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Retinal Cases & Brief Reports Nov 2023The purpose of this study was to describe the characteristic pattern of progression of pentosan polysulfate (PPS) maculopathy with multimodal retinal imaging in two...
BACKGROUND/PURPOSE
The purpose of this study was to describe the characteristic pattern of progression of pentosan polysulfate (PPS) maculopathy with multimodal retinal imaging in two patients, including one with over 9 years of follow-up.
METHODS
Two patients with PPS maculopathy were sequentially evaluated with near-infrared reflectance (NIR) and optical coherence tomography.
RESULTS
Near-infrared reflectance showed characteristic centrifugal progression of the parafoveal hyperreflective lesions toward the vascular arcades with the development of hyporeflective areas in both cases. Optical coherence tomography demonstrated focal retinal pigment epithelium (RPE) thickening that corresponded to the hyperreflective lesions on NIR. On subsequent optical coherence tomography scans, the hyperreflective areas resolved with the development of ellipsoid zone attenuation, RPE disruption, and atrophy, which colocalized with hyporeflectivity on NIR.
CONCLUSION
This report describes the progression of pentosan polysulfate maculopathy over almost 10 years of PPS treatment and highlights the importance of NIR as a tool for the diagnosis and monitoring of PPS maculopathy. Pentosan polysulfate lesions present as areas of focal RPE thickening with ensuing development of ellipsoid zone loss and RPE drop-out. The pathophysiology of PPS toxicity is unknown and may either result from primary RPE or choroidal toxicity.
Topics: Humans; Pentosan Sulfuric Polyester; Retina; Retinal Diseases; Macular Degeneration; Retinal Pigment Epithelium; Tomography, Optical Coherence; Fluorescein Angiography
PubMed: 35344532
DOI: 10.1097/ICB.0000000000001276 -
Canadian Journal of Ophthalmology.... Apr 2024Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis....
OBJECTIVE
Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis. Numerous reports have been published detailing retinal toxicity with the use of PPS. Studies characterizing this condition are primarily retrospective, and consequently, alert and screening systems need to be developed to actively screen for this disease. The goal of this study was to characterize ophthalmic monitoring trends of a PPS-using patient sample to construct an alert and screening system for monitoring this condition.
METHODS
A single-institution retrospective chart review was conducted between January 2005 and November 2020 to characterize PPS use. An electronic medical record (EMR) alert was constructed to trigger based on new PPS prescriptions and renewals offering ophthalmology referral.
RESULTS
A total of 1407 PPS users over 15 years was available for characterization, with 1220 (86.7%) being female, the average duration of exposure being 71.2 ± 62.6 months, and the average medication cumulative exposure being 669.7 ± 569.2 g. A total of 151 patients (10.7%) had a recorded visit with an ophthalmologist, with 71 patients (5.0%) having optical coherence tomography imaging. The EMR alert fired for 88 patients over 1 year, with 34 patients (38.6%) either already being screened by an ophthalmologist or having been referred for screening.
CONCLUSIONS
An EMR support tool can improve referral rates of PPS maculopathy screening with an ophthalmologist and may serve as an efficient method for longitudinal screening of this condition with the added benefit of informing pentosan polysulfate prescribers about this condition. Effective screening and detection may help determine which patients are at high risk for this condition.
Topics: Humans; Female; Male; Pentosan Sulfuric Polyester; Retrospective Studies; Eye; Retinal Diseases; Face
PubMed: 36878265
DOI: 10.1016/j.jcjo.2023.01.019 -
Journal of Vitreoretinal Diseases 2024To describe a case of pentosan polysulfate maculopathy progression with 13 years of follow-up imaging. A case was analyzed and a literature review performed. A...
To describe a case of pentosan polysulfate maculopathy progression with 13 years of follow-up imaging. A case was analyzed and a literature review performed. A 65-year-old woman was referred to the retina service for a second opinion of a bilateral progressive pigmentary maculopathy. Her medical history was significant for interstitial cystitis that was actively treated with daily pentosan polysulfate since 2003. Multimodal imaging and fundus examination were consistent with pentosan polysulfate maculopathy. A review of records showed previous fundus imaging dating back 13 years that permitted longitudinal assessment of the disease course. Imaging findings were more prominent than the fundus examination findings. There was a 5-year period from the onset of parafoveal atrophy to foveal involvement. A pseudopodial pattern of disease expansion was seen on fundus autofluorescence. To our knowledge, this case represents the longest documented follow-up imaging of the progression of pentosan polysulfate maculopathy in the literature.
PubMed: 38770071
DOI: 10.1177/24741264241228375 -
Journal of Inherited Metabolic Disease Mar 2024Lysosomal enzyme deficiency in mucopolysaccharidosis (MPS) I results in glycosaminoglycan (GAG) accumulation leading to pain and limited physical function....
Open-label, single-center, clinical study evaluating the safety, tolerability and clinical effects of pentosan polysulfate sodium in subjects with mucopolysaccharidosis I.
Lysosomal enzyme deficiency in mucopolysaccharidosis (MPS) I results in glycosaminoglycan (GAG) accumulation leading to pain and limited physical function. Disease-modifying treatments for MPS I, enzyme replacement, and hematopoietic stem cell therapy (HSCT), do not completely resolve MPS I symptoms, particularly skeletal manifestations. The GAG reduction, anti-inflammatory, analgesic, and tissue remodeling properties of pentosan polysulfate sodium (PPS) may provide disease-modifying treatment for musculoskeletal symptoms and joint inflammation in MPS I following ERT and/or HSCT. The safety and efficacy of PPS were evaluated in four subjects with MPS I aged 14-19 years, previously treated with ERT and/or HSCT. Subjects received doses of 0.75 mg/kg or 1.5 mg/kg PPS via subcutaneous injections weekly for 12 weeks, then every 2 weeks for up to 72 weeks. PPS was well tolerated at both doses with no serious adverse events. MPS I GAG fragment (UA-HNAc [1S]) levels decreased at 73 weeks. Cartilage degradation biomarkers serum C-telopeptide of crosslinked collagen (CTX) type I (CTX-I) and type II (CTX-II) and urine CTX-II decreased in all subjects through 73 weeks. PROMIS scores for pain interference, pain behavior, and fatigue decreased in all subjects through 73 weeks. Physical function, measured by walking distance and dominant hand function, improved at 49 and 73 weeks. Decreased GAG fragments and cartilage degradation biomarkers, and positive PROMIS outcomes support continued study of PPS as a potential disease-modifying treatment for MPS I with improved pain and function outcomes.
Topics: Humans; Biomarkers; Cartilage; Enzyme Replacement Therapy; Mucopolysaccharidosis I; Pain; Pentosan Sulfuric Polyester; Adolescent; Young Adult
PubMed: 38467596
DOI: 10.1002/jimd.12715 -
Journal of Pharmaceutical and... Oct 2023Several publications have recently proposed NMR spectroscopy to evaluate the critical quality attributes (CQA) of pentosan polysulfate sodium (PPS), the active...
Several publications have recently proposed NMR spectroscopy to evaluate the critical quality attributes (CQA) of pentosan polysulfate sodium (PPS), the active ingredient of Elmiron™ approved to treat interstitial cystitis. PPS is a polymer of sulfated β(1-4)-d-xylopyranose residues randomly substituted by 4-O-methyl-glucopyranosyluronic acid, containing, beyond the main xylose-2,3-O-disulfate repetitive unit, some minor residues that can be marker of both the starting material and preparation process. In the present study we assigned some previously unknown cross-peaks in H-C HSQC NMR of PPS related to its minor sequences adding additional details to its CQA. Four anomeric cross-peaks related to glucuronate-branched xylose and different sulfation pattern as well as the preceding xyloses were identified. Two minor process-related signals of monosulfated xyloses (unsubstituted in position 2 or 3) were also assigned. The isolation of a disaccharide fraction allowed the assignment of the reducing end xylose-α/β as well as the preceding xylose residues to be corrected. Additionally, the oversulfation of PPS allowed detection of the reducing end xylose-tri-1,2,3-O-sulfate. The newly identified cross-peaks were integrated into an updated quantitative NMR method. Finally, we demonstrated that an in-depth PPS analysis can be obtained using NMR instruments at medium magnetic fields (500 MHz/600 MHz), commonly available in pharmaceutical industries.
Topics: Pentosan Sulfuric Polyester; Monosaccharides; Xylose; Magnetic Resonance Imaging; Sulfates; Magnetic Resonance Spectroscopy
PubMed: 37619291
DOI: 10.1016/j.jpba.2023.115672 -
Retinal Cases & Brief Reports Sep 2023The purpose of this study was to describe a case of development of pentosan polysulfate sodium (PPS)-related maculopathy that exhibited potential improvement in imaging...
PURPOSE
The purpose of this study was to describe a case of development of pentosan polysulfate sodium (PPS)-related maculopathy that exhibited potential improvement in imaging findings after drug cessation.
METHODS
This study is a case report.
RESULTS
A 66-year-old woman presented with progressive pigmentary maculopathy associated with long-term PPS usage, including development of a choroidal neovascular membrane in her right eye. After discontinuation of PPS, her clinical course was notable for partial subjective and objective improvement in visual acuity, as well as partial improvement in outer retinal architecture on ocular coherence tomography, but persistence of retinal pigment epithelium atrophy and autofluorescence changes.
CONCLUSION
The course of retinopathy after discontinuation of PPS has yet to be fully determined and has so far been suggested to be progressive. Anatomical improvements seen in our case suggest that further investigations are warranted to determine whether there is potential for partial reversal of some changes in PPS maculopathy.
Topics: Female; Humans; Aged; Pentosan Sulfuric Polyester; Retinal Diseases; Macular Degeneration; Retina; Choroidal Neovascularization
PubMed: 37643033
DOI: 10.1097/ICB.0000000000001242 -
Brain Pathology (Zurich, Switzerland) Sep 2023Genetic Creutzfeldt-Jakob disease (gCJD) with V180I prion protein gene (PRNP) mutation shows weaker prion protein (PrP) deposition histologically compared with sporadic...
Genetic Creutzfeldt-Jakob disease (gCJD) with V180I prion protein gene (PRNP) mutation shows weaker prion protein (PrP) deposition histologically compared with sporadic CJD, and it is more difficult to detect protease-resistant prion protein in immunoblotting. However, we previously reported the autopsy case of a patient with V180I gCJD who was treated with pentosan polysulfate sodium (PPS); this case had increased protease-resistant PrP deposition. It has been suggested that PPS might reduce protease-resistant PrP; however, the detailed pharmacological and histopathological effects of PPS in humans remain unknown. We examined autopsied human brain tissue from four cases with V180I gCJD that were added to our archives between 2011 and 2021: two cases treated with PPS and two cases without PPS. We conducted a neuropathological assessment, including immunohistochemistry for PrP. We also performed immunoblotting for PrP on homogenate samples from each brain to detect protease-resistant PrP using both a conventional procedure and size-exclusion gel chromatography for the purification of oligomeric PrP. Both PPS-treated cases showed long survival time over 5 years from onset and increased PrP deposition with a characteristic pattern of coarse granular depositions and congophilic PrP microspheres, whereas the cases without PPS showed around 1-year survival from onset and relatively mild neuronal loss and synaptic PrP deposition. Although cortical gliosis seemed similar among all cases, aquaporin 4-expression as a hallmark of astrocytic function was increased predominantly in PPS cases. Immunoblotting of non-PPS cases revealed protease-resistant PrP in the oligomeric fraction only, whereas the PPS-treated cases showed clear signals using conventional procedures and in the oligomeric fraction. These unique biochemical and histopathological changes may reflect the progression of V180I gCJD and its modification by PPS, suggesting the possible existence of toxic PrP-oligomer in the pathophysiology of V180I gCJD and beneficial effects of PPS toward the aggregation and detoxication of toxic PrP-oligomer.
Topics: Humans; Creutzfeldt-Jakob Syndrome; Prions; Prion Proteins; Pentosan Sulfuric Polyester; Peptide Hydrolases; Mutation
PubMed: 37525413
DOI: 10.1111/bpa.13197 -
Retina (Philadelphia, Pa.) Sep 2023To refine the retinal phenotypes of suspected pentosan polysulfate sodium toxicity using ultra-widefield imaging.
PURPOSE
To refine the retinal phenotypes of suspected pentosan polysulfate sodium toxicity using ultra-widefield imaging.
METHODS
Patients with complete dosing profiles who visited the ophthalmology department and with ultra-widefield and optical coherence tomography imaging records were identified using electronic health records at a large academic center. Retinal toxicity was initially identified using previously published imaging criteria, while grading was categorized using both previously reported and new classification systems.
RESULTS
One hundred and four patients were included in this study. Twenty-six (25%) were identified as having toxicity from PPS. The mean duration of exposure and cumulative dose between the retinopathy group (162.7 months, 1,803.2 g) were longer and higher compared with the nonretinopathy group (69.7 months, 972.6 g) (both P < 0.001). There was variability of extramacular phenotype in the retinopathy group, with four eyes having only peripapillary involvement and six eyes having far peripheral extension.
CONCLUSION
Retinal toxicity in the setting of prolonged exposure and increased cumulative dosing from PPS therapy produces phenotypic variability. Providers should be aware of the extramacular component of toxicity when screening patients. Understanding the different retinal phenotypes may prevent continued exposure and reduce the risk of vision-threatening foveal-involving disease.
Topics: Humans; Pentosan Sulfuric Polyester; Fluorescein Angiography; Retina; Retinal Diseases; Tomography, Optical Coherence; Phenotype
PubMed: 37229759
DOI: 10.1097/IAE.0000000000003844 -
The Canadian Journal of Urology Jun 2024
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Cystitis, Interstitial; Anticoagulants
PubMed: 38912936
DOI: No ID Found -
Investigative Ophthalmology & Visual... Apr 2024
PubMed: 38687494
DOI: 10.1167/iovs.65.4.47