Fig. 6.3  Photomicrograph showing loss of inner limiting membrane (ILM) integrity above a vein

(v) and artery (a) (adapted from Wolter 1964, with permission)

6.3  The Vitreous As a Drug Reservoir

In ophthalmic drug delivery, the vitreous is employed as a drug reservoir for the treatment of posterior segment diseases such as age-related macular degeneration (Yoganathan et al. 2006; Parravano et al. 2010; Konstantinidis et al. 2009), uveitis (Antcliff et al. 2001; Young et al. 2001), cytomegalovirus retinitis (Dhillon et al. 1998; Guembel et al. 1999) and proliferative diabetic retinopathy (Hornan et al. 2010; Modarres et al. 2009). The relatively large gelled volume and the lack of strong morphological characteristics tend to suggest that it could be treated as a simple reservoir, allowing radial diffusion from the point of injection to the retinal tissues. As the skull largely encloses the posterior eye, introduction of the drug delivery system into the vitreous cavity is usually completed from the anterior aspect. It would then be expected that drug would freely diffuse throughout the gel quickly, achieving a uniform equilibrium at all points of retinal contact. This would make both the task of delivery and the calculation of appropriate dose very simple.

The anterior eye is constantly undergoing fluid turnover and, being closer to the exterior, is cooler. Thus it is reasonable to expect that convective forces might operate in the vitreous, especially if evidence of different viscosities could be found in central and peripheral zones or in the antral and distal regions. In addition, as we age, the vitreous compartment undergoes liquefaction and collapses, and the detachment of the posterior vitreous cortex from the retina provides two potential compartments, following posterior vitreous detachment (PVD). The issue concerning the contribution of flow processes to a non-uniform distribution is therefore a significant and inconvenient nuisance.