Abstract：
OBJECTIVE: To assess the impact of baseline data on psychophysical and morphological outcomes of subretinal voretigene neparvovec (VN) (Luxturna, Spark Therapeutics, Inc.) treatment.
METHODS: Single-center, retrospective, longitudinal, consecutive case series.
METHODS: Patients with RPE65-biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) treated between February 2020 and March 2022 with VN and oral immunosuppression according to the manufacturer\'s recommendation by one surgeon (F.G.H.).
METHODS: Retrospective analysis of surgical and clinical records, ancillary testing, and retinal imaging after VN therapy for RPE65-IRD. Descriptive statistics compared data at baseline up to 32 months post-treatment.
METHODS: Best-corrected visual acuity (BCVA), low-luminance VA (LLVA), Goldmann visual fields (GVFs), chromatic full-field stimulus threshold (FST) testing (FST), scotopic and photopic 2-color threshold perimetry (2CTP), and multimodal retinal imaging.
RESULTS: Thirty eyes of 19 patients were analyzed (10 pediatric patients < 20 years; 20 adult patients > 20 years of age; overall range: 8-40 years) with a median follow-up of 15 months (range, 1-32). The fovea was completely or partially detached in 16 eyes, attached in 12 eyes, and not assessable in 2 eyes on intraoperative imaging. Median BCVA at baseline was better in the pediatric group (P < 0.05) and did not change significantly independent of age. Meaningful loss of BCVA (≥ 0.3 logarithm of the minimal angle of resolution [logMAR]) occurred in 5 of 18 adult eyes, and a meaningful gain (≥-0.3 logMAR) occurred in 2 of 18 adult and 2 of 8 pediatric eyes. The LLVA and scotopic 2CTP improved considerably in pediatric patients. Scotopic blue FST improved at all ages but more in pediatric patients (8/8 eyes gained ≥ 10 decibels [dB]; P < 0.05). In pediatric patients, median GVF improved by 20% for target V4e and by 50% for target III4e (target I4e not detected). Novel atrophy developed in 13 of 26 eyes at the site of the bleb or peripheral of vascular arcades. Improvements in FST did not correlate with development of chorioretinal atrophy at 12 months. Mean central retinal thickness was 165.87 μm (± 26.26) at baseline (30 eyes) and 157.69 μm (± 30.3) at 12 months (26 eyes). Eight adult patients were treated unilaterally. The untreated eyes did not show meaningful changes during follow-up.
CONCLUSIONS: These data in a clinical setting show the effectiveness of VN therapy with stable median BCVA and mean retinal thickness and improvements of LLVA, FST, and 2CTP up to 32 months. Treatment effects were superior in the pediatric group. We observed new chorioretinal atrophy in 50% of the treated eyes.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
METHODS: Single-center, retrospective, longitudinal, consecutive case series.
METHODS: Patients with RPE65-biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) treated between February 2020 and March 2022 with VN and oral immunosuppression according to the manufacturer\'s recommendation by one surgeon (F.G.H.).
METHODS: Retrospective analysis of surgical and clinical records, ancillary testing, and retinal imaging after VN therapy for RPE65-IRD. Descriptive statistics compared data at baseline up to 32 months post-treatment.
METHODS: Best-corrected visual acuity (BCVA), low-luminance VA (LLVA), Goldmann visual fields (GVFs), chromatic full-field stimulus threshold (FST) testing (FST), scotopic and photopic 2-color threshold perimetry (2CTP), and multimodal retinal imaging.
RESULTS: Thirty eyes of 19 patients were analyzed (10 pediatric patients < 20 years; 20 adult patients > 20 years of age; overall range: 8-40 years) with a median follow-up of 15 months (range, 1-32). The fovea was completely or partially detached in 16 eyes, attached in 12 eyes, and not assessable in 2 eyes on intraoperative imaging. Median BCVA at baseline was better in the pediatric group (P < 0.05) and did not change significantly independent of age. Meaningful loss of BCVA (≥ 0.3 logarithm of the minimal angle of resolution [logMAR]) occurred in 5 of 18 adult eyes, and a meaningful gain (≥-0.3 logMAR) occurred in 2 of 18 adult and 2 of 8 pediatric eyes. The LLVA and scotopic 2CTP improved considerably in pediatric patients. Scotopic blue FST improved at all ages but more in pediatric patients (8/8 eyes gained ≥ 10 decibels [dB]; P < 0.05). In pediatric patients, median GVF improved by 20% for target V4e and by 50% for target III4e (target I4e not detected). Novel atrophy developed in 13 of 26 eyes at the site of the bleb or peripheral of vascular arcades. Improvements in FST did not correlate with development of chorioretinal atrophy at 12 months. Mean central retinal thickness was 165.87 μm (± 26.26) at baseline (30 eyes) and 157.69 μm (± 30.3) at 12 months (26 eyes). Eight adult patients were treated unilaterally. The untreated eyes did not show meaningful changes during follow-up.
CONCLUSIONS: These data in a clinical setting show the effectiveness of VN therapy with stable median BCVA and mean retinal thickness and improvements of LLVA, FST, and 2CTP up to 32 months. Treatment effects were superior in the pediatric group. We observed new chorioretinal atrophy in 50% of the treated eyes.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
摘要：
目的：评估基线数据对视网膜下VretigeneNeparvovec（VN，Luxturna®）治疗。
方法：单中心，回顾性,纵向,连续病例系列。
方法：在02-2020和03-2022之间由一名外科医生（FGH）根据制造商的建议进行VN和口服免疫抑制治疗的RPE65-IRD患者。
方法：回顾性分析手术和临床记录，RPE65-IRDVN治疗后的辅助测试和视网膜成像。描述性统计比较了基线直至治疗后24个月的数据。
方法：最佳矫正视力（BCVA），低亮度VA(LLVA)，戈德曼视野（GVF），彩色全场刺激阈值测试(FST)，暗视和明视双色阈值视野测定（2CTP），多模态视网膜成像。
结果：分析了30只眼/19例患者（10例儿科<20岁，20名成人（8-40岁，中位随访15个月，范围1-32）。在16例中，中央凹完全或部分脱离，在12例中附着，在术中成像中无法评估2只眼睛。基线时的中位BCVA在儿科组中更好（p<0.05），并且没有显著变化，与年龄无关。有意义的BCVA损失（≥0.3logMAR）发生在4/18成人眼，有意义的增益（≥-0.3logMAR）在2/18成人和2/8儿童的眼睛。LLVA和scotopic2CTP在儿科中有很大改善。苏格兰蓝FST在所有年龄段都得到了改善，儿科更多(8/8眼睛增益≥10dB，p<0.05)。在儿科，目标V4e的GVF中位数提高了20%,目标III4e的GVF中位数提高了50%(未检测到目标I4e).在血管拱廊的气泡和/或周围的13/26眼中出现了新的萎缩。FST改善与M12时脉络膜视网膜萎缩的发展无关。基线（30只眼）时的平均中央视网膜厚度为166.7μm（±25.45），M12（26只眼）时的平均中央视网膜厚度为157.69μm（±30.3）。8名成人患者接受了单方面治疗。未治疗的眼睛在随访期间没有显示有意义的变化。
结论：这些真实世界的数据显示VN治疗的有效性与稳定的中位BCVA和平均视网膜厚度，和LLVA的改进，FST和2CTP长达32个月。小儿组治疗效果优于对照组。我们在50％的治疗眼睛中观察到新的脉络膜视网膜萎缩。
方法：单中心，回顾性,纵向,连续病例系列。
方法：在02-2020和03-2022之间由一名外科医生（FGH）根据制造商的建议进行VN和口服免疫抑制治疗的RPE65-IRD患者。
方法：回顾性分析手术和临床记录，RPE65-IRDVN治疗后的辅助测试和视网膜成像。描述性统计比较了基线直至治疗后24个月的数据。
方法：最佳矫正视力（BCVA），低亮度VA(LLVA)，戈德曼视野（GVF），彩色全场刺激阈值测试(FST)，暗视和明视双色阈值视野测定（2CTP），多模态视网膜成像。
结果：分析了30只眼/19例患者（10例儿科<20岁，20名成人（8-40岁，中位随访15个月，范围1-32）。在16例中，中央凹完全或部分脱离，在12例中附着，在术中成像中无法评估2只眼睛。基线时的中位BCVA在儿科组中更好（p<0.05），并且没有显著变化，与年龄无关。有意义的BCVA损失（≥0.3logMAR）发生在4/18成人眼，有意义的增益（≥-0.3logMAR）在2/18成人和2/8儿童的眼睛。LLVA和scotopic2CTP在儿科中有很大改善。苏格兰蓝FST在所有年龄段都得到了改善，儿科更多(8/8眼睛增益≥10dB，p<0.05)。在儿科，目标V4e的GVF中位数提高了20%,目标III4e的GVF中位数提高了50%(未检测到目标I4e).在血管拱廊的气泡和/或周围的13/26眼中出现了新的萎缩。FST改善与M12时脉络膜视网膜萎缩的发展无关。基线（30只眼）时的平均中央视网膜厚度为166.7μm（±25.45），M12（26只眼）时的平均中央视网膜厚度为157.69μm（±30.3）。8名成人患者接受了单方面治疗。未治疗的眼睛在随访期间没有显示有意义的变化。
结论：这些真实世界的数据显示VN治疗的有效性与稳定的中位BCVA和平均视网膜厚度，和LLVA的改进，FST和2CTP长达32个月。小儿组治疗效果优于对照组。我们在50％的治疗眼睛中观察到新的脉络膜视网膜萎缩。
