Although photoacoustic microscopy (PAM) and optical coherence tomography (OCT) allow visualization of the retinal microvasculature, distinguishing early neovascularization from adjacent vessels remains challenging. Herein, gold nanostars (GNSs) functionalized with an RGD peptide were utilized as multimodality contrast agents for both PAM and OCT. GNSs have great absorption and scattering characteristics in the near-infrared region where most vasculature and tissue generates a less intrinsic photoacoustic signal while having a small size, excellent biocompatibility in vivo, and great photostability under nanosecond pulsed laser illumination. This enabled visualization and differentiation of individual microvasculature in vivo using multimodal PAM and OCT imaging. Detailed three-dimensional imaging of GNSs was achieved in an important choroidal neovascularization model in living rabbits. Through the administration of GNSs, PA contrast increased up to 17-fold and OCT intensities increased 167%. This advanced molecular-imaging platform with GNSs provides a unique tool for detailed mapping of the pathogenesis of the microvasculature.

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Purpose Corneal neovascularization (CNV) is the invasion of new blood vessels into the avascular cornea, leading to reduced corneal transparency and visual acuity, impaired vision, and even blindness. Current treatment options for CNV are limited. We developed a novel treatment method, termed photo-mediated ultrasound therapy (PUT), that combines laser and ultrasound, and we tested its feasibility for treating CNV in a rabbit model. Methods A suture-induced CNV model was established in New Zealand White rabbits, which were randomly divided into two groups: PUT and control. For the PUT group, the applied light fluence at the corneal surface was estimated to be 27 mJ/cm 2 at 1064-nm wavelength with a pulse duration of 5 ns, and the ultrasound pressure applied on the cornea was 0.43 MPa at 0.5 MHz. The control group received no treatment. Red-free photography and fluorescein angiography were utilized to evaluate the efficiency of PUT. Safety was evaluated by histology and immunohistochemistry. For comparison with the PUT safety results, conventional laser photocoagulation (LP) treatment was performed with standard clinical parameters: 532-nm continuous-wave (CW) laser with 0.1-second pulse duration, 450-mW power, and 75-µm spot size. Results In the PUT group, only 1.8% ± 0.8% of the CNV remained 30 days after treatment. In contrast, 71.4% ± 7.2% of the CNV remained in the control group after 30 days. Safety evaluations showed that PUT did not cause any damage to the surrounding tissue. Conclusions These results demonstrate that PUT is capable of removing CNV safely and effectively in this rabbit model. Translational Relevance PUT can remove CNV safely and effectively.