Parafoveal thinning of inner retina is associated with visual dysfunction in Lewy body diseases.
ABSTRACT: BACKGROUND:Retinal optical coherence tomography findings in Lewy body diseases and their implications for visual outcomes remain controversial. We investigated whether region-specific thickness analysis of retinal layers could improve the detection of macular atrophy and unravel its association with visual disability in Parkinson's disease. METHODS:Patients with idiopathic Parkinson's disease (n = 63), dementia with Lewy bodies (n = 8), and E46K mutation carriers in the ?-synuclein gene (E46K-SNCA) (n = 4) and 34 controls underwent Spectralis optical coherence tomography macular scans and a comprehensive battery of visual function and cognition tests. We computed mean retinal layer thicknesses of both eyes within 1-, 2-, 3-, and 6-mm diameter macular discs and in concentric parafoveal (1- to 2-mm, 2- to 3-mm, 1- to 3-mm) and perifoveal (3- to 6-mm) rings. Group differences in imaging parameters and their relationship with visual outcomes were analyzed. A multivariate logistic model was developed to predict visual impairment from optical coherence tomography measurements in Parkinson's disease, and cutoff values were determined with receiver operating characteristic analysis. RESULTS:When compared with controls, patients with dementia with Lewy bodies had significant thinning of the ganglion cell-inner plexiform layer complex within the central 3-mm disc mainly because of differences in 1- to 3-mm parafoveal thickness. This parameter was strongly correlated in patients, but not in controls, with low contrast visual acuity and visual cognition outcomes (P
Project description:PurposeThe purpose of the study was to evaluate the factors associated with development of parafoveal scotoma in early myopic normal tension glaucoma (NTG).Patients and methodsNinety-nine myopic NTG patients with mean deviation (MD) >-6.0 decibels (dB) were enrolled. Parafoveal scotoma was defined as a visual field (VF) defect within 10° of fixation with at least one point at P<1% lying at the four innermost central points. Systemic factors, optic disc characteristics including tilt ratio, rotation degree, ?-zone parapapillary atrophy, disc hemorrhage, and peripapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer (mGCIPL) thickness parameters using optical coherence tomography were evaluated. Logistic regression analysis was performed to identify factors associated with the development of parafoveal scotoma.ResultsThe mean spherical equivalent refractive error and MD were -6.07±2.83 diopters and -3.29±1.70?dB, respectively. Among 99 eyes, 42 (42.42%) showed parafoveal scotoma. Eyes with parafoveal scotoma had greater disc tilt, lesser disc rotation, lower MD, thinner minimum mGCIPL, and a higher proportion of VF defect in the superior hemifield than eyes without parafoveal scotoma. Multivariate logistic regression showed that all these parameters were significantly associated with development of parafoveal scotoma (P=0.047, P=0.011, P=0.032, P=0.010, and P=0.001, respectively).ConclusionIn addition to the previously reported risk factors, optic disc characteristics, such as tilt ratio and optic disc rotation, were also significantly associated with development of parafoveal scotoma in patients with myopic NTG.
Project description:PURPOSE:To categorize the structural progression pattern of glaucoma, as detected by optical coherence tomography guided progression analysis, with respect to the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL). METHODS:One hundred sixty-four eyes with primary open-angle glaucoma were studied. The structural progression pattern evaluated by optical coherence tomography guided progression analysis was classified using hierarchical cluster analysis. The clinical parameters, patterns of structural progression, and visual field (VF) changes were compared among the groups. RESULTS:Three groups were included: stable, progressive peripapillary RNFL thinning without macular GCIPL involvement, and progressive thinning of both the peripapillary RNFL and macular GCIPL. The third group, those with progressive peripapillary RNFL and macular GCIPL thinning, showed more progressive peripapillary RNFL thinning in the inferotemporal area and VF progression in the parafoveal area. Conversely, the 12 and 6 o'clock areas were the most common locations of progressive peripapillary RNFL thinning in the group without macular GCIPL involvement. CONCLUSIONS:Structural progression patterns of glaucoma can be categorized into three groups. The location of progressive peripapillary RNFL thinning is associated with progressive macular GCIPL thinning and pattern of VF changes in the affected area. Our results indicate that the use of only macular GCIPL analysis is inadequate for analyzing the structural progression of glaucoma.
Project description:To assess normal vessel flow density (VFD) in macular and peripapillary regions of eyes with no known ocular pathology using optical coherence tomography angiography (OCTA).AngioVue (Optovue, Fremont, CA, USA) was used to capture OCTA images. A 3 × 3 mm grid and a 4.5 × 4.5 mm grid was used to scan parafoveal and peripapillary regions, respectively. ReVue software was utilized to measure VFD in five sectors within the inner two circles of ETDRS grid in macular region and correlated to retinal thickness of same sectors. At optic disc, VFD was calculated in six sectors based on Garway-Heath map. Area and morphology of foveal avascular zone (FAZ) was correlated with VFD in central 1 mm. The influence of myopia on mean VFD was also assessed.Twenty-four eyes (mean age: 30 years) were analyzed. Mean VFD in macular sectors was 43.5 (±4.5) and 45.8 (±5.0) % in superficial and deep retinal plexuses, respectively. Mean VFD was significantly higher in deep retinal plexus compared to superficial retinal plexus in all sectors except central 1 mm (p < 0.05). Mean VFD in central 1 mm increases with an increase in central retinal thickness in both superficial and deep retinal plexuses (p < 0.001). Mean parafoveal VFD at level of both superficial and deep retinal plexuses decrease with an increase in spherical equivalent in myopics (p < 0.05). Mean VFD in myopics was found to be significantly lower in parafoveal region of deep retinal plexus (p < 0.05). Mean area of FAZ was 0.33 (±0.15) and 0.47 mm2 (±0.15) in superficial and deep retinal plexuses, respectively. Area of FAZ decreases with an increase in central 1 mm thickness and foveal VFD (p < 0.001).OCTA may be used to measure VFD in macular and peripapillary regions. Vessels in the parafoveal region are more densely packed in the deep retinal plexus leading to higher VFD compared to superficial plexus. Thicker retina in fovea translates into higher foveal VFD due to more compact arrangement of retinal layers and continuity of inner nuclear layer (INL). Myopia is associated with lower VFD in parafoveal region at level of deep retinal plexuses which may explain thinning of INL in myopics.
Project description:To evaluate the effect of a topical, nonsteroidal antiinflammatory drug, nepafenac 0.1%, in eyes with noncentral diabetic macular edema.Multicenter, double-masked randomized trial. Individuals with good visual acuity and noncentral-involved diabetic macular edema were randomly assigned to nepafenac 0.1% (N = 61) or placebo (nepafenac vehicle, N = 64) 3 times a day for 12 months. The primary outcome was mean change in optical coherence tomography retinal volume at 12 months.Mean baseline retinal volume was 7.8 mm. At 12 months, in the nepafenac and placebo groups respectively, mean change in retinal volume was -0.03 mm and -0.02 mm (treatment group difference: -0.02, 95% confidence interval: -0.27 to 0.23, P = 0.89). Central-involved diabetic macular edema was present in 7 eyes (11%) and 9 eyes (14%) at the 12-month visit (P = 0.79), respectively. No differences in visual acuity outcomes were identified. One study participant developed a corneal melt after using nepafenac in the nonstudy eye, which had a history of severe dry eye. No additional safety concerns were evident.In eyes with noncentral diabetic macular edema and good visual acuity, topical nepafenac 0.1% 3 times daily for 1 year likely does not have a meaningful effect on optical coherence tomography-measured retinal thickness.
Project description:BACKGROUNDS:To assess the changes in individual retinal layer thickness and visual function associated with gains in visual acuity after an intravitreal conbercept injection in the diabetic macular edema (DME) on spectral domain optical coherence tomography (SD-OCT) and microperimetry during 1-year follow-up. METHODS:Retrospective observational study. Twenty patients with clinically significant DME in the study eye were imaged by SD-OCT every 3 months and MP1 microperimeter in the third month while receiving anti-vascular endothelial growth factor (VEGF) (conbercept) treatment. In each patient, seven retinal layers were segmented in 98 scans covering a 6 mm × 6 mm area of the macula at baseline and during 1 year of treatment. An automatic, full-threshold microperimetry of the central field (10° × 10°, 40 stimulated points) with the MP1 microperimeter. Thickness and microperimetry changes were quantitatively measured and evaluated for their correlation with increases in visual acuity. RESULTS:Although thicknesses of the inner nuclear layer (INL) and the outer nuclear layer (ONL) were reduced the most after treatment (p < 0.05), decreases of the ganglion cell layer (GCL) (r = 0.591, p = 0.006) and inner plexiform layer (IPL) (r = 0.663, p = 0.001) in central subfield area was associated with best-corrected visual acuity (BCVA) gain, and had the best estimation of BCVA gain (adjust R2 = 0.544). Mean macular sensitivity in the central subfield was also well correlated with BCVA gain (r = 0.531, p = 0.016). CONCLUSIONS:Neural recovery occurred after the resolution of edema during conbercept treatment, due to the decreases in GCL and IPL associating with gains in vision and improved microperimetry.
Project description:To quantify the signal intensity of fundus autofluorescence (FAF) and evaluate its association with visual function and optical coherence tomography (OCT) findings in diabetic macular oedema (DMO).We reviewed 103 eyes of 78 patients with DMO and 30 eyes of 22 patients without DMO. FAF images were acquired using Heidelberg Retina Angiograph 2, and the signal levels of FAF in the individual subfields of the Early Treatment Diabetic Retinopathy Study grid were measured. We evaluated the association between quantified FAF and the logMAR VA and OCT findings.One hundred and three eyes with DMO had lower FAF signal intensity levels in the parafoveal subfields compared with 30 eyes without DMO. The autofluorescence intensity in the parafoveal subfields was associated negatively with logMAR VA and the retinal thickness in the corresponding subfields. The autofluorescence levels in the parafoveal subfield, except the nasal subfield, were lower in eyes with autofluorescent cystoid spaces in the corresponding subfield than in those without autofluorescent cystoid spaces. The autofluorescence level in the central subfield was related to foveal cystoid spaces but not logMAR VA or retinal thickness in the corresponding area.Quantified FAF in the parafovea has diagnostic significance and is clinically relevant in DMO.
Project description:To investigate the thickness of retinal layers and association with final visual acuity using spectral-domain optical coherence tomography (SD-OCT) in macular area of macula-off rhegmatogenous retinal detachment (RRD) patients after a successful macular re-attachment.In retrospective study, a total 24 eyes with macula-off RRD were enrolled. All patients underwent vitrectomy to repair RRD. Outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor layer (PR), retinal pigment epithelium (RPE) thicknesses were measured by the Spectralis (Heidelberg Engineering, Heidelberg, Germany) SD-OCT with automated segmentation software. The relationship between the thicknesses of each retinal layer and postoperative logarithm of the minimum angle of resolution scale (LogMAR) visual acuity was analyzed.OPL and RPE thicknesses were not significantly different between the retinal detachment eyes and fellow eyes (P = 0.839, 0.999, respectively). The ONL and photoreceptor thickness were significantly thinner in the retinal detachment eyes (P <0.001 and 0.001, respectively). In the univariate regression analysis, preoperative best corrected visual acuity (BCVA), ONL thickness and photoreceptor thickness showed association with the postoperative BCVA (P = 0.003, <0.001 and 0.024, respectively). In final multiple linear regression model, ONL thickness was the only variable significantly associated with postoperative BCVA (P = 0.044).Segmented ONL and photoreceptor thickness of retinal detachment eyes were significantly thinner than fellow eyes. Segmental analysis of the retinal layer in macular region may provide valuable information for evaluation RRD. And ONL thickness can be used as a potential biomarker to predict visual outcome after RRD repair.
Project description:Macular pigment (MP), which is composed of lutein/zeaxanthin/mezo-zeaxanthin, is concentrated in the central part of the retina, the macula. It protects the macula by absorbing short-wavelength light and suppressing oxidative stress. To evaluate whether MP levels are related to retinal neural protection and resulting health, we analyzed the association between the MP optical density (MPOD), and the macular thickness and volumes. Forty-three eyes of 43 healthy adult volunteers (21 men and 22 women; age: 22-48 (average 31.4 ± 1.1) years) were analyzed. Highly myopic eyes (<-6 diopters) were excluded. MPOD was measured using MPS2®, and the neural retinal thickness and volume were measured using optical coherence tomography. The mean MPOD was 0.589 ± 0.024, and it positively correlated with the central retinal thickness (P = 0.017, R = 0.360) and retinal volume of the fovea (1-mm diameter around the fovea; P = 0.029, R = 0.332), parafovea (1-3-mm diameter; P = 0.002, R = 0.458), and macula (6-mm diameter; P = 0.003, R = 0.447). In the macular area (diameter: 6 mm), MPOD was correlated with the retinal neural volume of the ganglion cell layer (P = 0.037, R = 0.320), inner plexiform layer (P = 0.029, R = 0.333), and outer nuclear layer (P = 0.020, R = 0.353). Thus, MPOD may help in estimating neural health. Further studies should determine the impact of MP levels on neuroprotection.
Project description:Aggregation of ?-synuclein is a defining molecular feature of Parkinson's disease, Lewy body dementia, and multiple systems atrophy. Hereditary mutations in ?-synuclein are linked to both Parkinson's disease and Lewy body dementia; in particular, patients bearing the E46K disease mutation manifest a clinical picture of parkinsonism and Lewy body dementia, and E46K creates more pathogenic fibrils in vitro. Understanding the effect of these hereditary mutations on ?-synuclein fibril structure is fundamental to ?-synuclein biology. We therefore determined the cryo-electron microscopy (cryo-EM) structure of ?-synuclein fibrils containing the hereditary E46K mutation. The 2.5-Å structure reveals a symmetric double protofilament in which the molecules adopt a vastly rearranged, lower energy fold compared to wild-type fibrils. We propose that the E46K misfolding pathway avoids electrostatic repulsion between K46 and K80, a residue pair which form the E46-K80 salt bridge in the wild-type fibril structure. We hypothesize that, under our conditions, the wild-type fold does not reach this deeper energy well of the E46K fold because the E46-K80 salt bridge diverts ?-synuclein into a kinetic trap-a shallower, more accessible energy minimum. The E46K mutation apparently unlocks a more stable and pathogenic fibril structure.
Project description:Retinal ganglion cells are distributed disproportionately with retinal eccentricity. Pattern electroretinogram (PERG) stimuli resulted in reduced responses with more eccentric stimuli. Therefore, we investigated whether PERG amplitude is associated with the location of visual field (VF) defect in primary open-angle glaucoma. Data from Twenty-nine glaucoma patients with a parafoveal scotoma (PFS) within the central 10° of fixation, 23 glaucoma patients with a peripheral nasal step (PNS), and 27 normal control subjects were analyzed in this study. Electroretinograms (ERGs) were obtained using a commercial ERG stimulator (Neuro-ERG). The thickness of the ganglion cell-inner plexiform layer (GCIPL) was measured using spectral-domain optical coherence tomography. A lower N95 amplitude was observed in both PFS and PNS compared to the normal control (Both P < 0.001). The N95 amplitude of the PFS group was significantly lower than that of the PNS group (P = 0.034). Average GCIPL thickness correlated positively with N95 amplitude (r = 0.368, P = 0.002), but did not correlate significantly with global mean sensitivity (r = 0.228, P = 0.073) or mean deviation on 24-2 standard automated perimetry (r = 0.173, P = 0.176). In conclusion, parafoveal VF defects were associated with the lower PERG amplitude. Therefore, it is necessary to take into account the location of VF defects in evaluating PERGs of glaucoma patients.