Progression of Capillary Hypoperfusion in Advanced Stages of Nonproliferative Diabetic Retinopathy: 6-month Analysis of RICHARD Study

Purpose: To evaluate the 6-month progression of retinal capillary perfusion in eyes with advanced stages of nonproliferative diabetic retinopathy (NPDR).

Design: RICHARD (NCT05112445), 2-year prospective longitudinal study.

Participants: Sixty eyes with Diabetic Retinopathy Severity Scale (DRSS) levels 43, 47, and 53 from 60 patients with type 2 diabetes. Fifty-one patients completed the 6-month evaluation.

Methods: Eyes were evaluated on Optos California (Optos plc) ultrawidefield fundus fluorescein angiography (UWF-FFA), swept-source OCT angiography (SS-OCTA) (PLEX Elite 9000, ZEISS) and spectral-domain OCTA (SD-OCTA) (CIRRUS HD-OCT 5000 Angioplex, ZEISS). DRSS classification was performed based on 7-field color fundus photographs (CFPs) complemented with Optos California UWF-fundus imaging.

Main outcome measures: Ischemic index was obtained from Optos. Vascular quantification metrics, namely foveal avascular zone, skeletonized vessel density (SVD), and perfusion density (PD) metrics, were acquired on OCTA in the superficial and deep capillary plexuses (SCP and DCP). Microaneurysm assessment was automatically performed based on CFP images using the RetmarkerDR (Retmarker SA, Meteda Group).

Results: Swept-source-OCTA metrics showed statistically significant differences between the advanced stages of NPDR. Differences between DRSS levels 47 and 53 were found at baseline in the inner ring (SVD, SCP: P = 0.005 and DCP: P = 0.042 and PD, SCP: P = 0.003) and outer ring (SVD, SCP: P = 0.007 and DCP: P = 0.030 and PD, SCP: P = 0.020 and DCP: P = 0.025). No significant differences were observed at baseline between DRSS levels 43 and 47. In SD-OCTA, the differences were similar but did not reach statistical significance. The total ischemic index showed an increase in association with diabetic retinopathy (DR) severity, but the differences between DRSS levels did not reach statistical significance. The number of microaneurysms also increased significantly with DR severity (P = 0.033). Statistically significant 6-month progression was detected with SS-OCTA in eyes with DRSS levels 47 and 53 but not in DRSS level 43. In eyes with DRSS level 53, 6-month progression was identified using a combination of metrics of capillary nonperfusion and microaneurysm counts.

Conclusions: In a 6-month period, significant microvascular disease progression can be identified in eyes with DRSS levels 47 and 53 by performing OCTA examinations and microaneurysm counting using CFP.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.