Ganglion cell layer thickening in well‐controlled patients with type 1 diabetes: an early sign for diabetic retinopathy?

Abstract

Purpose: To evaluate early changes in retinal layers using optical coherence tomography (OCT) in patients with long-standing type 1 diabetes (DM1) receiving intensified insulin therapy. Methods: In a cross-sectional case-control study 150 patients with DM1 and 150 age-and sex-matched healthy control participants underwent OCT imaging. Scans of both eyes were analysed for different layers (NFL, GCL (+IPL), INL, outer layer complex (OLC, including OPL, ONL and ELM) and photoreceptors (PR)) in all subfields of an ETDRS grid. All analyses were performed semi-automatically using custom software by certified graders of the Vienna Reading Center. ANOVA models were used to compare the mean thickness of the layers between patients and controls. Results: Six hundred eyes with 512 datapoints in 49 b-scans in each OCT were analysed. Mean thickness in patients/controls was 31.35 lm/30.65 lm (NFL, p = 0.0347), 76.7 lm/73.15 lm (GCL, p ≤ 0.0001), 36.29 lm/37.13 lm (INL, p = 0.0116), 114.34 lm/112.02 lm (OLC, p < 0.0001) and 44.71 lm/44.69 lm (PR, p = 0.9401). When evaluating the ETDRS subfields separately for clinically meaningful hypotheses, a significant swelling of the GCL in patients could be found uniformly and a central swelling for the OLC, whereas the distribution of NFL and INL thickening suggests that their statistical significance was not clinically relevant. Conclusion: These preliminary results demonstrate that preclinical retinal changes in patients with long-standing DM1 can be found by retinal layer evaluation. However, the changes are layer-specific, with significant thickening of the GCL and less so of the OLC suggesting a role as an early sign for diffuse swelling and the evolution of DME even in well-controlled diabetes.

Evidence for Structural and Functional Damage of the Inner Retina in Diabetes With No Diabetic Retinopathy

“… 47 , 56 For example, our quantification of RGCs assumes that cellular density within a given volume of tissue remains constant and the change in RGCs is accurately reflected by the change in volume. Moreover, as previously mentioned, inner retinal tissue thickening has also been described 53 in diabetic patients, likely due to subtle swelling of the neural tissue. This would make our assumption of constant density unreliable.…”

“…The measured impact of these factors on neuronal damage has been variable across different reports. 13 , 21 , 53 , 58 In our study population, the average duration of the disease was short. This was expected from our selection criteria, since patients with type 2 diabetes and no DR are likely to have only been recently diagnosed.…”

“…Indeed, when the normally thicker cp-RNFL was analyzed, a significant, albeit small, loss was identified in patients with DM. It is important to note that retinal thinning is not the only structural change observed in patients with DM and minimal DR. A comprehensive analysis by Gerendas et al 53 showed GCL-IPL thickening and attributed it to initial diffuse swelling prior to the development of evident macular oedema. However, these findings pertained to patients with type 1 diabetes, including people with mild DR.…”

Early Retinal Changes by OCT Angiography and Multifocal Electroretinography in Diabetes

“…With OCT, the analysis of single retinal layers thickness showed a slight progressive thinning of the inner retina layers, specifically RNFL, GCL, IPL, and INL and a mild thickening of ORL in diabetic eyes compared to controls, even if a statistically significant difference was not reached. The thinning of inner retina has already been reported, as secondary to increased apoptotic phenomena of the retinal neuronal cells in DM [29,30]. Histopathologic studies have shown that ganglion cells dendrites are the first cellular component damaged in diabetic models, followed by their axons and cellular bodies [31,32].…”

Ophthalmologic disorders in adolescents with type 1 diabetes

“…Fluorescein angiography is a method which accurately locates the sites of leakage of diseased vessels and ischemia zones, and OCT angiography allows us to accurately visualize vascular changes without the need for contrast agents. In addition, there are a number of other methods that allow accurate diagnosis of lesions within the eye at an early stage of their development [21][22][23]. Recently, Chinese authors have presented results of their research on the thickness of choroid, optic disc, and macular thickness in children with type 1 diabetes [24].…”