Sir,

Posner–Schlossman syndrome (PSS) (glaucomatocyclitic crisis) was characterized in 1948 by recurrent episodes of hypertensive iridocyclitis.1 The aetiology is unknown but current theories favour an infective origin especially herpes simplex virus (HSV).2 We present a case in which CMV DNA was identified following an acute relapse of PSS.

Case report

A 35-year-old immunocompetent Chinese man with a history of recurrent bilateral Posner–Schlossman syndrome (PSS) presented with acutely raised intraocular pressure (IOP) in the right eye. Prior to this, IOP was controlled with topical brimonidine to both eyes. He was diagnosed with a relapse of PSS and treated with topical steroids and latanaprost. After 1 week, the left eye suffered a similar relapse. Simultaneously, the right eye developed stromal oedema in the inferior cornea with anterior uveitis and the appearance of keratitic precipitates in a linear pattern typically seen in herpetic corneal endotheliitis (Figures 1 and 2). Oral acyclovir was commenced. The IOP in the left eye remained recalcitrant despite maximal topical therapy including latanaprost, timolol, and oral acetazolamide 250 mg qid for control, eventually requiring Ahmed tube implant surgery.

Figure 1
figure 1

Marked inferior corneal stromal oedema consistent with clinical herpetic endotheliitis.

Figure 2
figure 2

High magnification showing linear keratitic precipitates demarcating superior border.

The endotheliitis in the right eye waxed and waned with topical medications but failed to resolve completely. After about 5 weeks, an anterior chamber paracentesis was performed. Aqueous humour sent for polymerase chain reaction (PCR) was strongly positive for cytomegalovirus (1.5 × 106 copies/ml) but negative for HSV and varicella zoster virus (VZV). The PCR assay for the CMV DNA quantitation was based on the fluorescent resonance energy transfer (FRET) principle and had two primers and two probes. The sense primer had the sequence of 5′-CACTTCGGGGTCGCAAT and the antisense primer of 5′- CGGGTATCAACAACAGCAAGGA. The hybridization probes were the fluorescein-tagged 5′-GTTAAGGCTGCGTTCCACACCGT-(FL) and the LC Red 640-tagged 5′-LCRed640-CCCGAAAAGTAGCCGATCTG. The assay was performed on the LightCycler™ real-time PCR system (Roche Molecular Diagnostics). A concurrent blood serology for CMV IgM was negative, but IgG was positive. Complement fixation antibody was not significant at 1 : 16. Complete blood count (CBC) showed normal total white and differential counts with no lymphocytosis. The patient was otherwise well and apyrexial with no systemic symptoms throughout the whole period of follow-up.

Discussion

There are numerous postulations for the pathogenesis of Posner–Schlossman including abnormal vascular reactivity, autonomic dysregulation and infection.2, 3, 4, 5 Infective agents that have been most commonly implicated are HSV and CMV via immunologic response or direct infection. Bloch-Michel et al2 postulated the role of CMV from detection of antibodies in aqueous humour, but Yamamoto3 demonstrated only HSV DNA by PCR in patients during acute relapses of PSS. We present a case where acute relapse is associated with CMV detected by quantitative PCR. As far as we are aware, this has not been previously reported. These findings support an infective trigger and suggest that PSS may represent a spectrum of anterior segment manifestations of the herpesviridae family including HSV and CMV.

Evidence of an infective origin is suggested by the presentation of keratouveitis with endotheliitis, features that are reminiscent of classic ‘herpetic disciform-like keratitis’, soon after the acute relapse of PSS. The simultaneous and consecutive occurrence of inflammatory endotheliitis with onset of acute hypertensive uveitis compatible with relapse of PSS suggests a similar aetiological agent.6 We postulate that CMV, possibly a latent reactivation, was a trigger inciting an immunologic response responsible for both presentation of corneal endotheliitis and acute trabeculitis resulting in an intractable glaucoma. It has been shown that in relapse of PSS, HSV may cause trabeculitis resulting in elevation of IOP and corneal endotheliitis, possibly due to viral reactivation via the trigeminal nerve (V1).2, 7 It is likely that a similar mechanism for CMV reactivation accounted for our observations in this case.

Keratitic precipitates (KPs) in PSS are typically described as medium- to large-sized and stellate, a feature which is almost pathognomonic. Walter et al8 also demonstrated similar stellate KPs in CMV uveitis due to fibrin deposition around inflammatory cells. Under specular microscopy in patients with PSS, Pillai et al9 also observed a similar fibrin deposition around an individual KP resulting in a large conglomeration, giving rise to the classical ‘stellate’ appearance. These similarities further support a common aetiology between PSS and CMV or herpetic keratouveitis.

Conclusion

We postulate that PSS is not a distinct entity but may represent a spectrum of inflammatory responses to members of the herpesviridae family including CMV and HSV. An acute relapse may present with classic hypertensive cyclitis with or without other clinical manifestations of anterior segment inflammation indistinguishable from or even pathognomonic for ‘herpetic’ infections including corneal endotheliitis. This observation has implications on future treatment of this condition. Further investigations are necessary to confirm these postulations in large patient series.