title: Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity.
abstract: OBJECTIVE
  To evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma (POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  One hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older.
  
  
  METHODS
  Subjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system.
  
  
  METHODS
  Pupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7-14 log photons/cm(2) per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography [HRT]; Heidelberg Engineering, Heidelberg, Germany).
  
  
  RESULTS
  The pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r = -0.44; P = 0.005) as well as HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve head parameters.
  
  
  CONCLUSIONS
  In glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma.
authors: Program in Neuroscience and Behavioral Disorders, Duke-National University of Singapore Graduate Medical School, Singapore, Republic of Singapore.
authors: Annadata V
authors: AV
authors: Rukmini
authors: Program in Neuroscience and Behavioral Disorders, Duke-National University of Singapore Graduate Medical School, Singapore, Republic of Singapore; Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore.
authors: Dan
authors: D
authors: Milea
authors: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
authors: Mani
authors: M
authors: Baskaran
authors: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore.
authors: Alicia C
authors: AC
authors: How
authors: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore.
authors: Shamira A
authors: SA
authors: Perera
authors: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
authors: Tin
authors: T
authors: Aung
authors: Program in Neuroscience and Behavioral Disorders, Duke-National University of Singapore Graduate Medical School, Singapore, Republic of Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore. Electronic address: joshua.gooley@duke-nus.edu.sg.
authors: Joshua J
authors: JJ
authors: Gooley
mesh_terms: D000368:Aged; D044466:Asian People; D003430:Cross-Sectional Studies; D005260:Female; D005902:Glaucoma, Open-Angle / Q000145:classification / Q000175:diagnosis*; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology; D008027:Light; D008297:Male; D008875:Middle Aged; D009887:Ophthalmoscopy; D009901:Optic Nerve Diseases / Q000175:diagnosis*; D011681:Pupil Disorders / Q000175:diagnosis*; D012025:Reflex, Pupillary / Q000528:radiation effects*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D014065:Tonometry, Ocular; D014786:Vision Disorders / Q000175:diagnosis*; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology