Purpose To analyse and compare the classification of eyes with diabetic retinopathy using fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) performed either with AngioPlex or AngioVue. Methods This was an observational cross-sectional study of 50 eyes from 26 diabetic subjects. Two independent graders classified the FA angiograms, to assess the presence and severity of several characteristics according to the ETDRS Report 11, and a similar evaluation was performed for each 3×3 mm OCTA image from the superficial retinal layer and for the full retina slab. Results Percentages of non-gradable images for the outline of foveal avascular zone (FAZ) in the central subfield (CSF) were 29.0% for FA, 12.0% for AngioVue and 3.0% for AngioPlex. For capillary loss, percentages of non-gradable images in the CSF were 25.0% for FA, 11% for AngioVue and 0.0% for AngioPlex. For the inner ring (IR), percentages of non-gradable images were 12.5% for FA, 11.5% for AngioVue and 0.5% for AngioPlex. Agreement between graders was substantial for outline of FAZ. For capillary loss, the agreement was fair for the CSF, and moderate for the IR. Conclusions The OCTA allows better discrimination of the CSF and parafoveal macular microvasculature than FA, especially for FAZ disruption and capillary dropout, without the need of an intravenous injection of fluorescein. In addition, FA had also a higher number of non-gradable images. The OCTA can replace with advantage the FA, as a non-invasive and more sensitive procedure for detailed morphological evaluation of central macular vascular changes. Trial registration number NCT02391558, Pre-results.

The objective of this study was to evaluate the prevalence of different disease pathways (ischemia, neurodegeneration, and edema) in the initial stages of diabetic retinopathy. In this retrospective cross-sectional study, eyes were grouped by diabetic retinopathy severity using the 7-field Early Treatment Diabetic Retinopathy Study (ETDRS) protocol (levels 10–20, 35, and 43–47). Neurodegeneration was identified by thinning of the retinal nerve fiber layer and/or ganglion cell layer. Edema was identified by thickening of the inner nuclear layer, outer plexiform layer, or full retina. Ischemia was identified by metrics of retinal vessel density. Imaging was performed in 142 eyes from 142 patients (28% women) aged 52–88 years. Vessel density (ischemia) was significantly different between the ETDRS groups (P < 0.020). On multivariate regression analysis, it remained significantly different between stages of the disease and showed associations with age (P < 0.001), sex (P = 0.028), and metabolic control (P = 0.034). No significant differences between ETDRS groups were found in retinal thinning (neurodegeneration) or retinal thickness (edema). Eyes with the same ETDRS retinopathy grading from different patients with diabetes showed that the prevalence of different disease pathways varies between patients, even within the same severity group. Ischemia (capillary dropout) is the only disease pathway that shows correlation with retinopathy severity and metabolic control.

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.

Purpose: To evaluate the long-term safety and efficacy of intravitreal ranibizumab in the treatment of myopic choroidal neovascularization (CNV). Methods: Three-year retrospective, nonrandomized, interventional case series. Forty eyes of 39 patients with myopic CNV were included; 15 with previous photodynamic therapy, and 25 naïve eyes. Best-corrected visual acuity (BCVA) changes, central foveal thickness (CFT), and number of treatments were assessed, from baseline to month 36. Results: Mean visual acuity improved from 55.4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 59.7 letters at 12 months (p = 0.07), 61.8 letters at 24 months (p = 0.008) and 63.4 letters at 36 months (p = 0.039). Twenty-five percent of the patients gained ≧15 letters (3 lines) at 12 months, 30% at 24 months and 35% at 36 months. There was a mean reduction of 80 µm in CFT (p < 0.001). A mean of 4.1 injections were performed in the first year, 2.4 in the second year and 1.1 in the third year. Fifty-three percent of the eyes had no need for treatment during the third year of follow-up. Conclusions: Intravitreal ranibizumab seems to be an effective and safe therapeutic procedure to treat CNV in highly myopic eyes, with a high proportion of patients gaining or stabilizing BCVA at a 3-year follow-up.

Purpose To evaluate morphological and functional chorioretinal changes 5 years after standard photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). Methods A retrospective, nonrandomized study, including patients with chronic CSC treated with standard PDT and followed for at least 60 months. All patients underwent a complete ophthalmological examination, and the location and number of treatments were registered. Five or more years after treatment, subfoveal and non-subfoveal treated areas were evaluated with Spectralis optical coherence tomography and microperimetry. Results Seventeen eyes of 15 patients were included, with mean age of 48.3±8.4 years and a mean follow-up of 80.6± 12.4 months (range from 62 to 104 months). All eyes had neurosensory detachment (NSD) at baseline. Treatment was performed under the fovea in 58.8 % and in a non-foveal area in 41.2 % of the eyes. At the final visit all eyes had resolution of the NSD, with a statistical significant reduction in central macular thickness (p=0.005) and preserved neuroretinal thickness (p=0.839). There was a statistical difference between initial and final BCVA (p<0.001) and a mean gain of 8.4±7.8 letters. Subfoveal morphological changes in external limiting membrane (ELM) and in photoreceptor inner and outer segment junction (IS/OS) were correlated with final BCVA (p=0.015 and p=0.014 respectively), but not with the variation of BCVA. There was a statistical correlation between morphological changes in IS/OS line and retinal sensitivity in the central 12°and 2°(p=0.003 and p=0.002 respectively). The morphological changes in the subfoveal layers were not dependent on treatment location (p=0.154, p=0.644, and p=1.0 for ELM, IS/OS line, and retinal pigment epithelium respectively). Subfoveal final mean choroidal thickness was 295.1±68.7 μm, and showed no statistical difference from the normal population (p=0.633). Conclusions Morphological and functional chorioretinal changes, observed 5 or more years after standard PDT for chronic CSC, were not correlated with the location of treatment, neither with the progression of visual acuity or with the location of treatment, and are more likely to be related to the disease itself than with the treatment provided.

PURPOSE. To characterize 2-year changes occurring in neurodegeneration, edema, and capillary dropout in nonproliferative diabetic retinopathy. METHODS. Two-year prospective longitudinal observational cohort of eyes/patients with type 2 diabetes using spectral domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA). Eyes were examined three times with intervals of 1 year. Thickness of the full retina and layer-by-layer measurements were used to identify edema or neurodegeneration. OCTA vessel density maps of the retina were used to identify capillary dropout. Early Treatment Diabetic Retinopathy Study (ETDRS) classification was performed using the seven-field ETDRS protocol. RESULTS. A total of 62 eyes from 62 patients with diabetes were followed for 2 years. After verification for image quality, a total of 44 eyes from 44 patients (30% women) aged 52 to 80 years were retained for data analysis. There were 18 eyes with ETDRS grades 10 to 20, 17 eyes with ETDRS grade 35, and 9 eyes with ETDRS grades 43 to 47. During the 2-year follow-up period, there was a progressive increase in capillary dropout, whereas edema and neurodegeneration remained stable. In multivariate analysis, considering a model adjusted for age, sex, hemoglobin A 1C , visual acuity, and diabetes duration, vessel density remained significantly different between Diabetic Retinopathy Severity Scale groups (Wilks' λ = 0.707; P = 0.015) showing association with disease progression. CONCLUSIONS. Capillary dropout increased in a period of 2 years in eyes with minimal, mild, and moderate diabetic retinopathy, whereas the presence of edema and neurodegeneration remained stable.

PurposeTo test whether a single or composite set of parameters evaluated with optical coherence tomography angiography (OCTA), representing retinal capillary closure, can predict non-proliferative diabetic retinopathy (NPDR) staging according to the gold standard ETDRS grading scheme.Methods105 patients with diabetes, either without retinopathy or with different degrees of retinopathy (NPDR up to ETDRS grade 53), were prospectively evaluated using swept-source OCTA (SS-OCTA, PlexElite, Carl Zeiss Meditec) with 15×9 mm and 3×3 mm angiography protocols. Seven-field photographs of the fundus were obtained for ETDRS staging. Eyes from age-matched healthy subjects were also imaged as control.ResultsIn eyes of patients with type 2 diabetes without retinopathy or ETDRS levels 20 and 35, retinal capillary closure was in the macular area, with predominant alterations in the parafoveal retinal circulation (inner ring). Retinal capillary closure in ETDRS stages 43–53 becomes predominant in the retinal midperiphery with vessel density average values of 25.2±7.9 (p=0.001) in ETDRS 43 and 23.5±3.4 (p=0.001) in ETDRS 47–53, when evaluating extended areas of 15×9 protocol. Combination of acquisition protocols 3×3 mm and 15×9 mm, using SS-OCTA, allows discrimination between eyes with mild NPDR (ETDRS 10, 20, 35) and eyes with moderate-to-severe NPDR (ETDRS grades 43–53).ConclusionsRetinal capillary closure, quantified by SS-OCTA, can identify NPDR severity progression. It is located mainly in the perifoveal retinal capillary circulation in the initial stages of NPDR, whereas the retinal midperiphery is predominantly affected in moderate-to-severe NPDR.

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.