targets the ciliary body epithelium to reduce intraocular pressure (IOP). This study evaluated 6-month efficacy and safety of MP-TSCPC in primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEX) refractory to maximally tolerated topical therapy, and formally tested clinical equivalence between subtypes. Materials and Methods: In this single-arm prospective interventional cohort study with planned subgroup comparison, 58 eyes from 41 patients (POAG, 34; PEX, 24) underwent MP-TSCPC using the Cyclo G6 system with MicroPulse P3 probe at 2.0–2.2 W, 31.3% duty cycle, 90 s per hemisphere. IOP, best-corrected visual acuity (BCVA), antiglaucoma medications, and complications were recorded at baseline and at 30, 90, and 180 days. Six prespecified success criteria were evaluated, including the original ≥20% reduction threshold and the stricter Tekeli composite criteria. Outcomes are reported with 95% confidence intervals (CI) and Cohen’s d. Intra-subject correlation from bilateral inclusion was addressed through a linear mixed-effects model, generalized estimating equations, and a 1000-iteration sensitivity analysis with random one-eye-per-patient subsampling. Equivalence was assessed by two one-sided tests (TOST). Results: Baseline IOP was 26.50 ± 2.93 mmHg (POAG) and 25.92 ± 2.47 mmHg (PEX). At 180 days, mean IOP reduction was 32.1% (95% CI 30.1–34.1) in POAG and 28.8% (95% CI 26.9–30.7) in PEX, both p < 0.001 versus baseline, with very large within-group effect sizes (Cohen’s d 4.24 and 4.81). All eyes achieved ≥20% reduction; under Tekeli criterion A (IOP ≤ 18 mmHg AND ≥20% reduction), success was 67.6% (POAG) and 54.2% (PEX). A 3.2 percentage-point between-group difference at 180 days was statistically detectable unadjusted (p = 0.024) but lost significance after clustering adjustment (mixed-model p = 0.101); equivalence was formally established at the ±7 percentage-point margin (TOST p = 0.004). Medication burden decreased in 41.2% (POAG) and 50.0% (PEX) of eyes. BCVA was preserved in all eyes; no serious adverse events were recorded. Conclusions: MP-TSCPC produces clinically meaningful, progressive IOP reduction over 6 months in both POAG and PEX, with no serious complications and clinically equivalent efficacy between subtypes. Longer-term studies with formal recording of baseline severity descriptors are warranted to confirm durability. Trial registration: ISRCTN registry, ISRCTN62227730.

Background and Objectives: Type 2 diabetes mellitus (T2DM) causes retinal microvascular changes that precede clinically apparent diabetic retinopathy (DR). We aimed to identify which optical coherence tomography angiography (OCTA) biomarkers best distinguish eyes with T2DM without clinical DR from healthy controls and to evaluate machine learning classifiers trained on a comprehensive 68-parameter OCTA panel. Materials and Methods: In this prospective case–control study, 80 patients with T2DM without clinical DR and 33 controls underwent 3 × 3 mm macular OCTA using an Optovue RTVue Avanti System. After outlier screening, 221 eyes (155 T2DM, 66 controls) were analyzed. Sixty-eight OCTA parameters were extracted, covering FAZ morphometry (including foveal density FD-300), SCP and DCP vessel density and layer thickness, outer-retina and choriocapillaris flow, and a full retinal-thickness map. Between-group comparisons used the Mann–Whitney U test with Benjamini–Hochberg FDR correction. Logistic regression, random forest, and XGBoost classifiers were evaluated with patient-grouped 10-fold cross-validation; feature importance was quantified via SHAP. Results: Forty-two of 68 parameters reached FDR significance (q < 0.05). Deep capillary plexus vessel density was the most discriminative family (whole image rb = −0.66, q = 2.5 × 10⁻¹³; parafovea rb = −0.64). FD-300 was reduced in T2DM (median 47.55% vs. 51.86%; rb = −0.57; q = 1.0 × 10⁻¹⁰) and emerged as the top SHAP feature (mean |SHAP| = 0.81). FAZ circularity decreased without FAZ-area enlargement, and outer-retina flow was paradoxically elevated (rb = +0.39), consistent with a projection artifact. XGBoost using all 68 features achieved a patient-grouped cross-validated AUC of approximately 0.91, compared with 0.85 for conventional SCP + DCP whole-image density. No parameter correlated with current HbA1c in T2DM (all q > 0.98), and the well-controlled (<7%) and poorly controlled (≥7%) subgroups were indistinguishable across five of six principal biomarkers, consistent with metabolic memory. FD-300 remained independent after adjustment for hypertension, hyperlipidemia, and age (OR = 0.76; 95% CI 0.69–0.84; p < 0.001). Conclusions: A multi-compartment OCTA panel outperforms conventional two-layer vessel-density metrics in detecting preclinical diabetic microvasculopathy, although external validation is required before clinical use. FD-300 is the single most informative biomarker, while choriocapillaris and retinal thickness measures provide complementary, compartment-specific signals. Because the OCTA signature is decoupled from the current HbA1c, screening should not be deferred in well-controlled T2DM.