Longitudinal analysis of microvascular perfusion and neurodegenerative changes in early type 2 diabetic retinal disease

Abstract

AimTo prospectively monitor subclinical changes in capillary perfusion and retinal layer thickness in patients with type 2 diabetes and early diabetic retinal disease over 2 years.MethodsIn this longitudinal study we performed biannual retinal vascular imaging using optical coherence tomography angiography (RTVue) to analyse the foveal avascular zone (FAZ) area, perimeter, acircularity index (AI) and parafoveal superficial/deep vessel density (VD). Spectral-domain optical coherence tomography (Spectralis) was used to measure the thickness of nine macular layers and the peripapillary nerve fibre layer.ResultsAmong 117 eyes (58 left) of 59 patients (21 female), 105 had no diabetic retinopathy (DR), 6 mild and 6 moderate non-proliferative DR at baseline. We found DR progression in 13 eyes at year 2. The FAZ area (+0.008±0.002 mm2/year, p<0.0001), perimeter (+0.036±0.010 mm/year, p=0.006) and AI (+0.005±0.002/year, p=0.0280) increased significantly. A pronounced decrease was found in the superficial (−1.425±0.290%/year, p<0.0001) but not the deep VD. Inner neuroretinal loss was confined to the ganglion cell (−0.539±0.150 µm/year, p=0.0004) and the inner plexiform layer (−0.361±0.127 µm/year, p=0.0045). In the outer retina, we observed a statistically significant decrease in thickness in the outer plexiform, photoreceptor layer and pigment epithelium of −0.921±0.161 µm/year, −0.325±0.139 µm/year and −0.385±0.084 µm/year, respectively.ConclusionSubclinical signs of microangiopathy and neurodegeneration appear in parallel and are highly progressive even in the earliest stages of diabetic retinal disease.Trial registration number EudraCT20156000239634.

Detecting retinal neurodegeneration in people with diabetes: Findings from the UK Biobank

“…Additionally, this study shows that thinning persisted after controlling for the many confounding factors associated with retinal thickness measurements, and after excluding participants with DM who had more than mild DR. These findings are consistent with our prior findings from 45 participants with Type 1 DM where we showed progressive GC-IPL thinning over time and those of Aschauer et al showing GC-IPL thinning but no mRNFL thinning over time among patients with Type 2 DM [ 6 , 24 ]. A recent meta-analysis on this topic also showed a stronger association with GC-IPL thickness compared to mRNFL thickness between DM patients with no DR and controls [ 25 ].…”

“…Pooling the findings of those with DRN and those without DRN may be minimizing the overall differences in layer thickness between groups. Irrespective of the exact reasons for this finding, our results as well as that of others [ 24 ] suggest that GC-IPL thickness may be a more robust marker of early DRN changes compared to mRNFL.…”

“…In this study, participants, predominantly had type 2 DM, making it difficult to determine the exact date of diagnosis. Aschauer et al, in their study evaluating changes in retinal thickness over time among patients with Type 2 DM, also did not find an association with duration, likely due to the same reason [ 24 ]. Further studies are needed to identify patients who are at the highest risk of progressive DRN as treating them with neuroprotective agents, such as brimonidine and somatostatin may be beneficial, as shown in the EUROCONDOR trial [ 29 ].…”

Retinal Neurodegeneration in Diabetes: an Emerging Concept in Diabetic Retinopathy

“…It is very likely that the early neuronal and vascular changes in the diabetic retina are tightly coupled and dissecting the timeline of onset may continue to prove challenging. Indeed, a prospective longitudinal study of patients with type 2 diabetes demonstrated progressive decrease in the superficial vascular density along with thinning of the GCL and IPL over a two-year period, suggesting that these changes occur in parallel [ 79 •]. Kim et al also described a similar association between microvascular changes and inner retinal thinning in a retrospective analysis of 40 diabetic eyes without DR, highlighting the importance of neurovascular coupling in the retina [ 80 ].…”

Long-Term Retinal Neurovascular and Choroidal Changes After Panretinal Photocoagulation in Diabetic Retinopathy

“…A previous study quantified a set of the neurovascular parameters of OCTA related to the severity of DR, which might have potential clinical applications for DR staging ( 11 ). Previous longitudinal studies have shown that the microangiopathy and neurodegeneration appear in parallel and are highly progressive even in the early stage of DR ( 13 ), but few studies explored these features following PRP. To the best of our knowledge, the comprehensive retinal vascular and neural changes in the macular and peripapillary area and subfoveal choroidal thickness (SFCT) changes after PRP have not been reported.…”