Subfoveal neurosensory detachment flattening and observe (SNF-Ob) approach for the management of Ci-DMO - a multicentric study.

PURPOSE: To understand subfoveal neurosensory detachment flattening and observe (SNF-Ob) strategy and its relationship with visual acuity in the management of centre-involved diabetic macular oedema (Ci-DMO). METHODS: This was a multicentric retrospective observational study. We reviewed data of 188 eyes of 130 patients who presented with Ci-DMO with subfoveal neurosensory detachment (NSD) and treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents or steroids. The primary outcome was best corrected visual acuity (BCVA) measured at the time of the first subfoveal neurosensory detachment flattening (SNF) and at the end of follow-up. RESULTS: Eyes that achieved 20/50 (LogMAR = 0.40) or better at first SNF had mean LogMAR BCVA 0.38 ± 0.21, 0.24 ± 0.11 and 0.21 ± 0.15 at baseline, at the time of first SNF, and at the end of the last follow-up respectively. Mean LogMAR BCVA significantly improved from baseline to first SNF (p < 0.0001; 95% CI 0.115-0.183) and at the end of the last follow-up (p < 0.0001; 95% CI 0.126-0.213) with a change of Early Treatment Diabetic Retinopathy Study (ETDRS) 10 letters. There was no significant difference in improvement in BCVA from the first SNF and at the end of the last follow-up (p = 0.0781; 95% CI -0.002 to 0.046). CONCLUSIONS: Eyes presenting with Ci-DMO and subfoveal NSD are unlikely to improve at SNF with BCVA > 20/50 (LogMAR = 0.40). Further evidence is needed before the combination of good BCVA and SNF may be considered as endpoint of pharmacological therapy for DMO.

Retinal Displacement Following Rhegmatogenous Retinal Detachment Repair.

BACKGROUND AND OBJECTIVE: This study aimed to report retinal displacement incidence following rhegmatogenous retinal detachment (RRD) repair with pars plana vitrectomy (PPV), scleral buckle (SB), or combined SB/PPV. PATIENTS AND METHODS: A single-center, case series using Optos fundus autofluorescence (FAF) images was performed after RRD repair between April 2020 and February 2022. Retinal displacement was identified by imprinted retinal vessels on FAF imaging. RESULTS: One hundred ninety-four eyes were included. Ninety-seven (50.0%) eyes underwent PPV, 46 (23.7%) underwent SB, and 51 (26.3%) underwent SB/PPV. A total of 25/194 eyes (12.9%) had retinal vessel imprinting on FAF imaging consistent with retinal displacement. The SB/PPV group (9/51, 17.6%) and the PPV group (15/97, 15.5%) had significantly higher displacement rates when compared to the SB group (1/46, 2.2%; P = 0.017, P = 0.021, respectively). CONCLUSIONS: Retinal displacement after RRD repair is more prevalent after PPV. There was a low rate of displacement with SB. Retinal displacement was not associated with a visual acuity difference. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

RANDOMIZED TRIAL COMPARING MICROSERRATED VERSUS CONVENTIONAL INTERNAL LIMITING MEMBRANE FORCEPS FOR INTERNAL LIMITING MEMBRANE PEELING.

PURPOSE: To evaluate anatomic outcomes and surgeon response following the use of microserrated (Sharkskin, Alcon, Forth Worth, TX) internal limiting membrane (ILM) forceps compared with conventional (Grieshaber; Alcon) ILM forceps for peeling of the ILM. METHODS: Patients were prospectively assigned in a 1:1 randomized fashion to undergo ILM peeling using microserrated forceps or conventional forceps. Rates of retinal hemorrhages, deep retinal grasps, ILM regrasping, time to ILM removal, and surgeon questionnaire comparing the use of microserrated and conventional ILM forceps were analyzed. RESULTS: A total of 90 eyes of 90 patients were included in this study. The mean number of deep retinal grasps was higher in the conventional forceps group (1.51 ± 1.70 vs. 0.33 ± 0.56, respectively [P < 0.0001]). The mean number of failed ILM grasps was higher with conventional forceps (6.62 ± 3.51 vs. 5.18 ± 2.06 [P = 0.019]). Microserrated forceps provided more comfortability (lower number) in initiating the ILM flap (2.16 ± 0.85 vs. 1.56 ± 0.76, P < 0.001), comfortability in regrasping the ILM flap (2.51 ± 1.01 vs. 1.98 ± 0.89, P = 0.01), and comfortability in completing the ILM flap (2.42 ± 1.03 vs. 1.84 ± 1.02, P = 0.01). CONCLUSION: Surgeons utilizing the microserrated forceps experienced fewer deep retina grasps and fewer failed ILM grasps compared with conventional ILM forceps. The microserrated forceps was also a more favorable experience subjectively among the surgeons.

VITREORETINAL OUTCOMES FOLLOWING SECONDARY INTRAOCULAR LENS IMPLANTATION WITH PARS PLANA VITRECTOMY.

BACKGROUND: Retrospective cohort study of 561 adult patients undergoing secondary intraocular lens (IOL) implantation by vitreoretinal surgeons at a single institution from April 2015 to December 2020. METHODS: Patient historical factors, intraoperative/postoperative complications, and outcomes of IOL type (anterior chamber IOL versus scleral sutured IOL versus scleral fixated IOL versus. sulcus) were assessed. Primary outcomes were rates of postoperative retinal tears and rhegmatogenous retinal detachment. Secondary outcomes were rates of intraoperative endolaser, intraoperative retinal tear, and further IOL surgery. RESULTS: The incidence of intraoperative retinal tears was 7.3% and not significantly different between techniques. Rates of intraoperative endolaser use were 17.5% among all techniques and not significantly different between techniques. Rates of postoperative retinal tear were low (0%-2.7%). Rates of postoperative rhegmatogenous retinal detachment were not significantly different between techniques (anterior chamber IOL 9/198 [4.5%], SFIOL 1/54 [1.9%], scleral sutured IOL 14/274 [5.1%], sulcus 2/35 [5.7%], total 26/561 [4.6%], P = 0.79). Rates of repeat IOL surgery trended higher in sulcus lenses (anterior chamber IOL 5/198 [2.5%], SFIOL 4/54 [7.4%], scleral sutured IOL 16/274 [5.8%], sulcus 5/35 [14.3%], total 30/561 [5.3%], P = 0.12). CONCLUSION: Intraoperative endolaser use and intraoperative retinal tear are not uncommon in secondary IOL surgery and underscore the importance of careful vitreoretinal management among these patients.

SUPRACHOROIDAL TRIAMCINOLONE ACETONIDE FOR REFRACTORY POSTOPERATIVE CYSTOID MACULAR EDEMA.

PURPOSE: To investigate outcomes of suprachoroidal triamcinolone acetonide (XIPERE, Bausch + Lomb) for the treatment of refractory postoperative cystoid macular edema. METHODS: Medical records of patients receiving suprachoroidal triamcinolone acetonide for postoperative cystoid macular edema were reviewed. Primary outcomes were visual acuity and central foveal thickness. RESULTS: A total of 32 eyes from 32 patients with a median (interquartile range) follow-up duration of 6 (2-7) months and 1 (1-2) suprachoroidal triamcinolone acetonide injection were included; 19 (59.4%) had a history of vitrectomy. The median (interquartile range) central foveal thickness decreased from 492 (379-629) µm to 267 (187-388) µm at 1 month (P < 0.001), 362 (218-521) µm at 3 months (P = 0.005), and 339 (206-514) µm at the final visit (P < 0.001). The median logarithm of the minimal angle of resolution visual acuity improved from 0.65 (0.48-0.97, 20/89) at baseline to 0.54 (0.35-0.88, 20/69) (P = 0.058) at 1 month, 0.54 (0.33-0.84, 20/69) at 3 months (P = 0.121), and 0.60 (0.33-0.88, 20/80) at the final visit (P = 0.021). Vitrectomized eyes had similar findings. Six eyes (18.8%) developed elevated intraocular pressure (>24 mmHg) (range: 25-49 mmHg) with a median intraocular pressure elevation of 13.5 mmHg compared with baseline, and all had prior glaucoma or ocular hypertension. CONCLUSION: Suprachoroidal triamcinolone acetonide reduced macular edema and improved vision in refractory postoperative cystoid macular edema, including vitrectomized eyes. Intraocular pressure should be monitored, especially in those with a history of glaucoma or ocular hypertension.

Screen Failures in Clinical Trials in Retina.

PURPOSE: Disparities in clinical trials are a major problem because of significant underrepresentation of certain gender, racial, and ethnic groups. Several factors including stringent eligibility criteria and recruitment strategies hinder our understanding of retinal disease. Thus, we aimed to study the various reasons of screen failures and specific patient and study characteristics among screen failures. DESIGN: This is a cross-sectional retrospective study. METHODS: Screening data of 87 trials from 6 centers were analyzed. Study characteristics (disease studied, phase of trial, and route of drug administration) and patient demographics (age, gender, race, ethnicity, and employment status) were compared among different causes of screen failures. Screen failures were broadly classified into 6 categories: exclusion because of vision-based criteria, exclusion because of imaging findings, exclusion because of other factors, patient-related criteria, physician-related criteria, and miscellaneous. Descriptive statistics, Pearson chi-square test, and analysis of variance were used for statistical analysis. MAIN OUTCOME MEASURES: Prevalence of various reasons for screen failures in multiple trials and its trend among different study and patient characteristics. RESULTS: Among 87 trials and 962 patients, 465 (48.2%) patients were successfully randomized and 497 (51.8%) patients were classified as screen failures. The trials were conducted for various retinal diseases. Mean age was 76.50 ±10.45 years and 59.4% were females. Predominantly White patients (93.4%) and unemployed/retired patients (66.6%) were screened. Of the 497 screen failures, most were because of patients not meeting inclusion criteria of imaging findings (n = 221 [44.5%]) followed by inclusion of vision-based criteria (n = 73 [14.7%]), exclusion because of other factors (n = 75 [15.1%]), patient-related (n = 34 [6.8%]), physician-related (n = 28 [5.6%]), and miscellaneous reasons (n = 39 [7.8%]). Reason for screen failure was not available for 27 (5.4%) patients. A higher proportion of patients screened for surgical trials (15%) declined to participate in the study compared with noninvasive trials involving topical drugs and photobiomodulation (0%) (P = 0.02). CONCLUSIONS: Patients not meeting the imaging and vision-cased criteria were the most common reasons for screen failures. White patients and unemployed patients predominantly participated in clinical trials. Patients are more inclined to continue participation in noninvasive clinical trials compared with surgical trials. Better recruitment strategies and careful consideration of study criteria can aid in decreasing the rate of screen failures.

Exploring the Associated Genetic Causes of Diabetic Retinopathy as a Model of Inflammation in Retinal Diseases.

To investigate potential biomarkers and biological processes associated with diabetic retinopathy (DR) using transcriptomic and proteomic data. The OmicsPred PheWAS application was interrogated to identify genes and proteins associated with DR and diabetes mellitus (DM) at a false discovery rate (FDR)-adjusted p-value of <0.05 and also <0.005. Gene Ontology PANTHER analysis and STRING database analysis were conducted to explore the biological processes and protein interactions related to the identified biomarkers. The interrogation identified 49 genes and 22 proteins associated with DR and/or DM; these were divided into those uniquely associated with diabetic retinopathy, uniquely associated with diabetes mellitus, and the ones seen in both conditions. The Gene Ontology PANTHER and STRING database analyses highlighted associations of several genes and proteins associated with diabetic retinopathy with adaptive immune response, valyl-TRNA aminoacylation, complement activation, and immune system processes. Our analyses highlight potential transcriptomic and proteomic biomarkers for DR and emphasize the association of known aspects of immune response, the complement system, advanced glycosylation end-product formation, and specific receptor and mitochondrial function with DR pathophysiology. These findings may suggest pathways for future research into novel diagnostic and therapeutic strategies for DR.

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.

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.

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.

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.

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.

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.

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.

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.