Relationship of OCT-Based Diabetic Retinal Neurodegeneration to the Development and Progression of Diabetic Retinopathy: A Cohort Study

Abstract

Purpose: To evaluate the relationship between diabetic retinal neurodegeneration (DRN), as quantified by optical coherence tomography (OCT), to the development of diabetic retinopathy (DR), progression of DR, and development of proliferative DR (PDR).

Methods: This was a prospective cohort study, including 385 eyes with no DR or nonproliferative DR at baseline. The thicknesses of the macular ganglion cell-inner plexiform layer (m-GCIPL), macular retinal nerve fiber layer, and peripapillary RNFL (p-RNFL) were measured using Cirrus OCT (Carl Zeiss Meditec, Dublin, CA, USA). DR outcomes were determined from macula- and optic disc-centered fundus photographs, following the modified Airlie House classification system. Cox proportional hazards models were used to estimate hazard ratio (HR) adjusting for age, mean arterial blood pressure, diabetes mellitus duration, HbA1c, diabetic kidney disease, axial length, OCT signal strength, and disc area (for p-RNFL only).

Results: After a median follow-up of 6.2 years (range 5.0-7.7 years), 79 eyes developed DR, 99 eyes developed DR progression, and 38 eyes developed PDR. Thinner mean and sectorial m-GCIPL thicknesses were significantly associated with higher risk of DR development, with HRs ≥ 1.373 (1.023-1.843), except for the superonasal and superotemporal sectors. Similar to DR development, thinner m-GCIPL thicknesses were significantly associated with DR progression and PDR development, with HRs ranging from 1.306 (1.094-1.559) to 2.331 (1.524-3.566). Additionally, the inclusion of inferior m-GCIPL thickness significantly improved the predictive discrimination for DR development (C statistics: 0.661 vs. 0.705, P < 0.001), and DR progression (C statistics: 0.704 vs. 0.729, P < 0.001), as well as inferotemporal m-GCIPL for PDR development (C statistic: 0.917 vs. 0.930, P < 0.001) beyond established risk factors.

Conclusions: OCT measurements that elucidate DRN may enhance prognostic identification and predictive discrimination of DR development, DR progression, and PDR development beyond established risk factors.

Figure 1.

Study flowchart. PRP, pan-retinal photocoagulation.

Figure 2.

Relationships of baseline OCT measurements to the risk of DR development. The multivariable models were adjusted for baseline age, mean arterial blood pressure, diabetes mellitus duration, HbA1c, diabetic kidney disease, axial length, OCT signal strength, and disc area (disc area for p-RNFL only).

Figure 3.

Relationships of baseline OCT measurements to the risk of DR progression. The multivariable models were adjusted for baseline age, mean arterial blood pressure, diabetes mellitus duration, HbA1c, diabetic kidney disease, axial length, OCT signal strength, DR severity, and disc area (disc area for p-RNFL only).

Figure 4.

Relationships of baseline OCT measurements to the risk of PDR development. The multivariable models were adjusted for baseline age, mean arterial blood pressure, diabetes mellitus duration, HbA1c, diabetic kidney disease, axial length, OCT signal strength, DR severity and disc area (disc area for p-RNFL only).

Figure 5.

The discriminative performance of the multivariable model with and without the OCT measurements for identifying DR development, DR progression, and PDR development. The dash lines represented 0.661, 0.704, and 0.917 for DR development, DR progression, and PDR development, respectively. They represented the C-statistics that were obtained from the models without OCT measurement included. Asterisk indicates the significant difference of C-statistics between model without OCT measurement and with OCT measurement.