Different retinopathy phenotypes in type 2 diabetes predict retinopathy progression.

PURPOSE: To characterize the progression in retinopathy severity of different phenotypes of mild nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes. DESIGN AND METHODS: Patients with type 2 diabetes and mild NPDR (ETDRS 20 or 35) were followed in a 5-year longitudinal study. Examinations, including color fundus photography (CFP) and optical coherence tomography (OCT and OCTA), were performed at baseline, 6 months and then annually. Phenotype classification was performed based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Phenotype A is characterized by low MAT (< 6) and normal CRT; Phenotype B by low MAT (< 6) and increased CRT; and Phenotype C by higher MAT (≥ 6) with or without increased CRT. ETDRS grading of seven fields CFP was performed at the initial and last visits. RESULTS: Analysis of ETDRS grade step changes showed significant differences in diabetic retinopathy (DR) progression between the different phenotypes (p < 0.001). Of the 66 participants with phenotype A only 2 eyes (3%) presented 2-or-more-step worsening. None of the 50 participants characterized as phenotype B developed 2-step worsening, whereas 13 eyes (23.2%) characterized as phenotype C had 2-or-more-steps worsening. Phenotype C presents the higher risk for 2-or-more step worsening (OR: 15.94 95% CI: 3.45-73.71; p < 0.001) and higher sensitivity, correctly identifying 86.7% of cases at risk (AUC: 0.84 95% CI: 0.72-0.96; p < 0.001). Diabetic retinopathy severity progression was associated with HbA1c (p = 0.019), LDL levels (p = 0.043), and ocular factors as MAT (p = 0.010), MA formation rate (p = 0.014) and MA disappearance rate (p = 0.005). Capillary closure at 5-year follow-up, identified by lower vessel density (VD) on OCTA, was also associated with diabetic DR severity progression (p = 0.035). CONCLUSIONS: Different DR phenotypes in type 2 diabetes show different risks of retinopathy progression. Phenotype C is associated with increased HbA1c values and presents a higher risk of a 2-or-more-step worsening of the ETDRS severity score.

Retinopathy Phenotypes in Type 2 Diabetes with Different Risks for Macular Edema and Proliferative Retinopathy.

Our group reported that three diabetic retinopathy (DR) phenotypes: A, characterized by low microaneurysm turnover (MAT < 6) and normal central retinal thickness (CRT); B, low MAT (<6) and increased CRT, and C, high MAT (≥6), present different risks for development of macular edema (DME) and proliferative retinopathy (PDR). To test these findings, 212 persons with type 2 diabetes (T2D) and mild nonproliferative retinopathy (NPDR), one eye per person, were followed for five years with annual visits. Of these, 172 completed the follow-up or developed an outcome: PDR or DME (considering both clinically significant macular edema (CSME) and center-involved macular edema (CIME)). Twenty-seven eyes (16%) developed either CSME (14), CIME (10), or PDR (4), with one eye developing both CSME and PDR. Phenotype A showed no association with development of vision-threatening complications. Seven eyes with phenotype B and three with phenotype C developed CIME. Phenotype C showed higher risk for CSME development, with 17.41 odds ratio (p = 0.010), compared with phenotypes A + B. All eyes that developed PDR were classified as phenotype C. Levels of HbA1c and triglycerides were increased in phenotype C (p < 0.001 and p = 0.018, respectively). In conclusion, phenotype C identifies eyes at higher risk for development of CSME and PDR, whereas phenotype A identifies eyes at very low risk for vision-threatening complications.

Biocompatibility of a bioceramic silicone-based sealer in subcutaneous tissue.

This study evaluated the biocompatibility of a new silicone-based sealer (GuttaFlow Bioseal) in rat subcutaneous tissue and compared the results with those for GuttaFlow2 and AH Plus. Each of 16 Wistar rats received four subcutaneous tissue implants, namely, GuttaFlow Bioseal, GuttaFlow2, AH Plus, and one empty polyethylene tube. Eight rats were euthanized at day 8 and the remaining eight at day 30. Histological sections were stained with haematoxylin and eosin and analysed with a light microscope. Scores were established for inflammatory reaction, macrophage infiltrate, thickness of the fibrous capsule, and vascular changes. Differences between groups were assessed by using the Friedman test with Bonferroni correction. Histological analysis showed that GuttaFlow Bioseal had the lowest inflammatory reaction of all tested sealers at day 8. At day 30, the silicone-based sealers had similar inflammation profiles, but inflammation scores were nonsignificantly higher for AH Plus than for the negative control. The inflammatory reaction decreased from day 8 to day 30 in all sealers. GuttaFlow Bioseal had the most macrophage infiltrate. Under the present experimental conditions, GuttaFlow Bioseal induced limited inflammatory reactions at days 8 and 30, and initial inflammatory reactions to GuttaFlow2 and AH Plus subsided within 30 days. All tested sealers exhibited satisfactory biocompatibility at day 30 after subcutaneous implantation.