Preventive Inflammation Management with Steroids before Retreatment with Anti-VEGF after Severe Inflammation due to Brolucizumab.

PURPOSE: We report two successful cases of treatment by steroids after severe inflammation due to an intravitreal injection (IVI) of brolucizumab and their retreatment with another type of anti-vascular endothelial growth factor (VEGF), with steroid treatments to prevent severe inflammatory recurrence in patients with exudative age-related macular degeneration (AMD). CLINICAL CASES, CASE 1: An 88-year-old woman with exudative AMD in her left eye who had persistent subretinal fluid despite receiving an IVI, including ranibizumab and, subsequently, aflibercept. A switch to brolucizumab was decided. Two weeks after the third dose, she had a visual loss decreasing from 20/40 to counting fingers at 50 cm. Fundus examination revealed retinal whitening and perivenous sheathing. Fluoresceine angiography confirmed retinal arterial occlusion. Differential diagnoses were ruled out. She was treated with intravenous methylprednisolone and prednisolone eye drops. Three months after the treatment, visual acuity improved to 20/80 with no intraocular inflammation but subretinal fluid recurred. IVI of ranibizumab was rescheduled with preventive treatment by oral and local prednisolone without any inflammation recurrence. CASE 2: An 80-year-old man with exudative AMD in his right eye who had persistent subretinal fluid despite an IVI of aflibercept. Switching him to brolucizumab was decided. Two months after the third dose, he had blurred vision with no pain. Visual acuity decreased from 20/20 to 20/25. Examination showed 1+ anterior chamber cells and hyalitis. We confirmed the diagnosis of anterior uveitis with hyalitis. Differential diagnoses were ruled out. Treatment by prednisolone eye drops was initiated every 30 minutes for 1 day with a gradual decrease for 6 weeks. One week later, visual acuity improved to 20/20 with no inflammation. Three weeks later, subretinal fluid due to AMD increased. The patient was retreated by aflibercept with prednisolone eye drops, 48 hours before and after the IVI, with no recurrence of inflammation. DISCUSSION: Brolucizumab is one of the latest FDA-approved anti-VEGF agents for wet AMD. Since its wider use, few cases of severe ocular inflammation have been reported in post-marketing analysis. Because wet AMD recurrences should be expected after intraocular inflammation, insight is needed into treatment tolerance in cases that received further IVI retreatment. CONCLUSION: Our cases demonstrate that an IVI reinjection with a different anti-VEGF drug for exudative AMD recurrence can be safely reperformed. The use of local steroids could be effective in preventing recurrence of ocular inflammation after severe intraocular inflammation due to brolucizumab.

The impact of glucosamine on age-related macular degeneration in patients: A nationwide, population-based cohort study.

PURPOSE: To analyze the association between glucosamine (GlcN) use and the risk of age-related macular degeneration (AMD) using claims data from the National Health Insurance Research Database (NHIRD). METHODS: A retrospective, population-based study was conducted with NHIRD data from a 14-year period (2000-2013). Chi-squared and Student's t-tests were used to evaluate differences between the study and comparison cohorts for categorical and continuous variables, respectively. Risk factors for disease development were examined by the adjusted hazard ratio (aHR) with 95% confidence interval. Kaplan-Meier analysis was performed to compare the cumulative risk of AMD between the two cohorts. RESULTS: In total, 1,344 patients with GlcN treatment were enrolled in the study cohort and 5,376 patients without GlcN use were enrolled in the comparison cohort. The incidence rate of AMD was lower with GlcN use (3.65%) than without GlcN use (5.26%) (P = 0.014). GlcN use was associated with a lower risk of developing AMD among patients with hyperlipidemia, coronary artery disease, chronic obstructive pulmonary disease, stroke, other neurological disorders, or degenerative arthritis. Although the incidence of wet type AMD did not significantly differ (P = 0.91), the incidence of dry type AMD was lower in patients with GlcN use (2.9%) than those without GlcN use (4.84%) (P = 0.003). Kaplan-Meier analysis similarly revealed a lower rate of dry type AMD in patients with GlcN use compared to those without GlcN use (log-rank P = 0.004). CONCLUSIONS: GlcN treatment can decrease the risk of developing dry type AMD. Further prospective controlled studies are needed to determine the effectiveness of GlcN treatment in patients with AMD and the associated mechanism.

The Effect of Blue-Light Filtering Intraocular Lenses on the Development and Progression of Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the prevention of neovascular age-related macular degeneration (nAMD) after cataract surgery. DESIGN: Cohort study. PARTICIPANTS: Patients who underwent uneventful cataract surgery between 2007 and 2018 at the Ophthalmology Unit of Kymenlaakso Central Hospital, Kotka, Finland. METHODS: Subsequent nAMD rates were compared between patients who received BLF IOLs and those who received non-BLF IOLs. Kaplan-Meier and Cox regression analyses for the overall risk of nAMD developing were assessed. Best-corrected visual acuity (BCVA), foveal thickness, treatment interval, and total number of intravitreal injections were secondary outcomes. A separate analysis was performed on patients with pre-existing nAMD to assess the effect of BLF IOLs on nAMD progression. A single eye of each patient was included. MAIN OUTCOME MEASURE: Neovascular age-related macular degeneration-free survival. RESULTS: Included were 11 397 eyes of 11 397 patients with a mean age of 75.4 ± 8.3 years (62.5% women). The BLF IOL was used in 5425 eyes (47.6%), and the non-BLF IOL was used in 5972 eyes (52.4%). During follow-up (BLF IOL group, 55.2 ± 34.1 months; non-BLF IOL group, 50.5 ± 30.1 months; P < 0.001), 164 cases of new-onset nAMD were recorded (BLF group, n = 88; non-BLF group, n = 76). The nAMD-free survival was similar between the groups (P = 0.465, log-rank test). In a Cox regression analysis controlling for age, gender, and a documented diagnosis of macular degeneration, the use of a BLF IOL was not predictive of nAMD development (hazard ratio [HR], 1.075; 95% confidence interval [CI], 0.79-1.47; P = 0.652). In nAMD patients, secondary clinical outcomes at 1 year were comparable for BCVA (0.57 ± 0.4 logarithm of the minimum angle of resolution vs. 0.45 ± 0.4 logarithm of the minimum angle of resolution; P = 0.136), foveal thickness (285 ± 109 µm vs. 299 ± 103µm; P = 0.527), number of anti-vascular endothelial growth factor injections (6.5 ± 2.5 vs. 6.2 ± 2.7; P = 0.548), and treatment interval (7.5 ± 2.4 weeks vs. 8.1 ± 2.4 weeks; P = 0.271) for BLF and non-BLF IOLs, respectively. Similarly to patients in whom nAMD developed after the surgery, among patients with nAMD before surgery (BLF, n = 71; non-BLF, n = 74), the clinical outcomes again were comparable (all P > 0.05). CONCLUSIONS: In a large cohort of patients who underwent cataract surgery, the use of a BLF IOL resulted in no apparent advantage over a non-BLF IOL in the incidence of nAMD or its progression, nor in clinical variables related to nAMD severity.

Progression of Geographic Atrophy with Subsequent Exudative Neovascular Disease in Age-Related Macular Degeneration: AREDS2 Report 24.

PURPOSE: To examine whether the rate of geographic atrophy (GA) enlargement is influenced by subsequent exudative neovascular age-related macular degeneration (nAMD) and hence, to explore indirectly whether nonexudative nAMD may slow GA enlargement. DESIGN: Post hoc analysis of a controlled clinical trial cohort. PARTICIPANTS: Age-Related Eye Disease Study 2 participants 50 to 85 years of age. METHODS: Baseline and annual stereoscopic color fundus photographs were evaluated for (1) GA presence and area and (2) exudative nAMD presence. Two cohorts were constructed: eyes with GA at study baseline (prevalent cohort) and eyes in which GA developed during follow-up (incident cohort). Mixed-model regression of the square root of GA area was performed according to the presence or absence of subsequent exudative nAMD. MAIN OUTCOME MEASURES: Change over time in square root of GA area. RESULTS: Of the 757 eyes in the incident GA cohort, over a mean follow-up of 2.3 years (standard deviation [SD], 1.2 years), 73 eyes (9.6%) demonstrated subsequent exudative nAMD. Geographic atrophy enlargement in these eyes was significantly slower (0.20 mm/year; 95% confidence interval [CI], 0.12-0.28 mm/year) compared with the other 684 eyes in which subsequent exudative nAMD did not develop (0.29 mm/year; 95% CI, 0.27-0.30 mm/year; P = 0.037). Of the 456 eyes in the prevalent GA cohort, over a mean follow-up of 4.1 years (SD, 1.4 years), 63 eyes (13.8%) demonstrated subsequent exudative nAMD. Geographic atrophy enlargement in these eyes was similar (0.31 mm/year; 95% CI, 0.24-0.37 mm/year) compared with the other 393 eyes in which subsequent exudative nAMD did not develop (0.28 mm/year; 95% CI, 0.26-0.29 mm/year; P = 0.37). CONCLUSIONS: In eyes with recent GA, GA enlargement before the development of exudative nAMD seems slowed. This association was not observed in eyes with more long-standing GA, which have larger lesion sizes. Hence, perilesional nonexudative choroidal neovascular tissue (presumably present before the development of clinically apparent exudation) may slow enlargement of smaller GA lesions through improved perfusion. This hypothesis warrants further evaluation in prospective studies.

Can the Onset of Neovascular Age-Related Macular Degeneration Be an Acceptable Endpoint for Prophylactic Clinical Trials?

Many studies over the past 20 years have pursued the goal of preventing or deferring progression from early and intermediate age-related macular degeneration (AMD) to advanced AMD. The onset of neovascular AMD has been used as a primary endpoint in some prophylactic clinical trials because it is easy to assess and relatively well-defined. Nevertheless, the use of this endpoint for assessing progression of AMD lacks validation. The aims of this paper are to review the current practice of clinical trials investigating the prevention of progression of early or intermediate AMD to neovascular AMD, so-called prophylactic trials, as well as identify ongoing efforts to standardize endpoints and select the ideal population for such studies.

Screening Medications for Association with Progression to Wet Age-Related Macular Degeneration.

PURPOSE: There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to neovascular AMD (nAMD). If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data mining method that can simultaneously evaluate thousands of correlated hypotheses, while adjusting for multiple testing, to screen for associations between drugs and delayed progression to nAMD. DESIGN: We applied a nested case-control study to administrative insurance claims data to identify cases with nAMD and risk-set sampled controls that were 1:4 variable ratio matched on age, gender, and recent healthcare use. PARTICIPANTS: The study population included cases with nAMD and risk set matched controls. METHODS: We used a tree-based scanning method to evaluate associations between hierarchical classifications of drugs that patients were exposed to within 6 months, 7 to 24 months, or ever before their index date. The index date was the date of first nAMD diagnosis in cases. Risk-set sampled controls were assigned the same index date as the case to which they were matched. The study was implemented using Medicare data from New Jersey and Pennsylvania, and national data from IBM MarketScan Research Database. We set an a priori threshold for statistical alerting at P ≤ 0.01 and focused on associations with large magnitude (relative risks ≥ 2.0). MAIN OUTCOME MEASURES: Progression to nAMD. RESULTS: Of approximately 4000 generic drugs and drug classes evaluated, the method detected 19 distinct drug exposures with statistically significant, large relative risks indicating that cases were less frequently exposed than controls. These included (1) drugs with prior evidence for a causal relationship (e.g., megestrol); (2) drugs without prior evidence for a causal relationship, but potentially worth further exploration (e.g., donepezil, epoetin alfa); (3) drugs with alternative biologic explanations for the association (e.g., sevelamer); and (4) drugs that may have resulted in statistical alerts due to their correlation with drugs that alerted for other reasons. CONCLUSIONS: This exploratory drug-screening study identified several potential targets for follow-up studies to further evaluate and determine if they may prevent or delay progression to advanced AMD.

Benefits of micronutrient supplementation for reducing the risk of wet age-related macular disease and diabetic retinopathy: An update.

Age-related macular disease and diabetic retinopathy are chronic degenerative diseases characterised by progressive visual impairment. In Europe, age-related macular disease accounts for over 15% of blindness in adults over 50 years of age, and although the burden of diabetic retinopathy in terms of vision impairment is lower, vision loss associated with diabetic retinopathy is increasing with the rising prevalence of diabetes mellitus and the ageing of the population. Late-stage age-related macular disease can be subdivided into dry (non-neovascular) or wet (neovascular or exudative) forms. The large Age-Related Eye Disease Study 2 showed that supplementation with antioxidant nutrients reduces choroids neovascularisation and reduces the risk of progression of neovascular age-related macular disease. Antioxidant micronutrient supplements have also shown promising results in preventing the pathogenesis of retinopathy in animal models of diabetes. Age-related macular disease and diabetic retinopathy are understood to share some common pathophysiological characteristics, suggesting that micronutrients have an important role in ocular health in both conditions. This article will review the current evidence for the utility of micronutrients in preventing the development and progression of neovascular age-related macular disease and diabetic retinopathy.

Fibulin-7 C-terminal fragment and its active synthetic peptide suppress choroidal and retinal neovascularization.

Wet age-related macular degeneration (AMD) and diabetic retinopathy are the leading causes of blindness through increased angiogenesis. Although VEGF-neutralizing proteins provide benefit, inconsistent responses indicate a need for new therapies. We previously identified the Fibulin-7 C-terminal fragment (Fbln7-C) as an angiogenesis inhibitor in vitro. Here we show that Fbln7-C inhibits neovascularization in vivo, in both a model of wet AMD involving choroidal neovascularization (CNV) and diabetic retinopathy involving oxygen-induced ischemic retinopathy. Furthermore, a short peptide sequence from Fbln7-C is responsible for the anti-angiogenic properties of Fbln7-C. Our work suggests Fbln7-C as a therapeutic candidate for wet AMD and ischemic retinopathy.

Chitinase-3-Like-1 Promotes M2 Macrophage Differentiation and Induces Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration.

Purpose: Choroidal neovascularization (CNV) is the principal pathological factor contributing to blindness in neovascular age-related macular degeneration (nAMD). Infiltration of M2 macrophage is thought to contribute to CNV progress, although the way that regulates its differentiation remains unclear. Here, we investigate the role of CHI3L1 in M2 differentiation and angiogenesis in CNV. Methods: Serums from nAMD patients were tested for CHI3L1 expression. Mice were subjected to laser injury to induce CNV, and lesion expansion were tracked using fundus fluorescence angiography (FFA) and immunofluorescence analysis. Several strategies were taken to verify the contribution of M2 macrophage and CHI3L1: macrophage depletion by clodrosome, local CHI3L1 inhibition using intravitreally injection neutralize antibody (mAY), and depletion of CHI3L1 receptor (IL13-Ra2) by small-interfering RNA (siRNA). Tuber analysis was used to further determine angiogenetic effect of CHI3L1. Anti-VEGFA was used as positive control for mAY. Results: Serum levels of CHI3L1 were highly elevated in nAMD patients. CHI3L1 was expressed by infiltrating M2 macrophages and was elevated as CNV progress in a mice model. System macrophage depletion and local suppression of CHI3L1 alleviated CNV formation while enhancing anti-VEGFA therapeutic effect. Stimulation of macrophage with recombinant CHI3L1 activated MAPK signaling cascade and induced transition to M2, while siRNA knockdown of IL13-Ra2 abolished it. In an in vitro coculture system, supernatants from CHI3L1-stimulated M2 macrophages and promoted tube vascularization. Conclusions: These results unveil novel angiogenic regulation of CHI3L1 and M2 polarized macrophages in CNV development. These mechanistic insights may point to CHI3L1 as a new therapeutic target for treatment for nAMD.

Guía de práctica clínica para el diagnóstico y tratamiento de la degeneración macular relacionada a la edad: guía en versión extensa / Clinical practice guideline for the diagnosis and treatment of age-related macular degeneration: long version guide

Brindar recomendaciones y puntos de buenas prácticas clínicas basadas en evidencia para el adecuado diagnóstico y tratamiento de los pacientes con degenaración macular relacionada con la edad (DMRE), contestando a las siguientes preguntas: a) En personas mayores de 50 años, ¿cómo se debería diagnosticar y clasificar la DMRE? b) En personas con DMRE, ¿qué intervenciones deben usarse para prevenir la progresión de la enfermedad? c) En personas con DMRE exudativa, ¿se debería utilizar antiangiogénicos para el tratamiento de la enfermedad? d) En personas con DMRE exudativa, ¿se debería utilizar la terapia fotodinámica como tratamiento adyuvante? e) En personas con DMRE exudativa, ¿se debería utilizar corticoides intravítreos como tratamiento adyuvante? f) En personas con DMRE, ¿cuál es la mejor estrategia de seguimiento de la enfermedad?

Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration.

Purpose: There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Methods: Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. Results: There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. Conclusions: A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.

Single ocular injection of a sustained-release anti-VEGF delivers 6months pharmacokinetics and efficacy in a primate laser CNV model.

A potent anti-vascular endothelial growth factor (VEGF) biologic and a compatible delivery system were co-evaluated for protection against wet age-related macular degeneration (AMD) over a 6month period following a single intravitreal (IVT) injection. The anti-VEGF molecule is dimeric, containing two different anti-VEGF domain antibodies (dAb) attached to a human IgG1 Fc region: a dual dAb. The delivery system is based on microparticles of PolyActive™ hydrogel co-polymer. The molecule was evaluated both in vitro for potency against VEGF and in ocular VEGF-driven efficacy models in vivo. The dual dAb is highly potent, showing a lower IC50 than aflibercept in VEGF receptor binding assays (RBAs) and retaining activity upon release from microparticles over 12months in vitro. Microparticles released functional dual dAb in rabbit and primate eyes over 6months at sufficient levels to protect Cynomolgus against laser-induced grade IV choroidal neovascularisation (CNV). This demonstrates proof of concept for delivery of an anti-VEGF molecule within a sustained-release system, showing protection in a pre-clinical primate model of wet AMD over 6months. Polymer breakdown and movement of microparticles in the eye may limit development of particle-based approaches for sustained release after IVT injection.

Topical application of a G-Quartet aptamer targeting nucleolin attenuates choroidal neovascularization in a model of age-related macular degeneration.

Choroidal neovascularization (CNV) associated with the 'wet' form of age related macular degeneration (AMD) is one of the most common causes of central vision loss among the elderly. The 'wet' form of AMD is currently treated by intravitreal delivery of anti-VEGF agents. However, intravitreal injections are associated with complications and long-term inhibition of VEGF leads to macular atrophy. Thus, there is currently an unmet need for the development of therapies for CNV that target molecules other than VEGF. Here, we describe nucleolin as a novel target for the 'wet' form of AMD. Nucleolin was found on the surface of endothelial cells that migrate from the choroid into the subretinal space in the laser-induced model of 'wet' AMD. AS1411 is a previously described G-quartet oligonucleotide that has been shown to bind nucleolin. We found that AS1411 inhibited the formation of tubes by human umbilical vein endothelial cells (HUVECs) by approximately 27.4% in vitro. AS1411 co-localized with the site of laser induced CNV in vivo. Intravitreally injected AS1411 inhibited laser-induced CNV by 37.6% and attenuated infiltration of macrophages by 40.3%. Finally, topical application of AS1411 led to a 43.4% reduction in CNV. Our observations have potential implications for the development of therapies for CNV and specifically for the 'wet' form of AMD.

Cost-effectiveness of anti-oxidant vitamins plus zinc treatment to prevent the progression of intermediate age-related macular degeneration. A Singapore perspective.

PURPOSE: To determine if providing high dose anti-oxidant vitamins and zinc treatment age-related eye disease study (AREDS formulation) to patients with intermediate age-related macular degeneration (AMD) aged 40-79 years from Singapore is cost-effective in preventing progression to wet AMD. METHODS: A hypothetical cohort of category 3 and 4 AMD patients from Singapore was followed for 5 calendar years to determine the number of patients who would progress to wet AMD given the following treatment scenarios: (a) AREDS formulation or placebo followed by ranibizumab (as needed) for wet AMD. (b) AREDS formulation or placebo followed by bevacizumab (monthly) for wet AMD. (c) AREDS formulation or placebo followed by aflibercept (VIEW I and II trial treatment regimen). Costs were estimated for the above scenarios from the providers' perspective, and cost-effectiveness was measured by cost per disability-adjusted life year (DALY) averted with a disability weight of 0.22 for wet AMD. The costs were discounted at an annual rate of 3%. RESULTS: Over 5400 patients could be prevented from progressing to wet AMD cumulatively if AREDS formulation were prescribed. AREDS formulation followed by ranibizumab was cost-effective compared to placebo-ranibizumab or placebo-aflibercept combinations (cost per DALY averted: SGD$23,662.3 and SGD$21,138.8, respectively). However, bevacizumab (monthly injections) alone was more cost-effective compared to AREDS formulation followed by bevacizumab. CONCLUSION: Prophylactic treatment with AREDS formulation for intermediate AMD patients followed by ranibizumab or for patients who progressed to wet AMD was found to be cost-effective. These findings have implications for intermediate AMD screening, treatment and healthcare planning in Singapore.

Long-term outcome of intravitreal pegaptanib sodium as maintenance therapy in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate the results of a 3-year follow-up of intravitreal pegaptanib sodium injection as maintenance therapy for the treatment of neovascular age-related macular degeneration (AMD) in Japanese patients. METHODS: In this prospective, uncontrolled interventional study, 20 eyes of 19 patients with treatment-naïve AMD who had received 3 consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as the induction treatment and had shown clinical/anatomical improvement were enrolled. An intravitreal injection of 0.3 mg/0.09 mL pegaptanib sodium was administered as the maintenance therapy every 6 weeks. Booster treatments using ranibizumab were allowed if clinical deterioration was judged to be present. The primary outcome measures were the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) as evaluated using spectral-domain optical coherence tomography. RESULTS: Sixteen of the 20 eyes (80 %) were assessed at the 3-year follow-up. The mean logMAR BCVA improved significantly from 0.56 ± 0.31 before the induction treatment to 0.24 ± 0.25 at baseline (P < 0.001) and was well maintained at 156 weeks (0.25 ± 0.28, P = 0.938). Moreover, the mean CFT also decreased significantly from 346 ± 111 µm before the induction treatment to 232 ± 54 µm at baseline (P < 0.001) and was well preserved at 156 weeks (210 ± 59 µm, P = 0.278). Thirteen eyes (81.3 %) received an unscheduled booster treatment, and no severe systemic or ocular side effects occurred during follow-up. CONCLUSION: Intravitreal pegaptanib sodium injection as the maintenance therapy was effective in stabilizing the vision of patients with AMD in whom induction treatment led to improved BCVA, as evaluated at the 3-year follow-up.

The relationship of major American dietary patterns to age-related macular degeneration.

PURPOSE: We hypothesized that major American dietary patterns are associated with risk for age-related macular degeneration (AMD). DESIGN: Cross-sectional study. METHODS: We classified 8103 eyes in 4088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS). They were classified into control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765) by the AREDS AMD Classification System. Food consumption data were collected by using a 90-item food frequency questionnaire. RESULTS: Two major dietary patterns were identified by factor (principal component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the 2 patterns by calculating the 2 factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O = 0.74 (95% confidence interval (CI): 0.59-0.91; Ptrend =0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W = 1.56 (1.18-2.06; Ptrend = 0.01). For advanced AMD, the ORA5O was 0.38 (0.27-0.54; Ptrend < 0.0001), and the ORA5W was 3.70 (2.31-5.92; Ptrend < 0.0001). CONCLUSIONS: Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study.

Risk factors for exudative age-related macular degeneration in a large French case-control study.

PURPOSE: The purpose of the CAP (Creteil AMD PHRC-funded) Study was to analyze risk factors of exudative age-related macular degeneration (AMD) in a large French case-control population. PATIENTS AND METHODS: One thousand and twenty-four patients with exudative AMD and 275 controls were recruited. Information about lifestyle, medical history, and dietary intake were collected. Associations of risk factors were estimated using logistic regression. RESULTS: After multivariate adjustment, CFH Y402H and ARMS2 A69S polymorphisms were associated with very high risk for exudative AMD (OR = 6.21 and OR = 11.7, respectively, p < 0.0001). Risk for exudative AMD was increased in current smokers (OR = 3.79, p = 0.0003) and former smokers having quitted since less than 20 years ago (OR = 2.30, p = 0.002), but not in former smokers having quitted since 20 years or more ago (OR = 0.81, p = 0.43). Heavy smokers (at least 25 pack-years) were particularly at risk (OR = 3.61, p < 0.0001). Use of cooking oils rich in omega 3 fatty acids was significantly associated with a reduced risk of exudative AMD (OR = 0.55, 95 % CI: 0.36-0.84, p = 0.006), as well as a high consumption of fruits (OR = 0.60, 95 % CI: 0.37-0.98, p = 0.04), but not the consumption of fish, vegetables or oils rich in omega 6. High waist circumference was associated with increased risk for exudative AMD (OR = 2.53, p < 0.0001), but not hypercholesterolemia, hypertension, or body mass index. CONCLUSIONS: The CAP Study confirms major genetic risk factors for exudative AMD. It further documents the high risk in heavy smokers and the long persistence of risk after smoking cessation, and the associations with waist circumference and fruit consumption. Furthermore, we observed an inverse correlation between AMD and cooking oils harboring a beneficial omega-3 fatty acid profile.

Prevention and treatment of age-related macular degeneration: an update for pharmacists.

OBJECTIVE: Review the current recommendations for the prevention and treatment of age-related macular degeneration (AMD). DATA SOURCES: Articles indexed in PubMed (National Library of Medicine), the Cochrane Reviews and Trials, Dynamed, and Iowa Drug Information Service (IDIS) in the last 10 years using the key words macular degeneration, agerelated macular degeneration (AMD), AMD and treatment, AMD and prevention. STUDY SELECTION AND DATA EXTRACTION: Sixty-nine published papers were reviewed, and criteria supporting the primary objective were used to identify useful resources. DATA SYNTHESIS: The literature included practice guidelines, original research articles, review articles, product prescribing information, and supplement product information for the prevention and treatment of AMD. CONCLUSION: AMD is a leading cause of visual impairment in older adults. At present there is no cure for advanced AMD, but intravitreal vascular endothelial growth factor inhibitors minimize and even reverse vision loss in patients with AMD of the neovascular type. In the Age-Related Eye Disease Study (AREDS), participants with intermediate AMD who received a supplement combination of vitamins C and E, beta-carotene, and zinc had a greater delay in progression to advanced AMD than those participants who received a portion of these supplements. In the second AREDS, AREDS2, the addition of lutein + zeaxanthin, docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), or lutein + zeaxanthin and DHA + EPA to the complete AREDS formulation did not further reduce the risk of progression to advanced AMD. Subgroup analyses indicated that additional research with lutein + zeaxanthin supplementation is warranted as it was beneficial in participants with low dietary intake of lutein + zeaxanthin. A formulation without beta-carotene may be best for most patients, especially smokers or former smokers. Health care professionals will want to consider patient-specific information before recommending ocular health supplements.

Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study.

OBJECTIVE: To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing exudative age-related macular degeneration (AMD). DESIGN: The Nutritional AMD Treatment 2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study. PARTICIPANTS: Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye. METHODS: Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years. MAIN OUTCOME MEASURES: The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM). RESULTS: Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (-68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10-0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group. CONCLUSIONS: In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same effect on CNV incidence in the second eye as did the placebo. However, RBCM fatty acid measurements revealed that CNV incidence was significantly reduced in DHA-supplemented patients showing a steadily high EPA plus DHA index over 3 years. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.