Visual Function in Pentosan Polysulfate Sodium Maculopathy

Abstract

Purpose: Individuals with pentosan polysulfate sodium (PPS) maculopathy commonly report symptoms of prolonged dark adaptation and difficulty reading. We hypothesize that PPS maculopathy causes degradation of visual function not fully captured with visual acuity testing.

Methods: Subjects with PPS maculopathy underwent multimodal evaluation of retinal structure and function. Structural changes were graded as moderate or advanced. Patient-reported visual function was assessed with the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ-39) and Low Luminance Questionnaire (LLQ). Objective functional evaluations included Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), Pelli-Robson contrast sensitivity, mesopic microperimetry, and dark adaptometry. Functional testing results were correlated with structural disease category.

Results: Thirteen patients (26 eyes), median age 62 years (range, 37-76), completed the study. Median ETDRS letter score was 82 (Snellen equivalent 20/25). Median NEI-VFQ-39 and LLQ composite scores were 65 (range, 33-88) and 41 (range, 20-92), respectively. Median contrast sensitivity was 1.65 (range, 0.15-1.95), and median mesopic microperimetry average thresholds and percent reduced thresholds were 26 decibels (range, 0.4-28.6) and 21.6% (range, 0-100%), respectively. Median rod intercept time was 14.1 minutes (range, 4.4-20.0). Eyes with advanced disease based on retinal structure had significantly worse retinal function for several testing modalities.

Conclusions: PPS maculopathy causes considerable visual function degradation that is not fully captured with BCVA testing. There was good correlation between other measures of visual function and disease severity. These findings deepen our concern regarding this patient safety issue.

Figure 1.

PPS maculopathy fundus images. Fundus images of the left eye of three subjects sorted by disease severity: a subject with grade 1 disease on the left (subject 13; A, D), a subject with grade 2 disease in the middle (subject 7; B, E), and a subject with grade 3 disease on the right (subject 1; C, F). (A–C) Color fundus photographs demonstrating that all eyes show macular pigmentary changes, including pigment clumps amidst a background of yellowish subretinal deposits in milder eyes and center-threatening retinal pigment epithelium atrophy in severe cases (C). (D–F) Fundus autofluorescence images demonstrating fairly well-delineated areas of irregular hyper- and hypoautofluorescence signal involving the posterior pole. Center-threatening retinal pigment epithelium atrophy can be noted in severe cases (F). Note that, due to the small study size, subjects classified as either grade 1 or grade 2 were combined into one analysis group for this study.

Figure 2.

Macular sensitivity for two patients with differing disease severity. (A) Mesopic microperimetry demonstrated mildly subnormal sensitivities in a subject without RPE atrophy (subject 13). (B) In a subject with patchy paracentral atrophy (subject 9), microperimetry demonstrated deep scotomata associated with atrophy but only mildly subnormal sensitivity in areas outside of atrophy.