Ganglion Cell-inner Plexiform Layer Measurements Research Articles

Exploring the relationship between 24-2 visual field and widefield optical coherence tomography data across healthy, glaucoma suspect and glaucoma eyes.

To utilise ganglion cell-inner plexiform layer (GCIPL) measurements acquired using widefield optical coherence tomography (OCT) scans spanning 55° × 45° to explore the link between co-localised structural parameters and clinical visual field (VF) data. Widefield OCT scans acquired from 311 healthy, 268 glaucoma suspect and 269 glaucoma eyes were segmented to generate GCIPL thickness measurements. Estimated ganglion cell (GC) counts, calculated from GCIPL measurements, were plotted against 24-2 SITA Faster visual field (VF) thresholds, and regression models were computed with data categorised by diagnosis and VF status. Classification of locations as VF defective or non-defective using GCIPL parameters computed across eccentricity- and hemifield-dependent clusters was assessed by analysing areas under receiver operating characteristic curves (AUROCCs). Sensitivities and specificities were calculated per diagnostic category. Segmented linear regression models between GC counts and VF thresholds demonstrated higher variability in VF defective locations relative to non-defective locations (mean absolute error 6.10-9.93 dB and 1.43-1.91 dB, respectively). AUROCCs from cluster-wide GCIPL parameters were similar across methods centrally (p = 0.06-0.84) but significantly greater peripherally, especially when considering classification of more central locations (p < 0.0001). Across diagnoses, cluster-wide GCIPL parameters demonstrated variable sensitivities and specificities (0.36-0.93 and 0.65-0.98, respectively), with the highest specificities observed across healthy eyes (0.73-0.98). Quantitative prediction of VF thresholds from widefield OCT is affected by high variability at VF defective locations. Prediction of VF status based on cluster-wide GCIPL parameters from widefield OCT could become useful to aid clinical decision-making in appropriately targeting VF assessments.

Optical coherence tomography of the macular ganglion cell layer in children with neurofibromatosis type 1 is a useful tool in the assessment for optic pathway gliomas.

Optic pathway glioma (OPG) is a feared complication to neurofibromatosis type 1 (NF1) since it can cause visual impairment in young children. The main goal of screening is to detect symptomatic OPGs that require treatment. Optical coherence tomography (OCT) has been suggested as a tool for detection of neuro-retinal damage. To investigate whether the ganglion cell layer assessed by OCT is a reliable measure to identify and detect relapses of symptomatic OPGs in children with NF1. Children (3-6 years) with NF1, with and without known OPG and children with sporadic OPG (S-OPG) resident in the Stockholm area, were invited and followed in a prospective study during a three-year period. Brain magnetic resonance tomography (MRI) had been performed in children with symptoms of OPG. Outcome measures were VA in logMAR, visual field index (VFI), average thicknesses of the ganglion cell-inner plexiform layer (GC-IPL), and peripapillary retinal nerve fiber layer (pRNFL). There were 25 children with MRI-verified OPG and 52 with NF1 without symptomatic OPG. Eyes from NF1 patients without symptoms of OPG showed significantly better results in all four analyzed parameters compared to eyes with NF1-associated OPG. Mean GC-IPL measurements seemed stable and reliable, significantly correlated to pRNFL (correlation coefficient (r) = 0.662, confidence interval (CI) = .507 to .773 p<0.001), VA (r = -0.661, CI = -7.45 to -.551, p<0.001) and VFI (r = 0.644, CI = .452 to .774, p<0.001). GC-IPL measurements were easy to obtain and acquired at considerably younger age than pRNFL (5.6±1.5 vs 6.8±1.3; p<0.001). The mean GC-IPL thickness could distinguish well between eyes with OPG and eyes without symptomatic OPG in children with NF1. As thinning of GC-IPL assessed with OCT could indicate underlying OPG, it should be included in the screening protocol of children with questionable VA measurements and in particular in children with NF1.

Prediction of Retinal Ganglion Cell Counts Considering Various Displacement Methods From OCT-Derived Ganglion Cell-Inner Plexiform Layer Thickness.

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.

Ganglion cell-inner plexiform layer measurements derived from widefield compared to montaged 9-field optical coherence tomography

ABSTRACT Clinical relevance With equivalent inner retinal thickness measurements compared to a more conventional composite optical coherence tomography (OCT) protocol, Widefield optical coherence tomography (WF-OCT) is a clinically viable, time-saving option facilitating detection of ocular pathologies within the central 55° of the retina. Purpose To compare ganglion cell-inner plexiform layer (GCIPL) thicknesses obtained using a single WF-OCT scan and standard composite OCT scans acquired in 9 fields of gaze (9F-OCT). Methods Thirteen healthy participants underwent WF-OCT and 9F-OCT using the Spectralis OCT. The GCIPL was automatically segmented with a manual review for 9F-OCT and was manually segmented for WF-OCT. After registration, differences in GCIPL thicknesses were compared using 95% confidence intervals computed from one-sample t-tests and Bland-Altman analyses. Location-specific differences in B-scan tilt were analysed using Spearman correlations and linear regression models. To determine whether B-scan tilt influences GCIPL measurements, regression models of tilt versus differences between perpendicular and axial GCIPL thickness were applied. Results While scattered locations demonstrated significant GCIPL thickness differences between WF-OCT and 9F-OCT, most differences did not exceed the axial pixel resolution of the instrument of 3.87 µm. Bland-Altman analyses indicated no notable bias using WF-OCT. Moderate correlations indicating significant location-specific differences in B-scan tilt were observed for temporal, central and inferior B-scans (r = −0.62 to 0.72), with linear regression models predicting a maximum difference in the tilt of 4.65°. The quadratic regression model indicated that at tilts greater than 27.3°, perpendicular GCIPL measurements become increasingly thin relative to axial measurements. Conclusions GCIPL thicknesses and B-scan tilts from WF-OCT are comparable to 9F-OCT, indicating that WF-OCT can be applied clinically to obtain valid inner retinal OCT measurements over 55° of the central retina with relative ease. However, for peripheral locations, B-scan tilt may need to be considered when measuring GCIPL thicknesses.

Custom extraction of macular ganglion cell-inner plexiform layer thickness more precisely co-localizes structural measurements with visual fields test grids

We aimed to evaluate methods of extracting optical coherence tomography (OCT)-derived macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements over retinal locations corresponding to standard visual field (VF) test grids. A custom algorithm was developed to automatically extract GCIPL thickness measurements from locations corresponding to Humphrey Field Analyser 10-2 and 30-2 test grids over Goldmann II, III and V stimulus sizes from a healthy cohort of 478 participants. Differences between GCIPL thickness measurements based on VF test grids (VF-based paradigms) and the 8 × 8 grid, as per instrument review software, were analyzed, as were impacts of fovea to optic disc tilt and areas over which GCIPL thickness measurements were extracted. Significant differences between the VF-based paradigms and the 8 × 8 grid were observed at up to 55% of locations across the macula, with the greatest deviations at the fovea (median 25.5 μm, 95% CI 25.24–25.72 μm, P < .0001). While significant correlations with fovea to optic disc tilt were noted at up to 33% of locations distributed 6°–8° from the foveal center, there were no marked differences in GCIPL thickness measurements between VF-based paradigms using different stimulus sizes. As such, standard high-density OCT measurement paradigms do not adequately reflect GCIPL measurements at retinal locations tested with standard VF patterns, with the central macular region contributing most to the observed differences and with further correction required for fovea to optic disc tilt. Spatial direction of GCIPL thickness measurements will improve future comparisons of structure and function, thereby improving methods designed to detect pathology affecting the inner retina.

Local Macular Thickness Relationships between 2 OCT Devices

To compare local ganglion cell-inner plexiform layer (GCIPL) thickness measurements between 2 OCT devices and to explore factors that may influence the difference in measurements. Cross-sectional study. Sixty-nine glaucoma eyes (63 patients) with evidence of central damage or mean deviation (MD) of -6.0 dB or worse on a 24-2 visual field (VF). Cirrus and Spectralis OCT macular volume scans were exported, data from the central 20° of both OCT devices were centered and aligned, and 50× 50 arrays of 0.4°× 0.4° superpixels were created. We estimated nonparametric (Spearman's) correlations and used Bland-Altman plots to compare GCIPL thickness measurements between the two OCTs at the superpixel level. Factors that may have influenced the differences between thickness measurements between the two devices were explored with linear mixed models. Pooled and individual-eye Spearman's correlation and agreement between thickness measurements from the two devices. The median 24-2 VF MD was -6.8 dB (interquartile range [IQR], -4.9 to -12.3 dB). The overall pooled Spearman's correlation between the two devices for all superpixels and eyes was 0.97 (P < 0.001). The median within-eye correlation coefficient was 0.72 (IQR, 0.59-0.79). Bland-Altman plots demonstrated a systematic bias in most individual eyes, with Spectralis GCIPL measurements becoming larger than Cirrus measurements with increasing superpixel thickness. The average superpixel thickness and distance to the fovea influenced the thickness difference between the two devices in multivariate models (P < 0.001). Local macular thickness measurements from the Spectralis and Cirrus devices are highly correlated, but not interchangeable. Differences in thickness measurements between the two devices are influenced by the location of superpixels and their thickness.

Evaluation of retina nerve fiber layer, ganglion cell-inner plexiform layer and lamina cribrosa in clinically unilateral exfoliative glaucoma.

To compare retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GC-IPL), the lamina cribrosa depth (LCD) and thickness (LCT) in unilateral exfoliative glaucoma (EXG) patients with their fellow eyes without exfoliation and control eyes. This cross-sectional prospective single-center study consisted of 64 eyes of 32 patients with unilateral EXG and 35 eyes of controls. All subjects were examined with spectral domain optical coherence tomography for the RNFL and GC-IPL measurements. The LCD and LCT measurements were also obtained. The RNFL measurements at all quadrants were statistically thinner in EXG eyes than those in their eyes without EXG and control eyes (p < 0.001 for average, superior, temporal and inferior; p = 0.004 for nasal). The EXG group had deeper LCD than their eyes without EXG and control eyes (p < 0.001, for both). The fellow eyes of EXG group had also deeper LCD than control eyes, with no statistical significance (p = 0.058). The mean LCT was thinner in EXG eyes compared to those in the eyes without EXG and control eyes (p < 0.001, for both). The eyes without EXG and control eyes had similar LCT (p = 0.293). Recent developments in imaging technology give the clinician detailed structural information about optic nerve head and retina such as GC-IPL, LCD and LCT. In addition to follow-up of RNFL changes, these new parameters may be useful in recognizing progression in EXG patients.

Comparison of glaucoma diagnostic ability of ganglion cell-inner plexiform layer according to the range around the fovea

BackgroundTo compare the glaucoma diagnostic ability of the ganglion cell-inner plexiform layer (GCIPL) thickness depending on the range around the fovea using wide-angle, swept-source optical coherence tomography (SS-OCT).MethodsWe compared the glaucoma diagnostic utility of GCIPL parameters across multiple regions while centered on the fovea. In a wide-angle scan, the GCIPL for each 1-mm2 grid square of a 12 × 9 mm2 scan resulted in 108 data points. With respect to the range of the GCIPL measurements around the macula, the wide-angle scan images were classified into three zones. Zone 1 was defined as a narrow area; zone 2 was defined as a mid-sized area; and zone 3 was defined as a wide area. We recorded the quadrant GCIPL thickness, average, and minimum quadrant GCIPL within each zone. The areas under the receiver operating characteristic (AUROCs) curves were calculated to evaluate the glaucoma diagnostic utility.ResultsSixty-one eyes with glaucoma and 59 normal eyes were assessed. The minimum and average GCIPL measurements in zones 1–3 in eyes with glaucoma were significantly lower than those in normal eyes (P < 0.001). The AUROCs for the minimum and inferotemporal GCIPL in zone 1 and the inferotemporal GCIPL thickness in zone 2 were greater than 0.9 (0.945, 0.931, and 0.918, respectively).ConclusionsWide-angle scanning using SS-OCT will contribute to improvements in the detection of glaucomatous damage. The minimum and inferotemporal GCIPL in zone 1 may be more useful for detecting glaucoma than those in the conventional area.

Retinal nerve fiber layer and ganglion cell-inner plexiform layer measurements using handheld optical coherence tomography in normal children

Measurements of the ganglion cell complex (GCC), comprising the retinal nerve fiber, ganglion cell, and inner plexiform layers, can be correlated with vision loss caused by optic nerve disease. Handheld optical coherence tomography (HH-OCT) with sedation can be used in young children unamenable to traditional imaging. Purposeto report GCC measurements in normal children using the HH-OCT.

Macular Ganglion Cell Layer Assessment to Detect Glaucomatous Central Visual Field Progression

PurposeTo investigate the use of ganglion cell inner plexiform layer (GC-IPL) thickness, as measured by spectral domain optical coherence tomography, to detect central visual field (VF) progression.MethodsThis study included 384 eyes from 384 patients (219 preperimetric and 165 perimetric glaucomatous eyes; average follow-up, 4.3 years). Photographic assessment of retinal nerve fiber layer (RNFL) and serial VF analysis were performed to detect glaucoma progression in the central (within 10°) area. Study inclusion required at least five serial spectral domain optical coherence tomography exams at different visits. The long-term test-retest variability of average GC-IPL thicknesses was calculated in 110 stable preperimetric glaucomatous eyes. The sensitivity and specificity of GC-IPL measurements for the detection of central VF progression were calculated in an event-based analysis using the calculated variability as a cut-off and were compared with those of central RNFL photographic assessment.ResultsThe intersession test-retest variability, defined as the 95% confidence interval, was 1.76 µm for average GC-IPL thickness. The sensitivity and specificity of the average GC-IPL thickness for detecting central VF progression were 60.7% and 78.9%, respectively. Among six sectors, the inferonasal GC-IPL sector showed the highest sensitivity (53.6%). The sensitivity of the ≥1 sector GC-IPL to detect central VF progression was significantly higher than that of central RNFL photographic progression (p = 0.013). Other GC-IPL parameters showed comparable sensitivity and specificity to detect central VF progression compared with RNFL photographic progression.ConclusionsSerial GC-IPL measurements show comparable performance in the detection of central glaucomatous VF progression to RNFL photographic assessment.

Comparing the Structure-Function Relationship at the Macula With Standard Automated Perimetry and Microperimetry.

To compare the structure-function relationship between ganglion cell-inner plexiform layer (GCIPL) thickness measurements using spectral-domain optical coherence tomography (SDOCT) and visual sensitivities measured using standard automated perimetry (SAP) and microperimetry (MP) at the macula in glaucoma. In a prospective study, 45 control eyes (29 subjects) and 60 glaucoma eyes (45 patients) underwent visual sensitivity estimation at the macula (central 10°) by SAP and MP, and GCIPL thickness measurement at the macula by SDOCT. Structure-function relationships between GCILP thickness and visual sensitivity loss with SAP and MP at various macular sectors were assessed using the Hood and Kardon model. To compare structure-function relationship with SAP and MP, we calculated the number of data points falling outside the 5th and the 95th percentile values of the Hood and Kardon model with each of the perimeters. The number of points falling outside the 5th and 95th percentile values of the Hood and Kardon model ranged from 28 (superior sector) to 48 (inferonasal sector) with SAP and 33 (superior sector) to 49 (inferonasal sector) with MP. The difference in the number of points falling outside the 5th and 95th percentile values with SAP and MP was statistically insignificant (P > 0.05, χ(2) test) for all the sectors. Visual sensitivity measurements of both SAP and MP demonstrated a similar relationship with the GCIPL measurements of SDOCT at the macula in glaucoma.

Evaluation of the peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer measurements in patients with iron deficiency anemia with optical coherence tomography

Objective: To evaluate the thickness of the peripapillary retinal fiber layer (RNFL) and macula ganglion cell-inner plexiform layer (GCL+) using optical coherence tomography (OCT) in patients with iron deficiency (ID) anemia.Methods: This study included 73 eyes of 39 patients with ID anemia and 68 eyes of 34 age- and sex-matched healthy subjects. The measurements included the peripapillary RNFL thicknesses as average, 4 quadrant and 12 clock-hour (CH) based and macula GCL+ thicknesses as average and 6 quadrant based. All measurements were completed with Cirrus HD-OCT and the results were compared between the groups.Results: A total of 73 eyes of 39 patients with ID anemia and 68 eyes of 34 healthy subjects were included to the study. Regarding peripapillary RNFL thicknesses of the study and control patients, the values of average and quadrants revealed no significant differences between the groups. In CH sectors comparison, peripapillary RNFL thicknesses were significantly decreased only in CH4 (68.7 ± 14.5 μm in study versus 72.0 ± 13.4 μm in control patients, p = 0.049) and CH5 (93.4 ± 20.0μm in study versus 102.2 ± 20.1 μm in control patients, p = 0.01) sectors. All measured quadrants were statistically similar, when macula GCL+ thicknesses were compared between the groups. When the correlations between peripapillary RNFL and macula GCL+ thicknesses and serum hemoglobin and ferritin levels of study and control patients were calculated, the only statistically significant parameter was the correlation of peripapillary RNFL thickness in CH10 sector with serum ferritin level (p = 0.032, Spearman correlation coefficient: 0.369).Conclusion: The study revealed that peripapillary RNFL is thinner in nasal-inferior quadrant in patients with ID anemia. The measurements of macula GCL+ thicknesses were similar between the groups. Analyzing the retinal layers using OCT may provide valuable information in neurodegenerative events.

Long-Term Reproducibility of Macular Ganglion Cell Analysis in Clinically Stable Glaucoma Patients.

To investigate the long-term reproducibility of macular ganglion cell analysis in clinically stable glaucoma patients using spectral-domain optical coherence tomography (SD-OCT). One hundred nine eyes of 109 clinically stable open-angle glaucoma patients with a localized retinal nerve fiber layer (RNFL) defect and a corresponding macular ganglion cell-inner plexiform layer (GCIPL) defect were included in this retrospective, longitudinal study. Clinical stability was defined as showing no change on serial structural (stereo-disc and RNFL photography) and functional (visual field progression analysis) assessments. Three serial SD-OCT (Cirrus-HD) peripapillary and macular scans taken at 6-month intervals were analyzed. Intraclass correlation coefficient (ICC), coefficient of variation (CV), test-retest standard deviation (TRTSD), and tolerance limit of area and angular width of GCIPL defect and GCIPL thickness measurements were assessed. The ICC of the GCIPL thickness parameters ranged from 0.966 to 0.992, and the CV from 2.0% to 5.5%. The TRTSD was the lowest for the average GCIPL thickness (1.45 μm), the highest for the minimum GCIPL thickness (3.42 μm), and varied from 1.54 to 2.16 μm for the sectoral measurements. The ICC, CV, and TRTSD were 0.993, 3.9%, and 5.32° for angular width, and 0.930, 6.7%, and 0.27 mm2 for area of GCIPL defect. Measurement variances (TRTSD) for the GCIPL measurements showed no significant association with the glaucomatous severity. The macular GCIPL thickness and deviation maps showed excellent long-term intervisit reproducibility. Macular ganglion cell analysis can be considered as an effective means of monitoring glaucomatous progression in macula.

Early Macular Retinal Ganglion Cell Loss in Dominant Optic Atrophy: Genotype-Phenotype Correlation

To assess the peripapillary retinal nerve fiber and macular retinal ganglion cell (RGC) loss in patients with dominant optic atrophy (DOA) stratified by OPA1 mutation type. Cross-sectional study. We studied 39 patients from 28 pedigrees with DOA harboring heterozygous mutations in the OPA1 gene along with 45 age-matched healthy subjects. The retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) of patients with DOA were evaluated by optical coherence tomography (OCT) and compared to those of controls. Patients' eyes were divided into 4 groups based on increasing severity of visual loss (DOA1 to DOA4) and were stratified by OPA1 mutation type. The average thicknesses of the RNFL and GC-IPL were smaller in patients with DOA than in healthy controls (P < 0.0001). RNFL analysis showed a significant reduction of the average, superior and inferior quadrants thicknesses in the DOA4 group compared to the DOA1 group (P= 0.001, P= 0.002 and P= 0.001, respectively). GC-IPL analysis showed a significant thinning in the superotemporal and superior sectors in the patients with DOA2 compared to those with DOA1 (P= 0.046 and P= 0.04, respectively). Stratifying by mutation type, average, superior and nasal RNFL thinning was significantly more severe in missense mutations and had a presumed dominant-negative effect compared to mutations causing haploinsufficiency. The present study demonstrates that in DOA, loss of macular RGCs is the earliest pathologic event, better reflected by GC-IPL measurements, whereas RNFL thickness is a measure of spared axons in late stages of the disease. Thus, mild cases (DOA2) show significant macular RGC loss as opposed to substantial maintenance of RNFL thickness, which is significantly decreased only in severe cases (DOA4). A clear genotype/phenotype correlation emerged, stratifying OCT measures by OPA1 mutation type, missense mutations being the most severe.

Diagnostic Specificities of Retinal Nerve Fiber Layer, Optic Nerve Head, and Macular Ganglion Cell-Inner Plexiform Layer Measurements in Myopic Eyes

To evaluate and compare the diagnostic specificities of peripapillary retinal nerve fiber layer (RNFL) thickness, macular ganglion cell-inner plexiform layer (GC-IPL) thickness, and optic nerve head (ONH) measurements in nonglaucomatous myopic individuals. In a prospective, cross-sectional study, participants underwent a complete ophthalmic examination, a screening automated visual field test, and axial length measurement. The study eye then underwent optic nerve head and macular scanning using spectral-domain optical coherence tomography (OCT) instrumentation to determine RNFL thickness, GC-IPL thickness, and ONH measurements. False-positive rates for each of the OCT-derived parameters, using predefined criteria for an abnormal test, were calculated. Comparative analysis was performed using the McNemar test. Data from 43 eligible subjects were analyzed. The mean age was 30±6.8 years (range, 22 to 50 y) with an average axial length of 25.26±1.21 mm (range, 23.06 to 29.07 mm) and mean spherical equivalent of -4.50±1.93 D (range, -1.00 to -9.00 D). The false-positive rate was higher when using RNFL parameters compared with both ONH (47% vs. 7%, respectively; P<0.001) and GC-IPL (47% vs. 26%, respectively; P=0.049) parameters. The false-positive rate was higher when using GC-IPL parameters, compared with ONH parameters (26% vs. 7%, respectively; P=0.039). Caution should be exercised when relying on OCT-derived RNFL and GC-IPL thickness values to diagnose glaucoma in myopic individuals. OCT-derived ONH parameters perform better than RNFL and GC-IPL parameters and may increase diagnostic specificity in this population.