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is not as large; however, variations of up to a factor of 2.5 are still observed. As the injection volume increases, the effect of injection position would be dampened, with the upper limit of injection volume being a single injection that completely replaces the whole vitreous.

Table 4 lists the mean model calculated concentrations of fluorescein and fluorescein glucuronide in the vitreous as a function of the injection position, following either a 15 or a 100 mL injection. As mentioned earlier, the simulated mass of drug injected in each case was the same (30 mg). As indicated by the lower values of the mean fluorescein concentration at 24 hours, elimination of fluorescein was faster for the 100 mL central and lens-displaced injections than for the 15mL injections. However, when the fluorescein was injected closer to the retina or hyaloid membrane, elimination was higher for the 15 mL injections. These results are consistent with the fact that fluorescein is primarily eliminated across the retina. When the 15 mL injection is placed next to the retina, the flux of drug across the retina immediately after the injection is faster than for the 100 mL injection, due to the higher concentration within the 15 mL injection. This is illustrated by Figure 11, which shows the concentration of fluorescein adjacent to the retina on the symmetry axis of the vitreous following both the 15 and 100 mL retina-displaced injections. For the central and lens-displaced injections of fluorescein, elimination was higher for the 100 mL injection than for the 15 mL injection. In these cases, the 100 mL injection produces a higher concentration at the surface of the retina than the 15 mL injection, resulting in a higher rate of elimination. For injections of fluorescein glucuronide, the same trends were observed. Since fluorescein glucuronide is eliminated

Figure 11 Concentration of fluorescein at the vitreous site adjacent to the retina following a 15 or 100 mL injection adjacent the retina on symmetry axis of vitreous. The mass of fluorescein injected in each case was identical, resulting in higher peak concentrations adjacent to the retina following the 15 mL injection case and, therefore, a higher initial loss of fluorescein across the retina.

Figure 11 Concentration of fluorescein at the vitreous site adjacent to the retina following a 15 or 100 mL injection adjacent the retina on symmetry axis of vitreous. The mass of fluorescein injected in each case was identical, resulting in higher peak concentrations adjacent to the retina following the 15 mL injection case and, therefore, a higher initial loss of fluorescein across the retina.

mainly across the hyaloid membrane, the 15 mL injections placed closer to the hyaloid membrane (hyaloid-displaced and lens-displaced) resulted in lower mean concentrations at 24 hours than the 100 mL injections at the same locations, due to a higher initial rate of elimination across the hyaloid membrane. Figure 12 shows the concentration adjacent to the hyaloid membrane for the 15 and 100 mL hyaloid-displaced injections of fluorescein glucuronide. Similar to fluorescein, when the injection of fluorescein glucur-onide was not placed next to its elimination surface (central and retina-displaced), higher elimination is produced by the 100 mL injection.

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