title: Morphologic changes in the retina after selective retina therapy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Kyung Hee University Hospital, Kyung Hee University, 23, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
authors.forename: Ji Ho
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Kyung Hee University Hospital, Kyung Hee University, 23, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
authors.forename: Seung-Young
authors.initials: SY
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Kyung Hee University Hospital, Kyung Hee University, 23, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
authors.forename: Tae Gi
authors.initials: TG
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Eulji University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Eung Suk
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Kyung Hee University Hospital, Kyung Hee University, 23, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea. hwkwak@khu.ac.kr.
authors.forename: Hyung Woo
authors.initials: HW
authors.lastname: Kwak
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage; D001973:Bromodeoxyuridine / Q000008:administration & dosage; D049109:Cell Proliferation; D004261:DNA Replication; D005451:Fluorescein Angiography; D053685:Laser Therapy; D053844:Lasers, Solid-State / Q000627:therapeutic use*; D008855:Microscopy, Electron, Scanning; D064847:Multimodal Imaging; D010781:Photography; D011817:Rabbits; D012160:Retina / Q000473:pathology / Q000601:surgery*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery*; D041623:Tomography, Optical Coherence
chemical_list: D000963:Antimetabolites; D001973:Bromodeoxyuridine
keywords: Neurosensory retina; Optical feedback technique (OFT); Retinal pigment epithelium (RPE); Selective retina therapy (SRT)