San Francisco -- Understanding the cause of elevated IOP in patients with uveitis is the basis for developing a rational treatment plan, said Emmett Cunningham Jr., MD, PhD, MPH, at Glaucoma Symposium 2012.
Dr. Cunningham explained that there are four mechanisms underlying uveitic ocular hypertension/glaucoma: 1) inflammatory ocular hypertension syndrome (IOHS); 2) acute uveitic angle closure; 3) corticosteroid-induced; and 4) a mixed mechanism involving structural changes from chronic inflammation. Clinical clues, including recognition of the unique temporal relationship between the inflammation and IOP for each condition, helps guide the diagnosis.
In IOHS, IOP becomes elevated at the onset of inflammation and decreases as the inflammation resolves.
"Infection often underlies IOHS, and it's not clear whether the elevated IOP in these cases is the direct result of inflammation of the trabecular meshwork or infection-induced elevation of some intrinsic hypertensive factor(s), such as rho-kinases," noted Dr. Cunningham, director, uveitis service, California Pacific Medical Center, and adjunct clinical professor of ophthalmology, Stanford University School of Medicine.
Herpetic infection caused by herpes simplex virus (HSV), varicella zoster virus (VZV), or cytomegalovirus (CMV), is the prototypical cause of IOHS, and so it is important to look for signs of herpetic disease in patients who present with acute anterior uveitis. Clues include characteristic corneal findings and skin changes along with sector iris atrophy. Clinicians should also be aware of emerging reports, predominantly from Asia, of CMV infection as a cause of anterior uveitis in immunocompetent patients. Other causes of IOHS to consider include toxoplasmosis, sarcoidosis, syphilis, and Posner-Schlossman syndrome.
Treatment for IOHS includes corticosteroids to reduce the inflammation, a topical cycloplegic/mydriatic for patient comfort and to minimize the risk of posterior synechiae formation, and, when indicated, pathogen-specific antimicrobial therapy.
In acute uveitic angle closure, the IOP also rises temporally with the onset of inflammation. However, in this condition, IOP does not decrease when the anterior inflammation is successfully treated because the underlying cause of the angle closure, pupillary seclusion and iris bombe resulting from extensive posterior synechiae or uveal effusion, persists and must be addressed.
Pupillary seclusion with iris bombe is treated initially with laser iridotomy, although because inflammation increases the risk of iridotomy closure, surgical iridectomy may become needed. Oral corticosteroids are indicated to treat inflammatory uveal effusion.
The presentation of corticosteroid-induced IOP elevation in the uveitic patient differs from the preceding mechanisms because there is a delay between initiation of the medication and the increase in IOP. Corticosteroid-induced IOP elevation usually presents 2 to 4 weeks after treatment initiation, but the delay can be months or even years. It is almost never just a day or two, said Dr. Cunningham, adding that the likelihood that a corticosteroid will induce an IOP elevation is related to its potency for controlling inflammation.
While the natural tendency to manage corticosteroid-induced IOP elevation would be to back off on the corticosteroid, the primary dictum is to control the inflammation first and manage the IOP second.
"Be careful not to undertreat the uveitis because persistent active inflammation can result in other ocular complications, including loss of vision. Therefore, I don't begin tapering topical corticosteroids until the anterior chamber cell count is 1 + (5 to 15 cells) or less. If I need to control the inflammation and the corticosteroid is really causing a problem, then I will consider using an immunosuppressive medication instead," he said.
Dr. Cunningham noted that so-called "soft steroids," including loteprednol etabonate (Lotemax/Alrex, Bausch + Lomb), rimexolone (Vexol, Alcon), and low-concentration formulations of prednisolone acetate, should not be used as a strategy for mitigating corticosteroid-induced IOP elevation until the inflammation is controlled.
In the mixed mechanism cause, IOP is elevated as a result of chronic inflammation-induced permanent damage to the outflow system and/ or formation of peripheral anterior synechiae, causing angle closure. Included within this category are patients with Fuchs' heterochromic iridocyclitis (Fuchs' uveitis syndrome). Treatment for the IOP is based on the medical and surgical approaches generally used to manage glaucoma.
Ocular hypotensive decisions
For treating elevated IOP in patients with uveitis, Dr. Cunningbam says he typically starts with a beta-blocker based on their longstanding history of efficacy and safety, including a lack of pro-inflammatory activity. A topical carbonic anhydrase inhibitor is used as a second-line agent, but if a more potent IOP-lowering effect is needed, an oral carbonic anhydrase inhibitor is considered.
Alpha agonists are little used because in theory they may promote inflammation and cause redness. So, as a third line, Dr. Cunningham said he prescribes a prostaglandin analogue, which has the benefit of once-daily instillation.
"There is talk that the prostaglandin analogues are pro-inflammatory, but that has not been a problem in my experience, and in talking to glaucoma specialists who see patients with the most severe uveitic glaucoma, they too say it is generally not an issue," he commented.
As a caveat, however, Dr. Cunningham noted there have been a few case reports of reactivation of herpetic disease with initiation of latanoprost, and so for that reason, he does not use prostaglandin analogues in patients with herpetic anterior uveitic or herpetic keratitis.
Although rarely used for IOP-lowering anymore, Dr. Cunningham said he also does not use epinephrine, dipivefrin, or pilocarpine because they are pro-inflammatory.
Ocular hypertension/glaucoma in patients with uveitis is associated with four principal mechanisms. Appropriate management depends on determining the etiology of the IOP elevation.
Emmett Cunningham Jr., MD, PhD, MPH
* Zelefsky JR, Cunningham E. Jr., et al. Evaluation and management of elevated IOP in patients with uveitis. Ophthalmology, June 2010; Focal Points, Volume XXVIII, Number 6, Module 3 of 3.
Reviewed by Emmett Cunningham Jr., MD, PhD, MPH
Dr. Cunningham has no financial interest in any products he discussed,