Introduction

Glaucoma, a condition marked by optic nerve damage and progressive visual field defects, is a leading cause of vision loss1. Uveitis, an inflammation of the uvea, is exacerbated by several secondary ocular diseases. Uveitic glaucoma is one of the complications that can cause irreversible visual impairment in patients with uveitis2. Multiple pathologies can contribute to elevated IOP in uveitis patients. These include increased resistance to aqueous humor outflow due to inflammation or corticosteroid treatment, trabecular meshwork obstruction due to cell, fibrin, and debris precipitation, and angle closure caused by iris synechiae or anterior ciliary body rotation3,4. The most established treatment for glaucoma is to prevent the progression of visual field impairment by lowering IOP5,6. The first line of treatment is lowering IOP with ophthalmic drops1. If eye drops are ineffective in lowering IOP, oral acetazolamide or surgical intervention such as trabeculotomy or trabeculectomy may be considered7.

SLT is a laser therapy that reduces intraocular pressure by increasing aqueous humor outflow via selective wavelength laser targeting of the trabecular meshwork8. SLT has been used as a glaucoma treatment for several decades, and a recently published randomized controlled trial of SLT as a first line treatment for primary open-angle glaucoma (POAG) found promising results9,10. In addition to POAG, SLT is particularly thought to be an appropriate treatment for glaucoma with pigment deposits and pseudoexfoliation in the trabecular meshwork11,12. A recent multicenter cohort study demonstrated the efficacy and safety of first-line or second-line SLT for normal-tension glaucoma (NTG)13. Therefore, while the efficacy of SLT for uveitic glaucoma appears promising, it is generally considered a contraindicated treatment due to the risk of inducing inflammation and worsening uveitis through laser treatment of trabecular meshwork in uveitic glaucoma. Consequently, there have been very few reports of SLT treatment for uveitic glaucoma.

In this study, we carefully assessed the efficacy and safety of SLT in patients with uveitic glaucoma whose intraocular pressure was inadequately controlled with ophthalmic and oral treatments, paying close attention to the potential risk of exacerbation or recurrence of uveitis.

Results

Clinical characteristics of the patients

The characteristics of the patients included in this study are shown in Table 1. We analyzed 17 eyes from 13 patients. There were six male and seven female patients with a mean age of 67.6 ± 9.2 years. The average duration of uveitis was 3.24 ± 1.89 years. All eyes were diagnosed with uveitic glaucoma, with three eyes having steroid-induced glaucoma and one with normal tension glaucoma as comorbidities. Sarcoidosis caused uveitis in four eyes, posterior uveitis in two eyes, optic neuritis in 2, and idiopathic uveitis in nine eyes. Anatomically, four eyes were classified as anterior uveitis, and 13 as panuveitis.

Table 1 Characteristics of the patients and eyes at baseline.
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Efficacy of SLT on IOP

A summary of IOP and treatment before and post-SLT treatment for uveitic glaucoma is shown in Table 2. At baseline, the average IOP was 28.4 ± 6.50 mmHg, the average acetazolamide dosage (250 mg/tablet) was 2.76 ± 0.44 tablets/day, the average glaucoma treatment score (GTS) was 7.53 ± 1.07, the average inflammation score was 0.24 ± 0.31, the average frequency of steroid eye drops was 2.27 ± 1.64 times/day, and the average dosage of prednisolone (PSL) was 5.18 ± 8.97 mg/day.

Table 2 Summary of results before and after selective laser trabeculoplasty.
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Following SLT, the mean IOP at 1 month, 3 months, and 6 months was 18.2 ± 10.7 mmHg, 18.2 ± 9.5 mmHg, and 17.3 ± 9.4 mmHg, respectively, indicating a significant decrease compared to baseline (P = 0.0004, P < 0.0001, P < 0.0001, respectively) (Fig. 1). The changes from baseline were − 10.2 ± 7.6 mmHg, − 10.1 ± 5.8 mmHg, and − 11.0 ± 6.2 mmHg, respectively. The GTS at 1 month, 3 months, and 6 months post-SLT was 5.59 ± 2.21, 5.12 ± 2.09, and 4.71 ± 2.08, respectively, indicating a significant decrease compared to baseline (P = 0.0001, P = 0.0004, P = 0.0001, respectively). The number of acetazolamide tablets taken post-SLT at 1 month, 3 months, and 6 months was 1.35 ± 1.22, 0.65 ± 1.17, and 0.41 ± 0.87, respectively, which were significantly lower than at the time of SLT (P = 0.0010, P = 0.0001, P < 0.0001, respectively).

Fig. 1
figure 1

Intraocular Pressure at baseline and post-selective laser trabeculoplasty. * denotes P < 0.0005. **denotes P < 0.0001.

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Steroid responders

Three patients were identified as steroid responders, and among them, four were treated with SLT. One patient had sarcoidosis with multiple peripheral anterior synechiae (PAS) in the angles of both eyes. SLT laser treatment was performed on areas of the angle without PAS, resulting in a decrease in IOP. However, in both eyes, the IOP exceeded 21 mmHg again after one month, with similarly elevated IOP observed at three and six months, leading to their assessment of failures. The remaining two patients had idiopathic uveitis. Among these two patients, one experienced an increase in IOP one month after SLT treatment, resulting in classification as part of the failure group. The other patient achieved satisfactory IOP reduction up to six months following SLT treatment, and was classified as part of the success group. The four eyes of these three patients treated with SLT (three classified as failure and one as success) were not currently using steroid eye drops and were considered to have uveitic glaucoma. However, the influence of previous steroid eye drop use or oral administration cannot be ruled out. Therefore, we excluded the data of these three patients (four eyes) and recalculated the results, which are also listed in Tables 2 and 3. Excluding the four eyes, although the sample size decreased, the trend in statistical significance remained unchanged.

Table 3 Evaluation of factors involved in selective laser trabeculoplasty response at 6 months.
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Safety and adverse events of SLT

The safety and adverse events of SLT treatment for uveitic glaucoma are also summarized in Table 2. The inflammation score at 1 month, 3 months, and 6 months post-SLT was 0.26 ± 0.36, 0.18 ± 0.30, 0.05 ± 0.17, respectively. There was no significant difference from baseline. Furthermore, there were no cases of SUN Grade worsening by two or more during the observation period. The mean steroid eye drop frequency at 1 month, 3 months, and 6 months post-SLT was 1.76 ± 1.68, 1.41 ± 1.77, 0.94 ± 1.30, respectively. At 6 months post-SLT, the frequency was significantly lower than at baseline (P = 0.012). The amount of PSL administered at 1, 3, and 6 months post-SLT was 8.72 ± 2.11, 2.97 ± 4.94, and 2.68 ± 5.00, respectively, with no significant difference compared to baseline. No worsening of inflammatory findings or any other adverse events was observed before or after SLT. There were no cases in which the PSL dosage needed to be increased after SLT. Of the 17 eyes, five had trabeculotomy during the study period. All five eyes were phakic. Among them, three eyes had insufficient IOP reduction and exhibited multiple PAS in the angle, necessitating goniosynechialysis. For the remaining two, surgery was scheduled due to cataract progression, and a trabeculotomy was performed concurrently for glaucoma management. Therefore, all five eyes initially underwent trabeculotomy in conjunction with cataract surgery. In all cases, IOP was always less than 21 mmHg following trabeculotomy.

Factors related to the success of SLT treatment

Success rates at 1, 3, and 6 months post-SLT were 70.5%, 58.8%, and 64.7%, respectively (Table 2). A summary of the analysis of factors associated with SLT success and failure is presented in Table 3. In the comparison between the success and failure groups at 6 months post-SLT, the duration of uveitis was 1.37 ± 0.41 years and 1.97 ± 0.80 years, respectively, with a considerably shorter duration found in the success group (P = 0.032). Baseline intraocular pressure (IOP) was 25.5 ± 5.09 mmHg and 33.7 ± 5.57 mmHg in the success and failure groups, respectively. The success group had significantly lower IOP during SLT (P = 0.035). Age, sex, anatomical classification, baseline logarithms of the minimum angle of resolution (logMAR), inflammation score, GTS, steroid eye drop frequency, oral prednisolone dosage, number of SLT treatments, and number of eyes with PAS were all unrelated to success at 6 months after SLT. Among the six eyes in the failure group, three eyes (50.0%) had PAS. In contrast, among the 11 eyes in the success group, three eyes (27.3%) had PAS. The frequency of PAS was higher in the failure group; however, the difference did not reach statistical significance.

Discussion

This study included patients with uveitic glaucoma who had inadequate IOP despite full medication with eye drops and oral medications. At baseline, the mean IOP was 28.4 ± 6.50 mmHg. The mean IOP after SLT was less than 21 mmHg at all time points, and the average IOP reduction exceeded 10 mmHg. The mean IOP after SLT was less than 21 mmHg at all time points, and the average IOP reduction exceeded 10 mmHg. SLT is expected to have a longer-lasting and more stable effect on IOP reduction than drugs because of structural changes in the trabecular meshwork14. In addition to the positive responses of pseudoexfoliation and pigmentation glaucoma to SLT, the study found that uveitic glaucoma responds well to SLT.

Both IOP and GTSs decreased significantly after SLT. However, no patients achieved glaucoma treatment-free status with SLT alone. While one patient did not require eye drops or oral medications at 6 months, this was due to undergoing an additional trabeculotomy following SLT. In a POAG RCT comparing SLT to eye drop medication, 74.2% of patients in the SLT group achieved target IOP without using eye drops after 36 months9.

In this study, 12 of 17 eyes were taking oral acetazolamide at baseline, and the presence of refractory uveitic glaucoma patients in this study may have contributed to the lack of drop-free eyes. Although oral acetazolamide is expected to lower IOP by inhibiting the production of aqueous humor in the ciliary body, it is associated with side effects such as metabolic acidosis, fatigue, nausea, and extremity paresthesias15. It is often difficult to administer acetazolamide due to the patient’s underlying disease and the severity of side effects, so its use should be limited to temporary IOP reduction7. In this study, only two eyes needed oral acetazolamide after 6 months, including those that required additional surgery.

Multiple factors contribute to the pathogenesis of uveitic glaucoma, including increased outflow resistance caused by trabecular meshwork inflammation, as well as peripheral anterior and posterior iris synechiae3,4. Therefore, there is concern that SLT may cause excessive inflammation of the trabecular meshwork in patients with uveitic glaucoma, causing intraocular pressure to rise again and exacerbate uveitis. A previous report on SLT for pigmentary and pseudoexfoliative glaucoma found no significant exacerbation of the inflammatory process following SLT16. In contrast, another report described a patient with POAG who developed severe iridocyclitis in both eyes 3 weeks after SLT17. In this study, there were no cases in which the inflammation score increased by more than + 2. There were also no significant differences in inflammatory cell scores or the number of betamethasone eye drops administered prior to and following SLT. There were no other adverse events.

In this study, 64.7% of patients were clinically successful after 6 months without additional surgery, with an IOP of 21 mmHg or less and an IOP reduction of at least 20%. Zhou et al. found that SLT improved IOP reduction in steroid-induced glaucoma and had a lower failure rate with IOP reduction of less than 20% at any time greater than 3 weeks after SLT compared to POAG and pseudoexfoliative glaucoma18. Other studies have shown that SLT is effective in treating steroid-induced glaucoma19,20. In contrast, their study found that the failure rate after 6 months of SLT in uveitic glaucoma was nearly 80%18. The response to SLT treatment for uveitic glaucoma at six months in this study was higher than their results, however, the long-term efficacy remains uncertain at this time.

It was suggested that shorter disease duration and lower IOP at baseline played a role in SLT’s successful response. Anterior uveitis was associated with a good response to SLT in 4 of 4 patients, but there was no statistical difference. The inflammatory score at the time of SLT and the dose of PSL medication were not found to be associated with SLT, implying that inflammatory activity does not always influence the outcome of SLT. The frequency of PAS was considerably higher in the failure group; however, due to the small sample size in this study, the difference did not reach statistical significance. Patients who have had the disease for a long time may be more prone to angle closure due to peripheral anterior iris synechiae and organic abnormalities of the aqueous outflow pathway caused by chronic inflammation. All five eyes that underwent trabeculotomy had successful postoperative IOP reduction, indicating that direct incision of the trabecular meshwork via trabeculotomy results in solid IOP reduction. In POAG, SLT has been shown to reduce IOP with a lower risk of complications and comparable efficacy to MIGS trabeculotomy21. Furthermore, the presence or absence of SLT is less likely to influence the outcome of MIGS because SLT causes only minor changes in the anatomic structure of the angle22,23.

This was a retrospective study with a small number of cases, and the indications for SLT, procedure, and concurrent treatment were not standardized. Furthermore, some patients had surgery following SLT, making it difficult to accurately compare the effect of SLT on IOP reduction. To reduce the effect of survivorship bias caused by excluding patients who underwent additional surgery or analyzing postoperative values, patients who underwent surgery had their IOP measured immediately before the additional surgery applied to the subsequent years. Future prospective studies with larger patient populations are expected to determine the efficacy of SLT for uveitic glaucoma.

In conclusion, SLT treatment was performed on 17 eyes with uveitic glaucoma, resulting in 6 eyes classified as failures and 11 eyes as successes after 6 months. The findings of this study shed new light on the efficacy and safety of SLT for patients with refractory uveitic glaucoma. Given that SLT is less invasive than surgery and that there was little correlation between SLT and exacerbation of inflammation, it may be a viable treatment option for uveitic glaucoma with poor IOP control with ocular medications.

Methods

Study population and recruitment

The study included 17 eyes from 13 consecutive patients with uveitic glaucoma who were treated with SLT for glaucoma refractory to medical treatment at Yokohama City University Hospital between 2022 and 2023 and followed for more than 6 months. Medical records were retrospectively reviewed to determine the efficacy and safety of SLT for uveitic glaucoma. This study was authorized by the Institutional Review Board of Yokohama City University (F231200005). This study followed the Declaration of Helsinki guidelines, and the Institutional Review Board of Yokohama City University approved the research protocol. Due to the retrospective nature of the study, the Institutional Review Board of Yokohama City University waived the need of obtaining informed consent. Instead, patients were notified about the study via the hospital’s website, and an opt-out system was available to express their preferences regarding the use of their data.

SLT procedure

SLT was performed with the Tango: SLT/YAG Combination Laser System (Ellex, Adelaide, Australia). Following topical anesthesia, the Latina SLT Gonio Laser Lens (Ocular Instruments, Bellevue, Washington, USA) was used to apply laser treatment to the trabecular meshwork in a 360° pattern.

Observation parameters

The medical records were reviewed to determine the cause of uveitis, medications, IOP, best correct visual acuity, number of laser irradiations, GTS, inflammation score, and adverse events. Visual acuity was measured in logMAR. The intraocular pressure was measured using a Goldmann applanation tonometer or the iCare IC200 (iCare, Vantaa, Finland). The GTS was calculated using the following criteria: one point was assigned for each medication contained in an eye drop, and two points were assigned to combination drugs containing two agents. Furthermore, for the daily oral dose of acetazolamide 250 mg used to lower intraocular pressure, one tablet was worth one point. The total score for eye drops and acetazolamide comprised the GTS. Inflammation was assessed using the SUN classification for intra-anterior chamber inflammation and the NEI/SUN classification for vitreous opacity, with the sum of the two classifications calculated as the inflammation score24,25. At each followup time point of 1 month, 3 months, and 6 months after SLT, cases were defined as failures if IOP surpassed 21 mmHg, there was less than a 20% reduction in IOP, there was an increase in inflammation score of + 2 or more, or glaucoma surgery was performed after SLT. All other cases were deemed successful.

Outcome

The primary outcome measure was the success rate of SLT after 6 months. Secondary outcomes included a comparison of IOP, visual acuity, inflammation score, and GTS before and after SLT. In eyes that had additional glaucoma surgery following SLT, the IOP, GTS, and acetazolamide dose at the time of surgery were also applied to the observation points after surgery to minimize the effect of dropout bias. Patients who had cataract surgery or vitrectomy during the study period were excluded from the visual acuity analysis. The success and failure groups at the 6-month post-SLT observation point were compared to identify the factors that influenced the course of SLT therapy.

Statistical analysis

The Wilcoxon test was used to compare pre and post-SLT. The Mann–Whitney U test was used to compare the success and failure groups. Anatomic classification and SLT success were assessed using Fisher’s exact test. All statistical analyses were carried out using JMP Pro17.0 (SAS Institute Inc., Cary, NC, USA). P < 0.05 was deemed statistically significant with a two-tailed test.