Posner-Schlossman syndrome usually occurs in adults aged 20–50 years, but cases in 13-year-olds have also been reported. The only epidemiological study from Finland reported an incidence of 0.4 per 100,000 and a prevalence of 1.9 per 100,000.
About one-quarter of patients with Posner-Schlossman syndrome develop glaucomatous optic neuropathy, and progressive corneal endothelial cell loss is also documented as an important structural complication. Although once considered a “benign disease,” it is now recognized as not necessarily benign.
Posner-Schlossman syndrome is an iritis of unknown cause accompanied by acute intraocular pressure elevation that is unilateral and recurrent. The cause is unknown, but cytomegalovirus, herpes simplex virus, and other infections have been reported as etiologic factors.
QHow often do attacks of Posner-Schlossman syndrome occur?
A
The course is variable; some patients experience only one or two episodes in their lifetime, while others have many recurrences. Typically, attacks recur at intervals of several months to 1–2 years. In general, the frequency of attacks tends to decrease with age.
Elevated intraocular pressure: Usually 40–60 mmHg, sometimes above 60 mmHg. Characteristically, the pressure is disproportionately high relative to the degree of inflammation.
Keratic precipitates (KP): Small to medium-sized, well-defined, round, white KP. Usually few in number, predominantly in the inferior cornea. No pigmentation.
Mild anterior chamber inflammation: Mild iritis without significant cells or flare.
Corneal epithelial edema: Characteristically mild relative to the degree of intraocular pressure elevation.
Other Characteristic Findings
Open angle: The angle is open on gonioscopy (an important diagnostic criterion).
No posterior synechiae: They do not form despite the presence of anterior chamber inflammation.
Hypopigmentation: During remission, intraocular pressure is often lower than in the healthy eye, and the trabecular meshwork of the affected eye often shows less pigmentation compared to the healthy eye.
Pupillary dilation: The pupil is slightly dilated or the light reflex is sluggish. The conjunctiva is usually white, but mild ciliary injection may be observed.
Generally, the visual field is normal, but if attacks recur over a long period, visual field changes may occur. The risk of optic neuropathy increases with repeated attacks.
QWhy is the intraocular pressure elevation in Posner-Schlossman syndrome disproportionately high relative to the degree of anterior chamber inflammation?
A
Trabeculitis is considered the main mechanism. Inflammatory cell infiltration in the trabecular meshwork impedes aqueous humor outflow, leading to intraocular pressure elevation disproportionate to the degree of anterior chamber inflammation. Prostaglandins (especially PGE2) have also been reported to show a positive correlation with intraocular pressure.
The exact pathophysiology of Posner-Schlossman syndrome remains unknown, and several theories have been proposed.
Association with cytomegalovirus (currently the most prominent): Large studies in a Singapore cohort strongly support an association between cytomegalovirus and Posner-Schlossman syndrome. Cytomegalovirus has been detected in the aqueous humor of patients, leading to the idea that it may be the same disease as cytomegalovirus iritis, or partially overlapping.
Association with HSV/VZV: Although proposed in the past, acyclovir is not effective in treating or preventing Posner-Schlossman syndrome, and this is no longer considered a major theory.
Association with HLA-Bw54: 41% of Posner-Schlossman syndrome patients in a Japanese cohort carried the HLA-Bw54 haplotype (vs. 8% in controls). A commonality with Vogt-Koyanagi-Harada disease has also been suggested.
Association with Helicobacter pylori (H. pylori): An association between Posner-Schlossman syndrome and peptic ulcer has been noted, and a prospective study confirmed an association between anti-H. pylori serum IgG and Posner-Schlossman syndrome.
Autonomic dysfunction theory: Based on focal iris ischemia observed on iris angiography during attacks and prodromal phases.
Vascular endothelial dysfunction theory: There is a report that patients with Posner-Schlossman syndrome showed significant peripheral vascular endothelial dysfunction compared to age-matched controls.
In addition, if it can be confirmed that intraocular pressure normalizes and uveitis findings disappear during the interictal period, the diagnosis becomes certain.
PCR analysis for cytomegalovirus, HSV, and VZV is a definitive method to distinguish viral Posner-Schlossman syndrome from idiopathic Posner-Schlossman syndrome. If CMV is positive, the treatment strategy changes significantly (add ganciclovir eye drops or oral valganciclovir).
Note that some patients may require multiple aqueous humor samples to confirm CMV.
Prostaglandin analogs: effective for intraocular pressure control
Oral carbonic anhydrase inhibitors: may be used in acute phase when rapid intraocular pressure reduction is needed
If intraocular pressure is extremely high during an attack (40 mmHg or more), oral carbonic anhydrase inhibitors are also prescribed.
Anti-inflammatory treatment:
Since inflammation is mild, topical steroid eye drops such as 1% prednisolone acetate are used four times a day. Miotics (pilocarpine) should be avoided as they may worsen trabeculitis. Mydriatics are rarely used.
Additional treatment for cytomegalovirus-positive cases:
If cytomegalovirus DNA is detected in the aqueous humor by PCR, ganciclovir eye drops or oral valganciclovir should be included in the treatment.
During remission, no treatment is usually required. Follow up daily until intraocular pressure returns to baseline, then weekly while tapering anti-glaucoma eye drops and topical steroids.
Surgery is considered when intraocular pressure cannot be controlled with maximum medical therapy, or when there are signs of glaucomatous optic nerve damage or visual field changes. In a report of 8 patients with Posner-Schlossman syndrome who underwent trabeculectomy with mitomycin C (MMC), all patients were free of intraocular pressure-lowering medications at the end of follow-up.
The main mechanism of intraocular pressure elevation in Posner-Schlossman syndrome is thought to be trabeculitis. Intraoperative specimens of the trabecular meshwork have shown the presence of mononuclear cells, and electron microscopy has revealed mononuclear cells with long pseudopodia interposed between trabecular beams, potentially obstructing aqueous humor outflow. The origin of these mononuclear cells remains unknown.
The involvement of prostaglandin (PGE2) is also important. High levels of PGE2 have been detected in aqueous humor during attacks, and these levels correlate positively with intraocular pressure. Prostaglandin inhibitors (indomethacin) have also been shown to lower intraocular pressure. PGE2 is thought to worsen the disruption of the blood-aqueous barrier, allowing inflammatory cells to enter the anterior chamber and clog the trabecular meshwork.
When cytomegalovirus is involved, it is thought to infect corneal endothelial cells and other anterior segment tissues, causing chronic inflammation and trabecular meshwork dysfunction.
Effects on the optic nerve: During acute attacks, optic disc shape analysis may show transient cupping enlargement and decreased blood flow. Blood flow measurements may show reduced optic nerve perfusion in the peripapillary temporal and nasal sectors and at the optic disc margin. Cumulative mechanical and ischemic damage from repeated attacks leads to long-term glaucomatous optic nerve damage.
7. Latest research and future perspectives (research-stage reports)
When vascular endothelial dysfunction is confirmed in Posner-Schlossman syndrome, it has been suggested that addressing endothelial dysfunction with cardiovascular therapies such as aspirin may be explored as a future treatment. Further research is ongoing in this area.
Long-term Antiviral Therapy for Cytomegalovirus Anterior Uveitis
Evaluation of the efficacy and safety of long-term oral valganciclovir for Posner-Schlossman syndrome with confirmed cytomegalovirus is ongoing. Accumulation of evidence regarding the optimal duration and dosage for recurrence prevention is needed.
HLA-Bw54 and Genetic Background of Disease Susceptibility
Since HLA-Bw54 is frequently observed in Asian populations including Japanese, research is being conducted to elucidate the genetic predisposition for developing Posner-Schlossman syndrome. Identification of causative genes through linkage disequilibrium may lead to future therapeutic targets.
