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Klinische Monatsblatter Fur... Dec 2022Exogenously induced retinopathies can be caused by consumation of stimulating substances, systemic or ocular medications, vaccinations, light or irradiation. Some of the...
Exogenously induced retinopathies can be caused by consumation of stimulating substances, systemic or ocular medications, vaccinations, light or irradiation. Some of the effects are transient, whereas other effects induce irreversible toxic reactions. Retinal damage may develop either acutely with obvious relation to the damaging cause, but often may take a long duration of repeated use of a substance or medication. External stimulants (e.g. nicotine, alcohol, poppers, methanol) are the most frequent cause of exogenously induced retinal damage. Side effects from systemic drugs (e.g. hydroxychloroquine, ethambutol, MEK-, ERK-, FLT3-, checkpoint inhibitors, didanosin, pentosanpolysulfat sodium) or intravitreally applied drugs (e.g. antibiotics, VEGF-inhibitors) are less frequent. Ocular side effects associated with vaccinations are rare. Ambient light sources induce no damaging effects on the retina. Incorrect use of technical or medical light sources (e.g. laser pointers) without adherence to safety recommendations or unshielded observation of the sun might induce permanent retinal damage. Local or external irradiation might induce retinal vascular damage resulting in radiation retinopathy.
Topics: Humans; Retinal Diseases; Retina; Eye Diseases; Pentosan Sulfuric Polyester; Hydroxychloroquine; Drug-Related Side Effects and Adverse Reactions
PubMed: 36395811
DOI: 10.1055/a-1961-8166 -
Expert Opinion on Pharmacotherapy Jul 2018Interstitial cystitis (IC) and bladder pain syndrome (BPS) are chronic conditions that can be debilitating for patients. There is no consensus as to their etiology, and... (Review)
Review
INTRODUCTION
Interstitial cystitis (IC) and bladder pain syndrome (BPS) are chronic conditions that can be debilitating for patients. There is no consensus as to their etiology, and there are many proposed treatment algorithms. Oftentimes multimodal therapy, such as combining behavioral modification and physical therapy alongside pharmacotherapies, will be utilized. With the various treatment options available to patients and providers, there is an ever-growing need to implement evidence-based therapies.
AREAS COVERED
The authors explore the different pharmacotherapies as commonly recommended in the American Urological Association (AUA) and European Association of Urology (EAU) multitiered guidelines for IC/BPS treatment as well as other investigational therapies. Pharmacotherapies targeting bladder, pelvic, and/or systemic factors in the overall treatment of IC/BPS are discussed with a particular focus on evidence-based guideline therapies. This article also looks at emerging therapies of interest.
EXPERT OPINION
IC/BPS is a syndrome that requires a multimodal approach, including clinical phenotyping and directed therapy based on the patient's symptoms. The AUA and EAU provide guidelines for practitioners to follow, but adequate treatment requires the therapy to be targeted toward the patient's phenotypic domain.
Topics: Amitriptyline; Antibodies, Monoclonal; Antidepressive Agents, Tricyclic; Cimetidine; Cystitis, Interstitial; Histamine Antagonists; Humans; Hydroxyzine; Immunosuppressive Agents; Pentosan Sulfuric Polyester
PubMed: 29972328
DOI: 10.1080/14656566.2018.1491968 -
Ophthalmology. Retina Nov 2023
Topics: Humans; Pentosan Sulfuric Polyester; Visual Field Tests; Macular Degeneration; Retinal Diseases
PubMed: 37619623
DOI: 10.1016/j.oret.2023.08.009 -
Current Opinion in Ophthalmology May 2021The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to pentosan polysulfate sodium (PPS). (Review)
Review
PURPOSE OF REVIEW
The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to pentosan polysulfate sodium (PPS).
RECENT FINDINGS
PPS toxicity was described in 2018, and additional studies characterize it as dysfunction of the retinal pigment epithelium centered on the posterior pole, which can progress despite drug cessation. Requisite exposure can be as little as 0.325 kg and 2.25 years but averages closer to 1-2 kg and 10-15 years. Multimodal imaging should include near-infrared reflectance, optical coherence tomography, and fundus autofluorescence. Cross-sectional studies demonstrate evidence correlating cumulative dosing and the likelihood/severity of maculopathy. Early estimates of prevalence range from 12.7 to 41.7% depending on dosing, with overall rates around 20%.
SUMMARY
Reasonable evidence associates maculopathy with extended exposure to PPS, with an average reported incidence of around 20% in patients with long-term exposures. Patients with unexplained retinal pigment epithelium changes and difficulty with dark adaptation should be questioned regarding PPS exposure, and patients with known exposure to PPS should be examined. Further research is needed to refine screening protocols. Currently, providers should consider baseline examination and examination at 5 years and/or 500 g of exposure followed by yearly screening.
Topics: Anticoagulants; Drug-Related Side Effects and Adverse Reactions; Humans; Multimodal Imaging; Pentosan Sulfuric Polyester; Retinal Diseases; Retinal Pigment Epithelium
PubMed: 33710012
DOI: 10.1097/ICU.0000000000000754 -
ImmunoTargets and Therapy 2016Transmissible spongiform encephathalopathies or prion diseases are a group of neurological disorders characterized by neuronal loss, spongiform degeneration, and... (Review)
Review
Transmissible spongiform encephathalopathies or prion diseases are a group of neurological disorders characterized by neuronal loss, spongiform degeneration, and activation of astrocytes or microglia. These diseases affect humans and animals with an extremely high prevalence in some species such as deer and elk in North America. Although rare in humans, they result in a devastatingly swift neurological progression with dementia and ataxia. Patients usually die within a year of diagnosis. Prion diseases are familial, sporadic, iatrogenic, or transmissible. Human prion diseases include Kuru, sporadic, iatrogenic, and familial forms of Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. The causative agent is a misfolded version of the physiological prion protein called PrP(Sc) in the brain. There are a number of therapeutic options currently under investigation. A number of small molecules have had some success in delaying disease progression in animal models and mixed results in clinical trials, including pentosan polysulfate, quinacrine, and amphotericin B. More promisingly, immunotherapy has reported success in vitro and in vivo in animal studies and clinical trials. The three main branches of immunotherapy research are focus on antibody vaccines, dendritic cell vaccines, and adoptive transfer of physiological prion protein-specific CD4(+) T-lymphocytes. Vaccines utilizing antibodies generally target disease-specific epitopes that are only exposed in the misfolded PrP(Sc) conformation. Vaccines utilizing antigen-loaded dendritic cell have the ability to bypass immune tolerance and prime CD4(+) cells to initiate an immune response. Adoptive transfer of CD4(+) T-cells is another promising target as this cell type can orchestrate the adaptive immune response. Although more research into mechanisms and safety is required, these immunotherapies offer novel therapeutic targets for prion diseases.
PubMed: 27529062
DOI: 10.2147/ITT.S64795 -
Ophthalmic Surgery, Lasers & Imaging... Jul 2023To compare the risk factors for the development and progression of pigmentary retinopathy in patients exposed to pentosan polysulfate sodium (PPS).
BACKGROUND AND OBJECTIVE
To compare the risk factors for the development and progression of pigmentary retinopathy in patients exposed to pentosan polysulfate sodium (PPS).
MATERIALS AND METHODS
Retrospective cohort study of patients exposed to PPS with at least two follow-up visits with multimodal imaging.
RESULTS
A total of 97 patients were included (33 with PPS-associated retinopathy and 64 without). The average follow-up was 29.4 months, overall cumulative dose was 1,220 ± 910 g (1,730 ± 870 vs 959 ± 910; < 0.0001), and total PPS duration was 12.1 ± 7.1 years (16.0.2 ± 6.1 vs 10.1 ± 6.9; < 0.0001). The best-corrected visual acuity remained stable during follow-up. At presentation, the average area of the retinopathy in the worse eye was 54.1 ± 50 mm in the PPS-retinopathy group, worsening at a rate of 6.10 ± 10 mm/year. Patients who developed choroidal neovascular membranes (CNVMs) had faster rates of retinopathy progression (11.6 ± 12 vs 3.53 ± 7.6 mm/year, = 0.036). No patient had the exact same gene mutation.
CONCLUSION
PPS-associated pigmentary retinopathy can continue to progress over time, even after discontinuing the medication. CNVM development may be associated with faster rates of retinopathy progression. .
Topics: Humans; Pentosan Sulfuric Polyester; Follow-Up Studies; Retrospective Studies; Retinal Diseases; Retinitis Pigmentosa; Sodium
PubMed: 37310751
DOI: 10.3928/23258160-20230522-02 -
Ophthalmic Epidemiology Feb 2023We describe a retrospective cohort study investigating the prevalence of pentosan polysulfate sodium (PPS) maculopathy in patients with PPS exposure, as well as the...
PURPOSE
We describe a retrospective cohort study investigating the prevalence of pentosan polysulfate sodium (PPS) maculopathy in patients with PPS exposure, as well as the relationship between cumulative PPS exposure and the presence of PPS-maculopathy.
METHODS
Patients were identified through review of the electronic medical record system. Available diagnostic imaging was reviewed for signs of PPS-maculopathy. Patients were also contacted to determine cumulative exposure.
RESULTS
Of the 335 identified eligible patient records, 84 had sufficient diagnostic imaging. Sixteen patients had definitive signs of PPS-maculopathy, 6 had likely signs of PPS-maculopathy, and 62 had no signs. The mean cumulative PPS exposure and standard error of the mean (SEM) for patients with any signs of PPS-maculopathy was 1946.0 g (396.0 g), significantly higher than the mean cumulative PPS exposure for patients without such signs of 782.3 g (105.3 g). No significant difference in BCVA was noted. The odds ratio (OR, 95% confidence interval (95% CI)) of PPS-maculopathy was significantly elevated in patients with cumulative PPS exposures of 1500-2000 g [OR 4.72 (0.856-26.02 95% CI)] and greater than 2000 g [OR 28.33 (2.388-336.1, 95% CI)]. Logistic regression analysis confirmed a positive dose response relationship.
CONCLUSIONS
We describe the concerning incidence of PPS-maculopathy in a multispecialty ophthalmology practice's patient population and investigate the dose-dependency of PPS-maculopathy. Patients with PPS-maculopathy were shown to have a higher average exposure to PPS than those without the maculopathy. Patients with cumulative PPS exposures greater than 1500 g were shown to have an increased risk of PPS-maculopathy.
Topics: Humans; Pentosan Sulfuric Polyester; Prevalence; Retrospective Studies; Retinal Diseases; Macular Degeneration
PubMed: 35081852
DOI: 10.1080/09286586.2022.2031227 -
BMJ Open May 2024Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain...
INTRODUCTION
Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain relief; growing evidence suggests pentosan polysulfate sodium (PPS) is chondroprotective and could have anti-inflammatory effects in knee OA. This study aims to explore the efficacy and safety of oral PPS in symptomatic knee OA with dyslipidaemia.
METHODS AND ANALYSIS
MaRVeL is a phase II, single-centre, parallel, superiority trial which will be conducted at Royal North Shore Hospital, Sydney, Australia. 92 participants (46 per arm) aged 40 and over with painful knee OA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) will be recruited from the community and randomly allocated to receive two cycles of either oral PPS or placebo for 5 weeks starting at baseline and week 11. Primary outcome will be the 16-week change in overall average knee pain severity measured using an 11-point Numeric Rating Scale. Main secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life and other structural changes. A biostatistician blinded to allocation groups will perform the statistical analysis according to the intention-to-treat principle.
ETHICS AND DISSEMINATION
The protocol has been approved by the NSLHD Human Research Ethics Committee (HREC) (2021/ETH00315). All participants will provide written informed consent online. Study results will be disseminated through conferences, social media and academic publications.
TRIAL REGISTRATION NUMBERS
Australian New Zealand Clinical Trial Registry (ACTRN12621000654853); U1111-1265-3750.
Topics: Humans; Osteoarthritis, Knee; Pentosan Sulfuric Polyester; Dyslipidemias; Quality of Life; Male; Treatment Outcome; Female; Middle Aged; Clinical Trials, Phase II as Topic; Australia; Pain Measurement; Adult
PubMed: 38777590
DOI: 10.1136/bmjopen-2023-083046 -
Canadian Journal of Ophthalmology.... Feb 2022To evaluate whether pentosan polysulfate maculopathy manifests distinctive imaging features that can be differentiated from those found in age-related macular...
OBJECTIVE
To evaluate whether pentosan polysulfate maculopathy manifests distinctive imaging features that can be differentiated from those found in age-related macular degeneration (AMD).
METHODS
Local databases were queried to identify patients with a diagnosis of interstitial cystitis who were seen at the Emory Eye Center between May 2014 and January 2019 and who had fundus imaging available for review. Ninety patients met the eligibility criteria. Masked graders categorized patients based on imaging characteristics as follows: category 1: pentosan polysulfate maculopathy; category 2: AMD or drusen; category 3: neither; and category 4: unsure. Pentosan polysulfate exposure characteristics were compared among groups.
RESULTS
Of the 90 subjects evaluated, 79 (88%) were female and the median age was 61.5 years (range, 30-89). Seventeen patients were placed in category 1; 25 in category 2; 47 in category 3, and; 1 in category 4. Among categories 1 to 4, respectively, 17 (100%), 15 (60%), 28 (60%), and 0 patients had exposure to pentosan polysulfate (p = 0.007). Mean cumulative exposure to pentosan polysulfate across the four categories was 2.1, 0.36, 0.34, and 0 kg, respectively (p < 0.00001). Eyes with pentosan polysulfate maculopathy did not have typical drusen in the macula.
CONCLUSION
Although pentosan polysulfate maculopathy resembles some aspects of AMD, the two conditions can be differentiated with the use of multimodal fundus imaging.
Topics: Anticoagulants; Female; Humans; Macula Lutea; Macular Degeneration; Male; Middle Aged; Multimodal Imaging; Pentosan Sulfuric Polyester; Retinal Diseases
PubMed: 33722504
DOI: 10.1016/j.jcjo.2021.02.007 -
Ophthalmology. Retina Mar 2024To investigate the nationwide use of pentosan polysulfate (PPS) and screening practices for PPS maculopathy (PPM), with a focus on the timing and modalities used.
OBJECTIVE
To investigate the nationwide use of pentosan polysulfate (PPS) and screening practices for PPS maculopathy (PPM), with a focus on the timing and modalities used.
DESIGN
Population-based cohort study.
PARTICIPANTS
For evaluation of nationwide usage, 133 762 individuals who received PPS prescriptions between 2012 and 2021 were included. To investigate practice patterns, 55 487 individuals (referred to as overall users) who initiated PPS therapy between 2018 and 2020 were identified using the Health Insurance Review and Assessment database. After excluding patients with ophthalmic diseases before PPS administration, 34 857 PPS users without prior ophthalmic diseases were identified.
METHODS
Ophthalmic examinations performed after initiating PPS therapy were categorized as baseline and subsequent monitoring examinations. The timing and modalities employed for these examinations were analyzed. The annual trends in PPS utilization and maculopathy screening were evaluated by assessing the number of PPS users and determining the proportion of patients receiving retinal/macular examinations among these users.
MAIN OUTCOME MEASURES
Performance of baseline and subsequent monitoring examinations and timing and modalities used for screening.
RESULTS
The number of PPS users dramatically increased annually over the study period from 5494 in 2012 to 40 451 in 2021. However, the majority of PPS users did not undergo baseline or subsequent monitoring examinations for PPM. Only 27.2% and 12.4% of PPS users without prior ophthalmic disease underwent baseline and monitoring examinations, respectively. Funduscopy/fundus photography was the most commonly utilized, whereas OCT and fundus autofluorescence (FAF) were performed in only 45.2% and 5.3% of the PPS users without prior ophthalmic diseases for monitoring, respectively. The performance of the screening examinations differed significantly across the 3 different daily dose and duration groups (all P < 0.05).
CONCLUSIONS
This study highlights the lack of performance of baseline and monitoring examinations for maculopathy in most patients taking PPS in South Korea. The limited use of OCT and FAF suggests potential insensitivity in detecting PPM. These findings emphasize the need for improvements in screening practices, including increased awareness and referrals to ophthalmologists, utilization of more sensitive modalities, and regular monitoring to enable early detection of PPM.
FINANCIAL DISCLOSURE(S)
The authors have no proprietary or commercial interest in any materials discussed in this article.
Topics: Humans; Pentosan Sulfuric Polyester; Cohort Studies; Retinal Diseases; Macular Degeneration; Republic of Korea
PubMed: 37832716
DOI: 10.1016/j.oret.2023.10.005