A prospective multimodal imaging analysis and structure-function correlation in patients exposed to pentosan polysulfate

Abstract

Purpose : To study the anatomic and functional retinal changes in patients exposed to pentosan polysulfate (PPS) using multimodal imaging and mesopic microperimetry.

Methods : This is a prospective study including PPS-exposed eyes with and without maculopathy. Patients underwent color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF; Spectralis OCT2, Heidelberg Engineering), microperimetry (MAIA, CenterVue), and macular swept-source OCT angiography (SS-OCTA; PLEX® Elite 9000, Carl Zeiss Meditec) using 3×3, 6×6, and 12×12-mm protocols. SS-OCTA scans were processed with the macular density algorithm (v.0.7.3.3) on the ARI Network (Zeiss Portal v5.4) to calculate vessel density (VD) and foveal avascular zone (FAZ) metrics. 6x6-mm choriocapillaris slabs were processed with the Choriocapillaris Slab Imaging (v.0.2) algorithm on ARI Network; inner choroidal flow deficit percentage (ICFD%) was measured using the Phansalkar method on FIJI (NIH). All patients were given a genitourinary (GU) pain index questionnaire. Mann-Whitney U testing was used to compare the two groups.

Results : A total of 32 eyes in 16 patients (94% female; age: 61.6±13.0) were included; 4 patients (25%) had signs of maculopathy. There was no significant difference between maculopathy and non-maculopathy groups for age (p=0.21) or GU pain index score (p=0.86). Mean PPS lifetime dose was higher in patients with maculopathy than without (2436.4g ± 414.4 versus 812.1g ± 677.7, p<0.01). Ten eyes (31.25%) showed abnormal CFP findings including drusen (40%) and RPE irregularities (60%). One eye (3.1%) had a lamellar hole, and another (3.1%) had a full-thickness macular hole. FAF showed hypoautofluorescent spots in 6 eyes (18.8%) and hyperautofluorescent spots in 5 eyes (15.6%). The maculopathy group showed a significantly decreased sensitivity in microperimetry (p<0.01), a smaller average thickness of the outer nuclear layer (p=0.03), a greater ICFD% in 3x3mm and 6x6mm protocols, and a smaller FAZ area in 6x6mm and 12x12mm protocols (p<0.05).

Conclusions : Patients with PPS-related maculopathy showed lower retinal sensitivity, thinner outer nuclear layer, greater ICFD%, and smaller FAZ area compared to those without maculopathy. Multimodal imaging can provide biomarkers for early detection of PPS maculopathy and suggests that its pathogenesis may be related to choriocapillaris injury.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.