Age and myopia associated optical coherence tomography of retina and choroid in pediatric eyes

Purpose: To evaluate the association between retinal and choroidal thickness and volume along with choroidal vessel volume in children using optical coherence tomography (OCT) images. Methods: 113 normal eyes of children ranging from 5-17 years of age were imaged with a clinical OCT scanner (Optovue Inc., Fremont, USA). The retina, choroid and choroidal vessels were automatically segmented with algorithms. Parameters evaluated were thickness and volume. Location specific analyses of thickness were also performed at a distance of 2.5 mm from foveal center. Multivariate analyses of variance were used to analyze the effect of age and myopia. Manual segmentation of the fovea and subfoveal choroid thickness was also performed to compare with the algorithm segmentation. Results: There was excellent agreement between manual and automatic segmentation (intra-class correlation of 0.95). Within the same eye, total retinal and choroid thickness of nasal and temporal location were significantly lower than the superior and inferior thickness (P < 0.0001). With age (P = 0.026) and myopia (P < 0.001), foveal thickness increased. Choroid volume, vessel volume and temporal choroid thickness increased with increasing myopia (P < 0.05). There was significant positive correlation between choroid volume and retinal volume (r = 0.62, P < 0.0001), choroid volume and vessel volume (r = 0.48, P < 0.0001), and with foveal thickness (r = 0.31, P = 0.009). Choroid vessel volume also showed significant positive correlations with the other metrics (P < 0.05). Conclusion: Retinal and choroidal structural features were quantified simultaneously from OCT images. Magnitude of myopia had a greater effect on retino-choroid features than age in children

Weak to no correlation between quantitative high-resolution computed tomography metrics and lung function change in fibrotic diseases

Background Identifying systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients at risk of more rapid forced vital capacity (FVC) decline could improve trial design. The purpose of the present study was to explore the prognostic value of quantitative high-resolution computed tomography (HRCT) metrics derived by Imbio lung texture analysis (LTA) tool in predicting FVC slope. Methods This retrospective study used data from patients who were not treated with investigational drugs with and without background antifibrotic therapies in tocilizumab phase 3 SSc, lebrikizumab phase 2 IPF, and zinpentraxin alfa phase 2 IPF studies conducted from 2015 to 2021. Controlled HRCT axial volumetric multidetector computed tomography scans were evaluated using the Imbio LTA tool. Associations between HRCT metrics and FVC slope were assessed through the Spearman correlation coefficient and adjusted R2 in a linear regression model adjusted by demographics and baseline clinical characteristics. Results A total of 271 SSc and IPF patients were analysed. Correlation coefficients of highest magnitude were observed in the SSc study between the extent of ground glass, normal volume, quantification of interstitial lung disease, reticular pattern, and FVC slope (−0.25, 0.28, −0.28, and −0.33, respectively), while the correlation coefficients observed in IPF studies were in general <0.2. The incremental prognostic value of the baseline HRCT metrics was marginal after adjusting baseline characteristics and was inconsistent across study arms. Conclusion Data from the SSc and IPF studies suggested weak to no and inconsistent correlation between quantitative HRCT metrics derived by the Imbio LTA tool and FVC slope in the studied SSc and IPF population

Correlation of Volume of Macular Edema with Retinal Tomography Features in Diabetic Retinopathy Eyes

Optical coherence tomography (OCT) enables the detection of macular edema, a significant pathological outcome of diabetic retinopathy (DR). The aim of the study was to correlate edema volume with the severity of diabetic retinopathy and response to treatment with intravitreal injections (compared to baseline). Diabetic retinopathy (DR; n = 181) eyes were imaged with OCT (Heidelberg Engineering, Germany). They were grouped as responders (a decrease in thickness after intravitreal injection of Bevacizumab), non-responders (persistent edema or reduced decrease in thickness), recurrent (recurrence of edema after injection), and treatment naïve (no change in edema at follow-up without any injection). The post-treatment imaging of eyes was included for all groups, except for the treatment naïve group. All eyes underwent a 9 × 6 mm raster scan to measure the edema volume (EV). Central foveal thickness (CFT), central foveal volume (CFV), and total retinal volume (TRV) were obtained from the early treatment diabetic retinopathy study (ETDRS) map. The median EV increased with DR severity, with PDR having the greatest EV (4.01 mm(3)). This correlated positively with TRV (p < 0.001). Median CFV and CFT were the greatest in severe NPDR. Median EV was the greatest in the recurrent eyes (4.675 mm(3)) and lowest (1.6 mm(3)) in the treatment naïve group. Responders and non-responders groups had median values of 3.65 and 3.93 mm(3), respectively. This trend was not observed with CFV, CFT, and TRV. A linear regression yielded threshold values of CFV (~0.3 mm(3)), CFT (~386 µm), and TRV (~9.06 mm(3)), above which EV may be detected by the current scanner. In this study, EV provided a better distinction between the response groups when compared to retinal tomography parameters. The EV increased with disease severity. Thus, EV can be a more precise parameter to identify subclinical edema and aid in better treatment planning

Topographic clinical insights from deep learning-based geographic atrophy progression prediction

To explore the contributions of fundus autofluorescence (FAF) topographic imaging features to the performance of convolutional neural network-based deep learning (DL) algorithms in predicting geographic atrophy (GA) growth rate. Retrospective study with data from study eyes from three clinical trials (NCT02247479, NCT02247531, NCT02479386) in GA. The algorithm was initially trained with full FAF images, and its performance was considered benchmark. Ablation experiments investigated the contribution of imaging features to the performance of the algorithms. Three FAF image regions were defined relative to GA: Lesion, Rim, and Background. For No Lesion, No Rim, and No Background datasets, a single region of interest was removed at a time. For Lesion, Rim, and Background Shuffled datasets, individual region pixels were randomly shuffled. For Lesion, Rim, and Background Mask datasets, masks of the regions were used. A Convex Hull dataset was generated to evaluate the importance of lesion size. Squared Pearson correlation (r2) was used to compare the predictive performance of ablated datasets relative to the benchmark. The Rim region influenced r2 more than the other two regions in all experiments, indicating the most relevant contribution of this region to the performance of the algorithms. In addition, similar performance was observed for all regions when pixels were shuffled or only a mask was used, indicating intensity information was not independently informative without textural context. These ablation experiments enabled topographic clinical insights on FAF images from a DL-based GA progression prediction algorithm. Results from this study may lead to new insights on GA progression prediction

Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema.

Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p<5x10-8). The strongest association was rs2239785, (K150E) in APOL1. The second finding was rs10402468, which co-localized to PLVAP and ANKLE1 in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the gene APOL1, is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries. Trial Registration: NCT00473330, NCT00473382, NCT03622580, NCT03622593, NCT04108156