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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 Müller cells dysfunction (p = 0.02). In conclusion, DRIL, in DME eyes, seems to strictly depend on a major dysfunction of Müller cells, explaining its role not only as imaging biomarker, but also as visual function Müller cells-related parameter. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a form of diabetic microangiopathy, and vascular hyperpermeability in the macula leads to retinal thickening and concomitant reduction of visual acuity in diabetic macular edema (DME). In this review, we discuss multimodal fundus imaging, comparing the pathogenesis and interventions. Clinicians diagnose DME using two major criteria, clinically significant macular edema by fundus examination and center-involving diabetic macular edema using optical coherence tomography (OCT), to determine the appropriate treatment. In addition to fundus photography, fluorescein angiography (FA) is a classical modality to evaluate morphological and functional changes in retinal capillaries, e.g., microaneurysms, capillary nonperfusion, and fluorescein leakage. Recently, optical coherence tomography angiography (OCTA) has allowed us to evaluate the three-dimensional structure of the retinal vasculature and newly demonstrated that lamellar capillary nonperfusion in the deep layer is associated with retinal edema. The clinical application of OCT has accelerated our understanding of various neuronal damages in DME. Retinal thickness measured by OCT enables us to quantitatively assess therapeutic effects. Sectional OCT images depict the deformation of neural tissues, e.g., cystoid macular edema, serous retinal detachment, and sponge-like retinal swelling. The disorganization of retinal inner layers (DRIL) and foveal photoreceptor damage, biomarkers of neurodegeneration, are associated with visual impairment. Fundus autofluorescence derives from the retinal pigment epithelium (RPE) and its qualitative and quantitative changes suggest that the RPE damage contributes to the neuronal changes in DME. These clinical findings on multimodal imaging help to elucidate the pathology in the neurovascular units and lead to the next generation of clinical and translational research in DME. [ABSTRACT FROM AUTHOR]

Background: To compare the surgical status in idiopathic epiretinal membrane (IERM) patients with or without disorganization of retinal inner layers (DRIL) and to correlate with optical coherence tomography angiography (OCTA) and clinical data. Methods: In 74 eyes from 74 patients with IERM treated by surgery with 12-month follow-up. According to the superficial hemorrhage, the patients were divided into group A (no macular bleeding), group B (macular parafoveal bleeding) and group C (macular foveal bleeding). Optical coherence tomography (OCT) were evaluated for presence of DRIL,central retina thickness and integrity of the inner/outer segment layer recorded at baseline and at 1, 3, 6, and 12 months postoperatively and best-corrected visual acuity (BCVA) was recorded simultaneously. OCTA was conducted at 12 months postoperatively. Main outcome measures is correlation between DRIL and superficial hemorrhage in membrane peeling,and BCVA and OCTA outcomes postoperatively. Results: The rate of DRIL and BCVA had statistically significant differences between the three groups at the time points(baseline and 1, 3, 6, and 12 months after surgery), respectively (P < 0.001 for all). FD-300 value (P = 0.001)and DCP in all parafoveal regions (superior: P = 0.001; inferior: P = 0.002;Nasal: P = 0.014;Tempo: P = 0.004) in eyes with DRIL were lower than those without DRIL.There was a linear regression relationship between FD-300 and postoperative BCVA (P = 0.011). Conclusion: IERM Patients with DRIL have more intraoperative adverse events and limited benefits from surgery which should be considered in the decision whether to perform mebrane peeling.OCT-A provides more detailed vascular information that extends our understanding of persistent DRIL. [ABSTRACT FROM AUTHOR]

Background and Objectives: The identification of possible biomarkers that can predict treatment response among DME eyes is important for the individualization of treatment plans. We investigated optical coherence tomography (OCT)-based biomarkers that may predict the one-year real-life outcomes among diabetic macular edema (DME) eyes following treatment by intravitreal ranibizumab (IVR) injections. Materials and Methods: A total of 65 eyes from 35 treatment-naïve patients with DME treated with ranibizumab injection were recruited. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), and OCT scans were retrospectively recorded at baseline before treatment and at 3 months, 6 months, and 12 months after treatment. The OCT scans were evaluated for biomarkers of interest, which included central retinal thickness (CRT), amount and locations of hyperreflective foci (HRF), subretinal fluid (SRF), intraretinal cysts (IRC), large outer nuclear layer cyst (LONLC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudates (HE), epiretinal membrane (ERM), and vitreomacular interface (VMI). Correlations between these OCT biomarkers and outcome measures (visual and structural) were statistically analyzed. Results: A total of 65 eyes from 35 patients with DME were enrolled. The mean age was 64.2 ± 10.9 years old. Significant improvement in terms of mean BCVA (p < 0.005) and mean CRT was seen at final follow-up compared to baseline. The biomarkers of DRIL, LONLC, and SRF were found to be predictive for at least 50 μm CRT reduction after treatment (with odds ratio of 8.69, 8.5, and 17.58, respectively). The biomarkers of IRC, LONLC, and SRF were predictive for significant improvement in terms of BCVA and CRT after treatment. Finally, the number of HRF was predictive for both BCVA improvement and a CRT reduction of less than 100 μm after treatment. No serious complications were reported during the study. Conclusion: Our study demonstrated the utility of OCT biomarkers as therapeutic predictors of ranibizumab treatment among DME eyes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the presence of macular edema secondary to retinal vein occlusion (RVO)—both central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO)—3 years after diagnosis in patients who underwent intravitreal therapy and to identify potential prognostic factors and biomarkers of persistent macular edema. Methods: National multicenter, observational, exploratory, retrospective cohort study of 104 consecutive patients with macular edema secondary to RVO diagnosed from January 2014 to December 2015 with minimum 3-year follow-up time. Data analyzed included best-corrected visual acuity (BCVA), clinical and demographic data, and spectral domain optical coherence tomography parameters. Results: At final observation, median baseline central retinal thickness significantly improved from baseline 538 to 290 μm (p < 0.001) and complete macular edema resolution was achieved in 51.0% of patients (56.3% and 42.5% in BRVO and CRVO patients, respectively). BCVA also improved (p < 0.01). Logistic regression analysis revealed a relationship between recurrence of macular edema and disorganization of retinal inner layers (DRIL) at baseline (odds ratio = 2.88; p = 0.013). Conclusion: Good long-term anatomical and functional outcomes are achieved with intravitreal treatments in RVO patients. Anatomical success and visual gains seen in the first year were maintained throughout the entire follow-up, though DRIL is a major risk factor for recurrence. [ABSTRACT FROM AUTHOR]

Purpose: To determine the predictive values of baseline optical coherence tomography (OCT) abnormalities on 12-month visual acuity changes in eyes with macular edema (ME) caused by branch retinal vein occlusions (BRVO). Methods: We performed a post hoc analysis of data from 75 participants in the 12-month MARVEL trial. OCT abnormalities at baseline, including ganglion cell layer cystoid spaces (GCL), intraretinal hyper-reflective dots, and central subfield thickness (CST), were correlated with improvements in visual acuity and the number of anti-vascular endothelial growth factor injections required using a multivariate regression model. Results: Eyes with baseline CST > 500 μm had greater visual gains compared to those with CST

Purpose: To determine whether the disorganization of retinal inner layers (DRIL) on spectral-domain (SD) OCT is associated with visual outcomes in eyes with treatment-naive branch retinal vein occlusion (BRVO). Materials and Methods: Thirty-two eyes of 32 treatment-naive patients with macular edema (ME) due to BRVO receiving three initial consecutive monthly intravitreal ranibizumab were enrolled in this study. SD-OCT images from baseline, 3rd-month, 6th-month visits were observed and the presence and extent of DRIL was examined in the central 1-mm-wide foveal area. The efficacy of the ranibizumab treatment, assessed by best-corrected visual acuity (BCVA), was evaluated at baseline, 3-month and 6-month visits. Results: A total of 32 eyes were included and DRIL was present in 14 (43.7%) eyes at baseline and 9 eyes (28.1%) at 6th month (P:0.01). Baseline DRIL was found to be associated with lower baseline BCVA (0.46 LogMAR for without DRIL vs. 0.65 LogMAR for DRIL, P: 0.013) and higher central retinal thickness (405.7 vs. 442.8, P: 0.016). Decrease in DRIL intensity at 3-month follow-up was associated with increased visual acuity (VA) at 6 months (P:0.001) and baseline DRIL extent was a predictive parameter for 6 months improvement in VA (p:0.01). Sixmonth DRIL change was related to 6-month VA improvement (Pearson's correlation test, r=0.726, P<0.001). Conclusion: In the present study, it was observed that the improvement of BCVA was found to be related to the decrease of the DRIL intensity. Therefore, the presence of DRIL at baseline and extent of DRIL following treatment might serve as a potential SD-OCT biomarker for patients with ME secondary to treatment-naive-BRVO. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this retrospective study was to evaluate the disorganization of the retinal inner layers (DRIL) as a potential predictive factor of postoperative visual outcome in patients with idiopathic epiretinal membrane (iERM), treated with pars plana vitrectomy (PPV). Methods: Participants in the study were 46 consecutive patients diagnosed with iERM, who underwent PPV. Best corrected visual acuity (BCVA) measurement and spectral-domain optical coherence tomography (SD-OCT) were performed at baseline (preoperatively), and at months 3 and 6 postoperatively. DRIL and additional OCT parameters were assessed at 1-mm-wide foveal centered area. Results: DRIL was observed in 47.8% of patients at baseline. There was statistically significant improvement in BCVA and central retinal thickness (CRT) between baseline and months 6 and 12 in all patients. There was a statistically significant difference in BCVA and CRT change between patients with and without DRIL at months 6 and 12 compared to baseline, showing that there was a correlation between change in BCVA or CRT and baseline DRIL. Ellipsoid zone and external limiting membrane were intact in 91.3 and 95.7%, respectively, not affecting our results. Conclusions: Baseline DRIL has been shown to be predictive of postoperative visual outcome in patients with iERM, treated with PPV. [ABSTRACT FROM AUTHOR]

Purpose: To determine the predictive values of baseline optical coherence tomography (OCT) abnormalities on 12-month visual acuity changes in eyes with macular edema (ME) caused by branch retinal vein occlusions (BRVO).Methods: We performed a post hoc analysis of data from 75 participants in the 12-month MARVEL trial. OCT abnormalities at baseline, including ganglion cell layer cystoid spaces (GCL), intraretinal hyper-reflective dots, and central subfield thickness (CST), were correlated with improvements in visual acuity and the number of anti-vascular endothelial growth factor injections required using a multivariate regression model.Results: Eyes with baseline CST > 500 μm had greater visual gains compared to those with CST <500 μm (+21.09 vs +16.08 letters, P = 0.04). Eyes with hyper-reflective dots (+13.97 vs +19.93 letters, P = 0.02), and GCL cysts (+9.8 vs +18.9, P = 0.003) had inferior gains in visual acuity. Neurosensory macular detachments at the baseline did not affect gains in visual acuity. Ninety percent of the gain in visual acuity was recorded after two injections and was maintained until month 12.Conclusion: Baseline OCT of <500 μm, hyper-reflective dots, and GCL cystoid spaces are associated with poorer gains in visual acuity. Most of the visual gain occurs after two injections. [ABSTRACT FROM AUTHOR]