Jason Charng PhD , Jennifer A. Thompson PhD , Rachael C. Heath Jeffery MD , Amy Kalantary MD , Tina M. Lamey PhD , Terri L. McLaren BSc , Fred K. Chen PhD
{"title":"Censoring the Floor Effect in Long-Term Stargardt Disease Microperimetry Data Produces a Faster Rate of Decline","authors":"Jason Charng PhD , Jennifer A. Thompson PhD , Rachael C. Heath Jeffery MD , Amy Kalantary MD , Tina M. Lamey PhD , Terri L. McLaren BSc , Fred K. Chen PhD","doi":"10.1016/j.xops.2024.100581","DOIUrl":"10.1016/j.xops.2024.100581","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate progression rate estimation in long-term Stargardt disease microperimetry data by accounting for floor effect.</p></div><div><h3>Design</h3><p>Cohort study.</p></div><div><h3>Subjects</h3><p>Thirty-seven subjects (23 females, 14 males) with biallelic ABCA4 pathogenic or likely pathogenic variants and more than >2 years of longitudinal microperimetry data.</p></div><div><h3>Methods</h3><p>Cross-sectional and longitudinal microperimetry data (Grid A: 18° diameter, Grid B: 6° diameter; Macular Integrity Assessment microperimeter, dynamic range 0–36 decibels [dB]) was extracted from patients with biallelic mutation in the adenosine triphosphate-binding cassette subfamily A member 4 (<em>ABCA4</em>) gene. For each eye, mean sensitivity (MS) and responding point sensitivity (RPS) rates were extracted. Floor censored sensitivity (FCS) progression rate, which accounts for the floor effect at each locus by terminating calculation when scotoma was observed in 2 consecutive visits, was also calculated. In a subset of eyes with ≥1 scotomatous locus at baseline (Grid A), sensitivity progression of loci around the scotoma (edge of scotoma sensitivity [ESS]) was examined against other progression parameters. Paired <em>t</em> test compared progression rate parameters across the same eyes.</p></div><div><h3>Main Outcome Measures</h3><p>Microperimetry grid parameters at baseline and progression rates.</p></div><div><h3>Results</h3><p>A total of 37 subjects with biallelic <em>ABCA4</em> mutations and >2 years of longitudinal microperimetry data were included in the study. In Grid A, at baseline, the average MS and RPS were 16.5 ± 7.9 and 19.1 ± 5.7 dB, respectively. Similar MS (18.4 ± 7.6 dB) and RPS (20.0 ± 5.5 dB) values were found at baseline for Grid B. In Grid A, overall, MS, RPS, and FCS progression rates were −0.57 ± 1.05, −0.74 ± 1.24, and −1.26 ± 1.65 (all dB/year), respectively. Floor censored sensitivity progression rate was significantly greater than the MS or RPS progression rates. Similar findings were observed in Grid B (MS −1.22 ± 1.42, RPS −1.44 ± 1.44, FCS −2.16 ± 2.24, all dB/year), with paired <em>t</em> test again demonstrated that FCS had a significantly faster rate of decline than MS or RPS. In patients with progression data in both grids, MS, RPS, and FCS progression rates were significantly faster in the smaller Grid B. In 24 eyes with scotoma at baseline, fastest rate of decline was ESS combined with FCS compared with other progression parameters.</p></div><div><h3>Conclusions</h3><p>Incorporation of FCS can reduce confound of floor effect in perimetry analysis and can in turn detect a faster rate of decline.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001179/pdfft?md5=5a10ead90090ebe64a026d61cb8212f2&pid=1-s2.0-S2666914524001179-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141840548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pengxiao Zang PhD , Tristan T. Hormel PhD , Thomas S. Hwang MD , Yali Jia PhD
{"title":"Quantitative Volumetric Analysis of Retinal Ischemia with an Oxygen Diffusion Model and OCT Angiography","authors":"Pengxiao Zang PhD , Tristan T. Hormel PhD , Thomas S. Hwang MD , Yali Jia PhD","doi":"10.1016/j.xops.2024.100579","DOIUrl":"10.1016/j.xops.2024.100579","url":null,"abstract":"<div><h3>Purpose</h3><p>Retinal ischemia is a major feature of diabetic retinopathy (DR). Traditional nonperfused areas measured by OCT angiography (OCTA) measure blood supply but not ischemia. We propose a novel 3-dimensional (3D) quantitative method to derive ischemia measurements from OCTA data.</p></div><div><h3>Design</h3><p>Cross-sectional study.</p></div><div><h3>Participants</h3><p>We acquired 223 macular OCTA volumes from 33 healthy eyes, 33 diabetic eyes without retinopathy, 7 eyes with nonreferable DR, 17 eyes with referable but nonvision-threatening DR, and 133 eyes with vision-threatening DR.</p></div><div><h3>Methods</h3><p>Each eye was scanned using a spectral-domain OCTA system (Avanti RTVue-XR, Visionix/Optovue, Inc) with 1.6-mm scan depth in a 3 × 3-mm region (640 × 304 × 304 voxels) centered on the fovea. For each scanned OCTA volume, a custom algorithm removed flow projection artifacts. We then enhanced, binarized, and skeletonized the vasculature in each OCTA volume and generated a 3D oxygen tension map using a zero-order kinetics oxygen diffusion model. Each volume was scaled to the average retina thickness in healthy controls after foveal registration and flattening of the Bruch's membrane. Finally, we extracted 3D ischemia maps by comparison with a reference map established from scans of healthy eyes using the same processing. To assess the ability of the ischemia maps to grade DR severity, we constructed receiver operating characteristic curves for diagnosing diabetes, referable DR, and vision-threatening DR.</p></div><div><h3>Main Outcome Measures</h3><p>Spearman correlation coefficient and area under receiver operating characteristic curve (AUC) were used to quantify the ability of the ischemia maps to DR.</p></div><div><h3>Results</h3><p>The ischemia maps showed that the ischemic tissues were at or near pathologically nonperfused areas, but not the normally nonvascular tissue, such as the foveal avascular zone. We found multiple novel metrics, including inferred 3D-oxygen tension, ischemia index, and ischemic volume ratio, were strongly correlated with DR severity. The AUCs of ischemia index measured were 0.94 for diabetes, 0.89 for DR, 0.88 for referable DR, and 0.85 for vision-threatening DR.</p></div><div><h3>Conclusions</h3><p>A quantitative method to infer 3D oxygen tension and ischemia using OCTA in diabetic eyes can identify ischemic tissue that are more specific to pathologic changes in DR.</p></div><div><h3>Financial Disclosures</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001155/pdfft?md5=b7ecfcf304d2f9f069a370d571d1ba6c&pid=1-s2.0-S2666914524001155-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diane N. Sayah OD, PhD , Denise Descovich MD , Santiago Costantino PhD , Mark R. Lesk MD, MSc
{"title":"The Association between the Pulsatile Choroidal Volume Change and Ocular Rigidity","authors":"Diane N. Sayah OD, PhD , Denise Descovich MD , Santiago Costantino PhD , Mark R. Lesk MD, MSc","doi":"10.1016/j.xops.2024.100576","DOIUrl":"10.1016/j.xops.2024.100576","url":null,"abstract":"<div><h3>Purpose</h3><p>To assess the relationship between the pulsatile choroidal volume change (ΔV) and ocular rigidity (OR), an important biomechanical property of the eye.</p></div><div><h3>Design</h3><p>This is a prospective cross-sectional study.</p></div><div><h3>Subjects</h3><p>Two hundred seventeen participants (235 eyes) were included in this study. Of those, 18 eyes (18 participants) had exudative retinal disease, and 217 eyes (199 participants) had open-angle glaucoma (39.2%), suspect discs (12.4%), ocular hypertension (14.3%), or healthy eyes (34.1%).</p></div><div><h3>Methods</h3><p>Pulsatile choroidal volume change was measured using dynamic OCT, which detects the change in choroidal thickness during the cardiac cycle. Ocular rigidity was measured using an invasive procedure as well as using a validated optical method. Correlations between ΔV and OR were assessed in subjects with healthy eyes, eyes with glaucoma, or eyes with exudative retinal disease.</p></div><div><h3>Main Outcome Measures</h3><p>Ocular rigidity and pulsatile ocular volume change.</p></div><div><h3>Results</h3><p>In 18 eyes where OR was obtained invasively and ΔV was obtained noninvasively, a significant correlation was found between ΔV and OR (r<sub>s</sub> = −0.664, <em>P</em> = 0.003). Similarly, a strong inverse correlation was found between the noninvasive measurements of both ΔV and OR (r<sub>s</sub> = −0.748, <em>P</em> < 0.001) in a large cohort and maintained its significance across diagnostic groups (a more compliant eye is associated with greater ΔV). No correlation was found between ΔV and age, blood pressure, intraocular pressure, axial length, or diagnosis (<em>P</em> ≥ 0.05). Mean ΔV was 7.3 ± 3.4 μL for all groups combined with a range of 3.0 to 20.8 μL.</p></div><div><h3>Conclusions</h3><p>These results suggest an association between the biomechanics of the corneoscleral shell and pulsatile ocular blood flow, which may indicate that a more rigid eye exerts more resistance to pulsatile choroidal expansion. This highlights the dynamic nature of both blood flow and biomechanics in the eye, as well as how they may interact, leading to a greater understanding of the pathophysiology of ocular disease.</p></div><div><h3>Financial Disclosures</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400112X/pdfft?md5=ddd401d8b394fedad1dc8122bed5d1a8&pid=1-s2.0-S266691452400112X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keith Harrigian MS , Diep Tran MSc , Tina Tang MD , Anthony Gonzales OD , Paul Nagy PhD , Hadi Kharrazi MD, PhD , Mark Dredze PhD , Cindy X. Cai MD, MS
{"title":"Improving the Identification of Diabetic Retinopathy and Related Conditions in the Electronic Health Record Using Natural Language Processing Methods","authors":"Keith Harrigian MS , Diep Tran MSc , Tina Tang MD , Anthony Gonzales OD , Paul Nagy PhD , Hadi Kharrazi MD, PhD , Mark Dredze PhD , Cindy X. Cai MD, MS","doi":"10.1016/j.xops.2024.100578","DOIUrl":"10.1016/j.xops.2024.100578","url":null,"abstract":"<div><h3>Purpose</h3><p>To compare the performance of 3 phenotyping methods in identifying diabetic retinopathy (DR) and related clinical conditions.</p></div><div><h3>Design</h3><p>Three phenotyping methods were used to identify clinical conditions including unspecified DR, nonproliferative DR (NPDR) (mild, moderate, severe), consolidated NPDR (unspecified DR or any NPDR), proliferative DR, diabetic macular edema (DME), vitreous hemorrhage, retinal detachment (RD) (tractional RD or combined tractional and rhegmatogenous RD), and neovascular glaucoma (NVG). The first method used only International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes (<em>ICD-10 Lookup System</em>). The next 2 methods used a Bidirectional Encoder Representations from Transformers with a dense Multilayer Perceptron output layer natural language processing (NLP) framework. The NLP framework was applied either to free-text of provider notes (<em>Text-Only NLP System</em>) or both free-text and ICD-10 diagnosis codes (<em>Text-and-International Classification of Diseases</em> [<em>ICD</em>] <em>NLP System</em>).</p></div><div><h3>Subjects</h3><p>Adults ≥18 years with diabetes mellitus seen at the Wilmer Eye Institute.</p></div><div><h3>Methods</h3><p>We compared the performance of the 3 phenotyping methods in identifying the DR related conditions with gold standard chart review. We also compared the estimated disease prevalence using each method.</p></div><div><h3>Main Outcome Measures</h3><p>Performance of each method was reported as the macro F1 score. The agreement between the methods was calculated using the kappa statistic. Prevalence estimates were also calculated for each method.</p></div><div><h3>Results</h3><p>A total of 91 097 patients and 692 486 office visits were included in the study. Compared with the gold standard, the <em>Text-and-ICD NLP System</em> had the highest F1 score for most clinical conditions (range 0.39–0.64). The agreement between the <em>ICD-10 Lookup System</em> and <em>Text-Only NLP System</em> varied (kappa of 0.21–0.81). The prevalence of DR and related conditions ranged from 1.1% for NVG to 17.9% for DME (using the <em>Text-and-ICD NLP System</em>).</p></div><div><h3>Conclusions</h3><p>The prevalence of DR and related conditions varied significantly depending on the methodology of identifying cases. The best performing phenotyping method was the <em>Text-and-ICD NLP System</em> that used information in both diagnosis codes as well as free-text notes.</p></div><div><h3>Financial Disclosures</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001143/pdfft?md5=aee0aca9014224fef1aa919db24f5c88&pid=1-s2.0-S2666914524001143-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141844268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyi Chen MD , Wendy Yang BS , Ashley Fong MS , Noor Chahal BS , Abu T. Taha BS , Jeremy D. Keenan MD, MPH , Jay M. Stewart MD
{"title":"Sex Differences in Inflammation-Related Biomarkers Detected with OCT in Patients with Diabetic Macular Edema","authors":"Xinyi Chen MD , Wendy Yang BS , Ashley Fong MS , Noor Chahal BS , Abu T. Taha BS , Jeremy D. Keenan MD, MPH , Jay M. Stewart MD","doi":"10.1016/j.xops.2024.100580","DOIUrl":"10.1016/j.xops.2024.100580","url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate sex-based differences in inflammation-related biomarkers on spectral-domain OCT.</p></div><div><h3>Design</h3><p>Cross-sectional study.</p></div><div><h3>Participants</h3><p>Patients with diabetic macular edema (DME) between February 1, 2019, and March 31, 2023, without intravitreal anti-VEGF injection within the previous 6 months.</p></div><div><h3>Methods</h3><p>We reviewed each patient’s medical record for age, biological sex, race and ethnicity, most recent glycated hemoglobin A1c (HbA1c) level, visual acuity (VA), and central macular thickness (CMT). OCT biomarkers that have been found in literature to be associated with inflammation, including disorganization of retinal inner layers (DRIL), retinal hyperreflective retinal foci (HRFs), hyperreflective choroidal foci (HCFs), subfoveal neuroretinal detachment (SND), and perturbation in retinal nerve fiber layer thickness, ganglion cell layer thickness, and inner nuclear layer (INL) thickness were evaluated by graders masked to the clinical characteristics of the patients. We performed multivariable regression analyses with the OCT biomarkers as the outcome variables and sex, age, HbA1c, and CMT as independent variables.</p></div><div><h3>Main Outcome Measures</h3><p>OCT inflammation-related biomarkers, as listed above.</p></div><div><h3>Results</h3><p>Female patients were, on average, 2 years older than male patients (<em>P</em> = 0.041). There were no significant differences in race and ethnicity, HbA1c, VA, or CMT between male and female patients. After controlling for age, HbA1c, and CMT, we found male sex to be associated with more HRF (incidence rate ratio [IRR] = 1.19; 95% confidence interval [CI] = 1.10–1.29), more HCF (odds ratio = 2.01; 95% CI = 1.12–3.64), and thicker INL (7 μm thicker in males; 95% CI = 2–12). Sex was not a significant predictor for either DRIL or SND in the multivariable regression models. Patients with higher HbA1c were more likely to have more HRF (IRR = 1.02 per 1 point increase; 95% CI = 1.00–1.04) after controlling for other factors.</p></div><div><h3>Conclusions</h3><p>Male sex was correlated with more inflammation-related biomarkers on OCT including more HRF, more HCF, and thicker INL, after accounting for age, glycemic control, and amount of DME. Further studies are needed to evaluate the potential implications of these sex-based differences for individualized treatment.</p></div><div><h3>Financial Disclosures</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001167/pdfft?md5=fd1a7303565f3c755d6452f95c65ef8d&pid=1-s2.0-S2666914524001167-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jost B. Jonas MD , Songhomitra Panda-Jonas MD , Zhe Pan MD , Jie Xu MD , Ya Xing Wang MD
{"title":"Posterior Eye Shape in Myopia","authors":"Jost B. Jonas MD , Songhomitra Panda-Jonas MD , Zhe Pan MD , Jie Xu MD , Ya Xing Wang MD","doi":"10.1016/j.xops.2024.100575","DOIUrl":"10.1016/j.xops.2024.100575","url":null,"abstract":"<div><h3>Purpose</h3><p>To explore prevalence and associated factors of abnormalities of the posterior eye shape in dependence of axial length.</p></div><div><h3>Design</h3><p>Population-based study.</p></div><div><h3>Participants</h3><p>Of the participants (n = 3468) of the Beijing Eye Study, we included all eyes with an axial length of ≥25 mm, and a randomized sample of eyes with an axial length of <25 mm.</p></div><div><h3>Methods</h3><p>Using 30°-wide, serial horizontal, and fovea-centered radial, OCT images, we examined location and depth of the most posterior point of the retinal pigment epithelium/Bruch’s membrane line (PP-RPE/BML).</p></div><div><h3>Main Outcome Measures</h3><p>Prevalence and depth of an extrafoveal PP-RPE/BML.</p></div><div><h3>Results</h3><p>The study included 366 eyes (314 individuals). On the radial OCT scans, the PP-RPE/BML was located in the foveola in 190 (51.9%) eyes, in 121 (33.1%) eyes in the 6 o’clock part of the vertical meridian (distance to foveola: 1.73 ± 0.70 mm), and in 54 (14.8%) eyes in the 12 o’clock part of the vertical meridian (fovea distance: 2.01 ± 0.66 mm). On the horizontal OCT scans, the PP-RPE/BML was located in the foveola in 304 (83.1%) eyes, between foveola and optic disc in 36 (9.8%) eyes (fovea distance: 1.59 ± 0.76 mm), and temporal to the foveola in 26 (7.1%) eyes (fovea distance: 1.20 ± 0.60 mm). Higher prevalence of an extrafoveal PP-RPE/BML correlated with longer axial length (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.28, 1.89), higher corneal astigmatism (OR: 1.78; 95% CI: 1.14, 2.79), and female sex (OR: 2.74; 95% CI: 1.30, 5.77). The curvature of the RPE/BML at the posterior pole was similar to the RPE/BML curvature outside of the posterior pole in 309 (84.4%) eyes, and it was steeper (i.e., smaller curvature radius) in 57 (15.6%) eyes. In these eyes, axial length was longer (24.41 ± 1.78 mm versus 27.74 ± 1.88 mm; <em>P</em> < 0.001).</p></div><div><h3>Conclusions</h3><p>With longer axial length, the foveola is more often located outside of the geometrical posterior pole. It may be of importance for biometric axial length measurements. An extrafoveal location of the PP-RPE/BML may be due to an axial elongation-associated, meridionally asymmetric enlargement of Bruch’s membrane in the fundus midperiphery.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001118/pdfft?md5=42f31daebc61edd63d9f5d3810c4a00e&pid=1-s2.0-S2666914524001118-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141715410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriella Moraes MD, MSc , Robbert Struyven MD , Siegfried K. Wagner BMBCh, FRCOphth , Timing Liu BA , David Chong MBBChir , Abdallah Abbas iBSc, MBBS , Reena Chopra BSc , Praveen J. Patel MD, FRCOphth , Konstantinos Balaskas MD , Tiarnan D.L. Keenan BM BCh, PhD , Pearse A. Keane MD, FRCOphth
{"title":"Quantifying Changes on OCT in Eyes Receiving Treatment for Neovascular Age-Related Macular Degeneration","authors":"Gabriella Moraes MD, MSc , Robbert Struyven MD , Siegfried K. Wagner BMBCh, FRCOphth , Timing Liu BA , David Chong MBBChir , Abdallah Abbas iBSc, MBBS , Reena Chopra BSc , Praveen J. Patel MD, FRCOphth , Konstantinos Balaskas MD , Tiarnan D.L. Keenan BM BCh, PhD , Pearse A. Keane MD, FRCOphth","doi":"10.1016/j.xops.2024.100570","DOIUrl":"10.1016/j.xops.2024.100570","url":null,"abstract":"<div><h3>Purpose</h3><p>Application of artificial intelligence (AI) to macular OCT scans to segment and quantify volumetric change in anatomical and pathological features during intravitreal treatment for neovascular age-related macular degeneration (AMD).</p></div><div><h3>Design</h3><p>Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database.</p></div><div><h3>Participants</h3><p>A total of 2115 eyes from 1801 patients starting anti-VEGF treatment between June 1, 2012, and June 30, 2017.</p></div><div><h3>Methods</h3><p>The Moorfields Eye Hospital neovascular AMD database was queried for first and second eyes receiving anti-VEGF treatment and had an OCT scan at baseline and 12 months. Follow-up scans were input into the AI system and volumes of OCT variables were studied at different time points and compared with baseline volume groups. Cross-sectional comparisons between time points were conducted using Mann–Whitney <em>U</em> test.</p></div><div><h3>Main Outcome Measures</h3><p>Volume outputs of the following variables were studied: intraretinal fluid, subretinal fluid, pigment epithelial detachment (PED), subretinal hyperreflective material (SHRM), hyperreflective foci, neurosensory retina, and retinal pigment epithelium.</p></div><div><h3>Results</h3><p>Mean volumes of analyzed features decreased significantly from baseline to both 4 and 12 months, in both first-treated and second-treated eyes. Pathological features that reflect exudation, including pure fluid components (intraretinal fluid and subretinal fluid) and those with fluid and fibrovascular tissue (PED and SHRM), displayed similar responses to treatment over 12 months. Mean PED and SHRM volumes showed less pronounced but also substantial decreases over the first 2 months, reaching a plateau postloading phase, and minimal change to 12 months. Both neurosensory retina and retinal pigment epithelium volumes showed gradual reductions over time, and were not as substantial as exudative features.</p></div><div><h3>Conclusions</h3><p>We report the results of a quantitative analysis of change in retinal segmented features over time, enabled by an AI segmentation system. Cross-sectional analysis at multiple time points demonstrated significant associations between baseline OCT-derived segmented features and the volume of biomarkers at follow-up. Demonstrating how certain OCT biomarkers progress with treatment and the impact of pretreatment retinal morphology on different structural volumes may provide novel insights into disease mechanisms and aid the personalization of care. Data will be made public for future studies.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001064/pdfft?md5=ba7935cea71518e47f805f746ad59e08&pid=1-s2.0-S2666914524001064-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141985193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing Glaucoma Diagnosis: Employing Confidence-Calibrated Label Smoothing Loss for Model Calibration","authors":"Midhula Vijayan PhD, Deepthi Keshav Prasad PhD, Venkatakrishnan Srinivasan MTech","doi":"10.1016/j.xops.2024.100555","DOIUrl":"10.1016/j.xops.2024.100555","url":null,"abstract":"<div><h3>Objective</h3><p>The aim of our research is to enhance the calibration of machine learning models for glaucoma classification through a specialized loss function named Confidence-Calibrated Label Smoothing (CC-LS) loss. This approach is specifically designed to refine model calibration without compromising accuracy by integrating label smoothing and confidence penalty techniques, tailored to the specifics of glaucoma detection.</p></div><div><h3>Design</h3><p>This study focuses on the development and evaluation of a calibrated deep learning model.</p></div><div><h3>Participants</h3><p>The study employs fundus images from both external datasets—the Online Retinal Fundus Image Database for Glaucoma Analysis and Research (482 normal, 168 glaucoma) and the Retinal Fundus Glaucoma Challenge (720 normal, 80 glaucoma)—and an extensive internal dataset (4639 images per category), aiming to bolster the model's generalizability. The model's clinical performance is validated using a comprehensive test set (47 913 normal, 1629 glaucoma) from the internal dataset.</p></div><div><h3>Methods</h3><p>The CC-LS loss function seamlessly integrates label smoothing, which tempers extreme predictions to avoid overfitting, with confidence-based penalties. These penalties deter the model from expressing undue confidence in incorrect classifications. Our study aims at training models using the CC-LS and comparing their performance with those trained using conventional loss functions.</p></div><div><h3>Main Outcome Measures</h3><p>The model's precision is evaluated using metrics like the Brier score, sensitivity, specificity, and the false positive rate, alongside qualitative heatmap analyses for a holistic accuracy assessment.</p></div><div><h3>Results</h3><p>Preliminary findings reveal that models employing the CC-LS mechanism exhibit superior calibration metrics, as evidenced by a Brier score of 0.098, along with notable accuracy measures: sensitivity of 81%, specificity of 80%, and weighted accuracy of 80%. Importantly, these enhancements in calibration are achieved without sacrificing classification accuracy.</p></div><div><h3>Conclusions</h3><p>The CC-LS loss function presents a significant advancement in the pursuit of deploying machine learning models for glaucoma diagnosis. By improving calibration, the CC-LS ensures that clinicians can interpret and trust the predictive probabilities, making artificial intelligence-driven diagnostic tools more clinically viable. From a clinical standpoint, this heightened trust and interpretability can potentially lead to more timely and appropriate interventions, thereby optimizing patient outcomes and safety.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000915/pdfft?md5=427dfb03f669c0bff9531a39938549c2&pid=1-s2.0-S2666914524000915-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment of Retinal Volume in Individuals Without Ocular Disorders Based on Wide-Field Swept-Source OCT","authors":"Yoshiaki Chiku MD, Takao Hirano MD, PhD, Ken Hoshiyama MD, Yasuhiro Iesato MD, PhD, Toshinori Murata MD, PhD","doi":"10.1016/j.xops.2024.100569","DOIUrl":"10.1016/j.xops.2024.100569","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate retinal volume (RV) in eyes without retinal disease using wide-field swept-source OCT (SS-OCT).</p></div><div><h3>Design</h3><p>Observational, cross-sectional design.</p></div><div><h3>Participants</h3><p>A total of 332 eyes of 166 healthy participants.</p></div><div><h3>Methods</h3><p>The eyes were imaged with OCT-S1 (Canon) using a protocol centered on the fovea cube scans (20 × 23 mm) of SS-OCT images. Retinal volume (6-mm circle, 6–20-mm ring) and various parameters were evaluated in a multivariate analysis using a generalized estimating equation model. Each quadrant of the macula except for the fovea (1–6 mm in diameter) and peripheral ring (6–20 mm in diameter) was also evaluated.</p></div><div><h3>Main Outcome Measures</h3><p>Retinal volume.</p></div><div><h3>Results</h3><p>In the multivariate analysis, older age and longer axial length were associated with smaller macular RV, whereas older age and left eye were associated with smaller peripheral RV. The temporal area was significantly smaller than all other areas in the macula (1–6 mm), whereas the inferior area was significantly smaller than all other areas in the peripheral retina (6–20 mm).</p></div><div><h3>Conclusions</h3><p>In wide-field SS-OCT images, age and left eye are negatively correlated with peripheral RV. The thinnest part of the retinal quadrant differs between the macular and peripheral retinas.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001052/pdfft?md5=394b3468fb665e4d2094d378b0d55297&pid=1-s2.0-S2666914524001052-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dominic J. Williamson MSc , Robbert R. Struyven MD , Fares Antaki MD , Mark A. Chia MD , Siegfried K. Wagner MD, PhD , Mahima Jhingan MBBS , Zhichao Wu PhD , Robyn Guymer MBBS, PhD , Simon S. Skene PhD , Naaman Tammuz PhD , Blaise Thomson PhD , Reena Chopra PhD , Pearse A. Keane MD
{"title":"Artificial Intelligence to Facilitate Clinical Trial Recruitment in Age-Related Macular Degeneration","authors":"Dominic J. Williamson MSc , Robbert R. Struyven MD , Fares Antaki MD , Mark A. Chia MD , Siegfried K. Wagner MD, PhD , Mahima Jhingan MBBS , Zhichao Wu PhD , Robyn Guymer MBBS, PhD , Simon S. Skene PhD , Naaman Tammuz PhD , Blaise Thomson PhD , Reena Chopra PhD , Pearse A. Keane MD","doi":"10.1016/j.xops.2024.100566","DOIUrl":"10.1016/j.xops.2024.100566","url":null,"abstract":"<div><h3>Objective</h3><p>Recent developments in artificial intelligence (AI) have positioned it to transform several stages of the clinical trial process. In this study, we explore the role of AI in clinical trial recruitment of individuals with geographic atrophy (GA), an advanced stage of age-related macular degeneration, amidst numerous ongoing clinical trials for this condition.</p></div><div><h3>Design</h3><p>Cross-sectional study.</p></div><div><h3>Subjects</h3><p>Retrospective dataset from the INSIGHT Health Data Research Hub at Moorfields Eye Hospital in London, United Kingdom, including 306 651 patients (602 826 eyes) with suspected retinal disease who underwent OCT imaging between January 1, 2008 and April 10, 2023.</p></div><div><h3>Methods</h3><p>A deep learning model was trained on OCT scans to identify patients potentially eligible for GA trials, using AI-generated segmentations of retinal tissue. This method's efficacy was compared against a traditional keyword-based electronic health record (EHR) search. A clinical validation with fundus autofluorescence (FAF) images was performed to calculate the positive predictive value of this approach, by comparing AI predictions with expert assessments.</p></div><div><h3>Main Outcome Measures</h3><p>The primary outcomes included the positive predictive value of AI in identifying trial-eligible patients, and the secondary outcome was the intraclass correlation between GA areas segmented on FAF by experts and AI-segmented OCT scans.</p></div><div><h3>Results</h3><p>The AI system shortlisted a larger number of eligible patients with greater precision (1139, positive predictive value: 63%; 95% confidence interval [CI]: 54%–71%) compared with the EHR search (693, positive predictive value: 40%; 95% CI: 39%–42%). A combined AI-EHR approach identified 604 eligible patients with a positive predictive value of 86% (95% CI: 79%–92%). Intraclass correlation of GA area segmented on FAF versus AI-segmented area on OCT was 0.77 (95% CI: 0.68–0.84) for cases meeting trial criteria. The AI also adjusts to the distinct imaging criteria from several clinical trials, generating tailored shortlists ranging from 438 to 1817 patients.</p></div><div><h3>Conclusions</h3><p>This study demonstrates the potential for AI in facilitating automated prescreening for clinical trials in GA, enabling site feasibility assessments, data-driven protocol design, and cost reduction. Once treatments are available, similar AI systems could also be used to identify individuals who may benefit from treatment.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001027/pdfft?md5=d3fd08da8ceda3860a8f32aa944ff57b&pid=1-s2.0-S2666914524001027-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141949722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}