Characterization of 2-Year Progression of Different Phenotypes of Nonproliferative Diabetic Retinopathy

Abstract

Introduction: To characterize the two-year progression of risk phenotypes of nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D) Phenotype C, or ischemic phenotype, identified by decreased skeletonized retinal vessel density (VD), ≥ 2 SD over normal values, and Phenotype B, or edema phenotype, identified by increased retinal thickness, i.e. subclinical macular edema, and no significant decrease in VD. Methods: A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with 4 visits (baseline, 6-months, one-year and two-year). Ophthalmological examinations included best corrected visual acuity, color fundus photography (CFP) and optical coherence tomography (OCT) and OCT Angiography. Early Treatment Diabetic Retinopathy Study grading was performed at the baseline and last visits based on 7-fields CFP. Results: One hundred and twenty-two eyes from T2D individuals with NPDR fitted in the categories of phenotype B and C and completed the two-years follow-up. Sixty-five (53%) of the eyes were classified as phenotype B and 57 (47%) eyes as phenotype C. Neurodegeneration represented by thinning of the ganglion cell layer and inner plexiform layer was present in both phenotypes and showed significant progression over the two-year period (p<0.001). In phenotype C, significant progression in the two-year period was identified in decreased skeletonized VD (p=0.01), whereas in phenotype B microvascular changes involved preferentially decreases in perfusion density (PD, p=0.012). Phenotype B with changes in VD and PD (flow) and preferential involvement of the deep capillary plexus (p<0.001) is associated with development of center-involved macular edema. Discussion: In the two-year period of follow-up both phenotypes B and C showed progression in retinal neurodegeneration, with changes at the microvascular level characterized by decreases in PD in phenotype B and decreases in VD in phenotype C.

Retinal Capillary Nonperfusion in Preclinical Diabetic Retinopathy

“…The three different DR phenotypes for nonproliferative DR, previously described by our group [ 4 , 12 ], were identified based on the values of SVD in the SCP and CRT according to the following rules: phenotype C was identified by decreased values of SVD of SCP ≥2 standard deviations (SDs) of a reference healthy population, with or without increased CRT; phenotype B was characterized by SVD decreased in the SCP <2 SD and increased values of CRT (≥260 µm in women and ≥275 µm in men); phenotype A was identified by SVD decrease in the SCP <2 SD of a reference healthy population and normal CRT values (<260 µm in women and <275 µm in men). CRT reference values presented in this study are the reference for Zeiss Cirrus HD-OCT 5000.…”

“…It is nowadays essential in the study of vascular diseases like DR, to detect changes in skeletonized vessel and perfusion densities which are indicators of microvascular changes and capillary closure. Recent studies [ 3 , 4 ] have shown that OCTA and optical coherence tomography (OCT) can detect and distinguish different stages and mechanisms of DR progression, improving the characterization and follow-up of these patients.…”

Retinal neurodegeneration in eyes with NPDR risk phenotypes: A two‐year longitudinal study

“…Different risk phenotypes of NPDR progression have been previously identified by our group as A, B and C, based on the predominance of different disease pathways. In our initial characterisation of phenotypes, the presence of microvascular changes was identified by increased microaneurysm turnover (MAT) detected by a specific algorithm, the Retmarker, not widely used (Ribeiro et al, 2022). However, to facilitate comparison of our results by other groups and to translate the information gathered into general clinical practice, we decided in this 2‐year analysis to identify and characterise the ischaemia phenotype, phenotype C, by the presence of definite closure, decrease of skeletonised vessel density (SVD) in the retinal superficial capillary plexus (SVD in SCP ≥ 2 SD of healthy controls).…”

Central and Peripheral Involvement of the Retina in the Initial Stages of Diabetic Retinopathy

“…It is nowadays essential in the study of retinal vascular diseases like DR to identify ischemia by detecting changes in vessel and perfusion densities. 4,5 It has been suggested that the identification of peripheral lesions, using ultra-widefield fundus photography (UWF-FP), is associated with more severe disease progression. 6 However, a comparison between peripheral and central vascular changes in the initial stages of diabetic retinal disease is still lacking.…”

“…It is nowadays essential in the study of retinal vascular diseases like DR to identify ischemia by detecting changes in vessel and perfusion densities. 4,5…”