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Association Between Lamina Cribrosa Defects and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma.

ABSTRACT: Importance:Certain features of the lamina cribrosa may be associated with increased risk of glaucoma progression. Objectives:To compare the rates of retinal nerve fiber layer (RNFL) thinning in patients with open-angle glaucoma with or without lamina cribrosa (LC) defects and to evaluate factors associated with the rate of glaucoma progression in eyes with LC defects. Design, Setting, and Participants:This longitudinal cohort study designed in September 2017 and conducted at a tertiary glaucoma center in California included 51 eyes of 43 patients with LC defects and 83 eyes of 68 patients without LC defects followed up for a mean (SD) of 3.5 (0.8) years from April 2012 to May 2017. Main Outcomes and Measures:Focal LC defects were detected using swept-source optical coherence tomographic images. All participants underwent visual field testing and spectral-domain optical coherence tomography for RNFL thickness measurements every 6 months. Univariate and multivariable random-effects models were used to compare the rate of local and global RNFL loss. Results:The mean (95% CI) age at baseline for individuals with LC defects was 69.5 (65.4 to 73.6) years, and for those without LC defects, it was 69.6 (67.2-72.0) years; 18 individuals (41%) with LC defects and 35 individuals (51%) without LC defects were men; 6 individuals (14%) with LC defects and 17 individuals (25%) without were African American. The mean (95% CI) rate of global RNFL loss in eyes with LC defects was 2-fold faster than that in eyes without LC defects (-0.91 [-1.20 to -0.62] vs -0.48 [-0.65 to -0.31] μm/y; difference, -0.43 [-0.76 to -0.09] μm/y; P = .01). The rate of RNFL thinning was faster in the LC defect sectors than that in the unaffected sectors (difference, -0.90 [95% CI, -1.68 to -0.12] μm/y, P = .02). Thinner corneal thickness was the only factor that was associated with a faster rate of RNFL loss in eyes with LC defects (β2 = -0.09 [95% CI, -0.14 to -0.04], P = .001). No association was found between mean intraocular pressure during follow-up and the mean rate of RNFL thinning in eyes with LC defects (β2, -0.05 [95% CI, -0.17 to 0.06], P = .36). Conclusions and Relevance:These data suggest that LC defects are an independent risk factor for RNFL thinning and that glaucoma progression may correspond topographically to the LC defect location. Thinner corneal thickness in eyes with LC defects was associated with faster further glaucoma progression. In the management of open-angle glaucoma, LC findings may inform the likelihood and rate of glaucoma progression.

SUBMITTER: Moghimi S

PROVIDER: S-EPMC6459105 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo assess whether lamina cribrosa depth (LCD) reduction and the rate of change in LCD over time (ΔLCD/Δt) is associated with retinal nerve fiber layer (RNFL) thickness and the rate of RNFL thinning over time (ΔRNFL/Δt) to test the hypothesis that, in a long term, RNFL thinning occurs irrespectively to the displacement of the lamina cribrosa following glaucoma surgery.MethodsTwenty-nine primary open-angle glaucoma patients underwent glaucoma surgery. Sixteen patients underwent trabeculectomy and 13 patients undertook non-penetrating deep sclerectomy. Images of optic nerve head using spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging technology were obtained preoperatively, at one-, three-, six-month and follow-up postoperative visit from 12 to 29 months after surgery (1pv, 3pv, 6pv, and FUpv, respectively). Correspondingly, measurements of the circumpapillary RNFL thickness were acquired.ResultsIntraocular pressure decreased from 24.0±8.9 to 10.9±3.9mmHg at 6pv (P<0.001) and to 12.7±4.4mmHg at FUpv (P<0.001). LCD was reduced from 465.3±136.4μm to 402.9±126.4μm at 1pv (P<0.001) and maintained similar position at 6pv (394.3±118.4μm; P = 0.170 with respect to 1pv). A significant decrease in the LCD was noted at FUpv (342.8±90.3μm, P<0.001) with respect to 6pv. RNFL thickness increased significantly to 64.9±19.8μm at 1pv (P = 0.005) and subsequently decreased to baseline level at 3pv. Further statistically significant decrease in RNFL thickness with respect to previous visit was found at 6pv and at FUpv (56.4±15.6μm and 55.0±14.0μm, P = 0.023 and P = 0.045, respectively). A thinner RNFL thickness at FUpv was not related to the LCD at FUpv (P = 0.129) but was correlated with ΔLCD/Δt at FUpv (P = 0.003). The ΔRNFL/Δt at FUpv was statistically significantly correlated with ΔLCD/Δt at FUpv (P<0.001).ConclusionsThis is the first study that considers direct correlation between the rate of change in LCD with the rate of RNFL thinning over time. A thinner RNFL thickness following glaucoma surgery was associated with the rate of LCD reduction, not with position of the lamina cribrosa at the FUpv.

Project description:ImportanceEvaluation of structural optic nerve damage is a fundamental part of diagnosis and management of glaucoma. However, the relationship between structural measurements and disability associated with the disease is not well characterized. Quantification of this relationship may help validate structural measurements as markers directly relevant to quality of life.ObjectiveTo evaluate the relationship between rates of retinal nerve fiber layer (RNFL) loss and longitudinal changes in quality of life in glaucoma.Design, setting, and participantsObservational cohort study including 260 eyes of 130 patients with glaucoma followed up for a mean (SD) of 3.5 (0.7) years. All patients had repeatable visual field defects on standard automated perimetry (SAP) at baseline. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was performed annually, and spectral-domain optical coherence tomography and SAP were performed at 6-month intervals. A joint model was used to investigate the association between change in NEI VFQ-25 Rasch-calibrated scores and change in RNFL thickness, adjusting for confounding socioeconomic and clinical variables.Main outcomes and measuresAssociation between change in binocular RNFL thickness (RNFL thickness in the better eye at each point) and change in NEI VFQ-25 scores.ResultsProgressive binocular RNFL thickness loss was associated with worsening of NEI VFQ-25 scores over time. In a multivariable model adjusting for baseline disease severity and the rate of change in binocular SAP sensitivity, each 1-μm-per-year loss of RNFL thickness was associated with a decrease of 1.3 units (95% CI, 1.02-1.56) per year in NEI VFQ-25 scores (P < .001). After adjusting for the contribution from SAP, 26% (95% CI, 12%-39%) of the variability of change in NEI VFQ-25 scores was associated uniquely with change in binocular RNFL thickness. The P value remained less than .001 after adjusting for potential confounding factors.Conclusions and relevanceProgressive binocular RNFL thickness loss was associated with longitudinal loss in quality of life, even after adjustment for progressive visual field loss. These findings suggest that rates of binocular RNFL change are valid markers for the degree of neural loss in glaucoma with significant relationship to glaucoma-associated disability.

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Association Between Lamina Cribrosa Defects and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma.

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