Inner Nuclear Fluid Volume May Represent Superior Biomarker for Diabetic Macular Edema

OCT measurement
Ophthalmic test – OCT optical coherence tomography measurement. SLO Scan view of the macula in retina with vessels
The OCT finding correlates with reduced visual acuity, according to a study.

Fluid volume (FV) in the inner nuclear layer is strongly associated with visual acuity (VA), perhaps more so than other optical coherence tomography (OCT) biomarkers, according to a study published in the American Journal of Ophthalmology. 

The study included 125 eyes of 125 patients with diabetic macular edema (DME) (mean age: 60.5 years, 65 men, 60 women). Investigators measured intraretinal fluid volume via automated fluid detection algorithm on 3×3-mm optical coherence tomography (OCT) angiogram volume scans. Intraretinal fluids were divided into inner FV and outer FV based on retinal layer segmentations. The mean inner FV was 0.013 mm3 in 109 eyes (87%), and the mean outer FV was 0.042 mm3 in 124 eyes (99%). 

Univariate analysis showed that VA correlated significantly with inner FV (P <.0001), whole macular FV (P =.010), and central subfield thickness (CST) (P =.036), but not with outer FV. Multivariate analysis confirmed that inner FV (P =.004) was the only significant factor for baseline VA.

These correlations upheld their significance when the treatment-naïve group (n=33) and the eyes without prior laser treatments (n=93) were analyzed separately. This is evidenced by the fact that the area under the receiver operating characteristic curve (AROC) of inner FV for VA of 20/32 or poorer was significantly higher than the AROC of CST (0.66 vs 0.54, P =.018). 

”Inner FV may be a meaningful biomarker in the management of DME, which represents more specific pathologic changes in DME and has a stronger correlation with visual acuity compared to the commonly used CST,” according to the researchers. “A longitudinal study is needed to validate the clinical utility of inner FV.”

Study limitations include confounding due to intravitreal injections prior to OCT imaging and an inability to study changes in inner FV and VA over time due to the cross-sectional design.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Tsuboi K, You QS, Guo Y, et al. Association between fluid volume in inner nuclear layer and visual acuity in diabetic macular edema. Am J Ophthalmol. Published online December 20, 2021. doi:10.1016/j.ajo.2021.12.012