Clinical profile, demographic distribution, and management of Posner–Schlossman syndrome: An electronic medical record-driven data analytics from an eye care network in India

Abstract

Purpose:

To describe the clinical profile, demographics, and management of Posner–Schlossman syndrome (PSS) in patients presenting to a multitier ophthalmology hospital network in India.

Methods:

This cross-sectional hospital-based study included 3,082,727 new patients presenting between August 2010 and December 2021. Patients with a clinical diagnosis of PSS in at least one eye were included as cases. The data were collected using an electronic medical record system.

Results:

Overall, 130 eyes of 126 (0.004%) patients were diagnosed with PSS. The majority of the patients were male (81.75%) and had unilateral (96.83%) affliction. The most common age group at presentation was during the fourth decade of life, with 46 (36.5%) patients. The overall prevalence was higher in patients from a higher socioeconomic status (0.005%) presenting from the metropolitan geography (0.008%) and in professionals (0.014%). A significant number of patients (108; 83.08%) had a raised intraocular pressure of >30 mm of Hg. The majority of the eyes had mild or no visual impairment (better than 20/70) in 99 (76.15%) eyes. Keratic precipitates were found in 59 (45.38%) eyes, anterior chamber cells in 43 (33.08%) eyes, and iris atrophy in seven (5.38%) eyes. The majority of eyes (127; 97.69%) had open angles on gonioscopy. The average duration of use of topical steroids was 1.70 ± 0.76 months, and the average duration of use of topical antiglaucoma medications (AGMs) was 1.66 ± 0.81 months, with 35 eyes (26.92%) requiring continued AGMs. Among the surgical interventions, trabeculectomy was performed in nine (6.92%) eyes and cataract surgery in five (3.85%) eyes.

Conclusion:

PSS more commonly affects males presenting during the fourth decade of life from higher socioeconomic status and is predominantly unilateral. The majority of the eyes have mild or no visual impairment, open angles, and require surgical intervention in a tenth of the eyes.

Posner–Schlossman syndrome (PSS) or glaucomatocyclitic crisis was first reported in 1948 by Posner and Schlossman in a series of nine patients.[1] Since then, it has been described as an acute attack of unilateral, non-granulomatous anterior uveitis having recurrences and significantly high intraocular pressure (IOP).[1] From its first-ever description to the present day, more is being understood about this rare entity and its propensity to cause secondary chronic open-angle glaucoma.[2] Secondary glaucoma may range from increased IOP fluctuations to advanced glaucomatous damage of the optic nerve head with advanced visual field loss. This brings to the fore the importance of following up on these patients.

Symptoms are usually minimal and include blurring of vision and haloes with pain described mostly as mild discomfort.[1] On examination, there may be no inflammation or mild inflammation in the anterior chamber with or without accompanying keratic precipitates (KPs) on the corneal endothelium, corneal edema due to the high IOP, and open angles on gonioscopy, with most presenting with no glaucomatous damage (in the initial stages). Iris atrophy may be seen in recurrent cases.[3] The KPs are usually very scanty and are inferior stellar KPs and have been called “sentinel KPs.”[4] Most often, patients give a history of recurrence of these symptoms.

The etiology of this rare pathology is still debatable, varying from infections (autoimmune or allergy-induced)[5] to autonomic dysregulation[1] and vascular abnormalities.[6] Out of all the above, the infection theory is the only one with proven evidence, with the main cause being viruses[7] such as cytomegalovirus (CMV), varicella zoster virus (VZV), and herpes simplex virus (HSV), with few studies implicating Helicobacter pylori.[8] CMV DNA and/or CMV antibodies detected in the aqueous humor during an attack or even after a few weeks of the attack further corroborate the viral infection theory.[7] Furthermore, oral ganciclovir, valganciclovir, or intravitreal ganciclovir have shown satisfactory responses in patients.[9] Some patients even have relapses after discontinuation of therapy.[9] A study among Japanese patients suggests a close association of HLA-Bw54 with PSS, thereby indicating an immune-genetic role being played here.

Many pathomechanisms of the rise in IOP have been put forward, the most common being trabeculitis. Other mechanisms include trabecular obstruction by the debris of inflammation (open-angle mechanism) and the formation of peripheral anterior synechiae (PAS) in the angle-closure mechanism.[10]

The epidemiology of this entity and the role of surgical management have not been described in India to date. The purpose of the study is to present the clinical profile, demographics, and management of PSS at a large multitier ophthalmology network in India by using electronic medical record-driven analytics.

Methods

Study design, period, location, and approval

This cross-sectional observational hospital-based study included all patients presenting between August 2010 and December 2021 to a multitier ophthalmology network located in India.[11] The patient or the parents or guardians of the patient filled out a standard consent form for electronic data privacy at the time of registration. None of the identifiable parameters of the patient were used for analysis of the data. The clinical data of each patient who underwent a comprehensive ophthalmic examination were entered into a browser-based electronic medical records system (eyeSmart EMR) by uniformly trained ophthalmic personnel and supervised by an ophthalmologist using a standardized template.[12] The study adhered to the Declaration of Helsinki and was approved by the institutional ethics committee.

Cases

A total of 3,082,727 new patients presented to the tertiary and secondary centers of the multitier ophthalmology network during the study period. The eyeSmart EMR was screened for patients with a documented ocular diagnosis of PSS in one or both eyes. The diagnosis was made on the basis of the presence of mainly unilateral recurrent mild non-granulomatous iritis with cells in the anterior chamber, with/without fine KPs, elevated IOP, open angles on gonioscopy, without posterior synechiae or posterior uveitis, with the attack lasting few days to weeks. Other causes of uveitis were ruled out by certain investigations: tuberculin skin test, chest X-ray, venereal disease research laboratory test (VDRL), fluorescent treponemal antibody absorption test (FTA-ABS), IgG for toxoplasmosis, and serum angiotensin-converting enzyme (ACE) test. Exclusion criteria were patients with normal IOP (<21 mmHg), patients with any other ocular disease (other than cataract), previous intraocular surgery, and glaucoma secondary to other causes such as steroid-induced glaucoma and post-traumatic glaucoma. A total of 126 patient records were identified using this search strategy and were labeled as cases. A total of 130 eyes diagnosed with PSS in the above patients were further analyzed for clinical information.

Data retrieval and processing

The data of 126 patients included in this study were retrieved from the electronic medical record database and segregated into an Excel sheet. The columns included the data on patient demographics, clinical presentation, ocular diagnosis, and treatment information and were exported for analysis. The Excel sheet with the required data was then used for analysis by using the appropriate statistical software. The variables considered were prevalence, age, gender, urban-rural distribution, socioeconomic status, occupation, laterality, visual acuity, anterior segment findings, gonioscopy, IOP, fundus findings, medical treatment, and surgical treatment. Standardized definitions were used for occupation, region (urban, rural, and metropolitan), and socioeconomic status.[13,14,15,16,17] The visual acuity was classified according to the WHO guidelines.[18]

Statistical analysis

Descriptive statistics using mean ± standard deviation and median with interquartile range (IQR) were used to elucidate the demographic data. All tables for the different variables of demographic data, age, gender, visual acuity, and clinical features were drawn using Microsoft Excel (Microsoft Corporation 2018. Redmond, USA). The Chi-square test (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP) was used for univariate analysis to compare the categorical data. P value < 0.05 was considered significant.

Results

Prevalence

Of the 3,082,727 new patients who presented across the eye care network during the study period, 126 patients were diagnosed with PSS in at least one eye, translating into a prevalence rate of 0.004% (95%CI: ±0.0001%) or 40/million population.

Age

The mean age of the patients was 40.05 ± 12.86 years, whereas the median age was 38 (IQR: 31–49) years. The most common age group of the patients was 31–40 years (n = 46; 36.51%), followed by 21–30 years (n = 27; 21.43%). The distribution of patients in each age-decade is presented in Fig. 1.

Figure 1.

Decade-wise distribution of patients with Posner–Schlossman syndrome

Sex

There were 103 (81.75%) male and 23 (18.25%) female patients. The overall distribution of PSS was significantly greater in males (0.006%; 103/1,659,432) as compared to females (0.002%; 23/1,423,295) and was statistically significant (p = <0.00001). Among the patients diagnosed with PSS, the mean and median age were 39.22 ± 13.08 and 37 (IQR: 30–47) years for men and 43.78 ± 11.07 and 44 (IQR: 35–50) years for women, respectively. The overall mode was 32 years and was similar in men and women.

Urban-rural distribution

Of the 126 patients with PSS, 63 (50%) were from an urban locality, 35 (27.78%) were from a rural locality, and 28 (22.22%) patients presented from the metropolitan region. The overall prevalence of PSS in the metropolitan community (0.008%; 28/358,434) was higher as compared to the urban (0.005%; 63/1,341,267) or rural (0.003%; 35/1,383,026) community and was statistically significant (P < 0.01).

Socioeconomic status

Of the 126 patients with PSS, seven (5.56%) patients were from the lower socioeconomic class, 102 (80.95%) patients were from the lower middle class, 12 (9.52%) patients were from the upper middle class, and five (3.97%) patients from the upper class. The overall prevalence of PSS was significantly higher in the higher socioeconomic strata (0.005%; 119/2,363,156) as compared to lower socioeconomic strata (0.001%; 7/719,571) and was statistically significant (p = <0.00001).

Occupation

Of the 126 patients with PSS, 78 (61.9%) were professionals, 14 (11.11%) were homemakers, 10 (7.94%) were students, nine (7.14%) were agricultural workers, six (4.76%) were manual laborers, four (3.17%) were retired individuals, and the occupational category was not available/applicable in the remaining 5 (3.97%) patients. The overall prevalence of PSS in professionals (0.014%, 78/575,971) was significantly higher (P < 0.00001) in comparison to other professions.

Laterality

Of the 126 patients with PSS, 69 (54.76%) were affected in the right eye and 53 (42.06%) were affected in the left eye. In four (3.17%) patients, the affliction was bilateral in nature.

Presenting visual acuity

Of the 130 eyes, 99 (76.15%) eyes had mild or no visual impairment (visual acuity better than 20/70), eight (6.15%) eyes had moderate visual impairment (<20/70 to 20/200), one (0.77%) eye had severe visual impairment (<20/200 to 20/400), five (3.85%) eyes had blindness (>20/400 to 20/1200), two (1.54%) eyes had blindness (>20/1200 to PL), one (0.77%) eye had blindness (NPL), and the visual acuity was undetermined or unspecified in 14 (10.77%) eyes. The mean logMAR at presentation was 0.32 ± 0.76.

Anterior segment, gonioscopy, and optic disc findings

KPs were found in 59 eyes (45.38%), anterior chamber cells in 43 eyes (33.08%), and iris atrophy in seven eyes (5.38%). Among the 130 eyes, a cup: disc ratio of 0.1–0.4 was documented in 56 (43.08%) eyes, 0.5–0.7 in 23 (17.69%) eyes, and > 0.7 in 19 (14.62%) eyes. The gonioscopy findings showed an open angle in 127 (97.69%) eyes and a closed angle in 3 (2.31%) eyes. Fig. 2 shows the clinical, anterior segment optical coherence tomography (ASOCT) and visual-field changes in a patient who presented with multiple attacks of PSS and developed glaucomatous optic neuropathy.

Figure 2.

Clinical, visual field, and anterior segment optical coherence tomography (ASOCT) images of a 54-year-old male who presented with recurrent attacks of Posner–Schlossman syndrome. (a) Localized inferior corneal edema, (b) Incomplete bi-arcuate scotoma correlating with bipolar optic disc rim thinning, (c) Localized inferior corneal edema with keratic precipitates, (d) Keratic precipitates as seen on ASOCT

Intraocular pressure

Among the 130 eyes, IOP of 1–9 mmHg was documented in two (1.54%) eyes, 10–21 mmHg in 0 (0%) eyes, 22–30 mmHg in 12 (9.23%) eyes, and >30 mmHg in 108 (83.08%) eyes. The mean IOP was 33.69 ± 15.11 mmHg.

Ocular comorbidities

Among the 130 eyes, cataract was seen in 10 (7.69%) eyes and glaucoma in 41 (31.54%) eyes.

Medical treatment

At presentation 108 patients (83.08%) were on oral acetazolamide. 17 eyes (13.08%) were on one topical AGM, 64 (49.23%) were on two topical AGM, 36 (27.69%) were on three topical AGM, and two eyes (1.54%) were on four topical AGM. High-potency steroids were prescribed to 61 eyes (46.92%) and low-potency steroids to 32 eyes (24.62%). Oral antivirals prescribed included acyclovir in 16 patients (12.31%), valaciclovir in six patients (4.62%), and ganciclovir in one patient (0.77%).

Steroids were prescribed in the majority of cases for 1 or 2 months, with 51 eyes (39.23%) for a duration of 1 month and 52 eyes (40%) for a duration of 2 months. The rest were prescribed steroids for either a short duration or a longer duration. Five eyes (3.85%) were prescribed steroids for a short period of 2 weeks and 19 eyes (14.62%) were prescribed steroids for 3 months and one eye (0.77%) for 4 months. Thirty-five eyes (26.92%) were continued on AGMs till the last visit due to glaucomatous disc damage and target IOP not being achieved. The rest, however, required AGMs for a limited period during the attack, with five eyes (3.85%) requiring AGMs for 2 weeks, 36 eyes (27.69%) for 1 month, 29 eyes (22.31%) for 2 months, 13 eyes (10%) for 3 months, and one eye (0.77%) for 4 months.

In terms of documented recurrence, 24 eyes (18.46%) had one recurrent attack, 20 eyes (15.38%) had two recurrent attacks, 12 eyes (9.23%) had three attacks, six eyes (4.62%) had four attacks, one eye (0.77%) had five attacks, four eyes (3.08%) had six attacks, and 62 eyes (47.69%) had no documented recurrent attacks till the time of follow-up.

Surgical treatment

Among the 130 eyes, trabeculectomy was performed in nine (6.92%) eyes and cataract surgery in five (3.85%) eyes. As seen in Supplementary Table 1, there were five male patients and four female patients who required trabeculectomy, with all patients requiring surgery due to uncontrolled IOP despite maximal medical therapy and/or disc and visual field changes. The average age at presentation was 39.67 ± 13.71 years, with the baseline IOP being 42.11 ± 5.39 mmHg and an average number of AGMs of 3.33 (3–4). Before trabeculectomy, three eyes were on low-potency steroids, two were on high-potency steroids, two were on topical NSAIDs, and two were not using any topical steroids. The average follow-up of the patients was 403 ± 672 days, with an average of 5 ± 9 visits. The IOP on the final visit was 15.22 ± 6.01 mmHg, with four eyes requiring adjunctive AGM to control IOP. One eye had one recurrence, whereas the rest did not have any recurrence post-surgery. There were no intraoperative or postoperative complications.

Supplementary Table 1.

Demographic data of the patients with Posner–Schlossman syndrome along with data before and after trabeculectomy

Sex	Age at presentation	Laterality of disease	Highest IOP	Pre-op BCVA	Pre-op CD Ratio	No. of AGMs	Pre-op steroids	Post-op BCVA	Post-op F/U	IOP at last visit	Recurrences	Med added
M	35	OD	38	20/20	0.9 CDR, bipolar thinning	3	loteprednol	20/30p	3 years	10	Nil	Nil
F	29	OD	47	20/30	0.8 CDR sup notch, thin IR	3	loteprednol	20/30	2 years	14	Nil	1
M	69	OD	47	20/25	0.6 CDR, thin IR	3	nil	20/20	5 years	25	1	2
F	41	OD	40	20/30	0.3 CDR, NRR healthy	3	nepafanac	20/25p	5 weeks	6	Nil	Nil
M	39	OD	39	20/20	0.7 CDR, superior excavation	4	loteprednol	20/20	4 years	18	Nil	Nil
M	37	OS	41	20/20	0.9 bipolar notch	4	loteprednol	20/20p	1 month	23	Nil	1
F	35	OS	40	CFCF	0.9 CDR, bipolar notch	3	prednisolone	20/100p	2 years	15	Nil	Nil
M	21	OS	52	20/20	0.9 CDR, bipolar notch	3	ketorolac	20/60p	1 year	12	Nil	1
F	51	OS	35	HM+	Near total cupping	4	Nil

Discussion

This study sought to describe the clinical profile and demographic distribution of PSS in a large cohort of patients presenting to a multitier hospital network in India by using electronic medical records-driven data analytics. The primary purpose of the study was to determine the relative proportion and demographic profile of the PSS in the clinical care setup. The overall prevalence of PSS was 0.004% in patients who presented between 2010 and 2021 (11-year period).

Rates of incidence of the disease vary from region to region. PSS makes up 1.7%[19] to 4.3%[20] among all uveitis cases in Japan. In China, an annual incidence of 3.91 in 100,000 population has been reported.[21] In Finland, the incidence reported is 0.4 with a prevalence of 1.9/100000.[22]

In Europe, the common age group was 20–30 years of age,[22] whereas it was 30–50 years in Asia.[23] The occurrence of PSS in children or those above 60 years of age is rare.[24] The study in China, however, found a significant number of patients (12%) in the age group above 60 years of age. In our dataset, 1.53% of patients were under 20 years of age and 20.61% were above the age of 50 years. Therefore, a diagnosis of PSS cannot be excluded based on age.[21]

Males seem to be more at risk,[25,26] with the common age group being between the second and fifth decade.[22,23] An annual incidence of 4.33/100000 in men and 3.35/100000 in women has been reported in China.[21] Our study also corroborates the finding that PSS seems to be more common in males, particularly in the fourth decade of life.

Management strategies are concentrated on controlling the acute rise of IOP, controlling inflammation/uveitis (trabeculitits), and prevention of recurrence and complications such as long-term chronic glaucoma. Evidence, however, does exist that spontaneous resolution does occur, even without treatment.[27]

Topical steroids cause reduction of the uveitis/trabeculitis, but they are unlikely to reduce the rate of recurrence.[28] Topical steroids range from high-potency steroids such as prednisolone/dexamethasone to low-potency ones such as fluorometholone/loteprednol, with inflammation being controlled in either.[29] High-potency steroids were prescribed in a higher number of patients in our study.

Topical beta-blockers, carbonic anhydrase inhibitors (CAIs), and/or alpha agonists, or a combination of these, are used to curb the rise in IOP, with most cases requiring oral CAIs. Slow tapering or cessation can be done over a period of time with the resolution of the attack. Prostaglandin analogs and pilocarpine are usually avoided as they may aggravate the inflammation.[30]

Oral valganciclovir, although favorable in terms of success rate, has a high recurrence rate, most probably due to its virostatic property,[31] and its use would warrant monitoring of white blood cell count.[9] Acyclovir was most commonly prescribed in our patients. Intravitreal valganciclovir has been tried,[32] but is debatable as most of these cases would present with only anterior uveitis with no features of posterior uveitis.

Glaucoma filtration surgeries augmented with anti-metabolites or glaucoma drainage devices are reserved for recalcitrant high IOP cases or for cases with chronic glaucoma with glaucomatous optic neuropathy.[24,25,26,33,34] Different studies have reported different rates of glaucoma filtration surgeries. Trabeculectomy was performed in 8.46% of eyes in our setting. A study from South Korea showed rates of 6.1% for trabeculectomy and 15.3% for glaucoma drainage device (GDD).[25] The same study found that patients who required surgery were those with a higher IOP, increased frequency of attacks, higher number of topical anti-glaucoma medications, more iris changes, decreased corneal endothelial cell density, thinner RNFL, and worse mean deviation (MD) on visual fields.[25] Sheng et al.[35] described a higher success rate in cases undergoing either ExPRESS shunt and Ahmed glaucoma valve (AGV) as compared to trabeculectomy. None of our cases had undergone a glaucoma drainage device surgery. Our study reports less occurrence of recurrences post trabeculectomy.

The occurrence of glaucoma was as high as 41 eyes (31.54%) in our data. It has been hypothesized that mild inflammation does keep recurring, which goes undetected, leading to optic nerve damage and retinal nerve fiber layer (RNFL) thinning.[36] Therefore, it can be rationalized that continuation of glaucoma medications is important in patients who show glaucomatous optic nerve damage, those with a large cup: disc ratio, or focal thinning of neuroretinal rim,[10,24] with some even advocating to continue medications in those at risk of NAION, as cases of NAION post PSS have been reported.[37]

A few cases of bilateral PSS have been reported,[4,38,39,40] with some being described to have the attack at the same time bilaterally and others one after the other alternately. We noted four patients with this bilateral affliction.

The drawbacks of our study include the fact that it is retrospective in nature, where details of the history about the first attack or recurrent attacks are not very reliable. It also showed the prevalence rate as per the hospital population and may not reflect community prevalence. A better understanding of the pathomechanisms and risk factors of PSS is essential to prevent the onset of glaucoma, a preventable but irreversible case of loss of vision.

Conclusion

This study aimed to describe the epidemiology and clinical presentation of PSS in 3 million new patients presenting to a multitier ophthalmology hospital network in India. The findings show that PSS more commonly affects males presenting during the fourth decade of life from higher socioeconomic status and is predominantly unilateral. A quarter of the affected eyes are associated with glaucoma, and the majority of the eyes have mild or no visual impairment.

Financial support and sponsorship:

Hyderabad Eye Research Foundation.

Conflicts of interest:

There are no conflicts of interest.