Systemic and vitreous biomarkers - new insights in diabetic retinopathy.

PURPOSE: Diabetic retinopathy (DR) is a microvascular inflammatory and neurodegenerative disease. The purpose of this study was to analyze the relationship between DR severity and the levels of potential biomarkers in the serum and/or vitreous. METHODS: A prospective, consecutive, controlled, observational study was performed between June 2018 and January 2020. Blood and vitreous samples were collected on the day of vitrectomy in patients without diabetes and in patients with diabetes with epiretinal membrane, macular edema, and indication for vitrectomy. RESULTS: Transthyretin (TTR) was the only blood biomarker with levels statistically higher in patients with diabetes (p = 0.037). However, no correlation with DR severity was observed. Erythropoietin (EPO) was the only blood biomarker whose levels were associated with DR severity (p = 0.036). In vitreous samples, levels of EPO (p = 0.011), interleukin (IL)-6 (p < 0.001), IL-8 (p < 0.001), IL-17 (p = 0.022), monokine induced by interferon-γ (MIG) (p < 0.001), and interferon gamma-induced protein 10 (IP-10) (p = 0.005) were significantly higher in patients with diabetes. Additionally, in vitreous, IL-6, IL-8, MIG, and IPL-10 levels were also higher in more severe DR cases (p < 0.05). CONCLUSIONS: Among the studied biomarkers, vitreous IL-6, IL-8, MIG, and IP-10 were the ones whose levels had the strongest coherent relationship with DR severity prediction and, thus, have the best potential post-vitrectomy prognostic value.

Changes in Ganglion Cell Layer Thickness after Treatment with the 0.2 µg/day Fluocinolone Acetonide Implant in Vitrectomized and Nonvitrectomized Eyes with Diabetic Macular Edema.

INTRODUCTION: The objective of this study is to compare changes in ganglion cell layer (GCL) between vitrectomized and nonvitrectomized eyes with diabetic macular edema (DME) over a 2-year period following treatment with 0.2 µg/day fluocinolone acetonide (FAc) implant. METHODS: Eighteen vitrectomized (group 1) and 8 nonvitrectomized (group 2) eyes were included in this cohort study. Changes in central macula GCL thickness were measured using the Spectralis spectral domain-optical coherence tomography at baseline and 6, 12, and 24 months of follow-up. Other parameters analyzed included best-corrected visual acuity (BCVA), central foveal thickness (CFT), and intraocular pressure (IOP). RESULTS: Treatment with the FAc implant led to small reductions in mean global GCL thickness versus baseline and contrasts with the control group that was stable or slightly increased versus baseline. FAc therapy also led to improvements in mean BCVA and CFT that were observed at Month 6 and maintained to Month 24. For vitrectomized and nonvitrectomized eyes, no differences were observed between mean global GCL, BCVA, and CFT values during follow-up. Linear correlations revealed that in all groups mean BCVA at Month 24 positively correlated with mean GCL thickness at baseline and at Month 24. IOP remained stable throughout the 24 months. CONCLUSION: There was no evident retinal neurodegeneration in the 2-year period following treatment with FAc in both groups. GCL thickness may be a useful biomarker for assessing safety and effectiveness in patients with DME.

Vitrectomized versus non-vitrectomized eyes in diabetic macular edema response to ranibizumab-retinal layers thickness as prognostic biomarkers.

To evaluate the role of the vitreous in the management of diabetic macular edema with ranibizumab intravitreal injections in a pro re nata regimen. Prospective study of 50 consecutive eyes with diabetic macular edema treated with ranibizumab and 12 months of follow-up. Primary endpoint: to assess differences between non-vitrectomized and vitrectomized eyes in the number injections needed to control the edema. Secondary endpoints: comparison of groups regarding best corrected visual acuity, central foveal thickness and thickness of seven retinal layers. 46 eyes from 38 patients, 10 vitrectomized and 36 non-vitrectomized, completed the follow-up. At month 12, the two groups achieved an equivalent anatomical outcome and needed a similar number of ranibizumab intravitreal injections. In vitrectomized eyes final visual acuity was worse when baseline retinal nerve fiber layers in the central foveal subfield were thicker, showing a strong correlation (r = - 0.942, p < 0.001). A similar, albeit moderate correlation was observed in non-vitrectomized eyes (r = - 0.504, p = 0.002). A decrease of retinal nerve fiber layers inner ring thickness was correlated with a better final visual acuity only in vitrectomized eyes (r = 0.734, p = 0.016). The effect of diabetic macular edema seems to be worse in vitrectomized eyes, with a thinner inner retina reservoir.Clinicaltrials.govNCT04387604.

Long-Term Visual Function Effects of Pan-Retinal Photocoagulation in Diabetic Retinopathy and Its Impact in Real Life.

PURPOSE: To address the long-term visual function after bilateral pan-retinal photocoagulation (PRP) and its impact in real life, namely on visual field (VF) legal criteria to drive. To determine potential predictors related to clinical factors and treatment strategies. PATIENTS AND METHODS: Observational cross-sectional study. Eyes from diabetic patients diagnosed with diabetic retinopathy who underwent bilateral PRP, with or without macular treatments and with visual acuity legal criteria for non-professional driving were randomly assigned. Main outcomes were: demographic and clinical data including best corrected visual acuity; binocular visual field (EBST-Esterman Binocular Suprathreshold Test, Humphrey analyzer3®); contrast sensitivity (CS-Metrovision-MonPack3®); light scattering in the retina (HD Analyzer, Visiometrics®). RESULTS: Seventy-one diabetic patients included (44 men and 27 women), with a mean age of 62.2±11.8 years. PRP was performed, on average, 9.7±6.9 years before the study. The average EBST Score was 85.8±17.0 and the average CS (2-5cpd) was 19.5±2.9 dB in photopic and 14.2±4.1 dB in mesopic conditions. Through a multivariate regression model, after adjusting to the clinical and demographic factors as possible confounders, we found that treatment factors associated with worse results were the use of Argon laser for the EBST Score, the very confluent PRP for the number of non-viewed points in the central 30°x20° of the EBST and the presence of macular treatments for the CS tests. According to Portuguese law, 79% (n=56) of patients had minimal EBST amplitudes for non-professional driving. CONCLUSION: The functional results achieved in our sample are compatible with an active life, allowing most of the patients included to overcome the requirements of Portuguese legislation for driving light vehicles, namely at the level of the binocular visual field. These results highlight the role of PRP in the treatment of diabetic retinopathy in an era with evolving less aggressive laser options.