Disorganization of the Retinal Inner Layers as a Predictor of Visual Acuity in Eyes With Center-Involved Diabetic Macular Edema

Abstract

IMPORTANCE Biomarkers that predict future visual acuity (VA) in eyes with baseline diabetic macular edema (DME) would substantively improve risk assessment, management decisions, and selection of eyes for clinical studies targeting DME.OBJECTIVE To determine whether baseline or early change in the novel spectral domain-optical coherence tomography (SD-OCT) parameter disorganization of the retinal inner layers (DRIL) is predictive of VA in eyes with center-involved DME.DESIGN, SETTING, AND PARTICIPANTS At a tertiary care referral center for diabetic eye disease, a retrospective, longitudinal cohort study obtained demographics, VA, and SD-OCT images from baseline, 4-month, and 8-month visits in 96 participants (120 eyes) with diabetes mellitus and baseline center-involved DME (SD-OCT central subfield thickness, Ն320 μm for men and Ն305 μm for women). Exclusion criteria included substantial media opacity, cataract surgery within 6 months, and nondiabetic retinal pathology affecting VA. On SD-OCT, the 1-mm-wide retinal area centered on the fovea was evaluated by masked graders for DRIL extent, cysts, hyperreflective foci, microaneurysms, cone outer segment tip visibility, and external limiting membrane or photoreceptor disruption and reflectivity. MAIN OUTCOMES AND MEASURESVisual acuity and SD-OCT-derived retinal morphology. RESULTSGreater DRIL extent at baseline correlated with worse baseline VA (point estimate, 0.04; 95% CI, 0.02-0.05 per 100 μm; P < .001). An increase in DRIL during 4 months was associated with VA worsening at 8 months (point estimate, 0.03; 95% CI, 0.02-0.05 per 100 μm; P < .001). A multivariate model that included a 4-month change in VA, DRIL, and external limiting membrane disruption was predictive of an 8-month VA change (r = 0.80). Each approximately 300-μm DRIL increase during 4 months predicted a 1-line, 8-month VA decline. When DRIL increased at least 250 μm at 4 months, no eyes had VA improvement of at least 1 line at 8 months. When DRIL decreased at least 250 μm at 4 months, no eyes had VA decline of at least 1 line at 8 months, and 77.7% had VA improvement of at least 1 line.CONCLUSIONS AND RELEVANCE Disorganization of the retinal inner layers in the 1-mm foveal area is associated with VA, and change in DRIL predicts future change in VA. Early change in DRIL prospectively identifies eyes with a high likelihood of subsequent VA improvement or decline. Therefore, DRIL warrants further study as a robust, readily obtained, and noninvasive biomarker of future VA response in eyes with DME.

Repeated Dexamethasone Intravitreal Implant for the Treatment of Diabetic Macular Oedema Unresponsive to Anti-VEGF Therapy: Outcome and Predictive SD-OCT Features

“…Standard treatment for DME involves repetitive, invasive intraocular injections, increasing the burden on patients, physicians and healthcare resources [35]. Biomarkers that could predict the effect of a therapy on future VA in eyes with DME could improve risk assessment, management decisions, and selection of eyes for clinical studies [35].…”

Diabetic retinopathy: current understanding, mechanisms, and treatment strategies

“…OCT allows quantitative measurements of retinal thickness, as well as evaluation of morphologic changes in eyes with DR and DME. Potential neuroretinal biomarkers of visual acuity in eyes with DME based on OCT imaging have been suggested, including ganglion cell layer thinning, disorganization of the retinal inner layers, and photoreceptor disruption, although further validation is needed (44)(45)(46)(47). Recently, the technique of OCT angiography has also been utilized to create high-resolution perfusion maps of the central retinal vasculature (48).…”

Photoreceptor Integrity Predicts Response to Anti-VEGF Treatment

“…Other studies have demonstrated changes in the outer retinal microstructures related to VA and to visual fields [11]. Such evaluations have been conducted for diabetic patients but included patients with varying treatments and disease durations [5]. Visual outcome prediction by pretreatment photoreceptor integrity has been discussed in naïve diabetes mellitus patients receiving triamcinolone injection [12].…”

“…Fragmentation of ellipsoid and interdigitation lines was found to be associated with visual impairment in several retinal diseases such as ME, macular holes, epiretinal membranes, occult macular dystrophy and acute zonal occult outer retinopathy [3,5]. Direct assessment of photoreceptor microstructure integrity (ellipsoid and interdigitation zones) may also serve as a prognostic marker of treatment.…”

“…The ellipsoid and interdigitation lines were also found to be correlated with improvement in macular sensitivity after photodynamic therapy for chronic central serous chorioretinopathy [7]. In addition, increased visibility and reorganization of both ellipsoid and interdigitation lines over the course of 8 months was associated with VA improvement in treated patients (anti-VEGF antibody and focal laser) with diabetic ME [5]. Inspecting the microstructure of the photoreceptors may have an important role in assessing the visual function prognosis of ME patients.…”