Corneal clouding, causing visual impairment, is seen in nearly all patients with mucopolysaccharidosis type 1 (MPS-1). Hematopoietic cell transplantation (HCT) is able to stabilize disease in many organs. Residual disease in several tissues is being increasingly recognized, however. Data on the effect of HCT on ocular disease in patients with MPS-1 are contradictory. With this study, we aim to clarify the long-term effects of HCT on ocular disease in these patients. Best corrected visual acuity (BCVA), refraction, intraocular pressure (IOP), and slit-lamp biomicroscopic and fundoscopic examinations, including corneal clouding, were collected prospectively from 24 patients with MPS-1 who underwent HCT successfully between 2003 and 2018 (92% with >95% chimerism and normal enzyme activity after HCT). The course of corneal clouding and BCVA after HCT were analyzed using a linear mixed model. Other parameters studied were clinical phenotype, age at time of transplantation, and hematologic enzyme activity after transplantation. Outcomes of additional ophthalmologic tests were described. In addition, IDUA and α-galactosidase A (AGAL) enzyme activity and glycosaminoglycan (GAG) concentration in tear fluid were determined. Corneal clouding stabilized in the first years after HCT but increased rapidly beyond 3 years (P < .0001). BCVA and IOP also worsened over time (P = .01 and P < .0001, respectively). IDUA activity in tear fluid remained very low (P < .0001). After initial stabilization in the cornea, ongoing ocular disease and low IDUA activity in tear fluid is seen in patients with MPS-1 despite treatment with HCT, unveiling a weak spot of current standard therapy. New therapies that overcome these shortcomings are needed to improve the late outcomes of patients.

中文翻译：

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造血细胞移植后I型黏多糖贮积病患儿眼部疾病的纵向分析。

几乎所有患有1型粘多糖贮积病（MPS-1）的患者都可见到导致视力障碍的角膜混浊。造血细胞移植（HCT）能够稳定许多器官的疾病。但是，越来越多地认识到几种组织中的残留疾病。HCT对MPS-1患者眼部疾病的影响数据是矛盾的。通过这项研究，我们旨在阐明HCT对这些患者眼部疾病的长期影响。前瞻性收集了2003年至2018年成功接受HCT的24例MPS-1患者的最佳矫正视力（BCVA），屈光度，眼内压（IOP）以及裂隙灯生物显微镜和眼底镜检查，包括角膜混浊（92％ HCT后具有> 95％的嵌合率和正常的酶活性）。使用线性混合模型分析HCT后角膜混浊和BCVA的过程。研究的其他参数是临床表型，移植时的年龄和移植后的血液酶活性。描述了其他眼科检查的结果。另外，测定了泪液中的IDUA和α-半乳糖苷酶A（AGAL）酶活性和糖胺聚糖（GAG）浓度。HCT后的最初几年角膜混浊稳定下来，但超过3年迅速增加（P <.0001）。BCVA和IOP也随着时间的推移而恶化（分别为P = .01和P <.0001）。泪液中的IDUA活性仍然很低（P <.0001）。尽管使用HCT进行了治疗，但在MPS-1患者中，角膜最初稳定后，仍观察到持续的眼病和泪液中IDUA活性低，揭示当前标准疗法的薄弱环节。需要克服这些缺点的新疗法来改善患者的晚期结果。