title: Nondamaging Retinal Laser Therapy: Rationale and Applications to the Macula.
abstract: Retinal photocoagulation and nondamaging laser therapy are used for treatment of macular disorders, without understanding of the response mechanism and with no rationale for dosimetry. To establish a proper titration algorithm, we measured the range of tissue response and damage threshold. We then evaluated safety and efficacy of nondamaging retinal therapy (NRT) based on this algorithm for chronic central serous chorioretinopathy (CSCR) and macular telangiectasia (MacTel).
  
  
  
  Retinal response to laser treatment below damage threshold was assessed in pigmented rabbits by expression of the heat shock protein HSP70 and glial fibrillary acidic protein (GFAP). Energy was adjusted relative to visible titration using the Endpoint Management (EpM) algorithm. In clinical studies, 21 eyes with CSCR and 10 eyes with MacTel were treated at 30% EpM energy with high spot density (0.25-diameter spacing). Visual acuity, retinal and choroidal thickness, and subretinal fluid were monitored for 1 year.
  
  
  
  At 25% EpM energy and higher, HSP70 was expressed acutely in RPE, and GFAP upregulation in Müller cells was observed at 1 month. Damage appeared starting at 40% setting. Subretinal fluid resolved completely in 81% and partially in 19% of the CSCR patients, and visual acuity improved by 12 ± 3 letters. Lacunae in the majority of MacTel patients decreased while preserving the retinal thickness, and vision improved by 10 letters.
  
  
  
  Heat shock protein expression in response to hyperthermia helps define the therapeutic window for NRT. Lack of tissue damage enables high-density treatment to boost clinical efficacy, therapy in the fovea, and retreatments to manage chronic diseases.
authors.affiliation: Department of Ophthalmology, Federal University Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lavinsky
authors.affiliation: Department of Applied Physics, Stanford University, Stanford, California, United States 3Hansen Experimental Physics Laboratory, Stanford University, Stanford, California, United States.
authors.forename: Jenny
authors.initials: J
authors.lastname: Wang
authors.affiliation: Hansen Experimental Physics Laboratory, Stanford University, Stanford, California, United States 4Department of Ophthalmology, Stanford University, Stanford, California, United States.
authors.forename: Philip
authors.initials: P
authors.lastname: Huie
authors.affiliation: Department of Ophthalmology, Stanford University, Stanford, California, United States.
authors.forename: Roopa
authors.initials: R
authors.lastname: Dalal
authors.affiliation: Department of Ophthalmology, Stanford University, Stanford, California, United States 5Department of Ophthalmology, Kangwon National University, Chuncheon, South Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Stanford University, Stanford, California, United States 6Department of Ophthalmology, Gachon University Gil Medical Center, Incheon, South Korea.
authors.forename: Dae Yeong
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Hansen Experimental Physics Laboratory, Stanford University, Stanford, California, United States 4Department of Ophthalmology, Stanford University, Stanford, California, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Palanker
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020342:Finite Element Analysis; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D053685:Laser Therapy / Q000379:methods*; D008266:Macula Lutea / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008268:Macular Degeneration / Q000175:diagnosis / Q000378:metabolism / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011817:Rabbits; D013997:Time Factors; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity
chemical_list: D050884:HSP72 Heat-Shock Proteins