Vitrectomy status significantly alters early intravitreal bevacizumab and vancomycin distribution in ex vivo eyes
Background
Effective ocular drug delivery, particularly for conditions affecting the posterior segment like macular degeneration or diabetic retinopathy, often relies on intravitreal injections. However, the vitreous body acts as a significant barrier, influencing drug pharmacokinetics and requiring frequent, invasive injections. Surgical interventions like vitrectomy, which remove the vitreous, or the use of endotamponades (vitreous substitutes), are known to alter the ocular environment. Understanding how these changes impact the early distribution of therapeutic agents, especially large protein drugs like anti-VEGFs, is crucial for optimizing treatment protocols and improving drug efficacy.
Study Design
Researchers evaluated the early-phase spatial drug distribution of intravitreally injected bevacizumab and vancomycin in ex vivo human and porcine eyes. Porcine eyes were vitrectomized post-mortem and filled with balanced salt solution (BSS), silicone oil, or a hyaluronic acid-based hydrogel. Native non-vitrectomized human and porcine eyes served as controls. Drugs were labeled with Gallium-68 (68-Ga), and PET-CT imaging was performed for up to six hours post-injection to qualitatively and quantitatively assess intravitreal distribution.
Results
Radioactive labeling of bevacizumab and vancomycin with 68-Ga was successfully achieved. Vitrectomized eyes consistently demonstrated an increased early spatial spread for both tested drugs compared to eyes with a native vitreous body. Specifically, the intravitreal filled volume for bevacizumab was 36.5% in vitrectomized eyes versus 16.5% in native eyes (P < 0.0001). Similarly, vancomycin showed a filled volume of 31.8% in vitrectomized eyes compared to 12.0% in native eyes (P = 0.0146).
Key Findings
- Vitrectomized eyes increased early spatial spread of intravitreal bevacizumab from 16.5% (native) to 36.5% (vitrectomized) filled volume (P < 0.0001).
- Vitrectomized eyes increased early spatial spread of intravitreal vancomycin from 12.0% (native) to 31.8% (vitrectomized) filled volume (P = 0.0146).
- Bevacizumab diffused faster than vancomycin in native vitreous body.
- Bevacizumab was not soluble in silicone oil.
- Diffusion in hyaluronic acid-based hydrogel was slower than BSS-filled eyes in the early phase, but comparable to native vitreous for protein drugs.
Why It Matters
This study provides critical insights for clinicians and researchers designing intravitreal injection protocols, particularly for patients who have undergone vitrectomy or received endotamponades. The finding that vitrectomized eyes allow for significantly faster and wider drug distribution suggests that dosing regimens or injection frequencies might need adjustment in these patients. For instance, a lower dose or less frequent injections might achieve similar therapeutic concentrations, potentially reducing treatment burden and risks. The comparable early diffusion of protein drugs in hyaluronic acid-based hydrogels to native vitreous bodies also highlights the potential of these substitutes to maintain drug residence time, unlike BSS or silicone oil.
bevacizumab
vancomycin
vitrectomy
intravitreal-injection
drug-delivery
ophthalmology