PENTOSAN POLİSÜLFAT SODYUM TEDAVİSİ ALAN PRİMER MESANE AĞRISI SENDROMU HASTALARINDA PİGMENTER MAKULOPATİ İLİŞKİSİNİN DEĞERLENDİRİLMESİ
Amaç
Primer mesane ağrı sendromu (PMAS); suprapubik
bölgede ağrı, sık idrara çıkma, ani sıkışma hissi ve
nokturi gibi alt üriner sistem semptomlarının en az
birinin 6 haftadan uzun bir süre eşlik etmesi olarak
tanımlanmaktadır. Primer mesane ağrı sendromu tedavisinde
birçok alternatif tedavi olmasına rağmen
oral olarak onaylanan tek ilaç pentosan polisülfat sodyumdur
(PPS). Yaygın kullanımı sonrasında retinal
toksiteyle ilişkilendirilmesinden dolayı çalışmamızda
PPS kullanımı ile makulopati arasındaki ilişkiyi değerlendirmeyi
amaçladık.
Gereç ve Yöntem
2010-2020 yılları arasında tek merkezli PMAS tanısı
alıp sadece PPS kullanımından fayda görebilecek
alt grup ve fenotip değerlendirmesi (üriner ve non-ülseratif
organa özgü alt gruplar) sonucunda çalışmaya
dahil edildi. Çalışmadan özgeçmişinde dejeneratif
makulopatisi olan veya makulopatiye yatkınlık
yaratan hastalıkları olanlar çalışmadan çıkarılmışlardır.
Hastalara Snellen görme eşeli ile düzeltilmiş en
iyi görme keskinliği ölçümü, slit lamp biyomikroskop
ile ön segment ve fundus incelemesi yapıldı ve göz içi
basınçları ölçüldü. Renkli görme testi, arka segment
optik koherans incelemesi ve10-2 görme alanı testi
uygulandı ve fundus renkli ve otofloresans fotoğrafları
çekildi. Düzeltilmiş en iyi görme keskinliği, renkli görme
sonuçları, makula, koroid ve ortalama retina sinir
lifi kalınlıkları, görme alanı ortalama sapma değeri ve
fundus bulguları kaydedildi.
Bulgular
Çalışmaya dahil edilen toplam 15 hastanın 4’ü (%37,5)
erkek, 11’i (%73,3) kadındı. Hastaların yaş ortalamaları
53,3±11,2 olarak gözlendi. Takipleri sırasında ortalama
oral PPS kullanım süresi 33,01±10,59 ay ve
kümülatif oral PPS dozu 216,02±97,63 gr tanı süreleri
ise 66,64±39,37 ay olarak tespit edilmiştir. Hastaların
ortalama merkezi makula ve koroid kalınlığı sırasıyla
254,55±33,11 mikron, 261,82±34,22 mikron olarak ölçüldü.
Hastaların görme alanı sapma değeri ortalaması-
1,89±-1,25 dB, fundus-otofloresans görüntülerinde
ortalama retina sinir lif kalınlığı ise 98,1±17,62 mikron
ölçüldü. Ek olarak çalışmamızda ortalama kümülatif
dozun ve maruziyet süresinin altında ve üstündeki
hastaların da göz bulguları kendi içinde karşılaştırıldı.
Sonuç
Çalışmamızda kronik PPS kullanımı ile makulopati
arasında bir ilişki saptanmamıştır. Hasta grubunun
oluşturulmasında; diyabet ve hipertansiyon gibi ek
hastalıkları olan hastaların çıkartılması, fenotip ve alt
grup değerlendirmesi sonucunda homojen bir şekilde
oluşturulması son derece önemlidir.
EVALUATION OF THE ASSOCIATION OF PIGMENTARY MACULOPATHY IN PRIMARY BLADDER PAIN SYNDROME PATIENTS RECEIVING PENTOSAN POLYSULFATE SODIUM TREATMENT
Objective
Primary bladder pain syndrome (PBPS) is
characterized with suprapubic pain accompanied by
at least one lower urinary tract symptoms including
frequent urination, urinary urgency and nocturia for
more than 6 weeks. While there are many alternative
therapies for the treatment of PBPS, the only approved
oral medication is PPS (pentosan polysulfate sodium).
As it has been associated with retinal toxicity after
its widespread use, this study aims to evaluate the
relationship between PPS use and maculopathy.
Material and Methods
The patients diagnosed with PBPS between 2010
and 2020 who may only benefit from PPS use were
included into the study after subgroup and phenotype
assessment (urinary and non-ulcerative organspecific
subgroups). In our study, patients who had
history of degenerative maculopathy or diseases
predisposing to maculopathy (age-related macular
degeneration, diabetes mellitus, hypertension, chronic
vascular disorders, central serous chorioretinopathy,
retinal dystrophy, epiretinal membrane, and chronic
exposure to hydroxychloroquine) were excluded to
prevent possible misdirection. Patients underwent
best-corrected visual acuity assessment using Snellen
chart, anterior segment and fundus examination using
slit lamp biomicroscopy, and intraocular pressure
measurement. Color vision test (Ishihara test),
posterior segment optical coherence examination
and 10-2 visual field test were performed, and color
images of the fundus and autofluorescence imaging
were obtained. Best-corrected visual acuity, color
vision results, macular, choroidal and mean retinal
nerve fiber thicknesses, mean deviation of the visual
field and fundus findings were recorded.
Results
Out of 15 patients included into the study, 4 (37.5%)
were male and 11 (73.3%) were female. The mean
age of the patients was 53.3±11.2 years. During the
follow-up, the duration of oral PPS use was found to
be 33.01±10.59 months, cumulative oral PPS dose
to be 216.02±97.63 g and duration of diagnosis to
be 66.64±39.37 months. The mean central macular
thickness of the patients was measured to be
254.55±33.11 μm, and the mean choroidal thickness
to be 261.82±34.22 μm. Mean deviation of the visual
field of the patients was found to be -1.89 ±-1.25 dB.
The mean retinal nerve fiber thickness was measured
to be 98.1±17.62 μm from the fundus autofluorescence
images of the patients. Furthermore, in the present
study, the ocular findings of the patients who are at
below and above the mean cumulative dose and
exposure period were compared.
Conclusion
This study detected no correlation between longterm
PPS use and maculopathy. When forming
the patient group; it is crucial to exclude patients
with comorbidities such as diabetes mellitus and
hypertension, and to form a homogeneous group by
phenotype and subgroup assessment. Randomized,
prospective, multi-center studies are needed to better
assess this correlation.
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- 1. Hanno P and Dmochowski R: Status of international consensus
on interstitial cystitis/bladder pain syndrome/painful bladder syndrome:
2008 snapshot. Neurourology and Urodynamics 2009;
28: 274.
- 2. G C Curhan 1, F E Speizer, D J Hunter, S G Curhan, M J Stampfer
Epidemiology of interstitial cystitis: a population based
study. J Urol, 1999. 161: 549. https://www.ncbi.nlm.nih.gov/
pubmed/9915446
- 3. C Lowell Parsons 1, Vasiliki Tatsis. Prevalence of interstitial
cystitis in young women. Urology, 2004. 64: 866. https://www.
ncbi.nlm.nih.gov/pubmed/15533465
- 4. Oravisto, K.J. Epidemiology of interstitial cystitis. Ann Chir Gynaecol
Fenn, 1975. 64: 75. https://www.ncbi.nlm.nih.gov/pubmed/
1137336
- 5. Michael J Barry 1, Carol L Link, Mary F McNaughton-Collins,
John B McKinlay. Overlap of different urological symptom
complexes in a racially and ethnically diverse, community-based
population of men and women. BJU Int, 2008. 101: 45.
- 6. Sandra H Berry , Marc N Elliott, Marika Suttorp, Laura M Bogart,
Michael A Stoto, Paul Eggers et al. Prevalence of symptoms
of bladder pain syndrome/interstitial cystitis among adult
females inthe United States. J Urol, 2011. 186: 540. https: //
www. ncbi.nlm. nih. gov/pubmed/21683389
- 7. D. Engeler (Chair), A.P. Baranowski, B. Berghmans, J. Borovicka,
A.M. Cottrell, P. Dinis-Oliveira “EAU Guidelines on Chronic
Pelvic Pain” 2021, https://uroweb.org/guideline/chronic-pelvic-
pain/ ( 2 May 2021)
- 8. Hanno P, Lin A, Nordling J, Nyberg L, van Ophoven A, Ueda T,
et al. Bladder pain syndrome committee of the International Consultation
on Incontinence. Neurourol Urodyn. 2010;29(1): 191–8.
- 9. Frileux C. Un nouvel anticoagulant de synthèse le thrombocid
[Thrombocid:a newsynthetic anticoagulant]. Presse Med.
1951;59(8):159. 13
- 10. Koncz J, Bucherl E. Beitrag zur Wirkungsweise des Anticoagulans
Thrombocid [On the mode of action of thrombocid]. Klin
Wochenschr. 1951;29(37-38):650. doi:10.1007/BF01490174
- 11. van Ophoven A, Vonde K, Koch W, Auerbach G, Maag KP. Efficacy
of pentosan polysulfate for the treatment of interstitial cystitis/
bladder pain syndrome: results of a systematic review of
randomized controlled trials. Curr Med Res Opin. 2019;35(9):
1495–503.
- 12. Arndt van Ophoven, Kirsten Vonde, Winfried Koch, Günter Auerbach
& Klaus P. Maag.Efficacy of pentosan polysulfate for the
treatment of interstitial cystitis/bladder pain syndrome: results
of a systematic review of randomized controlled trials, Current
Medical Research and Opinion, 2019; 35:9, 1495-1503, DOI:
10.1080/03007995.2019.1586401
- 13. Taneja, R. (2020). Current status of oral pentosan polysulphate
in bladder pain syndrome/interstitial cystitis. International
Urogynecology Journal, 1-9.
- 14. Pearce WA, Chen R, Jain N. Pigmentary Maculopathy Associated
with Chronic Exposure to Pentosan Polysulfate Sodium.
Ophthalmology. 2018;125(11):1793‐1802. doi:10.1016/j.ophtha.
2018.04.026
- 15. Ludwig CA, Vail D, Callaway NF, Pasricha MV, Moshfeghi DM.
Pentosan PolysulfateSodium Exposure and Drug-Induced
Maculopathy in Commercially Insured Patients in the United
States. Ophthalmology. 2020;127(4):535‐543. doi:10.1016/j.
ophtha.2019.10.036
- 16. Jain N, Li AL, Yu Y, VanderBeek BL. Association of macular
disease with long-term use of pentosan polysulfate sodium: findings
from a US cohort [published online ahead of print, 2019
Nov 6]. Br J Ophthalmology. 2019; bjophthalmol-2019-314765.
doi:10.1136/bjophthalmol-2019-314765
- 17. Nickel JC, Shoskes D, Irvine‐Bird K. Clinical phenotyping of
women with interstitial cystitis/painful bladder syndrome: a key
to classification and potentially improved management.J Urol.
2009;182:155‐160.
- 18. Khullar, V., Chermansky, C., Tarcan, T., Rahnama'i, M. S., Digesu,
A., Sahai, Dmochowski, R. (2019). How can we improve the
diagnosis and management of bladder pain syndrome? Part
1: ICI‐RS 2018. Neurourology and urodynamics, 38, S66-S70.
- 19. Vora RA, Patel AP, Melles R. Prevalence of Maculopathy
Associated with Long-Term Pentosan Polysulfate Therapy.
Ophthalmology. 2020;127(6):835-836. doi:10.1016/j.ophtha.
2020.01.017
- 20. Ortho−McNeil−Janssen Pharmaceuticals, Elmiron (Pentosan
Polysulfate sodium). U.S. Food and Drug Administration website.
Available at: https://www.accessdata .fda.gov/drugsatfda
_docs/label/2008/020193s009lbl.pdf. RevisedJune 2020. Accessed
June 30, 2020.
- 21. Mogica, J. A. P., & De Elise, J. B. (2021). Pentosan polysulfate
maculopathy: what urologists should know in 2020. Urology,
147, 109-118.