Increased outer retinal volume (parafoveal and entire 3×3-mm macular scan) predicts DR progression over two years, highlighting its potential role as a clinically accessible biomarker for identifying eyes at higher risk for DR complications.
Key Findings
Results
Higher baseline outer retinal volume in the parafoveal and whole 3×3-mm scan area was significantly associated with diabetic retinopathy progression over two years.
The association was statistically significant at P < 0.001 for both parafoveal and whole scan outer retinal volume
Inner retinal volume showed no significant association with DR progression
Central subfield outer retinal volume was not reported as significant; the parafoveal (1-3 mm) and whole 3×3-mm regions were the significant predictors
Generalized Estimating Equations (GEE) were used to account for the correlation between two eyes from the same patient
Results
Outer retinal volume remained independently associated with higher odds of DR progression after adjusting for multiple covariates and correction for multiple comparisons.
Covariates adjusted for included baseline DR severity, hypertension, age, and lens status
Bonferroni correction was applied and the association remained significant at P < 0.001
This indicates the predictive value of outer retinal volume is independent of known clinical risk factors
Methods
Of 190 eyes from 121 patients followed over two years, 48 eyes (25.3%) from 39 patients demonstrated DR progression.
The study included 190 eyes from 121 patients across the DR severity spectrum without diabetic macular edema
48 eyes (25.3%; 39 patients) met the definition of progression
Progression was defined as DR worsening on fluorescein angiography, vision loss ≥10 letters at two years, or development of vitreous hemorrhage, initiation of pan-retinal photocoagulation, or anti-VEGF therapy at any point during follow-up
This was a longitudinal observational study with two-year follow-up
Methods
Baseline 3×3-mm macular OCT scans with manual correction of segmentation were used to derive inner and outer retinal volumes across three macular regions.
The three regions analyzed were: central subfield, 1-3 mm parafoveal area, and the whole 3×3-mm scan
Manual correction of automated segmentation was performed to improve accuracy
Both inner and outer retinal layer volumes were derived and analyzed separately
OCT-based volumetric measurements were the primary imaging biomarker evaluated
Conclusions
OCT-derived outer retinal volume is proposed as a clinically accessible prognostic biomarker for identifying eyes at higher risk for diabetic retinopathy complications.
The authors highlight that macular OCT is routinely performed in clinical practice, making this biomarker readily obtainable without additional testing
The findings support outer retinal volume as having prognostic value beyond current DR severity grading
The study population spanned the DR severity spectrum, suggesting broad applicability of the biomarker
What This Means
This research suggests that a specific measurement from routine eye imaging — the volume of the outer layer of the retina — can predict whether diabetic retinopathy (a diabetes-related eye disease) will worsen over the next two years. The study followed 190 eyes from 121 patients with diabetes, none of whom had diabetic macular edema (swelling of the central retina) at the start. Patients were followed for two years, and about one in four eyes (25.3%) showed worsening disease, defined by deterioration on specialized imaging, significant vision loss, or the need for treatments like laser therapy or injections. Eyes that had a larger outer retinal volume at the beginning of the study — particularly in the ring-shaped area just outside the central retina — were significantly more likely to progress, even after accounting for factors like disease severity, age, and blood pressure.
Importantly, only the outer retinal layer volume mattered; the inner retinal layer volume did not predict progression. This distinction may reflect specific biological processes happening in the outer retina during early diabetic damage, such as changes in the photoreceptors or supporting cells, that precede visible clinical worsening. The finding held up after rigorous statistical adjustment, suggesting it is a genuinely independent predictor rather than simply reflecting already-known risk factors.
This research suggests that ophthalmologists could potentially use standard OCT scans — equipment already present in most eye clinics — to better identify which patients with diabetic retinopathy are at greatest risk of complications, without needing additional or expensive tests. If validated in larger studies, incorporating outer retinal volume measurements into routine diabetic eye care could help prioritize closer monitoring or earlier treatment for high-risk patients.