Ectopic Ocular Surface Calcification in Patients With Hypophosphatasia Treated With Asfotase Alfa.

PURPOSE: To assess for ectopic ocular calcification in a series of patients with hypophosphatasia (HPP) treated with asfotase alfa, a recombinant tissue-nonspecific alkaline phosphatase.

METHODS

This is a retrospective analysis of subjects enrolled at Duke University Medical Center in ENB-009-10 (ClinicalTrials.gov: NCT01163149), a randomized controlled trial of asfotase alfa in adolescents and adults with HPP. Seven patients between the ages of 45 and 66 years diagnosed with HPP based on clinical features and low serum alkaline phosphatase levels were enrolled at our site. Subjects were randomized to receive either daily subcutaneous injections of asfotase alfa or no treatment. After 24 weeks, during the open-label extension phase, all subjects received treatment for at least 4 years. All subjects underwent comprehensive eye examinations at baseline and at 24-week intervals throughout the study to assess for development of ocular calcifications.

RESULTS

By week 120, all 7 subjects developed asymptomatic white refractile deposits in the interpalpebral perilimbal conjunctiva. Biopsy of the conjunctival lesions in 2 subjects revealed elastosis with subepithelial calcification. The lesions were nonprogressive and in 5 subjects exhibited some degree of regression.

CONCLUSIONS

Asfotase alfa was invariably associated with development of mild focal conjunctival calcification, likely through disinhibition of hydroxyapatite crystal propagation. The calcifications were not symptomatic or vision-threatening and should not preclude enzyme replacement therapy for patients with this rare and often debilitating disease.