Age-Related Macular Degeneration and Mortality in the Age-Related Eye Disease Study (AREDS): The Effect of Sex and Time.

PURPOSE: Age-related macular degeneration (AMD) shares similar risk factors and pathogeneses with cardiovascular diseases (CVDs). Epidemiologic studies over the past 2 decades analyzing the association between AMD and all-cause and CVD-specific mortality have failed to yield conclusive results. The purpose of this analysis is to investigate the sex-specific association between AMD and all-cause and CVD-specific mortality, and to assess whether duration of follow-up alters the strength of association. DESIGN: The database of Genotypes and Phenotypes (dbGaP) data set for the Age-Related Eye Disease Study, a randomized clinical trial of high-dose antioxidants in AMD prevention, with participants enrolled from 1992 to 1998 and followed through 2005, was used in the analysis. PARTICIPANTS: There were 4757 Age-Related Eye Disease Study participants aged 55 through 80 years (mean, 69.4 years; 44.1% male) recruited from 11 retinal specialty clinics. Participants had standard Age-Related Eye Disease Study AMD categories (category 1, n = 1117; category 2, n = 1062; category 3, n = 1621; category 4, n = 957). METHODS: The sex-specific adjusted hazard ratio (HRadj) between baseline AMD and all-cause and CVD-specific mortality was determined at multiple time points (e.g., 5, 7, 10, and all years), adjusting for age, race, diabetes, hypertension, angina, cancer, smoking, obesity, clinical trial antioxidant treatment category, and education. MAIN OUTCOME MEASURES: Sex-specific all-cause and CVD-specific mortality. RESULTS: Mean follow-up was 9.6 years (range, 0.5-12.5 years), with 1087 deaths (category 1, n = 197 [17.6%]; category 2, n = 200 [18.8%]; category 3, n = 356 [22.0%]; category 4, n = 326 [34.1%]). Sex-stratified models demonstrated sex differences; in women, a significant association between AMD category 4 and all-cause mortality existed compared with category 1 at each period (HRadj, 1.5-2.3; all P ≤ 0.005); similar category 4 findings were present with CVD-specific mortality, strengthening with shorter periods (HRadj, 1.9-4.6; all P ≤ 0.01). Among men, a significant association between all AMD stages and all-cause (HRadj, 1.5-2.3; all P ≤ 0.05) and CVD-specific mortality (HRadj, 1.6-4.0; all P ≤ 0.05) existed for nearly all periods. CONCLUSIONS: Substantial late AMD cases and deaths exceed those in previous population-based studies to better test mortality-related hypotheses. Age-related macular degeneration was significantly associated with all-cause and CVD-specific mortality. Relationships weakened over a longer duration of follow-up, and sex seems to modify the association. Future analyses are warranted to interrogate the possible clinical usefulness of these relationships.

Resveratrol based oral nutritional supplement produces long-term beneficial effects on structure and visual function in human patients.

BACKGROUND: Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. METHODS: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). RESULTS: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient's pathophysiology. No side effects were observed. CONCLUSIONS: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities.

An adaptable HPLC method for the analysis of frequently used antibiotics in ocular samples.

Four different antibiotics, delivered individually to rabbit eyes via hydrophilic intraocular lenses soaked in the drug solution prior to implantation, were measured in aqueous and vitreous humor samples from the eyes. To meet this analytical need, we developed a sensitive, high performance liquid chromatographic (HPLC) method for measuring the concentrations of moxifloxacin, gatifloxacin, linezolid, and cefuroxime in the ocular tissue. Separations were carried out on a LichroSpher RP-18 column, maintained at room temperature. The fluoroquinolones were eluted with a mobile phase consisting of 20% acetonitrile, in 0.1% trifluoroacetic acid (pH 3.0) with 30 mM tetrabutylammonium chloride. Linezolid and cefuroxime were eluted with 25% acetonitrile in 25 mM Na acetate buffer, pH 5.0. All elutions were isocratic. With ultraviolet detection, the lower limit of quantitation (LLOQ) for these compounds approached 1 ng (on-column injection). By using fluorescence detection, the LLOQ for the fluoroquinolones improved to 200 pg. The overall accuracy of the method was >or=90%. With minor modifications, the method was optimized for each of the agents, and the resulting analytical sensitivity made the method suitable for clinical investigations of the ocular penetration of these drugs.

Treating uveitis-associated hypotony with pars plana vitrectomy and silicone oil injection.

PURPOSE: The purpose of this study was to determine the effect on intraocular pressure (IOP) and visual acuity of treating uveitis-related hypotony in patients with vitrectomy and intravitreal silicone oil injection. METHODS: Patients who underwent pars plana vitrectomy and silicone oil injection for uveitis-associated hypotony treatment were identified retrospectively. The primary outcome was maintaining an IOP of > or =5 mmHg. Visual acuity improvement was defined as an increase in > or =2 lines of acuity. RESULTS: Twelve eyes of 10 patients were identified. Median preoperative IOP was 2 mmHg (range: 0-7 mmHg). Two of 12 eyes had an IOP of > or =5 mmHg at presentation. The number of eyes with an IOP of > or =5 mmHg was 7 of 12 eyes (58%) at 1 month, 4 of 12 eyes (33%) at 3 months, 6 of 12 eyes (50%) at 6 months, and 3 of 9 eyes (33%) at 1 year. Five of 12 eyes (42%) were reinjected between 1 and 3 times with silicone oil for recurring hypotony. Median presenting Snellen visual acuity was counting fingers (range: 20/125 to light perception). Seven of 9 eyes (78%) maintained their preoperative vision at 1 year. CONCLUSION: Intraocular pressure elevated modestly in most patients in this series. However, results were often transient, and some eyes required repeated silicone oil injections. Although silicone oil is reasonable to consider for the treatment and maintenance of IOP in patients with ocular hypotony secondary to uveitis, better treatments are needed.

Mycobacterium haemophilum: a rare cause of endophthalmitis.

Nontuberculous mycobacterial (NTM) infections are becoming an increasingly important complication in ophthalmology, particularly among immunocompromised patients. We report a case of NTM in a 66-year-old male immunosuppressed after cardiac transplantation. Chronic granulomatous iridocyclitis progressed to purulent endophthalmitis despite intraocular and systemic antimicrobial therapy. Direct immunoflourescent staining of the vitrectomy specimen revealed acid-fast bacilli. Biopsies of nodular skin lesions revealed non-caseating granulomas with acid-fast bacilli. Cultures of skin and eye biopsies yielded Mycobacterium haemophilum. Despite aggressive combination antimicrobial therapy, the eye was eventually enucleated. Resolution of systemic infection occurred with the addition of granulocyte macrophage-colony stimulating factor. This is the first reported case of M. haemophilum endophthalmitis.

Ultrasound biomicroscopic analysis of iris profile changes with accommodation in pigmentary glaucoma and relationship to age.

PURPOSE: To examine the effect of accommodation on iris profile in pigmentary glaucoma and its relationship to age. DESIGN: Interventional case series. METHODS: We measured change in iris profile with accommodation in 92 eyes of 92 patients with pigmentary glaucoma. RESULTS: Mean age was 42 years. Mean change in posterior iris excursion from nonaccommodated to accommodated state was 144.5 microm. (P < .001). Age was plotted against iris excursion with an estimated least-squares regression line. The estimated Pearson correlation coefficient was -0.60, (P < .001). Patients younger than 42 years of age had a mean change in excursion of 209.2 microm compared with 79.8 microm for those patients older than 42 years. (P < .001) CONCLUSION: This study found that there is a significant increase in posterior iris bowing in the accommodated state. Increasing age is associated with decreased posterior iris deviation. These findings add evidence to the theory of accommodation-induced reverse pupillary block in pigmentary glaucoma.