Purpose: The aim of this study was to analyze the factors associated with hyperreflective foci (HRF) in diabetic macular edema (DME) in treatment naïve eyes. Methods: This retrospective observational study included 131 eyes of 91 treatment naïve patients with DME. Details of ophthalmological examination with duration of vision loss and systemic parameters were noted. The spectral-domain optical coherence tomography (SD-OCT) images were analyzed for number and location of HRF and the associated imaging biomarkers. Results: Inner retinal (IR) HRF were seen in 88 eyes (67%), outer retinal (OR) in 28 (21%), and subretinal (SR) in 12 (9%). The IR had (7.1 ± 7) HRF, the OR (6.5 ± 4.8), and SR (3.9 ± 2.9). A greater proportion of eyes with HRF also had subretinal fluid (SRF), significantly higher blood pressure and lower serum triglycerides. Univariate linear regression analysis showed women (3 HRF greater vs. men, P = 0.04), eyes with cystoid spaces (2.95 more HRF vs. no cystoid spaces, P = 0.02), and SRF (2.96 more HRF vs. no SRF, P = 0.007) had more HRF, whereas higher triglycerides (1 HRF lesser per 50 mg lower TGL, P = 0.03) had lesser. Conclusion: Our study highlights the importance of HRF as an imaging biomarker in DME suggesting an inflammatory origin. Long-term observations of large cohorts with automated analysis can give more insights.

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