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Macular exudate in idiopathic intracranial hypertension affects outer retina and visual acuity. 特发性颅内高压症的黄斑渗出会影响外层视网膜和视力。
IF 2 Q2 OPHTHALMOLOGY Pub Date : 2024-09-24 DOI: 10.1136/bmjophth-2024-001810
Le Cao, Hang Wang, William Robert Kwapong, Jincheng Wan, Yuying Yan, Guina Liu, Rui Liu, Fayun Hu, Bo Wu

Background: Optical coherence tomography (OCT) is suggested as a potential tool for retinal biomarkers in idiopathic intracranial hypertension (IIH). We explored how macular exudate (ME) affects retinal structure in IIH and investigated its relationship with their clinical features.

Methods: Patients diagnosed with IIH and matched controls were enrolled. ME detection was done on fundus photography; swept-source OCT was used to image and measure the retinal sublayer thicknesses, including the retinal nerve fibre layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL) and outer retinal layer (ORL). IIH patients underwent lumbar puncture where intracranial pressure (ICP) was assessed.

Results: 195 eyes from 98 IIH patients (42 eyes had ME) and 224 eyes from 112 controls were included. IIH patients had thicker INL and ORL compared with controls (both p<0.001) while IIH eyes with ME had thicker INL and ORL thicknesses compared with eyes without ME (both p<0.05). In IIH patients, the retinal sublayer thicknesses correlated with their ICP levels, and GCIPL thickness correlated with visual acuity (VA). Furthermore, ME was associated with higher ICP, worse papilledema and lower VA (all p<0.001).

Conclusion: ME affects retinal thickness in IIH patients and is associated with more severe clinical features in IIH. OCT may provide biomarkers informative of clinical changes in IIH. Further longitudinal studies are needed to explore the evolution of ME and its relationship to VA and retinal structure.

背景:光学相干断层扫描(OCT)被认为是特发性颅内高压症(IIH)视网膜生物标志物的潜在工具。我们探讨了黄斑渗出物(ME)如何影响 IIH 患者的视网膜结构,并研究了其与临床特征的关系:方法:我们招募了确诊为 IIH 的患者和匹配的对照组。通过眼底摄影检测ME;使用扫源OCT成像并测量视网膜亚层厚度,包括视网膜神经纤维层、神经节细胞-内丛状层(GCIPL)、内核层(INL)和视网膜外层(ORL)。对 IIH 患者进行腰椎穿刺,评估颅内压(ICP):结果:共纳入98名IIH患者的195只眼睛(42只眼睛患有ME)和112名对照组患者的224只眼睛。与对照组相比,IIH 患者的 INL 和 ORL 更厚(均为 p):ME会影响IIH患者的视网膜厚度,并与IIH患者更严重的临床特征有关。OCT 可提供反映 IIH 临床变化的生物标志物。需要进一步开展纵向研究,探讨ME的演变及其与VA和视网膜结构的关系。
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引用次数: 0
Cellular pattern and orbital fat involvement are possible risk factors for the failure of corticosteroids in patients with pure idiopathic orbital inflammation syndrome: lessons from the French prospective SIOI cohort study (part II). 细胞模式和眼眶脂肪受累是导致纯特发性眼眶炎综合征患者皮质类固醇治疗失败的可能风险因素:法国前瞻性 SIOI 队列研究(第二部分)的启示。
IF 2 Q2 OPHTHALMOLOGY Pub Date : 2024-09-23 DOI: 10.1136/bmjophth-2024-001663
Ambre La Rosa, Matthieu Groh, Antoine Martin, Stéphane Tran Ba, Nahla Cucherousset, Frédéric Mouriaux, Neila Sedira, Emmanuel Héron, Olivier Galatoire, David Saadoun, Aïcha Abbas, Mboup Bassirou, Eric Vicaut, Robin Dhote, Sebastien Abad

Purpose: To better characterise the effects of corticosteroids on the course of pure idiopathic orbital inflammation syndrome (pIOIS).

Methods: This was a national, multicentre, prospective, non-interventional cohort study (SIOI). Among the 35 patients with histologically proven orbital inflammation who had previously been studied for their IgG4 immunostaining status, we selected those with a negative IgG4 status (ie, pIOIS) who received corticosteroids as single first-line treatment. Clinical, morphological and pathological findings at diagnosis and during follow-up from treatment initiation to study completion were analysed. Patients were assessed for their response to prednisone after the 24-month prospective phase in terms of remission (≤10 mg/d) or failure (>10 mg/d). Daily standard doses of prednisone (DSDP) were calculated at different time-points and compared between response groups.

Results: Of the 17 patients with pIOIS included in the final analysis, two-thirds received corticosteroids only. DSDP (mg/kg-day) were significantly higher at the time of failure in eight patients (47%) than in nine (53%) remitting at M24 (0.16 vs 0.045; p: 0.03). Notably, patients with pIOIS with a cellular pattern or orbital fat involvement tended to receive higher daily corticosteroid doses in the event of failure than remission (0.16 vs 0.045 and 0.12 vs 0.042, respectively). During treatment, maximal DSDP was 0.52 in failed patients.

Conclusion: The highest corticosteroid doses were insufficient to prevent failure in patients with pIOIS, particularly in those with a cellular pattern or orbital fat involvement. Large-scale interventional studies are now necessary to clarify prognostic factors and optimise corticosteroid management in patients with pIOIS.

目的:更好地描述皮质类固醇对纯特发性眼眶炎综合征(pIOIS)病程的影响:这是一项全国性、多中心、前瞻性、非干预性队列研究(SIOI)。在35例经组织学证实的眼眶炎症患者中,我们选择了IgG4免疫染色阴性的患者(即pIOIS)接受皮质类固醇激素作为单一一线治疗。我们对诊断时以及从开始治疗到研究结束的随访期间的临床、形态学和病理学结果进行了分析。在为期24个月的前瞻性研究阶段结束后,以缓解(≤10毫克/天)或失败(>10毫克/天)为标准评估患者对泼尼松的反应。在不同的时间点计算泼尼松的日标准剂量(DSDP),并在反应组之间进行比较:结果:在纳入最终分析的 17 名 pIOIS 患者中,三分之二仅接受了皮质类固醇治疗。8名患者(47%)在治疗失败时的DSDP(毫克/千克-天)明显高于9名(53%)在M24时缓解的患者(0.16 vs 0.045; p: 0.03)。值得注意的是,具有细胞模式或眼眶脂肪受累的 pIOIS 患者在治疗失败时的每日皮质类固醇剂量往往高于缓解时(分别为 0.16 vs 0.045 和 0.12 vs 0.042)。治疗期间,失败患者的最大DSDP为0.52:结论:最高剂量的皮质类固醇不足以防止 pIOIS 患者的治疗失败,尤其是那些细胞模式或眶脂肪受累的患者。现在有必要进行大规模干预研究,以明确预后因素,优化皮质类固醇对 pIOIS 患者的治疗。
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引用次数: 0
Comparing 24-hour IOP fluctuation slope curve between newly diagnosed ocular hypertension and primary open-angle glaucoma. 比较新诊断的眼压过高和原发性开角型青光眼的 24 小时眼压波动斜率曲线。
IF 2 Q2 OPHTHALMOLOGY Pub Date : 2024-09-23 DOI: 10.1136/bmjophth-2024-001821
Qing Zhang, Hui Feng, Ye Zhang, Dong Han, Guangxian Tang, Su Jie Fan, Hengli Zhang, Jing Jiang, Aiguo Lv, Shuning Li

Objective: To compare the 24-hour intraocular pressure (IOP) fluctuation slope curve between newly diagnosed patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG).

Methods and analysis: Newly diagnosed and untreated OHT and POAG patients who underwent 24-hour IOP monitoring were consecutively enrolled in the study. IOP measurements were taken every 2 hours from 8:00 to 6:00 hours the following day using an iCare PRO tonometer. Patients maintained their daily routines, with IOP measured in a seated position during the day and supine at night. The 24-hour IOP fluctuation indices, including peak, trough and overall fluctuation, were calculated. Differences in the 24-hour IOP fluctuation slope curves over time between groups were analysed using a generalised additive mixed model.

Results: 46 patients with OHT and 41 with POAG were included. From 2:00 to 10:00 hours, mean IOP increased by 0.69 mm Hg every 2 hours in the POAG group (p<0.0001) and by 0.40 mm Hg in the OHT group (p<0.0001). After 10:00, the IOP showed a downward trend, decreasing by 0.31 mm Hg in the POAG group (p<0.0001) and by 0.17 mm Hg in the OHT group (p=0.0003) every 2 hours. The rate of slope change in the upward phase differed significantly between the groups (0.30 mm Hg per 2 hours; p=0.02), as did the rate in the downward phase (0.14 mm Hg per 2 hours; p for interaction=0.04). Multivariate models showed that each 1 mm Hg increase in circadian and diurnal IOP fluctuation was associated with a 27% and 21% higher likelihood of POAG presence, respectively.

Conclusion: The 24-hour IOP slope curve differed between POAG and OHT, with a steeper slope observed in the POAG group. However, the study is limited by potential confounding factors, reliance on a single 24-hour measurement period and the need for further longitudinal studies to validate these findings.

目的比较新诊断的眼压过高(OHT)和原发性开角型青光眼(POAG)患者的 24 小时眼压波动斜率曲线:研究连续纳入了接受 24 小时眼压监测的新诊断和未经治疗的 OHT 和 POAG 患者。使用 iCare PRO 眼压计从 8:00 至次日 6:00 每 2 小时测量一次眼压。患者保持日常作息,白天坐姿测量眼压,晚上仰卧测量。计算 24 小时眼压波动指数,包括峰值、谷值和总体波动。采用广义相加混合模型分析了不同组间 24 小时眼压波动斜率曲线随时间变化的差异:结果:共纳入 46 名 OHT 患者和 41 名 POAG 患者。从 2:00 到 10:00,POAG 组的平均眼压每 2 小时上升 0.69 mm Hg(p 结论:OHT 组和 POAG 组的 24 小时眼压斜率曲线不同:POAG 组和 OHT 组的 24 小时眼压斜率曲线不同,POAG 组的斜率更陡。然而,这项研究受到了潜在混杂因素的限制,依赖于单一的 24 小时测量时间段,并且需要进一步的纵向研究来验证这些发现。
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引用次数: 0
Comparison of the accommodative amplitude measured with and without the use of a specialised accommodative rule in children. 比较使用和不使用专用适应规则测量的儿童适应振幅。
IF 2 Q2 OPHTHALMOLOGY Pub Date : 2024-09-20 DOI: 10.1136/bmjophth-2024-001829
Hassan Hashemi, Payam Nabovati, Mehdi Khabazkhoob, Abbasali Yekta, Mohammad Hassan Emamian, Akbar Fotouhi

Objective: To determine the agreement between measurements of accommodative amplitude (AoA) in children using a specialised accommodative rule and measurments without it.

Methods: A total of 502 children underwent optometric examinations, including the measurement of visual acuity, objective and subjective refraction. AoA measurements were done with and without the Berens accommodative rule. The measurements of AoA were conducted monocularly using a -4 D lens. A fixation stick containing English letters equivalent to 20/30 visual acuity and a long millimetre ruler was used to measure AoA without the accommodative rule. This measurement was performed by the two trained examiners. The agreement between these methods was reported by 95% limits of agreement (LoA) and interclass correlation coefficient (ICC).

Results: The mean age of the participants was 11.7±1.3 years (range: 9-15 years) and 52.4% were male. The mean AoA with and without the accommodative rule was 20.02±6.02 D and 22.46±6.32 D, respectively. The 95% LoA between the two methods was -12.5 to 7.5 D, and the ICC was 0.67 (95% CI 0.63 to 0.70). The 95% LoA was narrower in higher age groups and males compared with females (18.92 vs 20.87). The 95% LoA was narrower in hyperopes (16.83 D) compared with emmetropes (18.37 D) and myopes (18.27 D). The agreement was not constant and decreased in higher values of AoA.

Conclusion: There is a poor and non-constant agreement between the measurements of the AoA with and without the accommodative rule. The mean AoA was 2.5 D lower with using the accommodative rule.

目的确定使用专门的适应规则测量儿童的适应振幅(AoA)与不使用该规则测量之间的一致性:共有 502 名儿童接受了视力检查,包括视力、客观和主观屈光度的测量。在使用和不使用贝伦斯通融规则的情况下进行了视力测量。用-4 D镜片进行单眼视力测量。在不使用贝伦斯屈光规则的情况下,使用一个包含相当于 20/30 视力的英文字母的固定棒和一把长毫米尺来测量屈光度。该测量由两名训练有素的检查员进行。这些方法之间的一致性通过 95% 的一致性极限 (LoA) 和类间相关系数 (ICC) 进行报告:参与者的平均年龄为(11.7±1.3)岁(9-15 岁),52.4% 为男性。使用和不使用容纳规则的平均视差分别为 20.02±6.02 D 和 22.46±6.32 D。两种方法的 95% LoA 为 -12.5 到 7.5 D,ICC 为 0.67(95% CI 0.63 到 0.70)。与女性相比(18.92 vs 20.87),高年龄组和男性的 95% LoA 更窄。与散光(18.37 D)和近视(18.27 D)相比,远视眼(16.83 D)的 95% LoA 更窄。结论:结论:使用和不使用适应规则测量的视轴角膜屈光度之间的一致性很差,而且不稳定。使用适应规则时,平均视角降低了 2.5 D。
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引用次数: 0
Comparison of two digital alignment systems for toric intraocular lens implantation. 散光眼内透镜植入术中两种数字配准系统的比较。
IF 2.4 Q2 OPHTHALMOLOGY Pub Date : 2024-09-16 DOI: 10.1136/bmjophth-2024-001875
Johannes Zeilinger,Andreas Schlatter,Manuel Ruiss,Natascha Bayer,Martin Kronschläger,Oliver Findl
PURPOSETo compare the two most used digital alignment systems regarding precision, repeatability and loss of track.METHODS15 eyes of 15 patients older than 21 years with cataracts were included in this prospective study. The two systems were intraoperatively superimposed and recorded, and the alignment of the two displayed alignment axes was analysed regarding precision, repeatability and loss of track.RESULTSThere was a significant difference in precision and repeatability between the two digital alignment systems regarding the projected alignment axis. The deviation from the actual target axis was significantly different, with a mean of 0.34°±0.75° for the Zeiss system and 1.60°±1.08° for the Alcon system (p=0.03, n=14). The within-subject SD was significantly lower with 0.21° for the Zeiss system and 0.34° for the Alcon system (p=0.03, n=14).CONCLUSIONSThe Zeiss Callisto system showed a significantly lower deviation from the target axis, higher stability with eye movements and less need for microscope illumination than the Alcon system. Both systems showed high precision when compared with manual marking methods.TRIAL REGISTRATION NUMBERNCT05220683.
目的比较两种最常用的数字对位系统在精确度、可重复性和轨迹损失方面的差异。术中对两种系统进行了叠加和记录,并分析了两个显示对准轴的对准精度、可重复性和轨迹损失。结果两种数字对准系统在投射对准轴的精度和可重复性方面存在显著差异。与实际目标轴的偏差有显著差异,蔡司系统的平均偏差为 0.34°±0.75°,爱尔康系统的平均偏差为 1.60°±1.08°(P=0.03,n=14)。结论与爱尔康系统相比,蔡司 Callisto 系统偏离目标轴的程度明显较低,眼球运动的稳定性较高,对显微镜照明的需求较少。与手动标记方法相比,两种系统都显示出很高的精确度。
{"title":"Comparison of two digital alignment systems for toric intraocular lens implantation.","authors":"Johannes Zeilinger,Andreas Schlatter,Manuel Ruiss,Natascha Bayer,Martin Kronschläger,Oliver Findl","doi":"10.1136/bmjophth-2024-001875","DOIUrl":"https://doi.org/10.1136/bmjophth-2024-001875","url":null,"abstract":"PURPOSETo compare the two most used digital alignment systems regarding precision, repeatability and loss of track.METHODS15 eyes of 15 patients older than 21 years with cataracts were included in this prospective study. The two systems were intraoperatively superimposed and recorded, and the alignment of the two displayed alignment axes was analysed regarding precision, repeatability and loss of track.RESULTSThere was a significant difference in precision and repeatability between the two digital alignment systems regarding the projected alignment axis. The deviation from the actual target axis was significantly different, with a mean of 0.34°±0.75° for the Zeiss system and 1.60°±1.08° for the Alcon system (p=0.03, n=14). The within-subject SD was significantly lower with 0.21° for the Zeiss system and 0.34° for the Alcon system (p=0.03, n=14).CONCLUSIONSThe Zeiss Callisto system showed a significantly lower deviation from the target axis, higher stability with eye movements and less need for microscope illumination than the Alcon system. Both systems showed high precision when compared with manual marking methods.TRIAL REGISTRATION NUMBERNCT05220683.","PeriodicalId":9286,"journal":{"name":"BMJ Open Ophthalmology","volume":"17 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258311","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}
引用次数: 0
Microsporidial stromal keratitis: treatment outcomes, clinical manifestations, confocal microscopy and histopathology findings: a retrospective observational study. 小孢子菌基质角膜炎:治疗效果、临床表现、共聚焦显微镜检查和组织病理学结果:一项回顾性观察研究。
IF 2.4 Q2 OPHTHALMOLOGY Pub Date : 2024-09-16 DOI: 10.1136/bmjophth-2023-001581
Thurdkiat Saksurakan,Vilavun Puangsricharern,Buravej Assavapongpaiboon,Thanachaporn Kittipibul,Urassaya Pattanawong,Vannarut Satitpitakul,Usanee Reinprayoon,Ngamjit Kasetsuwan,Somchai Jongwutiwes,Wasee Tulvatana
OBJECTIVEMicrosporidial stromal keratitis (MSK) is an uncommon disease. Only several case series have been reported. We aimed to describe the clinical manifestations, histopathology and treatment outcomes of MSK.METHODS AND ANALYSISRetrospective data of MSK diagnosed between January 2009 and December 2020 at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand were retrieved. The diagnosis was made based on corneal scraping, corneal biopsy and corneal button histopathology findings. Detailed clinical characteristics, histopathological findings and treatment outcomes were reviewed and analysed.RESULTS21 patients with MSK with a mean age of 63.8 years (SD 12.2) had an indolent disease onset with a median of 9 months (IQR 2.2-12.0). Five patients (23.8%) experienced ocular traumas. Herpes stromal keratitis was the most common preliminary diagnosis (33.3%), followed by non-specific ulcers and fungal keratitis. The most common corneal finding was multifocal grey-white lesions with anterior to mid-stromal infiltration and fluffy borders (66.7%). Pathogens were identified by modified trichrome staining of corneal scrapings in 11 of 14 cases (78.6%). Histopathological examination showed positive Ziehl-Neelsen staining in 17 of 19 cases (89.5%). All patients received surgical treatment, with 18 receiving therapeutic penetrating keratoplasty (TPK), 2 undergoing deep anterior lamellar keratoplasty and 1 undergoing femtosecond laser-assisted anterior lamellar keratoplasty. The overall cure rate was 76.2% after the first surgery and 95.2% after the second surgery.CONCLUSIONMSK can be easily underdiagnosed. Clues to diagnosis included a history of chronic refractory stromal infiltration and typical corneal findings of deep stromal infiltration, without epithelial defects. TPK is the preferred treatment for MSK.
目的微孢子菌基质角膜炎(MSK)是一种不常见的疾病。目前仅有几例系列病例报道。我们的目的是描述 MSK 的临床表现、组织病理学和治疗效果。方法与分析检索了 2009 年 1 月至 2020 年 12 月期间在泰国曼谷朱拉隆功国王纪念医院确诊的 MSK 的回顾性数据。诊断依据是角膜刮片、角膜活检和角膜扣组织病理学检查结果。结果 21 名 MSK 患者的平均年龄为 63.8 岁(SD 12.2),起病隐匿,中位数为 9 个月(IQR 2.2-12.0)。五名患者(23.8%)曾遭受眼部创伤。疱疹性基质角膜炎是最常见的初步诊断(33.3%),其次是非特异性溃疡和真菌性角膜炎。最常见的角膜病变是多灶性灰白色病变,基质前部至中部浸润,边界蓬松(66.7%)。通过对角膜刮片进行改良三色染色,14 例病例中有 11 例(78.6%)确定了病原体。组织病理学检查显示,19 例病例中有 17 例(89.5%)Ziehl-Neelsen 染色呈阳性。所有患者均接受了手术治疗,其中 18 例接受了治疗性穿透角膜移植术(TPK),2 例接受了深层前板层角膜移植术,1 例接受了飞秒激光辅助前板层角膜移植术。第一次手术后的总治愈率为 76.2%,第二次手术后的总治愈率为 95.2%。诊断线索包括慢性难治性基质浸润病史和典型的角膜深层基质浸润,但无上皮缺损。TPK是治疗MSK的首选方法。
{"title":"Microsporidial stromal keratitis: treatment outcomes, clinical manifestations, confocal microscopy and histopathology findings: a retrospective observational study.","authors":"Thurdkiat Saksurakan,Vilavun Puangsricharern,Buravej Assavapongpaiboon,Thanachaporn Kittipibul,Urassaya Pattanawong,Vannarut Satitpitakul,Usanee Reinprayoon,Ngamjit Kasetsuwan,Somchai Jongwutiwes,Wasee Tulvatana","doi":"10.1136/bmjophth-2023-001581","DOIUrl":"https://doi.org/10.1136/bmjophth-2023-001581","url":null,"abstract":"OBJECTIVEMicrosporidial stromal keratitis (MSK) is an uncommon disease. Only several case series have been reported. We aimed to describe the clinical manifestations, histopathology and treatment outcomes of MSK.METHODS AND ANALYSISRetrospective data of MSK diagnosed between January 2009 and December 2020 at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand were retrieved. The diagnosis was made based on corneal scraping, corneal biopsy and corneal button histopathology findings. Detailed clinical characteristics, histopathological findings and treatment outcomes were reviewed and analysed.RESULTS21 patients with MSK with a mean age of 63.8 years (SD 12.2) had an indolent disease onset with a median of 9 months (IQR 2.2-12.0). Five patients (23.8%) experienced ocular traumas. Herpes stromal keratitis was the most common preliminary diagnosis (33.3%), followed by non-specific ulcers and fungal keratitis. The most common corneal finding was multifocal grey-white lesions with anterior to mid-stromal infiltration and fluffy borders (66.7%). Pathogens were identified by modified trichrome staining of corneal scrapings in 11 of 14 cases (78.6%). Histopathological examination showed positive Ziehl-Neelsen staining in 17 of 19 cases (89.5%). All patients received surgical treatment, with 18 receiving therapeutic penetrating keratoplasty (TPK), 2 undergoing deep anterior lamellar keratoplasty and 1 undergoing femtosecond laser-assisted anterior lamellar keratoplasty. The overall cure rate was 76.2% after the first surgery and 95.2% after the second surgery.CONCLUSIONMSK can be easily underdiagnosed. Clues to diagnosis included a history of chronic refractory stromal infiltration and typical corneal findings of deep stromal infiltration, without epithelial defects. TPK is the preferred treatment for MSK.","PeriodicalId":9286,"journal":{"name":"BMJ Open Ophthalmology","volume":"4 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258312","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}
引用次数: 0
Recurrent ocular toxoplasmosis is associated with interferon-gamma deficiency possibly due to genetic origin 复发性眼弓形虫病与干扰素-γ 缺乏有关,可能是遗传所致
IF 2.4 Q2 OPHTHALMOLOGY Pub Date : 2024-09-13 DOI: 10.1136/bmjophth-2024-001769
Nina Maria Hautala, Maija Joensuu, Teija Paakkola, Virpi Glumoff, Kaisa Kettunen, Janna Saarela, Mira Siiskonen, Zhi Chen, Katri Pylkäs, Timo Hautala
Objective Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT.Methods and analysis A recurrent OT patient population (n=9) was identified. Clinical history, ophthalmological findings and immunological properties were assessed. B and T cell immunophenotyping including interferon-gamma (IFN-γ) responses were analysed. An analysis of 592 immunodeficiency genes was performed.Results The patients experienced 2–7 OT episodes (average 3.7). The first episode occurred at an average of 23.8 (SD 10.1) years of age. All patients had anterior uveitis, vitritis and various fundus lesions of OT. The patients had lymphocyte maturation abnormalities; the proportion of naive CD4 +CD45RA+CCR7+ T cells was high in 5/9 cases, and the percentage of CD4+CD45RA−CCR7− T effector memory cells was reduced in 7/9 cases. An increased percentage of CD19+CD38lowCD21low activated B cells was observed in 5/9 cases. IFN-γ response was reduced in CD4+ (8.45±4.17 vs 21.27±11.0, p=0.025) and CD8+ (39.0±9.9 vs 18.1±18.1, p=0.017) T cells. Genetic analysis revealed several potentially harmful variants in immunologically active ERCC3, MANBA, IRF4, HAVCR2, CARMIL2, CD247, MPO, C2 and CD40 genes.Conclusion Our recurrent OT cases had deviations in lymphocyte maturation and IFN-γ responses possibly caused by genetic reasons. However, limitations of our study include failure to identify uniform genetic mechanisms. In addition, we cannot rule out the possibility that the immunological abnormalities can be triggered by chronic toxoplasmosis. Despite the limitations, our findings contribute to the understanding of ocular immunity and development of recurrent OT.
目的 眼弓形虫病(OT)可导致后葡萄膜炎,但复发性 OT 的病因尚不十分清楚。我们探讨了与复发性 OT 相关的临床、免疫学和遗传学特性。对临床病史、眼科检查结果和免疫学特性进行了评估。分析了B细胞和T细胞免疫分型,包括γ干扰素(IFN-γ)反应。对 592 个免疫缺陷基因进行了分析。首次发病的平均年龄为 23.8 岁(标准差 10.1 岁)。所有患者都有前葡萄膜炎、玻璃体炎和各种 OT 眼底病变。患者的淋巴细胞成熟异常;5/9 例患者的幼稚 CD4+CD45RA+CCR7+ T 细胞比例较高,7/9 例患者的 CD4+CD45RA-CCR7- T 效应记忆细胞比例降低。在 5/9 个病例中,观察到 CD19+CD38lowCD21low 活化 B 细胞的百分比增加。CD4+(8.45±4.17 vs 21.27±11.0,p=0.025)和CD8+(39.0±9.9 vs 18.1±18.1,p=0.017)T细胞的IFN-γ反应降低。遗传分析显示,在具有免疫活性的 ERCC3、MANBA、IRF4、HAVCR2、CARMIL2、CD247、MPO、C2 和 CD40 基因中存在几个潜在的有害变异。然而,我们研究的局限性包括未能确定统一的遗传机制。此外,我们也不能排除慢性弓形虫病引发免疫异常的可能性。尽管存在这些局限性,但我们的研究结果有助于理解眼部免疫和复发性 OT 的发展。
{"title":"Recurrent ocular toxoplasmosis is associated with interferon-gamma deficiency possibly due to genetic origin","authors":"Nina Maria Hautala, Maija Joensuu, Teija Paakkola, Virpi Glumoff, Kaisa Kettunen, Janna Saarela, Mira Siiskonen, Zhi Chen, Katri Pylkäs, Timo Hautala","doi":"10.1136/bmjophth-2024-001769","DOIUrl":"https://doi.org/10.1136/bmjophth-2024-001769","url":null,"abstract":"Objective Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT.Methods and analysis A recurrent OT patient population (n=9) was identified. Clinical history, ophthalmological findings and immunological properties were assessed. B and T cell immunophenotyping including interferon-gamma (IFN-γ) responses were analysed. An analysis of 592 immunodeficiency genes was performed.Results The patients experienced 2–7 OT episodes (average 3.7). The first episode occurred at an average of 23.8 (SD 10.1) years of age. All patients had anterior uveitis, vitritis and various fundus lesions of OT. The patients had lymphocyte maturation abnormalities; the proportion of naive CD4 +CD45RA+CCR7+ T cells was high in 5/9 cases, and the percentage of CD4+CD45RA−CCR7− T effector memory cells was reduced in 7/9 cases. An increased percentage of CD19+CD38lowCD21low activated B cells was observed in 5/9 cases. IFN-γ response was reduced in CD4+ (8.45±4.17 vs 21.27±11.0, p=0.025) and CD8+ (39.0±9.9 vs 18.1±18.1, p=0.017) T cells. Genetic analysis revealed several potentially harmful variants in immunologically active ERCC3, MANBA, IRF4, HAVCR2, CARMIL2, CD247, MPO, C2 and CD40 genes.Conclusion Our recurrent OT cases had deviations in lymphocyte maturation and IFN-γ responses possibly caused by genetic reasons. However, limitations of our study include failure to identify uniform genetic mechanisms. In addition, we cannot rule out the possibility that the immunological abnormalities can be triggered by chronic toxoplasmosis. Despite the limitations, our findings contribute to the understanding of ocular immunity and development of recurrent OT.","PeriodicalId":9286,"journal":{"name":"BMJ Open Ophthalmology","volume":"3 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258313","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}
引用次数: 0
Automatic retinal image analysis methods using colour fundus images for screening glaucomatous optic neuropathy 利用彩色眼底图像筛查青光眼性视神经病变的自动视网膜图像分析方法
IF 2.4 Q2 OPHTHALMOLOGY Pub Date : 2024-09-01 DOI: 10.1136/bmjophth-2023-001594
Chuying Shi, Jack Lee, Di Shi, Gechun Wang, Fei Yuan, Benny Chung-Ying Zee
Objectives Train an automatic retinal image analysis (ARIA) method to screen glaucomatous optic neuropathy (GON) on non-mydriatic retinal images labelled with the additional results of optical coherence tomography (OCT) and assess different models for the GON classification. Methods All the images were obtained from the hospital for training and 10-fold cross-validation. Two methods were used to improve the classification performance: (1) using images labelled with the additional results of OCT as the reference standard and (2) generating models using retinal features from the entire images, the region of interest (ROI) of the optic disc, and the ROI of the macula, and the combination of all the features. Results Overall, we collected 1338 images with paired OCT scans. In 10-fold validation, ARIA achieved sensitivities of 92.2 %, 92.7% and 85.7%, specificities of 88.8%, 86.7% and 80.2% and accuracies of 90.6%, 89.9% and 83.1% using the retinal features from the entire images, the ROI of the optic disc and the ROI of the macula, respectively. We found the model combining all the features has the best classification performance and obtained a sensitivity of 92.5%, a specificity of 92.1% and an accuracy of 92.4%, which is significantly different from other models (p<0.001). Conclusion We used two methods to improve the classification performance and found the best model to detect glaucoma on colour fundus retinal images. It can become a cost-effective and relatively more accurate glaucoma screening tool than conventional methods. Data are available on reasonable request.
目的 在标有光学相干断层扫描(OCT)附加结果的非眼底视网膜图像上训练一种自动视网膜图像分析(ARIA)方法,以筛查青光眼性视神经病变(GON),并评估 GON 分类的不同模型。方法 所有图像均来自医院,用于训练和 10 倍交叉验证。为了提高分类性能,我们采用了两种方法:(1)使用 OCT 附加结果标记的图像作为参考标准;(2)使用整个图像、视盘感兴趣区(ROI)和黄斑感兴趣区的视网膜特征以及所有特征的组合生成模型。结果 我们共收集了 1338 张成对 OCT 扫描图像。在 10 倍验证中,ARIA 使用整个图像、视盘 ROI 和黄斑 ROI 的视网膜特征,灵敏度分别达到 92.2%、92.7% 和 85.7%,特异度分别达到 88.8%、86.7% 和 80.2%,准确度分别达到 90.6%、89.9% 和 83.1%。我们发现,结合所有特征的模型分类效果最好,灵敏度为 92.5%,特异度为 92.1%,准确率为 92.4%,与其他模型相比差异显著(p<0.001)。结论 我们用两种方法提高了分类性能,并找到了在彩色眼底视网膜图像上检测青光眼的最佳模型。与传统方法相比,它可以成为一种经济有效且相对更准确的青光眼筛查工具。如有合理要求,可提供相关数据。
{"title":"Automatic retinal image analysis methods using colour fundus images for screening glaucomatous optic neuropathy","authors":"Chuying Shi, Jack Lee, Di Shi, Gechun Wang, Fei Yuan, Benny Chung-Ying Zee","doi":"10.1136/bmjophth-2023-001594","DOIUrl":"https://doi.org/10.1136/bmjophth-2023-001594","url":null,"abstract":"Objectives Train an automatic retinal image analysis (ARIA) method to screen glaucomatous optic neuropathy (GON) on non-mydriatic retinal images labelled with the additional results of optical coherence tomography (OCT) and assess different models for the GON classification. Methods All the images were obtained from the hospital for training and 10-fold cross-validation. Two methods were used to improve the classification performance: (1) using images labelled with the additional results of OCT as the reference standard and (2) generating models using retinal features from the entire images, the region of interest (ROI) of the optic disc, and the ROI of the macula, and the combination of all the features. Results Overall, we collected 1338 images with paired OCT scans. In 10-fold validation, ARIA achieved sensitivities of 92.2 %, 92.7% and 85.7%, specificities of 88.8%, 86.7% and 80.2% and accuracies of 90.6%, 89.9% and 83.1% using the retinal features from the entire images, the ROI of the optic disc and the ROI of the macula, respectively. We found the model combining all the features has the best classification performance and obtained a sensitivity of 92.5%, a specificity of 92.1% and an accuracy of 92.4%, which is significantly different from other models (p<0.001). Conclusion We used two methods to improve the classification performance and found the best model to detect glaucoma on colour fundus retinal images. It can become a cost-effective and relatively more accurate glaucoma screening tool than conventional methods. Data are available on reasonable request.","PeriodicalId":9286,"journal":{"name":"BMJ Open Ophthalmology","volume":"32 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181845","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}
引用次数: 0
Peripapillary retinal nerve fibre layer thinning in patients with X-linked retinoschisis. X 连锁视网膜裂孔症患者视网膜周围神经纤维层变薄。
IF 2 Q2 OPHTHALMOLOGY Pub Date : 2024-08-29 DOI: 10.1136/bmjophth-2024-001832
Peter Kiraly, Ana Uršula Gavrić, Felix F Reichel, Johannes Birtel, Luca Mautone, Yevgeniya Atiskova, Philipp Herrmann, Martina Jarc-Vidmar, Marko Hawlina, Susan M Downes, M Dominik Fischer

Aims: To assess peripapillary retinal nerve fibre layer (pRNFL) thickness in patients with X-linked retinoschisis (XLRS), as pRNFL thinning may limit functional improvements in gene therapy trials.

Methods: This retrospective multicentre study included 49 eyes from 25 patients diagnosed with XLRS. Data collected with multimodal imaging at baseline and last follow-up (when available) included age, best-recorded visual acuity (BRVA), central retinal thickness, macular volume (MV), presence and location of peripheral retinoschisis and pRNFL thickness in the global (G), superotemporal (TS), superonasal (NS), inferotemporal (TI), inferonasal (NI), nasal (N) and temporal (T) sectors. Retinal sensitivity, assessed by microperimetry, was also recorded for seven patients at baseline.

Results: pRNFL was thinner (below the fifth percentile) in at least one sector in 72% of right eyes and 79% of left eyes, with thinning across three or more sectors in 20% of right and 17% of left eyes. In 44% of cases, thinning occurred in the temporal sectors of both eyes, with no nasal sectoral thinning. Number of peripheral retinoschisis quadrants matched thinned pRNFL sectors. A strong positive correlation was found between MV and temporal pRNFL thickness (r=0.71, p<0.01), while weak negative correlation trends were noted with age (p=0.05) and BRVA (logMAR; p=0.12) related to temporal thickness of pRNFL sectors.

Conclusion: pRNFL thinning, predominantly sectoral and linked to macular or peripheral retinoschisis, occurs in about three-quarters of patients with XLRS, while diffuse thinning occurs in one-fifth. Temporal pRNFL thinning might occur only after the collapse of intraretinal cystoid cavities in the macula.

目的:评估X连锁视网膜裂孔症(XLRS)患者视网膜毛周神经纤维层(pRNFL)的厚度,因为pRNFL变薄可能会限制基因治疗试验中功能的改善:这项回顾性多中心研究包括 25 名确诊为 XLRS 患者的 49 只眼睛。基线和最后一次随访(如有)时通过多模态成像收集的数据包括年龄、最佳记录视力(BRVA)、中心视网膜厚度、黄斑体积(MV)、周围视网膜裂孔的存在和位置,以及全视网膜(G)、颞上视网膜(TS)、颞上视网膜(NS)、颞下视网膜(TI)、颞下视网膜(NI)、鼻侧视网膜(N)和颞侧视网膜(T)的 pRNFL 厚度。结果:72% 的右眼和 79% 的左眼至少有一个视区的 pRNFL 变薄(低于百分位数第五位),其中 20% 的右眼和 17% 的左眼有三个或更多视区变薄。在 44% 的病例中,双眼的颞区均出现视网膜变薄,鼻侧视网膜没有变薄。周边视网膜裂孔象限的数量与变薄的 pRNFL 扇区相匹配。结论:约四分之三的 XLRS 患者会出现 pRNFL 变薄,主要是扇形变薄,与黄斑或周边视网膜裂孔有关,而五分之一的患者会出现弥漫性变薄。时间性的 pRNFL 变薄可能只发生在黄斑视网膜内囊状腔塌陷之后。
{"title":"Peripapillary retinal nerve fibre layer thinning in patients with X-linked retinoschisis.","authors":"Peter Kiraly, Ana Uršula Gavrić, Felix F Reichel, Johannes Birtel, Luca Mautone, Yevgeniya Atiskova, Philipp Herrmann, Martina Jarc-Vidmar, Marko Hawlina, Susan M Downes, M Dominik Fischer","doi":"10.1136/bmjophth-2024-001832","DOIUrl":"10.1136/bmjophth-2024-001832","url":null,"abstract":"<p><strong>Aims: </strong>To assess peripapillary retinal nerve fibre layer (pRNFL) thickness in patients with X-linked retinoschisis (XLRS), as pRNFL thinning may limit functional improvements in gene therapy trials.</p><p><strong>Methods: </strong>This retrospective multicentre study included 49 eyes from 25 patients diagnosed with XLRS. Data collected with multimodal imaging at baseline and last follow-up (when available) included age, best-recorded visual acuity (BRVA), central retinal thickness, macular volume (MV), presence and location of peripheral retinoschisis and pRNFL thickness in the global (G), superotemporal (TS), superonasal (NS), inferotemporal (TI), inferonasal (NI), nasal (N) and temporal (T) sectors. Retinal sensitivity, assessed by microperimetry, was also recorded for seven patients at baseline.</p><p><strong>Results: </strong>pRNFL was thinner (below the fifth percentile) in at least one sector in 72% of right eyes and 79% of left eyes, with thinning across three or more sectors in 20% of right and 17% of left eyes. In 44% of cases, thinning occurred in the temporal sectors of both eyes, with no nasal sectoral thinning. Number of peripheral retinoschisis quadrants matched thinned pRNFL sectors. A strong positive correlation was found between MV and temporal pRNFL thickness (<i>r</i>=0.71, p<0.01), while weak negative correlation trends were noted with age (p=0.05) and BRVA (logMAR; p=0.12) related to temporal thickness of pRNFL sectors.</p><p><strong>Conclusion: </strong>pRNFL thinning, predominantly sectoral and linked to macular or peripheral retinoschisis, occurs in about three-quarters of patients with XLRS, while diffuse thinning occurs in one-fifth. Temporal pRNFL thinning might occur only after the collapse of intraretinal cystoid cavities in the macula.</p>","PeriodicalId":9286,"journal":{"name":"BMJ Open Ophthalmology","volume":"9 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104588","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}
引用次数: 0
Prostaglandin analogues signal detection by data mining in the FDA Adverse Event Reporting System database. 通过对 FDA 不良事件报告系统数据库的数据挖掘,发现前列腺素类似物信号。
IF 2 Q2 OPHTHALMOLOGY Pub Date : 2024-08-29 DOI: 10.1136/bmjophth-2024-001764
Homero Contreras-Salinas, María Soledad Romero-López, Oscar Olvera-Montaño, Lourdes Yolotzin Rodríguez-Herrera

Objective: This study aims to identify safety signals of ophthalmic prostaglandin analogues through data mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: A data mining search by proportional reporting ratio, reporting OR, Bayesian confidence propagation neural network, information component 0.25 and χ2 for safety signals detection was conducted to the FAERS database for the following ophthalmic medications: latanoprost, travoprost, tafluprost and bimatoprost.

Results: 12 preferred terms were statistically associated: diabetes mellitus, n=2; hypoacusis, n=2; malignant mediastinal neoplasm, n=1; blood immunoglobulin E increased, n=1; cataract, n=1; blepharospasm, n=1; full blood count abnormal, n=1; skin exfoliation, n=1; chest discomfort, n=1; and dry mouth, n=1.

Limitation of the study: The FAERS database's limitations, such as the undetermined causality of cases, under-reporting and the lack of restriction to only health professionals reporting this type of event, could modify the statistical outcomes. These limitations are particularly relevant in the context of ophthalmic drug analysis, as they can affect the accuracy and reliability of the data, potentially leading to biased or incomplete results.

Conclusions: Our findings have revealed a potential relationship due to the biological plausibility among malignant mediastinal neoplasm, full blood count abnormal, blood immunoglobulin E increased, diabetes mellitus, blepharospasm, cataracts, chest discomfort and dry mouth; therefore, it is relevant to continue investigating the possible drug-event association, whether to refute the safety signal or identify a new risk.

目的:本研究旨在通过对食品药品管理局不良事件报告系统(FAERS)数据库的数据挖掘,确定眼科前列腺素类似物的安全信号:本研究旨在通过对食品药品管理局不良事件报告系统(FAERS)数据库进行数据挖掘,识别眼科前列腺素类似物的安全信号:方法: 对FAERS数据库中的下列眼科药物进行数据挖掘搜索:拉坦前列腺素、曲伏前列腺素、他氟前列腺素和比马前列腺素,通过比例报告比、报告OR、贝叶斯置信度传播神经网络、信息成分0.25和χ2进行安全信号检测:12个首选术语在统计学上相关:糖尿病,n=2;听力减退,n=2;恶性纵隔肿瘤,n=1;血免疫球蛋白E增加,n=1;白内障,n=1;眼睑痉挛,n=1;全血细胞计数异常,n=1;皮肤脱落,n=1;胸部不适,n=1;口干,n=1:研究的局限性:FAERS 数据库的局限性,如病例的因果关系不确定、报告不足以及没有限制只有医疗专业人员才能报告此类事件等,都可能会影响统计结果。这些局限性与眼科药物分析尤为相关,因为它们会影响数据的准确性和可靠性,可能导致结果有偏差或不完整:我们的研究结果揭示了恶性纵隔肿瘤、全血细胞计数异常、血免疫球蛋白 E 增高、糖尿病、眼睑痉挛、白内障、胸部不适和口干之间因生物学合理性而可能存在的关系;因此,无论是为了反驳安全信号还是发现新的风险,继续调查药物与事件之间可能存在的关联都是有意义的。
{"title":"Prostaglandin analogues signal detection by data mining in the FDA Adverse Event Reporting System database.","authors":"Homero Contreras-Salinas, María Soledad Romero-López, Oscar Olvera-Montaño, Lourdes Yolotzin Rodríguez-Herrera","doi":"10.1136/bmjophth-2024-001764","DOIUrl":"10.1136/bmjophth-2024-001764","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to identify safety signals of ophthalmic prostaglandin analogues through data mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>A data mining search by proportional reporting ratio, reporting OR, Bayesian confidence propagation neural network, information component 0.25 and χ<sup>2</sup> for safety signals detection was conducted to the FAERS database for the following ophthalmic medications: latanoprost, travoprost, tafluprost and bimatoprost.</p><p><strong>Results: </strong>12 preferred terms were statistically associated: diabetes mellitus, n=2; hypoacusis, n=2; malignant mediastinal neoplasm, n=1; blood immunoglobulin E increased, n=1; cataract, n=1; blepharospasm, n=1; full blood count abnormal, n=1; skin exfoliation, n=1; chest discomfort, n=1; and dry mouth, n=1.</p><p><strong>Limitation of the study: </strong>The FAERS database's limitations, such as the undetermined causality of cases, under-reporting and the lack of restriction to only health professionals reporting this type of event, could modify the statistical outcomes. These limitations are particularly relevant in the context of ophthalmic drug analysis, as they can affect the accuracy and reliability of the data, potentially leading to biased or incomplete results.</p><p><strong>Conclusions: </strong>Our findings have revealed a potential relationship due to the biological plausibility among malignant mediastinal neoplasm, full blood count abnormal, blood immunoglobulin E increased, diabetes mellitus, blepharospasm, cataracts, chest discomfort and dry mouth; therefore, it is relevant to continue investigating the possible drug-event association, whether to refute the safety signal or identify a new risk.</p>","PeriodicalId":9286,"journal":{"name":"BMJ Open Ophthalmology","volume":"9 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104589","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}
引用次数: 0
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BMJ Open Ophthalmology
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