Abstract
Impervious encapsulation around Ahmed glaucoma valve (AGV) results in surgical failure raising intraocular pressure (IOP). Dysregulation of extracellular matrix (ECM) molecules and cellular factors might contribute to increased hydraulic resistance to aqueous drainage. Therefore, we examined these molecules in failed AGV capsular tissue. Immunostaining for ECM molecules (collagen I, collagen III, decorin, lumican, chondroitin sulfate, aggrecan and keratan sulfate) and cellular factors (αSMA and TGFβ) was performed on excised capsules from failed AGVs and control tenon’s tissue. Staining intensity of ECM molecules was assessed using Image J. Cellular factors were assessed based on positive cell counts. Histopathologically two distinct layers were visible in capsules. The inner layer (proximal to the AGV) showed significant decrease in most ECM molecules compared to outer layer. Furthermore, collagen III (p = 0.004), decorin (p = 0.02), lumican (p = 0.01) and chondroitin sulfate (p = 0.02) was significantly less in inner layer compared to tenon’s tissue. Outer layer labelling however was similar to control tenon’s for most ECM molecules. Significantly increased cellular expression of αSMA (p = 0.02) and TGFβ (p = 0.008) was detected within capsular tissue compared to controls. Our results suggest profibrotic activity indicated by increased αSMA and TGFβ expression and decreased expression of proteoglycan (decorin and lumican) and glycosaminoglycans (chondroitin sulfate). Additionally, we observed decreased collagen III which might reflect increased myofibroblast contractility when coupled with increased TGFβ and αSMA expression. Together these events lead to tissue dysfunction potentially resulting in hydraulic resistance that may affect aqueous flow through the capsular wall.
Highlights
Glaucoma drainage devices are useful in treating refractory glaucoma [1]
The overall success rate of these drainage devices appears to be similar in controlling intraocular pressure (IOP) and a major cause of attenuated long-term success is attributed to excessive fibrous reaction of the capsular tissue [4]
Excised capsule showed two distinct layers in all examined tissues. This included an outer layer that consisted of loosely arranged collagen bundles, spindle shaped fibroblasts and mature blood vessels that were variable in calibre and an inner layer that was composed of dense compact collagen bundles with several spindle shaped fibroblast and few mature thin walled blood vessels (Fig 1)
Summary
Available glaucoma drainage devices (GDDs) are Ahmed (New World Medical, Inc., Rancho Cucamonga, CA, USA), Baerveldt (Advanced Medical Optics, Inc., Santa Ana, CA, USA), Krupin (Eagle Vision, Inc., Memphis, TN, USA) and Molteno implants (Molteno Ophthalmic Ltd., Dunedin, New Zealand). They share a common design consisting of a small caliber silicone tube that is inserted into the eye and drains aqueous humor to an episcleral plate [2]. Progressive capsular fibrosis around the implant and relative impermeability of the shunt capsule in many cases results in clinical failure, necessitating further medical or surgical management
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