Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

A b b re v i a t i o n s :A I R g l u c o s e , acute insulin response to glucose; DI, disposition index; FSIGT, frequently sampled intravenous glucose tolerance test; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; S I , insulin sensitivity index.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Reduced -Cell Compensation to the Insulin Resistance Associated Wi t h O b e s ity in Members of Caucasian Familial Type 2 Diabetic Kindre d s O R I G I N A L A R T I C L EO B J E C T I V E -Both obesity and a family history of diabetes reduce insulin sensitivity, but the impact of obesity on insulin secretion among individuals predisposed to diabetes is uncertain. We used a pedigree-based approach to test the hypothesis that -cell compensation to the insulin resistance associated with obesity is defective among individuals predisposed to diabetes by virtue of a strong family history of type 2 diabetes before the development of diabetes or glucose intolerance.RESEARCH DESIGN AND METHODS -A total of 126 members of 26 families ascertained for at least a sib pair with type 2 diabetes with onset before age 65 years underwent a tolbutamide-modified frequently sampled intravenous glucose tolerance test (FSIGT). Family members included 26 individuals with impaired glucose tolerance and 100 individuals with no rmal glucose tolerance (NGT). The acute insulin response to glucose (AIR g l u c o s e ) was determ i n e d and insulin sensitivity (S I ) estimated by minimal model analysis of FSIGT data. The -cell compensation for insulin sensitivity was estimated from the disposition index (DI), calculated as the product of S I and AIR g l u c o s e . Obesity was measured by BMI. R E S U LT S -Among all individuals, BMI was a significant predictor of both S I and AIR g l u c o s e , as expected. However, BMI also significantly predicted DI (P = 0.002) after correcting for age, sex, family membership, and glucose tolerance status. The relationship of BMI and DI was confirm e d in 85 individuals with NGT who were aged 45 (P = 0.002) but not in 91 unrelated control individuals without a family history of diabetes. When normoglycemic individuals aged 45 were separated into three classes by BMI ( 27,(27)(28)(29)(30) 30), S I d e c reased pro g ressively and significantly with o b e s i t y, where as A I R g l u c o s e rose significantly from lean to most obese classes. In cont r a s t t o t h e e x p e c t a t i o n o f c o m p l e te -cell compensation with o b e s i t y, D I fell significantly (P = 0.004) among obese family members. This relationship was not observed in control subjects.C O N C L U S I O N S -Individuals with a genetic predisposition to diabetes show a re d u c e d -cell compensatory response to the reduced insulin sensitivity associated with obesity. We propose that this impaired compensation may be one manifestation of the underlying genetic defect in susceptible individuals. This finding helps explain the multiplicative ...

Given the overall slow rate of VA loss, VA is unlikely to be a sensitive outcome measure for treatment trials of Stargardt disease. However, given the faster decline in younger patients and those with no or mild visual impairment, VA may be a potential outcome measure for trials targeting such subgroups of patients. These observations will need to be assessed in a prospective study bearing in mind the inherent limitations of retrospective datasets.

This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

Purpose Analysis of macular pigment (MP) amount and distribution in patients with macular telangiectasia type 2 (MacTel) receiving oral zeaxanthin supplementation in a randomized, open-label interventional trial. Methods Eight MacTel patients were randomized to 10 mg or 20 mg of zeaxanthin per day. At each visit, the subjects were examined including best corrected visual acuity (BCVA), contrast sensitivity (CS), fundus biomicroscopy, color fundus photography (CFP), autofluorescence imaging (AFI), optical coherence tomography (OCT), and serum carotenoid levels. Patients were assessed at baseline and after 6, 12, 18, and 24 months of zeaxanthin supplementation. MP concentration was analyzed and calculated from AFI obtained at 488 nm excitation wavelength. Serum carotenoid levels were obtained using high-performance liquid chromatography (HPLC). Results The majority of subjects had definite increases in intensity of the macular pigment’s hypofluorescent ring, but none of them deposited macular pigment centrally at the fovea. Although some patients noted subjective improvements in vision, no objective improvements could be documented, and there were no changes in foveal OCT features. Yellowish, hypofluorescent crystals appeared in one subject’s macular region with no change in visual acuity. These inner retinal crystals disappeared several months after discontinuing her 20 mg zeaxanthin supplement. Conclusion Based on our study, zeaxanthin supplementation does not result in any visual benefit in patients with MacTel, and does not re-establish a normal peaked distribution of macular pigment in the fovea. One subject developed a novel, reversible crystalline maculopathy in response to zeaxanthin supplementation that was reminiscent of canthaxanthin crystalline maculopathy.