Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study.

BACKGROUND: Frequent anti-vascular endothelial growth factor A (VEGF-A) injections reduce the risk of rapid and severe vision loss in patients with neovascular age-related macular degeneration (nAMD); however, due to undertreatment, many patients lose vision over time. New treatments that provide sustained suppression of VEGF-A are needed. RGX-314 (currently known as ABBV-RGX-314) is an adeno-associated virus serotype 8 vector that expresses an anti-VEGF-A antigen-binding fragment, which provides potential for continuous VEGF-A suppression after a single subretinal injection. We report results on the safety and efficacy of subretinal injection of RGX-314 in patients with nAMD. METHODS: For this open-label, multiple-cohort, multicentre, phase 1/2a, dose-escalation study conducted at eight sites in the USA, we enrolled participants with nAMD aged 50-89 years who had previously been treated with anti-VEGF injections into five cohorts (with five different doses of RGX-314). To be eligible, participants had to have macular neovascularisation secondary to nAMD with subretinal or intraretinal fluid in the centre subfield, be pseudophakic (after cataract removal), and have a best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400 for the first participant in each cohort and between 20/40 and 20/400 for others. Subretinal injection of RGX-314 was done without a pre-bleb by a wet-laboratory-trained vitreoretinal surgeon. Cohort 1 received 3 × 109 genome copies per eye, cohort 2 received 1 × 1010, and cohort 3 received 6 × 1010. Two additional dose cohorts (cohort 4: 1·6 × 1011; cohort 5: 2·5 × 1011) were added. Participants were seen 1 day and 1 week after administration of RGX-314, and then monthly for 2 years (up to week 106). The primary outcome was safety of RGX-314 delivered by subretinal injection up to week 26. This analysis includes all 42 patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT03066258. FINDINGS: Between May 12, 2017, and May 21, 2019, we screened 110 patients for eligibility and enrolled 68. 42 participants demonstrated the required anatomic response to intravitreal ranibizumab and then received a single RGX-314 injection (dose range 3 × 109 to 2·5 × 1011 genome copies per eye) and were followed up for 2 years. There were 20 serious adverse events in 13 participants, of which one was possibly related to RGX-314: pigmentary changes in the macula with severe vision reduction 12 months after injection of RGX-314 at a dose of 2·5 × 1011 genome copies per eye. Asymptomatic pigmentary changes were seen in the inferior retinal periphery several months after subretinal injection of RGX-314 most commonly at doses of 6 × 1010 genome copies per eye or higher. There were no clinically determined immune responses or inflammation beyond that expected following routine vitrectomy. Doses of 6 × 1010 genome copies or higher resulted in sustained concentrations of RGX-314 protein in aqueous humour and stable or improved BCVA and central retinal thickness with few or no supplemental anti-VEGF-A injections in most participants. INTERPRETATION: Subretinal delivery of RGX-314 was generally well tolerated with no clinically recognised immune responses. RGX-314 gene therapy provides a novel approach for sustained VEGF-A suppression in patients with nAMD that has potential to control exudation, maintain vision, and reduce treatment burden after a single administration. Results from this study informed the pivotal programme to evaluate RGX-314 in patients with nAMD. FUNDING: RegenxBio.

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.

Artificial Intelligence, Digital Imaging, and Robotics Technologies for Surgical Vitreoretinal Diseases.

OBJECTIVE: To review recent technological advancement in imaging, surgical visualization, robotics technology, and the use of artificial intelligence in surgical vitreoretinal (VR) diseases. BACKGROUND: Technological advancements in imaging enhance both preoperative and intraoperative management of surgical VR diseases. Widefield imaging in fundal photography and OCT can improve assessment of peripheral retinal disorders such as retinal detachments, degeneration, and tumors. OCT angiography provides a rapid and noninvasive imaging of the retinal and choroidal vasculature. Surgical visualization has also improved with intraoperative OCT providing a detailed real-time assessment of retinal layers to guide surgical decisions. Heads-up display and head-mounted display utilize 3-dimensional technology to provide surgeons with enhanced visual guidance and improved ergonomics during surgery. Intraocular robotics technology allows for greater surgical precision and is shown to be useful in retinal vein cannulation and subretinal drug delivery. In addition, deep learning techniques leverage on diverse data including widefield retinal photography and OCT for better predictive accuracy in classification, segmentation, and prognostication of many surgical VR diseases. CONCLUSION: This review article summarized the latest updates in these areas and highlights the importance of continuous innovation and improvement in technology within the field. These advancements have the potential to reshape management of surgical VR diseases in the very near future and to ultimately improve patient care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

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.

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.

Primary Retinal Detachment Repair in Eyes Deemed High Risk for Proliferative Vitreoretinopathy: Surgical Outcomes in 389 Eyes.

PURPOSE: To evaluate surgical outcomes in eyes with primary rhegmatogenous retinal detachment (RRD) deemed at high risk for postoperative proliferative vitreoretinopathy (PVR). DESIGN: Retrospective, consecutive case cohort study. PARTICIPANTS: Eyes undergoing primary RRD repair with pars plana vitrectomy (PPV) or combined PPV with scleral buckling (PPV/SB) between January 1, 2016, and December 30, 2017, at Wills Eye Hospital. METHODS: Eyes were defined as "high risk" if ≥ 1 of the following risk factors for PVR was present on preoperative examination: preoperative PVR grade A or B, vitreous hemorrhage, RRD involving ≥ 50% of retinal area, presence of ≥ 3 retinal breaks, history of prior cryotherapy, presence of choroidal detachment, or duration of RRD > 2 weeks. Surgical failure was defined as an additional intervention required for the retinal reattachment. MAIN OUTCOMES MEASURES: Single surgery attachment success (SSAS) rate 3 months after first surgical intervention for primary RRD. RESULTS: Of 2053 reviewed charts, a total of 389 eyes (18.9%) met the definition of high risk and were included in the analysis. Mean patient age was 63.5 years. PPV/SB was performed in 125 (32.1%) eyes and PPV alone in 264 (67.9%) eyes. SSAS rate of the overall cohort was 71.5% at 3 months. SSAS rate was significantly higher in eyes treated with PPV/SB compared with PPV (80.8% vs. 67%, respectively, P = 0.006). On multivariate analysis, use of PPV/SB was the only feature associated with SSAS (odds ratio, 2.04; 95% confidence interval, 1.12-3.69, P = 0.019). CONCLUSION: In eyes with primary RRD and risk factors for PVR, overall SSAS was 71.5% after primary repair. In this cohort, use of PPV/SB was associated with a significantly higher SSAS compared with PPV alone. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

Neurotrophic keratopathy following rhegmatogenous retinal detachment surgery.

OBJECTIVE: To describe clinical characteristics and visual outcomes of eyes developing neurotrophic keratopathy (NK) following rhegmatogenous retinal detachment (RRD) repair. METHODS: All eyes with NK at Wills Eye Hospital following RRD repair from June 1, 2011, to December 1, 2020 were included. Patients with prior ocular procedures (other than cataract surgery), herpetic keratitis, and diabetes mellitus were excluded. RESULTS: During the study period, 241 patients were diagnosed with NK, and 8179 eyes underwent RRD surgery, giving a 9-year prevalence rate of 0.1% (95% CI, 0.1%-0.2%). Mean age was 53.4 ± 16.6 years during RRD repair and 56.5 ± 13.4 years during NK diagnosis. Mean time to NK diagnosis was 3.0 ± 5.6 years (range, 6 days to 18.8 years). Mean visual acuity before NK was 1.10 ± 0.56 logMAR (20/252 Snellen), and it was 1.01 ± 0.62 logMAR (20/205 Snellen) at final visit (p = 0.75). Six eyes (54.5%) developed NK <1 year following RRD surgery. Mean final visual acuity was 1.01 ± 0.53 logMAR (20/205 Snellen) in this group versus 1.01 ± 0.78 logMAR (20/205 Snellen) in the delayed NK group (p = 1.00). CONCLUSIONS: NK may present acutely or up to several years following surgery, with severity of corneal defects ranging from stage 1 to stage 3 NK. Surgeons should be mindful of the potential for this rare complication following RRD repair.

Incidence and Risk Factors for Retinal Detachment and Retinal Tear after Cataract Surgery: IRIS® Registry (Intelligent Research in Sight) Analysis.

Objective: To report the incidence of and evaluate demographic, ocular comorbidities, and intraoperative factors for rhegmatogenous retinal detachment (RRD) and retinal tear (RT) after cataract surgery in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight). Design: Retrospective cohort study. Participants: Patients aged ≥ 40 years who underwent cataract surgery between 2014 and 2017. Methods: Multivariable logistic regression was used to evaluate demographic, comorbidity, and intraoperative factors associated with RRD and RT after cataract surgery. Main Outcome Measures: Incidence and risk factors for RRD or RT within 1 year of cataract surgery. Results: Of the 3 177 195 eyes of 1 983 712 patients included, 6690 (0.21%) developed RRD and 5489 (0.17%) developed RT without RRD within 1 year after cataract surgery. Multivariable logistic regression odds ratios (ORs) showed increased risk of RRD and RT, respectively, among men (OR 3.15; 95% confidence interval [CI], 2.99-3.32; P < 0.001 and 1.79; 95% CI, 1.70-1.89; P < 0.001), and younger ages compared with patients aged > 70, peaking at age 40 to 50 for RRD (8.61; 95% CI, 7.74-9.58; P < 0.001) and age 50 to 60 for RT (2.74; 95% CI, 2.52-2.98; P < 0.001). Increased odds of RRD were observed for procedure eyes with lattice degeneration (LD) (10.53; 95% CI, 9.82-11.28; P < 0.001), hypermature cataract (1.61; 95% CI, 1.06-2.45; P = 0.03), complex cataract surgery (1.52; 95% CI, 1.4-1.66; P < 0.001), posterior vitreous detachment (PVD) (1.24; 95% CI, 1.15-1.34; P < 0.001), and high myopia (1.2; 95% CI, 1.14-1.27; P < 0.001). Lattice degeneration conferred the highest odds of RT (43.86; 95% CI, 41.39-46.49; P < 0.001). Conclusion: In the IRIS Registry, RRD occurs in approximately 1 in 500 cataract surgeries in patients aged > 40 years within 1 year of surgery. The presence of LD conferred the highest odds for RRD and RT after surgery. Additional risk factors for RRD included male gender, younger age, hypermature cataract, PVD, and high myopia. These data may be useful during the informed consent process for cataract surgery and help identify patients at a higher risk of retinal complications. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Progression of Geographic Atrophy: Retrospective Analysis of Patients from the IRIS® Registry (Intelligent Research in Sight).

Purpose: To evaluate disease progression and associated vision changes in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in 1 eye and GA or neovascular AMD (nAMD) in the fellow eye using a large dataset from routine clinical practice. Design: Retrospective analysis of clinical data over 24 months. Subjects: A total of 256 635 patients with GA from the American Academy of Ophthalmology (Academy) IRIS® Registry (Intelligent Research in Sight) Registry (January 2016 to December 2017). Methods: Patients with ≥ 24 months of follow-up were grouped by fellow-eye status: Cohort 1, GA:GA; Cohort 2, GA:nAMD, each with (subfoveal) and without subfoveal (nonsubfoveal) involvement. Eyes with history of retinal disease other than AMD were excluded. Sensitivity analysis included patients who were managed by retina specialists and had a record of imaging within 30 days of diagnosis. Main Outcome Measures: Change in visual acuity (VA), occurrence of new-onset nAMD, and GA progression from nonsubfoveal to subfoveal. Results: In total, 69 441 patients were included: 44 120 (64%) GA:GA and 25 321 (36%) GA:nAMD. Otherwise eligible patients (57 788) were excluded due to follow-up < 24 months. In both GA:GA and GA:nAMD cohorts, nonsubfoveal study eyes had better mean (standard deviation) VA at index (67 [19.3] and 66 [20.3] letters) than subfoveal eyes (59 [23.9] and 47 [26.9] letters), and 24-month mean VA changes were similar for nonsubfoveal (-7.6 and -6.2) and subfoveal (-7.9 and -6.5) subgroups. Progression to subfoveal GA occurred in 16.7% of nonsubfoveal study eyes in the GA:GA cohort and 12.5% in the GA:nAMD cohort. More new-onset study-eye nAMD was observed in the GA:nAMD (21.6%) versus GA:GA (8.2%) cohorts. Sensitivity analysis supported the robustness of the observations in the study. Conclusions: This retrospective analysis describes the natural progression of GA lesions and the decline in VA associated with the disease. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Durable vision improvement after a single intravitreal treatment with antisense oligonucleotide in CEP290-LCA: Replication in two eyes.

Purpose: An intravitreally injected antisense oligonucleotide, sepofarsen, was designed to modulate splicing within retinas of patients with severe vision loss due to deep intronic c.2991 + 1655A > G variant in the CEP290 gene. A previous report showed vision improvements following a single injection in one eye with unexpected durability lasting at least 15 months. The current study evaluated durability of efficacy beyond 15 months in the previously treated left eye. In addition, peak efficacy and durability were evaluated in the treatment-naive right eye, and re-injection of the left eye 4 years after the first injection. Observations: Visual function was evaluated with best corrected standard and low-luminance visual acuities, microperimetry, dark-adapted chromatic perimetry, and full-field sensitivity testing. Retinal structure was evaluated with OCT imaging. At the fovea, all visual function measures and IS/OS intensity of the OCT showed transient improvements peaking at 3-6 months, remaining better than baseline at ∼2 years, and returning to baseline by 3-4 years after each single injection. Conclusions and Importance: These results suggest that sepofarsen reinjection intervals may need to be longer than 2 years.

Intravitreal Nesvacumab (Anti-Angiopoietin-2) Plus Aflibercept in Neovascular AMD: Phase 2 ONYX Randomized Trial.

Purpose: To compare intravitreal nesvacumab (anti-angiopoietin-2) + aflibercept vs intravitreal aflibercept injection (IAI) in neovascular age-related macular degeneration (nAMD). Methods: Eyes were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, week 4, and week 8. The LD combo was continued every 8 weeks (q8w). At week 12, the HD combo was re-randomized to q8w or every 12 weeks (q12w) and IAI was re-randomized to q8w, q12w, or HD combo q8w through week 32. Results: The study comprised 365 eyes. At week 12, the mean best-corrected visual acuity (BCVA) gains from baseline were similar in the LD combo group, HD combo group, and IAI group (5.2 letters, 5.6 letters, and 5.4 letters, respectively); the mean central subfield thickness (CST) reductions were similar (182.2 µm, 200.0 µm, and 178.6 µm, respectively). The mean changes in BCVA and CST through week 36 were similar across groups. At week 12, complete retinal fluid resolution was observed in 49.1% (LD combo), 50.8% (HD combo), and 43.6% (IAI) of eyes; the proportions with a CST of 300 µm or less were similar across groups. Numerical trends at week 32 toward complete retinal fluid resolution with combination treatment were not maintained at week 36. Serious ocular adverse events were infrequent and comparable across groups. Conclusions: In nAMD, nesvacumab + aflibercept showed no additional BCVA or CST benefit over IAI monotherapy.

Recent advances in the management of proliferative diabetic retinopathy.

PURPOSE OF REVIEW: The prevalence of diabetic retinopathy continues to rise. This review highlights advances in imaging, medical, and surgical management of proliferative diabetic retinopathy (PDR) in recent years. RECENT FINDINGS: Ultra-widefield fluorescein angiography has been shown to better characterize which patients have predominantly peripheral lesions and who may advance to more advanced forms of diabetic retinopathy. This was well demonstrated in DRCR Retina Network's Protocol AA. Protocol S demonstrated that antivascular endothelial growth factor (VEGF) treatment alone can be useful in the management of select PDR patients - particularly those without high-risk features. However, a growing body of literature highlights how lapse in care is a significant concern in PDR patients, and tailoring one's approach to treatment based on patient needs is recommended. In patients with high-risk features or where there is concern for lost-to-follow-up, incorporation of panretinal photocoagulation in the treatment paradigm is recommended. Protocol AB highlighted how patients with more advanced disease may benefit from earlier surgical intervention for earlier visual recovery but that continued anti-VEGF treatment may result in similar visual outcomes over a longer period. Finally, earlier surgical intervention for PDR without vitreous hemorrhage (VH) or retinal detachment is being considered a potential option to minimize treatment burden. SUMMARY: Recent advances in imaging, as well as medical and surgical treatment options for PDR, have provided a deeper understanding of PDR management, which can be optimized for the individual patient.

Endophthalmitis following cataract surgery: visual outcomes, microbial spectrum and complications.

PURPOSE OF REVIEW: The aim of this study was to update visual outcomes, microbial spectrum and complications in eyes with endophthalmitis following cataract surgery. RECENT FINDINGS: A single-institution, retrospective review of eyes treated for endophthalmitis following cataract surgery between 2 January 2014 and 10 January 2017. This study included 112 cases of endophthalmitis following cataract surgery, 58 of which were culture-positive (51.8%). The most isolated organisms were coagulase-negative Staphylococci (56.9%). Oral flora were present in 17.2% of cases. At 6 months, 71.7% of patients achieved visual acuity of at least 20/200 and 51.7% achieved at least 20/40 or better. Visual acuity was better in culture-negative vs. culture-positive cases (∼20/290 vs. ∼20/80, P   =  0.03), and in nonoral flora-associated vs. oral flora-associated culture-positive cases (∼CF vs. ∼20/150, P   <  0.01). SUMMARY: Following postcataract surgery endophthalmitis, approximately 70% of eyes achieved vision of 20/200 or better and half achieved vision of 20/40 or better 6 months after treatment. Poor visual outcomes were seen in eyes with positive bacterial cultures and with oral flora.

Evaluating the Effect of Hypoglycemic Agents on Diabetic Retinopathy Progression.

BACKGROUND AND OBJECTIVE: Newer hypoglycemics such as dipeptidyl peptidase 4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists have been increasingly used in diabetes. This study aimed to assess the relationship between usage of these hypoglycemic agents and effect on diabetic retinopathy (DR). MATERIALS AND METHODS: Using the Vestrum Health Retina Database, patients with DR with 1 year follow-up after use of a hypoglycemic agent were included and stratified by agent, including no pharmacotherapy. RESULTS: Of 60,649 eyes, in 1 year after hypoglycemic agent usage, progression rates from severe nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) were the following: DPP-4 (17%), SGLT-2 (12%), GLP-1 (21%), metformin (18%), and none (20%). Progression rates from moderate NPDR to severe NPDR or PDR were the following: DPP-4 (11%), SGLT-2 (10%), GLP-1 (11%), metformin (10%), none (13%). Progression rates from mild NPDR to moderate/severe NPDR or PDR were the following: DPP-4 (6%), SGLT-2 (9%), GLP-1 (9%), metformin (7%), and none (10%). CONCLUSIONS: Within a large real-world database, patients prescribed GLP-1 agonists were found to have DR progression rates comparable to those of patients receiving no hypoglycemic agents. [Ophthalmic Surg Lasers Imaging Retina 2023; 54(3):158-165.].