Skip to main content

Advertisement

SpringerLink
Log in

Exfoliation syndrome: association with systemic diseases—the Maccabi glaucoma study

  • Glaucoma
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the relationship between exfoliation syndrome (XFS) and systemic diseases.

Methods

A population-based, retrospective study with control group was conducted using the electronic medical database of Maccabi Health Services, the second largest Health Maintenance Organization (HMO) in Israel. Study population included Maccabi members from January 2003 to April 2016. Cases consisted of patients diagnosed with XFS regardless of glaucoma. The control group included Maccabi members without XFS, matched on age, sex, and ancestry, that were examined by an ophthalmologist within the last year. Main outcome measures: Associations between XFS and systemic diseases.

Results

We identified 16,388 patients with XFS, in whom 40.3% (n = 6613) had glaucoma. The control group included 14,015 patients. Mean age was 78.3 ± 8.9 years and 76.2 ± 8.5 years for the XFS and control group, respectively. In unconditional logistic regression analyses, after adjusting for age, sex, and ancestry, XFS was significantly associated with risk of cardiovascular diseases including hypertension (OR 1.07, 95% CI 1.01–1.13, p = 0.02), myocardial infarction (OR 1.21, 95% CI 1.17–1.31, p < 0.0001), and congestive heart failure (OR 1.70, 95% CI 1.55–1.88, p < 0.0001) as well as higher risk for high creatinine (OR 1.28, 95% CI 1.2–1.37, p < 0.0001). Diabetes mellitus and body mass index were inversely associated with XFS (OR 0.70, 95% CI 0.67–0.73, p < 0.0001 and OR 0.88, 95% CI 0.84–0.93, p < 0.0001, respectively). Overall cancer diagnoses were more common in the XFS group (OR 1.05, 95% CI 1.0–1.1, p = 0.05). XFS was associated with more hospitalizations (mean 5 ± 5.3 hospitalizations in the XFS group and 3.3 ± 4.0 in the controls, p < 0.0001).

Conclusion

XFS is significantly associated with cardiovascular systemic diseases (in a population living in Israel and predominantly born in Russia).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

All data and materials can be shared on request.

References

  1. Ritch R (1994) Exfoliation syndrome—the most common identifiable cause of open-angle glaucoma. J Glaucoma 3:176–177. https://doi.org/10.1097/00061198-199400320-00018

    Article  CAS  PubMed  Google Scholar 

  2. Aboobakar IF, Johnson WM, Stamer WD et al (2017) Major review: Exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology. Exp Eye Res 154:88–103. https://doi.org/10.1016/j.exer.2016.11.011

    Article  CAS  PubMed  Google Scholar 

  3. Aung T, Ozaki M, Lee MC et al (2017) Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nat Genet 49:993–1004. https://doi.org/10.1038/ng.3875

  4. Schlötzer-Schrehardt UM, Koca MR, Naumann GO, Volkholz H (1992) Pseudoexfoliation syndrome. Ocular manifestation of a systemic disorder? Arch Ophthalmol (Chicago, Ill 1960) 110:1752–6. https://doi.org/10.1001/archopht.1992.01080240092038

  5. Ritch R, Schlötzer-Schrehardt U (2001) Exfoliation (pseudoexfoliation) syndrome: toward a new understanding. Proceedings of the First International Think Tank. Acta Ophthalmol Scand 79:213–7. https://doi.org/10.1034/j.1600-0420.2001.079002213.x

  6. Ritch R, Schlötzer-Schrehardt U, Konstas AGP (2003) Why is glaucoma associated with exfoliation syndrome? Prog Retin Eye Res 22:253–275

    Article  PubMed  Google Scholar 

  7. Schlotzer-Schrehardt U, Naumann GO (1994) A histopathologic study of zonular instability in pseudoexfoliation syndrome. Am J Ophthalmol 118:730–743. https://doi.org/10.1016/S0002-9394(14)72552-8

    Article  CAS  PubMed  Google Scholar 

  8. Conway RM, Schlötzer-Schrehardt U, Küchle M, Naumann GOH (2004) Pseudoexfoliation syndrome: pathological manifestations of relevance to intraocular surgery. Clin Exp Ophthalmol 32:199–210

    Article  PubMed  Google Scholar 

  9. Schlötzer-Schrehardt U, Naumann GOH (2006) Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol 141. https://doi.org/10.1016/j.ajo.2006.01.047

  10. Streeten BW, Li ZY, Wallace RN et al (1992) Pseudoexfoliative fibrillopathy in visceral organs of a patient with pseudoexfoliation syndrome. Arch Ophthalmol 110:1757–1762. https://doi.org/10.1001/archopht.1992.01080240097039

    Article  CAS  PubMed  Google Scholar 

  11. Anastasopoulos E, Topouzis F, Wilson MR et al (2011) Characteristics of pseudoexfoliation in the Thessaloniki Eye Study. J Glaucoma 20:160–166. https://doi.org/10.1097/IJG.0b013e3181d9d8bd

    Article  PubMed  Google Scholar 

  12. Bikbov MM, Zainullin RM, Gilmanshin TR et al (2020) Prevalence and associated factors of pseudoexfoliation in a Russian population: the Ural Eye and Medical Study. Am J Ophthalmol 210:158–166. https://doi.org/10.1016/j.ajo.2019.10.003

    Article  CAS  PubMed  Google Scholar 

  13. Chung H, Arora S, Damji KF, Weis E (2018) Association of pseudoexfoliation syndrome with cardiovascular and cerebrovascular disease: a systematic review and meta-analysis. Can J Ophthalmol 53:365–372. https://doi.org/10.1016/j.jcjo.2017.10.039

    Article  PubMed  Google Scholar 

  14. Levkovitch-Verbin H, Goldshtein I, Chodick G et al (2014) The Maccabi glaucoma study: prevalence and incidence of glaucoma in a large Israeli health maintenance organization. Am J Ophthalmol 158:402-408.e1. https://doi.org/10.1016/j.ajo.2014.04.026

    Article  PubMed  Google Scholar 

  15. World Health Organization (1978) International classification of diseases [9th] ninth revision, basic tabulation list with alphabetic index. https://apps.who.int/iris/handle/10665/39473. Accessed on 5th May 2021.

  16. Elhawy E, Kamthan G, Dong CQ, Danias J (2012) Pseudoexfoliation syndrome, a systemic disorder with ocular manifestations. Hum Genomics 6:22. https://doi.org/10.1186/1479-7364-6-22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schlotzer-Schrehardt U (2010) Oxidative stress and pseudoexfoliation glaucoma. Klin Monbl Augenheilkd 227:108–113. https://doi.org/10.1055/s-0028-1109977

    Article  CAS  PubMed  Google Scholar 

  18. Vessani RM, Ritch R, Liebmann JM, Jofe M (2003) Plasma homocysteine is elevated in patients with exfoliation syndrome. Am J Ophthalmol 136:41–46. https://doi.org/10.1016/S0002-9394(02)00077-1

    Article  CAS  PubMed  Google Scholar 

  19. Bleich S, Roedl J, Von Ahsen N et al (2004) Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma. Am J Ophthalmol 138:162–164. https://doi.org/10.1016/j.ajo.2004.02.027

    Article  CAS  PubMed  Google Scholar 

  20. Roedl JB, Bleich S, Reulbach U et al (2007) Homocysteine in tear fluid of patients with pseudoexfoliation glaucoma. J Glaucoma 16:234–239. https://doi.org/10.1097/IJG.0b013e31802d6942

    Article  PubMed  Google Scholar 

  21. Vardhan SA, Haripriya A, Ratukondla B et al (2017) Association of pseudoexfoliation with systemic vascular diseases in a South Indian population. JAMA Ophthalmol. https://doi.org/10.1001/jamaophthalmol.2017.0064

    Article  Google Scholar 

  22. Bettis DI, Allingham RR, Wirostko BM (2014) Systemic diseases associated with exfoliation syndrome. Int Ophthalmol Clin 54:15–28. https://doi.org/10.1097/IIO.0000000000000044

    Article  PubMed  Google Scholar 

  23. Schumacher S, Schlötzer-Schrehardt U, Martus P et al (2001) Pseudoexfoliation syndrome and aneurysms of the abdominal aorta. Lancet 357:359–360. https://doi.org/10.1016/S0140-6736(00)03645-X

    Article  CAS  PubMed  Google Scholar 

  24. Speckauskas M, Tamosiunas A, Jasinskas V (2012) Association of ocular pseudoexfoliation syndrome with ischaemic heart disease, arterial hypertension and diabetes mellitus. ACTA Ophthalmol 90:e470–e475. https://doi.org/10.1111/j.1755-3768.2012.02439.x

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mitchell P, Wang JJ, Smith W (1997) Association of pseudoexfoliation syndrome with increased vascular risk. Am J Ophthalmol 124:685–687. https://doi.org/10.1016/S0002-9394(14)70908-0

    Article  CAS  PubMed  Google Scholar 

  26. French DD, Margo CE, Harman LE (2012) Ocular pseudoexfoliation and cardiovascular disease: a national cross-section comparison study. N Am J Med Sci. https://doi.org/10.4103/1947-2714.101987

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wang W, He M, Zhou M, Zhang X (2014) Ocular pseudoexfoliation syndrome and vascular disease: a systematic review and meta-analysis. PLoS ONE 9:e92767. https://doi.org/10.1371/journal.pone.0092767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gonen T, Gonen KA, Guzel S (2014) What is the effect of pseudoexfoliation syndrome on renal function in patients without glaucoma? Curr Eye Res 39:188–193. https://doi.org/10.3109/02713683.2013.834940

    Article  PubMed  Google Scholar 

  29. Zakrzewski PA, Mackenzie PJ, Tsai G et al (2012) Does an association exist between pseudoexfoliation syndrome and chronic kidney disease? J Glaucoma 21:562–566. https://doi.org/10.1097/IJG.0b013e31821e83fe

    Article  PubMed  Google Scholar 

  30. Shrum KR, Hattenhauer MG, Hodge D (2000) Cardiovascular and cerebrovascular mortality associated with ocular pseudoexfoliation. Am J Ophthalmol 129:83–86. https://doi.org/10.1016/S0002-9394(99)00255-X

    Article  CAS  PubMed  Google Scholar 

  31. Ringvold A, Blika S, Sandvik L (2009) Pseudo-exfoliation and mortality. Acta Ophthalmol Scand 75:255–256. https://doi.org/10.1111/j.1600-0420.1997.tb00767.x

    Article  Google Scholar 

  32. Slettedal JK, Sandvik L, Ringvold A (2015) Ocular pseudoexfoliation syndrome and life span. EBIOM 2:765–769. https://doi.org/10.1016/j.ebiom.2015.05.024

    Article  Google Scholar 

  33. Svensson R, Ekström C (2015) Pseudoexfoliation and mortality: a population-based 30-year follow-up study. Acta Ophthalmol 93:162–164. https://doi.org/10.1111/aos.12402

    Article  PubMed  Google Scholar 

  34. Psilas KG, Stefaniotou MJ, Aspiotis MB (1991) Pseudoexfoliation syndrome and diabetes mellitus. Acta Ophthalmol 69:664–666

    Article  CAS  Google Scholar 

  35. Wood SD, Asefzadeh B, Fisch B et al (2011) The relationship between diabetes mellitus and exfoliation syndrome in a United States Veterans Affairs population: a case–control study. J Glaucoma 20:278–281. https://doi.org/10.1097/IJG.0b013e3181e3d483

    Article  PubMed  Google Scholar 

  36. Tarkkanen A, Reunanen A, Kivela T (2008) Frequency of systemic vascular diseases in patients with primary open-angle glaucoma and exfoliation glaucoma. Acta Ophthalmol 86:598–602. https://doi.org/10.1111/j.1600-0420.2007.01122.x

    Article  PubMed  Google Scholar 

  37. Miyazaki M, Kubota T, Kubo M et al (2005) The prevalence of pseudoexfoliation syndrome in a Japanese population: the Hisayama study. J Glaucoma 14:482–484. https://doi.org/10.1097/01.ijg.0000185436.15675.b3

    Article  PubMed  Google Scholar 

  38. Kim S, Lim S-H, Sung KR et al (2016) Prevalence of pseudoexfoliation syndrome and associated factors in South Koreans: The Korean National Health and Nutrition Examination Survey. Ophthalmic Epidemiol 23:298–302. https://doi.org/10.3109/09286586.2015.1131992

    Article  PubMed  Google Scholar 

  39. Jonas JB, Nangia V, Matin A et al (2013) Pseudoexfoliation: normative data and associations. The Central India Eye and Medical Study. PLoS ONE 8:10–15. https://doi.org/10.1371/journal.pone.0076770

    Article  CAS  Google Scholar 

  40. Zehavi-Dorin T, Pasquale LR, Levkovitch-Verbin H (2017) Exfoliation syndrome – The Maccabi Glaucoma Study. Invest Ophthalmol Vis Sci 58(8):5613

    Google Scholar 

Download references

Funding

This work was supported by The Glaucoma Foundation research grant.

Author information

Authors and Affiliations

  1. Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Tzukit Zehavi-Dorin, Elad Ben-Artsi & Hani Levkovitch-Verbin

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Nofar Nahum

Authors
  1. Tzukit Zehavi-Dorin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nofar Nahum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elad Ben-Artsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hani Levkovitch-Verbin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to study conception and design. Material preparation and data collection were performed by N.N. Data analysis and first draft of the manuscript was written by T.Z.D. All authors commented on previous versions of the manuscript and read and approved the final manuscript.

Corresponding author

Correspondence to Tzukit Zehavi-Dorin.

Ethics declarations

Ethics approval

The study was approved by the IRB of Maccabi Health Services.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The abstract with preliminary results was presented at the annual meeting of the Association for Research in Vision and Ophthalmology; May 2017; Baltimore, Maryland.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zehavi-Dorin, T., Nahum, N., Ben-Artsi, E. et al. Exfoliation syndrome: association with systemic diseases—the Maccabi glaucoma study. Graefes Arch Clin Exp Ophthalmol 259, 3027–3034 (2021). https://doi.org/10.1007/s00417-021-05241-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-021-05241-w

Keywords

Search

Navigation