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Sandrina Nunes, Torcato Santos, Isabel Pires, Conceição Lobo, Rui Bernardes, José Cunha-Vaz; Cluster Analysis Identification Of Early Diabetic Retinopathy Phenotypes. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1276.
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To identify different phenotypes in mild non-proliferative diabetic retinopathy (NPDR) in type-2 diabetic patients based on non-invasive ophthalmological examinations using cluster analysis.
Four-hundred and twelve (412) type-2 diabetic patients with mild NPDR were included in a 2-year observational and prospective study to establish the association between phenotypes and genotypes in NPDR. The 258 patients that completed the first 6-month of follow-up underwent: color fundus photography (CFP), optical coherence tomography (Stratus OCT, Carl Zeiss Meditech Inc.) and blood tests. Data from baseline and the 6-month visit was used in this analysis. The microaneurysm formation rate (MAFR) was computed from CFP using an automatic method for MA earmarking (RetmarkerDR, Critical Health SA). Retinal thickness (RT) maps were computed using proprietary software allowing for the RT value in the central 500 µm in diameter macular area to be computed. A cluster analysis was performed to identify early DR phenotypes using a non-hierarchical clustering method (Ward’s Method). The identified clusters (phenotypes) were thereafter correlated with the progression of DR to clinically significant macular edema (CSME).
The clustering solution suggests the existence of 3 different phenotypes of DR. One cluster (Phenotype 1) is characterized by normal values on both the MAFR and the RT (median values: 0 MA/year and 161.0 µm, respectively), the second cluster (Phenotype 2) is characterized by a high RT (median value: 192.7 µm), and the third cluster (Phenotype 3) is characterized by a high MAFR (median value: 5 MA/year). Thirteen (13) out of the 258 patients (5.0%) developed CSME after the 6-month period (10 from Phenotype 2 (11.5%) and 3 from Phenotype 3 (2.7%), P=0.021). Patients from phenotypes 2 and 3 presents a higher risk for DR progression to CSME (RR=1.571; 95%CI=[1.429; 1.728]).
Cluster analysis based on non-invasive techniques (color fundus photography and OCT) identified 3 different phenotypes of early DR confirming the previous findings from our research group in a different study/group of patients. Patients with high RT and/or high MAFR present a higher risk for DR progression to CSME (RR=1.571; 95%CI=[1.429; 1.728]).
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