Ophthalmology science最新文献

{"title":"Clinical Evidence of a Photoreceptor Origin in Diabetic Retinal Disease","authors":"Rithwick Rajagopal MD, PhD ,&nbsp;Timothy Kern PhD","doi":"10.1016/j.xops.2024.100591","DOIUrl":"10.1016/j.xops.2024.100591","url":null,"abstract":"<div><h3>Clinical Relevance</h3><p>Although diabetes is associated with a classic microvascular disease of the retina, it is also increasingly being recognized as a cause of retinal neuropathy. Preclinical evidence suggests that retinal neuropathy in diabetes manifests in part as photoreceptor dysfunction, preceding the development of vascular features in experimental models. It remains unknown whether such findings are relevant to patients with diabetes.</p></div><div><h3>Methods</h3><p>Here, we review 4 lines of clinical evidence suggesting that diabetes-associated photoreceptor pathology is linked to the development of retinal microvascular disease.</p></div><div><h3>Results</h3><p>First, a major population-based investigation of susceptibility loci for diabetic retinopathy (DR) implicated a photoreceptor protein product as a protective factor. Next, electroretinography and other studies of visual function collectively show that rod and/or cone-derived abnormalities occur decades before the development of vascular features of DR. Third, protection from DR seemingly develops in patients with coincident retinitis pigmentosa, as suggested by several case series. Finally, based on anatomic features, we propose that the beneficial effect of macular laser in DR occurs via ablation of diseased photoreceptors.</p></div><div><h3>Conclusions</h3><p>The evidence we present is limited due to the small patient populations used in the studies we cite and due to the lack of methodologies that allow causative relationships to be inferred. Collectively, however, these clinical observations suggest that photoreceptors are involved in early diabetic retinal disease and may in fact give rise to the classic features of DR.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosures may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100591"},"PeriodicalIF":3.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001271/pdfft?md5=03b8c3f460842b579f490019dd45ab72&pid=1-s2.0-S2666914524001271-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239014","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":"Phase I Study of Intravitreal Injection of Autologous CD34+ Stem Cells from Bone Marrow in Eyes with Vision Loss from Retinitis Pigmentosa","authors":"Susanna S. Park MD, PhD ,&nbsp;Gerhard Bauer ,&nbsp;Brian Fury MS ,&nbsp;Mehrdad Abedi MD ,&nbsp;Nicholas Perotti MD ,&nbsp;Dane Colead-Bergum MA ,&nbsp;Jan A. Nolta PhD","doi":"10.1016/j.xops.2024.100589","DOIUrl":"10.1016/j.xops.2024.100589","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the feasibility and safety of intravitreal injection of autologous CD34+ stem cells from bone marrow (BMSCs) in eyes with vision loss from retinitis pigmentosa (RP).</p></div><div><h3>Design</h3><p>Phase I prospective, open-label, single-center study.</p></div><div><h3>Participants</h3><p>Seven eyes (7 patients) with RP with best-corrected visual acuity (BCVA) of 20/60 to 20/400 or visual field constriction to within 10°.</p></div><div><h3>Methods</h3><p>A comprehensive examination with ETDRS BCVA, macular OCT, perimetry, and fluorescein angiography was performed at baseline, 1 to 3 months, and 6 months after study treatment. Bone marrow aspiration, isolation of CD34+ BMSCs under good manufacturing practice conditions, and intravitreal cell injection were performed on the same day. The CD34+ cells were isolated from bone marrow using a Ficoll gradient and the Miltenyi CliniMACS system. Isolated CD34+ cells were released for clinical use if viability, sterility, and purity met the release criteria accepted by the United States Food and Drug Administration for this clinical study.</p></div><div><h3>Main Outcome Measures</h3><p>Number of CD34+ cells isolated for injection and adverse events associated with study treatment during follow-up. Secondary outcome measures are changes in BCVA and perimetry.</p></div><div><h3>Results</h3><p>All isolated CD34+ cells passed the release criteria. A mean of 3.26 ± 0.66 million viable CD34+ cells (range 1.6 to 7.05 million) were injected intravitreally per eye. No adverse event was noted during the study follow-up except for 1 participant who was noted with transient cells in the anterior chamber with mild elevation in intraocular pressure at 18 hours after study injection which normalized by 24 hours. Best-corrected visual acuity remained within 2 lines of baseline or improved in all participants at 6 months follow-up. Perimetry was stable or improved in all eyes during study follow-up except 1 eye with transient improvement at 1 month and worsening of both eyes at 6 months.</p></div><div><h3>Conclusions</h3><p>Intravitreal injection of autologous CD34+ BMSCs is feasible and appears to be well tolerated in eyes with vision loss from RP. A larger randomized prospective study would be needed to evaluate further the safety and potential efficacy of this cell therapy for vision loss associated with RP.</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":"5 1","pages":"Article 100589"},"PeriodicalIF":3.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001258/pdfft?md5=26ee261925521bae1e4cb8e10d7ee52b&pid=1-s2.0-S2666914524001258-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239013","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":"Subconjunctival Administration of an Adeno-Associated Virus Expressing Stanniocalcin-1 Provides Sustained Intraocular Pressure Reduction in Mice","authors":"Gavin W. Roddy MD, PhD,&nbsp;Darrell Kohli MD,&nbsp;Parvin Niknam PhD,&nbsp;Mohammed E. Omer MBBS,&nbsp;Uttio Roy Chowdhury PhD,&nbsp;Kjersten J. Anderson,&nbsp;Johann M. Pacheco Marrero MD,&nbsp;Tommy A. Rinkoski MS,&nbsp;Michael P. Fautsch PhD","doi":"10.1016/j.xops.2024.100590","DOIUrl":"10.1016/j.xops.2024.100590","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;To investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained (IOP) lowering agent with a reduced ocular surface side effect profile.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;p&gt;In vivo preclinical investigation in mice.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;p&gt;C57BL/6J, DBA/2J, prostaglandin F (FP) receptor knockout mice.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Normotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 μL; 6 × 10&lt;sup&gt;9&lt;/sup&gt; viral genomes [VGs]) in 1 eye and the same volume and concentration of ssAAV2-green fluorescent protein (GFP) or the same volume of phosphate-buffered saline in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 × 10&lt;sup&gt;9&lt;/sup&gt; VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 × 10&lt;sup&gt;9&lt;/sup&gt; VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Prostaglandin F receptor knockout mice were injected subconjunctivally with 6 × 10&lt;sup&gt;9&lt;/sup&gt; VGs of ssAAV2-STC-1-FLAG or phosphate-buffered saline. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. Intraocular pressure was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1-FLAG and other treatments including daily topical latanoprost.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;p&gt;Intraocular pressure assessment.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Subconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 3 postinjection (17.4%; 17.1 ± 0.8 vs. 14.1 ± 0.8 mmHg, &lt;em&gt;P&lt;/em&gt; &lt; 0.001). After the IOP-lowering effect had waned, a second injection restored the ocular hypotensive effect. Subconjunctivally delivered ssAAV2-STC-1-FLAG lowered IOP in DBA/2J mice (16.9%; 17.8 ± 2.0 vs. 14.8 ± 0.9 mmHg, &lt;em&gt;P&lt;/em&gt; &lt; 0.001) and steroid-mediated ocular hypertensive mice (20.0%; 19.0 ± 0.6 vs. 15.2 ± 0.7 mmHg, &lt;em&gt;P&lt;/em&gt; &lt; 0.001) over the experimental period. This construct also reduced IOP to a similar extent in wild-type (15.9%) and FP receptor knockout (15.7%) mice compared with the fellow eye. A related construct also lowered IOP without the FLAG tag in a similar manner. Reduction in conjunctival TNFα was seen when comparing subconjunctivally delivered ssAAV2-STC-1-FLAG to daily topical latanoprost.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Subconjunctival delivery of the STC-1 transgene with a vector system may represent a novel treatment strategy for sustained IOP reduction and improved ocular to","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100590"},"PeriodicalIF":3.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400126X/pdfft?md5=923846108f994b5e9af7245756c01095&pid=1-s2.0-S266691452400126X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239012","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":"Re: Angela S Li et al Gradeability and Reproducibility of Geographic Atrophy Measurement in GATHER-1, a Phase II/III Randomized Interventional Trial","authors":"Siamak Sabour MD, PhD,&nbsp;Fariba Ghassemi MD","doi":"10.1016/j.xops.2024.100567","DOIUrl":"10.1016/j.xops.2024.100567","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 6","pages":"Article 100567"},"PeriodicalIF":3.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001039/pdfft?md5=610b539237d19b6d55b4f8213cb752b4&pid=1-s2.0-S2666914524001039-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961194","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":"Impact of Tumor Pigmentation in 6934 Patients with Uveal Melanoma at a Single Center","authors":"Samuel J. Goldstein BSPH,&nbsp;Ferris Bayasi MD,&nbsp;George Thomas MD,&nbsp;Matthew Barke MD,&nbsp;Michael K. Nguyen BA,&nbsp;Samantha Pastore BS,&nbsp;Carol L. Shields MD","doi":"10.1016/j.xops.2024.100585","DOIUrl":"10.1016/j.xops.2024.100585","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;To evaluate clinical features and outcomes associated with degree of tumor pigmentation in patients with uveal melanoma (UM) of the choroid and ciliary body.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;p&gt;Retrospective observational study.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;p&gt;Six thousand nine hundred thirty-four consecutive patients with choroidal or ciliary body melanoma between 1971 and 2007 from a single ocular oncology center.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Data on patient demographics, tumor characteristics, treatment approach, and clinical outcomes were collected. Comparisons between pigmented (&gt;80% pigmentation by surface area), partially pigmented (20%–80%), and nonpigmented tumors (&lt;20%) were performed using relevant hypothesis testing. Survival analyses for metastasis and melanoma-related death were conducted using the Kaplan–Meier method with log-rank tests for univariate comparisons. A multivariate Cox regression analysis was performed to assess the independent effects of multiple covariates on time-to-metastasis.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;p&gt;Extraocular extension, ocular melanocytosis, time to tumor recurrence, tumor location, and melanoma-related metastasis and death.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;There were 6934 eyes with UM and the degree of tumor pigmentation was classified as pigmented (n = 3762; 54%), partially pigmented (n = 2115; 31%), or nonpigmented (n = 1057; 15%). Pigmented UM was associated with extraocular extension (&lt;em&gt;P&lt;/em&gt; &lt; 0.001), ocular melanocytosis (&lt;em&gt;P&lt;/em&gt; = 0.003), earlier tumor recurrence (&lt;em&gt;P&lt;/em&gt; &lt; 0.001), and more anterior tumor epicenter location (ciliary body, and equator to ora serrata) (&lt;em&gt;P&lt;/em&gt; &lt; 0.001). Pigmented UMs also exhibited the highest 10-year metastasis rate at 26%, compared with 19% for partially pigmented UMs and 16% for nonpigmented UMs (&lt;em&gt;P&lt;/em&gt; &lt; 0.001). Kaplan–Meier survival curves demonstrated differences among the tumor pigmentation groups for melanoma-related metastasis (&lt;em&gt;P&lt;/em&gt; &lt; 0.001) and melanoma-related death (&lt;em&gt;P&lt;/em&gt; &lt; 0.001). Multivariate Cox regression analysis for melanoma-related metastasis showed that pigmented UMs had a 29% higher relative risk of developing metastasis compared with partially pigmented UMs (&lt;em&gt;P&lt;/em&gt; = 0.002) and a 54% higher relative risk of developing metastasis compared with nonpigmented UMs (&lt;em&gt;P&lt;/em&gt; &lt; 0.001).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Pigmented choroidal and ciliary body melanoma is more often associated with ocular melanocytosis, extraocular extension, anterior tumor epicenter, and earlier tumor recurrence. We also revealed that patients with pigmented UMs demonstrate a higher 10-year rate of metastatic disease and have decreased metastatic survival relative to partially pigmented and nonpigmented UMs.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosures&lt;/h3&gt;&lt;p&gt;Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.&lt;/p&gt;&lt;","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 6","pages":"Article 100585"},"PeriodicalIF":3.2,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001210/pdfft?md5=4d655f3e430b8f3aa54879df299e9a92&pid=1-s2.0-S2666914524001210-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141850483","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":"Lens Thickness in Infants and Children with Cataracts","authors":"Libby Wei MD ,&nbsp;Taylor Kolosky ,&nbsp;Sarah Byun ,&nbsp;Alexandra S. Dolgetta MD ,&nbsp;Moran R. Levin MD ,&nbsp;Jana A. Friedman MD ,&nbsp;Monica M. Manrique MD ,&nbsp;Isabelle Dortonne MD ,&nbsp;Camilo Martinez COA ,&nbsp;Marlet Bazemore MD ,&nbsp;Mohamad S. Jaafar MD ,&nbsp;William P. Madigan MD ,&nbsp;Laurence Magder PhD ,&nbsp;Janet L. Alexander MD, MS","doi":"10.1016/j.xops.2024.100588","DOIUrl":"10.1016/j.xops.2024.100588","url":null,"abstract":"<div><h3>Purpose</h3><p>The purpose of this study was to determine the association between lens thickness and cataract in participants aged 0 to 5 years.</p></div><div><h3>Design</h3><p>This was a prospective, multicenter, case–control study.</p></div><div><h3>Participants</h3><p>We enrolled 118 participants (171 eyes) aged 0 to 5 years, mean age 14.6 ± 17.0 months, range 0 to 60 months.</p></div><div><h3>Methods</h3><p>Lens thickness was measured on 342 ultrasound biomicroscopy (UBM) images.</p></div><div><h3>Main Outcome Measures</h3><p>Lens thickness; feasibility of lens thickness measurement from UBM images.</p></div><div><h3>Results</h3><p>The mean lens thickness among noncataracts was 3.60 ± 0.17 mm, compared with 3.16 ± 0.61 mm among cataracts (<em>P</em> &lt; 0.0001). Lens thickness &lt;3.5 mm was significantly associated with increased odds of cataract; adjusted odds ratio = 5.99 (95% confidence interval, 2.41–14.88; <em>P</em> &lt; 0.0003) among participants age 0 to 7 months. Lens thickness was significantly associated with cataract laterality among participants age 0 to 7 months (<em>P</em> &lt; 0.0001).</p></div><div><h3>Conclusions</h3><p>Quantitative UBM can be used to evaluate lens thickness in infants and children with congenital cataracts. The lens in congenital cataract eyes was thinner than that of controls among infants. Abnormal lens thickness was significantly associated with cataract. Future longitudinal studies will examine the association between lens thickness and postcataract surgery outcomes.</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":"5 1","pages":"Article 100588"},"PeriodicalIF":3.2,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001246/pdfft?md5=d926594c5f4edb7fbd5f74572e84042f&pid=1-s2.0-S2666914524001246-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847244","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":"Retinal Microstructural Changes Reflecting Treatment-Associated Cognitive Dysfunction in Patients with Lower-Grade Gliomas","authors":"Arina Nisanova BA ,&nbsp;Ashutosh Parajuli BS ,&nbsp;Bhavna Antony PhD ,&nbsp;Orwa Aboud MD, PhD ,&nbsp;Jinger Sun MD, PhD ,&nbsp;Megan E. Daly MD ,&nbsp;Ruben C. Fragoso MD, PhD ,&nbsp;Glenn Yiu MD, PhD ,&nbsp;Yin Allison Liu MD, PhD","doi":"10.1016/j.xops.2024.100577","DOIUrl":"10.1016/j.xops.2024.100577","url":null,"abstract":"<div><h3>Purpose</h3><p>To determine whether microstructural retinal changes, tumor features, and <em>apolipoprotein E (APOE) ε4</em> polymorphism are correlated with clinically detectable treatment-associated cognitive dysfunction (TACD) in patients with lower-grade gliomas.</p></div><div><h3>Design</h3><p>Cohort study.</p></div><div><h3>Participants and Controls</h3><p>Sixteen patients with lower-grade glioma at a United States academic ophthalmology department between January 2021 and November 2023. Normal controls were recruited from convenient sampling.</p></div><div><h3>Methods</h3><p>Montreal Cognitive Assessment (MoCA) scores and retinal changes were assessed in 6-month intervals. <em>Apolipoprotein E</em> genotyping was performed, and tumor details were recorded. Partial least-squares discriminant (PLSD) model was established to evaluate the association between TACD with <em>APOE</em> genotype, ophthalmic, and tumor features.</p></div><div><h3>Main Outcome Measures</h3><p>The main outcome measure was cognitive status as measured by the MoCA score and analyzed in relation to ophthalmic measurements, tumor features, and <em>APOE</em> genotype.</p></div><div><h3>Results</h3><p>Median time to first eye examination was 34 months (2–266) from tumor diagnosis and 23 months (0–246) from radiation. Nine patients (56%) had abnormal cognition (MoCA &lt;26/30). Montreal Cognitive Assessment scores were significantly worse in patients with temporal (22 ± 7.2) than frontal lobe tumors (26 ± 3.1, <em>P</em> = 0.02) and those with oligodendrogliomas (22 ± 4.1) than astrocytomas (26 ± 3.6, = 0.02). Patients with TACD had significant radial peripapillary capillary density loss (45% ± 4.6) compared with those with normal cognition (49% ± 2.6, <em>P</em> = 0.02). A PLSD model correlated MoCA scores with retinal nerve fiber thickness, intraocular pressure, foveal avascular zone, best-corrected visual acuity, months since first diagnosis, and tumor pathology (oligodendroglioma or not). Using these features, the model identified patients with TACD with 77% accuracy. <em>Apolipoprotein E</em> genotyping showed: 2 <em>ε2/ε3</em> (13%), 10 <em>ε3/ε3</em> (63%)<em>,</em> and 1 <em>ε3/ε4</em> (6%).</p></div><div><h3>Conclusions</h3><p>Retinal microstructural changes may serve as biomarkers for TACD in patients with lower-grade gliomas. Temporal lobe tumors and oligodendrogliomas may increase susceptibility to TACD. Utilization of retinal markers may enhance TACD diagnosis, progression monitoring, and inform management of lower-grade patients with glioma. A larger study with serial eye examinations is warranted to evaluate the role of <em>APOE ε</em>4 and develop a predictive model.</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":"4 6","pages":"Article 100577"},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001131/pdfft?md5=25ad236fa7ec07fef6003a7e446c9ab3&pid=1-s2.0-S2666914524001131-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845125","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":"Safety and Tolerability of Suprachoroidal Axitinib Injectable Suspension, for Neovascular Age-related Macular Degeneration; Phase I/IIa Open-Label, Dose-Escalation Trial","authors":"Mark R. Barakat MD ,&nbsp;David Brown MD ,&nbsp;Allen Hu MD ,&nbsp;Rahul N. Khurana MD ,&nbsp;Dennis Marcus MD ,&nbsp;Joel Pearlman MD, PhD ,&nbsp;Charles C. Wykoff MD, PhD ,&nbsp;Barry Kapik MS ,&nbsp;Thomas Ciulla MD, MBA","doi":"10.1016/j.xops.2024.100586","DOIUrl":"10.1016/j.xops.2024.100586","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the safety and tolerability of a single dose of axitinib injectable suspension (CLS-AX), a pan-anti-VEGF tyrosine kinase inhibitor (TKI), administered via suprachoroidal injection in patients with neovascular age-related macular degeneration (nAMD).</p></div><div><h3>Design</h3><p>Phase I/IIa, open-label, sequential dose escalation.</p></div><div><h3>Participants</h3><p>Anti-VEGF treatment-experienced patients with active subfoveal choroidal neovascularization secondary to nAMD.</p></div><div><h3>Methods</h3><p>The study included 4 cohorts (0.03, 0.10, 0.50, and 1.0 mg) of approximately 5 patients each enrolled in a dose-escalating fashion. Enrolled patients received intravitreal aflibercept (2 mg) followed by a single unilateral dose of CLS-AX 1 month later. All patients were followed monthly for 3 months with the option of an additional 3 months of extended follow-up for cohorts 2 to 4. End points included systemic and ocular safety and tolerability, visual acuity, retinal thickness, and need for aflibercept therapy.</p></div><div><h3>Main Outcome Measures</h3><p>The number of patients reporting treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), changes in ophthalmic examinations, and the number of patients qualifying for additional therapy for nAMD based on protocol-defined criteria.</p></div><div><h3>Results</h3><p>OASIS enrolled 27 patients with nAMD with mean age of 81 years, mean duration of nAMD diagnosis of 54 months, and between 5 and 90 prior anti-VEGF treatments. Twenty-six patients completed through 3 months, with 14 entering and completing the 3-month extension. No SAEs, drug-related TEAEs, or TEAEs leading to discontinuation were observed after CLS-AX administration; there were no adverse events related to ocular inflammation, vasculitis, intraocular pressure, or dispersion of drug into the vitreous or anterior chamber. Through 6 months, stable mean best-corrected visual acuity and stable mean central subfield thickness (CST) were observed, suggestive of TKI biologic effect. No aflibercept therapy was administered up to 3 months in 58% (15/26) of patients who completed 3 months of follow-up in OASIS. In the Extension, 57% (8/14) of patients went up to 6 months without receiving aflibercept therapy.</p></div><div><h3>Conclusions</h3><p>Up to 1.0 mg CLS-AX, a highly potent TKI targeted to the suprachoroidal space (SCS) via the SCS Microinjector, was well tolerated, with stable mean visual acuity and mean CST. A majority of patients followed for 6 months did not require aflibercept therapy.</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":"5 1","pages":"Article 100586"},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001222/pdfft?md5=7f4193eb9e1e0cf90b1d2460ea4427ec&pid=1-s2.0-S2666914524001222-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846467","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":"Estimating Uncertainty of Geographic Atrophy Segmentations with Bayesian Deep Learning","authors":"Theodore Spaide PhD ,&nbsp;Anand E. Rajesh MD ,&nbsp;Nayoon Gim ,&nbsp;Marian Blazes MD ,&nbsp;Cecilia S. Lee MD, MS ,&nbsp;Niranchana Macivannan PhD ,&nbsp;Gary Lee PhD, MEng ,&nbsp;Warren Lewis MS ,&nbsp;Ali Salehi PhD ,&nbsp;Luis de Sisternes PhD ,&nbsp;Gissel Herrera MD ,&nbsp;Mengxi Shen MD, PhD ,&nbsp;Giovanni Gregori PhD ,&nbsp;Philip J. Rosenfeld MD, PhD ,&nbsp;Varsha Pramil MD, MS ,&nbsp;Nadia Waheed MD, MPH ,&nbsp;Yue Wu PhD ,&nbsp;Qinqin Zhang PhD ,&nbsp;Aaron Y. Lee MD, MSCI","doi":"10.1016/j.xops.2024.100587","DOIUrl":"10.1016/j.xops.2024.100587","url":null,"abstract":"<div><h3>Purpose</h3><p>To apply methods for quantifying uncertainty of deep learning segmentation of geographic atrophy (GA).</p></div><div><h3>Design</h3><p>Retrospective analysis of OCT images and model comparison.</p></div><div><h3>Participants</h3><p>One hundred twenty-six eyes from 87 participants with GA in the SWAGGER cohort of the Nonexudative Age-Related Macular Degeneration Imaged with Swept-Source OCT (SS-OCT) study.</p></div><div><h3>Methods</h3><p>The manual segmentations of GA lesions were conducted on structural subretinal pigment epithelium en face images from the SS-OCT images. Models were developed for 2 approximate Bayesian deep learning techniques, Monte Carlo dropout and ensemble, to assess the uncertainty of GA semantic segmentation and compared to a traditional deep learning model.</p></div><div><h3>Main Outcome Measures</h3><p>Model performance (Dice score) was compared. Uncertainty was calculated using the formula for Shannon Entropy.</p></div><div><h3>Results</h3><p>The output of both Bayesian technique models showed a greater number of pixels with high entropy than the standard model. Dice scores for the Monte Carlo dropout method (0.90, 95% confidence interval 0.87–0.93) and the ensemble method (0.88, 95% confidence interval 0.85–0.91) were significantly higher (<em>P</em> &lt; 0.001) than for the traditional model (0.82, 95% confidence interval 0.78–0.86).</p></div><div><h3>Conclusions</h3><p>Quantifying the uncertainty in a prediction of GA may improve trustworthiness of the models and aid clinicians in decision-making. The Bayesian deep learning techniques generated pixel-wise estimates of model uncertainty for segmentation, while also improving model performance compared with traditionally trained deep learning models.</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":"5 1","pages":"Article 100587"},"PeriodicalIF":3.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001234/pdfft?md5=678a9a10974ce3ddf09356f4abea5102&pid=1-s2.0-S2666914524001234-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846967","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":"Comparison of Microperimetry and Static Perimetry for Evaluating Macular Function and Progression in Retinitis Pigmentosa","authors":"Masatoshi Fukushima MD ,&nbsp;Yan Tao MD ,&nbsp;Sakurako Shimokawa MD ,&nbsp;Huanyu Zhao MD ,&nbsp;Shotaro Shimokawa MD, PhD ,&nbsp;Jun Funatsu MD, PhD ,&nbsp;Takahiro Hisai MD ,&nbsp;Ayako Okita MD, PhD ,&nbsp;Kohta Fujiwara MD, PhD ,&nbsp;Toshio Hisatomi MD, PhD ,&nbsp;Atsunobu Takeda MD, PhD ,&nbsp;Yasuhiro Ikeda MD, PhD ,&nbsp;Koh-Hei Sonoda MD, PhD ,&nbsp;Yusuke Murakami MD, PhD","doi":"10.1016/j.xops.2024.100582","DOIUrl":"10.1016/j.xops.2024.100582","url":null,"abstract":"<div><h3>Purpose</h3><p>To compare the usefulness of microperimetry and static automated perimetry in patients with retinitis pigmentosa (RP), using macular anatomical metrics as a reference.</p></div><div><h3>Design</h3><p>Prospective observational study.</p></div><div><h3>Participants</h3><p>Forty-eight eyes of 48 patients with RP in Kyushu University Hospital who underwent microperimetry-3 (MP-3) and Humphrey Field Analyzer (HFA) 10-2 testing ≥3 times during ≥2 years were included.</p></div><div><h3>Methods</h3><p>Macular anatomy (ellipsoid zone [EZ] length) was assessed by OCT, and macular function was assessed by MP-3 (mean retinal sensitivity at radii 2°, 4°, and 8°) and HFA10-2 program (mean retinal sensitivity at radii 2°, 4°, and 8°). Correlations between functional and anatomical parameters were analyzed cross sectionally at baseline and longitudinally by comparing the rate of progression.</p></div><div><h3>Main Outcome Measures</h3><p>Correlation coefficients between anatomical and functional metrics.</p></div><div><h3>Results</h3><p>The mean age at baseline was 50.1 ± 12.3 years, and the mean follow-up period was 2.8 ± 0.7 years. At baseline, EZ length was significantly correlated with MP-3 mean retinal sensitivity at radii 2°, 4°, and 8° (Spearman’s ρ = 0.65, 0.84, 0.89; all <em>P</em> &lt; 0.005) and HFA10-2 mean retinal sensitivity at radii 2°, 4°, and 8° (Spearman’s ρ = 0.61, 0.73, 0.78; all <em>P</em> &lt; 0.005). Longitudinal analysis showed that the slope of EZ length (−88.92 μm/year) was significantly correlated with the slope of MP-3 retinal sensitivity at 8° radius (−0.62 decibels [dB]/year; Spearman’s ρ = 0.31, <em>P</em>=0.03) and the slope of HFA retinal sensitivity at 8° radius (−0.60 dB/year; Spearman’s ρ = 0.43, <em>P</em> &lt; 0.005).</p></div><div><h3>Conclusions</h3><p>Both MP-3 and HFA values were cross sectionally well-correlated with EZ length in patients with patients; however, these associations became weaker in the longitudinal analysis. This highlights the need for researchers to explore additional or more sensitive parameters to better monitor RP progression.</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":"4 6","pages":"Article 100582"},"PeriodicalIF":3.2,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001180/pdfft?md5=c461abfc8bfc9d216d0c70256a7d2651&pid=1-s2.0-S2666914524001180-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141850770","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}