Lamina Cribrosa Morphology Predicts Progressive Retinal Nerve Fiber Layer Loss In Eyes with Suspected Glaucoma.
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ABSTRACT:
SUBMITTER: Kim JA
PROVIDER: S-EPMC5768684 | biostudies-other | 2018 Jan
REPOSITORIES: biostudies-other
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Lamina Cribrosa Morphology Predicts Progressive Retinal Nerve Fiber Layer Loss In Eyes with Suspected Glaucoma.
Kim Jeong-Ah JA Kim Tae-Woo TW Weinreb Robert N RN Lee Eun Ji EJ Girard Michaël J A MJA Mari Jean Martial JM
Scientific reports 20180115 1
Although early diagnosis and treatment reduce the risk of blindness from glaucoma, the decision on whether or not to begin treatment in patients with suspected glaucoma is often a dilemma because the majority of patients never develop definite glaucoma. A growing body of evidences suggests that posterior bowing of the lamina cribrosa (LC) is the earliest structural change preceding the retinal nerve fiber layer (RNFL) loss in glaucomatous optic neuropathy. Based on this notion, we conducted a pr ...[more]
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Project description: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.
| S-EPMC6459105 | biostudies-literature
Project description:PurposeTo compare the rates of retinal nerve fiber layer (RNFL) loss in patients suspected of having glaucoma who developed visual field damage (VFD) with those who did not develop VFD and to determine whether the rate of RNFL loss can be used to predict the development of VFD.DesignProspective, observational cohort study.ParticipantsGlaucoma suspects, defined as having glaucomatous optic neuropathy or ocular hypertension (intraocular pressure, >21 mmHg) without repeatable VFD at baseline, from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study.MethodsGlobal and quadrant RNFL thickness (RNFLT) were measured with the Spectralis spectral-domain optical coherence tomography (SD-OCT; Spectralis HRA+OCT [Heidelberg Engineering, Heidelberg, Germany]). Visual field damage was defined as having 3 consecutive abnormal visual fields. The rate of RNFL loss in eyes developing VFD was compared to eyes not developing VFD using multivariate linear mixed-effects models. A joint longitudinal survival model used the estimated RNFLT slope to predict the risk of developing VFD, while adjusting for potential confounding variables.Main outcome measuresThe rate of RNFL thinning and the probability of developing VFD.ResultsFour hundred fifty-four eyes of 294 glaucoma suspects were included. The average number of SD-OCT examinations was 4.6 (range, 2-9), with median follow-up of 2.2 years (0.4-4.1 years). Forty eyes (8.8%) developed VFD. The estimated mean rate of global RNFL loss was significantly faster in eyes that developed VFD compared with eyes that did not develop VFD (-2.02 μm/year vs. -0.82 μm/year; P<0.001). The joint longitudinal survival model showed that each 1-μm/year faster rate of global RNFL loss corresponded to a 2.05-times higher risk of developing VFD (hazard ratio, 2.05; 95% confidence interval, 1.14-3.71; P = 0.017).ConclusionsThe rate of global RNFL loss was more than twice as fast in eyes that developed VFD compared with eyes that did not develop VFD. A joint longitudinal survival model showed that a 1-μm/year faster rate of RNFLT loss corresponded to a 2.05-times higher risk of developing VFD. These results suggest that measuring the rate of SD-OCT RNFL loss may be a useful tool to help identify patients who are at a high risk of developing visual field loss.
| S-EPMC4310561 | biostudies-literature
Project description:To determine whether focal abnormalities of the lamina cribrosa (LC) are present in glaucomatous eyes with localized retinal nerve fiber layer (RNFL) defects.Cross-sectional, observational study.We analyzed 20 eyes of 14 subjects with localized RNFL defects detected by masked grading of stereophotographs and 40 eyes of 25 age-matched healthy subjects recruited from the Diagnostic Innovations in Glaucoma Study at the University of California, San Diego.All eyes had stereoscopic optic disc photography and in vivo LC imaging using enhanced depth imaging optical coherence tomography (EDI-OCT). Two masked graders identified focal LC defects defined by a standardized protocol using 48 radial scan EDI-OCT images. The kappa coefficient was calculated as a measure of the reliability of interobserver agreement.The number of focal LC defects and the relationship between the location of LC defects and the location of localized RNFL defects.Of 20 eyes with a localized RNFL defect, 15 (75%) had ?1 LC defect compared with only 1 of 40 healthy eyes (3%). There were 13 eyes with localized RNFL defects that had 1 LC defect, 1 eye with 2 LC defects, and 1eye with 3 LC defects. The largest area LC defect was present in a radial line EDI-OCT scan corresponding with a localized RNFL defect in 13 of 15 eyes (87%). There was good agreement between graders as to whether an eye had an LC defect (kappa = 0.87; 95% confidence interval [CI], 0.73-1.00; P<0.001) and the location of the largest defect (kappa = 0.72; 95% CI, 0.44-1.00; P<0.001).Focal defects of the LC were frequently visible in glaucomatous eyes with localized RNFL defects. Focal abnormalities of the LC may be associated with focal retinal nerve fiber damage.
| S-EPMC3947348 | biostudies-literature
Project description:PurposeTo investigate the relationship between corneal hysteresis (CH) and progressive retinal nerve fiber layer (RNFL) loss in a cohort of patients with glaucoma followed prospectively over time.DesignProspective observational cohort study.MethodsOne hundred and eighty-six eyes of 133 patients with glaucoma were followed for an average of 3.8 ± 0.8 years, with a median of 9 visits during follow-up. The CH measurements were acquired using the Ocular Response Analyzer (Reichert Instruments, Depew, New York, USA) and RNFL measurements were obtained at each follow up visit using spectral-domain optical coherence tomography (SDOCT). Random-coefficient models were used to investigate the relationship between baseline CH, central corneal thickness (CCT), average intraocular pressure (IOP), and rates of RNFL loss during follow-up, while adjusting for potentially confounding factors.ResultsAverage baseline RNFL thickness was 76.4 ± 18.1 μm and average baseline CH was 9.2 ± 1.8 mm Hg. CH had a significant effect on rates of RNFL progression. In the univariable model, including only CH as a predictive factor along with time and their interaction, each 1 mm Hg lower CH was associated with a 0.13 μm/year faster rate of RNFL decline (P = .011). A similar relationship between low CH and faster rates of RNFL loss was found using a multivariable model accounting for age, race, average IOP, and CCT (P = .015).ConclusionsLower CH was significantly associated with faster rates of RNFL loss over time. The prospective longitudinal design of this study provides further evidence that CH is an important factor to be considered in the assessment of the risk of progression in patients with glaucoma.
| S-EPMC5758050 | biostudies-literature
Project description:ObjectiveTo examine microcystic inner nuclear layer (INL) changes in glaucomatous eyes and to determine associated factors.DesignRetrospective, cross-sectional, observational study.MethodsTwo hundred seventeen eyes of 133 patients with primary open angle glaucoma (POAG), 41 eyes of 32 patients with preperimetric glaucoma and 181 normal eyes of 117 subjects were ultimately included. Microcystic INL lesions were examined with infrared fundus images and with 19 vertical spectral domain optical coherence tomography (SD-OCT) images in the macular area.ResultsMicrocystic INL changes were observed in 6.0% of eyes with POAG, but none of the normal eyes or eyes with preperimetric glaucoma showed microcystic INL changes. The proportion of eyes with advanced glaucoma was significantly larger (P = 0.013) in eyes with microcystic lesions than without. The visual field mean deviation (MD) slope was also significantly worse (P = 0.027) in eyes with microcystic lesions. No significant differences were observed in age, sex, refraction, axial length, intraocular pressure, or MD value between eyes with and without microcystic INL lesions. In several cases, microcystic INL lesions occurred along with glaucomatous visual field progression. The retinal nerve fiber layer (RNFL) thickness (P = 0.013) and ganglion cell layer (GCL) + inner plexiform layer thickness (P = 0.023) were significantly lower in areas with microcystic lesions than without. The INL was also significantly thicker (P = 0.002) in areas with microcystic lesions.ConclusionsMicrocystic INL lesions in glaucomatous eyes are closely associated with RNFL and GCL thinning and correlated with worse MD slope. These INL lesions may indicate focal and progressive damage in glaucoma.
| S-EPMC4467090 | biostudies-literature
Project description:PRéCIS:: Bruch's membrane opening-minimum rim width (BMO-MRW) and circumpapillary retinal nerve fiber layer (cRNFL) thickness measures may be improved by comparing probability levels and accounting for blood vessel locations.PurposeTo understand the differences between 2 optical coherence tomography measures of glaucomatous damage: the BMO-MRW and cRNFL thickness.Materials and methodsOptical coherence tomography circle scans were obtained for an early glaucoma group (EG) of 88 eyes (88 patients) with 24-2 mean deviation better than -6.0 dB, and a broader group (BG) of 188 eyes (110 patients) with 24-2 mean deviation from -0.15 to -27.0 dB. On the basis of a commercial report, the cRNFL and BMO-MRW of each hemidisc was classified as abnormal if either of the 2 superior (inferior) sectors, temporal superior and nasal superior (temporal inferior and nasal inferior), was yellow or red (P<5%); and as normal if both were green (P≥5%). In addition, a post hoc analysis identified the reasons for disagreements on the basis of the presence (or absence) of glaucomatous damage at a hemidisc level (consensus of 4 experts).ResultsThe BMO-MRW and cRNFL measures agreed in 81.9% (broader group) and 73.9% (EG) of the hemidiscs. In both groups, an abnormal-BMO-MRW/normal-cRNFL disagreement was as common as a normal-BMO-MRW/abnormal-cRNFL. Of the 46 EG hemidisc disagreements, the number of "mistakes" for BMO-MRW (28) was nonsignificantly higher than for cRNFL (18) (P=0.15). Primary causes for disagreement were as follows: borderline significance level, a local defect, and aberrant blood vessel location.ConclusionsAlthough BMO-MRW and cRNFL measures agreed in the majority of hemidiscs, they still disagreed in over 25% of the EG hemidiscs. These measures may be improved by comparing actual probability levels and accounting for blood vessel locations. However, both can miss information available on retinal ganglion cell/retinal nerve fiber layer probability maps.
| S-EPMC8864542 | biostudies-literature
Project description:The aim of this study was to evaluate the regional variations of peripapillary choroidal thickness (PCT) in normal-tension glaucoma (NTG) patients with a retinal nerve fiber layer (RNFL) defect localized to a single superior or inferior hemifield. This is a retrospective, cross-sectional study.Ninety-five NTG patients and 53 normal subjects were divided into 3 groups: 34 eyes with a superior RNFL defect (group A), 61 eyes with an inferior RNFL defect (group B), and 53 normal eyes (group C). The average, quadrant, and clock-hour RNFL thickness (RNFLT) and PCT were measured using spectral-domain optical coherence tomography. Choroidal thickness ratio (CTR) was defined as the ratio of the measured PCT at a quadrant or a clock-hour position to the average PCT of an individual. The PCT, CTR, and RNFLT were compared among 3 groups.The average PCT of NTG patients was thinner compared to that of healthy subjects (154.17 vs. 180.65??m, P?<?.001). Although the average, quadrant, and clock-hour PCTs were not different between groups A and B, the CTR at 11 o'clock was significantly lower in group A compared to that of group B. The 11 o'clock CTR was an independent factor for the initial location of a RNFL defect (P?=?.03).Eyes with NTG showed regional differences in CTR according to the hemisphere location of their initial RNFL damage. Therefore, CTR may be more useful than the absolute PCT value to assess regional PCT differences in eyes with NTG.
| S-EPMC5999483 | biostudies-literature
Project description:Importance:Parapapillary choroidal microvasculature dropout (MvD) is considered one of pathophysiological manifestations of glaucomatous damage. Objective:To evaluate the longitudinal change in the parapapillary choroidal MvD in patients with primary open-angle glaucoma (POAG), and to determine whether this change is associated with progressive retinal nerve fiber layer (RNFL) thinning. Design, Setting, and Participants:This prospective observational case series was conducted at a tertiary referral center in Korea and included 68 patients with POAG who exhibited parapapillary choroidal MvD in en face optical coherence tomography (OCT) angiography (OCTA) images who were enrolled from the ongoing Investigating Glaucoma Progression Study from January 1, 2016, through July 31, 2018. The mean (SD) follow-up period was 2.5 (0.2) years and observers were masked to the clinical characteristics of the participants for measurements. The OCTA images were obtained twice at an interval of at least 2 years, during which the RNFL thickness was measured at least 4 times in serial OCT examinations. Microvasculature dropout was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. The MvD area was measured in the OCTA images obtained at the baseline and the final follow-up. The significance of changes in the MvD area was defined using the 95% Bland-Altman limits of agreement. The rate of RNFL thinning was determined by linear regression of the serial OCT RNFL thickness measurements. Main Outcomes and Measures:The association between the change in the MvD area and the rate of RNFL thinning. Results:Of 68 Korean participants, 37 (54.5%) were women, and the mean (SD) age was 54.3 (13.1) years. Among 68 eyes, 22 (32.4%) showed increases in the MvD area during the follow-up. Faster global RNFL thinning was associated with a larger baseline parapapillary atrophy β-zone (β = -0.55; 95% CI, -0.96 to -0.14; P = .01), disc hemorrhage detection during the follow-up period (β = -0.75; 95% CI, -1.67 to -0.34; P = .001), and a larger increase in the MvD area (β = -4.74; 95% CI, -7.72 to -1.75; P = .002). The MvD area was not associated with the rate of RNFL thinning at baseline or the final follow-up. Conclusions and Relevance:Microvasculature dropout enlargement was associated with progressive RNFL thinning in POAG.
| S-EPMC6547096 | biostudies-literature
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.
| S-EPMC4533995 | biostudies-literature
Project description:Compare performance of normalized reflectance index (NRI) and retinal nerve fiber layer thickness (RNFLT) parameters determined from optical coherence tomography (OCT) images for glaucoma and glaucoma suspect diagnosis.Seventy-five eyes from 71 human subjects were studied: 33 controls, 24 glaucomatous, and 18 glaucoma-suspects. RNFLT and NRI maps were measured using 2 custom-built OCT systems and the commercial instrument RTVue. Using area under the receiver operating characteristic curve, RNFLT and NRI measured in 7 RNFL locations were analyzed to distinguish between control, glaucomatous, and glaucoma-suspect eyes.The mean NRI of the control group was significantly larger than the means of glaucomatous and glaucoma-suspect groups in most RNFL locations for all 3 OCT systems (P<0.05 for all comparisons). NRI performs significantly better than RNFLT at distinguishing between glaucoma-suspect and control eyes using RTVue OCT (P=0.008). The performances of NRI and RNFLT for classifying glaucoma-suspect versus control eyes were statistically indistinguishable for PS-OCT-EIA (P=0.101) and PS-OCT-DEC (P=0.227). The performances of NRI and RNFLT for classifying glaucomatous versus control eyes were statistically indistinguishable (PS-OCT-EIA: P=0.379; PS-OCT-DEC: P=0.338; RTVue OCT: P=0.877).NRI is a promising measure for distinguishing between glaucoma-suspect and control eyes and may indicate disease in the preperimetric stage. Results of this pilot clinical study warrant a larger study to confirm the diagnostic power of NRI for diagnosing preperimetric glaucoma.
| S-EPMC3844555 | biostudies-literature