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Long-term wound healing affects trabeculectomy success
Expression of HLA-DR was no different between eyes with and without topical glaucoma medication.
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The main cause of filtering surgery failure is episcleral fibrosis and thickening of conjunctiva overlying the area of filtration, according to one investigator.
“The wound healing process is intense in the early postoperative period [after trabeculectomy], when most of the failures occur,” Barbara Cvenkel, MD, PhD, told Ocular Surgery News in regard to a study assessing the relationship among filtering bleb morphology, ocular surface changes and the outcome of trabeculectomy surgery.
“However, the process of wound healing and tissue remodeling continues life-long and results in an increasing failure rate with longer follow-up,” she said.
Among the many risk factors that influence the outcome of surgery are previous ocular surgery, ocular inflammation and long-term use of topical antiglaucoma medication.
“Also, in the absence of known risk factors for bleb failure and after the same uneventful trabeculectomy with mitomycin C, there is a difference in wound healing among patients short term and long term,” Cvenkel said.
Early, late differences
The presence of subconjunctival blood during the early postop period prevents aqueous outflow and can lead to inflammation and earlier scarring, especially when the amount of blood is larger than the scleral trap door, according to Cvenkel.
Conversely, in late bleb failure, gradual fibrosis and thickening of the conjunctiva are part of a process that goes on indefinitely, she said. Furthermore, the composition of aqueous and its changes and interactions with different cytokines may also play a role.
In a cross-sectional study of 85 eyes of 85 patients published in Journal of Glaucoma, Cvenkel and colleagues associated successful surgery with greater central and maximal bleb area and decreased vascularity of the central and peripheral portions of the bleb, but not with diminished expression of the inflammatory marker by ocular surface. Ocular surface changes were measured by the expression of the inflammatory marker HLA-DR.
“There is great variation in individual response after filtering surgery,” Cvenkel, who performed all of the trabeculectomies, said. “Some operated patients, despite similar topical treatment and appearance of the eye before surgery, have more intense postop inflammation and tendency for scarring with bleb failure. We were interested in the association between bleb morphology and the inflammation of conjunctiva overlying the surgical site.”
HLA-DR expression
In the study, 58 patients were deemed to have undergone successful trabeculectomy, and 27 had failed surgery. Bleb morphology was evaluated by slit lamp using the Moorfields Bleb Grading System (MBGS).
“We would expect more inflammation in eyes with failed blebs with higher expression of HLA-DR molecules on epithelial cells,” Cvenkel said. “In success eyes, the blebs had greater area and decreased vascularization compared to failed eyes.”
The mean MBGS scores for areas in the group that underwent successful trabeculectomy were 3.27 for the central bleb area, 3.80 for the maximal bleb area and 2.21 for height, compared to 2.03, 2.4 and 2.21, respectively, in the treatment failure group.
In contrast, vascularization scores for the success group were 2.44 for central bleb vascularity, 2.63 for peripheral bleb vascularity and 2.21 for vascularity of non-bleb conjunctiva, compared to 2.91, 3.02 and 2.24, respectively, in the treatment failure group.
The authors found no difference in the expression of HLA-DR on conjunctival epithelial and antigen-presenting cells between the eyes with and without eye glaucoma drops, or between eyes that underwent successful or failed trabeculectomy. However, there was an increased percentage of HLA-DR-positive antigen-presenting cells, or dendritic inflammatory cells, found in the success eyes.
“An increased number of dendritic cells in mitomycin-functioning blebs in impression cytology and in vivo confocal microscopy has also been observed by others,” Cvenkel said, citing a 2008 study in Ophthalmology. “That study of mitomycin-functioning blebs showed at the surface numerous microcysts that seemed to be abnormal goblet cells and are probably acting as channels for the passage of aqueous toward the ocular surface.”
In the current study, mitomycin was applied during surgery to 73 of the 85 eyes.
Microcyst involvement
To describe bleb classifications, Cvenkel and colleagues used MBGS, which does not include microcysts.
“Microcysts may be an important bleb characteristic in the long term, indicating transcellular pathway of aqueous at the level of goblet cells,” she said.
During trabeculectomy, the surgical fistula drains the aqueous from the anterior chamber into the subconjunctival space.
“Differences and changes in the composition of the aqueous bathing the surgical site can influence the scarring process,” Cvenkel said. “Increased aqueous level of activated TGF-beta 2, a potent stimulator of fibroblast activity, was associated with increased risk of scarring.”
A previous study by Cvenkel and colleagues on inflammatory molecules in aqueous humor and on ocular surface and glaucoma surgery outcome found that higher preoperative levels of TNF-alpha and IL-6 in aqueous humor increased the risk of failure in a group of patients followed 12 months after trabeculectomy, she said.
For successful trabeculectomy, in addition to the use of antimetabolites, postoperative care to reduce inflammation and limit excessive scarring is critical, according to Cvenkel.
“In summary,” she said, “functioning blebs, long term, have greater area, are less vascularized and have many microcysts.” – by Bob Kronemyer