Clinical Implications of Changes in Injection Conditions

From a clinical perspective, the results of changes in injection conditions are very significant. Retinal damage from excessive drug concentrations is observed periodically following an intravitreal injection. The results of this

Figure 12 Concentration of fluorescein glucuronide at the vitreous site adjacent to the hyaloid membrane following a 15 or 100 mL injection adjacent to the hyaloid membrane. The mass of fluorescein glucuronide injected in each case was identical, resulting in a higher peak concentration, adjacent to the hyaloid membrane following the 15 mL injection case and, therefore, a higher initial loss of fluorescein across the hyaloid membrane.

Figure 12 Concentration of fluorescein glucuronide at the vitreous site adjacent to the hyaloid membrane following a 15 or 100 mL injection adjacent to the hyaloid membrane. The mass of fluorescein glucuronide injected in each case was identical, resulting in a higher peak concentration, adjacent to the hyaloid membrane following the 15 mL injection case and, therefore, a higher initial loss of fluorescein across the hyaloid membrane.

modeling work show that enormous variations in local concentrations can arise due to variations in injection positions, suggesting that small deviations from a central injection position may contribute to retinal damage. For treatment of infectious diseases, a specific minimum inhibitory level of drug must be maintained for a specified length of time to eradicate the infectious agent. Due to the potentially devastating effects of a vitreoretinal infection, the antibiotics are used at the highest possible nontoxic doses (22); however, these studies indicate that a nontoxic dose injected at one location of the vitreous may be toxic if injected in a different location. Furthermore, the time interval the antibiotic drug remains above its therapeutic concentration at a specific site in the vitreous is dependent on the injection location.

The results are also relevant to early clinical trials or experiments with animal models, when the efficacy of new drugs is tested. Significant variability in the results may occur if care is not taken to ensure that the conditions of the intravitreal injections are kept constant. Although the injection positions that were examined in this study are extremes within the anatomy of the eye, a variation of only 5-8 mm from a central injection will produce these extremes. Slight changes in the injection conditions can easily produce these variations. Knowledge of concentration variations that are present at different sites within the vitreous will facilitate the optimization of administration techniques for diseases that affect the posterior segment of the eye.

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