Kavita P. Dhamdhere

Disruption of the Retinal Parafoveal Capillary Network in Type 2 Diabetes before the Onset of Diabetic Retinopathy

PURPOSE To establish, using adaptive optics scanning laser ophthalmoscopy (AOSLO), that the retinal parafoveal capillary network is altered before the onset of diabetic retinopathy in adult patients with type 2 diabetes. METHODS AOSLO videos were acquired in the parafoveal region of one eye from control subjects and from patients with type 2 diabetes and no retinopathy. Detailed images of the parafoveal capillary network were generated with custom motion contrast enhancement algorithms. The combination of AOSLO images and videos enabled the simultaneous assessment of several features of the parafoveal capillary network. Arteriovenous (AV) channels were identified by finding the least tortuous capillary channels connecting terminal arterioles to postcapillary venules. Measures of capillary dropout and capillary hemodynamics were also quantified. RESULTS The average tortuosity of AV channels was 26% higher in patients with type 2 diabetes when compared with controls, even though there were no signs of diabetic retinopathy in any of the eyes that were assessed (P < 0.05). In addition, the metrics of capillary dropout showed small changes (between 3% and 7%), leukocyte speed 14% lower, and pulsatility 25% higher, but none of these differences was statistically significant. CONCLUSIONS It is often difficult to find consistent changes in the retinal microvasculature due to large intersubject variability. However, with a novel application of AOSLO imaging, it is possible to visualize parafoveal capillaries and identify AV channels noninvasively. AV channels are disrupted in type 2 diabetes, even before the onset of diabetic retinopathy.

Subclinical capillary changes in non-proliferative diabetic retinopathy.

Purpose. To establish adaptive optics scanning laser ophthalmoscopy as a method to detect and characterize microscopic signs of diabetic retinopathy in capillaries and cone photoreceptors in the parafovea. Methods. Recently, adaptive optics scanning laser ophthalmoscope (AOSLO) has enabled noninvasive assessment of photoreceptors, capillaries, and leukocytes in the retinas of live human subjects. Repeated application of AOSLO imaging along with comparison to fluorescein angiography was used to track individual capillaries near the foveal avascular zone (FAZ) from one eye affected with severe non-proliferative diabetic retinopathy. Fluorescein angiography was used to identify clinical signs of diabetic retinopathy, such as microaneurysms and intraretinal microvascular abnormalities, and corresponding regions were imaged and assessed using the AOSLO. In addition, the structural integrity of photoreceptors and the spatial distribution of leukocytes around the parafoveal capillary network were quantitatively assessed. Results. Capillaries and cone photoreceptors were visualized using the AOSLO without the use of injected contrast agents. Although the majority of capillaries were stable over a period of 16 months, one capillary at the edge of the FAZ dropped out, leading to a small but significant increase in FAZ size. Longitudinal assessment of the capillaries also showed microaneurysm formation and disappearance as well as the formation of tiny capillary bends similar in appearance to intraretinal microvascular abnormalities. The leukocytes in the capillary network were found to preferentially travel through the same routes in all four visits, suggesting that these channels are robust against small changes to the surrounding capillaries. In this eye, cone photoreceptor spacing was increased in the fovea when compared with normal data but stable across all visits. Conclusions. AOSLO imaging can be used to longitudinally track capillaries, leukocytes, and photoreceptors in diabetic retinopathy. Capillary changes that can be detected include dropout of individual capillaries as well as formation and disappearance of microaneurysms.

Associations between Local Retinal Thickness and Function in Early Diabetes

PURPOSE To investigate, using multifocal electroretinography (mfERG) and optical coherence tomography (OCT), potential spatial associations between local neuroretinal function and local retinal thickness in patients with diabetes. METHODS Forty-five patients without retinopathy (10 with Type 1 diabetes; 35 with Type 2 diabetes; 49.9 ± 10.9 years old) and 29 age-similar controls (47.0 ± 12.8 years old) were studied. N1-P1 amplitude (AMP) and P1 implicit time (IT) of mfERGs within the central approximately 20° diameter were compared to spatially corresponding full retinal thickness measurements acquired by Stratus OCT3. AMP and IT were converted to Z-scores and retinal thickness was converted to percentile values. Local abnormalities were defined as P ≤ 0.023. Subject group differences were examined using t-tests. Retinal thickness was compared to mfERGs to determine spatial associations. RESULTS Average retinal thicknesses were similar for all subject groups. The Type 1 group and controls had similar IT and AMP. The Type 2 group had reduced AMP and longer IT than the controls and the Type 1 group (P < 0.001). Local associations between retinal thickness and mfERGs were not significant within any subject group or individuals, even for abnormal locations (P ≥ 0.09). Abnormalities in most measures were greater in the patient groups than in the controls (P < 0.008) except retinal thinning in the Type 1 group. CONCLUSIONS Local neuroretinal function is not associated with full retinal thickness measured locally in patients with diabetes and no retinopathy, even in abnormal locations. Full retinal thickness measured locally by OCT is not a surrogate for mfERGs in early diabetes. Neuroretinal function in Type 2 diabetes is worse than in Type 1 diabetes and controls. Fewer subjects in the Type 1 group could be a potential limitation.