Abstract：
OBJECTIVE: To assess the efficacy of voretigene neparvovec (VN) treatment by objective fixation stability and chromatic pupillometry testing in clinical practice.
METHODS: Retrospective cohort study with longitudinal follow-up.
METHODS: Twelve patients (aged 7-34 years) with RPE65-related inherited retinal dystrophies were treated at the same center with VN in both eyes.
METHODS: Patients treated at the same center with VN were evaluated over a 12-month posttreatment follow-up by subjective and objective tests. Furthermore, patients treated with VN who developed atrophy were compared with those who did not.
METHODS: Best-corrected visual acuity (BCVA), full-field stimulus threshold test (FST), semiautomated kinetic visual field (SKVF), microperimetry, and chromatic pupillometry over a 12-month follow-up.
RESULTS: Significant improvements of BCVA (P < 0.001), SKVF (P < 0.05), and FST (P < 0.001) were already observed 45 days after treatment and were maintained at the 12-month timepoint. Fixation stability, assessed by microperimetry, improved significantly (P < 0.05) after treatment. Chromatic pupillometry showed significant improvements (P < 0.05) at the 6- and 12-month timepoints. The increase in maximum pupillary constriction significantly (P < 0.001) correlated with higher retinal sensitivity in FST. Four patients developed multifocal retinal atrophy in both eyes, detected at the 6-month timepoint, but this atrophy was not generally associated with worse visual function outcomes.
CONCLUSIONS: This study explores objective outcomes in order to demonstrate the efficacy of VN treatment in addition to the tests normally performed in clinical practice. Our findings show a significant improvement of retinal function both in subjective assessments, such as BCVA, SKVF, and FST, and in objective measurements of fixation stability and maximum pupillary constriction. Moreover, the significant correlation between maximum pupillary constriction and light sensitivity thresholds corroborates the introduction of chromatic pupillometry as an objective test to better assess treatment outcomes in patients with inherited retinal dystrophies.
BACKGROUND: Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.
METHODS: Retrospective cohort study with longitudinal follow-up.
METHODS: Twelve patients (aged 7-34 years) with RPE65-related inherited retinal dystrophies were treated at the same center with VN in both eyes.
METHODS: Patients treated at the same center with VN were evaluated over a 12-month posttreatment follow-up by subjective and objective tests. Furthermore, patients treated with VN who developed atrophy were compared with those who did not.
METHODS: Best-corrected visual acuity (BCVA), full-field stimulus threshold test (FST), semiautomated kinetic visual field (SKVF), microperimetry, and chromatic pupillometry over a 12-month follow-up.
RESULTS: Significant improvements of BCVA (P < 0.001), SKVF (P < 0.05), and FST (P < 0.001) were already observed 45 days after treatment and were maintained at the 12-month timepoint. Fixation stability, assessed by microperimetry, improved significantly (P < 0.05) after treatment. Chromatic pupillometry showed significant improvements (P < 0.05) at the 6- and 12-month timepoints. The increase in maximum pupillary constriction significantly (P < 0.001) correlated with higher retinal sensitivity in FST. Four patients developed multifocal retinal atrophy in both eyes, detected at the 6-month timepoint, but this atrophy was not generally associated with worse visual function outcomes.
CONCLUSIONS: This study explores objective outcomes in order to demonstrate the efficacy of VN treatment in addition to the tests normally performed in clinical practice. Our findings show a significant improvement of retinal function both in subjective assessments, such as BCVA, SKVF, and FST, and in objective measurements of fixation stability and maximum pupillary constriction. Moreover, the significant correlation between maximum pupillary constriction and light sensitivity thresholds corroborates the introduction of chromatic pupillometry as an objective test to better assess treatment outcomes in patients with inherited retinal dystrophies.
BACKGROUND: Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.
摘要：
目的：在临床实践中通过客观固定稳定性和彩色瞳孔测量测试来评估VretigeneNeparvovec（VN）治疗的疗效。
方法：纵向随访的回顾性队列研究。
方法：12例（年龄7至34岁）RPE65相关遗传性视网膜营养不良患者在同一中心接受双眼VN治疗。
方法：在同一中心接受VN治疗的患者在治疗后的12个月随访中通过主观和客观测试进行评估。此外，对发生萎缩的VN患者与未发生萎缩的VN患者进行比较.
方法：最佳矫正视力（BCVA），全场激励阈值测试(FST),半自动动态视野（SKVF），显微视野,12个月随访结果：BCVA的显着改善（p<0.001），治疗后45天已经观察到SKVF(p<0.05)和FST(p<0.001),并维持在12个月时间点。固定稳定性,通过显微视野法评估，治疗后明显改善(p<0.05)。在6个月和12个月的时间点,色度瞳孔测量显示出显著的改善(p<0.05)。最大瞳孔收缩的增加显著(p<0.001)与FST中更高的视网膜敏感性相关。四名患者双眼出现多灶性视网膜萎缩，在6个月的时间点检测到，但这种萎缩通常与较差的视觉功能结局无关.
结论：这项研究是首次尝试在现实生活中使用客观测试以及在临床实践中通常进行的测试来证明VN治疗的有效性。我们的研究结果表明，视网膜功能在主观评估中都有显着改善，比如BCVA,SKVF和FST,以及固定稳定性和最大瞳孔收缩的客观测量。此外，最大瞳孔收缩量与光敏感度阈值之间的显著相关性证实了在遗传性视网膜营养不良患者中引入彩色瞳孔测量法作为一种客观测试,以更好地评估治疗结果.
方法：纵向随访的回顾性队列研究。
方法：12例（年龄7至34岁）RPE65相关遗传性视网膜营养不良患者在同一中心接受双眼VN治疗。
方法：在同一中心接受VN治疗的患者在治疗后的12个月随访中通过主观和客观测试进行评估。此外，对发生萎缩的VN患者与未发生萎缩的VN患者进行比较.
方法：最佳矫正视力（BCVA），全场激励阈值测试(FST),半自动动态视野（SKVF），显微视野,12个月随访结果：BCVA的显着改善（p<0.001），治疗后45天已经观察到SKVF(p<0.05)和FST(p<0.001),并维持在12个月时间点。固定稳定性,通过显微视野法评估，治疗后明显改善(p<0.05)。在6个月和12个月的时间点,色度瞳孔测量显示出显著的改善(p<0.05)。最大瞳孔收缩的增加显著(p<0.001)与FST中更高的视网膜敏感性相关。四名患者双眼出现多灶性视网膜萎缩，在6个月的时间点检测到，但这种萎缩通常与较差的视觉功能结局无关.
结论：这项研究是首次尝试在现实生活中使用客观测试以及在临床实践中通常进行的测试来证明VN治疗的有效性。我们的研究结果表明，视网膜功能在主观评估中都有显着改善，比如BCVA,SKVF和FST,以及固定稳定性和最大瞳孔收缩的客观测量。此外，最大瞳孔收缩量与光敏感度阈值之间的显著相关性证实了在遗传性视网膜营养不良患者中引入彩色瞳孔测量法作为一种客观测试,以更好地评估治疗结果.
