Comprehensive Ocular Characteristics in Cystinosis after Hematopoietic Stem-Cell Gene Therapy Over 24 Months

Characterize ocular structure and function in cystinosis and describe 24-month outcomes after autologous hematopoietic stem-cell gene therapy (HSCT).

Prospective, interventional case series.

Six individuals with genetically confirmed cystinosis undergoing HSCT. Both eyes were analyzed when evaluable.

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).

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.

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 µm) 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 µm OD and 305.6 µm 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.

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.