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Morphologic changes in the retina after selective retina therapy

  • Basic Science
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Abstract

Purpose

To investigate structural changes in the retina by histologic evaluation and in vivo spectral domain optical coherence tomography (SD-OCT) following selective retina therapy (SRT) controlled by optical feedback techniques (OFT).

Methods

SRT was applied to 12 eyes of Dutch Belted rabbits. Retinal changes were assessed based on fundus photography, fluorescein angiography (FAG), SD-OCT, light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) at each of the following time points: 1 h, and 1, 3, 7, 14 and 28 days after SRT. BrdU (5’-bromo-2’-deoxy-uridine) incorporation assay was also conducted to evaluate potential proliferation of RPE cells.

Results

SRT lesions at1 h after SRT were ophthalmoscopically invisible. FAG showed leakage in areas corresponding to SRT lesions, and hyperfluorescence disappeared after 7 days. SD-OCT showed that decreased reflectivity corresponding to RPE damage was restored to normal over time in SRT lesions. Histologic analysis revealed that the damage in SRT lesions was primarily limited to the retinal pigment epithelium (RPE) and the outer segments of the photoreceptors. SEM and TEM showed RPE cell migration by day 3 after SRT, and restoration of the RPE monolayer with microvilli by 1 week after SRT. At 14 and 28 days, ultrastructures of the RPE, including the microvilli and tight junctions, were completely restored. The outer segments of the photoreceptors also recovered without sequelae. Interdigitation between the RPE and photoreceptors was observed. BrdU incorporation assay revealed proliferation of RPE on day 3 after SRT, and peak proliferation was observed on day 7 after SRT.

Conclusion

Based on multimodal imaging and histologic assessment, our findings demonstrate that SRT with OFT could selectively target the RPE without damaging the neurosensory retina. Therefore, the use of SRT with OFT opens the door to the possibility of clinical trials of well-defined invisible and nondestructive retina therapy, especially for macular disease.

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Author notes

    Authors and Affiliations

    1. Department of Ophthalmology, Kyung Hee University Hospital, Kyung Hee University, 23, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea

      Ji Ho Yang, Seung-Young Yu, Tae Gi Kim & Hyung Woo Kwak

    2. Department of Ophthalmology, Eulji University College of Medicine, Daejeon, Republic of Korea

      Eung Suk Kim

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    1. Ji Ho Yang
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    2. Seung-Young Yu
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    3. Tae Gi Kim
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    Correspondence to Hyung Woo Kwak.

    Ethics declarations

    All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in this study involving animals were in accordance with the ethical standards of the institution or practice at which the study was conducted.

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    The authors received no financial support for this research.

    Conflict of interest

    All authors involved in this study certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; or expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

    Additional information

    Ji Ho Yang and Seung-Young Yu contributed equally to this work.

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    Yang, J.H., Yu, SY., Kim, T.G. et al. Morphologic changes in the retina after selective retina therapy. Graefes Arch Clin Exp Ophthalmol 254, 1099–1109 (2016). https://doi.org/10.1007/s00417-016-3331-0

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    • DOI: https://doi.org/10.1007/s00417-016-3331-0

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