Stingl Krunoslav T, Kuehlewein Laura, Weisschuh Nicole, Biskup Saskia, Cremers Frans P M, Khan M Imran, Kelbsch Carina, Peters Tobias, Ueffing Marius, Wilhelm Barbara, Zrenner Eberhart, Stingl Katarina
Center for Ophthalmology, University of Tübingen, Tübingen, Germany.
Praxis für Humangenetik Tübingen, Tübingen, Germany.
Transl Vis Sci Technol. 2019 Dec 20;8(6):45. doi: 10.1167/tvst.8.6.45. eCollection 2019 Nov.
Mutations in the gene cause early-onset retinal degeneration (EORD). Clinical disease progression markers, such as visual fields or electrophysiology, are not reliably measurable in most patients to follow the retinal function in patients with -mutations.
Ten patients (five females, five males; age 22-56 years) with EORD caused by mutations were examined in a cross-sectional manner using best corrected visual acuity (BCVA), perimetry, full-field and multifocal electroretinography, full-field stimulus threshold (FST), and pupillography to red and blue light. Disease duration was defined as the difference between the age at the first symptoms to the age at examination in years.
BCVA was quantifiable in six patients and ranged from light perception to 20/50. The visual field was measurable only in three patients who had the shortest disease duration. Full-field and multifocal electroretinography were not measurable in any patient. FST to blue and red light were measurable in all patients except the one with the longest disease duration; the thresholds ranged from -16.7 to 1.5 dB for red light and from -40.2 to 2.5 dB for blue light (0 dB = 0.01 cd.s/m) and showed correlations with disease duration ( = 0.87 for blue, = 0.65 for red, = 0.8 for blue-red difference). The maximal relative pupil constriction amplitude (MRA) showed low or no correlations with disease duration ( = -0.55 for blue, = -0.3 for red light); the blue-red difference in the post-illumination pupil responses (PIPR) showed no correlation with disease duration ( = -0.05). Compared to healthy eyes, the MRA to red and blue light was significantly decreased ( < 0.001) and the blue-red PIPR difference was significantly increased ( = 0.003).
FST features a valid clinical marker in late-stage early-onset retinitis pigmentosa caused by mutations correlating with disease duration. This indicates the potential as a progression marker of disease. The pupil responses to full-field chromatic stimuli show significant differences from the normal population: the remaining responses, although reduced, indicate a partially preserved inner retinal function despite severe photoreceptor dysfunction.
The functional measurements presented in this study present a valid clinical progression marker in late-stage early onset retinitis pigmentosa caused by biallelic mutations. Additionally, they can be used as outcome measures for safety and efficacy in clinical therapy trials.
该基因的突变会导致早发性视网膜变性（EORD）。在大多数患有该基因突变的患者中，诸如视野或电生理等临床疾病进展标志物并不能可靠地用于测量视网膜功能。
对10例由该基因突变导致EORD的患者（5名女性，5名男性；年龄22 - 56岁）进行横断面检查，采用最佳矫正视力（BCVA）、视野检查、全视野和多焦视网膜电图、全视野刺激阈值（FST）以及对红光和蓝光的瞳孔描记法。疾病持续时间定义为首次出现症状时的年龄与检查时年龄之差（以年为单位）。
6例患者的BCVA可量化，范围从光感至20/50。仅3例疾病持续时间最短的患者可测量视野。所有患者均无法测量全视野和多焦视网膜电图。除疾病持续时间最长的患者外，所有患者均可测量对红光和蓝光的FST；红光阈值范围为 - 16.7至1.5 dB，蓝光阈值范围为 - 40.2至2.5 dB（0 dB = 0.01 cd·s/m²），且与疾病持续时间相关（蓝光r = 0.87，红光r = 0.65，红蓝差值r = 0.8）。最大相对瞳孔收缩幅度（MRA）与疾病持续时间的相关性较低或无相关性（蓝光r = - 0.55，红光r = - 0.3）；光照后瞳孔反应（PIPR）的红蓝差值与疾病持续时间无相关性（r = - 0.05）。与健康眼睛相比，对红光和蓝光的MRA显著降低（P < 0.001），红蓝PIPR差值显著增加（P = 0.003）。
在由该基因突变引起的晚期早发性色素性视网膜炎中，FST是一个有效的临床标志物，与疾病持续时间相关。这表明其作为疾病进展标志物的潜力。对全视野色刺激的瞳孔反应与正常人群有显著差异：其余反应虽有所降低，但表明尽管存在严重的光感受器功能障碍，视网膜内层功能仍部分保留。
本研究中呈现功能测量结果在由双等位基因突变引起的晚期早发性色素性视网膜炎中是一个有效的临床进展标志物。此外，它们可作为临床治疗试验中安全性和有效性的疗效指标。
