Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression

JAMA Ophthalmology · 2022 · 165 citations

• Medicine
• Internal medicine
• Ophthalmology

Importance: After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up. Objective: To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD). Design, Setting, and Participants: This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022. Interventions: During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively. Main Outcomes and Measures: Self-reported lung cancer and late AMD validated with medical records. Results: This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48). Conclusions and Relevance: Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.

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.

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.

Demographic trends of open globe injuries in a large inpatient sample

Eye · 2020 · 20 citations

• Medicine
• Demography
• Pediatrics

Predictive factors of enucleation after open globe injuries

Graefe s Archive for Clinical and Experimental Ophthalmology · 2020 · 29 citations

• Medicine
• Pediatrics
• Surgery

Update on the Use of Anti-VEGF Drugs in the Treatment of Retinopathy of Prematurity

Journal of Pediatric Ophthalmology & Strabismus · 2020 · 18 citations

• Medicine
• Ophthalmology
• Surgery

Retinopathy of prematurity (ROP) is one of the many significant consequences of premature birth and remains one of the leading causes of visual impairment in infants. Originally, cryotherapy was used to prevent the complications of vitreous hemorrhage and retinal detachment. Subsequently, laser photocoagulation, which is at least as effective and possibly safer than cryoretinopexy, was adopted as the primary treatment for type 1 ROP (stage 2 or 3 disease in zone II with plus disease or any stage disease in zone I with plus disease or stage 3 disease in zone I without plus disease). Laser therapy has been proven effective, and has a degree of permanence that is yet to be matched by alternative treatments, but can be associated with significant ocular side effects such as myopia. Treatment of type 1 ROP with anti-vascular endothelial growth factor (VEGF) agents seems to have fewer ocular side effects than laser ablation of the retina, particularly if used to treat type 1 ROP in zone I. However, ROP recurrence is a real threat after anti-VEGF therapy and long-term systemic side effects of this therapy remain under evaluation. This review focuses on the ophthalmic and systemic benefits and risks of anti-VEGF therapies for ROP as compared to retinal photocoagulation. Anti-VEGF therapies have dramatically altered the management of ROP and have also been shown to be beneficial with regard to the visual prognosis of patients with ROP, but patients so treated require frequent short- and long-term follow-up to detect and manage potential complications associated with this form of treatment. Such information also will allow clinicians to characterize the efficacy, side effect profile, and utility of intravitreal anti-VEGF agents for this condition. Prospective studies are needed to identify the optimum anti-VEGF drug and dose. [J Pediatr Ophthalmol Strabismus. 2020;57(6):351-362.].