Importance Appropriately sized and well-centered capsulorhexis is key for high-quality phacoemulsification cataract surgery and can be achieved with digital-guidance devices. However, such devices are not readily available, warranting the need for a device-free manual auxiliary capsulorhexis technique. Objectives To determine if manual marking–assisted capsulorhexis (MMAC) is noninferior to a digital guidance–assisted capsulorhexis (DGAC) in capsulorhexis accuracy following phacoemulsification for age-related cataract. Design, Setting, and Participants This noninferiority randomized clinical trial was conducted between July 2021 and December 2021 at Zhongshan Ophthalmic Center, China, with follow-up through 1 month after surgery. Of 204 adults screened, 156 were included who were aged 55 to 80 years and had pupil diameter ≥6.5 mm after pupil dilation and Lens Opacities Classification System III with nuclear opalescence grade of 3.0 to 4.0. Patients were excluded if they had previous intraocular surgery or a diagnosed eye disease that might affect functions of lens suspensory ligament. Data were analyzed from September to December 2024. Interventions In the MMAC group, a lens caliper was used to measure and locate capsulorhexis position, subsequently applying its blunt head to mark the anterior lens capsule for capsulotomy guidance. In the DGAC group, a ring with predefined target diameter was projected to guide capsulorhexis. Main Outcomes and Measures The primary outcome was the median deviation of capsulorhexis diameter from the target diameter with a noninferiority margin of 0.2 mm. Secondary outcomes included ratio of ideal capsulorhexis, grades of capsulorhexis–intraocular lens (IOL) overlap, off-center distance of capsulorhexis, postoperative best-corrected visual acuity, IOL tilt, and decentration. Results Among 156 participants randomized into the MMAC group (mean [SD] age, 71 [7] years; 47 [60%] female) or DGAC group (mean [SD] age, 72 [7]; 47 [60%] female), median deviations comparing the capsulorhexis and target diameters were 0.22 mm (95% CI, 0.11-0.37) in the MMAC group vs 0.27 mm (95% CI, 0.14-0.52) in the DGAC group (difference, −0.05 mm; 95% CI, −0.16 to 0.07) for horizontal diameter and 0.27 mm (95% CI, 0.12-0.40) vs 0.33 mm (95% CI, 0.20-0.51) (difference, −0.06 mm; 95% CI, −0.17 to 0.05), respectively, for vertical diameters, both within the noninferiority margin of 0.20 mm. The proportion of ideal capsulorhexis was 96.2% (75 of 78) in the MMAC group and 88.5% (69 of 78) in the DGAC group (difference, 7.7%; 95% CI, −0.6 to 16.0), also within the noninferiority margin of −5.0%. Conclusions and Relevance The findings in this trial indicate that accuracy of capsulorhexis with MMAC was noninferior to DGAC. Since the MMAC technique does not require special equipment, it might be considered routinely in clinical practice settings if similar outcomes are obtained elsewhere. Trial Registration ClinicalTrials.gov Identifier:
{"title":"Manual Marking Guidance vs Digital Guidance System–Assisted Capsulorhexis in Phacoemulsification","authors":"Xiaoyun Chen, Zitian Liu, Ling Jin, Yingfeng Zheng, Lixia Luo, Yizhi Liu","doi":"10.1001/jamaophthalmol.2025.4448","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.4448","url":null,"abstract":"Importance Appropriately sized and well-centered capsulorhexis is key for high-quality phacoemulsification cataract surgery and can be achieved with digital-guidance devices. However, such devices are not readily available, warranting the need for a device-free manual auxiliary capsulorhexis technique. Objectives To determine if manual marking–assisted capsulorhexis (MMAC) is noninferior to a digital guidance–assisted capsulorhexis (DGAC) in capsulorhexis accuracy following phacoemulsification for age-related cataract. Design, Setting, and Participants This noninferiority randomized clinical trial was conducted between July 2021 and December 2021 at Zhongshan Ophthalmic Center, China, with follow-up through 1 month after surgery. Of 204 adults screened, 156 were included who were aged 55 to 80 years and had pupil diameter ≥6.5 mm after pupil dilation and Lens Opacities Classification System III with nuclear opalescence grade of 3.0 to 4.0. Patients were excluded if they had previous intraocular surgery or a diagnosed eye disease that might affect functions of lens suspensory ligament. Data were analyzed from September to December 2024. Interventions In the MMAC group, a lens caliper was used to measure and locate capsulorhexis position, subsequently applying its blunt head to mark the anterior lens capsule for capsulotomy guidance. In the DGAC group, a ring with predefined target diameter was projected to guide capsulorhexis. Main Outcomes and Measures The primary outcome was the median deviation of capsulorhexis diameter from the target diameter with a noninferiority margin of 0.2 mm. Secondary outcomes included ratio of ideal capsulorhexis, grades of capsulorhexis–intraocular lens (IOL) overlap, off-center distance of capsulorhexis, postoperative best-corrected visual acuity, IOL tilt, and decentration. Results Among 156 participants randomized into the MMAC group (mean [SD] age, 71 [7] years; 47 [60%] female) or DGAC group (mean [SD] age, 72 [7]; 47 [60%] female), median deviations comparing the capsulorhexis and target diameters were 0.22 mm (95% CI, 0.11-0.37) in the MMAC group vs 0.27 mm (95% CI, 0.14-0.52) in the DGAC group (difference, −0.05 mm; 95% CI, −0.16 to 0.07) for horizontal diameter and 0.27 mm (95% CI, 0.12-0.40) vs 0.33 mm (95% CI, 0.20-0.51) (difference, −0.06 mm; 95% CI, −0.17 to 0.05), respectively, for vertical diameters, both within the noninferiority margin of 0.20 mm. The proportion of ideal capsulorhexis was 96.2% (75 of 78) in the MMAC group and 88.5% (69 of 78) in the DGAC group (difference, 7.7%; 95% CI, −0.6 to 16.0), also within the noninferiority margin of −5.0%. Conclusions and Relevance The findings in this trial indicate that accuracy of capsulorhexis with MMAC was noninferior to DGAC. Since the MMAC technique does not require special equipment, it might be considered routinely in clinical practice settings if similar outcomes are obtained elsewhere. Trial Registration ClinicalTrials.gov Identifier: <jats:ext-l","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"53 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Importance Primary congenital glaucoma (PCG) surgery often leaves residual visual impairment in children. Evidence comparing rigid gas-permeable contact lenses (RGPCLs) vs spectacles for rehabilitation is needed. Objective To compare the use of RGPCLs vs continued spectacle wear for improving visual outcomes for children after PCG surgery. Design, Setting, and Participants This randomized clinical trial was conducted at Zhongshan Ophthalmic Center, a tertiary referral center in Guangzhou, China, from April 21, 2022, to August 21, 2023. Participants comprised 56 children (aged 4-15 years) with surgically managed PCG and poor spectacle response. Data were analyzed from October 11, 2023, to March 21, 2024. Interventions RGPCLs (n = 29) vs spectacles (n = 27) for 12 months, plus standardized amblyopia patching. Main Outcomes and Measures The primary outcome was change in worse-eye best-corrected visual acuity (BCVA) at 12 months measured by the Early Treatment Diabetic Retinopathy Study chart with tumbling-E optotypes with children wearing their current best refractive correction. Secondary outcomes included contrast sensitivity function and near stereoacuity. Results Among 56 (of a total of 83 screened participants) randomized participants, 48 (85.7%) completed at least 1 follow-up visit and were included in the primary analysis. Baseline demographic and ocular characteristics for the RGPCL group vs the spectacles group included a mean (SD) age of 7.7 (2.7) vs 7.2 (3.2) years, 13 (54.2%) vs 14 (58.3%) male, and 11 (45.8%) vs 10 (41.7%) female. At 12 months, 22 of 29 participants (76.0%) in the RGPCL group and 19 of 27 participants (70.4%) in the spectacles group completed the final visit. The mean (SD) baseline worse-eye spherical equivalent was −6.55 (6.43) vs −5.17 (5.27) diopters, the mean (SD) BCVA was 0.99 (0.71) vs 1.02 (0.74) logMAR (approximate Snellen equivalent 20/200), and the mean (SD) intraocular pressure was 14.98 (3.14) vs 13.36 (3.92) mm Hg in the RGPCL vs the spectacles group, respectively. At 1 year, the RGPCL group had greater BCVA improvement (mean [SD], 0.31 [0.28] vs 0.12 [0.33] logMAR; adjusted treatment difference, −0.19 logMAR; 95% CI, −0.36 to −0.02 logMAR [approximately 10 letters]; <jats:italic>P</jats:italic> = .03). Achievement of 2 or more lines of BCVA improvement occurred in 15 of 24 participants (62.5%) in the RGPCL group vs 9 of 24 participants (37.5%) in the spectacles group (odds ratio, 6.83; 95% CI, 1.81-25.73; <jats:italic>P</jats:italic> = .01). The RGPCL group had greater contrast sensitivity function improvement (0.40 [0.27] vs 0.13 [0.32]; adjusted treatment difference, 0.24 log units; 95% CI, −0.01 to 0.49; <jats:italic>P</jats:italic> = .04). Near stereoacuity of 60 arcseconds or less was achieved by 12 participants (50.0%) vs 6 of 24 participants (25.0%) (odds ratio, 6.96; 95% CI, 2.41-6.51; <jats:italic>P</jats:italic> = .001). No serious adverse events occurred. Conclusions and Relevance These findings
{"title":"Visual Outcomes of Children With Primary Congenital Glaucoma Receiving Different Refractive Corrections","authors":"Jinyun Jiang, Yin Hu, Yingting Zhu, Yimin Zhong, Chuqi Xiang, Shuoshuo Chen, Mengting Yu, Lei Fang, Shufen Lin, Xianghua Tang, Mingxin Lu, Weiyin Chen, Ling Jin, Xing Liu, Xiao Yang","doi":"10.1001/jamaophthalmol.2025.3976","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.3976","url":null,"abstract":"Importance Primary congenital glaucoma (PCG) surgery often leaves residual visual impairment in children. Evidence comparing rigid gas-permeable contact lenses (RGPCLs) vs spectacles for rehabilitation is needed. Objective To compare the use of RGPCLs vs continued spectacle wear for improving visual outcomes for children after PCG surgery. Design, Setting, and Participants This randomized clinical trial was conducted at Zhongshan Ophthalmic Center, a tertiary referral center in Guangzhou, China, from April 21, 2022, to August 21, 2023. Participants comprised 56 children (aged 4-15 years) with surgically managed PCG and poor spectacle response. Data were analyzed from October 11, 2023, to March 21, 2024. Interventions RGPCLs (n = 29) vs spectacles (n = 27) for 12 months, plus standardized amblyopia patching. Main Outcomes and Measures The primary outcome was change in worse-eye best-corrected visual acuity (BCVA) at 12 months measured by the Early Treatment Diabetic Retinopathy Study chart with tumbling-E optotypes with children wearing their current best refractive correction. Secondary outcomes included contrast sensitivity function and near stereoacuity. Results Among 56 (of a total of 83 screened participants) randomized participants, 48 (85.7%) completed at least 1 follow-up visit and were included in the primary analysis. Baseline demographic and ocular characteristics for the RGPCL group vs the spectacles group included a mean (SD) age of 7.7 (2.7) vs 7.2 (3.2) years, 13 (54.2%) vs 14 (58.3%) male, and 11 (45.8%) vs 10 (41.7%) female. At 12 months, 22 of 29 participants (76.0%) in the RGPCL group and 19 of 27 participants (70.4%) in the spectacles group completed the final visit. The mean (SD) baseline worse-eye spherical equivalent was −6.55 (6.43) vs −5.17 (5.27) diopters, the mean (SD) BCVA was 0.99 (0.71) vs 1.02 (0.74) logMAR (approximate Snellen equivalent 20/200), and the mean (SD) intraocular pressure was 14.98 (3.14) vs 13.36 (3.92) mm Hg in the RGPCL vs the spectacles group, respectively. At 1 year, the RGPCL group had greater BCVA improvement (mean [SD], 0.31 [0.28] vs 0.12 [0.33] logMAR; adjusted treatment difference, −0.19 logMAR; 95% CI, −0.36 to −0.02 logMAR [approximately 10 letters]; <jats:italic>P</jats:italic> = .03). Achievement of 2 or more lines of BCVA improvement occurred in 15 of 24 participants (62.5%) in the RGPCL group vs 9 of 24 participants (37.5%) in the spectacles group (odds ratio, 6.83; 95% CI, 1.81-25.73; <jats:italic>P</jats:italic> = .01). The RGPCL group had greater contrast sensitivity function improvement (0.40 [0.27] vs 0.13 [0.32]; adjusted treatment difference, 0.24 log units; 95% CI, −0.01 to 0.49; <jats:italic>P</jats:italic> = .04). Near stereoacuity of 60 arcseconds or less was achieved by 12 participants (50.0%) vs 6 of 24 participants (25.0%) (odds ratio, 6.96; 95% CI, 2.41-6.51; <jats:italic>P</jats:italic> = .001). No serious adverse events occurred. Conclusions and Relevance These findings","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"38 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1001/jamaophthalmol.2025.4031
Jonathan Meinke, Kristin Raming, Carolina Kessler, Frank G. Holz, Maximilian Pfau, Kristina Pfau
Importance Pseudoxanthoma elasticum (PXE) is a rare inherited disorder marked by progressive calcification of Bruch membrane (BrM). Characteristic retinal features, such as peau d’orange and continuously calcified BrM (also called coquille d’œuf ), reflect disease severity but lack reliable in vivo cross-sectional imaging correlates. Objective To identify high-resolution optical coherence tomography (HR-OCT) correlates of peau d’orange and continuously calcified BrM in patients with PXE. Design, Setting, and Participants This prospective case-control study was conducted at the Department of Ophthalmology, University Hospital, Bonn, Germany. HR-OCT imaging was performed in 37 eyes from 22 patients with PXE and 28 eyes from 16 healthy control participants between November 2024 and March 2025. These data were analyzed March 2025 to May 2025. Exposures Diagnosis of PXE based on clinical and genetic criteria. Healthy eyes served as controls. HR-OCT (axial resolution up to 3 μm) was measured in all study eyes. Main Outcomes and Measures Identification of structural alterations in the retinal pigment epithelium (RPE)/BrM complex on HR-OCT that corresponded to peau d’orange or continuous BrM calcification visible on fundus photography and infrared imaging. Results A total of 42 eyes from 22 patients with PXE (mean age, 50.2 [SD, 13.6] years; range 25.4-77.9 years; 13 female and 9 male) and 28 healthy eyes from 16 control study participants (mean age, 56.4 [SD, 16.8] years; range 23.5-78.6 years; 11 female and 5 male) were examined. HR-OCT imaging revealed a consistent structural transition within peau d’orange zones: from a multilayered RPE/BrM complex, including distinct outer segment interdigitation zone and RPE bands, in unaffected retina to a condensed, hyperreflective monolayer overlying BrM, with hyporeflective separation. In more advanced disease, additional changes included BrM breaks, irregular RPE morphology, reticular pseudodrusen, and serous neurosensory retinal detachment in the absence of macular neovascularization. These features were absent in control eyes (0 of 28). In eyes with type 1 macular neovascularization, layer splitting confirmed anatomical identification of the RPE and BrM. Angioid streaks on fundus imaging corresponded to focal BrM disruptions on HR-OCT. Conclusions and Relevance This study demonstrated that HR-OCT can identify distinct in vivo correlates of Bruch membrane calcification in PXE. The observed transition from multilayered to monolayer RPE/BrM architecture with accompanying hyporeflective separation may serve as a sensitive imaging biomarker of disease progression in future clinical trials. These findings support HR-OCT as a valuable tool for diagnosis, monitoring, and clinical trial end point development in PXE.
{"title":"High-Resolution Optical Coherence Tomography Correlates of Peau d’Orange in Pseudoxanthoma Elasticum","authors":"Jonathan Meinke, Kristin Raming, Carolina Kessler, Frank G. Holz, Maximilian Pfau, Kristina Pfau","doi":"10.1001/jamaophthalmol.2025.4031","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.4031","url":null,"abstract":"Importance Pseudoxanthoma elasticum (PXE) is a rare inherited disorder marked by progressive calcification of Bruch membrane (BrM). Characteristic retinal features, such as peau d’orange and continuously calcified BrM (also called <jats:italic toggle=\"yes\">coquille d’œuf</jats:italic> ), reflect disease severity but lack reliable in vivo cross-sectional imaging correlates. Objective To identify high-resolution optical coherence tomography (HR-OCT) correlates of peau d’orange and continuously calcified BrM in patients with PXE. Design, Setting, and Participants This prospective case-control study was conducted at the Department of Ophthalmology, University Hospital, Bonn, Germany. HR-OCT imaging was performed in 37 eyes from 22 patients with PXE and 28 eyes from 16 healthy control participants between November 2024 and March 2025. These data were analyzed March 2025 to May 2025. Exposures Diagnosis of PXE based on clinical and genetic criteria. Healthy eyes served as controls. HR-OCT (axial resolution up to 3 μm) was measured in all study eyes. Main Outcomes and Measures Identification of structural alterations in the retinal pigment epithelium (RPE)/BrM complex on HR-OCT that corresponded to peau d’orange or continuous BrM calcification visible on fundus photography and infrared imaging. Results A total of 42 eyes from 22 patients with PXE (mean age, 50.2 [SD, 13.6] years; range 25.4-77.9 years; 13 female and 9 male) and 28 healthy eyes from 16 control study participants (mean age, 56.4 [SD, 16.8] years; range 23.5-78.6 years; 11 female and 5 male) were examined. HR-OCT imaging revealed a consistent structural transition within peau d’orange zones: from a multilayered RPE/BrM complex, including distinct outer segment interdigitation zone and RPE bands, in unaffected retina to a condensed, hyperreflective monolayer overlying BrM, with hyporeflective separation. In more advanced disease, additional changes included BrM breaks, irregular RPE morphology, reticular pseudodrusen, and serous neurosensory retinal detachment in the absence of macular neovascularization. These features were absent in control eyes (0 of 28). In eyes with type 1 macular neovascularization, layer splitting confirmed anatomical identification of the RPE and BrM. Angioid streaks on fundus imaging corresponded to focal BrM disruptions on HR-OCT. Conclusions and Relevance This study demonstrated that HR-OCT can identify distinct in vivo correlates of Bruch membrane calcification in PXE. The observed transition from multilayered to monolayer RPE/BrM architecture with accompanying hyporeflective separation may serve as a sensitive imaging biomarker of disease progression in future clinical trials. These findings support HR-OCT as a valuable tool for diagnosis, monitoring, and clinical trial end point development in PXE.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"3 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1001/jamaophthalmol.2025.4214
John Placide, Sirichai Pasadhika
A previously healthy 31-year-old woman presents with acute unilateral anterior uveitis with hypopyon and an iris lesion and systemic symptoms, including headache, fatigue, and fever. What would you do next?
{"title":"Acute Unilateral Uveitis With Hypopyon and an Iris Lesion","authors":"John Placide, Sirichai Pasadhika","doi":"10.1001/jamaophthalmol.2025.4214","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.4214","url":null,"abstract":"A previously healthy 31-year-old woman presents with acute unilateral anterior uveitis with hypopyon and an iris lesion and systemic symptoms, including headache, fatigue, and fever. What would you do next?","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"78 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1001/jamaophthalmol.2025.4243
Paula Gish, Ivone Kim, Rachna Kapoor, S. Christopher Jones
Importance Apraclonidine, a topical α-2 adrenergic agonist, reverses anisocoria in patients with Horner syndrome, a disruption of the sympathetic chain to 1 eye and side of the face. In pediatric patients with anisocoria, apraclonidine is used off-label to exclude Horner syndrome. Objective To identify and characterize postmarketing case reports reported to the US Food and Drug Administration and reported in the medical literature of systemic toxicity in pediatric patients administered apraclonidine ophthalmic drops. Design, Setting, and Participants A search of the US Food and Drug Administration’s Adverse Event Reporting System and the medical literature was conducted from approval to September 18, 2024, for reports describing adverse events in pediatric patients who received apraclonidine ophthalmic drops. Participants included 21 children who developed systemic adverse events associated with use of apraclonidine ophthalmic drops. These data were analyzed from September 2024 to March 2025. Exposure Apraclonidine ophthalmic drops. Main outcomes and measures Reports describing nonsystemic adverse events, accidental oral ingestion, or duplicate reports for the same patient, and reports whose causal association with apraclonidine was unassessable, unclassifiable, or unlikely based on the World Health Organization–Uppsala Monitoring Center system were excluded. The assessment included demographic information, reason for use, concomitant medications, dose, latency, medical intervention, and outcome information. Results This case series included 21 patients (aged 12 days to 6 years; median age, 6 months) who developed systemic adverse events associated with use of apraclonidine ophthalmic drops. The most commonly reported adverse event was prolonged lethargy and unresponsiveness (17 of 21 [81%]) followed by clinically significant cardiorespiratory events (eg, apnea, hypoxia, bradycardia, blood pressure changes, or respiratory failure) (8 of 21 [38%]). Three cases required intubation. Most cases (16 of 21 [76%]) described patients younger than 1 year. The reason for use in most (12 of 16 [75%]) patients younger than 1 year was for diagnostic purposes. Conclusions and Relevance This case series suggests use of apraclonidine in pediatric patients poses a risk of central α-2 adrenergic agonist–induced central nervous system and respiratory depression. Clinicians who use apraclonidine in the pediatric population should be aware of potential serious systemic effects from ophthalmic use of the drug and be prepared to manage these.
{"title":"Systemic Toxicity With Use of Apraclonidine Ophthalmic Drops in Pediatric Patients","authors":"Paula Gish, Ivone Kim, Rachna Kapoor, S. Christopher Jones","doi":"10.1001/jamaophthalmol.2025.4243","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.4243","url":null,"abstract":"Importance Apraclonidine, a topical α-2 adrenergic agonist, reverses anisocoria in patients with Horner syndrome, a disruption of the sympathetic chain to 1 eye and side of the face. In pediatric patients with anisocoria, apraclonidine is used off-label to exclude Horner syndrome. Objective To identify and characterize postmarketing case reports reported to the US Food and Drug Administration and reported in the medical literature of systemic toxicity in pediatric patients administered apraclonidine ophthalmic drops. Design, Setting, and Participants A search of the US Food and Drug Administration’s Adverse Event Reporting System and the medical literature was conducted from approval to September 18, 2024, for reports describing adverse events in pediatric patients who received apraclonidine ophthalmic drops. Participants included 21 children who developed systemic adverse events associated with use of apraclonidine ophthalmic drops. These data were analyzed from September 2024 to March 2025. Exposure Apraclonidine ophthalmic drops. Main outcomes and measures Reports describing nonsystemic adverse events, accidental oral ingestion, or duplicate reports for the same patient, and reports whose causal association with apraclonidine was unassessable, unclassifiable, or unlikely based on the World Health Organization–Uppsala Monitoring Center system were excluded. The assessment included demographic information, reason for use, concomitant medications, dose, latency, medical intervention, and outcome information. Results This case series included 21 patients (aged 12 days to 6 years; median age, 6 months) who developed systemic adverse events associated with use of apraclonidine ophthalmic drops. The most commonly reported adverse event was prolonged lethargy and unresponsiveness (17 of 21 [81%]) followed by clinically significant cardiorespiratory events (eg, apnea, hypoxia, bradycardia, blood pressure changes, or respiratory failure) (8 of 21 [38%]). Three cases required intubation. Most cases (16 of 21 [76%]) described patients younger than 1 year. The reason for use in most (12 of 16 [75%]) patients younger than 1 year was for diagnostic purposes. Conclusions and Relevance This case series suggests use of apraclonidine in pediatric patients poses a risk of central α-2 adrenergic agonist–induced central nervous system and respiratory depression. Clinicians who use apraclonidine in the pediatric population should be aware of potential serious systemic effects from ophthalmic use of the drug and be prepared to manage these.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"109 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1001/jamaophthalmol.2025.3980
Jennifer A. Hamilton-Perais, David M. Wright, Amelia Lim, Ajay Mohite, Gerard Reid, Pearse Hillis, Cora Sheeran, Noemi Lois
Importance Retinal capillary nonperfusion seems crucial in the pathogenesis of sight-threatening diabetic retinopathy (DR); currently, no treatment prevents or reverts it. Objective To further the understanding of the association between retinal capillary nonperfusion and sensitivity in DR. Design, Setting, and Participants This prospective, longitudinal cohort study was conducted from April 18, 2018, to September 9, 2024, at a single center in the UK. Participants were followed up for up to 2 years; outcome assessors were masked. Adults (aged ≥18 years) with moderate or severe to very severe nonproliferative or proliferative DR with less than high-risk characteristics; at least 1 eye naive to treatment; no other retinal disorders; who were able to provide informed consent; and who were willing undergo retinal imaging were eligible for inclusion. Data analysis was performed from September 2024 to April 2025. Main Outcomes and Measures The primary outcome was the association between retinal sensitivity (110° projection perimetry) and retinal perfusion (ultra-widefield angiography) at baseline and changes at 1 and 2 years in the study eye. Results Of 66 people approached, 50 were eligible and recruited, and 44 individuals with at least 1 perimetric examination were included. Mean (SD) participant age was 52.1 (12.2) years, and 13 participants (29%) were female. Median hemoglobin A 1 c was 75.5 mmol/mol (9.1% of total hemoglobin [to convert from percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01]); mean (SD) best-corrected visual acuity letter score was 85.7 (4.7) (Snellen equivalent, 20/20). Mean retinal sensitivity deficit at baseline was associated with perfusion status, with larger deficits in nonperfused areas (n = 354; 11.8 dBs; 95% CI, 10.8-12.8) compared to perfused areas (n = 2092; 6.6 dB; 95% CI, 5.1-8.2; P &lt; .001). Only age correlated positively with sensitivity deficit (estimate, 0.2; 95% CI, 0.1-0.3; P = .006). A deficit of 5 dB or greater occurred in 711 of 2092 (34%) perfused areas; 105 of 354 (30%) nonperfused areas had normal sensitivity. Rates of sensitivity deficit change in perfused and nonperfused areas from baseline to 1 year were −0.20 dB/mo (95% CI, −0.24 to −0.16) and −0.28 dB/mo (95% CI, −0.41 to −0.15) (perfused vs nonperfused, P = .22), respectively (1464 areas); from baseline to 2 years, rates were −0.16 dB/mo (95% CI, −0.20 to −0.12) and −0.34 dB/mo (95% CI, −0.47 to −0.21) (perfused vs nonperfused, P = .007), respectively (542 areas). Conclusions and Relevance In this longitudinal cohort study, although retinal capillary perfusion status was associated with function, sensitivity loss occurred in some perfused areas and normal function in some nonperfused areas; sensitivity defic
{"title":"Retinal Sensitivity and Retinal Perfusion in Diabetic Retinopathy","authors":"Jennifer A. Hamilton-Perais, David M. Wright, Amelia Lim, Ajay Mohite, Gerard Reid, Pearse Hillis, Cora Sheeran, Noemi Lois","doi":"10.1001/jamaophthalmol.2025.3980","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.3980","url":null,"abstract":"Importance Retinal capillary nonperfusion seems crucial in the pathogenesis of sight-threatening diabetic retinopathy (DR); currently, no treatment prevents or reverts it. Objective To further the understanding of the association between retinal capillary nonperfusion and sensitivity in DR. Design, Setting, and Participants This prospective, longitudinal cohort study was conducted from April 18, 2018, to September 9, 2024, at a single center in the UK. Participants were followed up for up to 2 years; outcome assessors were masked. Adults (aged ≥18 years) with moderate or severe to very severe nonproliferative or proliferative DR with less than high-risk characteristics; at least 1 eye naive to treatment; no other retinal disorders; who were able to provide informed consent; and who were willing undergo retinal imaging were eligible for inclusion. Data analysis was performed from September 2024 to April 2025. Main Outcomes and Measures The primary outcome was the association between retinal sensitivity (110° projection perimetry) and retinal perfusion (ultra-widefield angiography) at baseline and changes at 1 and 2 years in the study eye. Results Of 66 people approached, 50 were eligible and recruited, and 44 individuals with at least 1 perimetric examination were included. Mean (SD) participant age was 52.1 (12.2) years, and 13 participants (29%) were female. Median hemoglobin A <jats:sub> 1 <jats:sc>c</jats:sc> </jats:sub> was 75.5 mmol/mol (9.1% of total hemoglobin [to convert from percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01]); mean (SD) best-corrected visual acuity letter score was 85.7 (4.7) (Snellen equivalent, 20/20). Mean retinal sensitivity deficit at baseline was associated with perfusion status, with larger deficits in nonperfused areas (n = 354; 11.8 dBs; 95% CI, 10.8-12.8) compared to perfused areas (n = 2092; 6.6 dB; 95% CI, 5.1-8.2; <jats:italic toggle=\"yes\">P</jats:italic> &amp;lt; .001). Only age correlated positively with sensitivity deficit (estimate, 0.2; 95% CI, 0.1-0.3; <jats:italic toggle=\"yes\">P</jats:italic> = .006). A deficit of 5 dB or greater occurred in 711 of 2092 (34%) perfused areas; 105 of 354 (30%) nonperfused areas had normal sensitivity. Rates of sensitivity deficit change in perfused and nonperfused areas from baseline to 1 year were −0.20 dB/mo (95% CI, −0.24 to −0.16) and −0.28 dB/mo (95% CI, −0.41 to −0.15) (perfused vs nonperfused, <jats:italic toggle=\"yes\">P</jats:italic> = .22), respectively (1464 areas); from baseline to 2 years, rates were −0.16 dB/mo (95% CI, −0.20 to −0.12) and −0.34 dB/mo (95% CI, −0.47 to −0.21) (perfused vs nonperfused, <jats:italic toggle=\"yes\">P</jats:italic> = .007), respectively (542 areas). Conclusions and Relevance In this longitudinal cohort study, although retinal capillary perfusion status was associated with function, sensitivity loss occurred in some perfused areas and normal function in some nonperfused areas; sensitivity defic","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"19 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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