Retina-choroid

Elliott et al. utilized a clenbuterol immunoassay to determine clenbuterol residues in cattle tissues and fluids. The LOD was 0.25 ug for liver. Animals were dosed with medicated feed (1.6 ug kg per day), and pairs were slaughtered during the medication phase and at 14,28, and 42 days after withdrawal. Clenbuterol concentrations in liver and retina/choroid samples were confirmed by GC/MS. Correlation coefficients between the ELISA and GC/MS were = 0.92 for retina/choroid samples and... 

In a study by Schoenwald et al., the conjunctival/scleral pathway yielded higher iris-ciliary body concentrations for all compounds evaluated with the exception of lipophilic rhodamine B (33). Romanelli et al. demonstrated the absorption of topical ocular bendazac into the retina-choroid via the conjunctival-scleral pathway (34). Noncomeal absorption was influenced more by physicochemical properties of the drag than characteristics of the formulation, whereas conversely transcomeal absorption could be influenced more by characteristics of the formulation. 

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). 

Roth S, Park SS, Sikorski CW, Osinski J, Chan R, et al. 1997. Concentrations of adenosine and its metabolites in the rat retina/choroid during reperfusion after ischemia. Curr Eye Res 16 875-885. 

The intrascleral implant is a device that is implanted in the sclera it delivers the drug through the sclera to the intraocular tissues (Fig. 5). Transscleral delivery may be an effective method of achieving therapeutic concentrations of drugs in the posterior segment (24-27). The intrascleral implant that incorporated betamethasone phosphate (BP) successfully delivered the drug to the retina/choroid and vitreous (28). The concentration of BP was maintained at a level that should suppress inflammation in the retina-choroid for more than eight weeks, and did not produce any ocular toxicity. 

We used 20 eyes of 20 pigmented rabbits to study in vivo release of BP from the implant and to evaluate pharmacodynamics in the ocular tissues after implantation. A scleral pocket was made at a depth of about one-half the total scleral thickness with a crescent knife 2 mm from the limbus. The scleral implant was inserted in the scleral pocket. At one, two, four, and eight weeks after implantation, animals were killed and four eyes were immediately enucleated at each time point. The concentrations of BP in the implants and samples of ocular tissues (aqueous humor, vitreous, and retina/choroid) were determined by HPLC. 

Figure 14 BP concentrations in the vitreous and the retina-choroid after intrascleral implantation of the BP-loaded implant. The values are shown as mean SD. Abbreviation BP, betamethasone phosphate. Source From Ref. 23.

Among the different prodrugs, biotin—C12-cidofovir 77c seems the most promising derivative. Indeed, compound 77c displayed a strong affinity for SMVT transporters, and provided an increased lipophilicity. Biodistribution was satisfactory, as well as its final intracellular conversion to cidofovir (in retina—choroid). Therefore, the authors concluded that novel... 

Melanin-affinity was reported for fluoroquinolones. Figure 4 shows the time course of lomefloxadn concentration in the ocular tissues after an intravitreal injection of 200 pig in pigmented and albino rabbits. Lomefloxadn concentration in the iris-ciliary body and retina-choroid was much higher in the pigmented rabbite than in the albino rabbits. Such difference between the pigmented and albino rabbits was absent in the ocular tissues without melanin such as the vitreous humor, the cornea and the lens. 

---