PurposeTo determine whether progressive retinal nerve fiber layer (RNFL) loss occurs in the contralateral eye of patients with glaucoma showing unilateral progression according to conventional diagnostic methods.DesignProspective, longitudinal, observational cohort study.ParticipantsThree hundred forty-six eyes of 173 patients (118 eyes with glaucoma and 228 eyes with suspect glaucoma at baseline) followed up for an average of 3.5±0.7 years.MethodsAll subjects underwent standard automated perimetry (SAP; Humphrey Field Analyzer; Carl Zeiss Meditec, Dublin, CA) and spectral-domain (SD) optical coherence tomography (OCT; Spectralis; Heidelberg Engineering, Inc., Carlsbad, CA) in both eyes at 6-month intervals. Eyes were determined as progressing by conventional methods if there was progression on masked grading of optic disc stereophotographs or SAP Guided Progression Analysis (GPA; Carl Zeiss Meditec; "likely progression"). Rates of change in SD OCT average RNFL thickness were obtained using a linear mixed effects model. Rate of global loss was calculated using a random coefficient model and compared for nonprogressing patients, progressing eyes, and fellow eyes of unilateral progressing patients.Main outcomes measuresRate of change in global RNFL thickness.ResultsThirty-nine subjects showed evidence of unilateral progression by GPA, disc photographs, or both during follow-up. Mean ± standard error rate of RNFL loss in eyes progressing by conventional methods was -0.89±0.22 μm/year (P<0.001). The contralateral eyes of these subjects also showed significant loss of RNFL over time (-1.00±0.20 μm/year; P<0.001). One hundred thirty-four subjects did not show progression by conventional methods in either eye. These eyes also showed a significant decline over time in average RNFL thickness (-0.71±0.09 μm/year; P<0.001); however, the rate of change in these eyes was slower than that of the contralateral eye of patients showing unilateral progression (P<0.001).ConclusionsLoss of RNFL thickness was seen in a substantial number of contralateral eyes of glaucoma patients showing unilateral progression by conventional methods. These findings indicate that assessment of RNFL thickness by SD OCT may show progressive glaucomatous damage that is not detected by visual fields or optic disc stereophotography