Assessment of Detailed Photoreceptor Structure and Retinal Sensitivity in Diabetic Macular Ischemia Using Adaptive Optics-OCT and Microperimetry

Abstract

Purpose: The purpose of this study was to assess density and morphology of cone photoreceptors (PRs) and corresponding retinal sensitivity in ischemic compared to nonischemic retinal capillary areas of diabetic eyes using adaptive optics optical coherence tomography (AO-OCT) and microperimetry (MP).

Methods: In this cross-sectional, observational study five eyes of four patients (2 eyes with proliferative diabetic retinopathy (DR) and 3 eyes moderate nonproliferative DR) were included. PR morphology and density was manually assessed in AO-OCT en face images both at the axial position of the inner-segment outer segment (IS/OS) and cone outer segment tips (COSTs). Retinal sensitivity was determined by fundus-controlled microperimetry in corresponding areas (MP-3, Nidek).

Results: In AO-OCT, areas affected by capillary nonperfusion showed severe alterations of cone PR morphology at IS/OS and COST compared to areas with intact capillary perfusion (84% and 87% vs. 9% and 8% of area affected for IS/OS and COST, respectively). Mean reduction of PR signal density in affected areas compared to those with intact superficial capillary plexus (SCP) and deep capillary plexus (DCP) perfusion of similar eccentricity was -38% at the level of IS/OS (P = 0.01) and -39% at the level of COST (P = 0.01). Mean retinal sensitivity was 10.8 ± 5.4 in areas affected by DCP nonperfusion and 28.2 ± 1.5 outside these areas (P < 0.001).

Conclusions: Cone PR morphology and signal density are severely altered in areas of capillary nonperfusion. These structural changes are accompanied by a severe reduction of retinal sensitivity, indicating the importance of preventing impaired capillary circulation in patients with DR.

Figure 1.

Example of manual counting of photoreceptor (PR) signals on en face AO-OCT images of a 58-year-old male patient with diabetes type II and moderate DR (patient 1). PR signals were manually counted in areas of 80 × 80 pixels (A, B; yellow box). Severe distortion and patchy loss of PR signals is seen in the area affected by SCP and DCP nonperfusion A. In contrast, PRs are densely packed and regularly arranged in an area of similar foveal eccentricity in the same eye where SCP and DCP perfusion was intact B. Weak PR signals are predominantly seen in the area affected by SCP and DCP nonperfusion A. These weak signals were also considered for PR density calculations A (red dots encircled in yellow). Very weak signals, clearly below the size of any PR signal found in areas with intact perfusion A (encircled in orange) were not considered for counting, since they either represent noise that derives from the underlying retinal pigment epithelium or severely damaged PRs. The representatively selected areas encircled in red serve to further illustrate PR signal counting A and B. Each small red dot inside the red circles represents one PR signal. The total number of PR signals inside each representatively counted area is written above the respective circle. The lower column (C, D) shows the same information as the upper column A and B without the red dots inside the red circles for better visibility of PR signals in these areas.

Figure 2.

Multimodal imaging of the right eye of a 58-year-old patient with diabetes type II and moderate DR (patient 1). OCTA shows impaired flow (dark areas) both at the superficial capillary plexus (SCP) (A) and deep capillary plexus (DCP) (B) superiorly to the fovea in the area within the white dotted line A and B. In the AO-OCT en face images severe PR signal attenuation at the level of ISOS and COST is seen in the ischemic areas (D, E; G, H, right from the white dotted line). In areas with intact SCP and DCP perfusion A to C (left half of the yellow box and green box) PRs are visualized as densely packed bright white dots G and H (left from the white dotted line; J, K) Analogously, the AO-OCT B-scans show hyporeflectivity or total loss of the individual PR signals both at the axial position of ISOS and COST in the ischemic areas (F2, F4; I2, I4, right half). In areas with intact perfusion the PR layer can visualized as two hyper-reflective and clearly separable bands, the upper corresponding to the ISOS, the lower to the COST, with the retinal pigment epithelium visible underneath (I1, I3, left half; L1, L3). In the ischemic area, retinal sensitivity was severely reduced C (red box; 7 dB), compared to the perfused region just temporal from the ischemic area C (yellow box; 27 dB) as well as the perfused area without adjacent ischemia C (green box; 32 dB).

Figure 3.

Multimodal imaging of a 34-year-old male patient with diabetes type I and moderate DR (patient 2). Optical coherence tomography angiography (OCTA) shows a small area of superficial capillary plexus (SCP) and deep capillary plexus (DCP) nonperfusion located in the temporal macula (A, B; upper white dotted circle). AO-OCT enface volumes revealed PR signal attenuation both at the axial position of IS/OS and COST in the area affected by DCP non-perfusion (D, E, lower half). In contrast, PR signals were bright a regularly aligned at the axial position of the IS/OS and COST in an area with intact SCP and DCP perfusion, just outside the area of DCP non-perfusion D and E (upper half) as well as in another spot with intact SCP and DCP perfusion A and C (green box and G, H). Analogously, the AO-OCT B-scans show hyporeflectivity or loss of PR signals in the area affected by DCP nonperfusion both at the level of IS/OS and COST (F4) compared to areas with intact SCP and DCP perfusion (F2, I2, I4). SD-OCT shows an intact PR layer in the area with intact DCP perfusion (F1, blue box). The PR layer seems to be intact, but is not as homogenous in the area affected by DCP nonperfusion (F3, violet box) compared to the area with intact DCP perfusion (F1, blue box). MP showed unaffected retinal sensitivity in the small area of DCP nonperfusion (27 to 30 dB) C (yellow box). In another spot with intact SCP and DCP perfusion, retinal sensitivity ranged from 29 dB to 31 dB C (green box). MP revealed severely reduced retinal sensitivity (7 dB) in an area with SCP and DCP nonperfusion A and C (within the lower white dotted circle). However, this spot was out of range for AO-OCT image acquisition. The tip of the orange arrow points at a small movement artefact D and E.