Measurement of Lens Autofluorescence Can Distinguish Subjects With Diabetes From Those Without

Abstract

Lens autofluorescence is increased in patients with diabetes mellitus, but clinical application has been limited by the lack of an instrument suitable for routine clinical use. We investigate possible uses of a new scanning confocal biomicroscope (1) to identify subjects with undiagnosed type 2 diabetes and (2) as a marker for the progression of diabetes. One hundred seventyeight subjects self-reported as normal and 53 subjects physician-diagnosed with diabetes or prediabetes were recruited. Measurements were collected using a ClearPath DS-120 Lens Fluorescence Biomicroscope calibrated with standards traceable to National Institute of Standards and Technology (NIST). Fluorescence intensities were corrected for age by subtracting the value expected from a regression of intensity versus age for normal subjects. This "fluorescence deviation" showed progressively higher values for normal, prediabetes, type 2 diabetes, and type 1 diabetes and a high degree of predictability of diabetes diagnosis. A receiver operating characteristics curve was used to determine sensitivity and specificity for prediction of diabetes type 2. At a fluorescence deviation of 2500, a sensitivity of 67% at 94% specificity was observed detection of type 2 diabetes. The progressively higher fluorescence deviations are consistent with the physiological mechanisms of accumulation of fluorescent advanced glycation end products as the subject ages. The sensitivity and specificity performance of the lens autofluorescence test for type 2 diabetes is comparable to the performance of glucose threshold tests. The statistically significant difference between fluorescence deviations of normal and type 2 diabetes supports the feasibility of lens autofluorescence to screen subjects for undiagnosed type 2 diabetes. Ophthalmic practices are points of care at which there may be a public health benefit for screening patients for undiagnosed diabetes.

Lens autofluorescence ratio as a noninvasive marker of peripheral diabetic neuropathy

“…29 In this study, we also found significant relationships between the LFR and both HbA 1c levels and the duration of diabetes, which is consistent with the literature. 33,34 On the other hand, we did not find any relation with age and lens fluorescence. One of the reasons may be that in most studies showing that increased fluorescence intensity is associated with increasing age the study population comprised of healthy volunteers.…”

“…13,17 Another possibility is that the effect of age on fluorescence intensity may not be observed in the presence of high blood sugar, because high blood sugar prominently affects the fluorescence intensity of the lens. 14,33,34 In conclusion, high LFR was found to be related with either small or large nerve fiber damage, or both. Although with the high specifity of the results, age-adjusted LFR measurements with the ClearPath DS-120 biomicroscope yield significant outcomes in the diagnosis of neuropathy, the instrument seems to have low sensitivity.…”

The assessment of autofluorescence of the crystalline lens in diabetic patients and healthy controls: can it be used as a screening test?

“…However, recently, a new confocal biomicroscope is available to measure lens AF in a fast, noninvasive, and reproducible manner. 8 , 14 The range of FRs which are used in this instrument was reported to change between 0.07 and 0.33 in 127 healthy subjects aged between 21 and 70. 7 Lens AF was found to increase with age.…”

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

“…Several studies have addressed the buildup of AGEs in long-lived proteins (Hammes et al, 1999; Sell et al, 1992; Vashishth, 2009). One human study that quantified autofluorescence of eye lens as an indicator of AGE accumulation with age (Cahn et al, 2014). The buildup of different AGEs (e.g., pentosidine) in the skin and increased crosslinking of collagen due to AGEs has been observed in the skin biopsies of diabetic patients (Monnier et al, 2005; Sell et al, 1992).…”