title: Risk of Visual Field Progression in Glaucoma Patients with Progressive Retinal Nerve Fiber Layer Thinning: A 5-Year Prospective Study.
abstract: To investigate whether progressive retinal nerve fiber layer (RNFL) thinning is predictive of progressive visual field (VF) loss in glaucoma.
  
  
  
  Prospective study.
  
  
  
  A total of 139 primary open-angle glaucoma patients (240 eyes) followed up for ≥5 years.
  
  
  
  Retinal nerve fiber layer imaging and VF testing were performed at ∼4-month intervals. Progressive RNFL thinning was determined by event analysis (Guided Progression Analysis [GPA]) and trend analysis (Trend-based Progression Analysis [TPA]) of serial registered RNFL thickness maps. VF progression was detected according to the Early Manifest Glaucoma Trial (EMGT) ("likely progression") and pointwise linear regression (PLR) criteria (≥3 contiguous locations with sensitivity change <0 decibels [dB]/year at P < 0.01). Hazard ratios (HRs) for predicting VF progression were calculated by Cox proportional hazard modeling with progressive RNFL thinning as a time-dependent covariate. The specificity of GPA/TPA for detection of RNFL changes was determined by the proportion of eyes with significant RNFL thinning/thickening in 25 normal subjects followed weekly for 8 consecutive weeks and the proportion with significant RNFL thickening in the glaucoma group.
  
  
  
  The HRs of VF progression.
  
  
  
  A total of 65 (27.1%) and 117 eyes (48.8%) had progressive RNFL thinning based on GPA and TPA, respectively, and 30 (12.5%) and 39 eyes (16.3%) had VF progression per the EMGT and PLR criteria, respectively, during follow-up. Eyes with progressive RNFL thinning had lower VF survival estimates and a faster decline of visual field index than eyes without. Progressive RNFL thinning predicted the development of VF progression with HRs of 8.44 (95% confidence interval, 3.30-21.61) (EMGT criteria) and 5.11 (2.51-10.42) (PLR criteria) for TPA and 3.95 (1.74-8.93) (EMGT criteria) and 3.81 (1.83-7.92) (PLR criteria) for GPA after controlling for baseline covariates. The specificities of GPA and TPA were 100% (83.4%-100.0%) in the normal group and 81.7% (76.2%-86.4%) and 84.2% (78.9%-88.6%), respectively, in the glaucoma group.
  
  
  
  Progressive RNFL thinning determined by GPA and TPA is predictive of detectable functional decline in glaucoma. This finding underscores the significance of detecting progressive RNFL thinning and its relevance to initiate or augment treatment for glaucoma patients. Regulatory authorities may consider progressive RNFL thinning as an outcome measure in clinical trials for evaluation of glaucoma treatment.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; Department of Mathematics and Statistics, Hang Seng Management College, Hong Kong, People's Republic of China.
authors.forename: Marco
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: Hamilton Glaucoma Center and the Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, La Jolla, California.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Weinreb
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Gilda
authors.initials: G
authors.lastname: Lai
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Vivian
authors.initials: V
authors.lastname: Chiu
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China. Electronic address: tlims00@hotmail.com.
authors.forename: Christopher Kai-Shun
authors.initials: CK
authors.lastname: Leung
mesh_terms: D000368:Aged; D018450:Disease Progression; D005189:False Positive Reactions; D005260:Female; D005500:Follow-Up Studies; D005902:Glaucoma, Open-Angle / Q000175:diagnosis*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009898:Optic Disk / Q000473:pathology; D009901:Optic Nerve Diseases / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012165:Retinal Ganglion Cells / Q000473:pathology*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D041623:Tomography, Optical Coherence / Q000379:methods; D014065:Tonometry, Ocular; D014786:Vision Disorders / Q000175:diagnosis*; D058609:Visual Field Tests; D014794:Visual Fields