Integrating imaging modalities for early detection of key microscopic abnormalities in diabetic retinopathy

A study led by Marie Elise Wistrup Torm, MD, reveals that combining noninvasive imaging techniques can detect microscopic abnormalities in diabetic retinopathy (DR) earlier and with greater detail than traditional fundus imaging. This suggests that these advanced methods offer a more precise, timely approach to diagnosing and managing DR, a leading cause of vision loss in patients with diabetes.¹ Torm is affiliated with the Department of Ophthalmology at the Center for Research in Eye Diseases, Rigshospitalet, Glostrup, Denmark, and the Faculty of Health and Medical Sciences at the University of Copenhagen, Denmark.

According to the investigators, retinal capillary imaging is particularly interesting for studying DR, which is the most common microvascular complication in diabetes,^1-4 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.^5-7

The investigators noted that microaneurysms and small hemorrhages are the first signs of DR to appear on fundus photographs, whereas loss of pericytes, basement membrane thickening, loss of endothelial cells, dilated or saccular capillaries, and nonperfused 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 nonperfusion, to clarify if they can be used as early biomarkers of DR,” they wrote. “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.”^8-10

In light of this, the investigative team evaluated the potential of a prototype high-resolution, multimodal retinal imaging instrument.12 for mapping capillary irregularity and occlusion in the earliest DR stages. The study included 11 patients (21 eyes) with very mild to moderate nonproliferative DR (NPDR); 11 eyes had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Ten healthy subjects were included. The imaging modalities included fundus photography, OCT, OCTA, adaptive optics scanning laser ophthalmoscopy (AO-SLO), AO-OCT, and AO-OCTA.

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 nondetectable flow rate, possibly because of hypoperfusion.” Aligning the corresponding en face AO-OCT and AO-OCTA images revealed nonperfused capillaries (ie, ghost vessels) in 1 patient with moderate NPDR.

The authors added that combined imaging modalities benefit early recognition of diabetic abnormalities. “The combination of multiple noninvasive imaging methods could identify prominent microscopic abnormalities in DR earlier and [in more detail] than conventional fundus imaging devices,” they concluded.

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(1):13450. doi: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(8):1165. doi:10.3390/jcm8081165

3. Karst SG, Lammer J, Radwan SH, et al. Characterization of in vivo retinal lesions of diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy. Int J Endocrinol. 2018;2018:7492946. doi:10.1155/2018/7492946

4. Chui TY, 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(3):290-302. doi:10.1111/opo.12273

5. Tam J, Dhamdhere KP, Tiruveedhula P, et al. Subclinical capillary changes in non-proliferative diabetic retinopathy. Optom Vis Sci. 2012;89(5):E692-E703. doi:10.1097/OPX.0b013e3182548b07

6. Ashton N. Studies of the retinal capillaries in relation to diabetic and other retinopathies. Br J Ophthalmol.1963;47(9):521-538. doi:10.1136/bjo.47.9.521

7. Stitt AW, Gardiner TA, Archer DB. Histological and ultrastructural investigation of retinal microaneurysm development in diabetic patients. Br J Ophthalmol. 1995;79(4):362-367. doi:10.1136/bjo.79.4.362

8. Joussen AM, Gardner TW, Kirchhof B, Ryan SJ, eds. Retinal Vascular Disease. Springer; 2007.

9. Nanegrungsunk O, Patikulsila D, Sadda SR. Ophthalmic imaging in diabetic retinopathy: a review. Clin Exp Ophthalmol. 2022;50(9):1082-1096. doi:10.1111/ceo.14170

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(12):8513-8522. doi:10.1167/iovs.14-15121

11. Sawada O, Ichiyama 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. Graefes Arch Clin Exp Ophthalmol. 2018;256(7):1275-1280. doi:10.1007/s00417-018-3992-y

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(1):9577. doi:10.1038/s41598-022-13631-1