Photo-Mediated Ultrasound Therapy for the Treatment of Corneal Neovascularization in Rabbit Eyes

Abstract

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.

Photo‐mediated ultrasound therapy for the treatment of retinal neovascularization in rabbit eyes

“…It can be achieved by measuring the traveling time of a laser-induced photoacoustic wave propagating from the target sample to the HIFU transduce as described previously. 23,25,27 To ensure the accuracy of measurement, the laser system outputted a 532 nm laser instead of 1064 nm during the measurement procedure, benefiting from the strong optical absorption of hemoglobin at 532 nm. When the switch in Figure 1A was connected to the position "2," the produced photoacoustic signal can be received by the HIFU transducer, then amplified by a pulser/receiver (PR 5072; Olympus), and finally displayed on an oscilloscope (TDS540; Tektronix).…”

“…21 Previously, we demonstrated the efficacy of PUT in safely removing neovascularization in both the choroid and the cornea of rabbit eyes. [21][22][23]25 In this study, PUT was applied to the treatment of RNV for the first time. The feasibility of PUT for RNV was tested via experiments on a DL-AAA induced RNV model in both New Zealand white (NZW) rabbits and Dutch Belted pigmented (DBP) rabbits, and the safety was evaluated by histology.…”

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“…For instance, the axial length (i.e., 18 mm), corneal thickness (540 to 560 μm), and curvature (8.3 to 9.0 mm in base curve radius) share many similarities to the human eye. In addition, a suture-induced rabbit CNV model has been well established to provide pathological similarity with human CNV ( 37 ). The animal procedures are as follows.…”

“…The VD was determined by counting each pixel along with the segmented CNV vessels. The relative VD at each time point was determined by normalizing the VD post-therapy to the VD pre-therapy as the following formula ( 37 )%VD=VD at the time post-therapyVD pre-therapy×100…”

“…For comparison, the current standard therapy, such as laser photocoagulation surgery, was implemented ( 37 ). A total of six rabbits were treated by applying a CW laser with pulse duration = 0.1 s, power = 450 mW, and laser spot size = 75 μm using the VITRA 532 nm Photocoagulator (Quantel Medical) equipped with a Zeiss SL130 Slit lamp adapter.…”