Diabetic macular ischaemia- a new therapeutic target?

• Published in: Progress in retinal and eye research Vol. 89; p. 101033
• Main Authors: Cheung, Chui Ming Gemmy, Fawzi, Amani, Teo, Kelvin YC, Fukuyama, Hisashi, Sen, Sagnik, Tsai, Wei-Shan, Sivaprasad, Sobha
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2022
• Subjects: Diabetes Mellitus; Diabetic macular ischaemia; Diabetic macular oedema; Diabetic retinopathy; Diabetic Retinopathy - therapy; Fluorescein Angiography - methods; Foveal avascular zone; Fundus Oculi; Humans; Ischemia - therapy; Macula Lutea - blood supply; Optical coherence tomography; Optical coherence tomography angiography; Retinal Vessels; Tomography, Optical Coherence - methods; Diabetic retinopathy; Diabetic macular ischaemia; Optical coherence tomography; Optical coherence tomography angiography; Diabetic macular oedema; Foveal avascular zone
• ISSN: 1350-9462; 1873-1635; 1873-1635
• DOI: 10.1016/j.preteyeres.2021.101033

Diabetic macular ischaemia (DMI) is traditionally defined and graded based on the angiographic evidence of an enlarged and irregular foveal avascular zone. However, these anatomical changes are not surrogate markers for visual impairment. We postulate that there are vascular phenotypes of DMI based on the relative perfusion deficits of various retinal capillary plexuses and choriocapillaris. This review highlights several mechanistic pathways, including the role of hypoxia and the complex relation between neurons, glia, and microvasculature. The current animal models are reviewed, with shortcomings noted. Therefore, utilising the advancing technology of optical coherence tomography angiography (OCTA) to identify the reversible DMI phenotypes may be the key to successful therapeutic interventions for DMI. However, there is a need to standardise the nomenclature of OCTA perfusion status. Visual acuity is not an ideal endpoint for DMI clinical trials. New trial endpoints that represent disease progression need to be developed before irreversible vision loss in patients with DMI. Natural history studies are required to determine the course of each vascular and neuronal parameter to define the DMI phenotypes. These DMI phenotypes may also partly explain the development and recurrence of diabetic macular oedema. It is also currently unclear where and how DMI fits into the diabetic retinopathy severity scales, further highlighting the need to better define the progression of diabetic retinopathy and DMI based on both multimodal imaging and visual function. Finally, we discuss a complete set of proposed therapeutic pathways for DMI, including cell-based therapies that may provide restorative potential.
•Diabetic macular ischaemia (DMI) may result in irreversible functional impairment.•Standardisation of optical coherence tomography angiography (OCTA) nomenclature is required.•Mechanistic pathways result in both vascular and neuronal changes in DMI.•Novel DMI trial endpoints that go beyond standard visual acuity are required.•Potential therapies need to prevent both neuronal and vascular changes in DMI.