Of the 3280 subjects (response rate, 78.7%) who participated in the SiMES, 769 (224 without HRT II imaging data, 195 with HRT II testing but with poor image quality, 144 with retinal abnormalities other than DR, and 206 with a history of ocular surgery [including 154 with cataract surgery and 52 with evidence of previous retinal laser ablation seen from fundus images]) were excluded. Compared with those included (n = 2511), excluded participants (n = 769) were more likely to be older and to have a more negative spherical equivalent, cataract, visual impairment, diabetes, and DR (all with P < 0.05). Other characteristics were similar (e.g., the proportion with glaucoma was 4.9% among those excluded and 4.5% among those included). Among persons with glaucoma (n = 112), 86 (76.8%) were categorized as having no diabetes, 15 (13.4%) as having diabetes without DR, and 11 (9.8%) as having DR. Among persons without glaucoma (n = 2399), the number of patients in these categories was 1901 (79.3%), 358 (14.9%) and 140 (5.8%), respectively. Based on visual field testing with the Humphrey perimeter, the average mean deviation of the glaucomatous eyes was −7.47 dB (SD, 7.43; range, −30.95–1.01).
We first assessed the relationships of diabetes and DR with HRT parameters by using both linear regression analysis and one way ANOVA. In multiple linear regression models after controlling for age, sex, IOP, axial length, and optic disc area size, the presence of DR was significantly associated with a thinner RNFL (β coefficient = −0.008;
P < 0.001). The significant association persisted in all four quadrants (all with
P < 0.01). Significant associations were also found between the presence of DR and increased CSM (data not shown). These findings were consistent with the data from one-way ANOVA with Bonferroni correction, illustrated in
Figure 1. We also examined the relationship of HbA1c with RNFL thickness (by 12 quantiles) and CSM (by 12 quantiles). Although linear regression analyses showed no significant association of HbA1c with RNFL thickness and CSM (
P > 0.05), there seemed to be a downward trend of RNFL thickness and an upward trend in CSM with increasing HbA1c after the 6th quantile (HbA1c = 5.9%). In addition, there appeared to be a downward trend in RNFL thickness when HbA1c was lower than 5.2% (1st quantile). Thus, the relationship between HbA1c and RNFL thickness appeared to be curvilinear.
We then described the areas under the receiver the operating characteristic (AUROC) curve for HRT II algorithms in this population. The AUROC was 73.4% (95% confidence interval [CI], 67.2–79.4) for the global MRA, 70.6% (95% CI, 65.9–75.2) for overall MRA, 74.2% (95% CI, 68.4–80.0) for Mikelberg-LDF, 71.4 (95% CI, 66.0–76.8) for Burk-LDF, 72.0% (95% CI, 66.2–77.9) for Bathija-LDF, and 82.1% (95% CI, 75.8–88.3) for SVM-Gauss.
Finally, we assessed the influence of diabetes and DR on sensitivities and false-positive rates for the HRT II algorithms. In logistic regression models, the sensitivities for these HRT II algorithms were dichotomized as binary variables (by fixing the specificities at 80% or 90%) and then treated as dependent variables. Likewise, the false-positive rates for HRT II algorithms were dichotomized (by fixing the false-negative rates at 40% or 60%) and then treated as dependent variables. We found that (1) the presence of diabetes without DR was associated with neither the sensitivities nor the false-positive rates for the HRT II algorithms (all with
P > 0.05, data not shown); (2) the presence of DR was not associated with the sensitivities for HRT II algorithms (
Table 1); and (3) the presence of DR was significantly associated with the false-positive rates for Burk-LDF and Bathija-LDF (
P < 0.05). The Burk-LDF and Bathija-LDF tended to yield higher false-positive rates for diagnosing glaucoma in persons with DR, compared with persons without DR. This difference was independent of optic disc size (
Fig. 2). These associations persisted in different levels of fixed false-negative rate (40% and 60%;
Table 2). The significant associations also persisted after adjustment for age, sex, optic disc size, IOP, and axial length.
We performed several subsidiary analyses. After the exclusion of eyes with macular edema, the associations between the presence of DR with false-positive rates for Burk-LDF or for Bathija-LDF were similar (data not shown). We also performed statistical analyses by separately or collectively including the 154 pseudophakic eyes, 52 eyes with evidence of panretinal photocoagulation (PRP), and 76 eyes with suspected glaucoma. We found that a history of cataract surgery or PRP and the presence of suspected glaucoma were significantly associated with smaller rim area, thinner RNFL, and larger cup-to-disc area in multivariate analysis (all with P < 0.05). The presence of DR remained significantly associated with the false-positive rates for Burk-LDF and for Bathija-LDF (all with P < 0.05).