Despite treatment advances, diabetic eye disease remains a leading cause of visual acuity (VA) loss worldwide. No methods to prospectively determine which patients will gain or lose vision exist, limiting individualized risk assessment and management. We investigated whether noninvasive, readily obtainable spectral domain optical coherence tomography parameters were correlated with VA in eyes with current or resolved center-involved diabetic macular edema (DME). Images were evaluated for disorganization of the retinal inner layers (DRIL), cysts, epiretinal membranes, microaneurysms, subretinal fluid, and outer layer disruption/reflectivity. DRIL affecting ≥50% of the 1-mm central retinal zone was associated with worse VA in all eyes, eyes with current edema, and eyes with resolved edema. Furthermore, early 4-month change in DRIL extent predicted VA change from baseline to 1 year. These data suggest that DRIL is a robust predictor of VA in eyes with present or previous DME and more highly correlated with VA than other widely used measures, such as retinal thickness. If further studies confirm DRIL as a predictive biomarker of future VA, physicians would gain a new tool of substantial clinical and investigative importance that could significantly change the approach to ophthalmic counseling and therapeutic management in patients with diabetes.

IMPORTANCE Macular edema (ME) prognosis and treatment response vary according to the underlying abnormalities. Biomarkers of visual acuity (VA) improvement could influence management decisions in different types of ME. OBJECTIVE To investigate whether disorganization of retinal inner layers (DRIL) and other spectral-domain optical coherence tomography (SD-OCT)-derived variables are associated with subsequent VA after ME resolution in both nondiabetic and diabetic ME. DESIGN, SETTING, AND PARTICIPANTS A retrospective, longitudinal cohort study in which Snellen VA testing and SD-OCT macular imaging were performed, was conducted at a tertiary referral eye center for retinal diseases. The medical records of all patients with ME from December 1, 2010, to December 31, 2012, were reviewed. The date of the last follow-up was June 1, 2013. Participants included 55 patients (70 eyes) with center-involved ME that had resolved during an 8-month period. Patients were grouped based on the source of ME (diabetic vs nondiabetic). Exclusion criteria included significant media opacity interfering with good-quality SD-OCT image acquisition. Masked graders analyzed the central 1500-μm macular region for changes, including cysts, DRIL length and extent, and outer retinal layers disruption. Intragrader and intergrader agreement Spearman rank correlation coefficients ranged from 0.70 to 0.93 for quantitative measurement, and κ values ranged from 0.88 to 1.00 for qualitative grading. MAIN OUTCOMES AND MEASURES Visual acuity and morphologic changes measured on SD-OCT. RESULTS In both groups, VA after ME resolution correlated with baseline VA. In diabetic ME involving a multivariable model including baseline VA and DRIL, total length was associated with subsequent VA as determined by a parameter estimate (PE) of 0.0003 (95% CI, 0-0.0006) (P = .03). The VA change during the 8-month period, after adjusting for baseline VA, was best associated with DRIL change (PE, 0.0002 [95% CI, 0-0.0003]; P = .04). Participants whose DRIL resolved, both early and late, showed improvement in their VA deficit at 8 months (least squares mean [SE], 41.3 [28.5] and 40.9 [37.5], respectively) compared with nonresolvers, whether inconsistent or persistent, whose VA worsened. After adjustment for baseline VA, eyes with persistent DRIL showed the largest difference in VA deficit compared with those with no baseline DRIL (−89.6 [27.2] vs 49.7 [19.6], respectively; P = .006). CONCLUSIONS AND RELEVANCE The presence of DRIL at baseline and its resolution pattern may be associated with subsequent VA after resolution of center-involved diabetic ME.

IMPORTANCEThe CTG18.1 triplet repeat expansion in TCF4 has recently been found to be a common functional variant contributing significant risk to the development of Fuchs endothelial corneal dystrophy (FECD) in Eurasian populations.OBJECTIVES To determine the effect of the expanded CTG18.1 allele of TCF4 on FECD severity and to correlate CTG triplet repeat allele length to the severity of FECD. DESIGN, SETTING, AND PARTICIPANTSIn a cross-sectional analysis, we studied 139 index cases (probands and unrelated individuals) with FECD recruited from a cornea referral practice at the University of Texas Southwestern Medical Center, Dallas, from April 2010 through February 2015. The triplet repeat polymorphism CTG18.1 was genotyped using a combination of short tandem repeat analysis, triplet repeat-primed polymerase chain reaction assay, and Southern blot analysis. Severity of FECD was graded using a modified Krachmer grading system (severity scale of 0-6 based on extent of confluent guttae). MAIN OUTCOMES AND MEASURESThe CTG triplet repeat length of the largest allele was compared with the Krachmer grade of FECD severity, keratoplasty proportion, and central corneal thickness in the white subset.RESULTS Eighty-five of 122 white index cases with FECD (69.7%) harbored the triplet repeat expansion. The mean (SD) Krachmer grade was 5.61 (0.76) in the group with the repeat expansion compared with 5.11 (1.05) in the group without the expanded repeats (P = .01). Forty-seven participants with the repeat expansion (55.3%) had undergone keratoplasty at the time of recruitment, compared with 13 (35.1%) of those without the expansion (P = .0497). There was a positive correlation of Krachmer grade to triplet repeat number (P = .002) and a nominal association of the keratoplasty proportion with triplet repeat number (P = .04). The mean (SD) central corneal thickness was 605.9 (50.5) μm in the group with the expanded repeats compared with 581.3 (50.5) μm in the group without the expansion (P = .04). CONCLUSIONS AND RELEVANCEThe Krachmer grade of disease severity was greater in FECD cases with the CTG18.1 triplet repeat expansion in TCF4 than in those without the expansion. The CTG triplet repeat allele length was positively correlated with the Krachmer grade of severity. The TCF4 triplet repeat expansion resulted in a more severe form of FECD, with clinical and surgical therapeutic implications.