Anti-VEGF therapy remains the mainstay treatment for neovascular age-related macular degeneration (nAMD), yet a subset of eyes exhibit resistance to standard treatment regimens. This study evaluates the safety and efficacy of double-dose intravitreal faricimab (12 mg) in a series of eyes with nAMD refractory to bevacizumab, aflibercept, and standard-dose faricimab. This retrospective case series included 26 eyes from 24 patients with treatment-resistant nAMD who received intravitreal faricimab 12 mg every 4 weeks for three loading injections, followed by a treat-and-extend regimen when anatomic stability was achieved. Primary anatomic outcomes included central subfield thickness (CST), central foveal thickness (CFT), maximum macular thickness (MMT), pigment epithelial detachment (PED) height and volume, and intraretinal (IRF), subretinal (SRF), and total retinal fluid (TRF) volumes. Best-corrected visual acuity (BCVA) served as the functional endpoint. Safety measures included intraocular pressure (IOP), intraocular inflammation, systemic adverse events, and new-onset geographic atrophy (GA). Over a mean follow-up of 10.6 months, significant anatomical improvements were observed, including reductions in CFT (p=0.0029), MMT (p=0.0007), CST (p=0.0067), PED maximum height (p=0.0241), and TRF (p=0.0341). PED volume significantly decreased at 4 weeks (p=0.0394) but was not sustained. IRF and SRF reductions were not individually significant. BCVA, which had declined significantly in the 24 weeks prior to switching (p≈0.04), remained stable throughout treatment with double-dose faricimab (p>0.6). At final visit, 57.7

PURPOSE:To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the incidence of age-related macular degeneration (AMD) and neovascular AMD (nAMD) among adults with diabetes. DESIGN:Retrospective, propensity score-matched cohort study. PARTICIPANTS:Adults with diabetes who initiated a GLP-1RA or another noninsulin antidiabetic agent. In Epic Cosmos, 2 797 686 GLP-1RA users were matched 1:1 to 2 797 686 active comparators. METHODS:We analyzed de-identified electronic health record data from Epic Cosmos and independently replicated the primary analyses in the University of California Health Data Warehouse. Individuals with prevalent AMD or nAMD and those with prior anti-VEGF treatment were excluded. One-to-one nearest-neighbor propensity score matching balanced demographics, diabetes duration, comorbidities, smoking, diabetic retinopathy, obesity, and eye-care utilization. Cumulative incidence at 1, 5, and 10 years was estimated using Kaplan-Meier methods, and adjusted associations were evaluated using multivariable Cox proportional hazards models. MAIN OUTCOME MEASURES:Incidence of any AMD and nAMD. RESULTS:In the matched Epic Cosmos cohort (total N = 5 595 372), GLP-1RA use was associated with lower cumulative incidence of any AMD at 1 year (0.187% [95% confidence interval {CI}, 0.182%-0.192%] vs. 0.294% [95% CI, 0.287%-0.301%]), 5 years (0.924% [95% CI, 0.907%-0.941%] vs. 1.278% [95% CI, 1.260%-1.296%]), and 10 years (5.561% [95% CI, 4.719%-6.549%] vs. 6.540% [95% CI, 6.017%-7.108%]); all P < 0.001. Unadjusted cumulative incidence of nAMD was also lower among GLP-1RA users at 1 year (0.047% vs. 0.065%), 5 years (0.280% vs. 0.340%), and 10 years (1.874% vs. 2.393%); all P < 0.001. In multivariable Cox models, GLP-1RA use was independently associated with lower hazard of any AMD (hazard ratio [HR], 0.84; 95% CI, 0.83-0.86; P < 0.001) and was not associated with an increased hazard of nAMD (HR, 1.00; 95% CI, 0.97-1.04; P = 0.79). In the independent University of California Health Data Warehouse cohort, GLP-1RA use was likewise associated with lower AMD incidence at 5 and 10 years, whereas nAMD incidence did not differ significantly between groups. CONCLUSIONS:Among adults with diabetes, GLP-1RA use was associated with lower incident AMD and was not associated with increased nAMD risk. These findings provide reassurance regarding ocular safety and support a potential protective association for earlier AMD phenotypes. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE:To evaluate the safety and efficacy of a dropless regimen using intravitreal decanted triamcinolone acetonide and moxifloxacin at the conclusion of pars plana vitrectomy (PPV), compared with standard postoperative topical therapy. METHODS:This retrospective study included consecutive patients undergoing PPV at a tertiary retina center. The dropless cohort (May-October 2025) received intravitreal decanted triamcinolone (5 mg) and moxifloxacin (500 μg). The control cohort, operated during the preceding 6 months, received topical moxifloxacin 0.5% and prednisolone acetate 1%. Outcomes included intraocular inflammation, intraocular pressure (IOP), central subfield thickness (CST), cystoid macular edema (CME), and best-corrected visual acuity (BCVA). A prespecified subgroup analysis was performed for epiretinal membrane (ERM). RESULTS:172 eyes were included (87 dropless, 85 topical). The dropless group demonstrated significantly less anterior chamber inflammation at week 2 (P = 0.0008) and at month 3 (P = 0.0223). Mean CST was lower at week 2 (P = 0.001), month 3 (P = 0.0009), and month 6 (P = 0.012). CME incidence was reduced (P < 0.001). BCVA improvement was greater in the dropless group at week 2 (+15 vs -2.5 ETDRS letters; P = 0.0003), month 3 (+25 vs +9.5 letters; P = 0.002), and month 6 (+20 vs +8 letters; P = 0.01). IOP was similar between groups, and no endophthalmitis occurred. Findings were consistent in the ERM subgroup. CONCLUSION:A dropless intravitreal regimen at the conclusion of PPV can be a safe and effective alternative to topical therapy, with reduced postoperative inflammation and CME and improved visual outcomes.

PURPOSE:Optical coherence tomography angiography is widely used to detect choroidal neovascularization in retinal diseases, but acquiring high-density raster scans can prolong acquisition time and increase motion artifacts due to patient fatigue. This study evaluates whether the 250 kHz ultrahigh-speed mode (3× faster than baseline) reduces scan time and motion artifacts while maintaining image quality compared with the FDA-approved 125 kHz mode. METHODS:Fifty-eight eyes underwent 10°×10° fovea-centered optical coherence tomography angiography imaging using both modes. In 38 choroidal neovascularization eyes, AngioTool was used to analyze vascular metrics. In 20 nonchoroidal neovascularization eyes, superficial foveal avascular zone area was measured using ImageJ. Two masked retina specialists graded paired images for image quality, motion artifacts, and clinical diagnosis. Acquisition time was recorded. RESULTS:The 250 kHz mode reduced acquisition time by 43% (17.5 ± 9.0 seconds vs. 33.6 ± 20.7 seconds, P < 0.00001). Image quality and motion artifacts favored the 250 kHz mode. Clinical diagnosis was rated similarly across modes. Quantitative metrics, including vessel area, junctions, lacunarity, and foveal avascular zone area, showed no significant differences (all P > 0.1). CONCLUSION:This is the first intraindividual comparison of Heidelberg's 250 kHz and 125 kHz optical coherence tomography angiography modes. The findings demonstrate that ultrahigh-speed scanning can enhance efficiency and image quality without compromising diagnostic or quantitative utility, highlighting its potential clinical impact pending Food and Drug Administration approval.

Abstract Artificial intelligence (AI) has shown promise in retinal imaging, yet its application to longitudinal optical coherence tomography angiography (OCTA) remains limited. This study developed and evaluated an AI model for classifying treatment response in neovascular age-related macular degeneration (nAMD) using paired OCTA images acquired before and after anti-VEGF therapy. In this retrospective cohort study, paired OCTA en-face images and corresponding OCT B-scans were collected for each treatment course. OCTA image pairs were manually segmented and aligned for AI input, while ground-truth labels (Improved, Unchanged, Worsened) were determined based on structural OCT findings and clinical visual acuity outcomes. After quality exclusion, 1033 OCTA pairs were included and divided into training, validation, and independent testing subsets. Two experienced retina specialists graded all OCTA pairs for comparison. On the test set, the AI model achieved an overall accuracy of 82.08%, with class-specific accuracies of 74.29% (worsened), 81.48% (unchanged), and 88.64% (improved). In contrast, overall human grading accuracy was 61.40%. Human graders were significantly more likely to misclassify treatment response than the AI model for all groups (odds ratio = 2.88; 95% CI 1.68–4.92; p < 0.0001). These findings demonstrate that AI-based paired OCTA analysis can provide a more accurate and objective assessment of treatment response in nAMD.

We identify two major limitations in the existing studies on retinal vessel segmentation: 1) Most existing works are restricted to one modality, i.e., the Color Fundus (CF). However, multi-modality retinal images are used every day in the study of the retina and diagnosis of retinal diseases, and the study of vessel segmentation on other modalities is scarce; 2) Even though a few works extended their experiments to new modalities such as the Multi-Color Scanning Laser Ophthalmoscopy (MC), these works still require fine-tuning a separate model for the new modality. The fine-tuning will require extra training data, which is difficult to acquire. In this work, we present a novel universal vessel segmentation model (URVSM) for multi-modality retinal images. In addition to performing the study on a much wider range of image modalities, we also propose a universal model to segment the vessels in all these commonly used modalities. While being much more versatile compared with existing methods, our universal model also demonstrates comparable performance to the state-of-the-art fine-tuned methods. To the best of our knowledge, this is the first work that achieves modality-agnostic retinal vessel segmentation and the first to study retinal vessel segmentation in several novel modalities (Code, model and 3 new retinal vessel segmentation datasets are available at https://github.com/JRC-VPLab/URVSM).

Purpose To report a case of iatrogenic trauma related choroidal neovascularization (CNV) Methods A 66 year old female presented with complaints of distortion of vision in the right eye. A diagnosis of epiretinal membrane (ERM) foveoschisis was made and the patient was recommended surgery. During surgery an inadvertent touch of the retina occurred. Post operatively, an iatrogenic choroidal neovascular membrane was diagnosed. Results Post-operative optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) revealed a CNV which was treated with intravitreal Bevacizumab. The visual acuity improved remarkably. The intraretinal and subretinal fluid resolved and the macula was almost completely dry at final visit. Conclusion ERM surgery is one of the common procedures in vitreoretinal surgery. Iatrogenic CNV is a reported but rare complication following inadvertent trauma during surgery. We report a successful outcome of iatrogenic CNV treated with intravitreal injections of Bevacizumab.

Purpose:To compare the assessment of clinically relevant retinal and choroidal lesions as well as optic nerve pathologies using a novel three-wavelength ultra-widefield (UWF) scanning laser ophthalmoscope with established retinal imaging techniques for ophthalmoscopic imaging. Methods:Eighty eyes with a variety of retinal and choroidal lesions were assessed on the same time point using Topcon color fundus photography (CFP) montage, Optos red/green (RG), Heidelberg SPECTRALIS MultiColor 55-color montage (MCI), and novel Optos red/green/blue (RGB). Paired images of the optic nerve, retinal, or choroidal lesions were initially diagnosed based on CFP imaging. The accuracy of the imaging was then evaluated in comparison to CFP using a grading scale ranging from -1 (losing imaging information) to +1 (gaining imaging information). Results:Eighty eyes of 43 patients with 116 retinal or choroidal pathologies, as well as 59 eyes with optic nerve imaging using CFP, MCI, RG, and RGB, were included in this study. Across all subgroups, RGB provided significantly more accurate clinical imaging with CFP as ground truth and compared to other modalities. This was true comparing RGB to both RG (P = 0.0225) and MCI (P < 0.001) overall. Although RGB provided more accurate clinical information overall, it was inferior to RG for melanocytic choroidal lesions (P = 0.011). Conclusions:RGB can be considered as a useful tool to detect characteristics of central, midperipheral, and peripheral retinal lesions. Regarding melanocytic choroidal lesions, RGB was inferior to RG, and MCI was inferior to both RG and RGB modalities due to color changes. Translational Relevance:Traditional retinal ultra-widefield imaging uses two wavelengths. Here, we evaluated three wavelengths for ultra-widefield imaging. We examined new optics (basic science) effect on patient imaging (clinical care).

Macular neovascularization (MNV) in age-related macular degeneration (AMD) remains a therapeutic challenge, especially in eyes resistant to conventional anti-VEGF therapy. This study evaluates the anatomical and functional response to Faricimab in patients with persistent fluid despite intensified Aflibercept treatment and explores potential benefits of dose escalation. This cross-sectional study included 25 eyes from 23 patients with active MNV resistant to standard anti-VEGF therapy. All had persistent fluid on OCT despite monthly injections and received off-label double-volume Aflibercept 4 mg (0.1 ml) for at least three doses. Eyes with persistent fluid were switched to Faricimab 6 mg. In non-responders, Faricimab was further escalated to 12 mg (0.1 ml). Retinal fluid volumes and pigment epithelium detachment (PED) were analyzed using AI-based OCT segmentation. MNV activity was assessed using AI-based OCTA analysis. Faricimab 6 mg significantly reduced PED volume (p < 0.05), especially after the first two injections. However, changes in intraretinal and subretinal fluid were not significant. In the Faricimab 12 mg subgroup, no additional anatomical benefit was observed. OCTA showed a trend toward reduced vascular activity after switching to Faricimab 6 mg, but no further change with dose escalation. In MNV eyes resistant to high-dose Aflibercept, Faricimab 6 mg provides meaningful anatomical improvement, particularly in PED volume. However, escalating Faricimab to 12 mg offers no additional benefit, suggesting therapeutic saturation at the standard dose.

PURPOSE:Although many studies have analyzed macular choroidal neovascularization (CNV) using optical coherence tomography angiography, few have focused on peripapillary CNV, which comprises approximately 10% of CNV cases. This study examines optical coherence tomography angiography vessel changes in patients with treated and untreated peripapillary CNV to better understand disease progression. METHODS:Nineteen eyes with peripapillary CNV secondary to neovascular age-related macular degeneration were retrospectively analyzed. Treated eyes (n = 13) received anti-VEGF injections after a modified pro re nata regimen, whereas untreated eyes (n = 6) without macular involvement were closely observed. Median follow-up was 11.9 months (treated) and 8 months (untreated). High-quality optical coherence tomography angiography scans centered on the CNV lesions were selected and analyzed using validated software (ImageJ and AngioTool). RESULTS:Treated eyes showed significant reductions in CNV lesion size, vessel density, and lacunarity after anti-VEGF therapy (ImageJ: P < 0.001; AngioTool: P = 0.0004). Untreated eyes exhibited significant lesion enlargement (ImageJ: P = 0.0356; AngioTool: P = 0.0013). None of the patients in the untreated group developed macular exudation during the study. CONCLUSION:Peripapillary CNV without macular involvement may be considered for short-term observation in selected cases, as these lesions appeared indolent and stable over the limited follow-up period in our cohort. The vessels in optical coherence tomography angiography in the treated group showed regression in size after anti-VEGF therapy. These findings will potentially help clinicians better understand this entity.

Objective: To perform a pointwise structure–function analysis of the ellipsoid zone (EZ) in retinitis pigmentosa (RP) using an artificial intelligence–based overlay to understand EZ structure–function relationships. Design: A single-center retrospective study. Subjects: Patients with clinically confirmed RP. Methods: Same-day spectral-domain OCT (SD-OCT) and microperimetry near-infrared images were overlaid in patients with confirmed RP. Overlay used a coarse alignment artificial intelligence model. Each locus, on a 68-point microperimetry grid spanning the central 20° of the macula, was identified on individual SD-OCT B-scans. Ellipsoid zone structure was graded at each locus on a 3-point scale: grade 0 = EZ not visible; grade 1 = EZ attenuated; grade 2 = EZ normal. Ellipsoid zone grades were correlated with microperimetry sensitivity scores recorded in decibels (dB). Main Outcome Measures: Correlation of EZ integrity on SD-OCT with microperimetric retinal sensitivity. Results: Fifty-one eyes from thirty-one patients with RP were included in the analysis, with 60 total overlays, including follow-up studies, resulting in 3985 test loci being graded. Patients had a mean age of 39.4 (32.8–46.0) years, with 41.9% being female. Mean best-corrected visual acuity was 0.166 (0.129–0.203) logarithm of the minimum angle of resolution. The overall mean sensitivity (MS) was 9.72 (7.32–12.12) dB, whereas MS was 6.02 (4.06–7.98) dB for grade 0 loci, 18.36 (16.35–20.36) dB for grade 1 loci, and 20.90 (18.87–22.93) dB for grade 2 loci. Differences in MS were significant between graded groups (P < 0.001). Correlation between EZ grade and sensitivity was 0.65 (0.64–0.67), whereas correlation of sensitivity with distance from the fovea was −0.41 (−0.43 to −0.39). Focusing on grade 0 loci, 57.5% had sensitivity scores >0 dB, and 4% had scores ≥20 dB, suggesting that these points had function despite no observable EZ on SD-OCT. Conclusions: We identified local EZ structure–function incongruencies in RP using a pointwise analysis of structure–function overlay. These loci of interest may be overlooked in analyses that average across the visual field. Preserved photoreceptor function, in the absence of visibly intact EZ, warrants further investigation. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

BACKGROUND AND OBJECTIVE:The purpose of this retrospective chart review was to evaluate the efficacy and safety of combined intravitreal long-acting corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) therapeutic agents for resistant cystoid macular edema associated with diabetic retinopathy, or diabetic macular edema (DME). PATIENTS AND METHODS:This study included 16 eyes of 15 patients. Patients with unresponsive DME, despite aggressive monthly monotherapy with steroid or anti-VEGF (decanted triamcinolone or 4 mg aflibercept) were included. Treatment consisted of simultaneous administration of anti-VEGF and decanted triamcinolone. Optical coherence tomography (OCT) and comprehensive ophthalmic exams were performed prior to treatment, as well as every 4 weeks (for 4 months), post-treatment. Main outcome measures were central retinal thickness (CRT) measured by OCT in microns and best-corrected visual acuity (BCVA). RESULTS:The mean treated disease duration (months) was 38.93 ± SD 8.73 [16-108]. There was a CRT reduction at post-combination 1 month (159.18 µm, P = 0.0003), 2 month (169.58 µm, P = 0.0038), 3 month visit (167.88 µm, P = 00.0200), and 4 month (212.88 µm, P = 0.0276). BCVA improved by 8.5 letters (P = 0.0216) at month 1. Improvement persisted with a mean of nine letters (P = 0.039) at month 2, 10 letters (P = 0.035) at month 3, and three letters (P = 0.638) at month 4. No ocular or systemic safety issues were noted after the combination therapy. CONCLUSION:Combination therapy of steroid and anti-VEGF results in clear anatomic and function improvement in eyes with DME that were resistant to monotherapy with anti-VEGF or monotherapy with steroids. The use of this combination has shown a therapeutic effect in treatment-resistant DME.

This paper presents the first study to apply tunable wavelet units (UwUs) for 3D retinal layer segmentation from Optical Coherence Tomography (OCT) volumes. To overcome the limitations of conventional max-pooling, we integrate three wavelet-based downsampling modules, OrthLattUwU, BiorthLattUwU, and LS-BiorthLattUwU, into a motion-corrected MGU-Net architecture. These modules use learnable lattice filter banks to preserve both low- and high-frequency features, enhancing spatial detail and structural consistency. Evaluated on the Jacobs Retina Center (JRC) OCT dataset, our framework shows significant improvement in accuracy and Dice score, particularly with LS-BiorthLattUwU, highlighting the benefits of tunable wavelet filters in volumetric medical image segmentation.

Toomey, Christopher B. M.D., Ph.D; Kalaw, Fritz Gerald P. M.D; Walker, Evan M.S; Freeman, William R. M.D Author Information

PURPOSE:To determine the impact of severity of age-related macular degeneration (AMD) on subjective treatment response in patients treated for dry eye disease. METHODS:A total of 203 eyes diagnosed with evaporative dry eye disease (DED) due to meibomian gland dysfunction were treated using the LipiFlow or MiBoFlo systems. From this cohort, 40 eyes with stable dry AMD (early, intermediate, or late stages) were included. Each participant completed the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness Questionnaire (SPEED) before treatment and at a 6-month follow-up. Changes in questionnaire scores were analyzed using one-way analysis of variance (ANOVA) to assess differences between AMD severity groups. RESULTS:Improvement in SPEED and OSDI scores, including vision related OSDI scores were observed across all AMD stages, with no significant differences between groups (p<0.05). CONCLUSION:Managing DED improved quality of life (QOL) in patients with AMD, regardless of retinal disease severity. This highlights the importance of treating coexisting ocular surface conditions to enhance patient outcomes, even in the presence of significant maculopathy.

In this study, we developed deep learning-based method to classify the type of surgery performed for epiretinal membrane (ERM) removal, either internal limiting membrane (ILM) removal or ERM-alone removal. Our model, based on the ResNet18 convolutional neural network (CNN) architecture, utilizes postoperative optical coherence tomography (OCT) center scans as inputs. We evaluated the model using both original scans and scans preprocessed with energy crop and wavelet denoising, achieving 72% accuracy on preprocessed inputs, outperforming the 66% accuracy achieved on original scans. To further improve accuracy, we integrated tunable wavelet units with two key adaptations: Orthogonal Lattice-based Wavelet Units (OrthLatt-UwU) and Perfect Reconstruction Relaxation-based Wavelet Units (PR-Relax-UwU). These units allowed the model to automatically adjust filter coefficients during training and were incorporated into downsampling, stride-two convolution, and pooling layers, enhancing its ability to distinguish between ERM-ILM removal and ERM-alone removal, with OrthLattUwU boosting accuracy to 76% and PR-Relax-UwU increasing performance to 78%. Performance comparisons showed that our AI model outperformed a trained human grader, who achieved only 50% accuracy in classifying the removal surgery types from postoperative OCT scans. These findings highlight the potential of CNN based models to improve clinical decision-making by providing more accurate and reliable classifications. To the best of our knowledge, this is the first work to employ tunable wavelets for classifying different types of ERM removal surgery.

Diabetic retinopathy (DR) is a major cause of vision impairment, with early detection playing a crucial role in preventing irreversible blindness. While deep learning-based automated DR grading has improved diagnostic efficiency, class imbalance in public datasets hinders reliable performance evaluation, particularly for underrepresented DR stages. Current state-of-the-art classifiers achieve high overall accuracy but suffer from poor balanced accuracy, limiting their real-world applicability. Inspired by recent advancements in diffusion models, we propose to mitigate class imbalance by generating synthetic fundus images. Unlike prior methods prioritizing visual quality, we introduce a semantic quality metric based on classifier-predicted likelihood to selectively filter synthetic samples that enhance classification performance. Furthermore, we incorporate explicit class constraint during diffusion model finetuning to generate more semantically relevant data. Experimental results demonstrate a significant improvement in balanced classification accuracy from 66.84 https://github.com/AlanZhang1995/ECC_DM_for_DR.git .