Using multiple imaging techniques to detect early microscopic abnormalities in diabetic retinopathy

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Marie Elise Wistrup Torm, MD, and colleagues reported that when they combined multiple non-invasive imaging methods, they were able to visualize prominent microscopic abnormalities earlier and in more detail in patients with diabetic retinopathy (DR) compared with conventional fundus imaging devices.¹ Torm is from the Department of Ophthalmology, Center for Research in Eye Diseases, Rigshospitalet, Glostrup, Denmark, and the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

The investigators explained that retinal capillary imaging is particularly interesting for studying DR, which is the most common microvascular complication in diabetes,^2-5 the elevated glycemic and associated glycemic instability of which lead to asymptomatic capillary wall abnormalities. These include pericyte loss, basement membrane thickening, endothelial cell loss, and dilated or saccular capillaries followed by formation of microaneurysms and small hemorrhages and loss of capillary perfusion.^6,7

“Microaneurysms and small hemorrhages are the first signs of DR to appear on fundus photographs, while loss of pericytes, basement membrane thickening, loss of endothelial cells, dilated or saccular capillaries, and non-perfused acellular capillaries are invisible on fundus photographs.⁸ Therefore, it is of interest to develop methods of in vivo imaging that can demonstrate these capillary abnormalities and non-perfusion, to clarify if they can be used as early biomarkers of DR. While fluorescein angiography and optical coherence tomography angiography [OCTA] can raise suspicion that capillary perfusion has been lost, they do so only by showing enlarged intercapillary spaces, the identification of which is made difficult by large variations in the anatomy of the healthy retina and its blood flow,^9-11” the authors stated.

In light of this, the investigative team evaluated the potential of a prototype high-resolution, multi-modal retinal imaging instrument¹² for mapping capillary irregularity and occlusion in the earliest DR stages.

The study included 11 patients (21 eyes) with very mild to moderate non-proliferative DR (NPDR); of these, 11 eyes had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Ten healthy subjects were also included. healthy subjects. The imaging modalities included fundus photography, OCT, OCTA, adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)).

The investigators reported, “Using AO-SLO, capillary looping, inflections, and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion.”

In one patient with moderate NPDR, non-perfused capillaries, ie, ghost vessels, were observed by aligning the corresponding en-face AO-OCT and AO-OCTA images.

The authors concluded that combined imaging modalities is beneficial for early recognition of diabetic abnormalities. “The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in DR earlier and more detailed than conventional fundus imaging devices.”

References:

1. Torm MEW, Pircher M, Bonnin S, et al. Detection of capillary abnormalities in early diabetic retinopathy using scanning laser ophthalmoscopy and optical coherence tomography combined with adaptive optics. Sci Rep. 2024;14:13450. https://doi.org/10.1038/s41598-024-63749-7

2. Palochak CMA, Lee HE, Song J, et al. Retinal blood velocity and flow in early diabetes and diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy. J Clin Med. 2019;8:1165.

3. Karst SG, Lammer J, Rahwan SH, et al. Characterization of in vivo retinal lesions of diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy. Int J Endocrinol. 2018:1–12.

4. Chui TYP, Pinhas A, Gan A, et al. Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy. Ophthalmic Physiol Opt. 2016;36:290–302.

5. Tam J, Dhamdhere KP, Tiruveedhula P, et al. Subclinical capillary changes in non-proliferative diabetic retinopathy. Optom Vis Sci. 2012;89:E692–E703.

6. Ashton N. Studies of the retinal capillaries in relation to diabetic and other retinopathies. Br J Ophthalmol. 1963;47:521–538.

7. Stitt AW, Gardiner TA, Archer DB. Histological and ultrastructural investigation of retinal microaneurysm development in diabetic patients. Br J Ophthalmol. 1995;79:362–367.

8. Joussen AM, Gardener TW, Kirchoff B, et al. Retinal Vascular Disease. New York: Springer, 2007.

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10. Arichika S, Uji A, Murakami T, et al. Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci. 2014;55:8513–8522.

11. Sawada O, Ichyama Y, Obata S, et al. Comparison between wide-angle OCT angiography and ultra-wide field fluorescein angiography for detecting non-perfusion areas and retinal neovascularization in eyes with diabetic retinopathy. Graefe Arch Clin Exp Ophthalmol. 2018;256:1275–1280.

12. Shirazi MF, Andilla J, Lefaudeux N, et al. Multi-modal and multi-scale clinical retinal imaging system with pupil and retinal tracking. Sci Rep. 2022;12:9577.