Posner-Schlossman Syndrome

doi:10.62055/14089873Xe

ABSTRACT

Posner-Schlossman Syndrome, known as glaucomatocyclitic crisis, is a unique presentation of inflammatory glaucoma. It is a rare clinical disorder that often goes undetected in patients or is misdiagnosed as non-granulomatous anterior uveitis or acute angle closure glaucoma. This case report serves to make eye care practitioners aware of how to diagnose and manage Posner-Schlossman Syndrome.

CASE REPORT

A sixty-seven old African American male presented with ocular pain in the left eye for one week. On his exam, a mild reduction of best corrected visual acuity was noted along with a mild anterior chamber reaction in the left eye. His intraocular pressure was significantly elevated, especially compared to his fellow eye. Following ancillary testing including gonioscopy, RNFL OCT, and visual field perimetry, a diagnosis of Posner-Schlossman Syndrome was made. The patient was treated with ocular hypotensive agents and a topical steroid to reduce intraocular pressure and inflammation.

CONCLUSION

Posner-Schlossman Syndrome is a rare clinical finding. As it is a diagnosis of exclusion, appropriate ancillary tests need to be performed. This condition needs to be treated promptly to avoid glaucomatous optic neuropathy.

Keywords: Posner-Schlossman Syndrome, anterior chamber reaction, elevated IOP, unilateral

INTRODUCTION

Posner Schlossman Syndrome (PSS), or glaucomatocyclitic crisis, is defined as a unilateral, recurrent, inflammatory glaucomatous ocular hypertensive disease.^1,2 PSS often goes undiagnosed due to patients having a normal intraocular pressure (IOP) between attacks and a lack of patient symptoms between attacks. The disease itself varies in its pattern; some patients may have frequent attacks with a short duration of symptoms while other patients have less frequent attacks but prolonged symptom-free intervals. When attacks recur, it affects the same eye. No matter how a patient presents, the goal is to control the IOP and minimize inflammation to prevent secondary glaucoma.²

 CASE REPORT

A sixty-seven-year-old African American male presented with ocular pain in the left eye for one week. He described it as mild pain inside the eye itself without any new photophobia, discharge, change in vision, trauma to the eye, or changes to systemic medication. His systemic history was positive for hypertension, vitamin D deficiency, anemia, herpes simplex, and a history of alcohol abuse. His current medications included cholecalciferol 25 mcg daily, acyclovir 200mg twice daily, and lisinopril 10 mg daily. No allergies were reported. His ocular history was positive for nuclear sclerotic cataracts in both eyes and simple myopia of both eyes with presbyopia. He denied any surgical ocular history or family ocular history. His best corrected visual acuity through a refraction of -3.25 sphere right eye was 20/25 and 20/25 left eye through a refraction of -1.25 sphere. His entrance testing was within normal limits; however, his pupils were noted to be minimally reactive in both eyes. Lids and lashes were clear, conjunctiva was white and quiet, and cornea was clear for the right eye. Using the Van Herick method, the temporal angle was assessed as ½:1 and nasal ¾:1 with a deep anterior chamber. Lids and lashes were clear and the conjunctiva of the left eye was noted to have trace diffuse injection with trace-1+ anterior chamber cells using the Standardization of Uveitis Nomenclature (SUN) criteria.³ There was no corneal edema, keratic precipitates, flare, hyphema, or hypopyon present. Using the Van Herick method to assess the angles in his left eye, both temporal and nasal angles were ¼:1 with a deep anterior chamber (Table 1).

 

Intraocular pressures, assessed using Goldmann Applanation Tonometry (GAT), were 16 mmHg and 45 mmHg in the right and left eyes, respectively. Gonioscopy was attempted, however the patient was unable to tolerate the procedure. Anterior segment ocular coherence tomography (OCT) was obtained to help analyze the angles. The right eye showed a wide-open angle without any abnormalities with a deep anterior chamber and flat iris approach and the left eye showed an open angle with a deep anterior chamber and a flat iris approach (Figure 1).

 

There were no angle abnormalities present such as plateau iris configuration or peripheral anterior synechiae. RNFL OCT was obtained and was reliable and within normal limits 360° in both eyes (Figure 2). Zeiss ganglion cell layer analysis was also obtained. This was also reliable and with borderline thinning superiorly and inferior thinning in the right eye and borderline thinning inferiorly in the left eye (Figure 3).

 

 

 

As he had no kidney disease and was not allergic to sulfa drugs, one 250 mg tablet of acetazolamide was administered in the office and one drop of timolol 0.5%-dorzolamide 2% (Cosopt) was instilled in the left eye. The patient was educated on the risks, benefits, and side effects of the medications that were being administered and he consented to their administration. Forty minutes later his IOP was checked, and it was 40 mmHg in the left eye. Another drop of Cosopt was instilled in the left eye. Thirty minutes later, the IOP in the left eye was 34 mmHg.

At this point of the exam, the patient was fatigued and wished to leave the eye clinic. He was prescribed Cosopt for use twice each day in the left eye, prednisolone acetate (Pred Forte) three times each day in the left eye, and one tablet of acetazolamide 250 mg to use within four hours.

He returned one day later and reported resolution of the pain in the left eye. He reported good medication compliance and denied any adverse reactions to the prescribed medications. His visual acuity, entrance testing, and anterior segment assessment findings remained stable to his prior exam with the exception of resolution of anterior chamber cells in the left eye. IOP obtained by GAT was 17 mmHg right eye and 19 mmHg left eye at 1:00 PM. Again, he was unable to tolerate gonioscopy. Both eyes were dilated with 1% tropicamide. Mild nuclear sclerotic cataracts and vitreous syneresis were noted OU. Both optic nerves were noted to have 0.20 cup-to-disc ratios, round without any thinning, pallor, or hemorrhaging. Both maculae were normal, retinal arteries and veins in a 2/3 ratio OU, and periphery within normal limits.

The patient was educated to return in five days for an IOP check and baseline visual field. Upon follow up, he again reported good compliance with his medications and continued absence of his initial symptoms. His visual acuity, entrance testing, and anterior segment assessment remained stable compared to his prior exam. His IOP via GAT was 18 mmHg in both the right and left eye at 1:22 PM. A 24-2 Humphrey visual field test was also obtained and had fair reliability OD and good reliability OS. Neither eye displayed any glaucomatous visual field defects (Figure 4). He was educated to continue Cosopt twice each day in the left eye, to taper Pred Forte to once daily in the left eye, and to follow up in one week.

 

At his return visit, the patient stated he stopped all his drops due to being completely asymptomatic. His visual acuity, entrance testing, and anterior segment assessment remained stable compared to his prior exam. His IOP via GAT was 17mmHg OD and 18 mmHg OS. The patient was educated on his condition and the importance of continuing Cosopt twice each day in the left eye. He was to return in three months for an eye pressure check.

DISCUSSION

PSS is most prevalent in the third and sixth decade of life with few incidents of pediatric cases reported.^4-6 One study in Finland found the prevalence to be 1.9 per 100,000.⁷ There is no racial or sexual predilection. The typical clinical presentation of PSS is unilateral ocular hypertension with mild anterior segment inflammation and few clinical symptoms, i.e. photophobia. Rarely, bilateral presentations have been reported.⁸ Patients typically do not report symptoms due to the recurrence of the inflammatory disease. In cases of extremely elevated IOP, patients may experience ocular pain and a decrease in visual acuity or haloes in their vision due to corneal edema.⁵ The intraocular pressure can range from 40 mmHg to 70 mmHg during an acute attack. Mild anterior chamber cell reaction is noted in conjunction with small keratic precipitates. Conjunctival injection is usually absent unless the IOP is very elevated, and heterochromia can occur if in a lighter-colored iris due to either sectoral or diffuse iris atrophy resulting from prolonged IOP elevation and tissue ischemia. In cases associated with a cytomegalovirus infection, there could be an associated endotheliitis. Endotheliitis appears as a coin-like opacity on the cornea with circumferential keratic precipitates and stromal edema.^9,10  On gonioscopy, the anterior chamber angles should appear open without any posterior synechiae or peripheral anterior synechiae present. The optic disc will appear normal during an acute attack. Prolonged periods of elevated IOP can lead to glaucomatous optic neuropathy and visual field deterioration.¹¹ One study found PSS patients who experience higher IOP between attacks, are positive steroid responders, have glaucomatous optic neuropathy, and visual field loss in both the non-affected eye and PSS eye are more likely to develop primary open angle glaucoma in either eye.²

Differential diagnoses of PSS include acute angle-closure glaucoma, uveitic glaucoma, herpetic keratouveitis, and Fuch’s Heterochromic Iridocyclitis (FHI). Like PSS, acute angle-closure glaucoma presents unilaterally with ocular pain and elevated IOP. Patients with acute angle      closure tend to experience more symptoms such as headaches, nausea, and vomiting. Other key clinical findings include a closed angle and peripheral anterior synechiae detected on gonioscopic evaluation. Uveitic glaucoma will also present with elevated IOP; however, unlike PSS, patients will have a significant anterior chamber reaction which contrasts with a mild reaction in PSS. Herpetic keratouveitis may also present with elevated IOP and mild anterior chamber reaction, but patients will present with a painful red eye and usually have a previous history of an ocular herpetic infection. Other clinical signs may also be present such as lid lesions, follicular conjunctivitis, or dendritic corneal ulcer. FHI may be harder to differentiate from PSS due to the possibility of iris heterochromia in each condition. FHI also presents with an elevated IOP, as high as 52 mmHg, and a mild anterior chamber reaction is noted. FHI has a high association with the development of posterior subcapsular cataracts. The key to differentiate these two is that FHI does not respond to anti-inflammatory agents.¹²

The cause and pathogenesis of PSS remains poorly understood, partially because unlike what is noted in uveitic glaucoma, the mild anterior chamber reaction does not correlate with the magnitude of IOP elevation. The proposed theory is that PSS is a trabeculitis, or inflammation of the trabecular meshwork, leading to decreased aqueous outflow which ultimately leads to elevated IOP. It remains unclear what causes the inflammation, whether it is infectious or strictly inflammatory. In polymerase chain reaction analysis studies, the presence of cytomegalovirus (CMV) and herpes simplex virus were identified.^13,14 Other studies analyzing the content of aqueous humor found during the acute phase an increase in the aqueous levels of prostaglandin, particularly prostaglandin E, which is positively correlated with IOP.⁸ Interestingly, during periods of remission, the same levels were decreased with a concurrent increase in aqueous outflow. This leads to the hypothesis that the outflow inhibition caused by a breakdown of the blood-aqueous barrier contributes to the release of inflammatory cells, clogging the trabecular meshwork.^15,16

PSS is usually self-limiting as the inflammation subsides and IOP normalizes within a few days to a few weeks. Despite its self-limiting nature, due to the risk of permanent damage, treatment is recommended to minimize inflammation, control the IOP, and possibly prevent recurrence.¹⁷ First-line therapy in acute attacks are beta-blockers, carbonic anhydrase inhibitors, and alpha agonists.¹⁸ Prostaglandin analogs are discouraged as they can exacerbate inflammation.       Pilocarpine is also discouraged as it can exacerbate trabeculitis.¹⁹

Intraocular inflammation is best managed with topical corticosteroids such as prednisolone, dexamethasone, or fluorometholone in those with mild inflammation, or topical/oral NSAIDs to avoid a steroid response.²⁰ Both anti-inflammatory and ocular hypotensive medications should be maintained until complete resolution of the attack.

In an acute attack, it is recommended to follow up with patients daily to monitor the IOP. As the IOP level begins to normalize and the patient’s inflammation resolves, the patient may be followed less frequently, such as weekly or monthly. If patients fail to adequately respond to maximum therapy or if there are multiple recurrences, an anterior chamber tap should be performed to detect the presence of CMV. Either PCR analysis of aqueous humor to assess viral DNA or lab viral titers for CMV, herpes simplex, and herpes zoster are recommended to strategize treatment.^21,22 For those CMV-positive PSS patients, a combination of oral ganciclovir and topical ganciclovir in the 0.15% and 2% range has been shown to reduce the viral load, lower IOP, and preserve the corneal endothelium, but it is not always effective at halting recurrences.^23,24 No advantage of intravitreal ganciclovir over oral ganciclovir was found when studied.²⁴ Long-term oral valganciclovir 900 mg twice daily for three weeks followed by 450 mg twice daily for a mean period of 20 months lowered the recurrence rate in patients in CMV-positive PSS patients. However, recurrence was found after treatment was ceased.²⁵ This is attributed to both valganciclovir being virostatic instead of virucidal and the eye’s immune privilege preventing complete eradication of the CMV infection.²⁴

For patients with multiple recurrences or prolonged attacks, surgery to control the IOP while avoiding complications of long-term topical steroids is advised. This is critical as the risk of developing open angle glaucoma is directly correlated with the number and duration of PSS attacks.⁴ Trabeculectomy has been shown to be safe and effective in PSS patients and should be considered as soon as patients start displaying any signs of glaucomatous damage as progression can occur rapidly in these patients.^26,27 Performing a trabeculectomy provides the added benefit of reducing inflammation and IOP spikes in PSS patients, as the filtering bleb formed by this procedure drains the anterior chamber cells through the aqueous, reducing any effect of trabeculitis and inflammatory activity in the anterior chamber.²⁸

Patient education on this condition is essential. Due to the lack of symptoms, it is estimated that as high as 45% of patients present with concomitant glaucomatous optic neuropathy at their initial visit.²⁹ It is recommended to keep patients on ocular hypotensive therapy between attacks as up to 26.5% of patients with PSS may develop glaucomatous optic neuropathy.³ PSS may also cause non-arteritic ischemic optic neuropathy. When the IOP is elevated during attacks, this leads to decreased perfusion of the optic nerve head, compromising blood flow, putting those with “discs at risk” at a higher likelihood of developing an infarction, swelling, and ischemia of the optic nerve head.³⁰

CONCLUSION

Posner-Schlossman Syndrome is a rare, unique condition. Patients are asymptomatic unless they experience a glaucomatocyclitic crisis, requiring prompt attention from their eye care provider to alleviate the pain from ocular inflammation and elevated intraocular pressure. Prompt treatment is critical to prevent ocular sequelae such as visual field loss and/or blindness.

 

REFERENCES:

1. Posner A, Schlossman A. Syndrome of unilateral recurrent attacks of glaucoma with cyclitic symptoms. Arch Ophthal. 1948;39:517-35.
2. Kass MA, Becker B, Kolker AE. Glaucomatocyclitic crisis and primary open-angle glaucoma. Am J Ophthalmol. 1973 Apr;75(4):668-73.
3. Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol.2005;140(3):509–516.
4. Jap A, Sivakumar M, Chee SP. Is Posner Schlossman syndrome benign?      2001;108:913-18.
5. Burnstein Y, Shelton K, Higginbotham EJ. Glaucomatocyclitic crisis in a child. Am J Ophthalmol. 1998;126:136-7.
6. Teekhasaenee C, Ritch R. Glaucomatocyclitic crisis in a child. Am Journal Ophthalmol.      1999;127:626-7.
7. Paivonsalo-Hietanen T, Tuominen J, Vaahtoranta-Lehtonen H, et al. Incidence and prevalence of different uveitis entities in Finland. Acta Ophthalmol Scand.      1997;75(1):76-81.
8. Hess LK, Lee GA, Shah P. Bilateral simultaneous presentation of Posner-Schlossman syndrome. Clin Exp Ophthalmol. 2017 Dec;45(9):925-927.
9. Hwang YS, Shen CR, Chang SH, Lai CC, Liu CL, Chen KJ, Lin KK, Chen TL, Hsiao CH. The validity of clinical feature profiles for cytomegaloviral anterior segment infection. Graefes Arch Clin Exp Ophthalmol. 2011 Jan;249(1):103-10.
10. Koizumi N, Suzuki T, Uno T, Chihara H, Shiraishi A, Hara Y, Inatomi T, Sotozono C, Kawasaki S, Yamasaki K, Mochida C, Ohashi Y, Kinoshita S. Cytomegalovirus as an etiologic factor in corneal endotheliitis. Ophthalmology. 2008 Feb;115(2):292-297.e3.
11. Darchuk V, Sampaolesi J, Mato L, Nicoli C, Sampaolesi R. Optic nerve head behavior in Posner-Schlossman syndrome. Int Ophthalmol. 2001;23(4-6):373-9.
12. Kanski JJ, Bowling B. Clinical ophthalmology: a systematic approach. Elsevier Health Sciences. 2011 Apr 28.
13. Bloch-Michel E, Dussaix E, Cerqueti P, Patarin D. Possible role of cytomegalovirus infection in the etiology of the Posner-Schlossmann syndrome. Int Ophthalmol.      1987;11:95-6.
14. Yamamoto S, Pavan-Lagston D, Tada R, et al. Possible role of herpes simplex virus in the origin of Posner-Schlossman syndrome. Am J Ophthalmol.1995;119:796-8.
15. Eakins KE. Increased intraocular pressure produced by prostaglandins E1 and E2 in the cat eye. Exp Eye Res. 1970;10:87-92.
16. Grant WM. Clinical measurements of aqueous outflow. Am J Ophthalmol.      1951;34:1603-5.
17. Pahlitzsch M, Torun N, Gonnermann J, Maier AK, Pleyer U, Bertelmann E, Joussen A, Klamann MK. Trabeculectomy ab interno (trabectome): yet another possibility in the treatment of uncontrolled glaucomatocyclitic crisis under systemic valganciclovir therapy?. 2015 Oct;29(10):1335-9.
18. Muthusamy P. Apraclonidine in the management of glaucomatocyclitic crisis.      Eye (London, England). 1994;8: 367-368.
19. Tripathy K, Geetha R. Latanoprost. 2023 May 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan.
20. Olson NY, Lindsley CB, Godfrey WA: Nonsteroidal anti-inflammatory drug therapy in chronic childhood iridocyclitis. Am J Dis Child.1988; 142:1289–1292.
21. Cao G, Tan C, Zhang Y, Kong X, Sun X, Ma Y, Chen J, Guan M. Digital droplet polymerase chain reaction analysis of common viruses in the aqueous humour of patients with Posner-Schlossman syndrome in Chinese population. Clin Exp Ophthalmol. 2019 May;47(4):513-520.
22. Rodier-Bonifas C, Cornut PL, Billaud G, Lina B, Burillon C, Denis P.      Cytomegalovirus research using polymerase chain reaction in Posner-Schlossman syndrome. J Fr Ophtalmol. 2011 Jan;34(1):24-9.
23. Su CC, Hu FR, Wang TH, et al. Clinical outcomes in cytomegalovirus-positive Posner-Schlossman syndrome patients treated with topical ganciclovir therapy. Am J Ophthalmol. 2014;158(5):1024-3.
24. Chee SP, Jap A. Cytomegalovirus anterior uveitis: outcome of treatment. Br J Ophthalmol. 2010 Dec;94(12):1648-52.
25. Sobolewska B, Deuter C, Doycheva D, Zierhut M. Long-term oral therapy with valganciclovir in patients with Posner-Schlossman syndrome. Graefes Arch Clin Exp Ophthalmol. 2014;252(1):117-24.
26. Dinakaran S, Kayarkar V. Trabeculectomy in the management of Posner-Schlossman syndrome. Ophthalmic Surg Lasers. 2002;33:321-22..
27. Zhong Y, Cheng Y, Liu X, Feng P. Trabeculectomy in the management of glaucomatocyclitic crisis with visual field defect. Ocul Immunol Inflamm.      2012;18:233-36.
28. Megaw R, Agarwal PK. Posner-Schlossman syndrome. Surv Ophthalmol.2017 May-Jun;62(3):277-285.
29. Wu KY. Glaucomatocyclitic crisis and glaucomatous optic neuropathy. Taiwan J Ophthalmol. 2015 Apr-Jun;5(2):49.
30. Biousse V, Newman NJ. Ischemic optic neuropathies. N Engl J Med. 2015;373(17):1677.