B iocom patibility in the C ontext o f G laucom a D rainage Devices

Key dim ensions o f biocom patibility in relation to GDD im plantation are: resistance to non-specific biological spoliation and tube occlusion, resistance to fibrotic encapsulation and drainage failure (foreign body reactions), reduced contact associated corneal endothelial dam age, and resistance to bacterial adhesion. Each o f these elem ents is considered below.

3.3.1 Protein & Cell A dhesion - Tube Occlusion

Valve m echanism s in glaucom a drainage devices (GDD s) have largely failed to provide consistent flow control and protection from hypotony. Lim itations o f currently m arketed valved devices have recently been exposed in theoretical (Lee

1998) experim ental (Prata 1995; Porter 1997) and clinical exam inations (Lim 1998).

Flow control in non-valved devices is critically dependent on the internal dim ensions o f the flow passage. For tube devices, resistance varies w ith the fourth pow er o f tube diam eter in accordance with Poiseuilie's law (M cEw en 1958). Small changes in diam eter induced by protein or cellular spoliation may lead to substantial changes in flow perform ance. Resistance to surface spoliation is therefore a key requirem ent for m aterials used in GDDs w hich seek to control flow using single or m ultiple small bore tubes as flow resistors.

Protein and cellular com ponents, w hich are likely to play an im portant role in tube surface spoilation in the post-operative aqueous environm ent, include fibrinogen, fibrin, and m acrophages. Sm all-bore filtration channels m ay also be capped o ff externally by scleral fibroblasts grow ing into a fibrin scaffold (Shahinian 1992).

3.3.2 Protein and Cell Adhesion - C hronic Inflam m ation & Bleb Fibrosis

As w ith all im planted biom aterials, G DD s stim ulate a foreign body reaction and a variable degree o f chronic inflam m ation. In the context o f GDD im plantation, this chronic inflam m atory process will lead to progressive fibrous encapsulation. This chain o f events lim its the filtration life o f all contem porary G DD s (Table 5; Chapter 1: Page 27).

In vivo studies using rabbits have suggested that both physical and chemical properties o f biom aterials m ay determ ine the level o f inflam m ation (A yyala 2000) and consequent fibrous encapsulation thickness (Jacob-Labarre et al 1996) related to subconjunctival im plants. A lthough the m echanism o f foreign body reactions is incom pletely understood, it is likely that fibrinogen adhesion is im portant in the initiation o f inflam m atory responses (Tang 1993). A dherent m acrophages may play a m ajor role (Schoen 1996) in orchestrating the cytokine drive to chronic inflam m ation.

3.3.3 Cell D am age - E ndothelial Failure

C om eal endothelial failure is a com m on com plication G D D s im plantation (Chapter 1), occurring in up to 34% o f cases after a m ean follow up o f two years in GDDs im plantation after previous com eal graft surgery (Beebe 1990).

The m echanism for endothelial failure after GDD im plantation is not fully understood. C ontinued small m ovem ents o f the tube elem ent relative to the com ea (m icro-m otion) transm itted from repeated m inor displacem ent o f the GDD plate elem ent during eye m ovem ent may be im portant in accelerating endothelial loss. This gradual attrition m ay be superim posed on significant intraoperative endothelial dam age, and dam age in the early postoperative period from m acroscopic contact between the im plant and the com ea in association w ith poor tube positioning or anterior cham ber shallowing.

Each o f these possible elem ents o f the m echanism for endothelial failure after GDD im plantation involves contact betw een the endothelium and the im plant. Studies o f com eal endothelial cell dam age resulting from standardised direct contact w ith intraocular lenses have shown variation betw een m aterials (K assar 1980, Barrett 1984, M ateo 1989, Balyeat 1989). A m aterial for w hich contact induced endothelial dam age is relatively low should help reduce endothelial loss in association w ith GDD im plantation.

3.3.4 Bacterial A dhesion - E ndophthalm itis

Endophthalm itis associated w ith GDD is a rare but serious com plication, w ith an overall incidence o f less than 0.5% (T able 6; C hapter 1: Page 29). The possible routes o f bacterial entry include; contam inated surgical instrum ents or GDD and GDD erosion. The initial adhesion o f bacteria to polym er substrata is a com plex process but can be assum ed to be dependent upon the host environm ent, m aterials and the type o f cells involved (G ristina 1996). O nce bacteria are organised w ithin a ‘biofilm ’ (G ristina 1987), they becom e relatively resistant to both antibiotics and host defence mechanisms.

3.4 Aim s

We set out to com pare PC-coated polym ethyl m ethacrylate (PM M A ) w ith m aterials used in existing and experim ental G DD s (Table 3; C hapter 1: Page 18) in a series o f

in vitro assays reflecting key dim ensions o f biocom patibility in the context o f GDD im plantation.