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Retinal pigment epithelial responses based on the irradiation density of selective retina therapy

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Abstract

Purpose

We evaluated the response of the retinal pigment epithelium (RPE) to high-density (HD) or low-density (LD)-selective retina therapy (SRT) with real-time feedback-controlled dosimetry (RFD) in rabbits.

Methods

Sixteen eyes of 8 Chinchilla Bastard rabbits underwent SRT with RFD (527-nm wavelength, 1.7-μs pulse duration), using automatically titrated pulse energy, by using optoacoustic dosimetry or real-time reflectometry. Fifty-six 25-μJ SRT, including LD-SRT (1-spot or 2-spot-spacing) and HD-SRT (4-spot, 7-spot, or 9-spot-no-spacing), were applied per eye. Color fundus photography and fundus fluorescein angiography (FFA) were used to confirm SRT spots 1-h post-SRT. Light microscopy and scanning electron microscopy (SEM) were performed at 2-h, 3-day, 7-day, and 1-month post-treatment.

Results

We tested 896 spots irradiated by SRT with RFD and confirmed that SRT lesions were adequate, based on invisibility on fundoscopy and visibility on FFA. On SEM, at 2-h post-SRT, flattened RPE cells were observed in the center of the SRT lesion. While normal RPE cells were clearly observed between LD-SRT lesions, healthy RPE cells were rare in HD-SRT lesions at 2-h post-treatment. At 7-day post-SRT, SEM revealed completely restored LD-SRT lesions with small or large RPE cells with microvilli, whereas HD-SRT lesions were covered with RPE cells without microvilli. At 1-month post-SRT, SEM revealed restored RPE cells with microvilli in HD-SRT lesions. On light microscopy, both HD- and LD-SRT lesions were completely restored with adjacent RPE cells and spared photoreceptors at 1-month post-treatment.

Conclusions

Although both HD- and LD-SRT lesions had recovered at 1-month post-SRT, LD-SRT lesions healed faster than HD-SRT lesions.

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Funding

This study was supported by the grant from South Korean Government’s Ministry of Trade, Industry and Energy (M000004912–00192937). This animal study was supported by Research Institute of Medical Science of Yeouido St. Mary’s hospital.

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Authors and Affiliations

Authors

Contributions

Conceived and designed the experiments: Young-Jung Roh; Performed the treatment: Young-Jung Roh; Analyzed the data: Seung Hee Jeon, Minhee Kim, Young-Jung Roh; Contributed reagents/materials/analysis tools: Seung Hee Jeon, Minhee Kim; Wrote the paper: Seung Hee Jeon, Minhee Kim, Young-Jung Roh; Approved final version of the manuscript: Seung Hee Jeon, Minhee Kim, Young-Jung Roh.

Corresponding author

Correspondence to Young-Jung Roh.

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Conflict of interest

YJ Roh has a patent related to real-time feedback dosimetry in South Korea, which is under the PCT application process. Lutronic and our research team jointly received funds from an international research and development project from the South Korean Government’s Ministry of Trade, Industry, and Energy (M000004912-00192937). Lutronic had a role in technical support.

Ethical approval

This study followed the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and was approved by the Institutional Animal Care and Use Committee of the Catholic University of Korea.

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Jeon, S., Kim, M. & Roh, YJ. Retinal pigment epithelial responses based on the irradiation density of selective retina therapy. Graefes Arch Clin Exp Ophthalmol 259, 101–111 (2021). https://doi.org/10.1007/s00417-020-04887-2

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