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Editors Selection IGR 15-3

Surgical Treatment: Trabeculectomy blebs

Comment by Steven Gedde on:

54350 Otago Glaucoma Surgery Outcome Study: cytology and immunohistochemistry of trabeculectomy blebs, Molteno AC; Bevin TH; Dempster AG et al., Investigative Ophthalmology and Visual Science, 2013; 54: 4991-4999

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Molteno and colleagues describe the histologic and immunohistochemical features of six blebs that were examined 6-26 years after trabeculectomy. All specimens demonstrated an intrascleral channel, and the tissues lining the channel were characterized by degenerative changes with loss of collagen fibers and few pyknotic cells. The superficial bleb consisted of moderately cellular and vascular connective tissue with branching, fluid filled channels covered by intact epithelium. Immunohistochemical staining showed migration of histiocytes from superficial blood vessel to deep layers where apoptosis of these cells occurred. Fas ligand positive proapoptotic death messengers were concentrated in the superficial conjunctiva of blebs. The authors have previously reported a similar pattern of cellular apoptosis and distribution of normal and altered extracellular matrix in the bleb capsule around Molteno implants.

Although the bleb of a trabeculectomy and aqueous shunt have similar histopathologic features, they have very different clinical characteristics. A trabeculectomy bleb is generally thin walled (especially when an adjunctive antifibrotic agent is used) and perilimbal, while the bleb overlying the end plate of an aqueous shunt is thick walled and located in the equatorial region of the globe. The authors hypothesize that migration of mesodermal cells from superficial blood vessels to deep tissues is associated with apoptosis and release of collagenolytic enzymes and minute membrane bound vesicles, which act as proapoptotic death messengers. These vesicles are carried by aqueous flow toward the superficial layers where they suppress inflammation and fibrosis by inducing apoptosis in metabolically active cells via the extrinsic pathway. The dynamic balance between an inflammatory fibroproliferative response and anti-inflammatory apoptotic fibrodegenerative response to aqueous is believed to be involved in bleb formation after trabeculectomy and aqueous shunt implantation.

The study is limited by the small number of eyes that were examined postmortem, and all were in patients of European descent. An antifibrotic agent was not administered intraoperatively or postoperatively in any of the study eyes. These agents are routinely used as adjuncts to filtering surgery, and they have been shown to alter the histopathologic features of the bleb. Despite these limitations, the authors have provided insight into the complex process of cell activation, migration, apoptosis, and death messenger formation involved in bleb creation. This information may prove valuable in developing new methods to suppress fibrosis and enhance the success of glaucoma surgery.

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