April 15, 2016
Results of a 25-year review of the complication rate in a well-defined population of patients with glaucoma treated with trabeculectomy at Mayo Clinic and Olmsted Medical Center suggest that the rate of trabeculectomy-related complications does not appear to be associated with mitomycin use. The long-term study shows more favorable outcomes than do studies that report higher complication risks during shorter study periods.
Cheryl L. Khanna, M.D., and a research team from Ophthalmology at Mayo Clinic's campus in Rochester, Minnesota, used data from the Rochester Epidemiology Project to determine the rate of trabeculectomy-related complications during the 25 years studied. Review results were published in JAMA Ophthalmology in 2015.
"Historically, trabeculectomy has been the surgical standard of care for patients with medically refractory glaucoma," says Dr. Khanna. "The introduction of adjunctive antimetabolite agents such as fluorouracil and mitomycin increased the success rate of trabeculectomy by reducing scarring at the filtration site, but these agents also have been reported to increase the rate of post-trabeculectomy complications. This 25-year review, however, did not show a linear trend in complications with mitomycin."
334 study participants, 460 eyes treated
Dr. Khanna and the research team identified 348 patients 18 years or older at the time of analysis who underwent trabeculectomy from Jan. 1, 1985, through Dec. 31, 2010. The average age at first trabeculectomy was 71 years. The average follow-up was 7.7 years. Follow-up visits were included through 2013.
In the 334 patients included in the study, 460 eyes underwent trabeculectomy. Among them, 159 eyes had complications, including:
- 100 eyes with early complications (less than three months)
- 59 eyes with late complications (three months or more) during the follow-up
- 10 eyes with both early and late complications
"The team recorded the concentration of mitomycin applied during surgery, intraoperative complications, and all postoperative complications and the occurrence of complications as they related to the mitomycin concentration administered during the operation," says Dr. Khanna. Complications included bleb leak, hypotony, hyphema, choroidal effusion, choroidal hemorrhage, blebitis and endophthalmitis.
Mitomycin and complications
The team completed comparisons among various concentrations of mitomycin through the Cox proportional hazards regression model, which used robust sandwich estimates to account for the potential correlations among the eyes for patients with both eyes in the study. Cumulative probabilities of short- and long-term complications were determined using the Kaplan-Meier method, and the relation to mitomycin concentration applied during trabeculectomy. Results indicate:
- The 20-year cumulative probability of early, late or any complication was 20 percent (95 percent confidence interval, or CI, 16 to 24 percent), 26 percent (95 percent CI, 15 to 36 percent), and 45 percent (95 percent CI, 38 to 52 percent), respectively.
- The cumulative probabilities of vision-threatening complications during 20 years were 2 percent (95 percent CI, 0 to 4 percent) for blebitis and 5 percent (95 percent CI, 1 to 9 percent) for endophthalmitis.
- There was no association between the rate of trabeculectomy complications and mitomycin dose.
"This study shows an overall lower rate of trabeculectomy-related complications than previous reports with shorter follow-ups published in Eye in 2002 and American Journal of Ophthalmology in 2012," says Dr. Khanna. "The 20-year cumulative probability of early complications, at 20 percent, is lower than the probability in other published reports, in which it ranged from 37 to 47 percent in the short term.
"At Mayo, the initial surgical intervention for uncontrolled open-angle glaucoma is trabeculectomy. In 2007, the concentration of mitomycin used was decreased from 0.4 to 0.2 mg/mL in an attempt to decrease the number of complications and, unless contraindicated by other risk factors, the use of mitomycin was standardized at 0.2 mg/mL.
"In this study, the complication rate was unchanged during the 25-year study period regardless of changes in mitomycin administration before and after 2007. An increase in mitomycin concentration applied in patients only with increased risk of trabeculectomy failure, the surgical technique used, the limited duration of mitomycin administration, and a conservative approach to mitomycin C application at Mayo may contribute to the lack of association between mitomycin C and complications."
For more information
Olayanju JA, et al. Trabeculectomy-related complications in Olmsted County, Minnesota, 1985 through 2010. Ophthalmology. 2015;133:574.
Edmunds B, et al. The National Survey of Trabeculectomy. III: Early and late complications. Eye. 2002;16:297.
Gedde SJ, et al. Treatment outcomes in the tube versus trabeculectomy (TVT) study after five years of follow-up. American Journal of Ophthalmology. 2012;153:789.