By John W. Boyle IV, MD, Peter A. Netland, MD, PHD, and Sarwat Salim, MD, FACS
Edited by Ingrid U. Scott, MD, MPH, and Sharon Fekrat, MD
This article is from September 2008 and may contain outdated material.
Glaucoma is one of the many potentially devastating complications of uveitis. The pathogenesis of uveitic glaucoma relates to alterations in aqueous production and composition, changes to the anterior chamber angle anatomy and the effects of corticosteroid treatment. The overall prevalence of glaucoma in eyes with uveitis varies from 10 to 20 percent but is much more common in chronic uveitis and can be as high as 46 percent.1
This article will review pathophysiology of uveitic glaucoma along with modalities available to control intractable glaucoma. It will also discuss two common ocular uveitic conditions associated with glaucoma, Fuchs’ heterochromic iridocyclitis and Posner-Schlossman syndrome, and the most common known cause of uveitis in children presenting with glaucoma, juvenile rheumatoid arthritis.
Pathogenesis
Intraocular pressure is regulated by a balance between aqueous humor production and its outflow. During episodes of intraocular inflammation, IOP is typically reduced because of aqueous humor hyposecretion from ciliary body inflammation and increased uveoscleral outflow. Over time, multiple mechanisms can increase the resistance to aqueous outflow during episodes of uveitis, thereby leading to elevated IOP.
Open-angle mechanisms are the most common causes of elevated IOP in uveitis. Typically, there is mechanical obstruction or dysfunction of the trabecular meshwork. It can be blocked by inflammatory cells, proteins, debris or fibrin liberated from a disrupted blood-aqueous barrier, resulting in obstruction of the aqueous outflow facility. Cytokines, released by inflammatory cells, further exacerbate inflammation and may stimulate neovascularization. In chronic cases of uveitis, obstruction of aqueous outflow may result from scarring and obliteration of trabecular meshwork beams or Schlemm’s canal or from overgrowth of a fibrovascular membrane in the angle.
Secondary angle-closure glaucoma can also result from a number of mechanisms in uveitic eyes. Angle closure with pupillary block occurs when inflammation in the anterior chamber causes 360 degrees of posterior synechiae that block the flow of aqueous from the posterior chamber to the anterior chamber, resulting in iris bombé and acute angle-closure glaucoma. Peripheral anterior synechiae formation is another common complication of intraocular inflammation in the anterior chamber. Peripheral anterior synechiae are typically broad-based and can result in total closure of the angle. Less commonly, a nonpupillary block angle-closure glaucoma can occur when inflammation and edema of the ciliary body cause the ciliary body to rotate forward, closing the anterior chamber angle.
Treatment of uveitis with corticosteroids often leads to elevated IOP. Secondary ocular hypertension from corticosteroid administration is dependent on the dose, the chemical structure of the corticosteroid compound, the frequency and route of delivery, the duration of treatment and the patient’s susceptibility to steroid use. Clinically, a corticosteroid response usually occurs within a few weeks after initiating therapy, but may occur at any time. In this situation, it is often difficult to distinguish between the side effects of the corticosteroids and the underlying inflammation. Only a small proportion of the normal population demonstrates corticosteroid responsiveness, but with impaired conventional outflow seen during intraocular inflammation, the corticosteroid response rate rises significantly. Corticosteroids have been reported to cause biochemical and morphological changes in the trabecular meshwork, decreasing aqueous outflow facility.
Medical Therapy
Treatment of uveitic glaucoma consists of controlling the intraocular inflammation and elevated IOP as well as treating any underlying systemic disease.
Inflammation may be controlled with the use of topical, periocular, intravitreal or systemic corticosteroids, and/ or topical and systemic nonsteroidal anti-inflammatory agents. Mydriatic-cycloplegic agents such as atropine 1 percent, homatropine 5 percent or cyclopentolate 1 percent are usually added to prevent or break posterior synechiae and to relieve the discomfort of ciliary muscle spasm.
Immunomodulatory therapy has improved outcomes for many uveitic diseases and is now an important component of long-term treatment of uveitic glaucoma. Traditionally, immunomodulatory medications were considered beneficial in cases where corticosteroids either exacerbate the underlying glaucoma or have been shown to be ineffective. Currently, immunomodulatory medications are used more broadly, providing improved long-term control of uveitis and systemic inflammatory conditions. .
For elevated IOP, topical beta-adrenergic antagonists, alpha2 agonists and carbonic anhydrase inhibitors are first-line agents in uveitic glaucoma. Miotics and prostaglandin analogs are relatively contraindicated in an inflamed eye since these drugs may worsen the inflammation by enhancing the breakdown of the blood-aqueous barrier. Prostaglandins should be avoided in eyes with herpetic keratouveitis because these drugs may exacerbate this condition. However, elevated IOP in stable, well-controlled uveitis may be cautiously treated with prostaglandins. Systemic hyperosmotic agents such as glycerin or mannitol can be employed to rapidly lower IOP in acute settings when there is marked elevation of IOP.
Surgical Therapy
Glaucoma filtration surgery is indicated when IOP is uncontrolled on maximally tolerated medical therapy. Success rates of trabeculectomy have been improved with the use of antimetabolites such as mitomycin C (MMC) or 5-fluorouracil (5-FU). Recently, Noble and colleagues performed trabeculectomy with MMC in 51 eyes with uveitic glaucoma and found success rates of 90 percent at one year and 79 percent at two years.2Ceballos and colleagues used either MMC or 5-FU in 44 eyes and found success rates of 78 percent at one year and 62 percent at two years.3
Glaucoma drainage devices have been used with increasing frequency in the management of uveitic glaucoma, either as the initial glaucoma surgery or when trabeculectomy has failed. Success rates of up to 94 percent at one year have been reported by Da Mata and colleagues.4 Recently, Papadaki and colleagues published long-term results of Ahmed glaucoma valve implantation in uveitic glaucoma, with success rates of 77 percent and 50 percent at one and four years, respectively.5 Ceballos and colleagues, using the Baerveldt glaucoma drainage implant in 24 eyes, had a success rate of 92 percent at one year, with most patients requiring no adjunctive medical therapy.6
Laser Therapy
Pupillary block glaucoma due to a secluded pupil from extensive posterior synechiae or fibrin membrane can be relieved with an argon and/or Nd:YAG laser iridotomy. In some cases, a surgical iridectomy may be required if the laser iridotomy closes secondary to intense inflammation
Argon laser trabeculoplasty is usually not useful in uveitic eyes because of angle alterations and has been shown to have low success rates in these patients.
Transscleral laser cyclophotocoagulation is reserved for cases where all other efforts to lower IOP have failed. This procedure should be used cautiously because patients with uveitis already have atrophic ciliary epithelium, and the risk of permanent hypotony is increased with a cyclodestructive procedure.
Specific Examples of Uveitic Syndromes
Fuchs’ heterochromic iridocyclitis is a rare, chronic form of iridocyclitis characterized by iris heterochromia, low-grade anterior chamber reaction with small stellate keratic precipitates, posterior subcapsular cataract and secondary open-angle glaucoma. This condition is usually unilateral, affecting the hypochromic eye, and affects men and women equally in the third to fourth decade. The glaucoma associated with Fuchs’ resembles that of primary open-angle glaucoma, and the prevalence has been reported to vary from 13 to 59 percent. Gonioscopy reveals an open angle without synechiae, although multiple fine vessels may be observed, arranged either radially or concentrically in the trabecular meshwork. The uveitis does not respond to corticosteroid therapy, and corticosteroids may worsen the IOP elevation. Treatment of the glaucoma is initiated with medical therapy. However, the glaucoma frequently fails to be controlled medically and often requires filtration surgery to control the IOP.
Glaucomatocyclitic crisis or Posner-Schlossman syndrome is an uncommon form of open-angle glaucoma characterized by recurrent attacks of mild anterior uveitis with marked elevations of IOP. This unilateral condition affects young to middle-aged adults, who present with blurred vision and eye pain. The iritis is mild and resolves spontaneously within a few weeks. The IOP is usually markedly elevated (in the 40- to 60-mmHg range) and returns to normal between attacks. However, with repeated attacks, a chronic secondary glaucoma may develop. Gonioscopy may reveal keratic precipitates on the trabecular meshwork, suggesting trabeculitis as the etiology of the elevated IOP. Another theory suggests that increased levels of aqueous prostaglandins may increase aqueous production. Treatment consists of corticosteroids and antiglaucoma medications during episodes.
Juvenile rheumatoid arthritis (JRA) is the most common known cause of childhood uveitis and a frequent cause of uveitic glaucoma. Glaucoma is reported to occur in up to 44 percent of patients with JRA with long-term follow-up.7 Since this disease requires prolonged corticosteroid use to control inflammation, corticosteroid-induced glaucoma occurs frequently. The effect of medical management is often temporary. For surgery, glaucoma drainage implants are preferred since there is a high risk of failure with trabeculectomy. Goniosurgery has also been reported as an alternative and effective surgical option in some of these patients.
Conclusion
Glaucoma is a frequent complication of uveitis arising from the inflammatory disease process itself or from the corticosteroids often used to treat this condition or both. Uveitic glaucoma can present via different mechanisms. Treatment should be first directed at treating the inflammation and the underlying systemic disease. Uncontrolled IOP is often managed with glaucoma medical therapy, and recalcitrant cases require surgical intervention, with improved long-term success rates reported with glaucoma drainage implants as compared with trabeculectomy.
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1 Netland, P. A. and N. C. Denton. Contemp Ophthalmol 2006;5:1–26.
2 Noble, J. et al. Can J Ophthalmol 2007;42:89–94.
3 Ceballos, E. M. et al. J Glaucoma 2002;11:189–196.
4 Da Mata, A. et al. Ophthalmology 1999;106:2168–2172.
5 Papadaki, T. G. et al. Am J Ophthalmol 2007;144:62–69.
6 Ceballos, E. M. et al. Ophthalmology 2002;109:2256–2260.
7 Foster, C. S. et al. Acta Ophthalmol Scand 2000;78:576–579.
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Dr. Boyle is a glaucoma fellow, Dr. Salim is assistant professor of ophthalmology and Dr. Netland is professor of ophthalmology. All are at the University of Tennessee, Memphis.