Introduction: Although there is abundant evidence that Posner-Schlossman syndrome (PSS) can lead to secondary glaucoma, data on the clinical differences between PSS patients with secondary glaucoma and those with intermittent intraocular pressure (IOP) elevation are sparse. Methods: This retrospective observational study included 52 patients (52 eyes) diagnosed with PSS and admitted to Zhongnan Hospital of Wuhan University between January 2019 and February 2022. Demographic characteristics and clinical features were gathered from admission records. Patients were divided into two groups: 27 cases with intermittent IOP elevation (group A) and 25 cases with secondary glaucoma (group B and C). Of the secondary glaucoma cases, 18 were further divided into the topical IOP-lowering medications group (group B) and 7 into the glaucoma surgery group (group C). Clinical characteristics of different groups were compared. Results: Compared to the intermittent IOP elevation group, PSS patients with secondary glaucoma had a longer course of disease, a higher incidence of iris depigmentation, lower best corrected visual acuity, lower endothelial cell density, and higher interferon-γ (IFN-γ) concentration and cytomegalovirus (CMV) deoxyribonucleic acid (DNA) copy number in the aqueous humor (all p < 0.05). Group C presented a higher CMV DNA copy number in the aqueous humor than groups A and B (p < 0.05). Compound trabeculectomy proved effective in group C, with a functional filter bleb and well-controlled IOP without disease progression after 1 year of follow-up. Conclusion: Distinctive characteristics existed between PSS patients with secondary glaucoma and those with intermittent IOP elevation. Compound trabeculectomy appears to be an effective treatment option when IOP cannot be controlled through topical medications.

Posner-Schlossman syndrome (PSS) is a disease of non-granulomatous anterior uveitis with recurrent episodes, often accompanied by elevated intraocular pressure (IOP) [1]. Historically, PSS was regarded as a self-limiting disease with a favorable prognosis, leading to the neglect of long-term follow-up and management, particularly regarding IOP. However, as research into PSS has advanced and long-term patient follow-ups have been conducted, it has been discovered that secondary glaucoma may develop in some cases [2, 3].

Patients with PSS exhibit diverse features of IOP [4, 5]. For some, elevated IOP may only persist during PSS episodes and then return to normal [1]. Approximately 26.4% of PSS patients develop glaucoma, which may present a protracted disease course with recurrent episodes and progressive damage to the optic nerve and visual field [5]. Some patients maintain well-controlled IOP with topical IOP-lowering medications during intermittent periods. In contrast, others may require IOP control through topical medications but fail to achieve it [2]. The specific mechanism underlying the IOP difference in PSS patients is still unclear.

In this study, we observed the clinical characteristics and aqueous humor detection results of PSS patients with different IOP features. We analyzed the efficacy of compound trabeculectomy to explore IOP management options for PSS patients.

Patients

This is a long-term, single-center, retrospective study. This study was authorized by the Institutional Review Board of Zhongnan Hospital of Wuhan University, Hubei, China and the Ethics Committee of Zhongnan Hospital of Wuhan University, Hubei, China (No. 2020098 K). Informed consent was not required due to the retrospective nature of the study. All procedures were in accordance with the tenets of the Declaration of Helsinki.

A total of 52 patients (52 eyes) were recruited at the Ophthalmology Department of Zhongnan Hospital of Wuhan University in China between January 2019 and February 2022. Medical records of PSS patients were screened and collected from the hospital database. Twenty-seven patients with PSS who experienced intermittent IOP elevation without glaucoma damage (27 eyes) were included in group A, and 18 PSS patients who developed secondary glaucoma but were effectively managed with topical IOP-lowering medications (18 eyes) were included in group B. Another 7 patients with PSS who developed secondary glaucoma and subsequently underwent glaucoma surgery (7 eyes) were included in group C.

The diagnostic criteria for PSS were as follows [1]: (1) recurrent intermittent, acute, mild non-granulomatous anterior uveitis; (2) IOP higher than 21 mm Hg; (3) keratic precipitates on corneal endothelial surface; (4) cell and flare in the anterior chamber; (5) open anterior chamber angle; and (6) no iris posterior synechiae or posterior inflammation. Secondary glaucoma development in PSS patients was defined by the following criteria: (1) persistent elevation of IOP in the affected eye (>21 mm Hg), with a bilateral IOP difference of >8 mm Hg; and (2) glaucomatous cupping and retinal nerve fiber layer (RNFL) loss accompanied by progressive visual field defects [6‒8].

Inclusion criteria are as follows: (1) participants aged between 18 and 85 years; (2) a diagnosis of unilateral PSS according to the study’s diagnostic criteria. Patients with PSS were divided into intermittent IOP elevation group (group A) and secondary glaucoma group. The secondary glaucoma group was further subdivided into the topical IOP-lowering medications group (group B) and the glaucoma surgery group (group C). The classification criteria are as follows: (1) group A (intermittent IOP elevation): IOP effectively managed with IOP-lowering medications during PSS episodes, maintaining normal IOP during intermittent periods, and not developing secondary glaucoma. (2) Group B (topical IOP-lowering medications): patients with secondary glaucoma exhibited well-controlled IOP using topical IOP-lowering medications during intermittent periods. (3) Group C (glaucoma surgery): secondary glaucoma has occurred; IOP remained uncontrolled despite four different types of topical IOP-lowering medications, patients underwent a compound trabeculectomy procedure.

Exclusion criteria are as follows: (1) a history of primary glaucoma or secondary glaucoma due to causes other than PSS (e.g., trauma or glucocorticoid use); (2) ocular inflammation unrelated to PSS; (3) vitreoretinal disorders; (4) systemic immune system diseases; and (7) incomplete medical records.

Clinical Data

Patients’ demographic and clinical characteristics were recorded. All patients underwent a complete ophthalmic examination, including age, sex, eye, course of disease, baseline best corrected visual acuity (logMAR scale), IOP in the attack phase, haze-like corneal edema, morphology of keratic precipitate, endothelial cell count (ECD), anterior segment optical coherence tomography, anterior chamber cell grade, pupil size, iris depigmentation, visual field mean deviation (MD) and pattern standard deviation and average RNFL thickness. All initial ocular findings were collected from PSS patients’ medical records upon admission and prior to treatment. Evaluation of anterior chamber inflammation was graded according to the criteria of the Standardization of Uveitis Nomenclature Working Group grading scheme (SUN Working Group 2005) [9].

Aqueous Humor Detection

After obtaining informed consent and before treatment initiation, all patients underwent anterior chamber puncture to collect aqueous humor samples. The samples were stored at 4°C and tested within 2 h. Viral deoxyribonucleic acid (DNA), including herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and varicella-zoster virus (VZV), was detected using multiplex real-time polymerase chain reaction. Nucleic acid extraction was performed using the Nucleic Acid Extraction and Purification Kit (magnetic bead method) (DAAN Gene Co., China) according to the manufacturer’s instructions. The genomic DNA of EBV and CMV in the aqueous humor was quantified using the EBV and CMV nucleic acid quantitative kit (DAAN Gene Co., China). The genomic DNA of HSV and VZV in the aqueous humor was quantified using the HSV and VZV nucleic acid quantitative kit (designed by the Department of Laboratory of Zhongnan Hospital of Wuhan University, China). Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, and IL-10 were measured using cytometric bead array. The Human Th1/Th2 subsets detection kit (Hangzhou Cellgene Biotech Co. Hangzhou, China) was utilized. All the steps were performed in strict accordance with the kit instructions. For aqueous humor polymerase chain reaction and cytokine analysis, about 50 μL of aqueous humor was required for each test.

Glaucoma Treatment

The treatment of secondary glaucoma in PSS patients is progressive. Topical IOP-lowering medications include carbonic anhydrase inhibitors, β-blockers, α-agonists, and prostaglandins. Uncontrolled IOP is defined as IOP ≥21 mm Hg, or IOP reduction from baseline of ≤20%, or the progression of visual field and optic nerve damage despite the maximum IOP-lowering medications. PSS patients with uncontrolled IOP underwent compound trabeculectomy (with mitomycin C [0.4 mg/mL]) performed by the same physician (M.K.). All patients provided informed consent before the procedure.

Statistical Analysis

Statistical analysis was performed using SPSS software (IBM SPSS Statistics 26.0, SPSS Inc., Chicago, IL, USA). Continuous variables were assessed for normality using the Shapiro-Wilk normality test. The mean ± standard deviation was used to describe continuous variables if they obeyed the normal distribution, and the median and interquartile spacing (IQR) were used to describe variables if not. Categorical variables were expressed as the patient number (n) and percentage. For continuous variables, the Mann-Whitney U-test was used for comparison between two groups, while the Kruskal-Wallis test was used for three-way comparisons among three groups. Categorical variables were compared using the χ2 test. The results were statistically considered significant when p value was <0.05.

This study involved 52 eyes of 52 PSS patients, aged 19–81 years, with an average age of 46.06 years. The majority were male patients (n = 36, 69.2%), while female patients accounted for 30.8% (n = 16).

Clinical characteristics and aqueous humor test results of the patients are presented in Tables 1 and 2. All eyes in this study had open anterior chamber angles. Compared to group A, groups B and C had a longer course of disease, higher incidence of iris depigmentation, lower ECD, more severe visual field defects, and thinner mean RNFL thickness (all p < 0.05). There were no differences between group B and group C for these indicators. Group B had a higher incidence of corneal edema (p = 0.005) and concentration of IFN-γ in the aqueous humor (p = 0.022) than group A. The CMV DNA copies in the aqueous humor were higher in group C compared with both group A and group B (all p < 0.05).

Table 1.

Comparison of clinical characteristics of PSS patients in three groups

VariablesGroup AGroup BGroup Cp value
Patients, n 27 18 
Gender, male, n (%) 18 (66.7) 14 (77.8) 4 (57.1) 0.498b 
Age, years, median (IQR) 50 (30–59) 50.5 (31.5–61.5) 40 (31–50) 0.851a 
Course of disease, m, median (IQR) 2 (0–12) 48 (22.5–102) 60 (48–120) 0.000a 
IOP, mm Hg, mean±SD 28 (17–40) 39 (28–55.25) 33 (24–37) 0.110a 
BCVA, median (IQR) 0.10 (0–0.30) 0.19 (0.08–0.55) 0.52 (0.30–1) 0.009a 
Haze-like corneal edema, n (%) 8 (29.6) 13 (72.2) 4 (57.1) 0.018b 
Anterior chamber angle 
 Open 27 18  
 Closure  
The morphology of KP, n (%)    0.250b 
 Mutton-fat 18 (66.7) 9 (50) 7 (100)  
 Dust-like 7 (25.9) 7 (38.9)  
 Brown 2 (7.4) 2 (11.1)  
Grade of anterior chamber cell, n (%)    0.130b 
 0–0.5+ 27 (100) 16 (88.9) 6 (85.7)  
 1+ 2 (11.1) 1 (14.3)  
Dilated pupil, n (%) 3 (11.1) 4 (22.2) 2 (28.6) 0.401b 
Iris depigmentation, n (%) 6 (22.2) 14 (77.8) 7 (100) 0.000b 
RNFLT, μm, mean±SD 96.52±15.43 81.33±20.97 96.52±15.43 0.004a 
MD, dB, mean±SD −2.63±1.88 −6.54±5.44 −16.51±8.67 0.000a 
PSD, dB, mean±SD 1.91±1.27 3.95±2.73 8.19±2.98 0.000a 
ECD, cell/mm2, median (IQR) 2,457.33±311.91 1,929.28±554.72 1,718.57±524.94 0.000a 
VariablesGroup AGroup BGroup Cp value
Patients, n 27 18 
Gender, male, n (%) 18 (66.7) 14 (77.8) 4 (57.1) 0.498b 
Age, years, median (IQR) 50 (30–59) 50.5 (31.5–61.5) 40 (31–50) 0.851a 
Course of disease, m, median (IQR) 2 (0–12) 48 (22.5–102) 60 (48–120) 0.000a 
IOP, mm Hg, mean±SD 28 (17–40) 39 (28–55.25) 33 (24–37) 0.110a 
BCVA, median (IQR) 0.10 (0–0.30) 0.19 (0.08–0.55) 0.52 (0.30–1) 0.009a 
Haze-like corneal edema, n (%) 8 (29.6) 13 (72.2) 4 (57.1) 0.018b 
Anterior chamber angle 
 Open 27 18  
 Closure  
The morphology of KP, n (%)    0.250b 
 Mutton-fat 18 (66.7) 9 (50) 7 (100)  
 Dust-like 7 (25.9) 7 (38.9)  
 Brown 2 (7.4) 2 (11.1)  
Grade of anterior chamber cell, n (%)    0.130b 
 0–0.5+ 27 (100) 16 (88.9) 6 (85.7)  
 1+ 2 (11.1) 1 (14.3)  
Dilated pupil, n (%) 3 (11.1) 4 (22.2) 2 (28.6) 0.401b 
Iris depigmentation, n (%) 6 (22.2) 14 (77.8) 7 (100) 0.000b 
RNFLT, μm, mean±SD 96.52±15.43 81.33±20.97 96.52±15.43 0.004a 
MD, dB, mean±SD −2.63±1.88 −6.54±5.44 −16.51±8.67 0.000a 
PSD, dB, mean±SD 1.91±1.27 3.95±2.73 8.19±2.98 0.000a 
ECD, cell/mm2, median (IQR) 2,457.33±311.91 1,929.28±554.72 1,718.57±524.94 0.000a 

BCVA, best corrected visual acuity; KP, keratic precipitate; SD, standard deviation; PSD, pattern standard deviation; MD, mean deviation.

aKruskal-Wallis tests.

bχ2 test.

Table 2.

Aqueous humor cytokines and virus copies in three groups

VariablesGroup AGroup BGroup Cp value
TNF-α, pg/mL, median (IQR) 0.82 (0–3.33) 0.53 (0.1–3.68) 2.42 (0.64–3.33) 0.524a 
IFN-γ, pg/mL, median (IQR) 0.49 (0–1.05) 1.60 (0.17–4.01) 1.77 (0.93–2.64) 0.008a 
IL-2, pg/mL, median (IQR) 3.25 (1.24–3.99) 2.36 (1.15–3.55) 3.8 (0.75–4.33) 0.621a 
IL-4, pg/mL, median (IQR) 2.44 (1.33–3.51) 0.83 (0.38–3.09) 1.52 (0.75–2.80) 0.158a 
IL-6, pg/mL, median (IQR) 14 (4.54–38.88) 49.03 (4.01–972.60) 26.38 (9.36–229.36) 0.289a 
IL-10, pg/mL, median (IQR) 2.56 (1.28–4.56) 4.78 (1.44–23.10) 5.74 (3.88–17.84) 0.154a 
EBV DNA copies, median (IQR) 0.389a 
HSV DNA copies, median (IQR) 0.629a 
CMV DNA copies, median (IQR) 405 (0–885) 0.000a 
VariablesGroup AGroup BGroup Cp value
TNF-α, pg/mL, median (IQR) 0.82 (0–3.33) 0.53 (0.1–3.68) 2.42 (0.64–3.33) 0.524a 
IFN-γ, pg/mL, median (IQR) 0.49 (0–1.05) 1.60 (0.17–4.01) 1.77 (0.93–2.64) 0.008a 
IL-2, pg/mL, median (IQR) 3.25 (1.24–3.99) 2.36 (1.15–3.55) 3.8 (0.75–4.33) 0.621a 
IL-4, pg/mL, median (IQR) 2.44 (1.33–3.51) 0.83 (0.38–3.09) 1.52 (0.75–2.80) 0.158a 
IL-6, pg/mL, median (IQR) 14 (4.54–38.88) 49.03 (4.01–972.60) 26.38 (9.36–229.36) 0.289a 
IL-10, pg/mL, median (IQR) 2.56 (1.28–4.56) 4.78 (1.44–23.10) 5.74 (3.88–17.84) 0.154a 
EBV DNA copies, median (IQR) 0.389a 
HSV DNA copies, median (IQR) 0.629a 
CMV DNA copies, median (IQR) 405 (0–885) 0.000a 

aKruskal-Wallis tests.

bχ2 test.

Clinical characteristics of group C patients are shown in Table 3. Four patients tested positive for CMV in the aqueous humor. One patient tested negative for CMV in the aqueous humor, but owl’s eye cells with highly reflective inclusion bodies were observed in the endothelial layer under confocal microscopy, shown in Figure 1a.

Table 3.

Clinical characteristics of patients with PSS who underwent glaucoma surgery

BCVAIris depigmen-tationCMV DNA copiesDiagnosis timeSurgery timeSurgical procedureMD, dBPSD, dBRNFLT, μmRNFLT 1 year after surgery, μmMD 1 year after surgery, dBPSD 1 year after surgery, dB
Patient 1 0.4 Yes 2,018 2,020.6 −22.21 2.00 67 67 −23.31 2.21 
Patient 2a 0.3 Yes 566 2,014 2,019.9 −18.94 9.98 55 53 −19.67 9.90 
Patient 3 0.2 Yes 885 2,014 2,020.6 −31.33 6.39 69 67 −32.21 7.21 
Patient 4 0.5 Yes 4,260 2,010 2,020.7 −15.52 9.17 41 40 −16.44 9.71 
Patient 5 0.5 Yes 2,005 2,020.6 −7.21 8.90 86 85 −7.47 8.56 
Patient 6 0.1 Yes 2,016 2,020.5 −20.83 10.0 78 76 −21.54 10.4 
Patient 7 0.01 Yes 405 2,015 2,020.3 −16.16 10.7 75 52 −18.76 10.8 
BCVAIris depigmen-tationCMV DNA copiesDiagnosis timeSurgery timeSurgical procedureMD, dBPSD, dBRNFLT, μmRNFLT 1 year after surgery, μmMD 1 year after surgery, dBPSD 1 year after surgery, dB
Patient 1 0.4 Yes 2,018 2,020.6 −22.21 2.00 67 67 −23.31 2.21 
Patient 2a 0.3 Yes 566 2,014 2,019.9 −18.94 9.98 55 53 −19.67 9.90 
Patient 3 0.2 Yes 885 2,014 2,020.6 −31.33 6.39 69 67 −32.21 7.21 
Patient 4 0.5 Yes 4,260 2,010 2,020.7 −15.52 9.17 41 40 −16.44 9.71 
Patient 5 0.5 Yes 2,005 2,020.6 −7.21 8.90 86 85 −7.47 8.56 
Patient 6 0.1 Yes 2,016 2,020.5 −20.83 10.0 78 76 −21.54 10.4 
Patient 7 0.01 Yes 405 2,015 2,020.3 −16.16 10.7 75 52 −18.76 10.8 

A: compound trabeculectomy. B: compound trabeculotomy combined with cataract phacoemulsification and intraocular lens implantation.

BCVA, best corrected visual acuity; PSD, pattern standard deviation; MD, mean deviation.

aPatient 2 had 2 recurrences of anterior chamber inflammation (1 month postoperatively and 6 months postoperatively), and both had an anterior chamber cell grade of 0.5+ but normal IOP (13 mm Hg and 16 mm Hg, respectively).

Fig. 1.

Results of follow-up examination in patient 3. a The owl’s eye cells (black arrow), which have highly reflective inclusion bodies, and multiple intranuclear inclusions arranged in a wheel-like pattern (white arrow) were observed in the endothelial layer. b, c Slit lamp examination and anterior segment optical coherence tomography were performed 1 year after surgery, and the filtering bleb had a good filtration function. a Heidelberg Retina Tomograph (HRT III/RCM), Heidelberg Engineering GmbH, Heidelberg, Germany. b Topcon slit lamp and camera, Topcon Corp., Tokyo, Japan. c CASIA, SS-1000, Tomey, Nagoya, Japan).

Fig. 1.

Results of follow-up examination in patient 3. a The owl’s eye cells (black arrow), which have highly reflective inclusion bodies, and multiple intranuclear inclusions arranged in a wheel-like pattern (white arrow) were observed in the endothelial layer. b, c Slit lamp examination and anterior segment optical coherence tomography were performed 1 year after surgery, and the filtering bleb had a good filtration function. a Heidelberg Retina Tomograph (HRT III/RCM), Heidelberg Engineering GmbH, Heidelberg, Germany. b Topcon slit lamp and camera, Topcon Corp., Tokyo, Japan. c CASIA, SS-1000, Tomey, Nagoya, Japan).

Close modal

In group C, the mean IOP was 16.14 ± 1.95 mm Hg at 1 day postoperatively, 16.00 ± 2.38 mm Hg at 1 week postoperatively, 16.00 ± 3.00 mm Hg at 1 month postoperatively, and 14.71 ± 2.43 mm Hg at 1 year postoperatively, with the mean IOP trend shown in Figure 2. Slit lamp examination and anterior segment optical coherence tomography revealed functional filter blebs for all patients 1 year after surgery, as shown in Figure 1b, c. The mean preoperative RNFL was 67.29 ± 15.11 μm, and the 1-year postoperative RNFL was 62.86 ± 15.46 μm. There were no significant differences using a paired t test (p = 0.204). One patient experienced two recurrences of anterior chamber inflammation (1 month and 6 months post-surgery), both with an anterior chamber cell grade of 0.5+ but normal IOP (13 mm Hg and 16 mm Hg, respectively). The remaining 6 patients had normal IOP and no anterior chamber inflammation within 1 year after surgery.

Fig. 2.

Preoperative and postoperative IOP changes in seven PSS patients who underwent compound trabeculectomy.

Fig. 2.

Preoperative and postoperative IOP changes in seven PSS patients who underwent compound trabeculectomy.

Close modal

Our findings indicated that PSS patients with glaucomatous damage exhibit different clinical characteristics compared to those with intermittent IOP elevation. Patients with glaucomatous damage have a longer course of disease, higher probability of iris depigmentation, elevated IFN-γ concentrations and CMV DNA copy numbers in the aqueous humor, and reduced ECD. Compound trabeculectomy seems to be an effective treatment for patients with uncontrolled IOP.

A longer course of disease is associated with glaucomatous damage in PSS patients. These individuals may experience a higher number of acute IOP elevation attacks, leading to hemodynamic instability or hypoperfusion of the optic disc. Garala et al. [10] conducted a retrospective analysis of secondary optic neuropathy caused by acute IOP elevation in PSS patients, hypothesizing that acute high IOP ischemia-reperfusion injury results in optic nerve damage.

Lower corneal ECD was observed in PSS patients with glaucomatous damage. Elevated IOP has been associated with healthy corneal endothelium and accelerated CEC loss in glaucoma [11‒14]. Moreover, benzalkonium chloride, a preservative commonly used in IOP-lowering medications, can be cytotoxic to CEC, exhibiting toxic side effects are both time- and dose-dependent [12, 15]. Hosogai et al. [16] demonstrated that human CMV can replicate in primary cultured human corneal endothelial cells, potentially inducing apoptosis of human CECs [17, 18].

PSS patients with glaucomatous damage are more likely to have iris depigmentation. In our study, all PSS patients who underwent glaucoma surgery developed iris depigmentation. Kam et al. [2] identified iris depigmentation as a clinical biomarker for predicting chronic or recurrent anterior uveitis CMV infection in a prospective cohort study [6]. Our findings are consistent with theirs, revealing that PSS patients with glaucomatous damage not only had iris depigmentation but also increased CMV DNA copy numbers in aqueous humor compared to controls. This suggests that iris depigmentation in PSS patients may result from a combination of elevated IOP and CMV infection. Consequently, it is essential to enhance IOP management in PSS patients presenting with iris depigmentation.

Increased IFN-γ concentrations and CMV DNA copy numbers were found in the aqueous humor of PSS patients with glaucomatous damage. Moreover, CMV DNA copy numbers were higher in PSS patients requiring glaucoma surgery than in other PSS patients. Changes in aqueous humor cytokine concentrations may impact the function of trabecular meshwork [19]. Burgos-Blasco et al. [20] also discovered elevated cytokine levels in the aqueous humor of a primary open-angle glaucoma population, including increased IFN-γ. IFN-γ is produced by helper T cells, cytotoxic T cells, and natural killer cells and has antiviral, immunomodulatory, and antitumor properties. Csösz speculated that IFN-γ might inhibit collagen synthesis and cause delayed epidermal wound healing [21]. CMV infection has also been shown to cause changes in cytokine levels in the aqueous humor, leading to upregulation of monocyte chemotactic protein-1, autocrine factor, and transforming growth factor-β1 expression, all of which are positively correlated with elevated IOP and may trigger fibrotic changes in human trabecular meshwork cells and elevated resistance in the Schlemm’s canal [22, 23]. CMV has been shown to replicate in human trabecular meshwork cells [24]. We speculate that CMV might infect trabecular meshwork cells, resulting in trabecular meshwork cell fibrosis and obstruction of the aqueous humor outflow system, but further experiments are needed to confirm this hypothesis.

In this study, despite treating PSS patients with aggressive topical IOP-lowering medications and progressively combining various topical IOP-lowering medications like carbonic anhydrase inhibitors, β-blockers, α-agonists, and prostaglandins, some patients still experienced high IOP. Glaucoma surgery serves as a last-resort intervention for patients with uncontrolled IOP. The current study indicated that PSS patients have a higher risk of fibrosis due to the presence of proinflammatory cytokines after trabeculectomy [25, 26]. However, in our study, the PSS patients with uncontrolled IOP who received compound trabeculectomy during the attack phase achieved well-controlled postoperative IOP and functional filter blebs. We hypothesized that certain cytokines in the aqueous humor of PSS patients might protect the conjunctival filtering bleb from fibrosis, but further studies are needed to verify this speculation. The results of this study and others suggest that compound trabeculectomy appears to be an effective surgical procedure for controlling IOP [27, 28].

The present study has some limitations. The sample size of this study was small, which may limit the generalizability of the findings. We did not perform gonioscopy in PSS patients, which could have provided additional insights into the disease progression and treatment response. Besides, a longer follow-up period for PSS patients who underwent glaucoma surgery would have been beneficial to better understand the long-term effects and outcomes of the intervention.

In summary, PSS patients with secondary glaucoma exhibit different clinical characteristics compared to those with intermittent IOP elevation. The differences include a longer course of disease, higher probability of iris depigmentation, higher IFN-γ concentrations and CMV DNA copy number in the aqueous humor, and lower ECD. Compound trabeculectomy appears to be an effective treatment option for patients with uncontrolled IOP. Clinicians should be aware of these specific characteristics and their potential implications for a poor prognosis in PSS patients with secondary glaucoma. Close monitoring of IOP and visual function in PSS patients is crucial to ensuring timely and appropriate treatment to preserve vision and improve patient outcomes.

This study meets the guidelines for human studies. The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The study was approved by the Human Research Ethics Committee of Zhongnan Hospital of Wuhan University (No. 2020098 K) and carried out in accordance with the Declaration of Helsinki. Informed consent was waived for this retrospective observational study. This was a retrospective study that did not require clinical trials registration.

The authors have no conflicts of interest to declare.

There is no relevant funding.

M.K. serves as the corresponding author. Q.W. and W.Z. are co-first authors of the article and made substantial contributions to the conception and design of the work as well as the acquisition, analysis, and interpretation of data. Y.L. and W.J.Z. made critical revisions and polished the article.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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