Corneal alterations associated with pseudoexfoliation syndrome and glaucoma: A literature review

A systematic literature review was performed evaluating articles examining the effects of pseudoexfoliation syndrome (PEX) and glaucoma (PEXG) on the cornea with a focus on the corneal endothelium. We searched for articles relevant to pseudoexfoliation syndrome, pseudoexfoliation glaucoma and corneal endothelial cell counts using Pubmed, Google Scholar Database, Web of Science and cochrane Library databases published prior to September of 2016. We then screened the references of these retrieved papers and performed a Web of Science cited reference search. corneal characteristics analyzed included central corneal thickness (ccT), corneal nerve density, endothelial cell density (EcD), polymegathism, and pleomorphism. These parameters were compared in the following populations: control, PEX, PEXG, and primary open angle glaucoma (POAG). Over 30 observational studies were reviewed. Most studies showed a statistically significant lower EcD in PEX and PEXG populations compared to controls. Overall, PEX eyes had a non-statistically significant trend of lower EcDs compared to PEXG eyes. No consistent trends were found when analyzing differences in ccT amongst control, PEX and PEXG groups. For the few studies that looked at corneal nerve characteristics, the control groups were found to have statistically significantly greater nerve densities than PEX eyes, which had significantly greater densities than PEXG eyes. EcD and corneal nerve densities may be potential metrics for risk-stratifying patients with PEX and PEXG. Our literature review provided further evidence of the significant negative influence PEX has on the cornea, worsening as patients convert to PEXG. Palko Joel 1 Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, MO Qi Owen 2 Department of Internal Medicine, Mercy Hospital, St. Louis, MO Sheybani Arsham 3 Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, MO Ritch R. Exfoliation syndrome-the most common identifiable cause of open-angle glaucoma. J Glaucoma 1994;3:176-177. Ringvold A. Epidemiology of the pseudo-exfoliation syndrome. Acta Ophthalmol Scand 1999;77(4):371-375. Jonasson F, Damji KF, Arnarsson A, Sverrison T, Wang L, Sasaki H, et al. Prevalence of open-angle glaucoma in Iceland: Reykjavik Eye Study. Eye 2003;17(6):747-753. Thorleifsson G, Magnusson KP, Sulem P, Walters GB, Gudbjartsson D, Stefansson H, et al. common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science 2007;317(5843):1397-1400. Ritch R, Schlötzer-Schrehardt U, Konstas AGP. Why is glaucoma associated with exfoliation syndrome? Prog Retin Eye Res 2003;22(3):253-275. Kivelä T, Hietanen J, Uusitalo M. Autopsy analysis of clinically unilateral exfoliation syndrome. Invest Ophthalmol Vis Sci 1997;38(10):2008-2015. Henry Jc, Krupin T, Schmitt M, Lauffer J, Miller E, Ewing MQ, et al. Long-term follow-up of pseudoexfoliation and the development of elevated intraocular pressure. Ophthalmology 1987;94(5):545-552. Konstm A. Glaucoma in eyes with exfoliation syndrome. In: 3rd International Glaucoma Symposium-IcS. Prague, Czech Republic; 2001. Jeng SM, Karger RA, Hodge DO, Burke JP, Johnson DH, Good MS. The risk of glaucoma in pseudoexfoliation syndrome. J Glaucoma 2007;16 (1):117-121. Konstas AG, Stewart Wc, Stroman GA, Sine cS. clinical presentation and initial treatment patterns in patients with exfoliation glaucoma versus primary open-angle glaucoma. Ophthalmic Surg Lasers 1997;28(2):111-117. Kahloun R, Attia S, Ksiaa I, Kacem I, Bouanene I, Zaouali S, et al. Anterior chamber aqueous flare, pseudoexfoliation syndrome, and glaucoma. Int Ophthalmol 2016;36(5):671-674. Zheng X. New findings for an old disease: Morphological studies on pseudoexfoliation syndrome-related keratopathy and binocular asymmetry. cornea 2013;32 Suppl 1:S84-90. Zheng X, Shiraishi A, Okuma S, Mizoue S, Goto T, Kawasaki S, et al. In vivo confocal microscopic evidence of keratopathy in patients with pseudoexfoliation syndrome. Invest Ophthalmol Vis Sci 2011;52(3):1755-1761. Kocabeyoglu S, Mocan Mc, Irkec M, Karakaya J. In Vivo confocal Microscopic Evaluation of corneas in Patients With Exfoliation Syndrome. J Glaucoma 2016;25(2):193-197. Brooks AM, Grant G, Robertson IF, Gillies WE. Progressive corneal endothelial cell changes in anterior segment disease. Aust N Z J Ophthalmol 1987;15(1):71-78. de Juan-Marcos L, cabrillo-Estévez L, Escudero-Domínguez FA, Sánchez-Jara A, Hernández-Galilea E. [Morphometric changes of corneal endothelial cells in pseudoexfoliation syndrome and pseudoexfoliation glaucoma]. Arch la Soc Espanñola Oftalmol 2013;88(11):439-444. Demircan S, Atas M, Yurtsever Y. Effect of torsional mode phacoemulsification on cornea in eyes with/without pseudoexfoliation. Int J Ophthalmol 2015;8(2):281-287. Hattori Y. [corneal endothelial examination of pseudoexfoliation syndrome]. Nihon Ganka Gakkai Zasshi 1990;94(10):957-963. Inoue K, Okugawa K, Oshika T, Amano S. Morphological study of corneal endothelium and corneal thickness in pseudoexfoliation syndrome. Jpn J Ophthalmol 2003;47(3):235-239. Kaljurand K, Teesalu P. Exfoliation syndrome as a risk factor for corneal endothelial cell loss in cataract surgery. Ann Ophthalmol(Skokie) 2007;39(4):327-333. Knorr HL, Jünemann A, Händel A, Naumann GO. [Morphometric and qualitative changes in corneal endothelium in pseudoexfoliation syndrome]. Fortschr Ophthalmol 1991;88(6):786-789. Miyake K, Matsuda M, Inaba M. corneal endothelial changes in pseudoexfoliation syndrome. Am J Ophthalmol 1989;108(1):49-52. Oltulu R, Satirtav G, Kayitmazbatir ET, Bitirgen G, Ozkagnici A, Karaibrahimoglu A. characteristics of the cornea in patients with pseudoexfoliation syndrome. Arq Bras Oftalmol 2015;78(6):348-351. Omura T, Tanito M, Doi R, Ishida R, Yano K, Matsushige K, et al. correlations among various ocular parameters in clinically unilateral pseudoexfoliation syndrome. Acta Ophthalmol. 2014;92(5):e412-3. Ostern AE, Drolsum L. corneal endothelial cells 6-7 years following cataract surgery in patients with pseudoexfoliation syndrome. Acta Ophthalmol 2012;90(5):408-411. Puska P, Vasara K, Harju M, Setälä K. corneal thickness and corneal endothelium in normotensive subjects with unilateral exfoliation syndrome. Graefe's Arch clin Exp Ophthalmol=Albr von Graefes Arch fuür Klin und Exp Ophthalmol 2000;238(8):659-663. Quiroga L, Lansingh Vc, Samudio M, Peña FY, carter MJ. characteristics of the corneal endothelium and pseudoexfoliation syndrome in patients with senile cataract. clin Experiment Ophthalmol 2010;38(5):449-455. Romero-Aroca P, Masip-Serra R, Martínez-Salcedo I, Salvat-Serra M, Fernández-Ballart J, Bautista-Pérez A. High prevalence of pseudoexfoliation syndrome and its complications in Tarragona in northeast Spain. Eur J Ophthalmol 2011;21(5):580-588. Sarowa S, Manoher J, Jain K, Singhal Y, Devathia D. Qualitative and quantitative changes of corneal endothelial cells and central corneal thickness in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Int J Med Sci Public Heal 2016;5(12):1. Tomaszewski BT, Zalewska R, Mariak Z. Evaluation of the endothelial cell density and the central corneal thickness in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. J Ophthalmol 2014;2014:123683. Vannas A, Setälä K, Ruusuvaara P. Endothelial cells in capsular glaucoma. Acta Ophthalmol 1977;55(6):951-958. Wali UK, Al-Mujaini AS, Al-Kharusi NS, Bialasiewicz AA, Rizvi SG. Quantitative and qualitative corneal endothelial morphology of omani patients with pseudoexfoliation syndrome. Sultan Qaboos Univ Med J 2008;8(3):300-305. Wang M, Sun W, Ying L, Dong X-G. corneal endothelial cell density and morphology in chinese patients with pseudoexfoliation syndrome. Int J Ophthalmol 2012;5(2):186-189. Wang L, Yamasita R, Hommura S. corneal endothelial changes and aqueous flare intensity in pseudoexfoliation syndrome. Ophthalmol J Int d'ophtalmologie Int J Ophthalmol Zeitschrift fuür Augenheilkd 1999;213(6):387-391. Wirbelauer c, Anders N, Pham DT, Wollensak J. corneal endothelial cell changes in pseudoexfoliation syndrome after cataract surgery. Arch Ophthalmol (chicago, Ill 1960) 1998;116(2):145-149. Yüksel N, Emre E, Pirhan D. Evaluation of corneal Microstructure in Pseudoexfoliation Syndrome and Glaucoma: In vivo Scanning Laser confocal Microscopic Study. curr Eye Res 2016;41(1):34-40. Oliveira-Soto L, Efron N. Morphology of corneal nerves using confocal microscopy. cornea 2001;20(4):374-384. Hayashi K, Manabe S-I, Yoshimura K, Kondo H. corneal endothelial damage after cataract surgery in eyes with pseudoexfoliation syndrome.