Project description:ObjectiveTo determine the effect of clinical and radiologic disease activity on the rate of thinning of the ganglion cell/inner plexiform (GCIP) layer and the retinal nerve fiber layer in patients with multiple sclerosis (MS) using optical coherence tomography (OCT).MethodsOne hundred sixty-four patients with MS and 59 healthy controls underwent spectral-domain OCT scans every 6 months for a mean follow-up period of 21.1 months. Baseline and annual contrast-enhanced brain MRIs were performed. Patients who developed optic neuritis during follow-up were excluded from analysis.ResultsPatients with the following features of disease activity during follow-up had faster rates of annualized GCIP thinning: relapses (42% faster, p = 0.007), new gadolinium-enhancing lesions (54% faster, p < 0.001), and new T2 lesions (36% faster, p = 0.02). Annual GCIP thinning was 37% faster in those with disability progression during follow-up, and 43% faster in those with disease duration <5 years vs >5 years (p = 0.003). Annual rates of GCIP thinning were highest in patients exhibiting combinations of new gadolinium-enhancing lesions, new T2 lesions, and disease duration <5 years (70% faster in patients with vs without all 3 characteristics, p < 0.001).ConclusionsMS patients with clinical and/or radiologic nonocular disease activity, particularly early in the disease course, exhibit accelerated GCIP thinning. Our findings suggest that retinal changes in MS reflect global CNS processes, and that OCT-derived GCIP thickness measures may have utility as an outcome measure for assessing neuroprotective agents, particularly in early, active MS.
Project description:PurposeTo investigate macular ganglion cell-inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs.Methods112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs.Result47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001) and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000). The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior) mGCIPL was thinnest in the same hemiretina in 26 eyes (90%). Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001) and inferior mGCIPL (P = 0.030) compared to glaucomatous eyes without a visible RNFL defect.ConclusionThe current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect.
Project description:Background/aimsTo investigate the patterns of retinal ganglion cell damage at different stages of glaucoma, using the circumpapillary retinal nerve fiber layer (RNFL) and macula ganglion cell-inner plexiform layer (GCIPL) thicknesses.MethodsIn 296 eyes of 296 glaucoma patients and 55 eyes of 55 healthy controls, the correlations of mean deviation (MD) with the superior and inferior quadrant RNFL/GCIPL thickness (defined as the average of three superior and inferior sectors, resp.) were analyzed.ResultsIn early to moderate glaucoma, most of the RNFL/GCIPL thicknesses had significant positive correlations with the MD. In advanced glaucoma, the superior GCIPL thickness showed the highest correlation with MD (r = 0.495), followed by the superior RNFL (r = 0.452) (all; P < 0.05). The correlation coefficient of the inferior RNFL thickness with MD (r < 0.471) was significantly stronger in early to moderate glaucoma compared to that in advanced glaucoma (r = 0.192; P < 0.001). In contrast, the correlations of the superior GCIPL thickness with MD (r = 0.452) in advanced glaucoma was significantly stronger compared to that in early to moderate glaucoma (r = 0.159; P < 0.001).ConclusionsThe most preserved region in advanced glaucoma appears to be the superior macular GCIPL, whereas the most vulnerable region for initial glaucoma is the inferior RNFL around the optic disc.
Project description:PurposeTo compare various displacement models using midget retinal ganglion cell to cone (mRGC:C) ratios and to determine viability of estimating RGC counts from optical coherence tomography (OCT)-derived ganglion cell-inner plexiform layer (GCIPL) measurements.MethodsFour Drasdo model variations were applied to macular visual field (VF) stimulus locations: (1) using meridian-specific Henle fiber length along the stimulus circumference; (2) using meridian-specific differences in RGC receptive field and counts along the stimulus circumference; (3) per method (2), averaged across principal meridians; and (4) per method (3), with the stimulus center displaced only. The Sjöstrand model was applied (5) along the stimulus circumference and (6) to the stimulus center only. Eccentricity-dependent mRGC:C ratios were computed over displaced areas, with comparisons to previous models using sum of squares of the residuals (SSR) and root mean square error (RMSE). RGC counts estimated from OCT-derived ganglion cell layer (GCL) and GCIPL measurements, from 143 healthy participants, were compared using Bland-Altman analyses.ResultsMethods 1, 2, and 5 produced mRGC:C ratios most consistent with previous models (SSR 3.82, 4.07, and 3.02; RMSE 0.22, 0.23, and 0.20), while central mRGC:C ratios were overestimated by method 3 and underestimated by methods 4 and 6. RGC counts predicted from GCIPL measurements were within 16% of GCL-based counts, with no notable bias with increasing RGC counts.ConclusionsSjöstrand displacement and meridian-specific Drasdo displacement applied to VF stimulus circumferences produce mRGC:C ratios consistent with previous models. RGC counts can be estimated from OCT-derived GCIPL measurements.Translational relevanceImplementing appropriate displacement methods and deriving RGC estimates from relevant OCT parameters enables calculation of the number of RGCs responding to VF stimuli from commercial instrumentation.
Project description:PurposeThe purpose of this study was to define the normal range of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) thickness in cynomolgus macaques, and explore their inter-relationship and correlation with age, refractive errors, and axial length (AL).MethodsIn this cross-sectional study, we measured biometric and refractive parameters, and pRNFL/mGCL/mIPL thickness in 357 healthy cynomolgus macaques. Monkeys were divided into groups by age and spherical equivalent (SE). Correlation and regression analyses were used to explore the relationship between pRNFL and mGCL/mIPL thickness, and their correlation with the above parameters.ResultsThe mean age, SE, and AL were 14.46 ± 6.70 years, -0.96 ± 3.23 diopters (D), and 18.39 ± 1.02 mm, respectively. The mean global pRNFL thickness was 95.06 ± 9.42 µm (range = 54-116 µm), with highest values in the inferior quadrant, followed by the superior, temporal, and nasal quadrants (P < 0.001). Temporal pRNFL thickness correlated positively with age (r = 0.218, P < 0.001) and AL (r = 0.364, P < 0.001), and negatively with SE (r = -0.270, P < 0.001). In other quadrants, pRNFL thickness correlated negatively with age and AL, but positively with SE. In the multivariable linear regression model, adjusted for sex and AL, age (β = -0.350, P < 0.001), and SE (β = 0.206, P < 0.001) showed significant associations with global pRNFL thickness. After adjusting for age, sex, SE, and AL, pRNFL thickness positively correlated with mGCL (β = 0.433, P < 0.001) and mIPL thickness (β = 0.465, P < 0.001).ConclusionsThe pRNFL/mGCL/mIPL thickness distribution and relationship with age, AL, and SE in cynomolgus macaques were highly comparable to those in humans, suggesting that cynomolgus monkeys are valuable animal models in ophthalmic research.
Project description:PurposeTo compare peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness measurements obtained with spectral domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) using an OCT-angiography scanning protocol, and their ability to distinguish among patients with glaucoma, glaucoma suspects (GS), and healthy controls (HC).MethodsCross-sectional study of 196 eyes (81 glaucoma, 48 GS, and 67 HC) of 119 participants. Participants underwent peripapillary and macular OCT with SD-OCT and SS-OCT. Parameters of interest were average and sector-wise pRNFL and mGCIPL thickness. Inter-device agreement was investigated with Bland-Altman statistics. Conversion formulas were developed with linear regression. Diagnostic performances were evaluated with area under the receiver operating characteristic curves.ResultsBoth SD-OCT and SS-OCT detected a significant pRNFL and mGCIPL thinning in glaucoma patients compared to HC and GS for almost all study sectors. A strong linear relationship between the two devices was present for all quadrants/sectors (R2 ≥ 0.81, P < 0.001), except for the nasal (R2 = 0.49, P < 0.001) and temporal (R2 = 0.62, P < 0.001) pRNFL quadrants. SD-OCT and SS-OCT measurements had a proportional bias, which could be removed with conversion formulas. Overall, the two devices showed similar diagnostic abilities.ConclusionsThickness values obtained with SD-OCT and SS-OCT are not directly interchangeable but potentially interconvertible. Both devices have a similar ability to discriminate glaucoma patients from GS and healthy subjects.Translational relevanceOCT-Angiography scans can be reliably used to obtain structural metrics in glaucoma patients.
Project description:IntroductionThinning of optical coherence tomography-measured retinal nerve fiber layer thickness and ganglion cell-inner plexiform layer (GC-IPL) thickness has been found in patients with Alzheimer's disease. However, the association of these retinal markers and cognition in nondemented elders may not be linear.MethodsThis cross-sectional study included 227 community-dwelling elders (age 65+ years). Multivariable regression analyses were performed to investigate the association between retinal nerve fiber layer/GC-IPL and global/domain-specific cognition.ResultsThe performance of global cognition decreased as mean GC-IPL of bilateral eyes deviated from the sample mean (77.5 μm) (quadratic GC-IPL: β = -0.49 × 10-2; 95% confidence interval: -0.74 × 10-2 to -0.23 × 10-2). Similar associations were also found for logical memory. No significant association was observed between retinal nerve fiber layer and cognition.DiscussionEither thinning or thickening of GC-IPL was associated with poor cognition in nondemented elderly (a U-shaped association). GC-IPL may serve as a noninvasive preclinical predictor of Alzheimer's disease.
Project description:PurposeTo evaluate the changes of retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and ganglion cell-inner plexiform layer (GCIPL) thicknesses and compare structure-function relationships of 4 retinal layers using spectral-domain optical coherence tomography (SD-OCT) in macular region of glaucoma patients.MethodsIn cross-sectional study, a total of 85 eyes with pre-perimetric to advanced glaucoma and 26 normal controls were enrolled. The glaucomatous eyes were subdivided into three groups according to the severity of visual field defect: a preperimetric glaucoma group, an early glaucoma group, and a moderate to advanced glaucoma group. RNFL, GCL, IPL, and GCIPL thicknesses were measured at the level of the macula by the Spectralis (Heidelberg Engineering, Heidelberg, Germany) SD-OCT with automated segmentation software. For functional evaluation, corresponding mean sensitivity (MS) values were measured using 24-2 standard automated perimetry (SAP).ResultsRNFL, GCL, IPL, and GCIPL thicknesses were significantly different among 4 groups (P < .001). Macular structure losses were positively correlated with the MS values of the 24-2 SAP for RNFL, GCL, IPL, and GCIPL (R = 0.553, 0.636, 0.648 and 0.646, respectively, P < .001). In regression analysis, IPL and GCIPL thicknesses showed stronger association with the corresponding MS values of 24-2 SAP compared with RNFL and GCL thicknesses (R2 = 0.420, P < .001 for IPL; R2 = 0.417, P< .001 for GCIPL thickness).ConclusionsSegmented IPL thickness was significantly associated with the degree of glaucoma. Segmental analysis of the inner retinal layer including the IPL in macular region may provide valuable information for evaluating glaucoma.
Project description:PurposeWe compared ganglion cell layer (GCL) and inner plexiform layer (IPL) rates of change (RoC) in patients with glaucoma suspect (GS) and established glaucoma (EG) to test the hypothesis that IPL thickness changes would occur earlier than GCL changes in eyes with early damage.DesignProspective, cohort study.MethodsA total of 64 GS eyes (46 patients) and 112 EG eyes (112 patients) with ≥2 years of follow-up and ≥3 macular optical coherence tomography scans were included. GCL and IPL superpixel thickness measurements were exported. A Bayesian hierarchical model with random intercepts/slopes and random residual variances was fitted to estimate RoC in individual superpixels. Normalized RoC and proportions of superpixels with significantly negative and positive GCL and IPL RoC were compared within the groups.ResultsThe average (SD) follow-up time and number of scans were 3.5 (0.7) years and 4.2 (1.0), respectively, in the GS group and 3.6 (0.4) years and 7.3 (1.1) in the EG group. Mean (SD) normalized RoC was faster for GCL than IPL (-0.69 [0.05] vs -0.33 [0.04]) in the GS group, whereas it was faster for IPL (-0.47 [0.03] vs -0.28 [0.02]) in EG eyes. GCL RoC were significantly negative in 24 of 36 superpixels compared with 8 of 36 for IPL (P < .001) in GS eyes. In the EG group, 23 of 36 superpixels had significant negative IPL RoC compared with 13 of 36 superpixels for GCL (P = .006).ConclusionsGCL thickness is more likely to demonstrate change over time compared with IPL in glaucoma suspects. There is no evidence of preferential IPL thinning in eyes with suspected early glaucoma damage.
Project description:A key principle of retinal organization is that distinct ON and OFF channels are relayed by separate populations of bipolar cells to different sublaminae of the inner plexiform layer (IPL). ON bipolar cell axons have been thought to synapse exclusively in the inner IPL (the ON sublamina) onto dendrites of ON-type amacrine and ganglion cells. However, M1 melanopsin-expressing ganglion cells and dopaminergic amacrine (DA) cells apparently violate this dogma. Both are driven by ON bipolar cells, but their dendrites stratify in the outermost IPL, within the OFF sublamina. Here, in the mouse retina, we show that some ON cone bipolar cells make ribbon synapses in the outermost OFF sublayer, where they costratify with and contact the dendrites of M1 and DA cells. Whole-cell recording and dye filling in retinal slices indicate that type 6 ON cone bipolars provide some of this ectopic ON channel input. Imaging studies in dissociated bipolar cells show that these ectopic ribbon synapses are capable of vesicular release. There is thus an accessory ON sublayer in the outer IPL.