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Evaluation of Parapapillary Choroidal Microvasculature Dropout and Progressive Retinal Nerve Fiber Layer Thinning in Patients With Glaucoma.

ABSTRACT: 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.

SUBMITTER: Kim JA

PROVIDER: S-EPMC6547096 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To 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.Prospective, observational cohort study.Glaucoma 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.Global 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.The rate of RNFL thinning and the probability of developing VFD.Four 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 ?m/year vs. -0.82 ?m/year; P<0.001). The joint longitudinal survival model showed that each 1-?m/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).The 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-?m/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.

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.

Project description:ObjectiveTo investigate whether fibromyalgia induces axonal damage in the optic nerve that can be detected using optical coherence tomography (OCT), as the retinal nerve fiber layer (RNFL) is atrophied in patients with fibromyalgia compared with controls.MethodsFibromyalgia patients (n = 116) and age-matched healthy controls (n = 144) were included in this observational and prospective cohort study. All subjects underwent visual acuity measurement and structural analysis of the RNFL using two OCT devices (Cirrus and Spectralis). Fibromyalgia patients were evaluated according to Giesecke's fibromyalgia subgroups, the Fibromyalgia Impact Questionnaire (FIQ), and the European Quality of Life-5 Dimensions (EQ5D) scale. We compared the differences between fibromyalgia patients and controls, and analyzed the correlations between OCT measurements, disease duration, fibromyalgia subgroups, severity, and quality of life. The impact on quality of life in fibromyalgia subgroups and in patients with different disease severity was also analyzed.ResultsA significant decrease in the RNFL was detected in fibromyalgia patients compared with controls using the two OCT devices: Cirrus OCT ganglion cell layer analysis registered a significant decrease in the minimum thickness of the inner plexiform layer (74.99±16.63 vs 79.36±3.38 ?m, respectively; p = 0.023), nasal inferior, temporal inferior and temporal superior sectors (p = 0.040; 0.011 and 0.046 respectively). The Glaucoma application of the Spectralis OCT revealed thinning in the nasal, temporal inferior and temporal superior sectors (p = 0.009, 0.006, and 0.002 respectively) of fibromyalgia patients and the Axonal application in all sectors, except the nasal superior and temporal sectors. The odds ratio (OR) to estimate the size effect of FM in RNFL thickness was 1.39. RNFL atrophy was detected in patients with FIQ scores <60 (patients in early disease stages) compared with controls in the temporal inferior sector (78.74±17.75 vs 81.65±3.61; p = 0.020) and the temporal superior sector (78.20±14.50 vs 80.74±3.88; p = 0.039) with Cirrus OCT; in the temporal inferior sector (145.85±24.32 vs 150.18±19.71; p = 0.012) and temporal superior sector (131.54±20.53 vs 138.13±16.67; p = 0.002) with the Glaucoma application of the Spectralis OCT; and in all sectors, except the average, nasal superior, and temporal sectors, and parameters with the Axonal application of the Spectralis OCT. Temporal inferior RNFL thickness was significantly reduced in patients with severe fibromyalgia (FIQ?60) compared with patients with mild fibromyalgia (FIQ<60; 145.85±24.32 vs 138.99±18.09 ?m, respectively; 145.43±13.21 vs 139.85±13.09 ?m, p = 0.032 with the Glaucoma application and p = 0.021 with the Axonal application). The subgroup with biologic fibromyalgia exhibited significant thinning in the temporal inferior and superior sectors (115.17±20.82 ?m and 117.05±24.19 ?m, respectively) compared with the depressive (130.83±22.97 ?m and 127.71±26.10 ?m, respectively) and atypical (128.60±26.54 ?m and 125.55±23.65 ?m, respectively) subgroups (p = 0.005 and 0.001 respectively).ConclusionsFibromyalgia causes subclinical axonal damage in the RNFL that can be detected using innocuous and non-invasive OCT, even in the early disease stages. The impact on the RNFL in the temporal sectors is greater in patients with biologic fibromyalgia, suggesting the presence of neurodegenerative processes in this subgroup of patients with fibromyalgia.

Project description:PurposeTo investigate factors associated with dropout of the parapapillary deep retinal layer microvasculature assessed by optical coherence tomography angiography (OCTA) in glaucomatous eyes.DesignCross-sectional study.ParticipantsSeventy-one eyes from 71 primary open-angle glaucoma (POAG) patients with β-zone parapapillary atrophy (βPPA) enrolled in the Diagnostic Innovations in Glaucoma Study.MethodsParapapillary deep-layer microvasculature dropout was defined as a complete loss of the microvasculature located within the deep retinal layer of the βPPA from OCTA-derived optic nerve head vessel density maps by standardized qualitative assessment. Circumpapillary vessel density (cpVD) within the retinal nerve fiber layer (RNFL) also was calculated using OCTA. Choroidal thickness and presence of focal lamina cribrosa (LC) defects were determined using swept-source optical coherence tomography.Main outcome measuresPresence of parapapillary deep-layer microvasculature dropout. Parameters including age, systolic and diastolic blood pressure, axial length, intraocular pressure, disc hemorrhage, cpVD, visual field (VF) mean deviation (MD), focal LC defects βPPA area, and choroidal thickness were analyzed.ResultsParapapillary deep-layer microvasculature dropout was detected in 37 POAG eyes (52.1%). Eyes with microvasculature dropout had a higher prevalence of LC defects (70.3% vs. 32.4%), lower cpVD (52.7% vs. 58.8%), worse VF MD (-9.06 dB vs. -3.83 dB), thinner total choroidal thickness (126.5 μm vs. 169.1 μm), longer axial length (24.7 mm vs. 24.0 mm), larger βPPA (1.2 mm2 vs. 0.76 mm2), and lower diastolic blood pressure (74.7 mmHg vs. 81.7 mmHg) than those without dropout (P < 0.05, respectively). In the multivariate logistic regression analysis, higher prevalence of focal LC defects (odds ratio [OR], 6.27; P = 0.012), reduced cpVD (OR, 1.27; P = 0.002), worse VF MD (OR, 1.27; P = 0.001), thinner choroidal thickness (OR, 1.02; P = 0.014), and lower diastolic blood pressure (OR, 1.16; P = 0.003) were associated significantly with the dropout.ConclusionsSystemic and ocular factors including focal LC defects more advanced glaucoma, reduced RNFL vessel density, thinner choroidal thickness, and lower diastolic blood pressure were factors associated with the parapapillary deep-layer microvasculature dropout in glaucomatous eyes. Longitudinal studies are required to elucidate the temporal relationship between parapapillary deep-layer microvasculature dropout and systemic and ocular factors.

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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Evaluation of Parapapillary Choroidal Microvasculature Dropout and Progressive Retinal Nerve Fiber Layer Thinning in Patients With Glaucoma.

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