Anterior Chamber and Retina

Drugs are cleared from the vitreous primarily by two routes. The anterior route involves drainage into the anterior chamber and clearance with aqueous turnover via bulk flow. The posterior route involves either active or passive permeation across the retina and RPE and subsequent systemic dissipation (71,72). There is evidence that for some, highly lipophilic, compounds clearance via the retinal blood vessels may also play an important role (73). 

FIGURE 24.1 Ocular and periocular tissues. EL, eyelid DD, drug droplet COR, cornea AC, anterior chamber PC, posterior chamber AOF, aqueous outflow tract (trabeculum meshwork and Schlemm canal) BCNJ, bulbar conjunctiva PCNJ, palpebral conjunctiva FCNJ, fornical conjunctiva FNX, fornix (conjunctival sac/cul-de-sac) SC, sclera IR, iris CB, ciliary body CHOR, choroid RET, retina ONH, optic nerve head V, vitreous L, lens Z, lens zonulae ORF, orbital fat. 

Careful ophthalmological examination shows a striking increase in the number of microfilariae in the anterior chamber of the eye in a significant minority of patients, and a new inflammatory infiltrate can appear during treatment in already damaged areas of the retina (SEDA-15,334). However, no permanent ocular sequelae have been documented. Most of the other ophthalmic symptoms, including edema and local inflammation, are those of the primary infection. 

Two primary mechanisms of vitreal drug distribution and elimination are (i) diffusion from the lens region toward the retina with elimination via the retina-choroid-sclera and (ii) anterior diffusion with elimination via the hyaloid membrane and posterior chamber (18). Distribution to the retina from an intravitreal injection site is relatively slow, considering juxtaposition of the vitreous and retina, with the time for maximum drug concentration (tmax) in retina typically achieved at 4 to 12 hours, and reflects the inefficiency of diffusion over the distances encountered within the vitreous body. For example, ranibizumab, an ocular specific monoclonal VEGF antibody, distributes to the retina with of 6 to 24 hours. While relatively rapid therapeutically, this is slow compared with the rate of redistribution in stirred compartments. (249). 

The dominant path of distribution and elimination in the vitreous depends on a molecule s physicochemical properties and its substrate affinity. Lipophilic compounds, such as fluorescein (250) or dexamethasone (251), and compounds subject to active transport mechanisms, tend to be eliminated via the retina (Fig. 16). On the other hand, hydrophilic substances, such as fluorescein glucuronide, and compounds with poor retinal permeability, such as fluorescein dextran, tend to exit the vitreous anteriorly through the hyaloid membrane into the posterior chamber and subsequently into the anterior chamber, where they are subject to elimination pathways for aqueous humor (250). In general, shorter vitreal half-lives are associated with elimination through the retina, with its high surface area, whereas longer half-lives are indicative of elimination through the hyaloid membrane. 

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