Systemic Diseases and the Cornea

Overview

Journal Exp Eye Res

Specialty Ophthalmology

Date 2021 Jan 24

PMID 33485845

Citations 36

Authors

Ruchi Shah

Cynthia Amador

Kati Tormanen

Sean Ghiam

Mehrnoosh Saghizadeh

Vaithi Arumugaswami

Ashok Kumar

Andrei A Kramerov

Alexander V Ljubimov

Affiliations

Soon will be listed here.

Abstract

There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism), infections with viruses (SARS-CoV-2, herpes simplex, varicella zoster, HTLV-1, Epstein-Barr virus) and bacteria (tuberculosis, syphilis and Pseudomonas aeruginosa), autoimmune and inflammatory diseases (rheumatoid arthritis, Sjögren's syndrome, lupus erythematosus, gout, atopic and vernal keratoconjunctivitis, multiple sclerosis, granulomatosis with polyangiitis, sarcoidosis, Cogan's syndrome, immunobullous diseases), corneal deposit disorders (Wilson's disease, cystinosis, Fabry disease, Meretoja's syndrome, mucopolysaccharidosis, hyperlipoproteinemia), and genetic disorders (aniridia, Ehlers-Danlos syndromes, Marfan syndrome). Corneal manifestations often provide an insight to underlying systemic diseases and can act as the first indicator of an undiagnosed systemic condition. Routine eye exams can bring attention to potentially life-threatening illnesses. In this review, we provide a fairly detailed overview of the pathologic changes in the cornea described in various systemic diseases and also discuss underlying molecular mechanisms, as well as current and emerging treatments.

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References

Abdelkader H, Patel D, McGhee C, Alany R . New therapeutic approaches in the treatment of diabetic keratopathy: a review. Clin Exp Ophthalmol. 2010; 39(3):259-70. DOI: 10.1111/j.1442-9071.2010.02435.x. View

Strianese D, Rossi F . Interruption of autoimmunity for thyroid eye disease: B-cell and T-cell strategy. Eye (Lond). 2019; 33(2):191-199. PMC: 6367473. DOI: 10.1038/s41433-018-0315-9. View

Lee H, Lee J, Kim M, Kariya Y, Miyazaki K, Kim E . Insulin-like growth factor-1 induces migration and expression of laminin-5 in cultured human corneal epithelial cells. Invest Ophthalmol Vis Sci. 2006; 47(3):873-82. DOI: 10.1167/iovs.05-0826. View

Kido S, Sugita S, Horie S, Miyanaga M, Miyata K, Shimizu N . Association of varicella zoster virus load in the aqueous humor with clinical manifestations of anterior uveitis in herpes zoster ophthalmicus and zoster sine herpete. Br J Ophthalmol. 2008; 92(4):505-8. DOI: 10.1136/bjo.2007.125773. View

Tsaousis K, Panagiotou D, Kostopoulou E, Vlatsios V, Stampouli D . Corneal oedema after phacoemulsification in the early postoperative period: A qualitative comparative case-control study between diabetics and non-diabetics. Ann Med Surg (Lond). 2016; 5:67-71. PMC: 4710706. DOI: 10.1016/j.amsu.2015.12.047. View

Zlatanovic G, Veselinovic D, Cekic S, Zivkovic M, dordevic-Jocic J, Zlatanovic M . Ocular manifestation of rheumatoid arthritis-different forms and frequency. Bosn J Basic Med Sci. 2010; 10(4):323-7. PMC: 5489043. DOI: 10.17305/bjbms.2010.2680. View

Li Q, Weng J, Mohan R, Bennett G, Schwall R, Wang Z . Hepatocyte growth factor and hepatocyte growth factor receptor in the lacrimal gland, tears, and cornea. Invest Ophthalmol Vis Sci. 1996; 37(5):727-39. View

McDermott A, Xiao T, Kern T, Murphy C . Non-enzymatic glycation in corneas from normal and diabetic donors and its effects on epithelial cell attachment in vitro. Optometry. 2003; 74(7):443-52. View

Kowluru R, Mohammad G . Epigenetics and Mitochondrial Stability in the Metabolic Memory Phenomenon Associated with Continued Progression of Diabetic Retinopathy. Sci Rep. 2020; 10(1):6655. PMC: 7171070. DOI: 10.1038/s41598-020-63527-1. View

10.

Depledge D, Sadaoka T, Ouwendijk W . Molecular Aspects of Varicella-Zoster Virus Latency. Viruses. 2018; 10(7). PMC: 6070824. DOI: 10.3390/v10070349. View

11.

Cabral-Macias J, Garcia-Montano L, Perezpena-Diazconti M, Aguilar M, Garcia G, Vencedor-Meraz C . Clinical, histopathological, and in silico pathogenicity analyses in a pedigree with familial amyloidosis of the Finnish type (Meretoja syndrome) caused by a novel gelsolin mutation. Mol Vis. 2020; 26:345-354. PMC: 7195602. View

12.

Ueno H, Hattori T, Kumagai Y, Suzuki N, Ueno S, Takagi H . Alterations in the corneal nerve and stem/progenitor cells in diabetes: preventive effects of insulin-like growth factor-1 treatment. Int J Endocrinol. 2014; 2014:312401. PMC: 3948593. DOI: 10.1155/2014/312401. View

13.

Wylegala E, Mocko L, Woyna-Orlewicz A, Teper S, Orzechowska-Wylegala B . [Diabetic complications within ocular surface]. Pol Merkur Lekarski. 2007; 21(125):495-7. View

14.

Fahnehjelm K, Ashworth J, Pitz S, Olsson M, Tornquist A, Lindahl P . Clinical guidelines for diagnosing and managing ocular manifestations in children with mucopolysaccharidosis. Acta Ophthalmol. 2011; 90(7):595-602. DOI: 10.1111/j.1755-3768.2011.02280.x. View

15.

Kosekahya P, Atilgan C, Atilgan K, Koc M, Tekin K, Caglayan M . Corneal Endothelial Morphology and Thickness Changes in Patients with Gout. Turk J Ophthalmol. 2019; 49(4):178-182. PMC: 6761378. DOI: 10.4274/tjo.galenos.2018.01947. View

16.

Amesty M, Alio Del Barrio J, Alio J . COVID-19 Disease and Ophthalmology: An Update. Ophthalmol Ther. 2020; 9(3):1-12. PMC: 7243216. DOI: 10.1007/s40123-020-00260-y. View

17.

Lamberts A, Euverman H, Terra J, Jonkman M, Horvath B . Effectiveness and Safety of Rituximab in Recalcitrant Pemphigoid Diseases. Front Immunol. 2018; 9:248. PMC: 5827539. DOI: 10.3389/fimmu.2018.00248. View

18.

Petrohelos M, Ticoulis D, Diamantacos P . Band keratopathy with bilateral deafness as a presenting sign of hyperparathyroidism. Br J Ophthalmol. 1977; 61(7):494-5. PMC: 1043019. DOI: 10.1136/bjo.61.7.494. View

19.

Samoila O, Gocan D . Clinical Outcomes From Cultivated Allogenic Stem Cells vs. Oral Mucosa Epithelial Transplants in Total Bilateral Stem Cells Deficiency. Front Med (Lausanne). 2020; 7:43. PMC: 7040221. DOI: 10.3389/fmed.2020.00043. View

20.

Yang R, Sha X, Zeng M, Tan Y, Zheng Y, Fan F . The influence of phacoemulsification on corneal endothelial cells at varying blood glucose levels. Eye Sci. 2011; 26(2):91-5. DOI: 10.3969/j.issn.1000-4432.2011.02.018. View