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Purpose: To investigate the association between baseline clinical characteristics of patients with diabetic macular edema (DME) and quantitative intravenous fluorescein angiography (IVFA) parameters., Methods: Consecutive patients with DME presenting with a central macular thickness (CMT) >310 μm were recruited from 2017-2023. Ultra-widefield IVFA images were analyzed with the RETICAD algorithm to extract quantitative measures of blood-retinal barrier (BRB) permeability, retinal perfusion, and blood flow. Univariable and multivariable regression models were used to investigate associations between IVFA parameters and baseline best-corrected visual acuity (BCVA), CMT, and macular volume., Results: The study population consisted of 56 eyes with DME, and seven eyes from healthy controls. In our multivariable analysis, BRB permeability measured in the central and peripheral retina was significantly associated with BCVA (p=0.003 and 0.002, respectively) and macular volume (p=0.025 and 0.045, respectively). Both central and peripheral BRB permeability were significantly higher in DME eyes relative to healthy controls (p<0.001)., Conclusion: Increased BRB permeability measured on IVFA in DME eyes was associated with a greater baseline macular volume and worse BCVA, suggesting its potential in providing an objective assessment of disease severity. Future research should explore the clinical utility of quantitative IVFA measurements in diverse patient populations.

Purpose: To investigate associations between quantitative vascular measurements derived from intravenous fluorescein angiography (IVFA) and baseline characteristics on optical coherence tomography (OCT) in neovascular age-related macular degeneration (nAMD) patients., Methods: The authors prospectively recruited patients with active choroidal neovascularization secondary to AMD over 50 years old, presenting to a single center in Toronto, Canada from 2017 to 2023. Ultra-widefield IVFA images were processed using the artificial intelligence RETICAD FAassist system to extract quantitative information on blood flow, perfusion, and blood-retinal-barrier (BRB) permeability. Associations between IVFA parameters with functional and anatomical outcomes were examined using univariable and multivariable regression models., Results: Eighty-one nAMD eyes and seven healthy control eyes were included. Compared with healthy controls, BRB permeability in the central and peripheral retina was significantly higher in nAMD patients (P < 0.001). On univariable analysis, BRB permeability measured centrally was significantly associated with central macular thickness (P = 0.035), whereas perfusion and blood flow measured centrally were significantly associated with macular volume (P = 0.043 and 0.037, respectively). On multivariable analysis, BRB permeability remained significantly associated with central macular thickness (P = 0.026)., Conclusion: Central BRB permeability measured on IVFA was significantly associated with baseline central macular thickness in nAMD patients. Future work should longitudinally explore associations between IVFA parameters and clinical characteristics in diverse nAMD populations.

Purpose: To evaluate the impact of pigment epithelial detachment (PED) thickness (i.e., height) and thickness variability on best-corrected visual acuity outcomes in patients with neovascular age-related macular degeneration in the Phase 3 HAWK and HARRIER trials., Methods: Optical coherence tomography images from the pooled brolucizumab 6 mg and aflibercept 2 mg arms were analyzed for the maximum PED thickness across the macula at baseline through to week 96. Best-corrected visual acuity outcomes were compared in patients with different PED thickness and variability cut-off thresholds., Results: Greater PED thickness at baseline or at week 12 was associated with lower mean best-corrected visual acuity gain from baseline to week 96 (baseline PED ≥200 µ m: +4.6 letters; <200 µ m: +7.0 letters; week 12 PED ≥100 µ m: +5.6 letters; <100 µ m: +6.6 letters). Eyes with the largest PED thickness variability from week 12 through week 96 gained fewer letters from baseline at week 96 (≥33 µ m: +3.3 letters; <9 µ m: +6.2 letters). Furthermore, increased PED thickness at week 48 was associated with higher prevalence of intraretinal and subretinal fluid., Conclusion: In this treatment-agnostic analysis, greater PED thickness and PED thickness variability were associated with poorer visual outcomes in patients with neovascular age-related macular degeneration and greater neovascular activity., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To compare foveal avascular zone (FAZ) geometric indices using optical coherence tomography angiography (OCTA) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). FAZ morphology was assessed as a possible imaging feature of retinal displacement., Methods: This ALIGN post hoc analysis included primary fovea-off RRDs that underwent successful PnR or PPV, and performed OCTA, and fundus autofluorescence at (FAF) 3 months postoperatively at St. Michael's Hospital, Toronto, Canada. FAZ area (mm 2 ), axial ratio, circularity, and roundness were measured, and FAF images were assessed for retinal displacement., Results: Seventy-two patients were included, 78% (56/72) were male mean age was 60 ± 9 years, and 60% (43/72) were phakic. Sixty-five percent (47/72) and 35% (25/72) underwent PnR and PPV, respectively. The mean baseline logarithm of the minimum angle of resolution visual acuity was 1.49 ± 0.76. FAZ circularity was lower after PPV (0.629 ± 0.120) versus PnR (0.703 ± 0.122); P = 0.016. Sixty-six patients had gradable FAF images. Retinal displacement was present in 29% (19/66), 84.2% (16/19) of which had displacement in the macula. FAZ circularity was lower in eyes with displacement in the macula (0.613 ± 0.110) versus those without displacement (0.700 ± 0.124); P = 0.015. There was a moderate negative correlation between 12-month aniseikonia and FAZ circularity(r = -0.262; P = 0.041)., Conclusion: FAZ circularity was lower after PPV and in eyes with retinal displacement in the macula. Circularity was negatively correlated with 12-month aniseikonia scores. FAZ circularity may be another imaging feature to consider postoperatively after RRD repair.

Purpose: This article aims to review current evidence on the development, diagnosis, and management of retinal pigment epithelium (RPE) tear during anti-vascular endothelial growth factor (VEGF) therapy., Methods: Literature searches were performed using MEDLINE/PubMed databases (cut-off date: August 2019)., Results: Three key recommendations were made based on existing literature and clinical experience: 1) Multimodal imaging with color fundus photography, optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence imaging, optical coherence tomography-angiography, and/or fluorescein angiography are recommended to diagnose RPE tear and assess risk factors. Retinal pigment epithelium tears can be graded by size and foveal involvement. 2) Patients at high risk of developing RPE tear should be monitored after each anti-VEGF injection. If risk factors worsen, it is not yet definitively known whether anti-VEGF administration should be more frequent, or alternatively stopped in such patients. Prospective research into high-risk characteristics is needed. 3) After RPE tear develops, anti-VEGF treatment should be continued in patients with active disease (as indicated by presence of intraretinal or subretinal fluid), although cessation of therapy should be considered in eyes with multilobular tears., Conclusion: Although evidence to support the assumption that anti-VEGF treatment contributes to development of RPE tear is not definitive, some data suggest this link., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To provide guidance on the management of patients with neovascular age-related macular degeneration and its subtypes who respond poorly to anti-vascular endothelial growth factor (anti-VEGF) therapy, and to identify cases where suspending anti-VEGF treatment may be warranted., Methods: Through a literature review and the combined knowledge and clinical experience of retinal experts, the Steering Committee of the Bayer-sponsored Vision Academy developed an algorithm for determining when to suspend anti-VEGF treatment of neovascular age-related macular degeneration in cases of futility., Results: Consideration of factors that may cause suboptimal response to anti-VEGF therapy, such as undertreatment or misdiagnosis of the underlying condition, and factors that may preclude continued treatment, such as injection- or drug-induced complications, is necessary for adjusting treatment protocols in patients who respond poorly to anti-VEGF. If poor response to treatment persists after switching to an alternative anti-VEGF agent and no change in response is observed after withholding treatment for a predetermined period of time ("treatment pause"), anti-VEGF treatment may be considered futile and should be suspended., Conclusion: This publication introduces an algorithm to guide the management of neovascular age-related macular degeneration in patients showing poor response to anti-VEGF treatment and provides expert guidance for suspending anti-VEGF treatment in cases of futility.

Purpose: To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema., Methods: A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 μm on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone., Results: Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P < 0.001), best-corrected Snellen visual acuity (P < 0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03)., Conclusion: Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.

Purpose: To identify favorable ocriplasmin candidates from a cohort of idiopathic full thickness macular hole surgery patients., Methods: The records of patients with full thickness macular hole who underwent pars plana vitrectomy surgery between 2011 and 2015 were reviewed. Clinical data collected included patient demographics, pre- and post-operative Snellen visual acuity, optical coherence tomography findings, and lens status. The authors defined "favorable" ocriplasmin candidates as patients with focal vitreomacular traction, no epiretinal membrane, and hole size ≤400 μm. The authors further categorized "optimal" candidates as age ≤65, phakic, no epiretinal membrane, with focal vitreomacular traction, and hole size ≤400 μm., Results: The records of 238 patients were assessed; 30.7% were male while mean age was 68.6 ± 8.3 years. The mean logMAR acuity was 1.2 (Snellen 20/317) preoperatively and 0.90 (Snellen 20/159) postoperatively. Optical coherence tomography findings indicated that 46.5% of the macular holes studied were less than ≤400 μm in size, 14.8% had an epiretinal membrane, and 25.3% had vitreomacular traction. A total of 17.7% of study patients were found to be favorable candidates, whereas 3.8% were optimal ocriplasmin candidates., Conclusion: Only a minority of full thickness macular hole surgical candidates in this cohort would be considered favorable ocriplasmin candidates.