Merle David A, Hertens Leen, Dimopoulos Spyridon, Kohl Susanne, Van Haute Manon, De Baere Elfride, De Bruyne Marieke, Janssens Barbara, Rüther Klaus, Huchzermeyer Cord, Mazzola Pascale, Nerinckx Fanny, Haack Tobias, Wolfram Lasse, Kempf Melanie, Kühlewein Laura, Stingl Krunoslav, Leroy Bart P, Stingl Katarina
Department of Ophthalmology, University Eye Clinic, Eberhard Karls University of Tübingen, Tübingen, Germany.
Institute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of Tübingen, Tübingen, Germany.
Transl Vis Sci Technol. 2025 Aug 1;14(8):8. doi: 10.1167/tvst.14.8.8.
Voretigene neparvovec is approved for RPE65-associated inherited retinal degeneration (RPE65-IRD) in the United States and the European Union. According to current knowledge, early treatment benefits efficacy. However, consensus on treating mild cases is lacking due to ambiguity in balancing clinical benefits with potential side effects. Therefore, we present short-term outcomes of four pediatric patients with milder types of RPE65-IRD.
Two unrelated pediatric patients were unilaterally treated at the University Eye Hospital in Tübingen, Germany. Another two unrelated pediatric patients were bilaterally treated at Ghent University Hospital, Belgium. Examinations were performed before and until at least 6 months after treatment, including best-corrected visual acuity, slit-lamp examination, fundus photography, short-wavelength fundus autofluorescence, optical coherence tomography, 90° kinetic perimetry, dark-adapted chromatic perimetry, and full-field stimulus threshold measurements.
Despite surgical challenges, treatment with voretigene neparvovec was successful in all four patients. All patients showed rod functional rescue with stable best-corrected visual acuity. Three patients suffered chorioretinal atrophy at the retinotomy site but none developed signs of fast-growing CRA. One case developed limited CRA in the bleb area, potentially related to inflammation in the subretinal space.
Treatment with voretigene neparvovec was safe and effective in patients with mild RPE65-IRD. Early treatment showed good functional outcomes. Also, treatment at stages without profound retinal degeneration might lower the risk of fast-growing CRA.
This study aids clinical decision-making in unclear cases by demonstrating that early treatment with voretigene neparvovec in mild RPE65-IRD provides functional benefits while minimizing the risk of fast-growing chorioretinal atrophy.
在美国和欧盟，维替泊汀已被批准用于治疗与RPE65相关的遗传性视网膜变性（RPE65-IRD）。根据目前的认知，早期治疗有利于提高疗效。然而，由于在平衡临床益处与潜在副作用方面存在不确定性，对于轻度病例的治疗尚无共识。因此，我们报告了4例轻度RPE65-IRD儿科患者的短期治疗结果。
2例无关的儿科患者在德国图宾根大学眼科医院接受了单侧治疗。另外2例无关的儿科患者在比利时根特大学医院接受了双侧治疗。在治疗前及治疗后至少6个月进行检查，包括最佳矫正视力、裂隙灯检查、眼底照相、短波眼底自发荧光、光学相干断层扫描、90°动态视野检查、暗适应色觉视野检查和全视野刺激阈值测量。
尽管手术存在挑战，但维替泊汀治疗在所有4例患者中均取得成功。所有患者的视杆功能均得到挽救，最佳矫正视力稳定。3例患者在视网膜切开部位出现脉络膜视网膜萎缩，但均未出现快速进展性脉络膜视网膜萎缩（CRA）的迹象。1例患者在泡状区域出现局限性CRA，可能与视网膜下间隙炎症有关。
维替泊汀治疗轻度RPE65-IRD患者安全有效。早期治疗显示出良好的功能预后。此外，在视网膜未发生严重变性的阶段进行治疗可能会降低快速进展性CRA的风险。
本研究表明，在轻度RPE65-IRD中早期使用维替泊汀进行治疗可提供功能益处，同时将快速进展性脉络膜视网膜萎缩的风险降至最低，有助于在不明确的病例中进行临床决策。
