Early surgical displacement of submacular hemorrhage without tissue plasminogen activator use: one-year outcomes.

OBJECTIVE: This study evaluated changes in best-corrected visual acuity and submacular hemorrhage (SMH) resolution in eyes after a single rapid subretinal displacement surgery using subretinal balanced saline solution and sterile air without tissue plasminogen activator (tPA). DESIGN: A retrospective comparative interventional analysis. PARTICIPANTS: Twenty-six eyes with thick SMH who underwent pars plana vitrectomy and subretinal fluid displacement without tPA from 2015 and 2021 and at least 1-year of follow-up. METHODS: Surgical intervention included a standard small-gauge pars plana vitrectomy with subretinal displacement using balanced saline solution with subretinal sterile air and partial gas-air fluid exchange. Main outcome measures included degree of subfoveal SMH displacement, best and final postoperative visual acuities, and adverse events. Snellen acuity was converted to logMARs for statistical analysis. RESULTS: The most common etiology associated with thick SMH (92.3%) was neovascular age-related macular degeneration. Within 1 month postoperatively, 21 patients (80.8%) saw complete subfoveal blood displacement. Most of the SMH surgical displacements were done within 1 week of presenting symptoms. Average preoperative duration of SMH was 3.60 ± 2.78 days (range, 1-12 days). Mean logMAR best-corrected visual acuity improved from 1.63 ± 0.58 (Snellen 20/800 baseline) to 0.90 ± 0.42 letters (Snellen 20/160) at last follow-up (p = 0.001). This study's visual acuity improvement is comparable with that of prior studies using tPA. Early postoperative complications included 1 retinal detachment, 1 vitreous hemorrhage, and 1 macular hole. CONCLUSION: Rapid surgery with subretinal balanced saline solution-sterile air injection without tPA was found to be effective for displacement of thick SMH with retinal function, visual acuity, and corneal refractive therapy improvement.

One-Year and 18-Month Outcomes in nAMD Patient Eyes Switched to Brolucizumab Alone versus to Brolucizumab Alternating with Other Anti-VEGF Agents.

Objective: Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF. Methods: The overall study population comprised eyes that were given ≥1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with ≥3 brolucizumab injections over ≥12 or ≥18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with ≥2 brolucizumab injections and ≥1 other anti-VEGF over ≥12 or ≥18 months. Results: A total of 482 eyes received ≥1 brolucizumab injection during the study period. Mean VA changes from baseline were -1.1±15.1 letters (BRO cohort; n = 174) and 1.3±13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0±13.5 letters (BRO cohort; n = 95) and -7.3±17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9±48.1 days (BRO cohort) and +11.1±17.3 days (ALT cohort) at Month 12 and +36.3±52.3 days (BRO cohort) and +14.0±19.9 days (ALT cohort) at Month 18. Mean changes in CMT were -35.2±108.1 µm (BRO cohort) and -31.5±91.2 µm (ALT cohort) at Month 12 and -38.9±75.0 µm (BRO cohort) and -9.0±59.9 µm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes. Conclusion: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD.

Real-World Frequency and Management of Ocular Adverse Events in Eyes with Neovascular Age-Related Macular Degeneration Treated with Brolucizumab.

INTRODUCTION: Intraocular inflammation (IOI)-related adverse events (AEs) that may result in severe vision loss have been associated with the anti-vascular endothelial growth factor brolucizumab. In this study, we investigate the timing, management and resolution of IOI-related AEs in a large cohort of patients treated with at least one injection of brolucizumab in routine clinical practice. METHODS: Retrospective review of medical records from patients with neovascular age-related macular degeneration treated with ≥ 1 brolucizumab injection between October 2019 and November 2021 at the Retina Associates of Cleveland, Inc. clinics. RESULTS: Of the 482 eyes included in the study, IOI-related AEs occurred in 22 (4.6%) eyes. Four (0.8%) eyes developed retinal vasculitis (RV) and of these, 2 (0.4%) had concomitant retinal vascular occlusion (RO). Most eyes [14/22 (64%)] developed the AE within 3 months and 4/22 (18%) within 3-6 months of the first brolucizumab injection. The median [interquartile range (IQR)] time from the last brolucizumab injection to development of the IOI-related AE was 13 (4-34) days. At the time of event, 3 (0.6%) eyes with IOI (no RV/RO) developed severe vision loss of ≥ 30 ETDRS letters, and a further 5 (1.0%) eyes (1 with IOI + RV, 1 with IOI + RV + RO) developed moderate vision loss of ≥ 15 letters compared with their last visual acuity (VA) prior to the AE. The median (IQR) vision loss was -6.8 (-19.9, -0.0) letters. Taking the best VA at either 3 or 6 months after AE resolution (or stability for occlusive events), VA decreased by ≥ 5 letters compared with prior to the AE in 3 (14%) of the 22 affected eyes, and was preserved (< 5-letter loss) in 18 (82%) eyes. CONCLUSIONS: In this real-world study, most IOI-related AEs occurred early after brolucizumab treatment initiation. With appropriate monitoring and management of IOI-related AEs, vision loss associated with brolucizumab may be limited.

Switching to brolucizumab: injection intervals and visual, anatomical and safety outcomes at 12 and 18 months in real-world eyes with neovascular age-related macular degeneration.

BACKGROUND: The anti-vascular endothelial growth factor (anti-VEGF) injection interval influences treatment burden and compliance in neovascular age-related macular degeneration (nAMD). This real-world study investigates visual acuity (VA), injection-interval extension, central macular thickness (CMT) and safety in nAMD eyes switched to the anti-VEGF agent brolucizumab and followed for up to 18 months. METHODS: This retrospective study included patients with nAMD who were switched from other anti-VEGF agents to brolucizumab only. Patient eyes were grouped into three nested cohorts with the overall cohort receiving ≥ 1 brolucizumab injection, the second receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 12 months and the third cohort receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 18 months. Study endpoints included changes from baseline at 12 or 18 months in VA, injection intervals, and CMT. Sub-group analyses were conducted using baseline injection interval length or baseline VA as qualifiers. RESULTS: Overall, 482 eyes received ≥ 1 brolucizumab injection; 174 eyes received ≥ 3 brolucizumab injections with ≥ 12 months of follow-up, and 95 eyes received ≥ 3 brolucizumab injections with ≥ 18 months of follow-up. VA (mean [95% confidence intervals]) remained stable relative to baseline after 12 months (- 1.1 [- 3.7, 1.6] letters; p = 0.42) and 18 months (0.0 [- 3.1, 3.1] letters; p = 0.98) of brolucizumab treatment, respectively, and pre-switch injection intervals or baseline VA had no notable effect. Following the switch to brolucizumab, injection intervals were extended from baseline to month 12 by 26.9 (19.7, 34.0) days (p < 0.0001), and eyes with pre-switch injection intervals < 8 weeks were able to have their injection intervals extended by 23.6 days longer than eyes with pre-switch injection intervals ≥ 8 weeks. At 18 months, injection intervals were extended by 36.3 (25.6, 46.9) days (p < 0.0001) compared to baseline. Following switch to brolucizumab, CMT was reduced at both 12 and 18 months (12 months: - 35.2 (- 51.7, - 18.8) µm, p < 0.0001; 18 months: - 38.9 (- 54.3, - 22.0) µm, p < 0.0001). Intraocular inflammation-related adverse events were reported in 4.6% of brolucizumab-treated eyes. CONCLUSIONS: This real-world study demonstrates that injection intervals may be significantly extended with maintained vision and reduced CMT in nAMD eyes switching to brolucizumab therapy from other anti-VEGFs.

Advancing Inclusive Research: Establishing Collaborative Strategies to Improve Diversity in Clinical Trials.

Well-characterized disparities in clinical research have disproportionately affected patients of color, particularly in underserved communities. To tackle these barriers, Genentech formed the External Council for Advancing Inclusive Research, a 14-person committee dedicated to developing strategies to increase clinical research participation. To help improve the recruitment and retention of patients of color, this article chronicles our efforts to tangibly address the clinical research barriers at the system, study, and patient levels over the last four years. These efforts are one of the initial steps to fully realize the promise of personalized health care and provide increased patient benefit at less cost to society. Instead of simply acknowledging the problem, here we illuminate the collaborative and multilevel strategies that have been effective in delivering meaningful progress for patients.

Racial disparities in the screening and treatment of diabetic retinopathy.

Diabetic retinopathy is a progressive disease and primary retinal vascular complication of diabetes mellitus, the third leading cause of blindness in the United States. Racial and ethnic minorities are more likely to suffer from diabetic retinopathy and diabetic macular edema, and typically undergo less screening. Lack of screening is due to a variety of factors, such as patient, provider, and institutional barriers. Due to the disparity in screening, minorities often present with more advanced stages of diabetic eye disease. As the minority population increases, the burden of treatment for these patients will also increase. It is imperative to understand the barriers and social determinants of health limiting visual outcomes in minority populations. Diabetic retinopathy and its complications are often preventable if detected and treated early. Advances in screening technology and intravitreal anti-VEGF injections have changed the landscape in preventing vision loss in diabetic patients.

Addressing unmet needs in diabetic retinopathy.

Diabetic retinopathy (DR), the primary retinal vascular complication of diabetes mellitus, is a progressive disease and a major cause of impaired vision and blindness, especially among individuals who are of working age. Early detection and treatment of DR can prevent 50% to 70% of its associated blindness. However, fewer than half of all US adults with diabetes adhere to guideline-recommended eye-screening schedules. Patients with DR typically have no symptoms in the early stage of the disease and may not seek medical evaluation until DR advances and results in vision impairment. These delays in diagnosis and treatment may result in visual impairment that is permanent and cannot be reversed. Although the direct medical costs of DR are substantial, the indirect costs of visual impairment with respect to loss of productivity, increased nursing home admissions, and decreased quality of life are far more copious. Greater adherence to eye screening guidelines among patients with diabetes is required to facilitate prompt diagnosis and early treatment of DR, and in doing so, reduce the resulting vision loss and economic burden associated with DR.

Fluocinolone acetonide 0.19 mg intravitreal implant improves foveal thickness and reduces treatment burden for up to 1 year in eyes with persistent diabetic macular edema.

Objective: To assess the effectiveness, safety, and treatment burden in eyes with persistent diabetic macular edema (DME) for up to 1 year after administration of 0.19 mg fluocinolone acetonide (FAc) implant (Iluvien®). Methods: This retrospective study at one private practice in the US included 40 eyes from 33 patients treated with an FAc implant. Eyes had previously been treated with VEGF antagonists, dexamethasone, or focal laser. The primary outcome was change in central foveal thickness from baseline. Data were also collected on demographics, visual acuity, intraocular pressure (IOP), use of IOP-lowering drugs for elevated IOP, lens clarity, and treatment burden before and after the implant. Results: Average duration of diabetes and DME at baseline was 19 and 5 years, respectively, and average glycated hemoglobin was 7.21%. Severity of diabetic retinopathy before the implant had a slight bimodal distribution: moderate nonproliferative diabetic retinopathy (35%) and proliferative diabetic retinopathy (40%). Improvements in central foveal thickness from baseline were evident at 3 months (mean change -74.2 µm, P<0.001) and sustained through 12 months (-55.3 µm; P=0.005) for most eyes. Mean visual acuity remained stable (66.2 letters at baseline versus 67.2 letters at 12 months, roughly equivalent to 20/50 vision; P=0.855). On average, eyes required one anti-VEGF injection every 1.9 months before and one every 6.6 months after the implant, while 60% of eyes did not require additional anti-VEGF injections. Small but significant increases in IOP at months 3, 6, and 9 were not sustained to month 12, and mean IOP was normal throughout follow-up. Conclusion: In patients with DME previously treated with a steroid, and treated according to licensed indications in the US, an FAc implant not only reduces the burden of disease in the real-world setting, but also the burden of injections and office visits for patients.

Binocular indirect panretinal laser photocoagulation for the treatment of proliferative diabetic retinopathy.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of indirect laser photocoagulation in eyes with severe preproliferative and proliferative diabetic retinopathy. PATIENTS AND METHODS: Retrospectively, 209 eyes were evaluated regarding the efficacy of indirect laser photocoagulation in eyes with no previous laser treatment, with previous laser treatment, and undergoing pars plana vitrectomy with indirect laser photocoagulation. Visual acuity and progression of retinopathy were documented. RESULTS: The no previous laser treatment group received a mean of 1,465 laser spots in an average of 1.3 sessions, with 80.8% of eyes having stable or improved vision. The previous laser treatment group received a mean of 1,149 laser spots in an average of 1.2 sessions, with 83% of eyes having stable or improved vision. The pars plana vitrectomy group received a mean of 1,039 laser spots in an average of 1.1 sessions, with improvement or stabilization of vision in 89.6% of eyes. CONCLUSIONS: Indirect panretinal photocoagulation should be considered for patients with diabetes when comfort, handicaps, and progression of severe retinopathy are a concern.