Purpose: Neovascularization occurs in eye diseases such as diabetic retinopathy and macular degeneration. To achieve improvement management of these eye diseases, we developed an image-guided photo-mediated ultrasound therapy (PUT) technique which concurrently applies nanosecond laser pulses and millisecond ultrasound bursts to precisely and safely remove microvessels in the eye.
Methods: Via the studies on the chicken embryo and rabbit eye models, the efficacy and the safety of PUT, as a novel anti-vascular technique, were validated. In parallel, we developed an integrated multi-modality imaging system combining photoacoustic microscopy (PAM), optical coherence tomography (OCT), and fluorescence microscopy (FM) for evaluating the neoangiogenesis in the eye. In this work, by combining the multi-modality imaging and the PUT, image-guided treatment of neoangiogenic vessels in the eye including choroidal, retinal, and corneal vasculatures were explored using the clinically relevant rabbit eye models.
Results: The image-guided PUT can precisely and efficiently remove choroidal vasculature by using safe ultrasound pressure and safe laser fluence. After a single treatment, the elimination of choroidal vasculature can sustain up to 4 weeks. The excellent safety was confirmed by histopathological analyses. The elimination of vessels in the treatment region was confirmed by fundus camera and fluorescence angiogram. PAM, by presenting much more vascular details with extremely high image quality, facilitates treatment monitoring and assessment in real time. In addition, during PUT, cavitation signals were observed by OCT, suggesting that OCT, with good sensitivity in detection microbubbles, can be another imaging modality for online monitoring and guidance of PUT.
Conclusion: Image-guided PUT holds promise as a novel, non-invasive method for treating eye neovascularization. With the guidance from the advanced multi-modality imaging, targeted treatment of microvessels in retina, choroidal, or corneal can be achieved with further enhanced safety and further improved efficacy, which is crucial for realizing personalized treatment with optimal outcome.
Funding Support, Disclosures, and Conflict of Interest: This work is supported in part by NIH under the grant numbers of R01EY029489 and 4K12EY022299.