Diagnosing and monitoring diabetic macular edema: structural and functional tests.

Diabetic macular edema remains a major cause of visual impairment in adults despite the use of intensive glycemic control, photocoagulation therapy and new intravitreal drugs in the treatment of this disease. Although early diagnosis and treatment lead to better results, we still have patients who become legally blind. Therefore, better structural and functional characterization of this disease is necessary in order to customize treatment

Diabetic Macular Edema With and Without Subfoveal Neuroretinal Detachment: Two Different Morphologic and Functional Entities

To assess specific morphologic and functional characteristics in eyes with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+) vs DME without SND (SND-)

Intraocular Metastases Secondary to Breast Carcinoma Correlates With Upregulation of Estrogen and Progesterone Receptor Expression in the Primary Tumor

To compare estrogen (ER), progesterone (PR), and human epidermal growth factor-2 (HER2) receptor expression in the primary tumor of patients affected by choroidal metastases from breast carcinoma (BC) versus those with extraocular metastases

The Disorganization of Retinal Inner Layers Is Correlated to Müller Cells Impairment in Diabetic Macular Edema: An Imaging and Omics Study

The disorganization of retinal inner layers (DRIL) is an optical coherence tomography (OCT) biomarker strictly associated with visual outcomes in patients with diabetic macular edema (DME) whose pathophysiology is still unclear. The aim of this study was to characterize in vivo, using retinal imaging and liquid biopsy, DRIL in eyes with DME. This was an observational cross-sectional study. Patients affected by center-involved DME were enrolled. All patients underwent spectral domain optical coherence tomography (SD-OCT) and proteomic analysis of aqueous humor (AH). The presence of DRIL at OCT was analyzed by two masked retinal experts. Fifty-seven biochemical biomarkers were analyzed from AH samples. Nineteen eyes of nineteen DME patients were enrolled. DRIL was present in 10 patients (52.63%). No statistically significant difference was found between DME eyes with and without DRIL, considering the AH concentration of all the analyzed biomarkers except for glial fibrillary acidic protein (GFAP), a biomarker of Muller cells dysfunction (p = 0.02). In conclusion, DRIL, in DME eyes, seems to strictly depend on a major dysfunction of Muller cells, explaining its role not only as imaging biomarker, but also as visual function Muller cells-related parameter

Aqueous Humor Biomarkers of M\ufcller Cell Activation in Diabetic Eyes.

PURPOSE: To identify early biomarkers of retinal M\ufcller cell activation in diabetic eyes with or without clinically detectable signs of diabetic retinopathy (DR). METHODS: This study was a cross-sectional comparative case series. The aqueous humor (AH) of 34 eyes was collected in 12 healthy controls, 11 diabetic patients without DR, and 11 diabetic patients with nonproliferative DR. Full ophthalmic examination and spectral-domain optical coherence tomography were performed in all eyes. Glial fibrillary acidic protein (GFAP), aquaporin 1 (AQP1), and aquaporin 4 (AQP4) were quantified in AH samples as biomarkers of M\ufcller cell activity by ELISA. Statistical analysis was performed with ANOVA followed by Tukey-Kramer post hoc test. RESULTS: There was no significant difference in the age among the three groups. Mean concentration of GFAP, AQP1, and AQP4 significantly increased in diabetic eyes versus controls (P < 0.05, for each comparison). Glial fibrillary acidic protein and AQP1 showed an approximate 2-fold increase, whereas AQP4 showed an approximate 25-fold increase in diabetics with DR versus controls. In diabetics without DR, AQP4 showed an approximate 6-fold increase versus controls. CONCLUSIONS: Glial fibrillary acidic protein, AQP1, and AQP4-biomarkers of M\ufcller cell activity-are significantly increased in human eyes with diabetes, confirming that M\ufcller cells are precociously affected by diabetes mellitus

Microperimetry and fundus autofluorescence in diabetic macular edema subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation.

Abstract PURPOSE: The purpose of this study was to evaluate and compare microperimetry and fundus autofluorescence (FAF) after subthreshold micropulse diode laser versus modified Early Treatment Diabetic Retinopathy Study photocoagulation for clinically significant diabetic macular edema. METHODS: A prospective randomized clinical trial including 62 eyes (50 patients) with untreated, center-involving, clinically significant diabetic macular edema was performed. All patients underwent best-corrected visual acuity determination (logarithm of the minimum angle of resolution), slit-lamp biomicroscopy, FAF, optical coherence tomography, microperimetry (macular sensitivity), and fluorescein angiography before and after treatment. Best-corrected visual acuity, optical coherence tomography, microperimetry, and FAF were repeated at 1-, 3-, 6-, 9-, and 12-month follow-up examinations. Fluorescein angiography was performed at baseline and at 6 and 12 months. RESULTS: Before treatment, demographic and macular parameters were not different between the two treatment groups. At 12 months, best-corrected visual acuity remained stable in both groups (P = 0.41 and P = 0.82), mean central retinal thickness decreased in both groups (P = 0.0002 and P < 0.0001), and mean central 4 degrees and 12 degrees retinal sensitivity increased in the micropulse diode laser group (P = 0.02 and P = 0.0075) and decreased in the Early Treatment Diabetic Retinopathy Study group (P = 0.2 and P = 0.0026). There was no significant difference in either best-corrected visual acuity or central retinal thickness between the 2 treatment groups (P = 0.48 and P = 0.29), whereas there was a significant difference in 4 degrees and 12 degrees retinal sensitivity (P = 0.04 and P < 0.0001). Fundus autofluorescence never changed in the micropulse diode laser group even after retreatment. In the Early Treatment Diabetic Retinopathy Study group, FAF increased up to 9 months and decreased in 6 eyes (20%) at 12 months. DISCUSSION: Micropulse diode laser seems to be as effective as modified Early Treatment Diabetic Retinopathy Study laser photocoagulation in the treatment of clinically significant diabetic macular edema. Micropulse diode laser treatment does not determine any change on FAF showing (at least) nonclinically visible damage of the retinal pigment epithelium. Microperimetry data encourage the use of a new, less aggressive laser therapeutic approach in the treatment of clinically significant diabetic macular edema

Determinants of Long-Term Survival in Metastatic Choroidal and Ciliary Body Melanoma

Peer reviewe

Patients with Neovascular Age-Related Macular Degeneration Requiring Intensive Intravitreal Aflibercept Treatment: An ARIES Post Hoc Analysis.

INTRODUCTION The aim of this post hoc analysis of the ARIES study is to explore the requirement for intravitreal aflibercept (IVT-AFL) treatment intervals of < 8 weeks (w) in patients with neovascular age-related macular degeneration (nAMD), and to assess vision and anatomic outcomes in such patients who require more intensive treatment. METHODS ARIES was a multicenter, randomized, phase 3b/4 study that investigated the efficacy of two IVT-AFL proactive, individualized, treat-and-extend regimens over 2 years in treatment-naïve patients with nAMD. Patients were determined as injection-intensive if the study investigator identified that a treatment interval of < 8 w was needed and if they had ≥ 1 interval of < 8 w after three initial monthly doses. Treatment intervals could be extended subsequently if extension criteria were met. This is a post hoc analysis of patients enrolled in ARIES and statistical analysis is descriptive. RESULTS Of 269 patients in the combined treatment arms, 23.0% (n = 62) were injection-intensive (Year 1: 13.8% [n = 37]; Year 2: 9.3% [n = 25]). Time from IVT-AFL initiation to injection-intensive determination varied (range, 16-100 w; median: 43.2 w). Mean treatment interval was 8.4 w before and 6.1 w after injection-intensive determination. Overall, 59.7% achieved treatment intervals of ≥ 8 w following injection-intensive determination. Vision improvements from baseline to Week 104 were smaller for injection-intensive patients than non-injection-intensive patients (mean [SD] best-corrected visual acuity change: + 2.3 [15.6] vs.  + 5.9 [12.3] letters). Anatomic outcomes were similar between injection-intensive and non-injection-intensive patients (central retinal thickness change from baseline to Week 104: - 160 [154] vs.  - 167 [136] µm). CONCLUSIONS In ARIES, 23% of treatment-naïve patients with nAMD experienced at least one treatment interval of < 8 w. Injection-intensive patients showed improved vision and anatomic outcomes. For most, treatment intervals could be extended to ≥ 8 w following injection-intensive determination. CLINICALTRIALS gov Identifier: NCT02581891