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Abstract 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

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]

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.

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.

PurposeTo identify optical coherence tomography (OCT) biomarkers that may predict functional and anatomical outcomes in diabetic macular edema (DME) patients treated with intravitreal dexamethasone (DEX) implant.Materials and MethodsSixty-four eyes from 50 patients with DME were enrolled. Best-corrected visual acuity (BCVA) and OCT biomarkers including central retinal thickness (CRT), subretinal fluid (SRF), intraretinal cysts (IRC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudate (HE), hyperreflective foci (HRF), epiretinal membrane (ERM), and vitreomacular interface (VMI) changes were evaluated at baseline and at 3, 6, and 12 months after treatment. Multiple logistic analysis was performed to evaluate each OCT biomarker as a predictive factor for functional and anatomical improvement at the end of treatment.ResultsThe presence of SRF at baseline was associated with a favorable outcome, with CRT improving by more than 100 μm after treatment from multivariate logistic regression analysis [odds ratio 6.16 (1.75–21.6)]. In addition, baseline SRF predicted a greater CRT improvement from multiple regression analysis (model R-square 0.11, p = 0.006). The reduction of DRIL, SRF, LONLC, IRC, and EZD were correlated with better CRT improvement (more than 100 μm) (P < 0.05). SRF and EZD recovery can also predict better visual prognosis (P < 0.05).ConclusionOCT biomarkers can be used to predict who may benefit the most after DEX treatment. We suggest that the DEX implant should be considered as a first line treatment in DME patients with SRF.

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.

Purpose: To identify optical coherence tomography (OCT) biomarkers that may predict functional and anatomical outcomes in diabetic macular edema (DME) patients treated with intravitreal dexamethasone (DEX) implant., Materials and Methods: Sixty-four eyes from 50 patients with DME were enrolled. Best-corrected visual acuity (BCVA) and OCT biomarkers including central retinal thickness (CRT), subretinal fluid (SRF), intraretinal cysts (IRC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudate (HE), hyperreflective foci (HRF), epiretinal membrane (ERM), and vitreomacular interface (VMI) changes were evaluated at baseline and at 3, 6, and 12 months after treatment. Multiple logistic analysis was performed to evaluate each OCT biomarker as a predictive factor for functional and anatomical improvement at the end of treatment., Results: The presence of SRF at baseline was associated with a favorable outcome, with CRT improving by more than 100 μm after treatment from multivariate logistic regression analysis [odds ratio 6.16 (1.75-21.6)]. In addition, baseline SRF predicted a greater CRT improvement from multiple regression analysis (model R-square 0.11, p = 0.006). The reduction of DRIL, SRF, LONLC, IRC, and EZD were correlated with better CRT improvement (more than 100 μm) ( P < 0.05). SRF and EZD recovery can also predict better visual prognosis ( P < 0.05)., Conclusion: OCT biomarkers can be used to predict who may benefit the most after DEX treatment. We suggest that the DEX implant should be considered as a first line treatment in DME patients with SRF., Competing Interests: H-SC was employed by NephroCare Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Chang, Meng, Lin, Lai, Hsia, Chen, Tien, Bair, Lin, Chen and Tsai.)