OCTA-based Assessment of Diabetic Macular Ischemia May Help Evaluate DR Progression

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The findings could provide insight into incorporating both OCTA and artificial intelligence for early detection of DMI and better enhancing the management of diabetic retinopathy.

An optical coherence tomography angiography (OCTA)-based evaluation of diabetic macular ischemia (DMI) may improve the evaluation of diabetic retinopathy (DR) progression, development of diabetic macular edema (DME), and deterioration of visual acuity, according to new research.1

The analysis suggested the presence of DMI on either the superficial capillary plexus (SCP) or deep capillary plexus (DCP) used in the study, or both plexuses, were significantly associated with improved discrimination performance for DR progression over 4 years of follow-up.

“Our findings might help ophthalmologists pay close attention to those presented with DMI, especially to those with DMI in both SCP and DCP, as it potentially provides additional risk assessment for DR progression,” wrote the investigative team, led by Carol Y. Cheung, PhD, from the Chinese University of Hong Kong Eye Center at Hong Kong Eye Hospital.

Identifying individuals at higher risk of vision-threatening DR is important to bolster management, as early and timely interventions are effective for the disease. Characterized by the enlargement and irregularity of the foveal avascular zone (FAZ), DMI has been implicated as a risk factor for DR progression, with current clinical trials looking to better define how DMI fits into the DR severity scale.2 In addition, recent literature has reported that the presence of DMI on OCTA could help predict retinal disease progression and visual acuity deterioration, further enhancing the management of DR.3

The current investigation looked to further understand the association of a previously developed deep learning based DMI algorithm with the subsequent risk of DR progression, DME development, and VA deterioration. The analysis addition investigated whether baseline SCP-DMI and DCP-DMI provides incremental predictive value for diabetic retinal disease progression and VA deterioration beyond other identified risk factors in a study cohort with diabetes.

Patients with diabetes were recruited from July 2015 and were follow-up with for at least 4 years. All patients underwent the same comprehensive ophthalmic assessment and interview-based questionnaires during each visit. Analysis occurred between June - December 2022.

The trial defined the presence of DMI as images exhibiting disruption of FAZ with or without additional areas of capillary nonperfusion in the macula, while its absence was defined as images presented with intact FAZ and normal distribution of vasculature. Study outcomes included DR progression (increase in ≥2 steps of severity level), DME development (occurrence of perceptible retinal thickening or presence of DME feature in macula over the follow-up), and visual acuity deterioration (decrease of ≥0.2 logMar lines compared with baseline).

A total of 321 eyes from 178 patients were included in the final analysis (85 [47.75%] female; mean age, 63 years). Among all included eyes, over a mean follow-up period of 50 months, 105 eyes (32.71%) had DR progression, 33 eyes (10.28%) developed DME, and 68 eyes (21.18%) had visual acuity deterioration. In the univariable Cox proportional hazard models, data showed age, duration of diabetes, fasting glucose, HbA1c, mean arterial blood pressure, baseline DR severity, ganglion cell-inner plexiform layer thickness, and smoking were significantly associated with DR progression and DME development in the study cohort.

The analysis revealed, independently, the presence of SCP-DMI (hazard ratio [HR], 2.69; 95% CI, 1.64 - 4.43; P <.001) and DCP-DMI (HR, 3.21; 95% CI, 1.94 - 5.30; P <.001), as well as the presence of both SCP-DMI and DCP-DMI (HR, 3.69; 95% CI, 1.80 - 5.16), were significantly associated with DR progression, after adjustment for the above risk factors. In addition, the presence of DCP-DMI was significantly associated with the development of DME (HR, 4.60; 95% CI, 1.15 - 8.20) and visual acuity deterioration (HR, 2.12; 95% CI, 1.01 - 5.22).

Investigators noted the current research may be the first longitudinal OCTA study suggesting the presence of DMI was associated with VA deterioration in a cohort with diabetes.

“Although there is currently no treatment specifically for DMI, the implication of the present study could be interpreted as follows: As DMI has been found to contribute to progressive visual loss among some patients with DR despite treatment, considering the intricate relations between DMI and DR, out results might advocate the early detection of DMI among a diabetes population to herald early intervention, such as stricter metabolic control, to mitigate both DMI and DR progression and subsequently arrest progression VA deterioration,” investigators wrote.


  1. Yang D, Tang Z, Ran A, et al. Assessment of Parafoveal Diabetic Macular Ischemia on Optical Coherence Tomography Angiography Images to Predict Diabetic Retinal Disease Progression and Visual Acuity Deterioration. JAMA Ophthalmol. Published online May 25, 2023. doi:10.1001/jamaophthalmol.2023.1821
  2. Cheung CMG, Fawzi A, Teo KY, et al. Diabetic macular ischaemia: a new therapeutic target? Prog Retin Eye Res. 2022;89:101033. doi:10.1016/j.preteyeres.2021.101033
  3. Tsai ASH, Gan ATL, Ting DSW, et al. Diabetic macular ischemia: correlation of retinal vasculature changes by optical coherence tomography angiography and functional deficit. Retina. 2020;40(11):2184-2190