Posner-Schlossman syndrome, also known as glaucomatocyclitic crisis, is an ocular condition with self-limited recurrent episodes of markedly elevated intraocular pressure (IOP) and nongranulomatous anterior chamber inflammation. It is most often classified as secondary inflammatory glaucoma.
In 1948, Posner and Schlossman first recognized glaucomatocyclitic crisis and described the features of this syndrome.[1] For this reason, the entity is often termed Posner-Schlossman syndrome (PSS). Their original paper identified key features of the condition, including recurrent episodes of mild cyclitis and uniocular involvement. Attack duration varies from a few hours to several weeks. Glaucomatocyclitic crisis is characterized by a slight decrease in vision, elevated IOP, and open anterior chamber angles, with normal visual fields and optic nerve appearance. In addition, IOP and outflow facility are normal between episodes.[2]
Since this original description, other cases attributed to glaucomatocyclitic crisis have been found to deviate from these criteria.[3]
Additional features that are now recognized are as follows:
Episodic changes in the trabecular meshwork lead to impairment of outflow facility and result in an elevation of IOP. These changes are accompanied by mild intraocular inflammation. In the acute phase of PSS, optic nerve head parameters and retinal flow rates were altered; however, all returned to normal without any permanent damage after resolution of the elevated IOP. Electroretinogram studies in the acute phase demonstrate a selective reduction in the S-cone b-wave.[7]
Glaucomatocyclitic crisis is a rare condition in the United States. It is more common in Asia and northern Europe.
In Finland, the incidence is 0.4 and the prevalence is 1.9 per 100,000 population.[8]
In Japan, among 2556 cases of uveitis, 1.8% had PSS.[9]
Prolonged IOP elevation results in damage to the optic nerve head and visual field defects typical of glaucomatous atrophy.[10, 11]
PSS almost exclusively affects individuals aged 20-50 years. However, there are reports of rare episodes in individuals older than 60 years, as well as in adolescence.[12]
Most studies report men to be at a higher risk of developing PSS.[6]
An uncomplicated course is usual for most patients. In properly diagnosed and treated patients, vision remains uncompromised. However, glaucomatous optic nerve atrophy is irreversible.
Appropriate discussion with patients and their families must include an emphasis on the recurrent nature of this disorder and its association with POAG. Patients should be educated about the medications, their limitations, and their adverse effects.
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.
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.
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:
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 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.
Digital infrared iris photography may yield informative image patterns.[37]
Perform gonioscopy to rule out closed-angle glaucoma.
Consider anterior chamber paracentesis and aqueous sampling to evaluate for CMV infection.
Microscopic examination of trabeculectomy specimens taken at the time of an acute attack reveals inflammation with an abundant mononuclear cell infiltration of the trabecular meshwork.
KPs seen in the setting on CMV endotheliitis are often medium-sized and coin-shaped lesions. On confocal microscopy of these lesions, the classic “owl eye cells” named for large endothelial cells containing nuclei of high reflection surrounded by a halo of low reflection are visible.[38]
Complete medical care for patients presenting with glaucomatocyclitic crisis includes a reasonably thorough history of present illness, a review of drug allergies and sensitivities, a targeted past medical history and review of systems, a complete eye examination, a careful explanation of the disorder in accordance with the patient's level of understanding, and a commitment to long-term follow-up care of the patient.[39]
Medical therapy should be individualized to meet the patient's needs. The favored initial treatment is a combined regimen of a topical NSAID to control the anterior uveitis and an antiglaucoma drug for the elevated IOP.
Treatment recommendations include the following:
The following can be considered:
Miotics and mydriatic agents are seldom used because they may have further deleterious effects on the blood-aqueous barrier and there is low risk for posterior synechiae formation. Long-acting periocular steroids are typically not recommended because of lingering IOP effects.
In the absence of underlying chronic glaucoma, antiglaucoma agents do not prevent recurrences of glaucomatocyclitic crisis; therefore, they are not necessary between episodes.
Topical and oral valganciclovir has recently been added as a treatment option in hopes of eliminating CMV in the anterior chamber, thus removing the infectious drive for uveitis. A 2010 retrospective study compared topical and oral valganciclovir and found that topical therapy had a higher failure rate; however, topical therapy yielded a lower recurrence rate. Multiple studies report that cessation of any form of antiviral therapy results in a high rate of recurrence, as valganciclovir is virostatic and not virucidal.[40] Long-term antiviral treatment is still being studied.
An occasional patient may require a filtering procedure, which is not effective in preventing recurrences of the episodes of iritis but may be useful in the management of high IOP seen with these episodes.[5, 41, 42]
Filtering surgery is generally not as effective in lowering IOP in uveitic glaucoma. During trabeculectomies in this population, higher levels of fibroblasts, lymphocytes, and macrophages are found in the conjunctiva, increasing the scarring of the bleb and decreasing the effectiveness of postoperative 5-FU subconjunctival injections.[43]
Laser trabeculoplasty likely provides no benefit in this population.
An ophthalmologist should be consulted to treat the elevated IOP and to provide long-term follow-up care for patients with POAG.
Patients with elevated IOP should be monitored carefully and frequently until the IOP normalizes and the medications are tapered off appropriately.
Annual visual field assessment is indicated in patients with ongoing optic nerve compromise or pressure irregularities. This assessment also helps in identifying those patients who are at risk of developing POAG.[35]
Long-term follow-up care of patients by an ophthalmologist is important.
A combined regimen of a topical NSAID and antiglaucoma medications is favored. NSAIDs reduce the inflammatory component by inhibiting the production of prostaglandins and antiglaucoma medications reduce the influx of new aqueous; both these effects rapidly control the IOP.
Clinical Context: A topical, ophthalmic NSAID. May facilitate outflow of aqueous humor and decrease vascular permeability. Any equivalent topical NSAID also can be used.
Clinical Context: An oral formulation of NSAIDs. It is rapidly absorbed and metabolism occurs in the liver.
Have analgesic, anti-inflammatory, and antipyretic activities. Inhibit cyclooxygenase activity and prostaglandin synthesis.
Clinical Context: Criterion standard for ophthalmic beta-blockers. May reduce elevated and normal IOP, with or without glaucoma, by reducing production of aqueous humor or by outflow.
Reduce IOP by decreasing aqueous humor production via inhibiting synthesis of cyclic adenosine monophosphate in the ciliary epithelium. Prior to prescribing, consider effects on asthma and COPD.
Clinical Context: Selective alpha-2 receptor that reduces aqueous humor formation and increases uveoscleral outflow.
Reduce IOP by reducing the formation of aqueous humor and increasing uveoscleral outflow.
Clinical Context: Topical formulation of carbonic anhydrase inhibitors.
Clinical Context: Oral formulation of carbonic anhydrase inhibitor. Used for adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma and preoperatively in acute angle-closure glaucoma when delay of surgery desired to lower IOP.
Carbonic anhydrase is an enzyme found in many tissues of the body, including the eye. It catalyzes a reversible reaction where carbon dioxide becomes hydrated and carbonic acid dehydrated. By slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport, it may inhibit carbonic anhydrase in the ciliary processes of the eye. This effect decreases aqueous humor secretion thus reducing IOP.
Clinical Context: Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Prior to use in PSS, consider the risk of steroid related increases in IOP.
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.