AimTo prospectively monitor subclinical changes in capillary perfusion and retinal layer thickness in patients with type 2 diabetes and early diabetic retinal disease over 2 years.MethodsIn this longitudinal study we performed biannual retinal vascular imaging using optical coherence tomography angiography (RTVue) to analyse the foveal avascular zone (FAZ) area, perimeter, acircularity index (AI) and parafoveal superficial/deep vessel density (VD). Spectral-domain optical coherence tomography (Spectralis) was used to measure the thickness of nine macular layers and the peripapillary nerve fibre layer.ResultsAmong 117 eyes (58 left) of 59 patients (21 female), 105 had no diabetic retinopathy (DR), 6 mild and 6 moderate non-proliferative DR at baseline. We found DR progression in 13 eyes at year 2. The FAZ area (+0.008±0.002 mm2/year, p<0.0001), perimeter (+0.036±0.010 mm/year, p=0.006) and AI (+0.005±0.002/year, p=0.0280) increased significantly. A pronounced decrease was found in the superficial (−1.425±0.290%/year, p<0.0001) but not the deep VD. Inner neuroretinal loss was confined to the ganglion cell (−0.539±0.150 µm/year, p=0.0004) and the inner plexiform layer (−0.361±0.127 µm/year, p=0.0045). In the outer retina, we observed a statistically significant decrease in thickness in the outer plexiform, photoreceptor layer and pigment epithelium of −0.921±0.161 µm/year, −0.325±0.139 µm/year and −0.385±0.084 µm/year, respectively.ConclusionSubclinical signs of microangiopathy and neurodegeneration appear in parallel and are highly progressive even in the earliest stages of diabetic retinal disease.Trial registration number EudraCT20156000239634.

The retinal nerve fiber layer (RNFL) is a fibrous tissue that shows form birefringence. This optical tissue property is related to the microstructure of the nerve fiber axons that carry electrical signals from the retina to the brain. Ocular diseases that are known to cause neurologic changes, like glaucoma or diabetic retinopathy (DR), might alter the birefringence of the RNFL, which could be used for diagnostic purposes. In this pilot study, we used a state-of-the-art polarization sensitive optical coherence tomography (PS-OCT) system with an integrated retinal tracker to analyze the RNFL birefringence in patients with glaucoma, DR, and in age-matched healthy controls. We recorded 3D PS-OCT raster scans of the optic nerve head area and high-quality averaged circumpapillary PS-OCT scans, from which RNFL thickness, retardation and birefringence were derived. The precision of birefringence measurements was 0.005°/µm. As compared to healthy controls, glaucoma patients showed a slightly reduced birefringence (0.129 vs. 0.135°/µm), although not statistically significant. The DR patients, however, showed a stronger reduction of RNFL birefringence (0.103 vs. 0.135°/µm) which was highly significant. This result might open new avenues into early diagnosis of DR and related neurologic changes.

Introduction Comparison of diabetic retinopathy (DR) severity between autonomous Artificial Intelligence (AI)-based outputs from an FDA-approved screening system and human retina specialists’ gradings from ultra-widefield (UWF) colour images. Methods Asymptomatic diabetics without a previous diagnosis of DR were included in this prospective observational pilot study. Patients were imaged with autonomous AI (IDx-DR, Digital Diagnostics). For each eye, two 45° colour fundus images were analysed by a secure server-based AI algorithm. UWF colour fundus imaging was performed using Optomap (Daytona, Optos). The International Clinical DR severity score was assessed both on a 7-field area projection (7F-mask) according to the early treatment diabetic retinopathy study (ETDRS) and on the total gradable area (UWF full-field) up to the far periphery on UWF images. Results Of 54 patients included (n = 107 eyes), 32 were type 2 diabetics (11 females). Mean BCVA was 0.99 ± 0.25. Autonomous AI diagnosed 16 patients as negative, 28 for moderate DR and 10 for having a vision-threatening disease (severe DR, proliferative DR, diabetic macular oedema). Based on the 7F-mask grading with the eye with the worse grading defining the DR stage 23 patients were negative for DR, 11 showed mild, 19 moderate and 1 severe DR. When UWF full-field was analysed, 20 patients were negative for DR, while the number of mild, moderate and severe DR patients were 12, 21, and 1, respectively. Conclusions The autonomous AI-based DR examination demonstrates sufficient accuracy in diagnosing asymptomatic non-proliferative diabetic patients with referable DR even compared to UWF imaging evaluated by human experts offering a suitable method for DR screening.

Purpose To study birefringence of the peripapillary retinal nerve fiber layer (RNFL) of diabetic eyes with no clinical signs of diabetic retinopathy (DR) or mild to moderate DR stages using spectral-domain polarization-sensitive (PS) optical coherence tomography (OCT). Methods In this observational pilot study, circular PS-OCT scans centered on the optic nerve head were recorded in prospectively recruited diabetic and age-matched healthy eyes. From averaged circumpapillary intensity and retardation tomograms plots of RNFL birefringence were obtained by a linear fit of retardation versus depth within the RNFL tissue for each A-scan position and mean birefringence values for RNFL calculated. Spectral-domain OCT imaging (Heidelberg Engineering) was performed to assess peripapillary RNFL thickness and macular ganglion cell complex (GCC). Results Out of 70 eyes of 43 diabetic patients (mean ± SD age: 50.86 ± 15.71) 36 showed no signs of DR, 17 mild and 17 moderate nonproliferative DR with no diabetic macular edema. Thirty-four eyes of 34 healthy subjects (53.21 ± 13.88 years) served as controls. Compared with healthy controls (0.143° ± 0.014°/µm) mean total birefringence of peripapillary RNFL was significantly reduced in subclinical diabetic eyes (0.131° ± 0.014°/µm; P = 0.0033), as well as in mild to moderate DR stages (0.125° ± 0.018°/µm, P < 0.0001) with borderline statistically significant differences between diabetic patients ( P = 0.0049). Mean birefringence values were significantly lower in inferior compared with superior RNFL sectors ( P < 0.0001) of diabetic eyes with no such difference detected in the healthy control group. Conclusions We identified evidence of early neuroretinal alteration in diabetic eyes through reduced peripapillary RNFL birefringence assessed by PS-OCT occurring before appearance of clinical microvascular lesions or GCC alterations.

In this retrospective study the morphological response of teleangiectatic capillaries (TCs) to focal laser treatment and the functional and morphological outcome after Indocyanine green angiography (ICGA)-guided laser therapy was evaluated. TCs in eyes with diabetic macular edema (DME) were treated with laser therapy. The immediate and subsequent reaction of the TCs lumina to direct photocoagulation was monitored with customized OCT single scans. Additionally, patients were treated with intravitreal anti-VEGF as needed. 12 eyes of 9 patients with treatment naive (6 eyes) and pretreated (6 eyes) DME were followed-up for a mean of 24 months (± 8.1SD). Best-corrected visual acuity improved from 0.25 logMar (± 0.2SD) to 0.12 (± 0.10SD; p = 0.06) at each patient’s last visit. During laser treatment a darkening of the TCs lumina was achieved in 91.3% of lesions. All these lesions fully resolved, whereas TCs, which showed no darkening of their lumen in OCT persisted and required re-treatment with laser. Additional anti-VEGF injections were indicated in only one eye (8.3%). The darkening of the TCs lumina visible in OCT might provide an image-biomarker that indicates successful coagulation of aneurysmatic lesions. Consequently, a significant functional and morphological improvement with need for anti-VEGF treatment in only one eye, was achieved.Information concerning the registration of the trial: date of registration: 11th of december, 2019. Trial registration number: 107/2019.