Secondary Logo

Journal Logo

Institutional members access full text with Ovid®


Vujosevic, Stela MD, PhD; Berton, Marianna MD; Bini, Silvia MD; Casciano, Margherita MD; Cavarzeran, Fabiano ScD; Midena, Edoardo MD, PhD

doi: 10.1097/IAE.0000000000000912
Original Study

Background: To assess and correlate early modifications in hyperreflective retinal spots (HRS), retinal sensitivity (RS), fixation stability, and best-corrected visual acuity (BCVA) after anti-vascular endothelial growth factor treatment in naive center-involving diabetic macular edema.

Methods: Cross-sectional comparative case–control series. Twenty diabetic patients underwent 3 consecutive intravitreal anti-vascular endothelial growth factor injections in the study eye (20 fellow eyes served as control), full ophthalmologic examination including spectral domain optical coherence tomography (Retinascan RS-3000; Nidek, Gamagori, Japan), and microperimetry (MP1; Nidek) at baseline (Visit-V1), 1 month after each injection (V2, V3, V4), and at 6 months (V5). Central retinal thickness, inner and outer retinal thickness, number of HRS, BCVA, RS, and bivariate contour ellipse area were evaluated by analysis of variance test with Bonferroni post hoc test. Correlation analyses were performed by Spearman correlation.

Results: In treated eyes, central retinal thickness and inner retinal thickness significantly decreased at V2, V3, V4 versus V1 (P < 0.03 at least for all); the mean number of HRS significantly decreased in both inner and outer retina at all follow-up visits versus V1 (P < 0.008 at least for all); mean RS and bivariate contour ellipse area remained statistically unchanged during the follow-up; BCVA significantly improved at V3, V4, and V5 versus V1 (P = 0.009 at least for all). In fellow eyes, central retinal thickness, HRS, RS, and BCVA did not change at any follow-up. The number of HRS correlated inversely with RS, directly with bivariate contour ellipse area, and not significantly with BCVA.

Conclusion: A significant decrease in HRS in the retina after anti-vascular endothelial growth factor treatment is documented. A decrease in HRS correlates with functional parameters, specifically RS. New parameters may be used for treatment evaluation in center-involving diabetic macular edema.

An increase in intraretinal hyperreflective spots detected on optical coherence tomography as small, punctiform whitish lesions has been reported in diabetic patients as signs of inflammatory response. The number of hyperreflective spots correlates inversely with retinal sensitivity. Anti-vascular endothelial growth factor treatment significantly reduces the number of hyperreflective spots in diabetic macular edema. Hyperreflective spots may add new information in treatment evaluation of diabetic macular edema.

*Department of Ophthalmology, University of Padova, Padova, Italy; and

Fondazione G.B. Bietti, IRCCS, Rome, Italy.

Reprint requests: Edoardo Midena, MD, PhD, Department of Ophthalmology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; e-mail:

Supported by the grant from the seventh Frame-work Programme (EUROCONDOR, FP7-278040). This research was financially supported, as G.B. Bietti Foundation is concerned, by the Ministry of Health and Fondazione Roma.

Paper partially presented as a free article at the EURETINA meeting 2014, London, United Kingdom.

None of the authors have any conflicting interests to disclose.

© 2016 by Ophthalmic Communications Society, Inc.