Clinical photon correlation spectroscopy evaluation of human diabetic lenses

Clinical research on cataract prevention requires an in vivo assessment of the lens of the eye that is non-invasive, quantitative and detects lens changes that precede lens opacification or cataract formation. The method of photon correlation spectroscopy or quasi-elastic light scattering spectroscopy provides such a non-invasive probe. The measurement, based on fluctuations in scattered light intensity caused by translational Brownian motion of the lens proteins, allows a determination of a protein diffusion coefficient and hence information on quaternary conformational changes of these protein scatterers. These protein changes have been observed in association with the presence of lens opacification. The occurrence of these changes prior to opacification, however, has still to be established. The analyses performed in this study were aimed at testing the hypothesis of an association between subclinical molecular changes in the lens as measured by quasi-elastic light scattering and the presence of selected risk factors for cataract. Measurements were made from 393 diabetics attending the Joslin Diabetes Center Eye Unit and 38 non-diabetic volunteers. Measurements at two different instrument sample times, 1.5 microseconds and 150 microseconds, allowed characterization of two different protein size distributions contributing to the quasi-elastically light scattered signal. Measurements performed at the 1.5 microseconds sample time demonstrated significantly decreased lens protein diffusivity in association with older age, higher grade of nuclear sclerosis and presence of diabetes. Statistically significant associations were also observed between lens protein diffusivity and diabetes related factors such as glycosylated hemoglobin level (diabetes control), duration of diabetes, age at onset of diabetes and type of diabetic therapy. The pattern of association exhibited between decreased protein diffusion coefficient and risk factor status is consistent with the patterns of increased risk previously demonstrated in cataract formation. Measurements performed at the 150 microseconds sample time demonstrated significantly decreased lens protein diffusivity in association with increasing age, female sex and glycosylated hemoglobin level. These associations differed significantly from those observed at the 1.5 microsecond sample time, thereby suggesting that these two sample times assess different species of lens proteins. The results of this analysis demonstrate the clinical utility of quasi-elastic light scattering as a rapid, non-invasive method to quantitate lens changes and assess methods of cataract prevention and treatment.