Ganglion Cell-inner Plexiform Layer Analysis Research Articles

Cardiovascular disease and thinning of retinal nerve fiber layer in a multi-ethnic Asian population: the Singapore epidemiology of eye diseases study.

Our study aimed to examine the relationship between cardiovascular diseases (CVD) with peripapillary retinal fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thickness profiles in a large multi-ethnic Asian population study. 6,024 Asian subjects were analyzed in this study. All participants underwent standardized examinations, including spectral domain OCT imaging (Cirrus HD-OCT; Carl Zeiss Meditec). In total, 9,188 eyes were included for peripapillary RNFL analysis (2,417 Malays; 3,240 Indians; 3,531 Chinese), and 9,270 eyes (2,449 Malays, 3,271 Indians, 3,550 Chinese) for GCIPL analysis. History of CVD was defined as a self-reported clinical history of stroke, myocardial infarction, or angina. Multivariable linear regression models with generalized estimating equations were performed, adjusting for age, gender, ethnicity, diabetes, hypertension, hyperlipidaemia, chronic kidney disease, body mass index, current smoking status, and intraocular pressure. We observed a significant association between CVD history and thinner average RNFL (β = -1.63; 95% CI, -2.70 to -0.56; p = 0.003). This association was consistent for superior (β = -1.79, 95% CI, -3.48 to -0.10; p = 0.038) and inferior RNFL quadrant (β = -2.14, 95% CI, -3.96 to -0.32; p = 0.021). Of the CVD types, myocardial infarction particularly showed significant association with average (β = -1.75, 95% CI, -3.08 to -0.42; p = 0.010), superior (β = -2.22, 95% CI, -4.36 to -0.09; p = 0.041) and inferior (β = -2.42, 95% CI, -4.64 to -0.20; p = 0.033) RNFL thinning. Among ethnic groups, the association between CVD and average RNFL was particularly prominent in Indian eyes (β = -1.92, 95% CI, -3.52 to -0.33; p = 0.018). CVD was not significantly associated with average GCIPL thickness, albeit a consistent negative direction of association was observed (β = -0.22, 95% CI, -1.15 to 0.71; p = 0.641). In this large multi-ethnic Asian population study, we observed significant association between CVD history and RNFL thinning. This finding further validates the impact of impaired systemic circulation on RNFL thickness.

Associations between Chronic Kidney Disease and Thinning of Neuroretinal Layers in Multiethnic Asian and White Populations

To evaluate the relationships between chronic kidney disease (CKD) with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness profiles of eyes in Asian and White populations. Cross-sectional analysis. A total of 5066 Asian participants (1367 Malays, 1772 Indians, and 1927 Chinese) from the Singapore Epidemiology of Eye Diseases Study (SEED) were included, consisting of 9594 eyes for peripapillary RNFL analysis and 8661 eyes for GCIPL analysis. Additionally, 45 064 White participants (87 649 eyes) from the United Kingdom Biobank (UKBB) were included for both macular RNFL analysis and GCIPL analysis. Nonglaucoma participants aged ≥ 40 years with complete data for estimated glomerular filtration rate (eGFR) were included from both SEED and UKBB. In SEED, peripapillary RNFL and GCIPL thickness were measured by Cirrus HD-OCT 4000. In UKBB, macular RNFL and GCIPL were measured by Topcon 3D-OCT 1000 Mark II. Chronic kidney disease was defined as eGFR < 60 ml/min/1.73 m2 in both data sets. To evaluate the associations between kidney function status with RNFL and GCIPL thickness profiles, multivariable linear regression with generalized estimating equation models were performed in SEED and UKBB data sets separately. Average peripapillary and macular RNFL thickness and macular GCIPL thickness. In SEED, after adjusting for age, gender, ethnicity, systolic blood pressure, antihypertensive medication, diabetes, hyperlipidemia, body mass index, smoking status, and intraocular pressure, presence of CKD (β=-1.31; 95% confidence interval [CI],-2.37 to-0.26; P= 0.015) and reduced eGFR (per10ml/min/1.73 m2; β=-0.32; 95% CI,-0.50 to-0.13; P= 0.001) were associated with thinner average peripapillary RNFL. Presence of CKD (β=-1.63; 95% CI,-2.42 to-0.84) and reduced eGFR (per10 ml/min/1.73 m2; β=-0.30; 95% CI,-0.44 to-0.16) were consistently associated with thinner GCIPL in SEED (all P < 0.001). In UKBB, after adjusting for the above-mentioned covariates (except ethnicity), reduced eGFR (per 10 ml/min/1.73 m2; β=-0.06; 95% CI,-0.10 to-0.01; P= 0.008) was associated with thinner macular RNFL and CKD (β=-0.62; 95% CI,-1.16 to-0.08; P= 0.024) was associated with thinner average GCIPL. We consistently observed associations between CKD and thinning of RNFL and GCIPL across Asian and White populations' eyes. These findings further suggest that compromised kidney function is associated with RNFL and GCIPL thinning. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association of Antihypertensive Medication with Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness

To evaluate the association between different classes of antihypertensive medication with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness in a nonglaucomatous multiethnic Asian population. Population-based, cross-sectional study. A total of 9144 eyes for RNFL analysis (2668 Malays, 3554 Indians, and 2922 Chinese) and 8549 eyes for GC-IPL analysis (2460 Malays, 3230 Indians, and 2859 Chinese) aged 44 to 86 years. Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for collection of data on medication and other variables. Intraocular pressure (IOP) readings were obtained by Goldmann applanation tonometry before pupil dilation for fundoscopy and OCT imaging. Blood pressure (BP) was measured with an automatic BP monitor. Mean arterial pressure (MAP) was defined as diastolic BP plus 1/3 (systolic BP - diastolic BP). Regression models were used to investigate the association of antihypertensive medication with OCT measurements of RNFL and GC-IPL. Average and sectoral RNFL and GC-IPL thickness. After adjusting for age, gender, ethnicity, MAP, IOP, body mass index (BMI), and presence of diabetes, we found that participants taking any type of antihypertensive medication (β=-0.83; 95% confidence interval [CI],-1.46 to-0.02; P= 0.01), specifically angiotensin-converting enzyme inhibitors (ACEIs) (β=-1.66; 95% CI,-2.57 to-0.75; P < 0.001) or diuretics (β=-1.38; 95% CI,-2.59 to-0.17; P < 0.05), had thinner average RNFL in comparison with participants who were not receiving antihypertensive treatment. Use of a greater number of antihypertensive medications was significantly associated with thinner average RNFL (P for trend= 0.001). This association was most evident in the inferior RNFL quadrant in participants using ACEIs (β=-2.44; 95% CI,-3.99 to-0.89; P= 0.002) or diuretics (β=-2.76; 95% CI,-4.76 to-0.76; P= 0.007). A similar trend was noted in our analysis of macular GC-IPL thickness. Use of 2 or more antihypertensive medications, ACEI, and diuretics were associated with a loss of structural markers of retinal ganglion cell health in a multiethnic Asian population.

Hierarchical Cluster Analysis of Peripapillary Retinal Nerve Fiber Layer Damage and Macular Ganglion Cell Loss in Open Angle Glaucoma.

PurposeTo 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).MethodsOne 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.ResultsThree 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.ConclusionsStructural 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.

Optical coherence tomography is highly sensitive in detecting prior optic neuritis.

To explore sensitivity of optical coherence tomography (OCT) in detecting prior unilateral optic neuritis. This is a retrospective, observational clinical study of all patients who presented from January 1, 2014, to January 6, 2017, with unilateral optic neuritis and OCT available at least 3 months after the attack. We compared OCT retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thicknesses between affected and unaffected contralateral eyes. We excluded patients with concomitant glaucoma or other optic neuropathies. Based on analysis of normal controls, thinning was considered significant if RNFL was at least 9 µm or GCIPL was at least 6 µm less in the affected eye compared to the unaffected eye. Fifty-one patients (18 male and 33 female) were included in the study. RNFL and GCIPL thicknesses were significantly lower in eyes with optic neuritis compared to unaffected eyes (p < 0.001). RNFL was thinner by ≥9 µm in 73% of optic neuritis eyes compared to the unaffected eye. GCIPL was thinner by ≥6 µm in 96% of optic neuritis eyes, which was more sensitive than using RNFL (p < 0.001). When using a threshold ≤1st percentile of age-matched controls, sensitivities were 37% for RNFL and 76% for GCIPL, each of which was lower than those calculated using the intereye difference as the threshold (p < 0.01). OCT, especially with GCIPL analysis, is a highly sensitive modality in detecting prior optic neuritis, which is made more robust by using intereye differences to approximate change. This study provides Class III evidence that OCT accurately identifies patients with prior unilateral optic neuritis.

Diagnostic ability of macular ganglion cell asymmetry in Preperimetric Glaucoma

BackgroundTo evaluate the diagnostic ability of macular ganglion cell asymmetry to diagnose preperimetric glaucoma (PPG), using Cirrus spectral domain optical coherence tomography (OCT).MethodsThis prospective study included 67 eyes of 67 patients with PPG and 67 eyes of 67 age- and refractive error-matched controls. We measured circumpapillary RNFL (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness and optic nerve head (ONH) parameters using OCT. Macular ganglion cell asymmetries were expressed as absolute difference and ratios between inferior hemisphere and superior hemisphere, inferotemporal (IT) and superotemporal (ST), IT and superonasal (SN), IT and inferonasal (IN), ST and IN as well as temporal and nasal. An asymmetry index was assigned by taking the absolute value of log10 of the ratio. The area under the receiver operating characteristics curve (AUROC), partial AUROC (pAUROC) ≥ specificities 90 and 95%, cutoff values and sensitivities at specificities 90 and 95% was analyzed.ResultsParameters with largest AUROCs were IT GCIPL thickness (0.784), average RNFL thickness (0.767), and average C/D (0.746). For macular asymmetry parameters, log IT/SN index had the largest AUROC (0.734), followed by log IT/IN index (0.725), and absolute difference of IT−SN GCIPL thickness (0.715). Performance was comparable between the best measures of asymmetry analysis (log IT/SN index) and those of cpRNFL, GCIPL, and ONH parameters (all P > 0.05). The IT/SN asymmetry index not only had the largest pAUROC based on the pAUROCs ≥90 and 95% specificity (0.044 and 0.019) but also had the highest diagnostic sensitivity at 90 and 95% specificities (52.2 and 46.3%).ConclusionsGCIPL asymmetry measurements have diagnostic ability comparable to cpRNFL, GCIPL, and ONH analysis for PPG. The best macular ganglion cell asymmetry parameter was IT/SN asymmetry index, which could be a new parameter to detect early structural changes in PPG.

Ganglion cell analysis at acute episode of nonarteritic anterior ischemic optic neuropathy to predict irreversible damage. A prospective study.

To assess the capability of ganglion cell-inner plexiform layer (GCIPL) thickness analysis by optical coherence tomography (OCT) to detect early neuronal loss in nonarteritic anterior ischemic optic neuropathy (NAION). Sixteen patients with unilateral NAION participated in this prospective study. Complete ophthalmologic evaluation including visual acuity, visual field (VF) test, and spectral domain optical coherence tomography (SD-OCT) of peripapillary retinal nerve fiber layer (pRNFL) and GCIPL thickness were performed in the acute phase (within 1week: 2.7 ± 2.1days) and at 2weeks, 1month, 3 and 6months after diagnosis. The mean time elapsed from acute episode to irreversible damage detection by GCIPL and pRNFL analysis was registered. Correlations between the GCIPL thinning and functional parameters such as best-corrected visual acuity (BCVA) and visual field indices [mean deviation (MD) and visual field index (VFI)] in acute and chronic phase were also analyzed. NAION eyes showed a significant thinning of the mean GCIPLminimum (min) compared to the unaffected eyes as early as 2.2days after symptoms onset (p = 0.017) and at each follow-up visit. (p ≤ 0.003). The mean GCIPL average (av) was also thinner in NAION eyes compared to uninvolved eyes at 1 (p = 0.003), 3 (p = 0.002) and 6months (p < 0.001). At the acute phase, 100% of NAION eyes showed significant pRNFL thickening, while abnormal thinning was evident in GCIPLav, GCIPLmin, and GCIPL deviation map analysis in 31.3, 56.3, and 62.5% of NAION eyes. The abnormal thinning rates increased to 43.8, 75, and 81.3% at 2weeks and to 62.5, 100, and 100% at 1month, respectively. At 2weeks, GCIPLmin thickness significantly correlated with both acute and chronic BCVA, MD, and VFI. Furthermore, the mean superior and inferior GCIPL thicknesses at 2weeks associated with corresponding mean inferior and superior hemifield MD at 6months. GCIPL analysis by SD-OCT can be considered as a useful biomarker to establish ganglion cell damage. GCIPL min and GCIPL deviation map are abnormally thinner in 56.3 % and 62.5 % of eyes at presentation, respectively. Therefore, both parameters are abnormally thinned in more than 50 % of eyes at presentation. At 2 weeks, GCIPL min thickness significantly correlated with chronic BCVA, MD and VFI; therefore, GCIPL min thickness can predict final visual dysfunction.

Pattern of Macular Ganglion Cell-Inner Plexiform Layer Defect Generated by Spectral-Domain OCT in Glaucoma Patients and Normal Subjects.

To elucidate patterns of macular ganglion cell-inner plexiform layer (GCIPL) defects by Cirrus optical coherence tomography (OCT) and examine the spatial relationship between GCIPL defect and visual field (VF) defect patterns. A total of 116 eyes of 116 normal subjects and 111 eyes of 111 glaucoma patients were included. The 227 study subjects underwent Cirrus OCT imaging in macular cube mode and reliable standard VF testing. Two ophthalmologists blindly classified GCIPL defect patterns and VF defects. The frequency distribution of GCIPL defect patterns and spatial relationships between GCIPL defects and VF defects were investigated. GCIPL defect patterns were classified as minimal, inner, outer, diffuse mild, diffuse severe, inferior confined, inferior dominant, superior confined, and superior dominant defects in normal controls (71.6%, 7.8%, 4.3%, 1.7%, 0%, 10.3%, 1.7%, 1.7%, and 0.9%, respectively) and in glaucoma patients (11.7%, 3.6%, 4.5%, 7.2%, 21.6%, 22.5%, 18.0%, 4.5%, and 6.3%, respectively). In mild and moderate glaucoma patients, the inferior confined type was most frequent (21.9% and 50.0%, respectively). However, the diffuse severe type was most frequent (59.1%) in advanced glaucoma patients. The locations of the VF defects corresponded to the locations of the GCIPL defects in glaucoma patients (P=0.012). Glaucomatous damage of the macula was common and more frequent in the inferior retina. GCIPL defect patterns as determined by SD-OCT imaging corresponded well with central VF defects. It seems macular GCIPL analysis may be useful for evaluating glaucomatous optic neuropathy.

Measurement of retinal nerve fiber layer and macular ganglion cell-inner plexiform layer with spectral-domain optical coherence tomography in patients with optic nerve head drusen.

To evaluate the effect of optic nerve head drusen (ONHD) on the retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) using Cirrus optical coherence tomography (OCT). Fifty-seven eyes of thirty patients with ONHD and thirty-eight eyes of twenty age-matched and sex-matched control subjects underwent circumpapillary and macular scanning using Cirrus OCT. The percentages of eyes with abnormal GCIPL and RNFL values according to the Cirrus normative data were analysed and compared. Overall, eyes with ONHD showed abnormally reduced values for average and minimum GCIPL thicknesses in 35 % and 45 % of cases compared to 2 % for both values in control eyes (P < 0.001). Average RNFL thickness comparison between eyes with ONHD and normal eyes revealed abnormal thinning in 33 % vs. 0 %, respectively (p = 0.002). The percentage of abnormal thinning increased with higher grades of ONHD for all the parameters evaluated, so that in grade III drusen, values were abnormally reduced in 80 % of eyes in all three analyses. Regarding buried ONHD, 30 % and 4 % of eyes had an abnormally reduced minimum GCIPL and average RNFL thickness, respectively. Furthermore, 26 % of these eyes had abnormal GCIPL exams with a normal or increased RNFL thickness. Both RNFL and GCIPL analysis reveal significant thinning in eyes with ONHD directly correlated with drusen severity. In buried ONHD, the abnormality rate was significantly higher with GCIPL compared to RNFL evaluation, suggesting that GCIPL analysis might be an early structural indicator of neuronal loss in the setting of thickened RNFL.

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.

A comparison of false positives in retinal nerve fiber layer, optic nerve head and macular ganglion cell-inner plexiform layer from two spectral-domain optical coherence tomography devices

The incidence of false positive (FP) results of optic coherence tomography (OCT) retinal nerve fiber layer (RNFL) color code in healthy subjects can be very high with Cirrus OCT. Recent evidence has shown that OCT parameters derived from macular ganglion cell-inner plexiform layer (GCIPL) have excellent ability to discriminate between normal eyes and eyes with early glaucoma. This was a prospective, cross-sectional study. One hundred eyes from 50 healthy volunteers underwent circumpapillary scanning by Cirrus and Spectralis OCT and macular scanning using Cirrus OCT. FP rates for each of the OCT parameters, using predefined criteria for an abnormal test were calculated. Comparative analysis was performed using the McNemar test. A generalized estimating equations model (GEE) was used to compare demographic and clinical factors between the eyes with normal findings and eyes with abnormal results. The overall RNFL color-code FP rate was significantly higher for Cirrus (39%) than for Spectralis (18%) (P = 0.000). The Spectralis RNFL FP rate showed no significant difference when compared to the FP rate by Cirrus GCIPL (13%) and ONH (11%) analysis. Axial length, mean spherical equivalent, presence of peripapillary atrophy, and tilted disc were significantly related to the RNFL FP occurrence displayed by both devices. Spectralis might be more specific than Cirrus when evaluating the RNFL thickness for Caucasians and moderate myopic population. GCIPL and ONH analysis might be more useful than RNFL thickness to evaluate this population using Cirrus OCT.