Recent studies have implicated long-term pentosan polysulfate use with vision loss from a newly described macular condition. Affected patients report difficulty with reading and adjusting to dim lighting, and they occasionally develop severe visual disability. Macular changes resemble those seen in age-related macular degeneration, potentially leading to misdiagnosis. The objectives of this Current Commentary are to summarize studies evaluating the association between pentosan polysulfate use and macular disease, to educate pentosan polysulfate prescribers about the clinical manifestations of this condition, and to provide recommendations for screening at-risk patients.

(Abstracted from Obstet Gynecol 2020;135:1091–1094) As the approved oral agent for interstitial cystitis, pentosan polysulfate sodium (PPS) has been widely used since its approval in 1996. Historically recognized adverse effects of PPS are not serious.

IMPORTANCE A unique pigmentary maculopathy was recently described in 6 patients with long-term exposure to pentosan polysulfate sodium (PPS), a long-standing oral therapy for interstitial cystitis.OBJECTIVE To characterize the exposure characteristics and clinical manifestations of PPS-associated maculopathy.DESIGN, SETTING, AND PARTICIPANTS In this multi-institutional case series, medical records of patients who exhibited the characteristic maculopathy in the setting of prior PPS exposure were retrospectively reviewed. Data were collected from August 1, 2012, to October 1, 2018, and data were analyzed from October 2018 to January 2019.MAIN OUTCOMES AND MEASURES Drug exposure, visual acuity, and retinal imaging characteristics.RESULTS Of the 35 included patients (70 eyes), 34 (97%) were female, and the median (range) age was 60 (37-79) years. The median (range) duration of PPS intake was 15 (3-22) years, and the median (range) cumulative exposure was 1.61 (0.44-4.31) kg. The leading visual symptoms were metamorphopsia, blurred vision, and prolonged dark adaptation. Median (range) logMAR visual acuity of all eyes was 0.10 (-0.12 to 1.18). Fundus examination often revealed hyperpigmented macular spots (34 of 64 eyes [53%]) with interspersed pale-yellow deposits, although less commonly in eyes that exhibited retinal pigment epithelial atrophy (6 of 26 eyes [23%]; P<.001). Optical coherence tomography showed foci of retinal pigment epithelium elevation or thickening associated with hyperreflectance on near-infrared reflectance imaging. Fundus autofluorescence imaging typically revealed a symmetric, confluent pattern of hyperautofluorescent and hypoautofluorescent spots that involved the fovea in all eyes and extended to the retinal periphery in 24 eyes (36%). Longitudinal evaluation demonstrated dynamic changes in pigmentary abnormalities.CONCLUSIONS AND RELEVANCE These findings suggest that PPS-associated maculopathy is a vision-threatening condition that can manifest in the setting of long-term exposure to the drug. Multimodal imaging posits a distinctive clinical phenotype, characterized in this cohort by dynamic alterations within the retinal pigment epithelium and at the retinal pigment epithelium-photoreceptor interface. Ongoing work might explore causality and direct screening guidelines.

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (MP47)1 Apr 2019MP47-03 CHRONIC EXPOSURE TO PENTOSAN POLYSULFATE SODIUM IS ASSOCIATED WITH RETINAL PIGMENTARY CHANGES AND VISION LOSS Jenelle Foote*, Adam Hanif, and Nieraj Jain Jenelle Foote*Jenelle Foote* , Adam HanifAdam Hanif , and Nieraj JainNieraj Jain View All Author Informationhttps://doi.org/10.1097/01.JU.0000556315.46806.caAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic bladder condition in which individuals are symptomatic of bladder or pelvic pain, urinary frequency, urgency and nocturia. For diagnosis, exclusion of other etiologies of these symptoms is necessary. Oral pentosan polysulfate sodium (PPS) is a second line oral medication for the treatment of IC/BPS per AUA Guidelines). We have recently observed vision-threatening retinal changes in a group of patients receiving chronic therapy for IC/BPS with PPS. METHODS: Subjects were identified by query of a local electronic medical record system for patients seen at the Emory Eye Center with self-reported current or previous use of PPS and retinal degeneration. Medical records were reviewed for patient demographics, medication history, history of visual symptoms, clinical examination results, and retinal imaging from modalities including wide-field fundus photography, fundus autofluorescence imaging (FAF), and optical coherence tomography (OCT). RESULTS: A total of 10 patients were identified, with a median age of 59 years (range 38-68), and median time since IC diagnosis of 19 years (range 4-40). The most commonly reported visual symptoms described were difficulty reading (7/10) and difficulty adapting to dim lighting (7/10). The median cumulative exposure to PPS was 2062 grams (range 325-2883.5), over a median duration of 186 months (range 27-240). Mean logMAR best corrected visual acuity in all eyes measured was 0.13 (Snellen equivalent 20/27). Dilated fundus examination revealed symmetric fairly pigmentary changes in the retina. Retinal imaging with FAF and OCT technologies further characterized these pigmentary lesions, demonstrating abnormalities primarily in the retinal pigment epithelium. Of note, 156 patients with a history of IC/BPS but without PPS exposure have undergone ophthalmic exam at our institution during the study period. On retrospective review of these medical records, none of them were diagnosed with this unique form of pigmentary maculopathy. CONCLUSIONS: We describe a potentially avoidable retinal degeneration phenomenon associated with chronic PPS exposure. Structural changes occur at the level of the retinal pigment epithelium, manifesting as characteristic pigmentary changes. While it remains unclear whether drug cessation will alter the course of retinal disease, we encourage affected patients to discontinue use, and patients with suggestive visual symptoms to undergo a comprehensive ophthalmic examination with OCT and FAF imaging. Source of Funding: None Atlanta, GA© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e688-e688 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jenelle Foote* More articles by this author Adam Hanif More articles by this author Nieraj Jain More articles by this author Expand All Advertisement PDF downloadLoading ...

This study was conducted to assess time-to-effect with darifenacin in patients with overactive bladder (OAB).

OBJECTIVE:• To show the superior efficacy of fesoterodine over tolterodine extended release (ER) in a placebo-controlled overactive bladder (OAB) trial with predefined treatment comparisons for both diary measures and patient-reported outcomes.MATERIALS AND METHODS:• In this 12-week, double-blind, double-dummy trial, subjects reporting >1 urgency urinary incontinence (UUI) episode and ≥8 micturitions per 24 h at baseline were randomized to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks), tolterodine ER 4 mg, or placebo. • Subjects completed 3-day bladder diaries, the Patient Perception of Bladder Condition (PPBC) and the Urgency Perception Scale (UPS) at baseline and weeks 1, 4 and 12 and the OAB Questionnaire at baseline and week 12.RESULTS:• A total of 2417 subjects were randomized. At week 12, fesoterodine 8 mg showed superiority over tolterodine ER 4 mg and placebo on UUI episodes (primary endpoint), micturitions, urgency and most other diary endpoints, and on the PPBC, UPS and all OAB Questionnaire scales and domains (all P < 0.05). • Superiority of fesoterodine 8 mg over tolterodine ER 4 mg was seen as early as week 4 (3 weeks after escalation to fesoterodine 8 mg). At week 1, fesoterodine 4 mg was superior to placebo on most diary variables, the PPBC and the UPS (all P < 0.05). Dry mouth and constipation rates were 28% and 4% with fesoterodine, 13% and 3% with tolterodine ER, and 5% and 2% with placebo. • Discontinuation rates as a result of adverse events were 5%, 3% and 2% for fesoterodine, tolterodine ER and placebo, respectively.CONCLUSIONS:• In this randomized study, which is the largest to compare antimuscarinic efficacy performed to date, fesoterodine 8 mg was superior to tolterodine ER 4 mg for UUI episodes, micturitions and urgency episodes, as well as for self-reported patient assessments of bladder-related problems, urgency, symptom bother and health-related quality of life. • The superiority of fesoterodine 8 mg over tolterodine ER 4 mg was observed as early as 3 weeks after escalation from fesoterodine 4 mg for most outcomes. These data may have important implications for the clinical management of OAB patients previously treated with tolterodine ER.

OBJECTIVES To evaluate the efficacy and safety of oxybutynin transdermal system (oxybutynin-TDS) in spinal cord injury patients with neurogenic detrusor overactivity and incontinence despite use of clean intermittent catheterization (CIC).METHODS This multicenter, open-label, dose-titration study included patients >= 18 years old. During an 8-week dose-titration period, oxybutynin-TDS doses were adjusted every 2 weeks, depending on symptoms. The primary efficacy end point was a change in daily number of CIC periods without leakage, from baseline to 8 weeks or last observation. Outcome parameters included 3-day voiding diary, CIC volume, and urodynamic parameters. Changes from baseline were analyzed with paired t tests.RESULTS Of 24 study participants (mean age, 41.9 years), 18 (75.0%) completed the study. Final oxybutynin-TDS doses were 7.8, 9.1, and 11.7 mg/d for 4, 9, and I I patients, respectively. Daily number of CIC periods without leakage increased significantly (mean change, 1.5 +/- 2.2; P = .0036) from baseline (2-4 +/- 1.8) to 8 weeks (3.9 +/- 1.9). CIC volume (P = .0029), reflex volume (P = .0466), maximal cystometric bladder capacity (P = .0009), and residual urine volume (P = .0023) all increased significantly, whereas detrusor pressure at maximal bladder capacity decreased significantly (P = .0457). The most common adverse events were application site reaction (12.5% of patients), dry mouth (8.3%), and abnormal vision (8.3%). No patient discontinued treatment because of an adverse event.CONCLUSIONS Oxybutynin-TDS was efficacious in spinal cord injury patients with neurogenic detrusor overactivity and was well tolerated at up to 3 times the standard dose. UROLOGY 74: 741-745, 2009. (C) 2009 Elsevier Inc.

Aim: To evaluate the efficacy, tolerability and safety of darifenacin, an M-3 selective receptor antagonist, in the subgroup of older patients from a pooled analysis of three phase III, multicentre, randomized, double-blind clinical trials in patients with overactive bladder (OAB).Patients and methods: 317 patients aged >= 65 years with OAB symptoms (urge incontinence, urgency and frequency) received up to 12 weeks' oral treatment with darifenacin 7.5 mg or 15 mg once daily or matching placebo. Efficacy was evaluated from daily electronic diary records. Safety endpoints included withdrawal rates and treatment-related adverse events.Results: Darifenacin treatment of patients aged >= 65 years was associated with a dose-related, significant improvement of all the major symptoms of OAB. At week 12, the median reduction in incontinence episodes/ week was greater with darifenacin 7.5 mg or 15 mg than in the corresponding placebo arms (66.7% vs. 34.8% and 75.9% vs. 44.8%, respectively, both p < 0.001). Both doses were also significantly superior to placebo in improving micturition frequency (both p < 0.001), bladder capacity (volume voided) (darifenacin 7.5 mg, p = 0.018, darifenacin 15 mg, p < 0.001), and the frequency of urgency episodes (both p < 0.001). Darifenacin was well tolerated. The most common treatment-related adverse events were dry mouth (7.5 mg, 20.6%; 15 mg, 30.9%; placebo, 4.5%) and constipation (7.5 mg, 18.6%; 15 mg, 23.6%; placebo, 6.4%), typically mild or moderate. Use of constipation remedies (laxatives, stool softeners or fibre supplements) was low and similar between groups (7.5 mg, 10.3%; 15 mg, 16.4%; placebo, 10.0%). There were few withdrawals due to treatment-related adverse events (7.5 mg, 1.0%; 15 mg, 9.1%; placebo, 2.7%), and no nervous system or cardiovascular safety concerns.Conclusions: The results demonstrate excellent efficacy, tolerability and safety with darifenacin 7.5 mg and 15 mg once-daily treatment for OAB in older patients. (c) 2005 Elsevier B.V. All rights reserved.

OBJECTIVES:To evaluate the efficacy, tolerability and safety of a flexible-dosing strategy with darifenacin, an M(3)-selective receptor antagonist, in patients with symptoms of overactive bladder (OAB). PATIENTS AND METHODS:In this multicentre double-blind 12-week study, 395 patients (aged 22-89 years; 84% female) with OAB symptoms for >6 months were randomized (2 : 1) and received once-daily treatment with darifenacin controlled-release tablets 7.5 mg (268 patients) or matching placebo (127). After 2 weeks of treatment, the efficacy, safety and tolerability were assessed and the dose increased to 15 mg once daily (pseudo-increase for placebo recipients) if additional efficacy was required by both the patient and physician. In the week before clinic visits (at 2 and 12 weeks), patients recorded incontinence episodes (primary efficacy endpoint) and several secondary efficacy variables in an electronic daily diary. Safety and tolerability were evaluated from withdrawal rates and adverse-event reports. RESULTS:The treatment groups had comparable baseline characteristics. Similar proportions of darifenacin (59%) and placebo (68%) recipients increased the dose at 2 weeks; at 12 weeks patients on darifenacin (overall group) had a significantly greater reduction in the median number of incontinence episodes per week than had those on placebo, at - 8.2 (-62.9%) and - 6.0 (-48.1%), respectively (P = 0.035). There were also significant improvements in voiding frequency (P = 0.001), bladder capacity (volume voided; P = 0.036), frequency of urgency (P < 0.001), severity of urgency (P = 0.013) and number of significant leaks/week (i.e. incontinence episodes needing a change of clothing or pads, per week; P = 0.010) for darifenacin over placebo. Subset analysis suggested that some patients (those remaining on darifenacin 7.5 mg) were more sensitive to darifenacin than those who increased the dose, based on both efficacy and adverse events. Continued treatment with 7.5 mg for 'sensitive' patients, and an increased dose (to 15 mg) for remaining patients, resulted in comparable outcomes by 12 weeks. The most common treatment-related adverse events were mild-to-moderate dry mouth and constipation, which led to discontinuation in < 3.0% of darifenacin-treated patients and < 1.0% of the placebo group. Central nervous system and cardiovascular adverse events were comparable to those with placebo. CONCLUSIONS:Darifenacin appears to be an effective, well-tolerated and flexible treatment for patients with OAB, allowing individualized dosing according to patient needs.

Purpose: An incompetent urethral sphincter can be a significant factor contributing to urinary incontinence in patients with neurogenic bladders. We review our experience with 12 men who underwent a puboprostatic sling.Materials and Methods: The study included 12 men (mean age 37.1 years) with neurogenic bladder due to spinal cord injury in 9 and spina bifida in 3. All patients were diagnosed with urethral incompetence based on fluorourodynamic evaluation. Medical therapy failed in all 12 patients and all complained of urine leakage with activity. All patients underwent placement of an autologous fascial sling distal to the prostatic urethra via an abdominal approach. Ten patients also underwent simultaneous bladder augmentation to correct high intravesical pressures.Results: Followup, ranged from 1 to 39 months (average 14.25). All patients manage the bladder with intermittent catheterization. Of the patients 8 are completely dry between catheterizations and 2 had significant improvement with only minimal leakage (1 pad per day), with an overall success rate of 83%. One patient improved initially but subsequently underwent placement of an artificial urinary sphincter for residual stress incontinence. In 1 patient several external sphincterotomies failed despite adequate sling placement. There were no complications related to the placement of the sling and all patients are able to perform intermittent catheterization without difficulty.Conclusions: In select male patients the puboprostatic sling can be an effective and safe method to treat urethral incompetence secondary to neurogenic voiding dysfunction.

PURPOSE:We evaluated the use of collagen in women with stress urinary incontinence and urethral hypermobility. MATERIALS AND METHODS:We treated 90 patients with stress urinary incontinence and urethral hypermobility with 1 to 3 injections of Contigen implant (C. R. Bard, Inc., Covington, Georgia) between June 1996 and October 1998. Observations at 3, 6 and 12 months included continence grade, 7-day voiding diaries and quality of life questionnaires. Abdominal leak point pressure was determined at baseline and 12 months. RESULTS:At the 6-month followup 68 patients remained in the study, of whom 30 (44%) were dry and 24 (35%) were improved. Of the 58 patients who reached the 12-month followup 19 (33%) were dry and 19 (33%) were improved. Considering all patients entered into the study at 6 months 30 (33%) were dry and 24 (27%) were improved. Of the original 90 patients 19 (21%) were dry and 19 (21%) were improved at 12 months. The probability of maintaining initial improvement for 12 months was 44%. The success of bulking agent therapy was not predicted by the initial incontinence grade. Improved continence grade correlated with improved leak point pressure. CONCLUSIONS:This therapy is appropriate in women with urethral hypermobility who wish to avoid surgical risks and in those in whom surgery is ill advised.

PURPOSE:We present the experience of the North American UroLume Multicenter Study Group with removal of the UroLume endoprosthesis.MATERIALS AND METHODS:A total of 160 neurologically impaired patients were enrolled in the North American UroLume Multicenter Study Group for detrusor external sphincter dyssynergia application. Analysis was performed in 2 groups of patients in which the device was removed during insertion and after implantation, respectively.RESULTS:Device retrieval was required during insertion in 21 patients (13%) mainly due to misplacement or migration in 17. Extraction was done with minimal complications and in all but 2 cases subsequent UroLume implantation was successful. Of 158 men with the device in place 31 (19.6%) required removal. In 34 procedures 44 devices were removed, mainly due to migration. Time from implantation to removal ranged from 4 days to 66 months (mean 22 months). The UroLume was removed en bloc in 20 cases and in parts or wire by wire in 19. The majority of patients had no or minimal complications after extraction. Only 2 patients had serious temporary complications, including bleeding and urethral injury, with no lasting consequences. No malignancy developed as a result of UroLume insertion.CONCLUSIONS:While there is a potential for urethral injury and bleeding, UroLume endoprosthesis removal is largely a simple procedure with minimal complications and consequences.

PURPOSE:We determine the long-term efficacy and safety of the UroLume stent as minimally invasive treatment for external detrusor-sphincter dyssynergia in spinal cord injured men. MATERIALS AND METHODS:A total of 160 spinal cord injured men with a mean age plus or minus standard deviation of 36.3 +/- 12.1 years (range 16 to 74) were prospectively treated with an endoprosthesis at 15 centers as part of the North American UroLume trial for external detrusor-sphincter dyssynergia. Urodynamic parameters, including voiding pressure, residual urine volume and bladder capacity, were compared before treatment and at 1, 2, 3, 4 and 5 years after treatment. RESULTS:Mean voiding pressure was 75.1 +/- 28.2 cm. water before treatment in the 160 patients, and 37.4 +/- 23.9 at year 1 in 97, 39.5 +/- 22.2 at year 2 in 84, 42.6 +/- 27.3 at year 3 in 61, 46.3 +/- 33.2 at year 4 in 57 and 44.2 +/- 28.9 cm. at year 5 in 41 after stent insertion (p <0.001). Residual urine volume decreased after stent placement and was maintained throughout the 5-year followup (p <0.001). Mean cystometric capacity remained constant from 269 +/- 155 before insertion to 337 +/- 182 ml. 5 years later (p = 0.17). Hydronephrosis and autonomic dysreflexia improved or stabilized in most patients with functioning stents. Stent explant was necessary in 24 patients (15%), of whom 4 (16.7%) had another stent implanted. CONCLUSIONS:The UroLume stent demonstrates long-term safety and efficacy for the treatment of external detrusor-sphincter dyssynergia. The outcome was similar in men with and without previous sphincterotomy.

Twelve subjects experiencing stress urinary incontinence caused by spinal injury or myelomeningocele were treated by periurethral injection of a bulking agent, glutaraldehyde cross-linked (GAX) collagen. Of the 11 subjects who completed the program, seven were either cured or improved and four were only slightly improved or no better following injection. The valsalva (abdominal) leak point pressure (LPP) rose an average of 57 cm H2O (pre-treatment mean of 60 cm H2O versus post-treatment mean of 117 cm H2O) and none of the patients experienced significant complications during the mean follow-up period of 24 months. Every subject injected was able to maintain an intermittent catheterization program after treatment. These data support the use of GAX collagen as an alternative or adjunct therapy to pharmacotherapy, surgical reconstruction or implantation of a prosthesis in the management of stress urinary incontinence in the neuropathic urethra.

The 2 major urological objectives in treating the child with myelomeningocele are to preserve renal function and achieve continence. We report our success in managing these cases with nonsurgical therapy. From 1981 to 1991, 45 patients with myelomeningocele 1 to 15 years old were evaluated urodynamically before and after initiating nonsurgical treatment. Pretreatment urodynamics identified 2 groups. Group 1 consisted of 31 patients with leak point pressure of 40 cm. water or more of whom 10 had grades II to V/V vesicoureteral reflux and 4 had moderate or severe hydronephrosis. Group 2 consisted of 14 incontinent patients with leak point pressure of less than 40 cm. water and no reflux or hydronephrosis. Both groups were treated with intermittent catheterization, anticholinergic medications and fluid restriction. Within a mean followup of 5.5 years nonsurgical intervention resulted in lowering maximum detrusor pressure at maximum cystometric capacity to less than 40 cm. water in 22 of 31 group 1 patients (71%), and in resolving vesicoureteral reflux in 7 of 10 (70%) and hydronephrosis in 3 of 4 (75%) group 1 patients. Of 4 patients in group 1 with persistent high grade vesicoureteral reflux or severe hydronephrosis 3 (10%) required augmentation cystoplasty. With nonsurgical management 18 patients (40%) were completely continent, 18 (40%) required 2 or less pads daily and 9 (20%) required more than 2 pads daily. Nonsurgical management alone was effective in preserving the upper urinary tract in 90% of patients and it provided satisfactory continence in 80%. Surgical management should be reserved for the minority of patients whose upper tract changes do not resolve and for those whose degree of continence is not satisfactory with nonsurgical management.