Glaucoma and Infectious Disease
Glaucoma is a chronic and progressive optic neuropathy that results in characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. Glaucoma is the second most common cause of blindness worldwide, and the leading cause of irreversible blindness in the world, affecting more than 70 million people. As it progresses, glaucoma may be asymptomatic and is therefore rarely detected by the individual until symptoms and vision loss are severe.
Secondary glaucoma results from an underlying condition or cause. Causes of secondary glaucoma can include trauma, tumors, medications, autoimmune conditions, and infections. There are a variety of different infections that have been associated with secondary glaucoma.
HSV, CMV, VZV and Rubella
Herpes simplex virus (HSV), Cytomegalovirus (CMV), and Varicella Zoster Virus (VZV) are enveloped double stranded DNA viruses. Rubella Virus is an enveloped positive stranded RNA virus. These viruses are associated with anterior uveitis and subsequent development of increased intraocular pressure and glaucoma. It is estimated that between 10-40% of patients with virus-associated anterior uveitis develop secondary glaucoma. CMV is an established cause of secondary glaucoma and can lead to IOP levels greater than 30 mmHg. The number of episodes of IOP peaks that occur during the course of the infection is an important indicator for the development of chronic glaucoma. Elevated IOP may result from trabecular meshwork damage by the virus or increased viscosity of the aqueous humor due to increased protein and fibrin production as well as the presence of inflammatory cells. Studies have shown that most patients develop open angle glaucoma, but angle closure glaucoma can develop due to peripheral anterior and posterior synechiae.
Adenovirus is a non-enveloped, double-stranded DNA virus that commonly causes upper respiratory tract infections. It may also cause pharyngoconjunctival infections. These infections typically resolve spontaneously without any lasting impacts. Common ocular manifestations of adenovirus include hemorrhagic or epidemic keratoconjunctivitis.
Animal model research has shown that transfer of the adenovirus genome into rodent eyes leads to elevated intraocular pressure and decreased outflow of aqueous humor. There has been at least one report of adenovirus keratoconjunctivouveitis with elevated intraocular pressure and secondary glaucoma in vivo in humans.
H. pylori is a gram-negative spirochete. It has a very high prevalence worldwide, with an estimated 58% colonization rate of the global population. It is commonly associated with gastric manifestations such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma. However, it has also been found to be associated with open-angle glaucoma and normal tension glaucoma due to inflammation, the release of vasoactive factors, and dysfunction of the trabecular meshwork via oxidative stress.
Listeria monocytogenes is a gram-positive bacilli. It is a facultative anaerobe that has a characteristic “tumbling” motion at room temperature. Listeria commonly infects immunocompromised individuals, older adults, or neonates. Infections can result in septicemia or meningitis and are often transmitted through food such as raw meats or milk. Listeria can also be transmitted transplacentally. Intraocular listeriosis is a rare but severe condition. It can present with a dark hypopyon, endophthalmitis, elevated intraocular pressure, eye pain, and vision loss. Glaucoma in ocular listeriosis may be due to inflammation and iris necrosis and pigment dispersion.
Mycobacterium tuberculosis is an aerobic, acid-fast, gram positive rod that causes a chronic infectious disease known as tuberculosis (TB). Mycobacterium leprae is a closely related gram-positive, obligate intracellular parasite associated with Hansen’s disease, or leprosy. Although rare, mycobacterium infection can have several ocular manifestations. This may be particularly true in immunocompromised patients, such as patients with AIDS. Studies have shown that patients with TB may have elevated intraocular pressure and development of glaucoma. Glaucoma can occur from chronic anterior uveitis due to TB, including synechial angle closure and pupillary block. M. leprae is also associated with secondary angle closure and glaucoma due to intraocular inflammation.
Acanthamoeba is a protozoan parasite that can act as a pathogen. It exists in air, soil, and water and its life cycle includes a trophozoite and cyst stage. Acanthamoeba causes a fatal central nervous system disease known as granulomatous amebic encephalitis. The most common ocular manifestation is amebic keratitis.
Acanthamoeba keratitis has been associated with secondary glaucoma in individuals without a prior history of glaucoma, ocular hypertension, or intraocular surgery. Histological evaluation demonstrates that the trabecular meshwork is chronically inflamed, resulting in synechiae and angle closure in these individuals.
Gnathostoma is a helminth parasite found in tropical and subtropical regions including Southeast Asia and Latin America. The third-stage larvae can cause the parasitic infection known as the food-borne disease known as Gnathostomiasis. Gnathostoma can lead to cutaneous symptoms as well as visceral symptoms, affecting the respiratory, gastrointestinal, genitourinary and central nervous systems.
There are a variety of ocular manifestations including uveitis, iritis, retinal scarring and detachment, intraocular hemorrhage, and glaucoma. There has been a case in which this parasite (specifically Gnathostoma spinigerum) was located in the anterior chamber, leading to acute anterior uveitis and uveitic glaucoma.
Prion diseases are fatal neurodegenerative diseases. While some of these diseases are heritable, some are transmissible through body fluids and act as an infectious brain disease. They may be transmitted through direct contact with body fluids, tissue transplant, or indirectly through the environment. Prions (PrPSc) are conformational isoforms of normal proteins (PrPC) expressed on human cell membranes, specifically on neuronal cells. The presence of the prion leads to a conformational change of the normal protein, which eventually leads to neuronal cell death.
Prion diseases can lead to a variety of ocular manifestations, including open-angle glaucoma. Specifically, the conformational change of the normal protein PrPC leads to destabilization of the extracellular matrix. This increases the resistance of the trabecular meshwork, decreasing drainage of aqueous humor, elevating the intraocular pressure. The increase in IOP results in optic nerve degeneration and vision loss.
- Prum Jr BE, Rosenberg LF, Gedde SJ, et al. Primary open-angle glaucoma preferred practice pattern guidelines. Ophthalmology. 2016;123(1):P41-P111. doi:10.1016/j.ophtha.2015.10/053
- Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma. JAMA. 2014;311(18):1901-1911. doi:10.1001/jama.2014.3192
- Shimizu A, Maruyama K, Yokoyama Y, et al. Characteristics of uveitic glaucoma and evaluation of its surgical treatment. Clin Ophthalmol. 2014;8:2383-2389. doi: 10.2147/OPTH.S72383
- Pohlmann D, Pahlitzsch M, Schlickeiser S, et al. Virus-associated anterior uveitis and secondary glaucoma: Diagnostics, clinical characteristics, and surgical options. PLoS One. 2020;15(2):e0229260. doi:10.1371/journal.pone.0299260
- Jones III R, Pasquale LR, Pavan-Langston D. Herpes simplex virus: an important etiology for secondary glaucoma. Int Ophthal. 2007;47(2):99-107.
- Hoeksema L, Jansonius NM, Los LI. Risk factors for secondary glaucoma in herpetic anterior uveitis. Am J Ophthalmol. 2017;181:55-60.
- Hara J, Ishibashi T, Fujimoto F, et al. Adenovirus type 10 keratoconjunctivitis with increased intraocular pressure. Am J Ophthalmol. 1980;90(4):481-484. doi:10.1016/s0002-9394(14)75015-9
- Shepard AR, Millar JC, Pang IH, et al. Adenovirus gene transfer of active human transforming growth factor-β2 elevates intraocular pressure and reduces outflow facility in rodent eyes. Investig Ophthalmol Vis Sci. 2010;51:2067-2076. doi:10.1167/iovs.09-4567
- Doulberis M, Papaefthymiou A, Polyzos SA, et al. Association between active Helicobacter pylori infection and glaucoma: A systematic review and meta-analysis. Microorganisms. 2020;8(6):894. doi:10.3390/microorganisms8060894
- Zeng J, Liu H, Liu X, Ding C. The relationship between Helicobacter pylori infection and open-angle glaucoma: A meta-analysis. Invest Ophthalmol Vis Sci. 2015;56(9):5238-5245. doi:10.1167/iovs.15-17059
- Izzotti A, Sacca S, Bagnis A, Recupero S. Glaucoma and Helicobacter pylori infection: correlations and controversies. Br J Ophthalmol. 2009;93:1420-1427. doi: 10.1136/bjo.2008.150409
- Alkatan HM, Al-Dhibi HA, Edward DP, Al-Rajhi AA. Pigmented hypopyon in association with Listeria monocytogenes endophthalmitis: an interesting case report following refractive surgery procedure with literature review. Middle East Afr J Ophthalmol. 2014; 21: pp. 40-43.
- Ibraheem M, Vance S, Jackson KA, et al. Vision loss following intraocular listeriosis associated with contaminated cantaloupe. Case Rep Ophthalmol. 2013;4(2):7-11. doi:10.1159/000351858
- Aldaas K, Challa P, Weber DJ, Fleischman D. Infections and glaucoma. Surv Ophthalmol. 2022;67(3):637-58.
- Egbagbe EE, Omoti AE. Ocular disorder in adult patients with tuberculosis in a tertiary care hospital in Nigeria. Middle East Afr J Ophthalmol. 2008;15(2). doi:10.4103/0974-9233.51996
- Parikh R, Thomas S, Muliyil J, Parikh S, Thomas R. Ocular manifestation in treated multibacillary Hansen's disease. Ophthalmology. 2009;116:2051-2057.
- Walton RC, Ball SF, Joffrion VC: Glaucoma in Hansen's disease. Br J Ophthalmol. 1991;75:270-272.
- Marciano-Cabral F, Cabral G. Acanthamoeba spp as agents of disease in humans. Clin Microbiol Rev. 2003;16(2):273-307. doi:10.1128/CMR.16.2.273-307.2003
- Kelley PS, Dossey AP, Patel D, et al. Secondary glaucoma associated with advanced acanthamoeba keratitis. Eye Contact Lens. 2006;32(4):178-182. doi:10.1097/01.icl.0000189039.68782.fe
- Herman JS, Chiodini PL. Gnathostomiasis, another emerging imported disease. Clin Microbiol Rev. 2009;22(3):484-492. doi:10.1128/CMR.00003-09
- Konwattananon W, Wiriyabanditkul T, Supwatjariyakul W, Somkijrungroj T. Intracameral gnathostomiasis: A case report and literature review. Ocul Immunol Inflamm. 2022;31(5):1092-1096. doi:10.1080/09273948.2022.2073239
- Maddox RA, Belay ED, Curns AT, Zou WQ, Nowicki S, Lembach RG, Geschwind MD, Haman A, Shinozaki N, Nakamura Y, Borer MJ. Creutzfeldt–Jakob disease in recipients of corneal transplants. Cornea. 2008;27(7):851.
- Singh N, Chaudhary S, Ashok A, Lindner E. Prions and prion diseases: insights from the eye. Exp Eye Res. 2020;199:108200. doi:10.1016/j.exer.2020.108200