Tianyu Liu MD , Margaret Runner MD , Tamer H. Mahmoud MD, PhD , Antonio Capone Jr. MD , Kimberly A. Drenser MD, PhD , Sandeep Randhawa MD , George A. Williams MD , Lisa J. Faia MD
{"title":"A Modified Intravitreal Methotrexate Protocol for the Prevention of Proliferative Vitreoretinopathy after Silicone Oil Removal","authors":"Tianyu Liu MD , Margaret Runner MD , Tamer H. Mahmoud MD, PhD , Antonio Capone Jr. MD , Kimberly A. Drenser MD, PhD , Sandeep Randhawa MD , George A. Williams MD , Lisa J. Faia MD","doi":"10.1016/j.oret.2024.10.006","DOIUrl":"10.1016/j.oret.2024.10.006","url":null,"abstract":"<div><h3>Objective</h3><div>To utilize a modified intravitreal (IVT) methotrexate (MTX) protocol for the prevention of proliferative vitreoretinopathy (PVR) after silicone oil (SO) removal (SOR).</div></div><div><h3>Design</h3><div>Single-center nonrandomized retrospective comparative case series.</div></div><div><h3>Subjects</h3><div>Eyes with grade C PVR who underwent retinal detachment (RD) repair and SO placement between 2019 and 2022 with ≥6 months of follow-up after SOR. A control group of age- and sex-matched eyes was included.</div></div><div><h3>Methods</h3><div>Eyes were treated with 1 of 2 MTX protocols. Eyes in Group 1 received 6 IVT MTX injections after SO placement and another 6 IVT MTX injections after SOR. Eyes in Group 2 received 6 IVT MTX after SO placement only. Each series of 6 IVT MTX injections (400 μg/0.1 mL) consisted of 3 injections every 2 weeks followed by 3 injections every 4 weeks.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome was the retinal attachment rate at 6 months post-SOR without redetachment or reoperation. Secondary outcomes included change in visual acuity and rates of complications after SOR.</div></div><div><h3>Results</h3><div>Fifty-two eyes of 52 patients (13 Group 1, 13 Group 2, 26 control) (mean age 59.8 years, 80.8% male) were included with a mean follow-up of 31.0 months. In aggregate, Group 1 and Group 2 eyes received a median (interquartile range [IQR]) of 6 (5.25, 7) IVT MTX injections pre-SOR; eyes in Group 1 received a median (IQR) of 5 (3, 6) IVT MTX injections post-SOR. Twelve (92.3%) Group 1 eyes, 11 (84.6%) Group 2 eyes, and 21 (80.8%) control eyes had primary retinal attachment at 6 months post-SOR (<em>P</em> > 0.05). Visual acuity outcomes did not significantly differ between groups (<em>P</em> > 0.05). Rates of epiretinal membrane (ERM) and cystoid macular edema (CME) were significantly lower in Group 1 eyes (7.7% and 15.4%) compared with Group 2 (53.8% and 92.3%) and control (44.3% and 65.4%) eyes, respectively (<em>P</em> < 0.05).</div></div><div><h3>Conclusions</h3><div>The use of IVT MTX injections in eyes with PVR undergoing RD repair was associated with a high rate of primary retinal attachment after SOR. Eyes that received IVT MTX injections after SOR had significantly lower rates of ERM and CME than eyes that did not.</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":19501,"journal":{"name":"Ophthalmology. Retina","volume":"9 4","pages":"Pages 314-321"},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471481","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}
Ankur Nahar BS , Dean Eliott MD , Robert L. Avery MD , Jose Pulido MD , Ralph C. Eagle Jr. MD , Jacqueline R. Carrasco MD , Courtney Crawford MD , Tatyana Milman MD , Anna M. Stagner MD
{"title":"Retinal Vasculopathy and Choroiditis after Pegcetacoplan Injection","authors":"Ankur Nahar BS , Dean Eliott MD , Robert L. Avery MD , Jose Pulido MD , Ralph C. Eagle Jr. MD , Jacqueline R. Carrasco MD , Courtney Crawford MD , Tatyana Milman MD , Anna M. Stagner MD","doi":"10.1016/j.oret.2024.10.005","DOIUrl":"10.1016/j.oret.2024.10.005","url":null,"abstract":"<div><h3>Purpose</h3><div>To report the detailed histopathology of 2 enucleated eyes from 2 patients who developed severe visual loss associated with retinal hemorrhages, vessel sheathing, and vascular nonperfusion after administration of an initial dose of intravitreal pegcetacoplan, and propose, with supportive histopathology, the pathogenesis of the clinical syndrome previously termed hemorrhagic occlusive retinal vasculitis.</div></div><div><h3>Design</h3><div>Case series.</div></div><div><h3>Subjects</h3><div>Two enucleated eyes from 2 patients treated with intravitreal pegcetacoplan.</div></div><div><h3>Methods</h3><div>Retrospective, multicenter, consecutive clinical-pathologic analysis.</div></div><div><h3>Main Outcome Measures</h3><div>Histopathologic review and immunophenotypic characterization.</div></div><div><h3>Results</h3><div>Both patients presented with inflammation and significant vision loss 9 days after the initial injection of pegcetacoplan with no subsequent improvement and underwent enucleation for pain control. Histologic examination of the enucleated eyes (patient 1 at 4 months postinjection and patient 2 at 40 days) revealed extensive vascular thrombosis, retinal hemorrhages and necrosis, and a dense inflammatory infiltrate in the uvea and, variably, the optic nerve, episclera, and muscle tendons composed of predominantly of T cells, macrophages, and eosinophils. Notably, the inflammatory infiltrate was absent from the retina. In addition, 1 eye demonstrated multiple foci of glomerular-like vascular proliferations in the uveal tract and thrombosis with focal recanalization of vessels in the optic nerve.</div></div><div><h3>Conclusions</h3><div>Drug-induced, immune-mediated, retinal vasculopathy and choroiditis (DIRVAC) is a rare complication after pegcetacoplan injection. Although some limitations arise in interpretation of histopathologic findings because of compensatory changes in the eyes over time (before enucleation), the authors propose that the combined clinical, histopathologic, and immunohistochemical findings suggest a mixed-type, delayed hypersensitivity reaction as the mechanism of initial injury.</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":19501,"journal":{"name":"Ophthalmology. Retina","volume":"9 4","pages":"Pages 352-366"},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471485","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 Meta-analysis for Myopic Macular Neovascularization Identified a Novel Susceptibility Locus and Revealed a Shared Genetic Susceptibility with Age-Related Macular Degeneration","authors":"Kazuya Morino MD , Masahiro Miyake MD, PhD , Masao Nagasaki PhD , Takahisa Kawaguchi PhD , Shogo Numa MD, PhD , Yuki Mori MD, PhD , Shota Yasukura MD , Masahiro Akada MD , Shin-Ya Nakao MD , Ai Nakata MD , Hiroki Hashimoto BS , Ryoko Otokozawa BAgr , Koju Kamoi MD, PhD , Hiroyuki Takahashi MD, PhD , Yasuharu Tabara PhD , Fumihiko Matsuda PhD , Kyoko Ohno-Matsui MD, PhD , Akitaka Tsujikawa MD, PhD","doi":"10.1016/j.oret.2024.09.016","DOIUrl":"10.1016/j.oret.2024.09.016","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify the susceptibility loci for myopic macular neovascularization (mMNV) in patients with high myopia.</div></div><div><h3>Design</h3><div>A genome-wide association study (GWAS) meta-analysis (meta-GWAS).</div></div><div><h3>Participants</h3><div>We included 2783 highly myopic individuals, including 608 patients with mMNV and 2175 control participants without mMNV.</div></div><div><h3>Methods</h3><div>We performed a meta-analysis of 3 independent GWASs conducted according to the genotyping platform (Illumina Asian Screening Array [ASA] data set, Illumina Human610 BeadChip [610K] data set, and whole genome sequencing [WGS] data set), adjusted for age, sex, axial length, and the first to third principal components. We used DeltaSVM to evaluate the binding affinity of transcription factors (TFs) to DNA sequences around the susceptibility of single nucleotide polymorphisms (SNPs). In addition, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci.</div></div><div><h3>Main Outcome Measures</h3><div>The association between SNPs and mMNV in patients with high myopia.</div></div><div><h3>Results</h3><div>The meta-GWAS identified rs56257842 at <em>TEX29</em> <em>- LINC02337</em> as a novel susceptibility SNP for mMNV (odds ratio [OR]<sub>meta</sub> = 0.62, <em>P</em><sub>meta</sub> = 4.63 × 10<sup>−8</sup>, I<sup>2</sup> = 0.00), which was consistently associated with mMNV in all data sets (OR<sub>ASA</sub> = 0.59, <em>P</em><sub>ASA</sub> = 1.71 × 10<sup>−4</sup>; OR<sub>610K</sub> = 0.63, <em>P</em><sub>610K</sub> = 5.53 × 10<sup>−4</sup>; OR<sub>WGS</sub> = 0.66, <em>P</em><sub>WGS</sub> = 4.38 × 10<sup>−2</sup>). Transcription factor-wide analysis showed that the TFs ZNF740 and EGR1 lost their binding affinity to this locus when rs56257842 had the C allele (alternative allele), and the WNT signaling-related TF ZBTB33 gained binding affinity when rs56257842 had the C allele. When we examined the associations of AMD susceptibility loci, rs12720922 at <em>CETP</em> showed a statistically significant association with mMNV (OR<sub>meta</sub> = 0.52, <em>P</em><sub>meta</sub> = 1.55 × 10<sup>−5</sup>), whereas rs61871745 near <em>ARMS2</em> showed a marginal association (OR<sub>meta</sub> = 1.25, <em>P</em><sub>meta</sub> = 7.79 × 10<sup>−3</sup>).</div></div><div><h3>Conclusions</h3><div>Our study identified a novel locus associated with mMNV in high myopia. Subsequent analyses offered important insights into the molecular biology of mMNV, providing the potential therapeutic targets for mMNV. Furthermore, our findings imply shared genetic susceptibility between mMNV and AMD.</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":19501,"journal":{"name":"Ophthalmology. Retina","volume":"9 4","pages":"Pages 367-377"},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569252","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":"Bilateral Retinocytoma in a Child: A Rare Presentation","authors":"Vijitha S. Vempuluru MD, Swathi Kaliki MD","doi":"10.1016/j.oret.2024.08.016","DOIUrl":"10.1016/j.oret.2024.08.016","url":null,"abstract":"","PeriodicalId":19501,"journal":{"name":"Ophthalmology. Retina","volume":"9 4","pages":"Page e35"},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292679","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}
Srikanta Kumar Padhy MD , Deepika C. Parameswarappa MS , Sumant Sharma MD , Tapas Ranjan Padhi MS , Subhadra Jalali MS , Brijesh Takkar MD , Raja Narayanan MS
{"title":"Widefield Retinal Imaging in Gyrate Atrophy","authors":"Srikanta Kumar Padhy MD , Deepika C. Parameswarappa MS , Sumant Sharma MD , Tapas Ranjan Padhi MS , Subhadra Jalali MS , Brijesh Takkar MD , Raja Narayanan MS","doi":"10.1016/j.oret.2024.10.016","DOIUrl":"10.1016/j.oret.2024.10.016","url":null,"abstract":"<div><h3>Objective</h3><div>To profile a cohort of gyrate atrophy patients classified by widefield retinal imaging and correlate the structural, biochemical, and functional characteristics.</div></div><div><h3>Design</h3><div>Retrospective observational cohort study.</div></div><div><h3>Participants</h3><div>Sixty-five patients (129 eyes) with gyrate atrophy.</div></div><div><h3>Methods</h3><div>Data of participants with a diagnosis of gyrate atrophy were retrieved from their electronic medical records (January 2015 to December 2023). Retinal involvement was classified into 3 zones using widefield retinal images. Zone 3 had atrophic patches in the area anterior to the equator; zone 2 had involvement limited to the arcades but posterior to the equator; zone 1 had involvement within the vascular arcades and/or peripapillary region, with or without any other zone involvement. Macular assessment was performed using swept-source OCT (n = 104). Flash electroretinogram (ERG) was performed in 40 eyes. Serum ornithine levels (n = 35) were measured, and genetic analysis was conducted (n = 18).</div></div><div><h3>Main Outcome Measures</h3><div>Demography, patient profile, zone of retina involved, macular features, and serum ornithine levels.</div></div><div><h3>Results</h3><div>The average age at presentation was 26.4 (range, 5–67) years; the majority were male. Nyctalopia (n = 35, 53.8%) and blurred vision (n = 29, 44.6%) were the most common symptoms. Positive family history was reported in 32.3% of patients. Most eyes were myopic (69.8% <−3 diopters). Posterior subcapsular cataracts were documented in 36.4% of eyes. The highest frequency of retinal area affected was zone 1 (57.14%), followed by zone 2 (33.33%) and zone 3 (9.52%), correlating with the age at presentation. Foveoschisis was observed in 57.7% of eyes, with a higher prevalence in eyes with zone 1 disease. Elevated serum ornithine levels (>163 μmol/L) were found in 77.14% of patients. The ERG showed nonrecordable (n = 32) or severely reduced (n = 8) responses in scotopic and photopic phases. Genetic analysis of 18 patients identified mutations in the <em>OAT</em> gene, including a novel missense variant (c.290T>C).</div></div><div><h3>Conclusions</h3><div>This large cohort of patients with gyrate atrophy revealed symmetrical involvement, predominantly in zone 1. Most patients presented between the first and third decades, experienced nyctalopia, vision reduction, early posterior subcapsular cataracts, and varying degrees of myopia. Zone 1 involvement was strongly associated with foveoschisis and visual compromise.</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":19501,"journal":{"name":"Ophthalmology. Retina","volume":"9 4","pages":"Pages 392-401"},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505232","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}