ABSTRACT

Purpose: To identify structural and functional outcome measures among patients with Rho-positive autosomal dominant Retinitis Pigmentosa (adRP) to aid neuroprotection trial design.

Methods: This was a retrospective cohort study of 52 patients with Rho-positive adRP. We measured Goldmann Visual Fields (GVF) constriction in four sectors (nasal, temporal, inferior, superior), and sectoral Ellipsoid Zone (EZ) width degeneration using Spectral Domain Optical Coherence Tomography (OCT) scans. Disease progression trajectories were projected using mixed effects modeling.

Results: Superior GVF was most constricted at presentation and had the shallowest trajectory (less steep negative slope); Inferior GVF was less constricted (corrected p < .001) and had a steeper negative slope (corrected p = .019) than superior GVF. Temporal EZ was most stable on OCT with a relatively shallow negative trajectory (corrected p = .011).

Conclusions: Patients’ superior visual fields presented with more constriction and subsequently had a shallow negative slope suggesting the corresponding inferior retina may be “burned out” at presentation. Targeted therapies for adRP will likely show a greater efficacy signal if delivered to the superior and nasal retina, which may demonstrate more change on OCT and GVF over the course of a neuroprotection trial.

Translational Relevance: Mixed effects analysis of sectoral visual field constriction and EZ degeneration in Rho-positive adRP can prove useful in monitoring therapeutic efficacy and identifying targets for local therapies.

摘要

目的：确定 Rho 阳性常染色体显性色素性视网膜炎 (adRP) 患者的结构和功能结果测量，以帮助神经保护试验设计。

方法：这是一项对 52 名 Rho 阳性 adRP 患者进行的回顾性队列研究。我们使用光谱域光学相干断层扫描 (OCT) 扫描测量了四个扇区（鼻、颞、下、上）的戈德曼视野 (GVF) 收缩和扇区椭圆体区 (EZ) 宽度退化。使用混合效应模型预测疾病进展轨迹。

结果: 优越的 GVF 在就诊时最狭窄，轨迹最浅（负斜率较小）；与优越的 GVF 相比，劣质 GVF 的收缩较小（校正后的p < .001）并且负斜率更陡峭（校正后的p = .019）。时间 EZ 在 OCT 上最为稳定，负轨迹相对较浅（校正后的p = .011）。

结论：患者的上视野呈现出更多的收缩，随后有一个较浅的负斜率，表明相应的下视网膜可能在就诊时“烧毁”。如果将 adRP 的靶向治疗传递到上视网膜和鼻部视网膜，可能会显示出更大的疗效信号，这可能会在神经保护试验过程中显示 OCT 和 GVF 的更多变化。

转化相关性：对 Rho 阳性 adRP 中的扇形视野收缩和 EZ 变性的混合效应分析可以证明在监测治疗效果和确定局部治疗的目标方面很有用。