Researchers Identify Candidate Factors Associated With Visual Impairment in Diabetic Eyes

Using optical coherence tomography, researchers found that length of disorganization of retinal inner layer, length of external ellipsoid zone disruption, and foveal avascular zone circularity were associated with visual impairment in treatment-naïve patients with diabetes.

Using optical coherence tomography (OCT), researchers found that length of disorganization of retinal inner layer (DRIL), length of external ellipsoid zone (EZ) disruption, and foveal avascular zone (FAZ) circularity were associated with visual impairment in treatment-naïve patients with diabetes. Results of the retrospective observational study were published in Scientific Reports.

By 2040, an estimated 624 million individuals will be affected by diabetes, and diabetic retinopathy (DR) is currently the most common ocular condition worldwide. DR, although asymptomatic at an early stage, can lead to severe vision loss. The condition is the leading cause of blindness in working-age adults and affects approximately one-third of the population with diabetes.

“Diagnosis of DR relies on the detection of microvascular lesions, which is divided into two stages based on their clinical findings: nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR),” researchers explained.

OCT has been proven to aid in detection and monitoring of diabetic macular edema (DME) and diabetic macular ischemia (DMI)—two of the main vision-threatening complications of DR. The process “is a non-invasive and fast imaging modality that offers imaging of cross-sectional structures of the retina using low coherence interferometry and captures high-resolution two-dimensional images from scattered light from different layers of the retina.” Similarly, OCT angiography (OCTA) is a development of OCT that detects movements of red blood cells and blood flow contrasts. Using OCTA, researchers are able to visualize retinal and choroidal microvasculature without dye injections.

Previous studies have revealed some quantitative OCTA metrics linked to the severity of DR and DME. To determine which factors are correlated with visual acuity in treatment-naïve patients with diabetes, investigators conducted OCT and OCTA on 183 eyes (123 patients) with type 2 diabetes (T2D) who presented to a single medical center in Japan between May 2019 and July 2020.

All participants completed an ophthalmologic examination including best corrected visual acuity and axial length measurements, among other tests. Mean (SD) patient age was 61.9 (12.3) years and the majority (n = 66) were male. Fifty-five controls (62 eyes) were also included in the study, with a mean age of 64.4 (12.5) years. Of those with diabetes, 92 did not have DR (NDR), 67 had NPDR, and 24 had PDR. Researchers found “no significant differences in age, intraocular pressure, axial length, duration of diabetes, estimated glomerular filtration rate (eGFR), frequency of hypertension (HT) and dyslipidemia (DL) in the DR groups compared to the control group.”

More severe DR was associated with significantly lower visual acuity, higher glycated hemoglobin (A1C), and higher systolic blood pressure and diastolic blood pressure (P < .05 for all).

Multivariate analyses based on OCT and OCTA findings revealed:

  • Length of DRIL (β = 0.24; P < .01), length of EZ disruption (β = 0.35; P < .001) and FAZ circularity (β = −0.14; P < .05) were significant factors affecting visual acuity.
  • A significant positive correlation between length of DRIL and length of EZ disruption (r = 0.71; P < .01).
  • FAZ circularity had a significant negative correlation with length of DRIL and length of EZ disruption (r = − 0.33 and − 0.31; both P < .01).
  • Central retinal thickness, number of inner hyperreflective foci, number of outer hyperreflective foci, height of intraretinal fluid, height of subretinal fluid, length of external limiting membrane disruption, vessel density of superficial capillary plexus (SCP), and FAZ area had no significant correlation with visual acuity.

“Although the mechanism of DRIL formation is unknown, it is hypothesized that DM-induced microvascular damages inside the retina may represent structural deformation identified as DRIL based on OCT images,” researchers wrote. PDR may also form a fibrovascular membrane that creates traction on the macula, marking another potential mechanism associated with vascular abnormality and mechanical stress involved in DRIL formation.

Several processes, including destructed blood-retinal barrier (BRB) associated with diabetes, may account for the correlation between EZ integrity and visual acuity. Analyses showed that “EZ disruption was found in 10.9% of all patients [with diabetes], 10.4% in NPDR and 54.2% in PDR, which occurred more frequently in the advanced stages of the disease,” and patients with high frequency of EZ exhibited significantly poorer visual acuity.

When it comes to the role of FAZ circularity, investigators noted that because macular edema can result in decreased vascular elasticity due to mechanical stretching that results in blockage of blood vessels, the condition can also change FAZ contours. Results showed that eyes with poor visual acuity had more irregular shapes of FAZ. “Assessing both the size and shape of FAZ is probably important for detecting pathological alteration of the macula in DR,” authors said.

Although the study found that length of DRIL, EZ disruption, and FAZ circularity could play an important role in impaired visual function in diabetic eyes, there is a lack of information on how these 3 factors correlate with one another. In addition, “it remains open to debate whether diabetic retinal neuropathy is the cause or effect of microangiopathy under chronic hyperglycemia.”

The limited number of subjects and retrospective design of the study mark limitations, and a larger sample size in prospective studies can help confirm results. Researchers also did not include demographic information such as age, duration of diabetes, and hypertension in the analysis.

Because the data collected were only from a single visit, authors cautioned it is impossible to use results to judge risks of disease progression or predict treatment response to DR.

“To protect the eyesight of diabetic patients, it is necessary to find ways to prevent the gradual loss of neurons in the retina,” authors concluded. “Further studies are required to prove the validated association between OCT-based retinal structural abnormalities and visual function in diabetic eyes.”


Endo H, Kase S, Tanaka H, et al. Factors based on optical coherence tomography correlated with vision impairment in diabetic patients. Sci Rep. Published online February 4, 2021. doi:10.1038/s41598-021-82334-w