Abstract：
OBJECTIVE: To analyze the genetic findings, clinical spectrum, and natural history of Best vitelliform macular dystrophy (BVMD) in a cohort of 222 children and adults.
METHODS: Single-center retrospective, consecutive, observational study.
METHODS: Patients with a clinical diagnosis of BVMD from pedigrees with a likely disease-causing monoallelic sequence variant in the BEST1 gene.
METHODS: Data were extracted from electronic and physical case notes. Electrophysiologic assessment and molecular genetic testing were analyzed.
METHODS: Molecular genetic test findings and clinical findings including best-corrected visual acuity (BCVA), choroidal neovascularization (CNV) rates, and electrophysiologic parameters.
RESULTS: Two hundred twenty-two patients from 141 families were identified harboring 69 BEST1 variants. Mean age at presentation was 26.8 years (range, 1.3-84.8 years) and most patients (61.5%) demonstrated deterioration of central vision. Major funduscopic findings included 128 eyes (30.6%) with yellow vitelliform lesions, 78 eyes (18.7%) with atrophic changes, 49 eyes (11.7%) with fibrotic changes, 48 eyes (11.5%) with mild pigmentary changes, and 43 eyes (10.3%) showing a vitelliruptive appearance. Mean BCVA was 0.37 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/47) for the right eye and 0.33 logMAR (Snellen equivalent, 20/43) for the left eye at presentation, with a mean annual loss rate of 0.013 logMAR and 0.009 logMAR, respectively, over a mean follow-up of 9.7 years. Thirty-seven patients (17.3%) received a diagnosis of CNV over a mean follow-up of 8.0 years. Eyes with CNV that received treatment with an anti-vascular endothelial growth factor (VEGF) agent showed better mean BCVA compared with eyes that were not treated with an anti-VEGF agent (0.28 logMAR [Snellen equivalent, 20/38] vs. 0.62 logMAR [Snellen equivalent, 20/83]). Most eyes exhibited a hyperopic refractive error (78.7%), and 13 patients (6.1%) received a diagnosis of amblyopia. Among the 3 most common variants, p.(Ala243Val) was associated with a later age of onset, better age-adjusted BCVA, and less advanced Gass stages compared with p.(Arg218Cys) and p.(Arg218His).
CONCLUSIONS: BVMD shows a wide spectrum of phenotypic variability. The disease is very slowly progressive, and the observed phenotype-genotype correlations allow for more accurate prognostication and counselling.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
METHODS: Single-center retrospective, consecutive, observational study.
METHODS: Patients with a clinical diagnosis of BVMD from pedigrees with a likely disease-causing monoallelic sequence variant in the BEST1 gene.
METHODS: Data were extracted from electronic and physical case notes. Electrophysiologic assessment and molecular genetic testing were analyzed.
METHODS: Molecular genetic test findings and clinical findings including best-corrected visual acuity (BCVA), choroidal neovascularization (CNV) rates, and electrophysiologic parameters.
RESULTS: Two hundred twenty-two patients from 141 families were identified harboring 69 BEST1 variants. Mean age at presentation was 26.8 years (range, 1.3-84.8 years) and most patients (61.5%) demonstrated deterioration of central vision. Major funduscopic findings included 128 eyes (30.6%) with yellow vitelliform lesions, 78 eyes (18.7%) with atrophic changes, 49 eyes (11.7%) with fibrotic changes, 48 eyes (11.5%) with mild pigmentary changes, and 43 eyes (10.3%) showing a vitelliruptive appearance. Mean BCVA was 0.37 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/47) for the right eye and 0.33 logMAR (Snellen equivalent, 20/43) for the left eye at presentation, with a mean annual loss rate of 0.013 logMAR and 0.009 logMAR, respectively, over a mean follow-up of 9.7 years. Thirty-seven patients (17.3%) received a diagnosis of CNV over a mean follow-up of 8.0 years. Eyes with CNV that received treatment with an anti-vascular endothelial growth factor (VEGF) agent showed better mean BCVA compared with eyes that were not treated with an anti-VEGF agent (0.28 logMAR [Snellen equivalent, 20/38] vs. 0.62 logMAR [Snellen equivalent, 20/83]). Most eyes exhibited a hyperopic refractive error (78.7%), and 13 patients (6.1%) received a diagnosis of amblyopia. Among the 3 most common variants, p.(Ala243Val) was associated with a later age of onset, better age-adjusted BCVA, and less advanced Gass stages compared with p.(Arg218Cys) and p.(Arg218His).
CONCLUSIONS: BVMD shows a wide spectrum of phenotypic variability. The disease is very slowly progressive, and the observed phenotype-genotype correlations allow for more accurate prognostication and counselling.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
摘要：
目的：分析遗传结果，222名儿童和成人的最佳卵黄样黄斑营养不良（BVMD）的临床谱和自然史。
方法：单中心回顾性研究，连续的,观察性研究。
方法：临床诊断为BVMD的患者，来自BEST1基因中可能有致病单等位基因变异的家系。
方法：数据是从电子和物理案例笔记中提取的。分析了电生理评估和分子遗传学测试。
方法：分子遗传学检测，临床发现，包括最佳矫正视力（BCVA），脉络膜新生血管（CNV）率，和电生理参数。
结果：确认了来自141个家庭的222例患者（男性127例，女性95例），拥有69个BEST1变体，包括22种新颖的变体。出现时的平均年龄为26.8岁（范围1.3-84.8岁），大多数患者（61.5％）出现中央视力恶化。报告时的主要眼底检查结果包括：128眼（30.6％）有黄色卵黄样病变，78眼（18.7%）伴有萎缩性改变，49眼（11.7%）伴有纤维化改变，48只眼（11.5％），轻度色素性变化，43只眼（10.3％）表现为卵黄破裂。演示时，右眼的平均BCVA为0.37LogMAR（20/47），左眼的平均BCVA为0.33LogMAR（20/43）。平均随访9.6年，年平均损失率分别为0.013LogMAR和0.009LogMAR。37例患者（17.3％）被诊断为CNV，平均随访时间为8.0年（范围0-55年）。与未用抗VEGF治疗的眼睛相比,接受抗VEGF治疗的具有CNV的眼睛具有更好的平均VA(0.28LogMAR(20/38)对0.62LogMAR(20/83)。大多数眼睛表现出远视性屈光不正（185/235，78.7％），13例（6.1％）被诊断为弱视。在三种最常见的变体中，p.A243V与发病年龄较晚有关，与p.R218C和p.R218H相比，年龄调整后的VA和Gass分期较低
结论：BVMD表现出广泛的表型变异性。这种疾病进展非常缓慢，观察到的表型-基因型相关性允许更准确的预测和咨询。
方法：单中心回顾性研究，连续的,观察性研究。
方法：临床诊断为BVMD的患者，来自BEST1基因中可能有致病单等位基因变异的家系。
方法：数据是从电子和物理案例笔记中提取的。分析了电生理评估和分子遗传学测试。
方法：分子遗传学检测，临床发现，包括最佳矫正视力（BCVA），脉络膜新生血管（CNV）率，和电生理参数。
结果：确认了来自141个家庭的222例患者（男性127例，女性95例），拥有69个BEST1变体，包括22种新颖的变体。出现时的平均年龄为26.8岁（范围1.3-84.8岁），大多数患者（61.5％）出现中央视力恶化。报告时的主要眼底检查结果包括：128眼（30.6％）有黄色卵黄样病变，78眼（18.7%）伴有萎缩性改变，49眼（11.7%）伴有纤维化改变，48只眼（11.5％），轻度色素性变化，43只眼（10.3％）表现为卵黄破裂。演示时，右眼的平均BCVA为0.37LogMAR（20/47），左眼的平均BCVA为0.33LogMAR（20/43）。平均随访9.6年，年平均损失率分别为0.013LogMAR和0.009LogMAR。37例患者（17.3％）被诊断为CNV，平均随访时间为8.0年（范围0-55年）。与未用抗VEGF治疗的眼睛相比,接受抗VEGF治疗的具有CNV的眼睛具有更好的平均VA(0.28LogMAR(20/38)对0.62LogMAR(20/83)。大多数眼睛表现出远视性屈光不正（185/235，78.7％），13例（6.1％）被诊断为弱视。在三种最常见的变体中，p.A243V与发病年龄较晚有关，与p.R218C和p.R218H相比，年龄调整后的VA和Gass分期较低
结论：BVMD表现出广泛的表型变异性。这种疾病进展非常缓慢，观察到的表型-基因型相关性允许更准确的预测和咨询。
