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Purpose: Complications associated with intravitreal anti-VEGF therapies are reported inconsistently in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process., Design: Systematic review and Delphi consensus process., Participants: Twenty-five international retinal specialists participated in the Delphi consensus survey., Methods: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists who voted on inclusion, exclusion, rephrasing, and addition of complications. Furthermore, surveys determined specifiers for the selected complications. This iterative process helped to refine the final classification system., Main Outcome Measures: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration., Results: After screening 18 229 articles, 130 complications were categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 complications (70%) after 3 rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 complications (52%) in the final list. A total of 14 complications (11%) met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds also were excluded from the final classification system after the Delphi process terminated. In addition, 47 of 75 proposed complication specifiers (63%) were included based on participant agreement., Conclusions: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

There have been recent advances in basic research and clinical studies in polypoidal choroidal vasculopathy (PCV). A recent, large-scale, population-based study found systemic factors, such as male gender and smoking, were associated with PCV, and a recent systematic review reported plasma C-reactive protein, a systemic biomarker, was associated with PCV. Growing evidence points to an association between pachydrusen, recently proposed extracellular deposits associated with the thick choroid, and the risk of development of PCV. Many recent studies on diagnosis of PCV have focused on applying criteria from noninvasive multimodal retinal imaging without requirement of indocyanine green angiography. There have been attempts to develop deep learning models, a recent subset of artificial intelligence, for detecting PCV from different types of retinal imaging modality. Some of these deep learning models were found to have high performance when they were trained and tested on color retinal images with corresponding images from optical coherence tomography. The treatment of PCV is either a combination therapy using verteporfin photodynamic therapy and anti-vascular endothelial growth factor (VEGF), or anti-VEGF monotherapy, often used with a treat-and-extend regimen. New anti-VEGF agents may provide more durable treatment with similar efficacy, compared with existing anti-VEGF agents. It is not known if they can induce greater closure of polypoidal lesions, in which case, combination therapy may still be a mainstay. Recent evidence supports long-term follow-up of patients with PCV after treatment for early detection of recurrence, particularly in patients with incomplete closure of polypoidal lesions., (Copyright © 2023 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Purpose: To develop and validate OCT and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti-vascular endothelial growth factor (VEGF) monotherapy and to determine whether OCT alone can be used to guide photodynamic therapy (PDT) treatment., Design: Clinical study evaluating diagnostic accuracy., Participants: Patients with nAMD who received 3-month anti-VEGF monotherapy but had persistent activity defined as subretinal fluid or intraretinal fluid at month 3 assessments., Methods: In phase 1, international retina experts evaluated OCT and CFP of eyes with nAMD to identify the presence or absence of features due to PCV. The performance of individual and combinations of these features were compared with ICGA. In phase 2, these criteria were applied to an independent image set to assess generalizability. In a separate exercise, retinal experts drew proposed PDT treatment spots using only OCT and near-infrared (NIR) images in eyes with PCV and persistent activity. The location and size of proposed spot were compared with ICGA to determine the extent of coverage of polypoidal lesions (PLs) and branching neovascular network (BNN)., Main Outcome Measures: Sensitivity and specificity of CFP and OCT criteria to differentiate PCV from nAMD and accuracy of coverage of OCT-guided PDT compared with ICGA., Results: In eyes with persistent activity, the combination of 3 non-ICGA-based criteria (sharp-peaked pigment epithelial detachment [PED], subretinal pigment epithelium [RPE] ring-like lesion, and orange nodule) to detect PCV showed good agreement compared with ICGA, with an area under the receiver operating characteristic curve of 0.85. Validation using both an independent image set and assessors achieved an accuracy of 0.77. Compared with ICGA, the OCT-guided PDT treatment spot covered 100% of PL and 90% of the BNN., Conclusions: In nAMD eyes with persistent activity, OCT and CFP can differentiate PCV from typical nAMD, which may allow the option of adjunct PDT treatment. Furthermore, OCT alone can be used to plan adjunct PDT treatment without the need for ICGA, with consistent and complete coverage of PL., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the impact of delaying anti-vascular endothelial growth factor (VEGF) treatment of active disease at any point during a patient's treatment journey on clinical outcomes in a real-world cohort of patients with neovascular age-related macular degeneration (nAMD)., Design: Longitudinal cohort study., Participants: Consecutive treatment-naive nAMD eyes commencing anti-VEGF monotherapy (bevacizumab, ranibizumab, or aflibercept) from January 2014 from a tertiary eye center in Singapore., Methods: We conducted a real-world study using registry data comparing delayed re-treatment (defined as not receiving treatment at 2 or more monitoring visits when disease was graded as active) versus timely re-treatment (defined as receiving treatment when disease was active)., Main Outcome Measures: The primary outcome was the change in visual acuity (VA) in the timely and delayed re-treatment groups at 12 months., Results: Data from 286 eyes were included and categorized into the timely (188 [66%]) or the delayed (98 ([34%]) group. The mean numbers of anti-VEGF injections over 12 months were similar: 5.6 (standard deviation [SD], 2.9) versus 4.9 (SD, 3.2; P = 0.11) for the timely and delayed groups, respectively. Timely treated patients showed larger gains in VA (6.4 letters [SD, 8.1 letters] vs. 1.2 letters [SD, 5.3 letters; P = 0.04), a higher proportion with VA of 6/12 or better (30% vs. 8%; P = 0.01), and greater reduction in OCT-measured central subfield thickness (135 μm [SD, 154 μm] vs. 87.8 μm [SD, 129 μm]; P = 0.04) at 12 months. A longer delay between detection of active disease and re-treatment was associated with poorer vision outcomes (0.02-letter decrease/day; P = 0.03; R 2  = 0.29)., Conclusions: Although it has been established that adequate numbers of injections are required for favorable outcomes, timely re-treatment of active disease also is important. This should be emphasized to patients to ensure optimal outcomes in real-world clinical settings., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report long-term changes in intraocular pressure (IOP) in eyes receiving vascular endothelial growth factor (VEGF) inhibitors for various retinal conditions over 12 and 24 months in routine clinical practice., Design: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness!, Participants: Treatment-naïve eyes receiving monotherapy with VEGF inhibitors (ranibizumab [0.5 mg], aflibercept [2 mg], or bevacizumab [1 mg]) with at least 3 injections from December 2013 through December 31, 2018, and at least 12 months of follow-up., Methods: Intraocular pressure was measured at each clinical visit for all eyes as part of routine practice., Main Outcome Measures: The primary outcome was the mean change in IOP (in millimeters of mercury) at 12 months. The following secondary IOP outcome measures were investigated at 12 and 24 months: (1) mean change in IOP from baseline and (2) proportion of clinically significant IOP increase defined as an elevation of at least 6 mmHg to an IOP of more than 21 mmHg at any point during the follow-up., Results: We identified 3429 treatment-naïve eyes (395 receiving bevacizumab, 1138 receiving aflibercept, and 1896 receiving ranibizumab) with complete IOP data from 3032 patients with 12 months of follow-up data, of which 2125 (62%) had 24 months of follow-up data. The overall mean IOP change was -0.5 mmHg (95% confidence interval CI, -0.6 to -0.3 mmHg) at 12 months and -0.4 mmHg (95% CI, -0.6 to -0.3 mmHg) at 24 months, whereas the proportions of clinically significant IOP increases were 5.6% and 8.8%, respectively. A lower mean IOP change and fewer IOP elevations at 12 and 24 months was observed in eyes receiving aflibercept than in those receiving bevacizumab and ranibizumab (P ≤ 0.01 for both comparisons at each time point and outcome). Eyes with pre-existing glaucoma demonstrated more IOP increases over 12 and 24 months (odds ratio [OR], 2.2 [95% CI, 1.2-3.8; P = 0.012] and 2.1 [95% CI, 1.1-3.8; P = 0.025], respectively)., Conclusions: Mean IOP did not change significantly from baseline to 12 and 24 months in eyes receiving VEGF inhibitors, whereas clinically significant IOP elevations occurred in a small proportion of eyes. Aflibercept was associated with fewer clinically significant IOP elevations, whereas eyes with pre-existing glaucoma were at a higher risk., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the 12-month real-world visual and disease activity outcomes of eyes with polypoidal choroidal vasculopathy (PCV) treated with a combination of photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) injections (combination group) versus those eyes treated with anti-VEGF monotherapy alone with rescue PDT being used as required (monotherapy group)., Design: Database comparative observational study., Participants: Eyes with PCV as graded in the Fight Retinal Blindness! database from Australia, New Zealand, Singapore, and Switzerland., Methods: Clinical information from a multisite, international registry of neovascular age-related macular degeneration was analyzed with an intention-to-treat approach., Main Outcome Measures: Primary outcome measure was the change in visual acuity in logMAR letters over 12 months between the two groups analyzed with intention-to-treat approach., Results: Forty-one and 152 eyes received combination therapy and anti-VEGF monotherapy, respectively. All anti-VEGF agents were pooled, and bevacizumab represented 66.1% of injections administered. The adjusted mean change in visual acuity between the combination group and monotherapy group at 12 months was +16.9 letters (95% confidence interval [CI], 10.6-23.3 letters) and +8.2 letters (95% CI, 5.2-11.3 letters), respectively (P = 0.02). Proportion of inactive lesions and mean time to inactivity was 85.3% and 80.7 days (95% CI, 62.8-98.5 days), respectively, in the combination group compared with 76.8% and 150.4 days (95% CI, 132.8-168.0 days), respectively, in the monotherapy group (P = 0.01). The mean number of injections of anti-VEGF agent between the combination and monotherapy groups was 4.3 injections (95% CI, 3.6-5.2 injections) and 6.4 injections (95% CI, 5.9-6.9 injections), respectively (P = 0.01)., Conclusions: The real-world outcomes for treatment of PCV showed larger gains in vision, higher proportion of inactive lesions, quicker time to inactivity, and fewer injections administered in the combination group compared with the monotherapy group. These findings are consistent with current evidence reporting the advantages of combination therapy for PCV., (Copyright © 2018 American Academy of Ophthalmology. All rights reserved.)

Purpose: To describe the clinical characteristics and outcome of eyes with extrafoveal polypoidal choroidal vasculopathy (PCV) treated with argon laser., Design: Prospective cohort, noninterventional study., Methods: A prospective study of Asian patients with extrafoveal PCV, confirmed on indocyanine green angiography and treated with argon laser with and without anti-vascular endothelial growth factor (VEGF) therapy. Patients were followed-up over 12 months with visual, angiographic, and structural outcomes recorded., Results: Of the 93 eyes with PCV at baseline, 33 eyes (35.5%) in 31 patients had extrafoveal involvement and were treated with argon laser. Foveal involvement with fluid or blood at baseline was apparent in 23 eyes (69.7%), despite the extrafoveal location of 1 or more polyps. Of these 33 eyes, 12 (36.4%) also received anti-VEGF injections (median, 2.5 injections) over the 12-month period. Two eyes received photodynamic therapy rescue during subsequent follow-up and were excluded for visual outcome analysis. In the remaining 31 eyes, mean visual acuity improved from 0.57 logarithm of the minimal angle of resolution (logMAR) units (range, 0.00 to 2.0 logMAR; standard deviation, 0.51 logMAR) at baseline to 0.39 logMAR (range, 0.00 to 2.0 logMAR; standard deviation, 0.43 logMAR) at month 12 (P = .01), with a mean gain in visual acuity of 9.0 letters at month 12. Stable or improved vision (defined as losing 5 letters or fewer) was achieved in 28 eyes (90.3%). Use of anti-VEGF was associated with significantly thicker central subfield at baseline (347.6 vs 258.1 μm; P = .02) and resulted in similar vision and OCT results at month 3 and 12 compared with eyes that did not receive anti-VEGF., Conclusions: Argon laser treatment with selected use of anti-VEGF therapy achieves stable or improved visual outcome in most eyes with extrafoveal PCV, including eyes with fluid or blood affecting the fovea at presentation., (Copyright © 2013 Elsevier Inc. All rights reserved.)