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Is pseudoexfoliation syndrome a risk factor for cardiovascular diseases? /Psodoeksfoliyasyon sendromu kardiyovaskuler hastaliklar icin bir risk faktoru mudur?

Pseudoexfoliation syndrome (PEX) is an age related, generalized disorder of the extracellular matrix characterized by the multifocal production and progressive accumulation of a fibrillar extracellular material in intra- and extraocular tissue, which is the result of either an excessive production or insufficient breakdown or both (1). PEX was first described in 1917 by a Finnish ophthalmologist J.G. Lindberg. Although it has been known for a near a century, its physiopathology is not known yet. However, it is thought to be a systemic biochemical process (2). Pseudoexfoliation syndrome may affect up to 30% of people older than 60 years (3) and may lead to open angle glaucoma in about half of patients with PEX (4). Diagnosis is done by visualization of the typical dandruff-like material at the papillary margin or the anterior lens surface with slit-lamp biomicroscope.

More than 20 years ago, aggregates of PEX material were identified by electron microscopy in autopsy specimens of heart, lung, liver, kidney, gall bladder and cerebral meninges in 2 patients with ocular PEX (5, 6). In these extraocular locations, PEX material was primarily found in connective tissue portions of visceral organs, often in the periphery of blood vessels, and seemed to originate from connective tissue fibroblasts, smooth and striated muscle cells, and heart muscle cells. These findings suggested that ocular PEX syndrome is part of a general disorder of the extracellular matrix and that patients with PEX may suffer from increased comorbidity.

After these observations, a great interest was born about the extraocular manifestations and physiopathology of PEX. Sensorineural hearing loss was defined and its mechanism is attributed to deposition of exfoliation material in the organ of Corti or its vascular supply (7). Recent studies showed that total antioxidant status in the plasma was decreased (8, 9), serum antiphospholipid antibody levels were elevated, which is a risk factor for cardiovascular and cerebrovascular diseases (10), connective tissue growth factor was increased (11) in patients with PEX. In addition, significant alterations in cardiovagal regulation and impairment of conduit artery function (12), lower ankle brachial index (13), increased concentrations of serum hydroxyproline, which predicts collagen turnover status (14), increased homocysteine levels (15, 16), impaired endothelial functions, and increased carotid intima-media thickness (16) were reported to be associated with PEX.

These accumulating data and the Blue Mountains Eye study (17) suggest an association between, PEX and increased rate of cardiovascular mortality. However this suggestion is not confirmed by other studies (18, 19).

The study on this issue of the Anatolian Journal of Cardiology (20) addresses impairment of aortic functions in patients with PEX. I think it is an important study to understand the coexistence of pathologic manifestations of PEX. We slowly begin to understand single pieces of the whole puzzle by the aid of these studies.

In conclusion, ocular PEX might be an important marker for patients being at risk for cardiovascular and cerebrovascular diseases. However, it may be premature to recommend a general check-up for PEX patients on principle, until results of prospective, randomized, multicenter clinical trials have positively linked PEX with an increased risk for cardiovascular disease.

References

(1.) Ritch R, Schlotzer-Schrehardt U. Exfoliation (pseudoexfoliation) syndrome: toward a new understanding. Proceedings of the First International Think Tank. Acta Ophthalmol Scand 2001; 79: 213-7. [CrossRef]

(2.) Schlotzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol 2006; 141: 921-37. [CrossRef]

(3.) Ritch R, Schlotzer-Schrehardt U. Exfoliation syndrome. Surv Ophthalmol 2001; 45: 265-315. [CrossRef]

(4.) Ritch R. Exfoliation syndrome-the most common identifiable cause of open-angle glaucoma. J Glaucoma 1994; 3: 176-7. [CrossRef]

(5.) Schlotzer-Schrehardt UM, Koca MR, Naumann GO, Volkholz H. Pseudoexfoliation syndrome. Ocular manifestation of a systemic disorder? Arch Ophthalmol 1992; 110: 1752-6. [CrossRef]

(6.) Streeten BW, Li ZY, Wallace RN, Eagle RC Jr, Keshgegian AA. Pseudoexfoliative fibrillopathy in visceral organs of a patient with pseudoexfoliation syndrome. Arch Ophthalmol 1992; 110: 1757-62. [CrossRef]

(7.) Paliobei VP Psillas GK, Mikropoulos DG, Haidich AB, Constantinidis J, Konstas AG. Hearing evaluation in patients with exfoliative and primary open-angle glaucoma. Otolaryngol Head Neck Surg 2011; 145: 125-30. [CrossRef]

(8.) Abu-Amero KK, Kondkar AA, Mousa A, Osman EA, Al-Obeidan SA. Decreased total antioxidants status in the plasma of patients with pseudoexfoliation glaucoma. Mol Vis 2011; 17: 2769-75.

(9.) Cumurcu T, Gunduz A, Ozyurt H, Nurcin H, Atis O, Egri M. Increased oxidative stress in patients with pseudoexfoliation syndrome. Ophthalmic Res 2010; 43: 169-72. [CrossRef]

(10.) Altintas O, Yuksel N, Sonmez GT, Ozkan B, Altintas L, Caliskan S, et al. Serum antiphospholipid antibody levels in pseudoexfoliation. J Glaucoma 2011 Mar 16. [Epub ahead of print]

(11.) Browne JG, Ho SL, Kane R, Oliver N, Clark AF, O'Brien CJ, et al. Connective tissue growth factor is increased in pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci 2011; 52: 3660-6. [CrossRef]

(12.) Visontai Z, Horvath T, Kollai M, Hollo G. Decreased cardiovagal regulation in exfoliation syndrome. J Glaucoma 2008; 17: 133-8. [CrossRef]

(13.) Praveen MR, Shah SK, Vasavada AR, Diwan RP, Shah SM, Zumkhawala BR, et al. Pseudoexfoliation as a risk factor for peripheral vascular disease: a case-control study. Eye (Lond) 2011; 25: 174-9. [CrossRef]

(14.) Yagci R, Ersoz I, Aydin B, Beyaz E, Gurel A, Durmus M, et al. Aqueous humor and serum concentration of hydroxyproline in pseudoexfoliation syndrome. J Glaucoma 2007; 16: 225-9. [CrossRef]

(15.) Roedl JB, Bleich S, Reulbach U, Rejdak R, Kornhuber J, Kruse FE, et al. Homocysteine in tear fluid of patients with pseudoexfoliation glaucoma. J Glaucoma 2007; 16: 234-9. [CrossRef]

(16.) Koz C, Turkcu F, Gurbuz Koz O, Yokusoglu M, Baysan O, Yarangumeli A, et al. Endothelial function and novel risk factors in pseudoexfoliation syndrome. Turkiye Klinikleri J Med Sci 2009; 29: 1510-6.

(17.) Lee AJ, Wang JJ, Kifley A, Mitchell P. Open-angle glaucoma and cardiovascular mortality: the Blue Mountains Eye Study. Ophthalmology 2006; 113: 1069-76. [CrossRef]

(18.) Brajkovic J, Kalauz-Surac I, Ergegovic A, Miletic-Juric A, Susic N, Buric Z. Ocular pseudoexfoliation syndrome and internal systemic disease. Acta Clin Croat 2007; 46 (Suppl 1): 57-61.

(19.) Speckauskas M, Tamosiunas A, Jasinskas V. Association of ocular pseudoexfoliation syndrome with ischaemic heart disease, arterial hypertension and diabetes mellitus. Acta Ophthalmol 2012 May 2. doi: 10.1111/j.17553768.2012.02439.x. [Epub ahead of print]. [CrossRef]

(20.) Alpaslan M, Karalezli A, Borazan M, Ekinci Koktekir B, Muderrisoglu IH. Decreased aortic root elasticity; a novel systemic manifestation of the pseudoexfoliation syndrome: An observational study. Anadolu Kardiyol Derg 2012; 12: 00.00.

Mehmet Yokusoglu

Department of Cardiology, Giilhane Military Medical Academy,

Ankara-Turkey

Conflict of interest: None declared.

Address for Correspondence/Yazisma Adresi: Dr. Mehmet Yokusoglu, Gulhane Tip Akademisi, Kardiyoloji Anabilim Dal?, Etlik, Ankara-Turkiye Phone: +90 312 304 42 67 Fax: +90 312 304 42 50 E-mail: myokusoglu@yahoo.com

Accepted Date/Kabul Tarihi: 22.05.2012 Available Online Date/Cevrimici Yay?n Tarihi: 07.06.2012

doi:10.5152/akd.2012.156
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Title Annotation:Editorial Comment/Editoryel Yorum
Author:Yokusoglu, Mehmet
Publication:The Anatolian Journal of Cardiology (Anadolu Kardiyoloji Dergisi)
Date:Sep 1, 2012
Words:1130
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