Identification of anomalous features of intravitreal injections using micro-computed tomography.

PURPOSE: To identify anomalous features that impact drug delivery in the eye as a result of intravitreal injections using micro-computed tomography imaging. METHODS: Three-dimensional micro-computed tomography images were acquired following an intravitreal injection of 0.03 mL of contrast agent into ex vivo porcine eyes (n = 24). A baseline scan was acquired prior to injection to detect any abnormalities in the eyes. Acquisition continued at various time intervals up to 230 min post-injection. RESULTS: Air bubbles were clearly visible within the vitreous of 21 eyes following injections. There was a total of 36 air bubbles in the 21 eyes and the volume of the air bubbles ranged from 0.01 µL to 1.50 µL. It was found the size of the air bubbles decreased over the scanning period. Furthermore, many of the injected boli in the eye specimens did not have the commonly assumed spherical shape; rather, a variety of other shapes resulted. CONCLUSION: The presence of air bubbles and inconsistent bolus shapes have indicated that intravitreal injections have high variability. It is only through the realization of these anomalous features that the efficacy of intravitreal drug delivery will be improved through a consistent and accurate injection technique.

A framework for modeling ocular drug transport and flow through the eye using micro-CT.

This study uses micro-computed tomography (micro-CT) imaging for assessment of concentration and transport mechanisms of ocular drug surrogates following intravitreal injection. Injections of an iodinated contrast agent were administered to enucleated porcine eyes prior to scanning over 192 min. Image analysis was performed using signal profiles and regions of interest that corresponded to specific iodine concentrations. Diffusion coefficients of the injected iodine solutions were calculated using nonlinear regression analysis with a diffusion model. There was a predominantly diffusive component in the movement of the contrast to the back of the eye in the horizontal (sagittal & coronal) directions, with ultimate retinal fate observed after 120 min. The diffusion coefficients were found to have a mean of 4.87 × 10(-4) mm(2) s(-1) and standard deviation of 8.39 × 10(-5) mm(2) s(-1) for 150 mg ml(-1) iodine concentration and 6.13 × 10(-4) ± 1.83 × 10(-4) mm(2) s(-1) for 37.5 mg ml(-1) concentration. However, it should be noted that these coefficients were time dependent and were found to decay as the diffusion front interacted with the retinal wall. A real-time, accurate, non-invasive method of tracking a bolus and its concentration is achieved using a high spatial resolution and fast scanning speed micro-CT system.