Microaneurysm Counting as a Biomarker for the Hyperperfusion Stage of Nonproliferative Diabetic Retinopathy
Luís Mendes1, Ana Rocha1,2,3,4, Marta Lopes1
1AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.
Introduction:
This study aimed to investigate the utility of microaneurysm (MA) counting as a tool for characterizing the hyperperfusion stage of nonproliferative diabetic retinopathy (NPDR) and to examine the hypothesis that MAs can serve as a surrogate biomarker for the presence of intraretinal microvascular abnormalities (IRMAs).
Methods:
Forty-nine (n = 49) eyes with type 2 diabetes mellitus with NPDR were included in this analysis: 12 with Early Treatment Diabetic Retinopathy Study (ETDRS) levels 43 and 37 with levels 47-53. Automated MA detection was performed using the RetmarkerDR software (Retmarker SA, Meteda Group, Italy), alongside manual detection, both done in the central retina (field 2). Based on MA counts, microaneurysm turnover (MAT) was computed. IRMAs were manually counted based on swept-source optical coherence tomography (SS-OCT) angiography on PLEX® Elite 9000 (ZEISS, Dublin, CA, USA). The statistically significant differences between ETDRS groups were studied by comparing Mann-Whitney U test p values (significance value < 0.05). The correlation between the presence of MAs and IRMAs and MAT and IRMAs was examined using Spearman correlation analysis.
Results:
There was an observed increase in the number of IRMAs, MAs, and MAT values as NPDR progressed, independently of the counting method used. Specifically, this increase was noted when transitioning from ETDRS groups characterized by the predominance of the hypoperfusion stage (ETDRS 43) to those associated with the hyperperfusion stage (ETDRS 47-53). When MAs were counted manually, a moderate correlation was identified between the number of MAs and the presence of IRMAs (ρ = 0.40; p value = 0.005). Additionally, a similar correlation was found between MAT and the presence of IRMAs (ρ = 0.43; p value = 0.002).
Conclusions:
This study underscores the potential relevance of MAs as a pivotal indicator of the hyperperfusion stage of NPDR and supports their role as surrogate biomarkers for IRMAs. These results suggest a role for MA counting in the assessment and management of diabetic eye disease.
Insights
Microaneurysm (MA) counting can indicate the hyperperfusion stage of nonproliferative diabetic retinopathy (NPDR). MAs show potential as surrogate biomarkers for intraretinal microvascular abnormalities (IRMAs), aiding in diabetic eye disease assessment.
Area of Science:
- Ophthalmology
- Diabetic Retinopathy Research
- Medical Imaging Analysis
Background:
- Nonproliferative diabetic retinopathy (NPDR) is a leading cause of vision loss.
- Characterizing NPDR stages is crucial for timely intervention.
- Microaneurysms (MAs) are early indicators of diabetic retinopathy.
Purpose of the Study:
- To evaluate microaneurysm (MA) counting for characterizing NPDR hyperperfusion.
- To test if MAs can serve as surrogate biomarkers for intraretinal microvascular abnormalities (IRMAs).
Main Methods:
- Analysis of 49 eyes with type 2 diabetes mellitus and NPDR.
- Automated and manual MA detection using RetmarkerDR software.
- Manual counting of IRMAs via swept-source OCT angiography.
- Correlation analysis between MA counts, microaneurysm turnover (MAT), and IRMAs.
Main Results:
- Increased IRMAs, MAs, and MAT values correlated with NPDR progression.
- A moderate correlation was found between manual MA counts and IRMAs (ρ=0.40, p=0.005).
- A similar correlation existed between MAT and IRMAs (ρ=0.43, p=0.002).
Conclusions:
- Microaneurysm counting shows potential for identifying NPDR hyperperfusion.
- MAs may serve as reliable surrogate biomarkers for IRMAs.
- MA counting could enhance the assessment and management of diabetic eye disease.
Related Concept Videos
Diabetic Retinopathy
Diabetic Nephropathy


