Comprehensive Ocular Characteristics in Cystinosis after Hematopoietic Stem-Cell Gene Therapy Over 24 Months.
Publication Year:
2026
PubMed ID:
41672367
Public Summary:
Cystinosis is a rare inherited disease that causes a substance called cystine to build up inside cells throughout the body. In the eyes, cystine forms crystals in the cornea (the clear front surface of the eye), which can lead to light sensitivity, discomfort, and visual problems over time.
This study followed six people with cystinosis who received a new hematopoietic stem cell gene therapy approach called CTNS-RD-04. This therapy uses a patient’s own blood-forming stem cells, which are modified in the laboratory to carry a healthy copy of the faulty gene and then returned to the patient. The goal is to help the body better manage cystine buildup.
Researchers carefully examined the structure and function of the eyes before treatment and over a two-year period afterward. At the start of the study, most participants had good visual acuity (sharpness of vision), but many had reduced contrast sensitivity (difficulty distinguishing objects from their background) and visible cystine crystals in the cornea. Imaging also showed increased thickness in parts of the cornea and retina.
Over 24 months after gene therapy, most measures of vision and eye structure remained stable. There were mild changes in corneal and retinal thickness over time, but no major worsening of vision. One consistent finding was a gradual decrease in the sensitivity of the cornea. Light sensitivity generally remained stable or improved.
Overall, these results suggest that eye findings in cystinosis have recognizable patterns and that, over two years following gene therapy, most visual and structural eye measures remained stable. Continued eye monitoring is important, and corneal nerve function may be a useful marker in future studies of new treatments.
Scientific Abstract:
PURPOSE: Characterize ocular structure and function in cystinosis and describe 24-month outcomes after autologous hematopoietic stem-cell gene therapy (HSCT). DESIGN: Prospective, interventional case series. PARTICIPANTS: Six individuals with genetically confirmed cystinosis undergoing HSCT. Both eyes were analyzed when evaluable. METHODS: Examinations were performed at baseline and at approximately 1 to 5, 12, and 18 to 24 months after infusion. Measurements included best-corrected visual acuity (BCVA), Pelli-Robson contrast sensitivity (CS), intraocular pressure, corneal sensation, corneal pachymetry, topography, tear osmolarity, Schirmer I, slit-lamp examination, dilated fundus examination, and anterior-segment and macular optical coherence tomography (OCT). MAIN OUTCOME MEASURES: BCVA, CS, central and peripheral corneal thickness (CCT, PCT), corneal sensation, tear metrics and photophobia, macular OCT metrics including central macular thickness (CMT) and intraretinal hyperreflective dots, and presence of corneal and conjunctival crystals. RESULTS: At baseline, BCVA was preserved (mean logMAR 0.08 OD and 0.063 OS), whereas CS was frequently reduced (means 1.50 OD and 1.35 OS, with 3 of 4 impaired). Diffuse corneal crystals were present in all participants, and conjunctival crystals in most. CCT was elevated (median 579 microm) while PCT and keratometry were largely within normal ranges. Tear hyperosmolarity occurred in 4 of 5 participants despite generally normal Schirmer I. Macular OCT showed increased CMT (means 280.8 microm OD and 305.6 microm OS) with subtle intraretinal hyperreflective dots consistent with crystalline deposits. No corneal edema was observed. Over 24 months, BCVA and CS remained largely stable. CCT, PCT, and CMT showed mild, nonuniform fluctuations that often peaked at 12 months with partial regression by 24 months. The most consistent longitudinal change was a progressive reduction in corneal sensation toward low measurable values. Photophobia was stable or improved, refraction changes were minor, and intraocular pressure remained within normal limits. CONCLUSIONS: Cystinosis demonstrates a distinctive multimodal ocular phenotype characterized by corneal crystals, increased central corneal and macular thickness, and reduced CS despite preserved acuity. Across 2 years after HSCT, most structural and functional measures were stable, while corneal hypoesthesia progressed. These findings support continued ophthalmic surveillance and highlight corneal nerve function as a potential endpoint for future trials.