GLAUCOMATOCYCLITIC CRISIS

Signs and Symptoms

The initial precipitating event in glaucomatocyclitic crisis (GCC) is the acute onset of a mild, self-limiting uveitis followed by a disproportionately large intraocular pressure (IOP) elevation. Glaucomatocyclitic crisis typically occurs between ages 20 and 50.1-3 It is considered uncommon after age 60 and before age 20, though there have been instances of children with the condition.4

Glaucomatocyclitic crisis is typically recurrent and unilateral, with a duration of attack from a few hours to several weeks, though, most resolve within days.5-7 When it recurs, it afflicts the same eye. Bilateral, simultaneous involvement is highly uncommon.8, 9

Patient complaints include mildly blurred vision, as well as ocular and periorbital discomfort; however, they may possibly report no symptoms at all.5-7, 10 There may be a slightly injected eye with a mild anterior chamber inflammatory reaction and centrally located keratic precipitates.1,2 Flare, though common in uveitis, is not common in GCC. Synechiae typically do not form. Classic uveitic symptoms of pain, photophobia and lacrimation are absent in GCC. There is a markedly elevated IOP, ranging between 30mm Hg and 40mm Hg, although there have been cases where IOP has exceeded 70mm Hg.1,2,6,7,10 The elevated IOP serves to disrupt the sodium-potassium pump on the corneal endothelium, with resultant corneal edema and associated symptoms of blurred vision and halos.

As far back as 1947, GCC was identified and classically described by Drs. Posner and Schlossman.1 Their description was so thorough and accurate, standing the test of time, that the condition has been also synonymously known as Posner-Schlossman syndrome. Their historic, insightful description characterized the condition as follows:

(1) Elevated intraocular pressure appears nearly simultaneously with inflammatory cells in the anterior chamber, followed by one to 20 unpigmented keratic precipitates on the corneal endothelium. Posterior synechiae are never formed.

(2) The eye is white or there may be minimal dilation of the conjunctival vessels without ciliary flush.

(3) The anterior chamber angles are open gonioscopically.

(4) The condition is unilateral. (Today, bilateral cases—while rare—are recognized as possible.)

(5) The presenting symptoms include slight discomfort, colored halos, visual blurring and an absence of frank pain. The patient may also be completely asymptomatic.

(6) The attacks last from hours to one month, but typically spontaneously resolve within two weeks.

(7) The episodes may recur with varying frequency and are unpredictable and unprovoked.

Pathophysiology

Glaucomatocyclitic crisis has long been considered an idiopathic inflammatory disease preferentially affecting the trabecular meshwork. Both herpes zoster and cytomegalovirus (CMV) have been associated with glaucomatocyclitic crisis.11-13 Additionally, aqueous samples aspirated from patients in glaucomatocyclitic crisis have been positive for genomic fragments of herpes simplex virus (though no live virus has been sampled), whereas no such genetic material is found in normal patients.14 Currently, there is ample evidence of viral involvement in GCC, particularly for CMV.15-17 However, CMV is not invariably present in the aqueous humor of all eyes with GCC; thus, the understanding of the pathophysiology of this syndrome remains incomplete.

The trabecular meshwork is innervated by the trigeminal nerve (V1), which serves as a conduit for virus to reach the eye. It has been postulated that viral-induced inflammation of the trabecular meshwork (acute trabeculitis) impedes the tissue’s aqueous processing ability. This is supported by GCC’s status as a nongranulomatous uveitic syndrome with no pronounced inflammatory cellular response causing mechanical obstruction of the trabecular meshwork, nor synechiae development leading to angle closure. The inflammatory cells visible in GCC are mononuclear phagocytes.6

During GCC episodes, there is a measurable increase in prostaglandin levels in the aqueous, particularly prostaglandin E, which correlates particularly well with IOP elevation. During periods of remission, there is a marked decrease in the level of aqueous prostaglandins as well as an increased outflow facility.18 A likely hypothesis is that prostaglandin E incites the trabecular meshwork inflammation.14 Further, prostaglandins serve to increase the permeability of the ciliary blood vessels, leading to fluid diffusion from the ciliary body and increased aqueous production.19

Fluorescein flow studies demonstrate that during the acute phase of GCC, there is increased flow of aqueous into the anterior chamber compared to the normal fellow eye. There is also decreased aqueous production when an eye is not in crisis. This indicates that the rise in IOP is due not only to reduced aqueous drainage but also increased aqueous humor production.18

Studies using confocal scanning laser tomography to measure optic disc topography during and after GCC episodes postulate a theory of plasticity. Patients demonstrated significant decreases in glaucomatous disc topography following IOP reduction. There were also significant increases in disc rim area and volume following cessation of the attack. These studies noted that there can be an increase in cupping during attack and that a reversal of cupping and optic disc topography improvement can be achieved with IOP reduction.20,21

Management

As GCC is an inflammatory condition, the most effective treatment for both the inflammation and the secondary IOP elevation is a topical steroid.1,5-8 In that the inflammation is mild, doses of a steroid such as prednisolone acetate 1% greater than hourly are not necessary. As synechiae are unlikely to occur and patients are only minimally uncomfortable, cycloplegia is also usually unnecessary. However, the use of a mild cycloplegic agent is not contraindicated and may be employed on a case-by-case basis.

Successful reduction of intraocular pressure in glaucomatocyclitic crisis has been documented with carbonic anhydrase inhibitors, topical beta-blockers and alpha-2 adrenergic agonists.22-24 However, all medications employed to reduce intraocular pressure should only be used adjunctively with anti-inflammatory therapy. Obviously, since GCC is an inflammatory condition, miotics and prostaglandin analogs should be avoided as they can exacerbate inflammation. Additionally, laser trabeculoplasty should be avoided due to the potential to further inflame the trabecular meshwork. In extremely recalcitrant cases, trabeculectomy remains a viable option in IOP management.25,26

There are some controversies and peculiarities involving GCC. While it has been considered that GCC is a benign and self-limiting disease, that clearly is not always the case.2,27 While permanent glaucomatous damage is not typical, it can occur, especially in patients with frequent recurrences and prolonged attacks, and there appears to be a positive association with primary open-angle glaucoma development.1,2,5,28 There have also been instances of non-arteritic anterior ischemic optic neuropathy (NAAION) developing during GCC episodes.29,30 It has been postulated that the markedly elevated IOP in patients with small, crowded discs further compromises blood flow. Optic atrophy has also been reported following recurrent GCC episodes, presumably from a similar pathophysiology.31

As it has been shown that a significant number of eyes with GCC likely have a viral etiology such as herpes or CMV, anti-viral therapy remains a consideration. Recently, it has been shown that valganciclovir (Valcyte, Genentech), an oral anti-CMV agent, is effective both at managing the acute form of the syndrome as well as suppressing recurrent outbreaks. It is noted that these results were in eyes that demonstrated CMV in the aqueous humor with no other virus present or had failed previous acyclovir therapy.32,33 The dosage was 900mg BID for two weeks, followed by 450mg BID as long-term suppression therapy. Cessation of therapy usually resulted in recurrence.

Because it has never been proven that all cases of GCC are due to CMV or any virus, blanket recommendation of using oral antiviral medications to manage or suppress GCC has no evidenced-based support.

Clinical Pearls

In most cases, GCC is a benign, self-limiting disease. Occasionally, however, it is not.

The initial presentation of GCC is easily missed. Often, a patient will present with a unilaterally elevated IOP with no apparent or obvious cause. A mild anterior chamber reaction can initially be missed in a cursory evaluation.

Always address management preferentially towards inflammation control and secondarily towards IOP reduction. In that the pressure elevation is secondary to inflammatory processes, steroids will have the added benefit of reducing IOP in this condition.

Many cases of GCC with modest pressure elevations can be successfully managed with steroids alone.

Patients with moderate to heavy anterior chamber reactions, ocular pain and redness who are otherwise moderately symptomatic probably do not have GCC, but rather uveitic glaucoma that may require more aggressive management and systemic testing.

GCC is not only idiopathic but idiosyncratic as well. That is, the patient may have extremely elevated IOP but will be minimally symptomatic and unlikely to manifest immediate permanent glaucomatous damage. We have seen GCC patients present with IOP in excess of 70mm Hg yet be only mildly bothered by slightly blurred vision. A patient with a similar IOP rise from acute angle-closure glaucoma will be significantly ill and risk profound vision loss, which may perhaps be permanent.

There is strong support for a viral etiology in many eyes with GCC, but there are no controlled clinical studies examining the use of oral acyclovir as a suppressant therapy. Even so, acyclovir may be a safe option to try in patients with vision loss from multiple or prolonged recurrences.

1. Posner A, Schlossman A. Syndrome of unilateral recurrent attacks of glaucoma with cyclitic symptoms. Arch Ophthalmol 1948; 39:517-35.

2. Jap A, Sivakumar M, Chee SP. Is Posner Schlossman syndrome benign? Ophthalmology. 2001;108(5):913-8.

3. Ritcher R, Shields MB, Krupin T. The Glaucomas. St Louis; Mosby 1989:1205-20.

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11. Bloch-Michel E, Dussaix E, Cerqueti P, et al. Possible role of cytomegalovirus infection in the etiology of the Posner-Schlossman syndrome. Int Ophthalmol 1987; 11(2):95-6.

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14. Yamamoto S, Pavan-Langston D, Tada R, et al. Possible role of herpes simplex virus in the origin of Posner-Schlossman syndrome. Am J Ophthalmol 1995; 119(6):796-98.

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16. Yang SY, Chen MJ, Chen KH,et al. Cytomegalovirus and herpes simplex virus as causes of bilateral anterior uveitis in an immunocompetent patient. J Chin Med Assoc. 2011;74(1):48-50.

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18. Grant WM. Clinical measurements of aqueous outflow. Arch Ophthalmol 1951; 46:113-24.

19. Eakins K. Increased intraocular pressure produced by prostaglandins E1 and E2 in the cat eye. Exp Eye Res 1970; 10:87-92.

20. Park KH, Hong C. Reversal of optic disc topography in patients with glaucomatcyclitic crisis after remission of attack. J Glaucoma 1998;7(4):225-9.

21. Darchuk V, Sampaolesi J, Mato L, et al. Optic nerve head behavior in Posner-Schlossman syndrome. Int Ophthalmol. 2001;23(4-6):373-9.

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23. Ohno S, Ichiisi A, Matsuda H. Hypertensive effects of Carteolol on intraocular pressure elevation and secondary glaucoma associated with endogenous uveitis. Ophthalmologica 1989;199:41-5.

24. Muthusamy P. Apraclonidine in the management of glaucomatocyclitic crisis. Eye 1994; 8(3):367-8.

25. Dinakaran S, Kayarkar V. Trabeculectomy in the management of Posner-Schlossman syndrome. Ophthalmic Surg Lasers. 2002; 33(4):321-2.

26. Zhong Y, Cheng Y, Liu X, Feng P. Trabeculectomy in the management of glaucomatocyclitic crisis with visual field defect. Ocul Immunol Inflamm. 2010;18(3):233-6.

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28. Kass MA, Becker, B, Kolker AE. Glaucomatocycltic crisis and primary open angle glaucoma. Am J Ophthalmol 1973;75:668-73.

29. Irak I, Katz BJ, Zabriskie NA, et al. Posner-Schlossman syndrome and nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2003;23(4):264-7.

30. Kim R, Van Stavern G, Juzych M. Nonarteritic anterior ischemic optic neuropathy associated with acute glaucoma secondary to Posner-Schlossman syndrome. Arch Ophthalmol. 2003;121(1):127-8.

31. Kim TH, Kim JL, Kee C. Optic disc atrophy in patient with Posner-Schlossman syndrome. Korean J Ophthalmol. 2012;26(6):473-7.

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33. Wong VW, Chan CK, Leung DY, Lai TY. Long-term results of oral valganciclovir for treatment of anterior segment inflammation secondary to cytomegalovirus infection. Clin Ophthalmol. 2012;6:595-600.