Serum chemokines were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those who had less severe retinopathy. Elevated levels of the chemokines and cell adhesion molecules were also identified in eyes of a donor with ischemic diabetic retinopathy. These findings provide evidence to support the role of inflammation in the pathogenesis of diabetic retinopathy.

There is a significant genetic component associated with the risk of developing age-related macular degeneration (AMD), a leading cause of blindness among older people in Western countries. Based on the recognized role of CX3CR1, a chemokine receptor, in other age-related complex diseases and the possible involvement of the immune system in AMD pathogenesis, we tested for an association between CX3CR1 sequence variation/expression and AMD by screening two CX3CR1 single nucleotide polymorphisms (SNPs), V249I and T280M, among AMD patients and controls, and determining the level of CX3CR1 expression in AMD and normal eye tissues. PRINCIPAL FINDINGS1. An association between CX3CR1 1249/M280 alleles and AMD A significant increased prevalence of M280 and 1249 carriers or alleles was found among AMD cases vs. controls. Distribution of CX3CR1V249I and T280M did not deviate from Hardy-Weinberg equilibrium in any group (Table 1). A quantitative correlation between CX3CR1 1249/M280 and the prevalence of AMD phenotypeAs indicated in Table 1, the odds ratios (OR) of clinically diagnosed AMD compared with controls were 1.86 and 1.94 in terms of carrying 1249 and M280, respectively; however, the OR of pathologically diagnosed AMD reached 3.57 in terms of carrying M280. A higher OR was found for the clinically diagnosed AMD group compared with the aged controls whereas a lower OR was observed for the AMD group compared with the blood donor population of a much younger age. Allele frequency analysis yielded similar results (see full text version).3. Lower expression of CX3CR1 in the AMD maculae from individual bearing CX3CR1 T/M280 compared with individual bearing CX3CR1 T/T280

OBJECTIVE—Diabetes is a leading cause of morbidity and mortality. The purpose of this study is to assess the associations between diabetes complications and mortality in the Early Treatment Diabetic Retinopathy Study (ETDRS). RESEARCH DESIGN AND METHODS—We examined demographic, clinical, and laboratory characteristics of the 3,711 subjects enrolled in the ETDRS, a randomized controlled clinical trial designed to evaluate the role of laser photocoagulation and aspirin therapy for diabetic retinopathy. The outcome assessed was all-cause mortality. Multivariable Cox proportional hazards regression was used to assess associations between diabetes complications and mortality for type 1 and type 2 diabetes separately. RESULTS—The 5-year estimates of all-cause mortality were 5.5 and 18.9% for patients with type 1 and type 2 diabetes, respectively. In patients with type 1 diabetes, amputation (hazard ratio [HR] 5.08 [95% CI 2.06–12.54]) and poor visual acuity (1.74 [1.10–2.75]) remained significantly associated with mortality, after adjusting for other diabetes complications and baseline characteristics. In patients with type 2 diabetes, macrovascular disease and worsening levels of nephropathy, neuropathy, retinopathy, and visual acuity are associated with progressively increasing risks of mortality, after controlling for other baseline risk factors. CONCLUSIONS—Amputation is the strongest predictor for mortality in patients with type 1 diabetes. All complications independently predict mortality in patients with type 2 diabetes. There is an increased risk for mortality as the degree of each complication worsens. Additional studies are needed to investigate the effectiveness of tertiary prevention to decrease mortality in these patients.

Macular sensitivity and fixation quality undergo progressive change during the GA progression, reflecting alterations in macular function extending beyond the GA lesion proper. Microperimetric measurements may provide useful functional outcome measures for the clinical study of GA.

␣7 nicotinic acetylcholine receptors (nAChRs) modulate network activity in the CNS. Thus, functional regulation of ␣7 nAChRs could influence the flow of information through various brain nuclei. It is hypothesized here that these receptors are amenable to modulation by tyrosine phosphorylation. In both Xenopus oocytes and rat hippocampal interneurons, brief exposure to a broad-spectrum protein tyrosine kinase inhibitor, genistein, specifically and reversibly potentiated ␣7 nAChR-mediated responses, whereas a protein tyrosine phosphatase inhibitor, pervanadate, caused depression. Potentiation was associated with an increased expression of surface ␣7 subunits and was not accompanied by detectable changes in receptor open probability, implying that the increased function results from an increased number of ␣7 nAChRs. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis was shown to be a plausible mechanism for the rapid delivery of additional ␣7 nAChRs to the plasma membrane. Direct phosphorylation/ dephosphorylation of ␣7 subunits was unlikely because mutation of all three cytoplasmic tyrosine residues did not prevent the genisteinmediated facilitation. Overall, these data are consistent with the hypothesis that the number of functional cell surface ␣7 nAChRs is controlled indirectly via processes involving tyrosine phosphorylation.

The 12-y incidence of CGA and NV AMD in participants at moderate-to-high risk of these outcomes was lowest for those reporting the highest consumption of omega-3 LCPUFAs. If these results are generalizable, they may guide the development of low-cost and easily implemented preventive interventions for progression to advanced AMD. This trial was registered at clinicaltrials.gov as NCT00594672.

Purpose of review Age-related macular degeneration, a leading cause of visual loss in older adults, has limited therapeutic options. This review describes the current literature on the role of nutritional supplementation in primary and secondary prevention of AMD. Recent findings Many observational studies have explored the association between diet, nutrient intake, and AMD. In particular, high dietary intakes of omega 3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalent and incident AMD. However, the Age-Related Eye Disease Study (AREDS) is the only large-scale randomized controlled clinical trial to show a 25% beneficial effect of nutritional supplementation in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye at 5 years of follow-up. Based on the results of AREDS, these patients are recommended to take AREDS formulation of vitamins C, E, beta-carotene, and zinc with copper. Summary At the present time, there is insufficient evidence in the literature to recommend routine nutritional supplementation in healthy adults for primary prevention of AMD. However, patients with intermediate risk of AMD or advanced AMD in one eye should consider taking AREDS-type supplements. Observational studies have also suggested benefit from increased dietary intake of macular xanthophylls and omega-3 fatty acids. These are currently being evaluated prospectively in a randomized controlled clinical trial, the Age-Related Eye Disease Study 2 (AREDS2).

Purpose To evaluate the safety and efficacy of finasteride, an inhibitor of dihyroxytestosterone (DHT) synthesis, in the treatment of chronic central serous chorioretinopathy (CSC). Methods Five patients with chronic CSC were prospectively enrolled in this pilot study. Patients were administered finasteride (5mg) daily for 3 months, following which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity (BCVA), center-subfield macular thickness and subretinal fluid volume as assessed by optical coherence tomography (OCT). Serum DHT, serum testosterone, and urinary cortisol were also measured. Results There was no change in mean BCVA. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months, and rose to levels that were below baseline by 6 months. The changes in both OCT parameters paralleled changes in serum DHT level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased following discontinuation of finasteride. In the remaining patient, both OCT parameters normalized with finasteride and remained stable when the study medication was discontinued. Conclusion Finasteride may represent a novel medical treatment for chronic CSC. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of CSC. Summary Pilot study to evaluate finasteride for treatment of chronic central serous chorioretinopathy suggests efficacy and tolerability.