Influence of preoperative glaucoma medication on long-term outcomes of trabeculectomy

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In a retrospective study, a team of Korean researchers identified key factors influencing the long-term outcomes of trabeculectomy in patients with primary open-angle glaucoma (POAG) who were treated by a single surgeon. The study evaluated the association between preoperative topical glaucoma medication containing preservatives and long-term trabeculectomy outcomes in 309 eyes from 201 patients with POAG, followed for over 10 years.

The research team includes Somi Lee, MD, Min Gu Huh, MD, and Soon Cheol Cha, MD, all from the Department of Ophthalmology, Yeungnam University College of Medicine and Yeungnam University Hospital, Daegu, Korea, and Do Young Park, MD, PhD, Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.¹

"By specifically measuring exposure to topical glaucoma medications using the Glaucoma Medication Intensity Index (GMII), we established it as a significant risk factor for trabeculectomy failure," the researchers wrote. "Our analysis revealed that the GMII, along with the patient's age at the time of surgery and the occurrence of cataract surgery after trabeculectomy, was significantly associated with surgical failure."

The GMII was used to quantify the cumulative preoperative exposure to glaucoma medications. Kaplan–Meier analysis showed cumulative success rates of 89.3%, 59.2%, and 46% at 1, 10, and 20 years postoperatively. At 20 years, the success group had a significantly lower GMII (3.28 vs. 8.74, p = 0.004). A GMII threshold of ≥ 4.35 was associated with poorer long-term IOP control and shorter surgical success duration.¹

Cox regression analysis identified advanced age at surgery, higher GMII, and subsequent cataract surgery as significant risk factors for trabeculectomy failure. These findings highlight the adverse impact of prolonged preoperative use of glaucoma medications on long-term surgical outcomes, with GMII emerging as a valuable predictor to guide preoperative management strategies.¹

"These findings suggest that both age-related and surgery-induced alterations in conjunctival characteristics significantly affect sustained aqueous outflow through the filtering bleb," the researchers noted. "Moreover, the prolonged use of multiple topical glaucoma medications may induce chronic conjunctival changes that adversely affect bleb formation and function."

Glaucoma is a chronic, progressive optic neuropathy characterized by optic nerve damage, leading to irreversible visual field loss and potentially blindness if not properly managed. The primary risk factor for the development and progression of glaucoma is elevated IOP, which can cause mechanical and ischemic damage to the optic nerve head. Lowering the IOP is crucial for preventing further optic nerve damage and halting the progression of visual field defects associated with glaucoma.

Glaucoma is primarily treated with topical medications that reduce IOP, including prostaglandin analogs, beta-blockers, alpha agonists, and carbonic anhydrase inhibitors. However, when these medications fail to control IOP or when the disease progresses, surgical intervention becomes necessary. Trabeculectomy is considered the gold standard among various surgical techniques, due to its long-term efficacy in maintaining stable IOP levels.

However, the researchers noted that trabeculectomy can fail over time, and potential risk factors for failure include a history of previous ocular surgeries, the type of glaucoma (e.g., neovascular or uveitic), and race, particularly among Black individuals.

"Our study also showed that the GMII was significantly lower in the success group than in the failure group at 10, 15, and 20 years after trabeculectomy," the researchers observed. "In addition, the longer the trabeculectomy success was maintained, the lower the GMII values."

The researchers also noted that their findings are consistent with those of previous studies, which suggest that GMII may be a major risk factor for trabeculectomy failure.

"These findings also suggest that optimizing the timing of surgery to avoid prolonged exposure to glaucoma medications, as indicated by the GMII, can improve long-term surgical outcomes," they pointed out.

Preservatives in topical glaucoma medications are known to increase the number of macrophages, lymphocytes, and fibroblasts in the conjunctiva and Tenon’s capsule, leading to chronic inflammation.

"All patients in our study used preservative-containing glaucoma medications before trabeculectomy, complicating the determination of the direct effects of preservatives on surgical outcomes," the researchers wrote. "Previously, it has been reported that both preservatives and active ingredients in glaucoma medications can increase subepithelial collagen thickness in the conjunctiva."

Additionally, the researchers noted that secondary changes, such as dry eye, corneal erosion, or eyelid inflammation, may occur due to medication use, further altering the conjunctiva. Thus, the prolonged use of glaucoma medications can lead to chronic changes in the conjunctiva and Tenon’s capsule, potentially affecting bleb formation and function after trabeculectomy.

Future research is needed to investigate the microscopic changes in the conjunctiva and Tenon’s capsule caused by various preservatives and active components of glaucoma medications.

"Our study also identified age at the time of surgery as a significant factor associated with trabeculectomy failure," the researchers pointed out.

The effect of patient age on surgical outcomes varies across studies. Some studies have reported poorer surgical prognosis in younger patients due to rapid and severe conjunctival fibrosis, while others have found no difference between younger and older patients.¹

In this study, patients aged < 40 years with juvenile-onset angle-closure glaucoma (JOAG) had better surgical outcomes and long-term success rates after trabeculectomy.

"This suggests that, despite having more Tenon’s capsule, younger patients can form long-lasting functional blebs if aqueous humor filtering is maintained continuously, and inflammatory and fibrotic responses are effectively suppressed after surgery," the researchers wrote.

The researchers also pointed out that older patients who underwent trabeculectomy without prolonged use of glaucoma medications, due to high IOP, exhibited blebs similar to those of younger patients—characterized by thin walls, transparency, and minimal vascularization. Further studies using anterior segment optical coherence tomography (AS-OCT) could help clarify how preoperative glaucoma eye drop use or patient age affects postoperative bleb morphology.

The study had several limitations. As a retrospective analysis, it included only patients with more than 10 years of follow-up after trabeculectomy, resulting in high dropout rates, primarily due to advanced age, associated comorbidities, or stable conditions managed by local clinics.¹

"Although this may introduce bias in calculating long-term success rates, we included all patients with long-term follow-up, regardless of surgical success, which we believe is valid for analyzing factors related to long-term surgical outcomes," the researchers noted. "However, further prospective studies are required to validate our findings."

Second, the researchers defined surgical success as maintaining an IOP below 15 mm Hg without glaucoma medication post-trabeculectomy. This criterion resulted in lower success rates compared to other studies that set a higher IOP threshold (e.g., 21 mm Hg) or included the use of glaucoma medications.

"However, we believe that this stringent criterion reflects the functionality of the bleb more accurately and allows for a better assessment of the long-term effects of glaucoma medications on the conjunctiva," they wrote.

Additionally, the strong correlation between age and GMII in this cohort may have obscured the independent effects of GMII on trabeculectomy failure. Further studies with larger cohorts are required to determine whether GMII can serve as an independent predictor of surgical outcomes, particularly across different age groups.¹

"The prolonged preoperative use of glaucoma eye drops is a risk factor for trabeculectomy failure," the researchers concluded. "The GMII can clinically quantify the cumulative use of glaucoma medications and help determine the optimal timing of surgery. Further research is needed to understand how long-term use of these medications affects conjunctival changes, as well as bleb formation and function after trabeculectomy."

Reference

1. Lee, S., Park, D.Y., Huh, M.G. et al. Influence of preoperative glaucoma medication on long-term outcomes of trabeculectomy. Sci Rep 14, 28341 (2024). https://doi.org/10.1038/s41598-024-79637-z