Evaluating Signs of Microangiopathy Secondary to Diabetes in Different Areas of the Retina with Swept Source OCTA.

Purpose: The purpose of this study was to compare perfusion parameters of the parafovea with scans outside the parafovea to find an area most susceptible to changes secondary to diabetic retinopathy (DR). Methods: Patients with different DR severity levels as well as controls were included in this cross-sectional clinical trial. Seven standardized 3 × 3 mm areas were recorded with Swept Source Optical Coherence Tomography Angiography: one centered on the fovea, three were temporal to the fovea, and three nasally to the optic disc. The capillary perfusion density (PD) of the superficial capillary complex (SCC) and deep capillary complex (DCC) as well as the fractal dimension (FD) were generated. Statistical analyses were done with R software. Results: One hundred ninety-two eyes (33 controls, 51 no-DR, 41 mild DR, 37 moderate/severe DR, and 30 proliferative DR), of which 105 patients with diabetes and 25 healthy controls were included (59 ± 15 years; 62 women). Mean PD of the DCC was significantly less in patients without DR (parafovea = 0.48 ± 0.03; temporal = 0.48 ± 0.02; and nasal = 0.48 ± 0.03) compared to controls (parafovea = 0.49 ± 0.02; temporal = 0.50 ± 0.02; and nasal = 0.50 ± 0.03). With increasing DR severity, PD and FD of the SCC and DCC further decreased. Conclusions: Capillary perfusion of the retina is affected early by diabetes. PD of the DCC was significantly reduced in patients with diabetes who did not have any clinical signs of DR. The capillary network outside the parafovea was more susceptible to capillary perfusion deficits compared to the capillaries close to the fovea. Trial Registration: clinicaltrial.gov, NCT03765112, https://clinicaltrials.gov/ct2/show/NCT03765112?term=NCT03765112&rank=1.

Retinal and Choroidal Perfusion Status in the Area of Laser Scars Assessed With Swept-Source Optical Coherence Tomography Angiography.

Purpose: To evaluate the perfusion status of the retina and choriocapillaris in the area of laser scars on swept-source optical coherence tomography angiography (OCTA) images of eyes previously treated with panretinal photocoagulation (PRP). Methods: Cross-sectional exploratory analysis of swept-source OCTA images, which were retrospectively reviewed for laser scars. The appearance of the capillary networks in the area of previous laser were evaluated following a three-step grading system (normal/sparse/missing capillary network). The superficial and deep capillary plexus of the retina and the choriocapillaris were graded separately. Results: A total of 3140 laser scars in 54 eyes of 31 patients (13 female, mean age 57 ± 12 years) were included in this analysis. In the retina, 6.8% of the superficial and deep capillary network in the area evaluated appeared normal, 58% and 56% sparse, and 35% and 37% missing. Capillary dropout in the retina was not restricted to the area of prior laser treatment. The choriocapillaris decorrelation signal was either sparse (61%) or completely missing (38%) within the laser scar area. The perfusion of the choriocapillaris appeared normal in the area adjacent to laser scars. Conclusions: Capillary non-perfusion in the choriocapillaris was found within the laser scar area. Laser treatment seems to cause sustained non-perfusion of choriocapillaris in the area treated.

Atrophy of the central neuroretina in patients treated for diabetic macular edema.

PURPOSE: To examine the prevalence of central retinal atrophy in patients treated for diabetic macular edema (DME) in a clinical setting. METHODS: Retrospective data analysis of patients with DME, focusing on those who developed central retinal thinning after DME treatment at the Department of Ophthalmology, Medical University Vienna. Patient characteristics and clinical data including best-corrected visual acuity (BCVA), spectral domain optical coherence tomography and fluorescence angiography images were reviewed and DME treatment strategies analysed using descriptive statistics. The correlation between visual acuity and ocular, systemic or DME treatment factors was calculated using linear regression models and ancovas. RESULTS: A total of 6684 outpatient visits by 1437 patients with diabetes were analysed. Out of 149 patients, who had had a central subfield thickness (CST) below 200 µm, 32 (36 eyes) had previously been diagnosed with a centre involving DME with an average CST of 473 ± 103 µm and average visual acuity of 0.62 ± 0.44 logMAR at first presentation. At the time of central atrophy, 29 (81%) out of 36 eyes had a history of laser treatment, 11 (31%) a vitrectomy, 32 (88%) repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF; mean 5.3 ± 3.8) and 22 (61%) intravitreal corticosteroid injections (mean 2.5 ± 2.7). Visual function (0.67 ± 0.43 logMAR) at the time of atrophy was not significantly correlated to central retinal thickness (191 ± 7 µm) or any other ocular, systemic or treatment factors. CONCLUSIONS: Only 4% of patients treated for DME developed central retinal thinning in our observation period. On average, our atrophy patients had higher CST and lower BCVA when they first presented with DME compared to the overall DME cohort, and they received a combination of intravitreal injections and laser for DME treatment. Central retinal atrophy might not be attributed to excessive use of intravitreally applied anti-VEGF or any other DME therapy alone.

THREE-DIMENSIONAL ANALYSIS OF RETINAL MICROANEURYSMS WITH ADAPTIVE OPTICS OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To characterize retinal microaneurysms (MAs) in patients with diabetes using adaptive optics optical coherence tomography (AOOCT) and compare details found in AOOCT with those found in commercially available retinal imaging techniques. METHODS: Patients with diabetes and MA in the macular area were included in this pilot study. The area of interest, identified in standard fluorescein angiography, was imaged using an AO fundus camera and AOOCT. Microaneurysms were characterized in AOOCT (visibility, reflectivity, feeding/draining vessels, and intraretinal location) and compared with findings in AO fundus camera, OCT angiography, and fluorescein angiography. RESULTS: Fifty-three MAs were imaged in 15 eyes of 10 patients. Feeding and/or draining vessels from both capillary plexus could be identified in 34 MAs in AOOCT images. Of 45 MAs imaged with OCT angiography, 18 (40%) were visible in the superior plexus, 12 (27%) in the deep capillary plexus, and 15 MAs (33%) could not be identified at all. Intraluminal hyperreflectivity, commonly seen in AO fundus camera, corresponded only in 8 of 27 cases (30%) to intraluminal densities seen in AOOCT. CONCLUSION: Adaptive optics OCT imaging revealed that MAs located in the inner nuclear layer were connected to the intermediate and/or deep capillary plexus. Intraluminal hyperreflectivity seen on AO fundus camera images originated from a strong reflection from the vessel wall and only in a third of the cases from intraluminal clots. Currently, AOOCT is the most expedient in vivo imaging method to capture morphologic details of retinal microvasculature in 3D and in the context of the surrounding retinal anatomy.

Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes.

Purpose: We evaluate diabetic microaneurysm (MA) features on high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) and their correlations with visual acuity (VA) and local retinal pathology on spectral domain optical coherence tomography (SDOCT). Methods: Diabetic participants underwent VA testing and AOSLO and SDOCT imaging of MAs. AOSLO images were graded for MA dimension, wall hyperreflectivity (WH), intraluminal hyperreflectivity (IH), and perfusion pattern. SDOCTs centered on each MA were graded for disorganization of the retinal inner layers (DRIL) and other neuroretinal pathology. Results: We imaged 109 MAs (30 eyes). Multivariate modeling, including statistically significant covariates from bivariate analyses, associated WH with greater MA size (P = 0.001) and DRIL (P = 0.04). IH was associated with perfusion (P = 0.003) and MA visibility on photographs (P = 0.0001), and larger MA size with partial perfusion (P = 0.03), MA ring signs (P = 0.0002), and photographic visibility (P = 0.01). Multivariate modeling revealed an association of WH and VA with DRIL. Conclusions: AOSLO imaging demonstrates associations of hyperreflective MA walls with MA size and adjacent DRIL, as well as the presence of DRIL with lower VA. This study identifies a correlation between vascular and neural pathology associated with VA decline. Further studies of MA structure and neuroretinal disorganization may enable novel approaches to assess anatomic and functional outcomes in the diabetic eye.

Characterization of In Vivo Retinal Lesions of Diabetic Retinopathy Using Adaptive Optics Scanning Laser Ophthalmoscopy.

PURPOSE: To characterize hallmark diabetic retinopathy (DR) lesions utilizing adaptive optics scanning laser ophthalmoscopy (AOSLO) and to compare AOSLO findings with those on standard imaging techniques. METHODS: Cross-sectional study including 35 eyes of 34 study participants. AOSLO confocal and multiply scattered light (MSL) imaging were performed in eyes with DR. Color fundus photographs (CF), infrared images of the macula (Spectralis, Heidelberg), and Spectralis spectral domain optical coherence tomography SDOCT B-scans of each lesion were obtained and registered to corresponding AOSLO images. MAIN OUTCOME MEASURES: Individual lesion characterization by AOSLO imaging. AOSLO appearance was compared with CF and SDOCT imaging. RESULTS: Characterized lesions encompassed 52 microaneurysms (MA), 20 intraretinal microvascular abnormalities (IRMA), 7 neovascularization (NV), 11 hard exudates (HE), 5 dot/blot hemorrhages (HEM), 4 cotton wool spots (CWS), and 14 intraretinal cysts. AOSLO allowed assessment of perfusion in vascular lesions and enabled the identification of vascular lesions that could not be visualized on CF or SDOCT. CONCLUSIONS: AOSLO imaging provides detailed, noninvasive in vivo visualization of DR lesions enhancing the assessment of morphological characteristics. These unique AOSLO attributes may enable new insights into the pathological changes of DR in response to disease onset, development, regression, and response to therapy.

Association of Changes in Macular Perfusion With Ranibizumab Treatment for Diabetic Macular Edema: A Subanalysis of the RESTORE (Extension) Study.

Importance: Anti-vascular endothelial growth factor treatment is the first-line therapy in the treatment of center-involving diabetic macular edema. Data on capillary perfusion changes under repeated treatment in a possibly compromised vascular network are limited. Objective: To evaluate the association of repeated ranibizumab injections on macular perfusion in patients with diabetic macular edema. Design, Setting, and Participants: This study analyzed prospectively collected data from the 12-month RESTORE core study and the 24-month open label RESTORE extension study, which assessed the efficacy and safety of ranibizumab in patients with visual impairment due to diabetic macular edema. Of 345 patients with center-involving diabetic macular edema who had enrolled in the 12-month RESTORE core study, 240 entered the 24-month RESTORE extension study. Of these, 83 (34.6%) received ranibizumab, 83 (34.6%) received ranibizumab and laser combination therapy, and 74 (30.8%) received laser monotherapy in the first year of the study; 208 completed the 24-month extension study. Fluorescence angiography images were taken from each participant twice each year graded by Vienna Reading Center on severity of capillary loss in the parafoveal area, regularity of the foveal avascular zone outline, and measurement of the size of the foveal avascular zone, following a standardized protocol. Data analysis took place from July 2014 through December 2017. Main Outcomes and Measures: Change in 3 fluorescence angiography perfusion parameters over the course of treatment. Results: Mean (SD) patient age was 62.6 (8.8) years; 124 of 208 (59.2%) were male and 197 of 208 (94.6%) were white. The number of patients with definite altered foveal avascular zone regularity at baseline was 103 of 240 patients (42.9%); another 118 patients (49.2%) had questionably altered regularity at baseline. Definitive capillary loss was found in 65 of 240 patients (27.1%) at baseline. Mean (SD) foveal avascular zone size at baseline was 0.261 (0.232) mm2 in ranibizumab monotherapy, 0.231 (0.219) mm2 in ranibizumab and macular laser combination therapy, and 0.201 (0.13) mm2 in laser monotherapy. No treatment arm experienced significant increase in foveal avascular zone size at any time in the study period. At month 36, ranibizumab monotherapy resulted in a mean increase of 0.073 mm2 (95% CI, 0.005-0.142 mm2) and combination therapy resulted in a mean increase of 0.117 mm2 (95% CI, 0.045-0.188 mm2), but no changes were statistically significant. No changes occurred in foveal avascular zone regularity in any treatment group, and no differences were found in capillary loss around the fovea in the 3 treatment groups; neither element could be correlated with visual acuity or central retinal thickness. Conclusions and Relevance: Repeated ranibizumab treatment was not associated with impaired macular perfusion in our study cohort. Because our data do not suggest a harmful effect of anti-vascular endothelial growth factor therapy on capillary integrity, patients with severe microangiopathy and advanced capillary dropout should not be denied these treatments.

Detailed analysis of retinal morphology in patients with diabetic macular edema (DME) randomized to ranibizumab or triamcinolone treatment.

PURPOSE: Our purpose was to compare the impact in diabetic macula edema (DME) of two intravitreal drugs (0.5 mg ranibizumab vs. 8 mg triamcinolone) on changes in retinal morphology in spectral-domain optical coherence tomography (SD OCT) images, color fundus photography (CF) and fluorescein angiography (FA) images during a 1-year follow-up. METHODS: Post hoc analysis was conducted of morphologic characteristics in OCT, FA and CF images of eyes with a center involving DME that were included in a prospective double-masked randomized trial. Eligible patients were divided at random into two groups receiving either pro re nata treatment with 0.5 mg ranibizumab or 8 mg triamcinolone after a fixed loading dose. OCT and CF images were acquired at monthly visits and FA images every three months. RESULTS: Twenty-five eyes of 25 patients (ranibizumab: n = 10; triamcinolone: n = 15) were included in this study. Patients treated with ranibizumab showed better visual acuity results after 12 months than patients receiving triamcinolone (p = 0.015) although edema reduction was similar (p = 0.426) in both groups. The initial effect on macular edema shedding after a single ranibizumab injection could be amplified with the following two injections of the loading dose. After a single injection of triamcinolone the beneficial initial effect on the macula edema faded within 3 months. Subretinal fluid and INL cystoid spaces diminished early in the course of treatment while fluid accumulation in the ONL seemed to be more persistent in both treatment arms. In FA, the area of leakage diminished significantly in both treatment arms. After repeated injections the morphologic OCT and FA characteristics of the treatment arms converged. CONCLUSIONS: Despite the higher dosage of triamcinolone, both therapies were safe and effective for treating diabetic macular edema. Fluid accumulation in the INL and subretinal space was more responsive to therapy than fluid accumulation in the ONL. Clinicaltrials.gov : NCT00682539.