History
In general, the symptomatology of glaucomatocyclitic crisis is vague. Most commonly, a crisis presents with slight discomfort. The patient may be pain-free despite significantly elevated IOP.
In the setting of elevated IOP, the patient may report blurred vision or halo vision if there is resultant corneal edema. Typically, they note a history of past attacks of blurred vision lasting several days, which recur monthly or yearly. Each crisis may last several hours to a few weeks.
Patients follow a variable clinical course; some experience 1 or 2 episodes in their lives, while others have multiple recurrences over many years. Typically, these episodes decrease in frequency with advancing age.
Physical
On examination, the eye appears quiet with no injection. The pupil often is dilated slightly or sluggishly reactive. The anterior chamber is deep and has an open angle on gonioscopy, which should be performed in all cases to differentiate PSS from angle-closure glaucoma.
IOP usually is elevated in the range of 40-60 mm Hg. IOP is related to the duration of uveitis, not to the degree of uveitis. Eyes with active inflammatory disease often have wide swings in IOP that can lead to glaucomatous damage. The elevated IOP in PSS can last for several hours to a few weeks; therefore, it may be missed on initial examination. If the elevated IOP is of significant duration and elevation, corneal epithelial edema develops.
Signs of anterior inflammation are characteristically minimal with faint flare, rare cells, and only a few keratic precipitates (KPs). KPs are typically stellate, flat, nonpigmented, and concentrated over the inferior half of the endothelium. [13] Fine KPs appear after 2-3 days of elevated IOP and resolve rapidly. The inflammation never leads to the development of posterior synechiae or peripheral anterior synechiae. Fresh precipitates may appear with each episode of increased IOP.
Heterochromia, described in the original paper by Posner and Schlossman, is no longer considered a characteristic of this syndrome.
Typical of inflammatory conditions, early segmental iris ischemia and associated late iris-vessel congestion have been observed. These vessels leak on iris fluorescein angiography.
Causes
The etiology of glaucomatocyclitic crisis has been a topic of debate. Several factors have been postulated as contributors to the development of glaucomatocyclitic crisis, to include the following:
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Abnormal vascular process
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Autonomic defect
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Allergic condition
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Variation of developmental glaucoma
Description of a final common pathway usually includes a reference to changes in the trabecular meshwork leading to a reduction of outflow facility. However, some authors describe an increase in aqueous production.
Transfer coefficients of fluorescein in aqueous in the anterior chamber, by flow and by diffusion, are elevated during attacks of glaucomatocyclitic crisis. Between attacks, both coefficients return to normal. [22]
Elevations in IOP are postulated to be secondary to inflammation of the trabecular meshwork, which may be mediated by prostaglandins or cytokines. [23]
Prostaglandins, especially prostaglandin E, have been found in higher concentration in the aqueous humor of patients during acute attacks. These levels return to normal between episodes. [24, 25]
In a study using rabbit eyes, prostaglandin E was shown to contribute to a breakdown of the blood-aqueous barrier. The vascular effects of prostaglandins may contribute to the tortuosity seen in iris vessels and the leakage demonstrated with fluorescein angiography of the iris. To confuse matters, in another animal study, elevated prostaglandins increased outflow facility, which would contribute to a lower IOP and, thus, not be consistent with the reduced outflow facility seen in patients with glaucomatocyclitic crisis during an acute episode. [26] Another theory purports an increased aqueous production resulting from elevated levels of aqueous prostaglandins.
In summary, the exact mechanism by which prostaglandins regulate IOP has not been described, but a direct correlation between elevated levels of prostaglandins in the aqueous humor and the level of IOP has been found during acute attacks of glaucomatocyclitic crisis.
Cytokines have also been found to be elevated in patients with uveitic glaucoma. Interleukin (IL)–6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-a, and vascular endothelial growth factor were found to be elevated in 143 patients with uveitis glaucoma undergoing trabeculectomy. These elevations were found to be significant compared to healthy controls. [27] The significance of these levels remains unknown.
Most recently, CMV has become the accepted infectious precursor to uveitis in PSS. CMV PCR was performed in 73 cases of refractory anterior segment inflammation. CMV DNA was identified in 24 cases, and a higher number of DNA copies was found to be a risk factor for significant IOP elevation. [28]
In the setting of PSS, CMV PCR testing of aqueous biopsy samples has been positive in varying percentages. The percentages vary by location but typically range from 38% to as high as 75% in one study. [6, 29, 30] A causal relationship of CMV, confirmed via PCR testing of aqueous taps, has prompted the evaluation of topical and oral antiviral agents in immunocompetent patients. [31, 32, 33, 34]
Evidence also shows that glaucomatocyclitic crisis may be associated with POAG. Patients with a 10-year or longer history of PSS are 3 times more likely to develop visual field changes and optic disc changes. [35] These patients may have a higher than normal incidence of corticosteroid responsiveness, leading to an elevated IOP. This must be kept in mind during the treatment of this disorder with corticosteroids.
Associations with certain allergic conditions and gastrointestinal diseases, most notably peptic ulcer disease, have been described. [36]
Complications
Complications are related to prolonged IOP elevations secondary to aqueous outflow impairment, resulting in damage to the optic nerve head and visual field compromise. Three mechanisms are identified with these prolonged elevations, as follows: (1) underlying POAG, (2) prolonged steroid administration, and (3) increased frequency of recurrent glaucomatocyclitic attacks.
