TENAYA and LUCERNE

Ophthalmology · 2024 · 163 citations

• Medicine

PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Glaucoma Secondary to Intraocular Tumors

2024-05-28

The association between unilaterally elevated intraocular pressure (IOP) and intraocular tumor has been appreciated for many years. 1 Because intraocular neoplasms are far from common, this occurrence is rarely encountered in general ophthalmologic practice. However, when present, it is critically important to recognize. The presence of intraocular cancer represents one of the few situations in ophthalmology in which delay in diagnosis and/or inappropriate surgical intervention (eg, filtering surgery) can not only threaten vision but life as well.

Intravitreal Aflibercept Injection vs Sham as Prophylaxis Against Conversion to Exudative Age-Related Macular Degeneration in High-risk Eyes

JAMA Ophthalmology · 2021-03-18 · 33 citations

IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) agents may provide a prophylactic effect in high-risk eyes with intermediate dry age-related macular degeneration (AMD) against conversion to exudative AMD (eAMD), lowering the risk of vision loss. OBJECTIVE: To evaluate intravitreal aflibercept injection (IAI) as prophylaxis against the conversion to eAMD in high-risk eyes at 24 months. DESIGN, SETTING, AND PARTICIPANTS: This single-masked, sham-controlled, randomized clinical trial performed at 4 US clinical sites enrolled patients with intermediate AMD in 1 eye (study eye), defined as presence of more than 10 medium drusen (≥63 to <125 μm), at least 1 large druse (≥125 μm), and/or retinal pigmentary changes, and eAMD in the fellow eye. Patients were treated from June 23, 2015, to March 13, 2019. INTERVENTIONS: Intravitreal aflibercept injection (2 mg) or sham quarterly injection for 24 months (1:1 randomization). MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients with conversion to eAMD at month 24 characterized by development of choroidal neovascularization, as assessed by leakage on fluorescein angiography and fluid on spectral-domain optical coherence tomography by an independent masked reading center. RESULTS: Of 128 patients enrolled, 127 (63 in the IAI group and 64 in the sham group) were included in the primary analysis (68 men [53.5%]; mean [SD] age, 76.5 [8.1] years). Baseline demographic and clinical characteristics were balanced between the groups. By month 24, 6 patients (9.5%) in the IAI group and 7 (10.9%) in the sham group developed eAMD (P = .98). Patients with a history of eAMD for longer than 2 years in their fellow eye at baseline showed a lower rate of conversion to eAMD in the study eye compared with those with a history of eAMD for 2 years or less in the fellow eye. Safety was consistent with previous studies involving intravitreal anti-VEGF injections. CONCLUSIONS AND RELEVANCE: In this evaluation of quarterly anti-VEGF exposure as prophylaxis to reduce conversion of eyes with high-risk dry AMD to eAMD, the rates of conversion were not lower in the IAI group compared with the sham treatment group at month 24. Understanding the mechanism of conversion to eAMD and therapies that could prevent this event remains an important unmet need. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02462889.

Longitudinal Follow-up of Vascularized Drusen

2021-06-21

Intraocular Pressure–Related Events After Anti–Vascular Endothelial Growth Factor Therapy for Macular Edema Due to Central Retinal Vein Occlusion or Hemiretinal Vein Occlusion

JAMA Ophthalmology · 2021 · 14 citations

• Medicine
• Ophthalmology
• Surgery

IMPORTANCE: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are used to treat a variety of posterior segment conditions, including some associated with glaucoma, such as macular edema due to central retinal vein occlusion (CRVO). Therefore, information regarding intraocular pressure (IOP)-related events associated with anti-VEGF therapies is important to help balance the risks and benefits over the course of therapy. OBJECTIVE: To investigate IOP-related events among participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of a randomized clinical trial that included 312 participants with macular edema secondary to CRVO or hemiretinal vein occlusion (HRVO) who were not taking IOP-lowering medications at baseline. First randomization occurred on September 14, 2014, and contained data through data freeze on April 1, 2020. Analysis took place from April 2020 through December 2020. INTERVENTIONS: Study participants were initially randomized to 6 monthly intravitreal injections of aflibercept or bevacizumab. At month 6, protocol-defined good responders were rerandomized to continued monthly or treat-and-extend dosing of their originally assigned study drug, and protocol-defined poor or marginal responders were switched to alternative treatment. After month 12, participants were treated as per investigator discretion. MAIN OUTCOMES AND MEASURES: Three different outcomes: (1) IOP elevation more than 10 mm Hg from baseline, (2) IOP to a level higher than 35 mm Hg, and (3) IOP-lowering incisional or laser surgery. RESULTS: Of the 312 participants meeting inclusion criteria (138 [44.2%] were female; mean [SD] age, 67.8 [12.1] years), 25 (8.0%) had IOP elevation more than 10 mm Hg over baseline through month 60, and 5 (1.6%) had IOP higher than 35 mm Hg. The 60-month Kaplan-Meier cumulative incidence of IOP elevation more than 10 mm Hg over baseline was 0.13 (95% CI, 0.08-0.19), and the 60-month Kaplan-Meier cumulative incidence of IOP higher than 35 mm Hg was 0.02 (95% CI, 0.01-0.06), and did not differ among participants initially randomly assigned to receive aflibercept or bevacizumab. Three participants (1.0%) underwent IOP-lowering incisional surgery, and 3 participants (1.0%) underwent IOP-lowering glaucoma laser surgery. CONCLUSIONS AND RELEVANCE: Intravitreal anti-VEGF injections are used to treat some conditions associated with glaucoma, such as macular edema due to CRVO, and the rates of IOP-related events in this trial support monitoring IOP in eyes treated with anti-VEGF therapy for macular edema associated with CRVO or HRVO for up to 60 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01969708.

The Influence of Universal Face Mask Use on Endophthalmitis Risk after Intravitreal Anti–Vascular Endothelial Growth Factor Injections

Ophthalmology · 2021 · 47 citations

• Medicine
• Ophthalmology
• Optometry

Lapses in Care Among Patients Assigned to Ranibizumab for Proliferative Diabetic Retinopathy

JAMA Ophthalmology · 2021 · 32 citations

• Medicine
• Ophthalmology
• Pediatrics

IMPORTANCE: The follow-up schedule for individuals with eyes treated with anti-vascular endothelial growth factor agents for proliferative diabetic retinopathy (PDR) requires that patients return frequently for monitoring and repeated treatment. The likelihood that a patient will comply should be a consideration in choosing a treatment approach. OBJECTIVE: To describe completion of scheduled examinations among participants assigned to intravitreous injections of ranibizumab for PDR in a multicenter randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis evaluates data from a randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012. Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. Data were analyzed from April 2019 to July 2021. INTERVENTIONS: Ranibizumab injections for PDR or macular edema. MAIN OUTCOMES AND MEASURES: A long lapse in care of 8 or more weeks past a scheduled examination, dropout from follow-up, visual acuity at 5 years. RESULTS: Among 170 participants, the median age was 51 years, and 44.7% were female. Through 5 years of follow-up, 94 of 170 participants (55.3%) had 1 or more long lapse in care. Median time to the first long lapse was 210 weeks, and 69 of 94 participants (73.4%) returned for examination after the first long lapse. Fifty of 170 participants (29.4%) dropped out of follow-up by 5 years. Among the 120 participants who completed the 5-year examination, median change from baseline in visual acuity was -2 letters for participants who had 1 or more long lapse compared with +5 letters for those without a long lapse (P = .02). After multivariable adjustment, the odds ratio (95% CI) for baseline associations with 1 or more long lapse was 1.21 (1.03-1.43) for each 5-letter decrement in visual acuity score, 2.19 (1.09-4.38) for neovascularization of the disc and elsewhere, and 3.48 (1.38-8.78) for no prior laser treatment for diabetic macular edema. CONCLUSIONS AND RELEVANCE: Over 5 years, approximately half of the participants assigned to ranibizumab for PDR had a long lapse in care despite substantial effort by the DRCR Retina Network to facilitate timely completion of examinations. The likelihood of a long lapse in care during long-term follow-up needs to be considered when choosing treatment for PDR. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01489189.

The influence of universal face mask use on endophthalmitis risk after intravitreal anti-vascular endothelial growth factor injections during the COVID-19 pandemic

2021-06-21

Purpose : Routine use of face masks for both patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the COVID-19 pandemic. This study evaluates the impact of physician, ancillary staff, and patient face mask use on rates and outcomes of post-injection endophthalmitis. Methods : In this retrospective comparative cohort study, all eye receiving intravitreal antiVEGF factor injections from 10/1/2019 to 7/31/2020 were included from twelve centers. Cases were divided into a no face mask group if no face masks were worn by the physician or patient during intravitreal injections or a universal face mask group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections. The main outcome measures were rate of endophthalmitis, visual acuity, and microbial spectrum. Results : Of 505,968 intravitreal injections administered, 85 of 294,514 (0.0289%;1 in 3,464 injections) cases of endophthalmitis occurred in the no face mask group, and 45 of 211,454 (0.0213%;1 in 4,699 injections) cases occurred in the universal face mask group (odds ratio, 0.74;95%CI, 0.51-1.18;p=0.097;Table 1). In the no face mask group, there were 27 cases (0.0092%;1 in 10,908 injections) of culture-positive endophthalmitis compared to 9 cases (0.004%;1 in 23,494 injections) in the universal face mask group (OR, 0.46;95%CI, 0.22-0.99;p=0.041). Three cases of oral flora-associated endophthalmitis occurred in the no face mask group (0.001%;1 in 98,171 injections) compared to one (0.0005%;1 in 211,454) in the universal face mask group (p=0.645). At endophthalmitis presentation, mean logMAR visual acuity was 2.04 for no face mask group compared to 1.65 for the universal face mask group (p=0.022), although no difference was observed three months after treatment (p=0.764;Table 2). Conclusions : Universal face mask use during intravitreal anti-VEGF injections did not show a statistically significant reduction in presumed endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Future studies are warranted to assess the role of face mask use to reduce endophthalmitis risk, particularly that due to oral flora.

Reply

Retina · 2021-06-30

Bonnell, Alyssa C. MD*; Mantopoulos, Dimosthenis MD, PhD†; Fine, Howard F. MD, MHSc‡,§; Shah, Sumit P. MD‡,§; Wheatley, H. Matthew MD‡,§; Prenner, Jonathan L. MD‡,§ Author Information

Analysis of choriocapillaris flow impairment in intermediate age-related macular degeneration as a predictor of progression to exudative choroidal neovascularization

2020-06-10