SUPRACHOROIDAL SPACE INJECTION TECHNIQUE: Expert Panel Guidance.

PURPOSE: To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience. METHODS: A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection. RESULTS: Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel. Current clinical evidence and physician experience supported SCS injection as a safe and effective method for delivering retinal and choroidal therapeutics. The panel established consensus on the rationale for SCS injection, including potential benefits relative to other intraocular delivery methods and current best practices in patient preparation, pre- and peri-injection management, SCS-specific injection techniques, and postinjection management and follow-up. CONCLUSION: These expert panel guidelines may support and promote standardization of SCS injection technique, with the goal of optimizing patient safety and outcomes. Some aspects of the procedure may reasonably be modified based on the clinical setting and physician judgment, as well as additional study.

Enhanced durability and evolution of retreatment criteria of intravitreal antivascular endothelial growth factor agents for diabetic macular edema.

PURPOSE OF REVIEW: The increasing prevalence of diabetic macular edema (DME) necessitates an updated review of treatment modalities. While the shift from laser to anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed patient outcomes, benefits of these agents are not fully realized in real-world implementation relative to the setting of controlled clinical trials. This review outlines the evolution of intravitreal anti-VEGF treatment extension protocols for DME that reflect efforts to address treatment adherence challenges while optimizing visual outcomes. RECENT FINDINGS: Recent studies highlight the efficacy of extended-interval dosing with anti-VEGF agents in managing DME. Trials such as RISE/RIDE, VISTA/VIVID, and LUCIDATE have established the foundation of these regimens by demonstrating sustained visual gains with continuous treatment. However, newer trials including PROTOCOL T, KESTREL/KITE, YOSEMITE/RHINE, and PHOTON have furthered this concept, revealing that less frequent dosing of various anti-VEGF agents can maintain similar visual acuity and anatomical outcomes to traditional monthly injections. SUMMARY: The reviewed findings suggest a paradigm shift in DME treatment toward less frequent anti-VEGF injections. This has significant implications for clinical practice, potentially leading to greater adherence to treatment regimens and sustained visual function in patients, while minimizing treatment burden and healthcare costs. Further investigation into the long-term effects of extended dosing intervals is required.

Considerations for the Identification and Management of Geographic Atrophy: Recommendations from an Expert Panel.

Newly approved treatments for patients with geographic atrophy are changing the treatment paradigm, highlighting the need for eye care providers (ECPs) to have a set of recommendations on how to best manage GA patients. Here, we outline how to identify various stages of age-related macular degeneration including geographic atrophy (GA) by examining optimal management scenarios implicating various ECPs and reviewing treatment considerations for patients with GA. Early identification of GA will lead to optimal patient outcomes, while a standardized management scenario will reduce clinical burden among ECPs treating patients with GA.

Conversion to faricimab after prior anti-vascular endothelial growth factor therapy for persistent diabetic macular oedema.

BACKGROUND: To assess the anatomical and functional outcomes in eyes with persistent diabetic macular oedema (pDME) on chronic anti-vascular endothelial growth factor therapy switched to intravitreal faricimab. METHODS: Patients with pDME on chronic anti-vascular endothelial growth factor therapy that were switched to faricimab and received at least three injections at our institution between April 2022 and May 2023 were included in this study. Patients were excluded if they had complete response to previous treatment but were switched to extend treatment intervals if they had steroid or laser treatment for DME within 6 months prior to switch. Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT) and Snellen visual acuity (VA) were obtained before and after three intravitreal faricimab injections. Generalised estimating equations were used to analyse the change in CFT and VA. RESULT: During the study period, 69 eyes of 53 patients met inclusion criteria. The mean age was 68.6±9.0 years. The mean number of injections prior to switch was 18.1±16.0. Pre-switch mean logarithm of the minimal angle of resolution VA was 0.40±0.30 (Snellen equivalent 20/50) and 0.38±0.27 (Snellen equivalent 20/48) after three faricimab injections (p=0.397). Mean CFT improved from 380±155 microns to 323±147 microns (p<0.001). No ophthalmic or systemic adverse events occurred during the study period. CONCLUSIONS: Intravitreal faricimab can improve anatomic outcomes while maintaining visual acuity in eyes with pDME previously treated with anti-VEGF therapy.

Risk of Endophthalmitis Based on Cumulative Number of Anti-VEGF Intravitreal Injections.

PURPOSE: To determine the risk of endophthalmitis in eyes undergoing intravitreal injections (IVIs) of anti-VEGF based on cumulative number of injections per eye. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients from a single center undergoing IVIs of ranibizumab, aflibercept, or bevacizumab. METHODS: Eyes were divided into quartiles based on injection number causative of endophthalmitis between January 1, 2011, and June 1, 2022. MAIN OUTCOME MEASURES: Interquartile clinical outcomes and cumulative risk of endophthalmitis per injection and per eye. RESULTS: A total of 43 393 eyes received 652 421 anti-VEGF injections resulting in 231 endophthalmitis cases (0.035% per injection, 1 in 2857), of which 215 were included. The cumulative endophthalmitis risk increased from 0.0018% (1 in 55 556) after 1 injection to 0.013% (1 in 7692) after 11 injections (0.0012 percentage point change), versus 0.014% (1 in 7143) after 12 injections to 0.025% (1 in 4000) after 35 injections (0.00049 percentage point change), versus 0.025% (1 in 4000) after 36 injections to 0.031% (1 in 3226) after 66 injections (0.00017 percentage point change), versus 0.031% (1 in 3226) after 63 injections to 0.033% (1 in 3030) after 126 injections (0.000042 percentage point change) (P < 0.001). Likewise, the cumulative endophthalmitis risk per eye increased from 0.028% (1 in 3571) to 0.20% (1 in 500) between injections 1 and 11 (0.018 percentage point change), versus 0.21% (1 in 476) to 0.38% (1 in 263) between injections 12 and 35 (0.0075 percentage point change), versus 0.38% (1 in 263) to 0.46% (1 in 217) between injections 36 and 66 (0.0026 percentage point change), versus 0.46% (1 in 217) to 0.50% (1 in 200) between injections 67 and 126 (0.00063 percentage point change) (P < 0.001). CONCLUSIONS: The cumulative endophthalmitis risk per injection and per eye increased with greater number of injections received but appeared to do so at a higher rate during earlier injections and at a lower rate further into the treatment course. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

OCT-Based Description of Spontaneous Reattachment of Macula-Off Tractional Retinal Detachment With Significant Vision Improvement.

Purpose: To describe the clinical course and optical coherence tomography (OCT) features of patients with spontaneous reattachment of macula-off tractional retinal detachments (TRDs). Methods: Findings on clinical examination and OCT were evaluated. Results: Four eyes of 4 patients with a history of macula-off TRD secondary to diabetic retinopathy (n = 3) or sickle cell retinopathy (n = 1) were included. OCT confirmed spontaneous resolution of the macular RD without complete posterior vitreous separation in all eyes. The median (interquartile range [IQR]) time from TRD diagnosis to OCT-confirmed foveal reattachment was 6 months (10.25; range, 1-12 months). The median logMAR visual acuity (VA) at the time of macula-off TRD was 0.544 (IQR, 0.452; Snellen 20/70), which improved to 0.350 (IQR, 0.156; Snellen 20/45), with reattachment characterized by OCT (P = .068). Conclusions: Nonsurgical spontaneous retinal reattachment and significant VA improvement can occur in eyes with a TRD, albeit rarely. In these cases, no OCT evidence of posterior vitreous separation was found, suggesting that some relaxation of the contractile fibrovascular membranes occurred.

Exudation in Patients With Neovascular Age-Related Macular Degeneration Treated With the Port Delivery System or Monthly Injections.

PURPOSE: To evaluate for the presence, severity, and type of exudation at each study visit for a subgroup of patients with neovascular age-related macular degeneration from the Archway and Portal trials. DESIGN: Retrospective analysis of prospectively obtained data. METHODS: Spectral-domain optical coherence tomography scans from each study visit of 44 patients from the Port Delivery System (PDS) arm and 32 patients from the monthly injection arm of Archway were evaluated, and composites of horizontal scans through the fovea were created. Each composite was graded for the presence, type, and severity of exudation and impact on best-corrected visual acuity. RESULTS: After PDS implantation, 20 of 44 eyes (45%) never showed any exudation in the fovea, 2 (5%) never showed exudation in the fovea but had several missed visits, whereas 15 (34%), 3 (7%), and 4 (9%) showed mild, moderate, or severe exudation at 1 or more study visits, respectively. When exudation was present, it was most commonly subretinal fluid (50%). Of 32 patients randomized to monthly injections, 15 (47%) had no exudation in the fovea during monthly injections or after PDS implantation. Fluctuation of exudation in the fovea over time was seen in some patients after PDS implantation or during monthly injections with little or no identifiable impact on best-corrected visual acuity. In the 7 eyes with moderate or severe exudation in the fovea after PDS implantation, final vision was good in 5 (20/25 in 3, 20/40 in 1, and 20/50 in 1) and 2 had reduced vision from submacular hemorrhage. CONCLUSIONS: The PDS provides excellent control of exudation in the fovea in patients with neovascular age-related macular degeneration, and when exudation occurs, it often resolves without a negative impact on vision.

KESTREL and KITE Phase 3 Studies: 100-Week Results With Brolucizumab in Patients With Diabetic Macular Edema.

PURPOSE: To report the 100-week outcomes from the KESTREL and KITE trials. DESIGN: Two phase 3, double-masked, active-controlled, randomized trials. METHODS: Patients with diabetic macular edema (DME) were randomized 1:1:1 to brolucizumab 3 mg/6 mg (BRO3/BRO6) or aflibercept 2 mg (AFL) in KESTREL (N = 566) or 1:1 to BRO6 or AFL in KITE (N = 360). BRO3/BRO6 arms received 5 loading doses every 6 weeks (q6w) followed by q12w dosing, with an option to adjust to q8w at predefined disease activity assessment visits. In KITE, at week 72, based on the disease stability assessment, treatment intervals could be extended by 4 weeks in the BRO6 arm. AFL arms received 5 monthly loading doses followed by fixed q8w dosing. RESULTS: At week 100, change from baseline in BCVA (letters) was +8.8 for BRO6 and +10.6 for AFL in KESTREL; and +10.9 for BRO6 and +8.4 for AFL in KITE. In both studies, fewer BRO6 subjects had intraretinal fluid and/or subretinal fluid than AFL subjects. Results were achieved with 32.9% (KESTREL) and 47.5% (KITE) of BRO6 subjects maintained on q12w and q12w/q16w dosing, respectively. Intraocular inflammation rates for BRO6 vs AFL were 4.2% vs 1.1% (KESTREL) and 2.2% vs 1.7% (KITE), of which retinal vasculitis rates were 0.5% vs 0% in KESTREL, with no cases in KITE. Retinal vascular occlusion rates were 1.6% vs 0.5% (KESTREL) and 0.6% in both treatment arms in KITE. CONCLUSIONS: Results show the long-term efficacy and durability of brolucizumab in improving visual and anatomical outcomes in DME; the overall safety profile of brolucizumab remained unchanged through year 2.

Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study.

PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel2). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients undergoing surgery for MacTel2-associated full-thickness macular hole (MTMH). METHODS: Standardized data collection sheet distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH. RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% female, 72% White, 21% East or South Asian, 2% African American, and 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peeling, preoperative visual acuity (VA) was 0.667 ± 0.423 logarithm of the minimum angle of resolution (logMAR). Minimum hole diameter (MHD) was 305.5 ± 159.4 µm (range, 34-573 µm). Sixteen of 34 ILM peels (47%) resulted in MTMH closure. At postoperative month 6, VA was stable at 0.602 ± 0.516 logMAR (P = 0.65). VA improved by at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was 0.878 ± 0.552 logMAR. MHD was 440.8 ± 175.5 µm (range, 97-697 µm), which was significantly larger than for ILM peels (P < 0.01). Twenty of 22 ILM flaps (90%) resulted in MTMH closure, which was significantly higher than for ILM peels (P < 0.01). At postoperative month 6, VA improved to 0.555 ± 0.405 logMAR (P < 0.05). VA improved by at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was 1.460 ± 0.391 logMAR. MHD was 390.2 ± 203.7 µm (range, 132-687 µm). All 5 ARTs (100%) resulted in MTMH closure. At postoperative month 6, VA was stable at 1.000 ± 0.246 logMAR (P = 0.08). Visual acuity improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. Internal limiting membrane flaps achieved better anatomic and functional outcomes than ILM peeling alone. Autologous retinal transplantation may be an option for refractory MTMHs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical Outcomes of Faricimab in Patients with Previously Treated Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the anatomic and functional outcomes in eyes with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF therapy in response to intravitreal faricimab. DESIGN: Retrospective, interventional, consecutive case series. SUBJECTS: Patients with previously treated nAMD who received ≥ 4 consecutive injections of faricimab were included. The study period was from March through November 2022. METHODS: Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT), maximum fibrovascular pigment epithelial detachment (fvPED) height, and Snellen visual acuity (VA) were obtained. Generalized estimating equations were used to analyze the change in CFT, maximum fvPED height, and logarithm of the minimum angle of resolution VA. MAIN OUTCOME MEASURES: Change in CFT, maximum fvPED height, and Snellen VA before faricimab and after ≥ 4 faricimab intravitreal injections. RESULTS: During the study period, 218 eyes of 191 patients met inclusion criteria. Mean age was 79.9 (range, 70.6-89.2) years. The mean number of intravitreal anti-VEGF injections received before faricimab was 34.2 (range, 6.4-62). The following results were found after ≥ 4 faricimab injections. Mean logarithm of the minimum angle of resolution VA before switching to faricimab was 0.58 (Snellen VA ∼20/76; range, 20/22-20/264) and was 0.55 (Snellen VA ∼20/71; range, 20/21-20/235; P = 0.20) after switching. Mean maximum fvPED height was 195.0 (range, 50.2-339.8) µm before switching to faricimab and improved to 165.0 (range, 33.6-296.4; P < 0.001) µm after switching. Mean CFT was 354.8 (range, 184.7-524.9) µm before switching to faricimab and improved to 306.6 (range, 144.4-468.8; P < 0.001) after switching. The proportion of eyes with intraretinal fluid was 36.7% (80/218 eyes) before switching, and decreased to 24.8% (54/218 eyes, P < 0.001) after switching. The proportion of eyes with subretinal fluid was 53.2% (116/218 eyes) before switching and decreased to 26.6% (58/218 eyes, P < 0.001) after switching. CONCLUSIONS: Intravitreal faricimab may improve anatomic outcomes in patients with previously treated nAMD, while maintaining VA in the short-term. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Safety and efficacy of ixoberogene soroparvovec in neovascular age-related macular degeneration in the United States (OPTIC): a prospective, two-year, multicentre phase 1 study.

Background: Gene therapy, successfully used in rare, monogenetic disorders, may prove to be a durable management approach for common, polygenetic conditions, including neovascular age-related macular degeneration (nAMD). Repeated injections, oftentimes monthly, and possibly for decades, of vascular endothelial growth factor antagonists (anti-VEGF), is the standard for nAMD. We hypothesised that an in-office, intravitreal administration of ixoberogene soroparvovec (ixo-vec, formerly ADVM-022), a single-dose gene therapy encoding for the proven anti-VEGF protein, aflibercept, would transform retinal cells to continually produce aflibercept to minimise treatment burden in nAMD. Methods: In this two-year, open-label, prospective, multicentre phase 1 study, patients with nAMD responding to anti-VEGF were assigned to four cohorts differing by ixo-vec dose (2 × 1011 vs 6 × 1011 vector genomes (vg/eye)) and prophylactic steroids (oral prednisone vs topical difluprednate). The primary outcome was the type, severity, and incidence of ocular and systemic adverse events (AEs); secondary endpoints included vision, central subfield thickness (CST), and the number of supplemental injections. This study was registered with ClinicalTrials.gov, NCT03748784. Findings: Thirty patients with nAMD were enrolled between November 14, 2018 and June 30, 2020 at nine study sites in the United States. No systemic ixo-vec related AEs were noted. Across both dose groups the most common adverse event was anterior chamber cell, which was reported in 11 participants in the 6 × 1011 dose group and in 7 participants in the 2 × 1011 dose group; intraocular inflammation was responsive to topical corticosteroids, with no anterior chamber cells or vitreous cells observed in 2 × 1011 vg/eye patients at the end of the study. Vision and CST remained stable throughout two years with annualised anti-VEGF injections reduced by 80% (10.0 mean annualised anti-VEGF injections to 1.9) in 2 × 1011 vg/eye and 98% (9.8 mean annualised anti-VEGF injections to 0.2) in 6 × 1011 vg/eye cohorts. Interpretation: Ixo-vec was generally well-tolerated, maintained vision, and improved anatomical outcomes in nAMD, with a substantial reduction in anti-VEGF injections. A single administration of an in-office gene therapy, with vectorised protein with an already established clinical benefit, has the potential to revolutionise the management of common ocular disorders requiring ongoing, frequent therapeutic interventions. Funding: Adverum Biotechnologies.

Optimizing Visual Outcomes in Patients With Neovascular Age-Related Macular Degeneration: the Potential Value of Sustained Anti-VEGF Therapy.

Neovascular age-related macular degeneration (nAMD) leads to irreversible central vision loss if untreated. Frequent administration of anti-vascular endothelial growth factor (anti-VEGF) injections inhibits disease activity with excellent functional and morphological benefits. However, these injections pose a heavy therapeutic burden, and treatment discontinuation is common. Although current anti-VEGF treatment paradigms, such as treat-and-extend, mitigate treatment burden while still leading to acceptable vision outcomes, they fail to sustain initial vision gains for many. Novel longer-acting anti-VEGF therapies may reduce the overall burden on nAMD patients. Gene therapy might offer a paradigm shift by providing continuous expression of anti-VEGF, potentially decreasing treatment requirements and improving long-term vision outcomes. [Ophthalmic Surg Lasers Imaging Retina 2023;54:654-659.].

Geographic Atrophy Management Consensus (GA-MAC): a Delphi panel study on identification, diagnosis and treatment.

BACKGROUND/AIMS: With a paradigm shift in geographic atrophy (GA) treatments now available, establishing consensus on the identification and diagnosis of the disease along with considerations for management of patients with GA will assist eye care professionals (ECP) in their day-to-day practices, leading to improved patient outcomes. METHODS: A modified Delphi panel process (Geographic Atrophy Management Consensus) consisting of three total surveys and one virtual live meeting held between survey 2 and survey 3. Data were collected from July to October 2022. Participants included expert members of the eye care community that have demonstrated outstanding leadership among peers: a steering committee with three ECPs and a 15-member panel divided between five optometrists, five comprehensive ophthalmologists and five retina specialists. Consensus on statements related to the management of patients with GA was calculated using the RAND/UCLA Appropriateness Method. RESULTS: At the conclusion of the third survey, consensus was reached on 91% of the 77 statements. Critical consensus topics include: (1) optical coherence tomography as the favoured method to diagnose and monitor GA, (2) preferred practice patterns regarding referral of patients to retina specialists and (3) treatment criteria given the advent of emerging therapeutics for GA. CONCLUSIONS: Generating awareness of early signs of disease development, progression and identifying the best tools to evaluate GA establishes ideal management and referral strategies. Given the paradigm shift in GA management driven by approved therapies, coupled with the fact that the disease is progressive resulting in devastating vision loss, these strategies are critical to ensure best overall outcomes.

Outcomes of Intentionally Suspending Treatment in Eyes With Advanced Neovascular Age-Related Macular Degeneration.

PURPOSE: To determine the outcomes of intentionally suspending anti-vascular endothelial growth factor (anti-VEGF) injections in eyes with advanced neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective cohort study. METHODS: The study sample comprised 93 patients with nAMD and best available Snellen visual acuity (VA) ≤20/400 in which anti-VEGF treatment was suspended by the treating physician. VA and optical coherence tomography (OCT) characteristics were evaluated to determine visual and anatomical outcomes up to 24 months after treatment suspension. RESULTS: A total of 93 eyes from 93 patients who had received a mean of 16 anti-VEGF injections over a mean of 962 (SD 562) days were included. Comparing the treatment suspension visit to 24 months later, no significant change in mean central foveal thickness (163 [SD 118, range 19-704] µm vs 164 [SD 217, range 19-1468], P = .97), greatest lesion diameter (2547 [SD 1294, range 134-5707] µm vs 2442 [SD 1158, range 421-5305] µm, P = .43), greatest lesion thickness (194 [SD 136, range 0-618] µm vs 205 [SD 131, range 0-573] µm, P = .40), or VA (1.87 [SD 0.37], 20/1482, vs 1.94 [SD 0.28], 20/1741, P = .16) was found. In total, 7 eyes (7.5%) restarted treatment following a mean of 977 (SD 450) days after treatment suspension. CONCLUSIONS: Suspension of anti-VEGF injections in eyes with advanced nAMD and VA ≤20/400 may be reasonable in cases where the treating physician deems additional treatment is unlikely to provide benefit. Although the visual and anatomical findings remained stable after treatment suspension in most, a small number restarted anti-VEGF therapy, suggesting that eyes should still be monitored for disease progression.

VITRECTOMY FOR VITREOUS HEMORRHAGE ASSOCIATED WITH RETINAL VEIN OCCLUSION: Visual Outcomes, Prognostic Factors, and Sequelae.

PURPOSE: To report the outcomes of pars plana vitrectomy for vitreous hemorrhage (VH) associated with retinal vein occlusion and to identify prognostic indicators. METHODS: Interventional, retrospective consecutive case series between 2015 and 2021. RESULTS: The study included 138 eyes of 138 patients (64 female and 74 male); 81 patients had branch retinal vein occlusion and 57 had central retinal vein occlusion. The mean age was 69.8 years. The mean duration between the diagnosis of VH and surgery was 79.6 ± 115.3 (range, 1-572) days. The mean follow-up was 27.2 months. The logarithm of the minimum angle of resolution visual acuity significantly improved from 1.95 ± 0.72 (Snellen equivalent, 20/1782) to 0.99 ± 0.87 (20/195) at 6 months and to 1.06 ± 0.96 (20/230) at the final visit (both P < 0.001). The visual acuity at 6 months improved by three or more lines in 103 eyes (75%). Postoperative complications during follow-up included recurrent VH in 16 eyes (12%) (of which 8 eyes underwent reoperations), rhegmatogenous retinal detachment in six eyes (4%), and new neovascular glaucoma in three eyes (2%). Worse final visual acuity was significantly associated with older age ( P = 0.007), concurrent neovascular glaucoma ( P < 0.001), central retinal vein occlusion ( P < 0.001), worse preoperative visual acuity ( P < 0.001), postoperative new neovascular glaucoma ( P = 0.021), and postoperative retinal detachment ( P < 0.001). The duration of VH was not associated with visual outcomes ( P = 0.684). Preoperative antivascular endothelial growth factor injections and tamponade did not prevent postoperative recurrent VH. CONCLUSION: Pars plana vitrectomy is effective for VH associated with retinal vein occlusion, regardless of the duration of hemorrhage. However, pre-existing risk factors and postoperative sequelae may limit visual recovery.

Risk Factors and Outcomes of Postoperative Macular Hole Formation after Vitrectomy for Myopic Traction Maculopathy: SCHISIS Report No. 2.

PURPOSE: To evaluate the incidence, pathogenesis, risk factors, and treatment outcomes of postoperative macular hole (MH) after pars plana vitrectomy (PPV) for myopic traction maculopathy (MTM). DESIGN: Multicenter, interventional, retrospective case series. SUBJECTS: Consecutive eyes that underwent PPV for MTM with a minimum 6-month follow-up. METHODS: We investigated the characteristics and treatment outcomes of postoperative MH after MTM surgery. MAIN OUTCOME MEASURES: Incidence, risk factors, and anatomic and visual outcomes of postoperative MH. RESULTS: We included 207 eyes (207 patients) with a mean follow-up of 25.9 months. During follow-up, 24 (11.6%) eyes developed MH (10 with concurrent MH retinal detachment); 15 eyes within 30 days (early), 4 eyes between 31 and 180 days (intermediate), and 5 eyes after 180 days (late). Logistic regression analysis revealed male gender (odds ratio [OR], 2.917; 95% confidence interval [CI], 1.198-7.100; P = 0.018), thinner preoperative choroidal thickness (OR, 0.988; 95% CI, 0.976-1.000; P = 0.048), and use of indocyanine green for internal limiting membrane peeling (OR, 2.960; 95% CI, 1.172-7.476; P = 0.022) as significant risk factors for postoperative MH. Internal limiting membrane peeling with a fovea-sparing technique tended to protect against postoperative MH, but it was not statistically significant (P = 0.096), because 1 eye still developed MH. Postoperative MHs were treated by observation (6 eyes), in-office octafluoropropane (C3F8) gas injection (7 eyes), or PPV (11 eyes). Macular hole closure was achieved in 20 eyes (83%). The hole closure rate was 67% (4/6 eyes) after observation, 71% (5/7 eyes) after C3F8 gas injection, and 91% (10/11 eyes) after PPV. However, visual outcomes were significantly worse for eyes with postoperative MH than those without (0.38 ± 0.43 vs. 0.68 ± 0.46; P = 0.002). CONCLUSIONS: Postoperative MH may occur in 11.6% of patients with MTM at any time after surgery. Retreatment resulted in relatively favorable anatomic closure but unfavorable visual outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk Factors for Epiretinal Membrane After Rhegmatogenous Retinal Detachment Repair: Quantitative Ultra Widefield Imaging Analysis.

BACKGROUND AND OBJECTIVE: To utilize quantitative ultra widefield retinal imaging to investigate the risk factors associated with the incidence and severity of postoperative epiretinal membrane (ERM) in patients who underwent primary rhegmatogenous retinal detachment (RRD) repair. PATIENTS AND METHODS: This retrospective study included patients who underwent pars plana vitrectomy (PPV) with scleral buckle (SB) for RRD, without a prior history of ERM, and who underwent ultra widefield imaging postoperatively between June 2020 and February 2022. The size and location (distance from the macula) of the drainage retinotomy and the area of peripheral pathology, including retinal breaks and laser scars, were quantitatively measured with cloud-based software. The severity of postoperative ERM formation at 6 months was graded from grade 1 to 4. We investigated the risk factors that were significantly associated with the incidence and severity of postoperative ERM at 6 months. RESULTS: We included 80 eyes (80 patients) in this study. Postoperative ERM developed in 37 eyes (46%) at 6 months. The severity of ERM was grade 1 in 24 eyes (65%), grade 2 in 6 eyes (16%), grade 3 in 4 eyes (11%), and grade 4 in 3 eyes (8%). Postoperative ERM was not associated with the presence or the location of drainage retinotomy (P = 0.836 and 0.820, respectively). However, it was significantly associated with larger surface area of drainage retinotomy (P = 0.039). In addition, postoperative ERM was significantly associated with a larger area of peripheral pathology (P = 0.012), a larger extent of RRD (P = 0.013), vitreous hemorrhage (P = 0.026), redetachment within 6 months (P = 0.022), use of silicone oil as a tamponade (P = 0.047), and number of surgeries within 6 months (P = 0.027). These factors, in addition to 360° endolaser, were also significantly associated with the severity of postoperative ERM. In multivariable linear regression analysis, the only variable that remained statistically significant was the size of the drainage retinotomy (P = 0.023). CONCLUSION: The pathogenesis of postoperative ERM is multifactorial. Large drainage retinotomies may increase the risk of ERM formation. [Ophthalmic Surg Lasers Imaging Retina 2023;54:206-216.].

Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results.

PURPOSE: To report 2-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD). DESIGN: Phase 3, randomized, multicenter, open-label, active-comparator-controlled trial. PARTICIPANTS: Patients with previously treated nAMD diagnosed within 9 months of screening and responsive to anti-vascular endothelial growth factor therapy. METHODS: Patients were randomized 3:2 to PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab). Patients were followed through 4 complete refill-exchange intervals (∼2 years). MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline averaged over weeks 44 and 48, weeks 60 and 64, and weeks 88 and 92 (noninferiority margin, -3.9 ETDRS letters). RESULTS: The PDS Q24W was noninferior to monthly ranibizumab, with differences in adjusted mean change in BCVA score from baseline averaged over weeks 44/48, 60/64 and 88/92 of -0.2 (95% confidence interval [CI], -1.8 to +1.3), +0.4 (95% CI, -1.4 to +2.1) and -0.6 ETDRS letters (95% CI, -2.5 to +1.3), respectively. Anatomic outcomes were generally comparable between arms through week 96. Through each of 4 PDS refill-exchange intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS Q24W patients assessed did not receive supplemental ranibizumab treatment. The PDS ocular safety profile was generally unchanged from primary analysis. Prespecified ocular adverse events of special interest (AESI) were reported in 59 (23.8%) PDS and 17 (10.2%) monthly ranibizumab patients. The most common AESI reported in both arms was cataract (PDS Q24W, 22 [8.9%]; monthly ranibizumab, 10 [6.0%]). Events in the PDS Q24W arm included (patient incidence) 10 (4.0%) conjunctival erosions, 6 (2.4%) conjunctival retractions, 4 (1.6%) endophthalmitis cases, and 4 (1.6%) implant dislocations. Serum ranibizumab sampling showed that the PDS continuously released ranibizumab over the 24-week refill-exchange interval and ranibizumab serum concentrations were within the range experienced with monthly ranibizumab. CONCLUSIONS: The PDS Q24W showed noninferior efficacy to monthly ranibizumab through approximately 2 years, with approximately 95% of PDS Q24W patients not receiving supplemental ranibizumab treatment in each refill-exchange interval. The AESIs were generally manageable, with learnings continually implemented to minimize PDS-related AEs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Biosimilars for retinal diseases: United States-Europe awareness survey (Bio-USER - survey).

PURPOSE: To assess the awareness of biosimilar intravitreal anti-VEGF agents among retina specialists practicing in the United States (US) and Europe. METHODS: A 16-question online survey was created in English and distributed between Dec 01, 2021 and Jan 31, 2022. A total of 112 respondents (retinal physicians) from the US and Europe participated. RESULTS: The majority of the physicians (56.3%) were familiar with anti-VEGF biosimilars. A significant number of physicians needed more information (18.75%) and real world data (25%) before switching to a biosimilar. About one half of the physicians were concerned about biosimilar safety (50%), efficacy (58.9 %), immunogenicity (50%), and their efficacy with extrapolated indications (67.8 %). Retinal physicians from the US were less inclined to shift from off-label bevacizumab to biosimilar ranibizumab or on-label bevacizumab (if approved) compared to physicians from Europe (p=0.0001). Furthermore, physicians from the US were more concerned about biosimilar safety (p=0.0371) and efficacy compared to Europe (p= 0.0078). CONCLUSIONS: The Bio-USER survey revealed that while the majority of retinal physicians need additional information regarding the safety, efficacy and immunogenicity when making clinical decisions regarding their use. Retinal physicians from US are more comfortable in continuing to use off-label bevacizumab compared to physicians from Europe.