Glaucoma Associated With Systemic Disease

Clinicians must be familiar with these associations so that they can initiate treatment.

By Lisa S. Gamell, MD, and Brian H. Chen, MD
 

In the past, glaucoma was defined by increased IOP, but it is now considered a progressive optic neuropathy that may signify the final pathway of numerous disorders. Although elevated IOP remains the most significant risk factor for glaucomatous damage, it is certainly not the only one. Mechanical pressure, vascular insult, oxidative damage, mitochondrial disorders, genetic disorders, excitotoxicity, and disorders of cellular death are among the myriad theorized causes of glaucomatous disc damage. Many of these risk factors are poorly understood, and others remain to be discovered.

The list of systemic disorders associated with glaucoma is long, and several are covered elsewhere in this issue of Glaucoma Today. This article will briefly review inflammatory and infectious glaucoma, other systemic disease-associated glaucoma, and medication-associated glaucoma.

INFLAMMATORY AND INFECTIOUS GLAUCOMA

Ocular inflammation or infection is an important cause of increased IOP. The mechanism of the elevated pressure may be obstruction of the trabecular meshwork by accumulated inflammatory debris such as protein or fibrin, macrophages, and T lymphocytes; swelling of trabecular lamellae; loss and/or damage to trabecular endothelial cells; or direct trabecular injury. Other mechanisms include obstruction of episcleral venous outflow or the canal of Schlemm or secondary angle-closure glaucoma (ACG; see Inflammatory and Infectious Conditions Associated With Raised IOP).1


Systemic Inflammatory and Infectious Conditions Associated With Raised IOP

  • Acute retinal necrosis
  • Behçet disease
  • HLA-B27–related acute anterior uveitis
  • Juvenile idiopathic arthritis-associated uveitis
  • Sarcoidosis
  • Vogt-Koyanagi-Harada syndrome
  • Acquired immunodeficiency syndrome
  • Cytomegalovirus retinitis
  • Congenital rubella
  • Disseminated meningococcemia
  • Hansen disease (leprosy)
  • Herpes virus-associated uveitis
  • Lyme disease
  • Onchocerciasis
  • Syphilis
  • Toxocariasis
  • Toxoplasmosis

It is of the utmost importance to address the underlying cause of inflammation or infection. In general, the treatment of inflammatory and infectious glaucoma is three-pronged:

  • Underlying systemic disease, if present, is treated with antiinfectives for infection, antiinflammatory medication (eg, steroids, nonsteroidal antiinflammatory drugs), systemic immunosuppression (eg, methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, cyclophosphamide), and biologic agents (eg, infliximab, etanercept, adalimumab, rituximab).
  • Ocular inflammation is treated with antiinfectives (eg, intravitreal antibiotics), antiinflammatory medication (eg, topical, depot, intravitreal, or systemic steroids, nonsteroidal antiinflammatory drugs), and pupillary dilatation (eg, cycloplegic and sympathomimetic agents).
  • Elevated IOP is treated medically with aqueous suppressants and/or surgically with filtration, glaucoma drainage devices, or cyclodestructive procedures.

When the eye is inflamed, continued reassessment of the mechanism of elevated IOP is imperative to target treatment effectively. Steroids should be used thoughtfully, and patients should be observed for steroidinduced IOP spikes.

GLAUCOMA ASSOCIATED WITH OTHER SYSTEMIC DISEASE

Besides inflammatory and infectious glaucoma, a number of other systemic diseases are associated with primary glaucoma (see Systemic Disorders Associated With Elevated IOP). Again, it is important to assess the underlying cause of the increased IOP and to treat the systemic disease accordingly. The clinician must perform a careful inspection of the anterior segment, gonioscopy, and tonometry. Patients with Marfan syndrome, homocystinuria, or Weill-Marchesani syndrome, for example, may be prone to lens-induced and pupillary-block glaucoma.2 Glaucoma associated with syndromes often present in childhood. These children frequently do not respond as well to medical glaucoma treatment as do adults, so the former patient population may require goniosurgery (eg, goniotomy, trabeculotomy).


Systemic Disorders Associated With Elevated IOP

  • Axenfeld-Rieger syndrome
  • Crouzon syndrome (craniofacial dysostosis)
  • Cushing disease
  • Bing-Neel syndrome
  • Trisomy 21
  • Trisomy 16-18 (Edward syndrome)
  • Trisomy 13-15 (Patau syndrome)
  • Turner syndrome
  • 9p syndrome
  • Cockayne syndrome
  • Cretinism (juvenile hypothyroidism)
  • Cystinosis
  • Dental-ocular-cutaneous syndrome
  • Diabetes
  • Diamond-Blackfan syndrome
  • Ehlers-Danlos syndrome
  • Familial histiocytic dermatoarthritis syndrome
  • Fetal alcohol syndrome
  • Gorlin-Goltz syndrome
  • Hallermann-Streiff syndrome (oculomandibulofacial dyscephaly)
  • Homocystinuria
  • Kartagener syndrome
  • Kimmelstiel-Wilson syndrome
  • Klinefelter syndrome
  • Klippel-Trénaunay-Weber syndrome
  • Krabbe disease
  • Krause syndrome
  • Lowe (oculocerebrorenal) syndrome
  • Marfan syndrome
  • Meyer-Schwickerath-Weyers syndrome
  • Miller (Wilms aniridia) syndrome
  • Mucopolysaccharidosis
  • Neurofibromatosis (von Recklinghausen)
  • Nevus of Ota (oculodermal melanocytosis)
  • PHACES syndrome
  • Pierre Robin syndrome
  • Prader-Willi syndrome
  • Rubinstein-Taybi syndrome
  • Sickling disorders
  • Stickler syndrome
  • Sturge-Weber syndrome
  • Treacher Collins syndrome
  • Ullrich syndrome (dyscraniopygophalangy)
  • Von Hippel-Lindau disease
  • Waardenburg syndrome
  • Wagner syndrome
  • Weber-Christian disease
  • Weil-Marchesani syndrome
  • X-linked mental retardation syndrome
  • Zellweger (cerebrohepatorenal) syndrome

MEDICATION ASSOCIATED WITH GLAUCOMA

Drugs used to treat systemic disease may raise the IOP. This response usually occurs within a few weeks of initiating steroid therapy, but it can present at any time thereafter. Patients treated with corticosteroids may develop elevated IOP and glaucomatous optic nerve damage.3 Although a majority of patients respond to topically applied or intravitreal corticosteroids, some may develop elevated IOP while on intravenous, oral, or inhaled steroids. Stopping the offending agent usually returns the IOP to baseline, but in some instances, continued pressure control is needed.

Medications prescribed for a variety of systemic conditions may also precipitate an episode of acute ACG. The mechanisms behind the acute ACG may vary. Some patients with anatomically narrow angles are predisposed to an acute attack while taking anticholinergic or sympathomimetic drugs, tricyclic antidepressants, monoamine oxidase inhibitors, antihistamines, antiparkinsonian drugs, antipsychotic medications, and antispasmodic agents. Some anesthetics, most notably ketamine and succinylcholine, may also raise IOP.4 Sulfa-containing medications like topiramate may cause angle closure via anterior rotation of the ciliary body and/or choroidal effusion. Topiramate-induced angle closure can present with impressive IOP elevation, shallowing of the anterior chamber, and a myopic shift. This type of angle closure should not be treated with laser iridotomy; rather, it usually responds to aqueous suppressants, cycloplegia, and discontinuation of the offending agent.

CONCLUSION

Glaucomatous optic nerve damage can be viewed as an endpoint of multiple systemic factors. Besides merely treating the IOP, it is important for the clinician to be familiar with the multiple systemic associations with glaucoma, to re-evaluate treatment frequently, and to target the underlying disease process, if present.

Brian H. Chen, MD, is a glaucoma fellow at USF Eye Institute in Tampa, Florida.

Lisa S. Gamell, MD, is the glaucoma fellowship director at USF Eye Institute and an associate professor of ophthalmology at the USF Health Morsani College of Medicine, both located in Tampa, Florida. Dr. Gamell may be reached at (813) 523-6722; lgamell@health.usf.edu.

  1. Siddique SS, Suelves AM, Baheti U, Foster CS. Major review: glaucoma and uveitis. Surv Ophthalmol. 2013;58(1):1-10.
  2. Allingham RR, Samji K, Freedman S, et al, eds. Shields Textbook of Glaucoma. 5th ed. Baltimore, MD: Lippincott Williams and Wilkins; 2005.
  3. Becker B. Intraocular pressure response to topical corticosteroids. Invest Ophthalmol. 1965;4:198-205.
  4. Razeghinejad MR, Pro MJ, Katz LJ. Non-steroidal drug-induced glaucoma. Eye. 2011;25(8):971-980.
 

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