title: Analysis of Inner and Outer Retinal Thickness in Patients Using Hydroxychloroquine Prior to Development of Retinopathy.
abstract: OBJECTIVE
  Retinopathy is a known risk of long-term use of hydroxychloroquine sulfate. However, whether the inner as well as outer retina are involved before retinopathy develops and whether changes in the retina might signal impending toxic effects during screening remain unknown.
  
  
  OBJECTIVE
  To determine the degree of inner and outer retinal involvement in short- and long-term use of hydroxychloroquine before the development of retinopathy.
  
  
  METHODS
  This retrospective medical record review of spectral-domain optical coherence tomography (SD-OCT) findings was performed at an academic medical center. Thirty-two patients without retinopathy and with high-quality SD-OCT images were studied. Twenty-seven patients were age matched (49-65 years old) for comparison of retinal layers among patients who used the drug less than 5 years (n = 12) or longer than 15 years (n = 15) at the initial visit. Populations were also defined (without age limitation) for comparison of change during 25 to 52 months of follow-up among patients with initial use of less than 5 years (n = 7) or longer than 15 years (n = 8). Data were collected from 2010 to 2015.
  
  
  METHODS
  Measurements of inner and outer retinal thickness in SD-OCT images using commercial software and a Stanford pixel-by-pixel segmentation software that also provided topographic maps of thickness dimensions and change.
  
  
  RESULTS
  Thirty-two patients (5 men and 27 women) were included in the analysis. Measurements of inner retinal thickness between short- and long-term hydroxychloroquine users (n = 27) in different retinal regions, and during a median 39 months of follow-up (n = 15), showed no statistically significant differences or change. Similarly, no significant differences or changes were identified in outer retinal thickness except for the final visit of 1 patient who developed focal parafoveal thinning, a toxic effect of hydroxychloroquine use. Cirrus ganglion cell analysis measurements were inaccurate in the presence of outer retinal damage.
  
  
  CONCLUSIONS
  The inner retina appears not to be involved in hydroxychloroquine-induced retinopathy to any clinically relevant degree within the limitations of our sample size. No clinically apparent warning of outer retinal damage was seen in the SD-OCT images of long-term hydroxychloroquine users until the actual appearance of focal retinopathy. Early detection of hydroxychloroquine-induced retinopathy is known to prevent visual acuity loss and serious progression after the therapy is stopped, and these data suggest that screening should seek distinct new areas of retinopathy (shown by topographic thickness maps) rather than long-term progressive thinning.
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Luis
authors.initials: L
authors.lastname: de Sisternes
authors.affiliation: Byers Eye Institute at Stanford, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Julia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Radiology, Stanford University, Stanford, California3Department of Medicine (Biomedical Informatics), Stanford University, Stanford, California.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Rubin
authors.affiliation: Byers Eye Institute at Stanford, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Marmor