Pentosan Polysulfate Maculopathy versus Inherited Macular Dystrophies: Comparative Assessment with Multimodal Imaging

Purpose: To evaluate whether pentosan polysulfate (PPS) maculopathy manifests distinctive characteristics that permit differentiation from hereditary maculopathies with multimodal fundus imaging.

Design: Retrospective review.

Participants: Emory Eye Center databases were queried for the following International Classification of Diseases codes from May 20, 2014, through October 22, 2019: 362.70 (unspecified hereditary retinal dystrophy), 362.74 + H35.52 (pigmentary retinal dystrophy), 362.76 + H35.54 (dystrophies primarily involving the retinal pigment epithelium), and H35.50 (unspecified macular degeneration).

Methods: Fundus images for each patient were evaluated, including color fundus photographs, fundus autofluorescence images, and spectral-domain OCT images. Cases with imaging sufficient for diagnostic classification were analyzed. Masked graders classified patient images as follows: highly suggestive of PPS maculopathy; some features resembling PPS maculopathy, but not classic disease; and clearly distinct from PPS maculopathy.

Main outcome measures: Sensitivity and specificity for identification of PPS maculopathy by masked reviewers.

Results: A total of 1394 patients were evaluated, and 1131 had imaging sufficient for classification. Fifteen patients were categorized as having findings highly suggestive of PPS maculopathy; 25 patients showed some features resembling PPS maculopathy but not classic disease; and 1091 patients showed evidence of disease clearly distinct from PPS maculopathy. All 10 patients with PPS maculopathy in this dataset were correctly categorized as having PPS maculopathy. Five patients without PPS exposure were categorized incorrectly as having PPS maculopathy. This represented a 100% sensitivity and 99.6% specificity for identification of PPS maculopathy by masked review of fundus imaging in this dataset.

Conclusions: The imaging characteristics of PPS maculopathy allow for differentiation from hereditary maculopathies even in the absence of known exposure to the drug.