Pentosan Polysulfate Maculopathy: Prevalence, Spectrum of Disease, and Choroidal Imaging Analysis Based on Prospective Screening

Purpose: To describe the prevalence and spectrum of disease of pentosan polysulfate (PPS) maculopathy in a large multimodal retinal imaging study and to report the results of choroidal vascularity index (CVI) analysis. Design: Prospective cohort study Methods: Of 741 patients prescribed PPS within a large university database, 100 (13.4%) with any consumption agreed to participate in a prospective screening investigation. Multimodal retinal imaging including near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) was performed in all patients. Characteristic findings of affected patients were identified, and affected and unaffected cohorts were compared. CVI, defined as stromal choroidal area (SCA) divided by the total choroidal area, was analyzed. Results: The prevalence of PPS maculopathy was 16%. NIR illustrated punctate hyperreflective lesions with early presentation. FAF illustrated a speckled macular network of hypo-and hyperautofluorescence colocalized with multifocal hyperreflective retinal pigment epithelial lesions on SD-OCT. Advanced cases demonstrated varying degrees of atrophy. The affected cohort exhibited significantly greater mean PPS therapy duration, mean daily dosage, and mean cumulative dosage (19.5 +/- 5.5 years, 433.9 +/- 137.6 mg, 3,103.1 +/- 1,402.2 g) compared with the unaffected cohort (7.1 +/- 6.6 years, 291.6 +/- 177.6 mg, 768.4 +/- 754.8 g). SCA was significantly lower and CVI was significantly greater in the affected vs the unaffected group. Conclusions: This prospective cohort study identified a prevalence of PPS maculopathy of 15%-20% among PPS users who agreed to participate. A spectrum of findings may be observed with multimodal retinal imaging. Significant choroidal abnormalities associated with this characteristic maculopathy may provide surrogate markers of macular toxicity. (Am J Ophthalmol 2021;227: 125138. Published by Elsevier Inc.)

Automated summary

This study revealed a prevalence of 16% for PPS maculopathy, with affected patients showing longer PPS therapy duration and higher cumulative dosage. Multimodal retinal imaging aids in observing characteristic findings of the disease, while choroidal abnormalities may serve as surrogate markers for macular toxicity.