Search

Purpose To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential. Design Multicenter, open-label, single- and multiple-dose phase 1 study. Methods Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm2 and best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, 15 mg) or received 2 doses NGM621 15 mg 4 weeks apart in the multidose phase and were followed for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments. Results All 15 participants completed the 12-week study. There were no serious adverse events and no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points. Conclusions In this small, open-labelled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.

In eyes with neovascular AMD, early persistent retinal dryness response to anti-VEGFs was associated with clinically relevant improvements in vision-related function and a greater visual acuity gain compared with when intraretinal fluid was present.

Purpose To evaluate the real-world utility of the ForeseeHome monitoring device (Notal Vision, Ltd., Tel Aviv, Israel) for the detection of conversion from intermediate age-related macular degeneration (iAMD) to neovascular AMD (nAMD) and to compare with results published by the Home Monitoring of the Eye (HOME) study. Design Retrospective analysis of electronic health records. Participants Eyes prescribed use of the ForeseeHome device across 4 retinal practices in the United States. Methods Usage information was collected from the online ForeseeHome portal for all eyes prescribed the device. For a predetermined subset of eyes, additional clinical information was collected through chart review and analyzed for clinical utility. Main Outcome Measures Frequency and length of use, number of eyes that used the device, number of eyes that established a baseline measurement, number of eyes that converted to nAMD, and number of alerts. Results Seven hundred seventy-five eyes of 448 patients were prescribed use of the ForeseeHome device. Six hundred forty-nine eyes (83.7%) used the device at least once; among this population, 478 (73.7%) established a baseline measurement. Patients who established a baseline measurement were significantly younger than those who did not (P Conclusions Compared with the prospective HOME study, the utility of the ForeseeHome device in the current analysis of clinical practice application was limited. A meaningful proportion of eyes never used the device or could not establish a baseline measurement. Overall frequency of use was low, and continuous use of the device decreased over time. A need exists for improvement in home monitoring technology for eyes with iAMD at risk of conversion to nAMD.

BackgroundThe 0.2 µg/day fluocinolone acetonide (FAc) implant delivers continuous, low-dose, intravitreal corticosteroid for the treatment of diabetic macular oedema (DMO). This ongoing, 3-year, observational clinical trial provides long-term, ‘real-world’ safety results for the FAc implant in DMO.MethodsThis 24-month interim analysis of a prospective, observational study investigated patients with DMO receiving the commercially available intravitreal 0.2 µg/day FAc implant. The primary outcome was incidence of intraocular pressure (IOP)-lowering procedures. Other IOP-related signals and their relationship to previous corticosteroid exposure, best-corrected visual acuity, central subfield thickness (CST), ocular adverse events and frequency of other treatments were also measured.ResultsData were collected from 95 previously steroid-challenged patients (115 study eyes) for up to 36 months pre-FAc and 24 months post-FAc implant. Mean IOP for the overall population remained stable post-FAc compared with pre-FAc implant. IOP-related procedures remained infrequent (two IOP-lowering surgeries pre-FAc; two trabeculoplasties and four IOP-lowering surgeries post-FAc). Mean visual acuity was stable post-FAc (mean improvement of 1–3 letters) and fewer DMO treatments were required per year following FAc implant. Mean CST was significantly reduced at 24 months post-FAc implant (pConclusionFew IOP-related procedures were reported during the 24 months post-FAc implant. Positive efficacy outcomes were noted after treatment, with stabilisation of vision and reduction in inflammation, demonstrated by CST. The FAc implant has a favourable benefit–risk profile in the management of DMO, especially when administered after a prior steroid challenge.Trial registration numberNCT02424019.

The Ang/Tie2 pathway complements VEGF-mediated activity in retinal vascular diseases such as DME, AMD, and RVO by decreasing vascular integrity, increasing neovascularization, and increasing inflammatory signaling. Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials. Recent Year 1 data from phase III clinical trials YOSEMITE, RHINE, TENAYA, and LUCERNE have confirmed the efficacy, safety, durability, and superiority of faricimab in patients with DME and nAMD. Faricimab, if approved, may significantly decrease treatment burden in patients with retinal vascular diseases to a greater extent than would current standard of care anti-VEGF injections.

The real-world performance of a home telemonitoring strategy (ForeseeHome AMD Monitoring System®, Notal Vision, Inc.,Manassas VA, USA) was evaluated and compared to the device arm of the AREDS2-HOME study among patients with intermediate AMD (iAMD) who converted to neovascular AMD (nAMD). All patients with confirmed conversion to nAMD who used the home monitoring system from 10/2009 through 9/2018 were identified by Notal Vision Diagnostic Clinic’s medical records. Selected outcome variables were evaluated, including visual acuity (VA) at baseline and at conversion, and change in visual acuity (VA) from baseline to time of conversion. In total, 8991 patients performed 3,200,999 tests at a frequency of 5.6 ± 3.2 times/week. The 306 eyes that converted from iAMD to nAMD over the study period (a 2.7% annual rate) were included in the analyses. There was a median (interquartile range) change of −3.0 (0.0–(−10.0)) letters among converted eyes, 81% [95% confidence interval (72–88%)] maintained a VA ≥ 20/40 at the time of conversion, while 69% of the conversion detections were triggered by system alerts. The real-world performance of an at-home testing strategy was similar to that reported for the device arm of the AREDS2-HOME study. The home telemonitoring system can markedly increase early detection of conversion to nAMD.

Importance Outcome data are limited regarding early experience with brolucizumab, the most recently approved anti–vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD). Objective To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD. Design, Setting, and Participants This retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020. Exposures Treatment with brolucizumab IVI, 6 mg. Main Outcomes and Measures Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety. Results A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, −2.7 to 4.3;P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) μm and was 269.8 (66.5) μm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm;P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision. Conclusions and Relevance In this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.

To evaluate diabetic retinopathy (DR) outcomes with ranibizumab (Lucentis, Genentech, Inc., South San Francisco, CA) treatment in patients with DR and diabetic macular edema (DME) at high risk of progression to proliferative disease.Post hoc analysis of the phase 3 RIDE (ClinicalTrials.gov identifier, NCT00473382) and RISE (ClinicalTrials.gov identifier, NCT00473330) clinical trials of ranibizumab for the treatment of DME.Seven hundred forty-six patients with baseline fundus photographs and randomized for treatment.Diabetic retinopathy outcomes were assessed through month 36 by baseline DR severity level. Diabetic retinopathy severity was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS).Two-step or more or 3-step or more improvement or worsening on the ETDRS DRSS and time to new proliferative event (composite end point).At baseline, most patients were distributed evenly among mild or moderate nonproliferative DR (NPDR; ETDRS DRSS, 35/43), moderately severe or severe NPDR (ETDRS DRSS, 47/53), and proliferative DR (ETDRS DRSS, 60-75; 28.8%, 33.2%, and 31.1%, respectively). At month 24, rates of 2-step or more improvement with ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham treatment were highest among patients with baseline DR levels 47/53 (78.4%, 81.1%, and 11.6%, respectively) compared with patients with baseline DR levels 35/43 (10.3%, 15.8%, and 1.4%, respectively) or 60 through 75 without panretinal photocoagulation (31.0%, 36.4%, and 6.7%, respectively; all ranibizumab vs. sham comparisons, P0.05). In patients with baseline DR levels 47/53, ranibizumab treatment reduced the probability of patients experiencing a new proliferative event at month 36 by 3 times compared with sham treatment (12.4% and 11.9% vs. 35.2% for ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham, respectively). In patients with baseline DR levels 47/53 who achieved 2-step or more DR improvement, improvements were independent of all assessed baseline characteristics (P0.4).Ranibizumab treatment resulted in DR improvements in all 3 baseline DR severity subsets examined. The greatest benefits in DR improvement occurred in patients with baseline moderately severe to severe NPDR (DR levels 47/53). Diabetic retinopathy improvements were rapid, clinically meaningful, and sustained through month 36.

ObjectiveTo investigate if the mean central retinal thickness (CRT) amplitude, measured between visits, is consistently decreased when switching from discontinuous to continuous therapy for diabetic macular oedema (DME) following fluocinolone acetonide (FAc) administration.Methods and analysisIn this retrospective cohort study, all patients with DME treated with FAc at a single centre were included. The primary outcome was CRT amplitude changes measured at each visit prior to and after FAc administration. Secondary outcomes included average number of DME treatments before and after FAc injection, visual acuity and intraocular pressure changes.ResultsNineteen eyes were included. The mean (SD) follow-up after FAc was 399 (222) days. The mean (SD) CRT amplitude before FAc was 194.6 (114.90) µm, and following FAc administration, the amplitude decreased to 70.8 (94.23) µm (95% CI −189.5 to −58.1; p≤0.001). After FAc, the number of treatments required per month significantly decreased from an average of 1 treatment every 2.7 months to every 6 months (p=0.009).ConclusionIn patients with DME, the CRT amplitude values and number of treatments significantly decrease following FAc administration while maintaining vision. Further studies are needed to evaluate the significance of these interesting findings.

A comprehensive literature search suggests that anti–vascular endothelial growth factor therapy is effective in treating eyes with pigment epithelial detachment due to neovascular age-related macular degeneration. This therapy should focus primarily on vision gains because there is no apparent correlation between anatomical and functional improvement in most eyes with pigment epithelial detachment and neovascular age-related macular degeneration., Purpose: This review aimed to determine the optimal management of retinal pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) based on review of available evidence in the literature. Methods: A comprehensive literature review evaluates previous retrospective and prospective studies that assessed the treatment of PEDs in nAMD. Results: Studies illustrated that anti–vascular endothelial growth factor (VEGF) therapy can be effective in eyes with PED secondary to nAMD. Similar visual outcomes are associated with different anti-VEGF treatments. Higher anti-VEGF doses may improve anatomical response, without correlation with vision improvement. Fibrovascular PEDs may be difficult to treat, but even these eyes can gain vision with anti-VEGF therapy. A retinal pigment epithelial tear may develop in 15% to 20% of eyes with PEDs after anti-VEGF therapy, especially in PEDs greater than 500 µm to 600 µm in height; however, vision may stabilize with continued therapy. Atrophy may complicate eyes with PED and nAMD after anti-VEGF therapy, especially in association with complete PED resolution. Conclusion: Available literature suggests that anti-VEGF therapy is safe and efficacious for PED and nAMD. Treatment should focus on vision gains rather than PED resolution because there is no apparent correlation between anatomical and functional improvement in most eyes with PED and nAMD.