Person:

Cavallerano, Jerry

Objective: To assess complication prevalence and identify protective factors in patients with diabetes duration of (\geq)50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors. Research Design and Methods: Cross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for (\geq)50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA(_{1c}), lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup. Results: A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter. Conclusions: The Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy.

Objectives: To evaluate the effect of pupillary dilation on electronic-ETDRS visual acuity (EVA) in diabetic subjects and to assess post-dilation EVA as a surrogate for pre-dilation visual acuity (VA). Methods and Design: DRCR.net-protocol refraction and EVA were measured pre- and post-dilation in diabetic subjects by independent, masked examiners. Results: In 129 eyes of 66 subjects, median [25th, 75th percentiles] pre-dilation EVA score was 69 [54, 86] (Snellen-equivalent 20/40-1 [20/80-1, 20/20+1]). Pre-dilation VA was ≥20/20, 20/25-20/40, 20/50-20/80, and <20/80 in 29%, 19%, 26%, and 26% of eyes, respectively. Median EVA change post-dilation was -3 letters [-7, 0]. EVA change was ≥15 letters (≥ 3 ETDRS lines) in 9% of eyes and ≥10 letters (≥ 2 ETDRS lines) in 19% of eyes. Extent of change (range +12 to -25 letters) was associated with baseline VA. No relationship was identified between EVA change and gender, race, lens status, refractive error, DR severity, or primary cause of vision loss. Conclusions: In an optimized clinical trial setting, there is a decline in best-corrected EVA after dilation in diabetic subjects. The large range and magnitude of VA change preclude using post-dilation EVA as a surrogate for undilated VA.

Purpose: To compare visual acuity (VA) scores obtained after autorefraction or using a pinhole occluder to scores obtained after refraction according to a standard clinical research protocol. Design: Prospective, comparative case series Participants: One hundred and ten study participants (209 eyes) with diabetes mellitus and a broad range of diabetic retinopathy severity and visual acuity (VA). Methods: VA was measured after autorefraction by a Topcon KR-8000 autorefractor as well as after a Diabetic Retinopathy Clinical Research Network (DRCR.net) protocol manual refraction. The order of testing was randomized and examiners were masked to the source of each refraction. A second VA measurement, utilizing an identical DRCR.net manual refraction, was made in a subset of eyes (N = 144, 69%) in order to establish test-retest variability for comparison purposes. All eyes underwent VA testing using a pinhole occluder. Main Outcome Measures: Best corrected VA as measured by the Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Test© (E-ETDRS). Results: In all eyes, the median E-ETDRS VA letter score (EVA) obtained after manual refraction (MR-EVA) was 69 (Snellen equivalent 20/40), ranging from 4 to 93 (20/800 to 20/16). The median MR-EVA was slightly better than the median EVA obtained after autorefraction (AR-EVA), with a median difference (AR-EVA – MR-EVA) of −1 letter (25th, 75th percentiles: −4, 2 letters). The absolute difference between AR-EVA and MR-EVA was similar to the test-retest variability of MR-EVA alone. In contrast, MR-EVA was better than EVA obtained using a pinhole occluder (PH-EVA), (median PH-EVA – MR-EVA: −4 letters [−9, 0]), and had significantly less test-retest variability (P<0.001). Generally, the spherical equivalent of autorefraction was slightly more hyperopic (or less myopic) than the spherical equivalent of manual refraction (median difference: +0.25 Diopters [0, +0.63 Diopters]). Conclusions: Given the substantial time and effort required for training and certification of study protocol refractionists, and the similarity between AR-EVA and MR-EVA, further evaluation of autorefraction, but not pinhole occluder testing, as an alternative to the current clinical research gold standard of ETDRS protocol manual refraction in study participants with diabetic retinopathy is warranted.