Pentosan polysulfate sodium (PPS) maculopathy is a recently described condition of macular toxicity. We report the prevalence (15%), the clinical characteristics, and the multimodal imaging (MMI) features of PPS maculopathy based on a final prospective analysis of a cohort of 154 subjects and highlight the association with inflammatory bowel disease (IBD). In addition, we summarize the most recent and relevant literature on PPS maculopathy.This study and other recent analyses provide solid evidence of the toxic effects of PPS on the retina and choroid and refute the concept that the maculopathy is an association of the underlying disease, interstitial cystitis. Moreover, this study and others raise a major concern that PPS may also be toxic to the bowel. Vigilant surveillance of patients receiving this potentially harmful drug is critical.We review the recommended screening guidelines, the pathophysiology and MMI spectrum of disease, the differential diagnosis including MMI clues to an accurate diagnosis, and the progression of retinopathy that can take place despite discontinuation of the drug, emphasizing the critical importance of early detection of toxicity.

Purpose: To report a case of nonparaneoplastic autoimmune retinopathy in a patient with a diagnosis of Lambert–Eaton myasthenic syndrome. Methods: Case report. Main outcome measures included findings on retinal examination and analysis of fundus autofluorescence, spectral-domain optical coherence tomography, and full-field electroretinogram. Vitamin A levels and results of antiretinal antibody testing and paraneoplastic workup are also presented. Results: A 47-year-old male presented with a 1-year history of bilateral vision loss and nyctalopia. Past medical history was significant for Lambert–Eaton myasthenic syndrome, confirmed by positive voltage-gated calcium channel antibodies, and thymectomy reported as thymic follicular hyperplasia. Optical coherence tomography showed bilateral diffuse outer retinal atrophy and ellipsoid zone loss. Fundus autofluorescence displayed a bull's pattern of hyperautofluorescence around each fovea. Full-field electroretinogram showed an extinguished rod response and a severely depressed cone response in each eye. Conclusion: We describe a case of nonparaneoplastic autoimmune retinopathy in a patient with Lambert–Eaton myasthenic syndrome. Multimodal retinal imaging and electroretinogram confirmed the presence of autoimmune retinopathy with severe rod–cone degeneration. The association of this myasthenic syndrome with AIR is novel.

Purpose: To evaluate the prevalence and risk factors for development of paravascular inner retinal defects (PIRDs) using en face optical coherence tomography.Methods: This is a retrospective cross-sectional study. En face and cross-sectional optical coherence tomography images were reviewed (9 x 9 mm or 12 x 12 mm). Paravascular inner retinal defects were classified as either Grade 1 (i.e., paravascular inner retinal cysts) when the lesion was confined within the nerve fiber layer without any communication to the vitreous cavity or Grade 2 (i.e., paravascular lamellar hole) when the defects communicated to the vitreous. Paravascular inner retinal defect grading was correlated with presence of high myopia, stage of posterior vitreous detachment, and presence of epiretinal membrane and retinoschisis.Results: Of 1,074 patients (2,148 eyes), PIRDs were detected in 261 eyes with a prevalence of 261 per 2,148 eyes (12.2%) and 176 per 1,074 patients (16.4%). A total of 116 eyes (44.4%) displayed Grade 2 PIRDs while 145 eyes (55.6%) were Grade 1. In the multivariate logistic regression model, the presence of partial/complete posterior vitreous detachment, retinoschisis, and epiretinal membrane was significantly correlated with PIRDs (OR = 2.78 [1.7-4.4], P < 0.001; OR = 2.93 [1.7-5], P< 0.001; and OR = 25.9 [2.8-242.5], P < 0.001, respectively). The presence of partial/complete posterior vitreous detachment and epiretinal membrane was also significantly associated with Grade 2 PIRDs versus Grade 1 PIRDs (P = 0.03 and P < 0.001).Conclusion: Our results indicate that wide-field en face optical coherence tomography facilitates the identification of PIRDs over a large area of retina with a single capture. The presence of PIRDs was significantly associated with posterior vitreous detachment, epiretinal membrane, and retinoschisis, confirming the role of vitreoretinal traction in the pathogenesis of PIRDs.

PURPOSE:The purpose of this study was to report a unique case of pentosan polysulfate sodium (PPS) maculopathy with remarkable rapid progression over 2 years. These findings show the importance of early detection of macular disease to limit toxic exposure and reduce the risk of progression.METHODS:Multimodal retinal imaging including fundus autofluorescence, near-infrared reflectance with pseudocolor, and spectral domain optical coherence tomography was performed in an elderly patient with a history of PPS therapy (cumulative dose of 1,205 g) at baseline and 2 years later.RESULTS:Baseline multimodal retinal imaging failed to show significant macular findings of PPS toxicity in either eye, but on repeat evaluation 2 years later, advanced features of PPS maculopathy were detected in both eyes with fundus autofluorescence, near-infrared reflectance, pseudocolor, and spectral domain optical coherence tomography.CONCLUSION:This report describes a remarkable case of rapid progression of PPS maculopathy as documented with multimodal retinal imaging. The dramatic progression of macular findings over just 2 years underscores the importance of early detection and prompt withdrawal of therapy, if systemically feasible, to retard the development and rate of progression of PPS maculopathy.

PURPOSE: To compare choriocapillaris flow deficit (CC-FD) analysis using optical coherence tomography angiography (OCTA) in eyes of patients treated with high cumulative dosages of pentosan polysulfate sodium (PPS) but no signs of retinal toxicity versus healthy age-matched controls. DESIGN: Retrospective clinical cohort study. METHODS: Patients treated with PPS for interstitial cystitis with a cumulative dose of > 1000 g underwent multimodal imaging screening to exclude evidence of PPS maculopathy or other retinal findings. All study patients and age-matched healthy controls completed a 3 x 3 mm macular volume scan OCTA using the SOLIX full-range OCT. En face OCTA images at the level of the CC were exported and CC-FDs were computed and compared be-tween groups. RESULTS: Fifteen patients treated with PPS and 15 age -matched controls were included. The mean PPS cumulative dose was 1974 +/- 666 g over a mean of 17.6 +/- 6.8 treatment years. All patients registered a visual acuity of 20/25 or better and normal fundus autofluores-cence (FAF), OCT, multicolor, near-infrared reflectance (NIR), and ultra-widefield fundus color and autofluores-cence images. The CC-FD was 32.7 +/- 3.6% in the PPS group compared with 28.6 +/- 4.3% in the control group ( P = .023). CONCLUSIONS: Patients treated with PPS long enough to accumulate dosages > 1000 g showed significant CC flow impairment before the development of macular toxicity signs with OCT, NIR, and FAF compared with age -matched normal controls. Thus, the choroid may be the earliest manifestation of ocular toxicity, predating the development of clinically evident retinal pigment epithelium (RPE) injury. The subsequent RPE disruption may be the result of choriocapillaris impairment or primary PPS toxicity. Assessment of the CC on OCTA may be a useful tool for early detection of toxicity, although further longitudinal studies are required. (c) 2022 Elsevier Inc. All rights reserved.)

Sumoylation is an important post‐translational modification that provides a rapid and reversible means for controlling the activity, subcellular localization, and stability of target proteins. We have examined the covalent attachment of the small ubiqutin‐like modifier (SUMO) proteins to a consensus sequence ([psi]KXE) on the soluble epoxide hydrolase (EPHX2; sEH) enzyme. This enzyme has epoxide hydrolase activity on the C‐terminal domain and a phosphatase activity on the N‐terminus. Polymorphism in EPHX2 have been recently discovered (K55R) that is associated with risk of incident of coronary heart disease events. Interestingly, features of the sEH N‐terminal catalytic site showing a consensus site for SUMOylation (VKEP) with lysine residue at position 160. This and another human‐specific site of SUMOylation (MKGE with lysine residue at position 55), suggest a post‐translational modification and regulatory mechanism of sEH by SUMOylation. Our primary aim of this study was to determine whether sEH can be in vitro SUMOylated and defines its regulatory role of SUMOylation in its both C and N‐terminus activity. Indeed, SUMOylated process catalyzes the formation of polymeric chains of SUMO‐2 and SUMO‐3 on sEH in vitro, and was detected in vivo. We also identified the SUMOylated site on the sEH sequence and revealed its regulatory mechanism. Supported by NIEHS Grant R37 ES02710, NIEHS SBRP Grant P42 ES04699.