Ophthalmology science最新文献

{"title":"Deep Learning with Disc Photos or OCT Scans in Glaucoma Detection","authors":"Abhilash Katuru ,&nbsp;In Young Chung MBBS, MPH ,&nbsp;Iyad Majid ,&nbsp;Lucy Q. Shen MD ,&nbsp;Mengyu Wang PhD","doi":"10.1016/j.xops.2025.100877","DOIUrl":"10.1016/j.xops.2025.100877","url":null,"abstract":"<div><h3>Objective</h3><div>To determine whether a deep learning (DL) model using retinal nerve fiber layer thickness (RNFLT) maps from OCT scans can detect glaucoma, defined by functional visual field (VF) impairment, more accurately than a DL model using disc photos (DPs). A secondary objective was to assess the diagnostic performance of these DL models across demographic groups (race, sex, and ethnicity).</div></div><div><h3>Design</h3><div>Retrospective cohort study at a tertiary glaucoma center utilizing OCT and DP datasets collected between 2011 and 2022.</div></div><div><h3>Participants</h3><div>Out of the 16 936 DP and OCT image sets, patients with Cirrus OCT images with a quality score ≥6 of 10 and reliable 24-2 Humphrey VF tests (fixation loss ≤33%, false-negative rate ≤20%, false-positive rate ≤20%), taken within 30 days of OCT, were included. Disc photos were obtained within 6 months of OCT. Data were randomly selected for training and testing of the DL models.</div></div><div><h3>Testing</h3><div>Development of DL models utilizing either OCT RNFLT maps or DPs to detect glaucoma based on VF-defined functional impairment.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome was the area under the curve (AUC) for glaucoma detection, comparing the OCT-based DL model with the DP-based model. The secondary outcome was the AUC across demographic groups.</div></div><div><h3>Results</h3><div>The OCT-based DL model achieved an AUC of 0.90, significantly outperforming the DP-based model (AUC = 0.86, <em>P</em> &lt; 0.005) with superior performance consistent across demographic groups. The OCT and DP model accuracies varied significantly by demographic groups. For the OCT model, AUCs were 0.93, 0.92, and 0.92 for Asians, Blacks, and Whites (<em>P</em> &lt; 0.005); 0.89 for women versus 0.93 for men (<em>P</em> = 0.005); and 0.92 for Hispanics versus 0.94 for non-Hispanics (<em>P</em> &lt; 0.005). For the DP model, corresponding AUCs for race were 0.87, 0.90, and 0.82 (<em>P</em> &lt; 0.005); for sex, 0.856 versus 0.862 (<em>P</em> &lt; 0.005); and for Hispanics, 0.85 versus 0.79 (<em>P</em> &lt; 0.005).</div></div><div><h3>Conclusions</h3><div>When glaucoma diagnosis was based on functional deficit, the OCT-based DL model offered greater accuracy in detecting glaucoma than the DP-based model, likely due to its use of objective and quantitative RNFLT measurements. This work supports the use of OCT-based DL models for glaucoma detection, while observed demographic disparities underscore the need for equitable datasets to ensure fair DL-driven glaucoma diagnosis across populations.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100877"},"PeriodicalIF":4.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Prediction of Cardiovascular Risk in Type 1 Diabetes Mellitus Using Radiomic Features from Multimodal Retinal Images","authors":"Ariadna Tohà-Dalmau MSc ,&nbsp;Josep Rosinés-Fonoll MD ,&nbsp;Enrique Romero PhD ,&nbsp;Ferran Mazzanti PhD ,&nbsp;Ruben Martin-Pinardel MSc ,&nbsp;Sonia Marias-Perez MD ,&nbsp;Carolina Bernal-Morales MD, PhD ,&nbsp;Rafael Castro-Dominguez OD, MSc ,&nbsp;Andrea Mendez OD, MSc ,&nbsp;Emilio Ortega MD, PhD ,&nbsp;Irene Vinagre MD, PhD ,&nbsp;Marga Gimenez MD, PhD ,&nbsp;Alfredo Vellido PhD ,&nbsp;Javier Zarranz-Ventura MD, PhD","doi":"10.1016/j.xops.2025.100874","DOIUrl":"10.1016/j.xops.2025.100874","url":null,"abstract":"<div><h3>Purpose</h3><div>To develop a machine learning (ML) algorithm capable of determining cardiovascular (CV) risk in multimodal retinal images from patients with type 1 diabetes mellitus (T1DM), distinguishing between moderate, high, and very high-risk levels.</div></div><div><h3>Design</h3><div>Cross-sectional analysis of a retinal image data set from a previous prospective OCT angiography (OCTA) study (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> NCT03422965).</div></div><div><h3>Participants</h3><div>Patients with T1DM included in the progenitor study.</div></div><div><h3>Methods</h3><div>Radiomic features were extracted from color fundus photographs (CFPs), OCT, and OCTA images, and ML models were trained using these features either individually or combined with clinical data (demographics and systemic data, OCT + OCTA commercial software metrics, ocular data, blood data). Different data combinations were tested to determine the CV risk stages, defined according to international classifications.</div></div><div><h3>Main Outcome Measures</h3><div>Area under the receiver operating characteristic curve mean and standard deviation for each ML model and each data combination.</div></div><div><h3>Results</h3><div>A data set of 597 eyes (359 individuals) was analyzed. Models trained only with the radiomic features achieved area under the curve (AUC) values of (0.79 ± 0.03) to identify moderate risk cases from high and very high-risk cases, and (0.73 ± 0.07) for distinguishing between high and very high-risk cases. The addition of clinical variables improved all AUC values, obtaining (0.99 ± 0.01) for identifying moderate cases, and (0.95 ± 0.02) for differentiating between high and very high-risk cases. For very high CV risk, radiomics combined with OCT + OCTA metrics and ocular data achieved an AUC of (0.89 ± 0.02) without systemic data input. The performance of the models was similar in unilateral and bilateral eye image data sets.</div></div><div><h3>Conclusions</h3><div>Radiomic features obtained from retinal images are helpful to discriminate and classify CV risk labels, differentiating risk categories. The addition of demographics and systemic data combined with ocular data differentiate high from very high CV risk cases, and interestingly OCT + OCTA metrics with ocular data identify very high CV risk cases without systemic data input. These results reflect the potential of this oculomics approach for CV risk assessment.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100874"},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suprachoroidal Injection of Topotecan for Retinoblastoma: A Preclinical Study","authors":"Arun D. Singh MD ,&nbsp;Vishal Raval MD ,&nbsp;Sandeep Kumar PhD ,&nbsp;Anthony Daniels MD","doi":"10.1016/j.xops.2025.100875","DOIUrl":"10.1016/j.xops.2025.100875","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess whether levels of topotecan that are expected to be therapeutic against retinoblastoma tumors can be achieved within the retina and choroid by suprachoroidal injection (SCI) and to assess toxicity and safety in vivo.</div></div><div><h3>Design</h3><div>Pharmacokinetics and dose escalation toxicity study.</div></div><div><h3>Subjects</h3><div>New Zealand white rabbits.</div></div><div><h3>Methods</h3><div>In a pharmacokinetic study (N=18), aqueous, vitreous, retina, choroid, and plasma were separated and harvested serially (15, 30, 60, 120, and 360 minutes) following SCI. Topotecan (lactone) levels were measured and pharmacokinetic parameters were calculated. In the dose escalation toxicity study (N=8), toxicity was evaluated by ocular examination, fundus photography, OCT, full-field electroretinography (ffERG), and tissue histology. A single SCI of 50 μg/0.05 mL or two consecutive SCI totaling 100 μg/0.1 mL (N=4 rabbits per group) were administered.</div></div><div><h3>Main Outcome Measures</h3><div>Topotecan (lactone) tissue levels and ocular toxicity (25% reduction in ffERG).</div></div><div><h3>Results</h3><div>Following a single SCI of 50 μg topotecan, high levels of topotecan were achieved rapidly in both the retina and choroid. Retinal levels peaked by 15 minutes (12400±7336 ng/gm) followed by rapid decline to 2899±1361 ng/gm by 30 minutes, and then slower progressive decline that reached lowest levels at 360 minutes (469 ng/gm). Half-life (T_1/2) in the retina was 24.8 minutes. Choroidal levels were 3.3-fold higher than retina with a similar rapid decline pattern. Vitreous level was highest at 15 min (278 ng/mL) with a slow progressive decline until 360 min (16.9 ng/ml). Plasma (mean 4.3±2.6 ng/ml) and aqueous (peak at 120 min, mean 87 ng/ml) levels remained low throughout the study. There were no signs of ocular toxicity or other adverse ocular events on either clinical examination, serial imaging studies, ffERG, or histology following sacrifice at 28 days.</div></div><div><h3>Conclusions</h3><div>A single SCI of topotecan (50 μg/0.05 ml) achieved selective tissue distribution of its lactone moiety (retina/plasma, 1377.8) that was 23-fold higher than that reported with intraarterial chemotherapy (58.9) and more than 1000-fold higher than intravenous chemotherapy (1.32). These retinal levels were nontoxic and were 885-fold higher than the known topotecan IC50 for human retinoblastoma cells (IC50 14 ng/gm). Our findings support potential benefit of SCI of topotecan for patients with retinoblastoma.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100875"},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Association Study and Rare Variant Association Studies of Strabismus in the All of Us Research Program","authors":"Kyoung A Viola Lee MPH ,&nbsp;Corey Tesdahl ,&nbsp;Inas F. Aboobakar MD ,&nbsp;Ashish Jain PhD ,&nbsp;Mayra Martinez Sanchez PhD ,&nbsp;Kimberly Jin BA ,&nbsp;Isdin Oke MD ,&nbsp;Mary C. Whitman MD, PhD","doi":"10.1016/j.xops.2025.100873","DOIUrl":"10.1016/j.xops.2025.100873","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Despite significant evidence of a genetic contribution to strabismus, precise genetic mechanisms have not been identified. There are distinct population differences in the prevalence of strabismus and its subtypes. This study aimed to explore the genetic contributions to strabismus in different ancestral groups.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Case-control.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;The &lt;em&gt;All of Us&lt;/em&gt; Research Program includes genotypic and phenotypic data from a diverse population of adults (age ≥18 years at time of enrollment) across the United States. Among participants with whole-genome sequences available, strabismus cases were identified based on diagnosis codes from their electronic health record. Participants with conditions associated with acquired strabismus, such as trauma, thyroid eye disease, tumor, or stroke, were excluded from the case and control cohorts. The final cohort consisted of 1579 cases and 121 490 controls of European (EUR) ancestry, 235 cases and 40 602 controls of Admixed American (AMR) ancestry, and 365 cases and 53 577 controls of African American (AFR) ancestry. Individuals of other ancestral groups were not included due to small numbers of strabismus-affected participants.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Genome-wide association study of common variants (minor allele frequency &gt;1%) and rare variant association study at the gene level for strabismus.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Individual single nucleotide polymorphisms (SNPs) significantly associated with strabismus and genes with significant burden of rare variants in strabismus.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Genome-wide association study identified one locus with 3 significant SNPs (rs2247113, rs2667037, and rs2715926) in intron 1 of &lt;em&gt;PLA2R1&lt;/em&gt; in the AFR group, and 2 loci, one in &lt;em&gt;RIMBP2&lt;/em&gt; intron (rs184071225) and one intergenic (rs191788703), in the AMR group. Rare variant association study revealed 33 genes with a statistically significant (&lt;em&gt;P&lt;/em&gt; value &lt; 5 x 10&lt;sup&gt;-5&lt;/sup&gt;) increased burden of variants: 9 in the EUR cohort: &lt;em&gt;ZNF468&lt;/em&gt;, &lt;em&gt;CMYA5&lt;/em&gt;, &lt;em&gt;NSUN4&lt;/em&gt;, &lt;em&gt;TEX45&lt;/em&gt;, &lt;em&gt;ICAM3&lt;/em&gt;, &lt;em&gt;ADAMTS20&lt;/em&gt;, &lt;em&gt;FANCI&lt;/em&gt;, &lt;em&gt;HLA-DQB1&lt;/em&gt;, and &lt;em&gt;GRIN3B&lt;/em&gt;; 14 in the AMR cohort: &lt;em&gt;RIMBP1&lt;/em&gt;, &lt;em&gt;UCKL1&lt;/em&gt;, &lt;em&gt;EHBP1L1&lt;/em&gt;, &lt;em&gt;CLTCL1&lt;/em&gt;, &lt;em&gt;HELB&lt;/em&gt;, &lt;em&gt;TULP2&lt;/em&gt;, &lt;em&gt;APOB&lt;/em&gt;, &lt;em&gt;SMPD3&lt;/em&gt;, &lt;em&gt;OBSCN&lt;/em&gt;, &lt;em&gt;NLRP8&lt;/em&gt;, &lt;em&gt;PLOD1&lt;/em&gt;, &lt;em&gt;NUP214&lt;/em&gt;, &lt;em&gt;OR6J1&lt;/em&gt;, and &lt;em&gt;NOP10&lt;/em&gt;; and 10 in the AFR cohort: &lt;em&gt;C4orf54&lt;/em&gt;, &lt;em&gt;PIGG&lt;/em&gt;, &lt;em&gt;OR10D3&lt;/em&gt;, &lt;em&gt;MKNK1&lt;/em&gt;, &lt;em&gt;KNCN&lt;/em&gt;, &lt;em&gt;MS4A14&lt;/em&gt;, &lt;em&gt;CSN2&lt;/em&gt;, &lt;em&gt;BDKRB1&lt;/em&gt;, &lt;em&gt;IL1RL1&lt;/em&gt;, and &lt;em&gt;ISM2&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Genetic associations with strabismus differed between ancestry groups, although genes in similar pathways, such as synaptic signaling and structural muscle proteins, were found in multiple groups. This h","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100873"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover","authors":"","doi":"10.1016/S2666-9145(25)00161-7","DOIUrl":"10.1016/S2666-9145(25)00161-7","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 4","pages":"Article 100863"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proliferative Diabetic Retinopathy Disproportionately Impacts Distressed Communities Near a Northeastern Academic Center","authors":"Akua A. Frimpong BS ,&nbsp;Thomas L. Chang BS ,&nbsp;June-Marie Weiss MA, MEd ,&nbsp;Brittany G. Assanah-Lewis MD ,&nbsp;Ming-Chen Lu MS ,&nbsp;Kristen Harris Nwanyanwu MD, MBA","doi":"10.1016/j.xops.2025.100872","DOIUrl":"10.1016/j.xops.2025.100872","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify the associations between social determinants of health (SDoH) and the progression of proliferative diabetic retinopathy (PDR).</div></div><div><h3>Design</h3><div>Secondary analysis of a retrospective cohort study.</div></div><div><h3>Participants</h3><div>We extracted data from electronic medical records of individuals at the Yale Eye Center or Dana Eye Clinic, ages ≥18 years, who had a documented diagnosis of nonproliferative diabetic retinopathy (NPDR) at their first recorded (index) ophthalmology visit within the study period.</div></div><div><h3>Methods</h3><div>We identified participants with NPDR whose disease progressed to PDR during the study time period. We assigned Distressed Communities Index (DCI) scores using participants’ zip codes and created a visualized geographic distribution of scores using ArcGIS. We assessed differences in sociodemographic and health characteristics between participants whose disease progressed to PDR and those whose disease did not progress using 2-sample <em>t</em> tests, chi-square, and Fisher exact tests where appropriate. We used logistic regression to assess the associations between SDoH and progression to PDR. We conducted a time-to-event analysis using Cox proportional hazards regression, adjusting for relevant confounders.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome was the progression from NPDR to PDR.</div></div><div><h3>Results</h3><div>Among the 1354 participants, 137 (10%) developed PDR within the study's 7-year period. Of the 137, 54% were male, 46% were aged ≥65 years, 35% identified as White or Caucasian, and 34% identified as Black or African American. Those whose disease progressed to PDR had significantly worse DCI scores compared to those whose disease did not progress (mean [standard deviation 64 (26) vs. 58 (27), <em>P</em> = 0.015). Unadjusted logistic regression revealed a significant association between DCI and progression to PDR (<em>P</em> = 0.037), whereas the adjusted model did not (<em>P</em> = 0.124).</div></div><div><h3>Conclusions</h3><div>Participants with disease progression to PDR were more likely to live in disadvantaged areas. Using socioeconomic data and geographic mapping to identify high-risk populations may help health care professionals implement early screening and provide better resources for those at risk of retinal disease progression.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100872"},"PeriodicalIF":4.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Macular Tissue Integrity Index as a Novel Biomarker in Geographic Atrophy","authors":"Bethany M. Erb MD ,&nbsp;Elaine Botros ,&nbsp;Thomas F. Saunders OD ,&nbsp;Anna-Maria Haas MD ,&nbsp;Rick Voland PhD ,&nbsp;Rachel Linderman PhD ,&nbsp;Amitha Domalpally MD, PhD ,&nbsp;Karl G. Csaky MD","doi":"10.1016/j.xops.2025.100871","DOIUrl":"10.1016/j.xops.2025.100871","url":null,"abstract":"<div><h3>Purpose</h3><div>The rate of geographic atrophy (GA) enlargement is commonly used as an outcome in clinical trials. However, this metric typically lacks specificity for central macular involvement and structure–function relationships. We propose a targeted approach in monitoring GA progression within the central macula, highlighting the limited benefit of including GA expansion beyond the 3-mm perifoveal zone when analyzing visual function. This study evaluates how retinal tissue and photoreceptor integrity within the central 1-mm and 3-mm circles centered on the fovea correlate with visual function.</div></div><div><h3>Design</h3><div>Retrospective, longitudinal analysis of a GA clinical trial cohort.</div></div><div><h3>Subjects</h3><div>Forty-three eyes from 43 participants enrolled in GA clinical trials.</div></div><div><h3>Methods</h3><div>Baseline and 1-year fundus autofluorescence (FAF) and OCT scans were analyzed. The percentages of non-GA areas within the 1-mm and 3-mm circles centered on the fovea were quantified to calculate the Macular Tissue Integrity Index (MTII) using FAF images. The percentages of intact ellipsoid zones within the same circles were used to define the EZ Integrity Index (EZII). Longitudinal changes in MTII and EZII were compared to overall GA area growth and change in visual acuity (VA).</div></div><div><h3>Main Outcome Measures</h3><div>Correlations between MTII, EZII, GA area, and VA (best-corrected VA [BCVA] and low-luminance VA [LLVA]) were assessed.</div></div><div><h3>Results</h3><div>Macular Tissue Integrity Index and EZII within the central 1 mm correlated significantly with BCVA (R² = 0.20, P = 0.003 and R² = 0.29, P &lt; 0.001, respectively), while EZII in the 3-mm zone correlated with both BCVA and LLVA (R² = 0.17, P &lt; 0.01 for both). Changes in MTII or EZII over time were not associated with GA area growth or with baseline integrity indices.</div></div><div><h3>Conclusions</h3><div>Macular Tissue Integrity Index and EZII are novel biomarkers for macular photoreceptor integrity, with distinct correlations to BCVA and LLVA depending on the measurement zone. These findings support the utility of MTII and EZII in assessing macular integrity and highlight the heterogeneity of GA progression, warranting further validation in larger studies.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100871"},"PeriodicalIF":4.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Sphingomyelins as Biomarkers for Diabetic Retinal Neurodegeneration: The Maastricht Study","authors":"Siddhita A. Jadhav MSc ,&nbsp;Birke J. Benedikter PhD ,&nbsp;Sara B.A. Mokhtar MSc ,&nbsp;Frank C.T. van der Heide MD, PhD ,&nbsp;Govindasamy Kumaramanickavel MD ,&nbsp;Marleen M.J. van Greevenbroek PhD ,&nbsp;Carroll A.B. Webers MD, PhD ,&nbsp;Tos T.J.M. Berendschot PhD","doi":"10.1016/j.xops.2025.100870","DOIUrl":"10.1016/j.xops.2025.100870","url":null,"abstract":"<div><h3>Objective</h3><div>Sphingomyelin (SM) may play a role in the early stages of diabetic retinopathy. Early diagnosis of diabetic retinopathy is crucial for preventing the irreversible vision loss associated with this condition. This study aimed to examine the link between SM and key indicators of diabetic retinopathy, namely retinal neurodegeneration, including corneal nerve measures, retinal layer thickness, and mean retinal sensitivity. Understanding these relationships may help identify early biomarkers and therapeutic targets for preventing or slowing the progression of diabetic retinopathy.</div></div><div><h3>Design</h3><div>We used data from the Maastricht Study, a large population-based observational cohort with oversampling of individuals with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Subjects</h3><div>In this study, SM levels were examined across 3 study groups: (1) individuals with normal glucose metabolism; (2) prediabetes; and (3) T2DM.</div></div><div><h3>Methods</h3><div>Fasting plasma SM levels were measured using the nuclear magnetic resonance platform from Nightingale Health.</div></div><div><h3>Main Outcomes and Measures</h3><div>Linear regression analysis was conducted to assess the link between total plasma SM (determinant) and indicators of retinal neurodegeneration (outcomes), including corneal nerve measures, mean retinal sensitivity, and retinal thickness, while adjusting for potential confounders affecting SM metabolism.</div></div><div><h3>Results</h3><div>Among the 3598 individuals examined, the average plasma levels of total SM were significantly lower in individuals with T2DM (<em>P</em> &lt; 0.001) than those with prediabetes and the control group, even after stratification by lipid-modifying medication usage. In regression analysis, after full adjustment, lower levels of SM were associated with reduced mean retinal sensitivity: β (95% confidence interval) for the right eye (n = 1934), 0.088 (0.012, 0.164) and for the left eye (n = 1925), 0.111 (0.033, 0.189). However, no significant correlations were found with other indicators of retinal neurodegeneration.</div></div><div><h3>Conclusions</h3><div>Lower levels of plasma SMs were linked to reduced retinal sensitivity in individuals with diabetes, indicating their involvement in early neurodegenerative alterations in the diabetic retina. These findings suggest that SMs could be explored as potential biomarkers for detecting diabetic retinal neurodegeneration at an early stage of diabetes. However, further research is essential to clarify the biological pathways involved and to evaluate the effectiveness of SMs as clinical biomarkers.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100870"},"PeriodicalIF":4.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vivo Comparison of Intracameral and Intravitreal Implantation of a Timolol Maleate Miniaturized Injectable Delivery System Device","authors":"Chu Jian Ma MD, PhD ,&nbsp;Youning Zhang MD ,&nbsp;Daniel A. Bernards PhD ,&nbsp;Michele Bloomer MD ,&nbsp;John Dickson BS ,&nbsp;Jayakumar Rajadas PhD ,&nbsp;Murty Vyakarnam PhD ,&nbsp;Tejal A. Desai PhD ,&nbsp;Robert B. Bhisitkul MD, PhD","doi":"10.1016/j.xops.2025.100868","DOIUrl":"10.1016/j.xops.2025.100868","url":null,"abstract":"<div><h3>Purpose</h3><div>Miniaturized injectable delivery system (MIDS) devices engineered for zero-order release of timolol maleate are evaluated for intracameral (IC) or intravitreal (IVT) injection for ocular safety, effects on intraocular pressure (IOP) reduction, and target tissue drug concentrations.</div></div><div><h3>Design</h3><div>Preclinical study with in vitro testing of MIDS drug delivery devices together with intraocular injection of the devices in normotensive rabbit eyes.</div></div><div><h3>Subjects</h3><div>Twenty-four New Zealand rabbits received intraocular injections of MIDS devices.</div></div><div><h3>Methods</h3><div>Timolol maleate MIDS devices were injected IC or IVT into normotensive New Zealand rabbit eyes (n = 24), with weekly ophthalmic examinations and IOP measurements for 8 or 16 weeks. Eight weeks postimplantation, eyes were enucleated for quantification of tissue drug concentrations by liquid chromatography with tandem mass spectrometry and histology on whole globes.</div></div><div><h3>Main Outcome Measures</h3><div>Drug release pharmacokinetics; ocular safety and biocompatibility; IOP; and blood and target tissue drug concentrations.</div></div><div><h3>Results</h3><div>At 8 weeks, IOP in experimental eyes was lowered by 11.1 ± 2.9% (n = 5, <em>P</em> = 0.019) and 18.1 ± 2.6% (n = 6, <em>P</em> &lt; 0.001), for IC and IVT devices, respectively. In extended studies of IVT devices, IOP was numerically lower at 16 weeks by 8.5 ± 5.1% (n = 3, <em>P</em> = 0.24). Intracameral versus IVT injections achieved different tissue distributions (in ng/g; except for aqueous in ng/mL): aqueous 28.5 ± 2.7 vs. 4.5 ± 1.2 (<em>P</em> &lt; 0.001), vitreous 0.3 ± 0.1 vs. 37.2 ± 11.0 (<em>P</em> = 0.010), and ciliary body 14.4 ± 1.8 vs. 50.9 ± 10.8 (<em>P</em> = 0.011). Intraocular inflammation and drug- or device-related adverse effects were absent on examinations and histopathology. Blood drug concentration was below the quantitation limit (&lt;0.4 ng/ml).</div></div><div><h3>Conclusions</h3><div>Intravitreal and IC devices showed similar IOP reductions; IVT injection led to a higher drug concentration in the target ciliary body tissue, and in normotensive rabbit eyes showed general reduction of IOP over 8 weeks, indicating the potential of MIDS technology to address issues of patient adherence with glaucoma eye drops.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100868"},"PeriodicalIF":4.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macular Thinning and Microvasculature Abnormalities in Children with Sickle Cell Disease: A Longitudinal Analysis","authors":"Sally S. Ong MD ,&nbsp;Ann Nampomba MS ,&nbsp;Sara Rahman BS ,&nbsp;Loka Thangamathesvaran MD ,&nbsp;Grace Reilly MD ,&nbsp;Jianqiao Ma ScM ,&nbsp;Jay Vaidya PhD ,&nbsp;Sophie Lanzkron MD, MHS ,&nbsp;Adrienne W. Scott MD","doi":"10.1016/j.xops.2025.100862","DOIUrl":"10.1016/j.xops.2025.100862","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess longitudinal changes in retinal thickness and vessel density (VD) in pediatric sickle cell disease (SCD).</div></div><div><h3>Design</h3><div>A prospective cohort study.</div></div><div><h3>Participants</h3><div>Children (&lt;18 years old) with HbSS and HbS variant (HbSC and HbS thalassemia) genotypes were enrolled from a university-based retina subspecialty clinic from 2017 to 2019 and followed for ≥2 years.</div></div><div><h3>Methods</h3><div>Participants received 3 × 3 and 6 × 6 mm OCT and OCT angiography scans at baseline and at each follow-up visit.</div></div><div><h3>Main Outcome Measures</h3><div>Retinal thickness, superficial capillary plexus (SCP), and deep capillary plexus (DCP) VD were compared over time.</div></div><div><h3>Results</h3><div>Children with HbSS (n = 14) and HbS variant (n = 14) genotypes with ≥1 follow-up were included in the study (total 56 eyes). For HbSS, rates of retinal thinning per year were significant in the inner retina in the nasal, inferior, and total parafovea (<em>P</em> = 0.002, 0.003, and 0.03 respectively), temporal and total perifovea (<em>P</em> = 0.01 and 0.02); in the middle retina in the superior perifovea (<em>P</em> = 0.04); and in the total retina in the superior, nasal, and total perifovea (<em>P</em> &lt; 0.001, = 0.01, and 0.009). For HbS variant, the rate of retinal thinning was significant in the inner retina in the superior parafovea (<em>P</em> = 0.002) only. Vessel density did not change in the SCP in HbSS subjects in any of the subfields studied but increased significantly in the SCP in HbS variant subjects in the nasal and inferior parafovea (<em>P</em> = 0.02 and 0.045) and superior and nasal perifovea (<em>P</em> = 0.03 and 0.004). Vessel density in the DCP increased in the HbSS group in all the subfields studied (<em>P</em> &lt; 0.05) and in the HbS variant group in the temporal parafovea (<em>P</em> = 0.02).</div></div><div><h3>Conclusions</h3><div>Progressive retinal thinning, predominantly in the inner retinal layers, was particularly notable in children with HbSS disease. This was observed in conjunction with the lack of an increase in the SCP VD in the HbSS group when compared with the HbS variant group. These findings suggest that microstructural and microvasculature abnormalities in the macula start in childhood in SCD, especially for those with HbSS disease.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100862"},"PeriodicalIF":3.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}