Controversies and Disparities in the Management of Age-Related Macular Degeneration.

Age-related macular degeneration is a leading cause of blindness in patients aged 50 years and older. Prior to the 21st century, there were no effective treatments for this devastating disease. However, the last 20 years have heralded the development of treatments for both the nonexudative and exudative forms. The invention of AREDS vitamin supplements and anti-VEGF therapies forever changed the treatment of dry and wet age-related macular degeneration, respectively. The rapid adoption and expansion of these vision preserving treatments has created controversy regarding their cost, burden of administration, development, and use of new technologies, genetic considerations, and observed societal disparities. Many of these controversies and disparities persist today and will require further research to resolve.

Higher Intake of Polyunsaturated Fatty Acid and Monounsaturated Fatty Acid is Inversely Associated With AMD.

Purpose: To evaluate the association between dietary fat intake and the presence of AMD. Methods: Cross-sectional, observational study with cohorts prospectively recruited from the United States and Portugal. AMD was diagnosed based on color fundus photographs with the AREDS classification. A validated food frequency questionnaire was used to calculate the percent energy intake of trans fat, saturated fat, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA). Odds ratio (OR) and 95% confidence intervals for quintile of amount of FA were calculated. Multiple logistic regression was used to estimate the OR. Results: We included 483 participants, 386 patients with AMD and 97 controls. Higher intake of trans fat was associated with a 2.3-fold higher odds of presence of AMD (P for trend = 0.0156), whereas a higher intake of PUFA (OR, 0.25; P for trend = 0.006) and MUFA (OR, 0.24; P for trend < 0.0001) presented an inverse association. Subgroup analysis showed that higher quintile of trans fat was associated with increased odds of having intermediate AMD (OR, 2.26; P for trend = 0.02); and higher quintile of PUFA and MUFA were inversely associated with intermediate AMD (OR, 0.2 [P for trend = 0.0013]; OR, 0.17 [P for trend < 0.0001]) and advanced AMD (OR, 0.13 [P for trend = 0.02]; OR, 0.26 [P for trend = 0.004]). Additionally, a statistically significant effect modification by country was noted with inverse association between MUFA and AMD being significant (OR, 0.04; P for trend < 0.0001) for the Portugal population only. Conclusions: Our study shows that higher dietary intake of trans fat is associated with the presence of AMD, and a higher intake of PUFA and MUFA is inversely associated with AMD.

HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

PURPOSE: To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). METHODS: Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. RESULTS: Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; ß = 0.30, P = 0.045), taking AREDS vitamins (ß = 5.51, P < 0.001), and family history of AMD (ß = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (ß = 1.84, P = 0.006), taking AREDS supplements (ß = 1.67, P = 0.021) and alcohol intake (ß = 0.07, P = 0.017). CONCLUSION: Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization.

Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.