Retinal Ganglion Cell-inner Plexiform Layer Research Articles

Macular Ganglion Cell–Inner Plexiform Layer Loss Precedes Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma with Lower Intraocular Pressure

To investigate which clinical measures influence whether an individual demonstrates earliest glaucomatous structural progression on peripapillary retinal nerve fiber layer (pRNFL) or macular ganglion cell-inner plexiform layer (mGCIPL). Prospective, longitudinal cohort study. Two hundred seventy-one eyes from 207 individuals with statistically significant evidence of glaucomatous progression on OCT Guided Progression Analysis (GPA) software were drawn from a total of 1271 eyes from 686 individuals categorized as glaucoma suspect or having early manifest glaucoma undergoing glaucoma surveillance. Individuals demonstrating earliest evidence of longitudinal progression on mGCIPL GPA event analysis were compared with individuals demonstrating evidence of earliest longitudinal progression on pRNFL GPA event analysis. Correlation of OCT event change analysis with intraocular pressure (IOP), clinical variables, and baseline thickness of the pRNFL and mGCIPL. Intraocular pressure, baseline pRNFL thickness, baseline mGCIPL thickness, and systemic hypertension were associated with location of first progression. Eyes demonstrating earliest longitudinal progression on mGCIPL had significantly lower maximum-recorded pretreatment IOP (mean difference, 3.90 mmHg; 95% confidence interval [CI], 2.37-5.43 mmHg; P < 0.001). The interval between progression on pRNFL and progression on mGCIPL increased by 12.4 months for every 5-mmHg increase in IOP (95% CI, 10.32-15.72 months). Eyes demonstrating earliest longitudinal progression on mGCIPL showed significantly lower baseline average pRNFL thickness than eyes progressing on pRNFL first (mean difference, 7.07 μm; 95% CI, 4.38-9.77 μm; P < 0.001). Eyes progressing first on mGCIPL parameters were 3.03 times more likely to demonstrate a new paracentral field defect than eyes progressing first on pRNFL parameters (odds ratio, 3.03; 95% CI, 1.26-7.28; P= 0.01). Clinical features, particularly pretreatment IOP, influence whether structural glaucoma progression is detected earlier with mGCIPL or pRNFL imaging. These data support the usefulness of mGCIPL imaging in addition to pRNFL analysis for detection of glaucoma progression, particularly in patients with normal IOP.

Changes in Peripapillary Microvasculature and Retinal Thickness in the Fellow Eyes of Patients With Unilateral Retinal Vein Occlusion: An OCTA Study.

To evaluate changes in peripapillary microvascular parameters in the fellow eyes of patients with unilateral retinal vein occlusion (RVO) using optical coherence tomography angiography (OCTA) and to determine the relationships between peripapillary microvasculature and retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness. Eighty-three patients with unilateral RVO (50 patients with branch RVO and 33 with central RVO) and 83 normal controls were enrolled. OCTA (Cirrus HD-OCT 5000 with AngioPlex) 6 × 6-mm scans centered on the optic disc were acquired. Peripapillary vessel density (VD) and perfusion density (PD) were automatically calculated. The average RNFL and GC-IPL thicknesses in the fellow eyes of RVO patients were significantly thinner than in normal controls (93.5 vs. 96.6 μm, P = 0.013 and 81.3 vs. 84.1 μm, P = 0.003, respectively). In the fellow eyes of patients with unilateral RVO, the peripapillary VD of the inner ring, outer ring, and full area (17.47, 18.50, and 17.89, respectively) were significantly lower than those of controls (17.87, 18.87, and 18.27, respectively). The peripapillary PD of the inner ring, outer ring, and full area (0.456, 0.467, and 0.456, respectively) were also significantly lower than those of controls (0.468, 0.476, and 0.466, respectively). RNFL and GC-IPL thicknesses were correlated with both peripapillary VD and PD. OCTA revealed that peripapillary microvascular parameters in the fellow eyes of patients with unilateral RVO were decreased, and GC-IPL and RNFL thinning were also observed. The RNFL and GC-IPL thicknesses were positively correlated with both peripapillary VD and PD.

Aqueous semaphorin 3A level correlates with retinal macular oedema and ganglion cell degeneration in patients with retinal vein occlusion

To investigate the semophorin 3A (SEMA3A) level in aqueous humor of patients with retinal vein occlusion (RVO) and explore the correlation of SEMA3A with macular oedema and ganglion cell degeneration in RVO. This comparative study prospectively included 41 consecutive patients (41 eyes) with RVO who had intravitreal anti-VEGF injections from March 2014 to March 2015 for cystoid macular oedema (CME) or neovascular glaucoma (NVG). The patients were divided into three groups according to the fluorescein angiograghy (FFA): central retinal vein occlusion (CRVO) group (n=15), branch retinal vein occlusion (BRVO) group (n=15) and NVG group (secondary to CRVO, n=11). The patients who had undergone cataract surgery (n=16) during the same period served as controls. The SEMA3A concentration in aqueous humor collected before the initial anti-VEGF injection was determined by enzyme-linked immunosorbent assay (ELISA). Central retinal thickness (CRT), cube volume (CV) and ganglion cell-inner plexiform layer (GC-IPL) thickness was analysed by spectral-domain optical coherence tomography (SD-OCT). Semaphorin 3A level in CRVO group (1.52±1.23ng/ml) and NVG group (1.67±0.98ng/ml) were significantly higher than the control group (0.66 ± 0.58ng/ml; both p<0.05). Moreover, SEMA3A level in CRVO group was higher than BRVO group (1.52±1.23ng/ml versus 0.53±0.37ng/ml; p<0.05). SEMA3A level was positively correlated with CRT and CV in both BRVO group (CRTr=0.6535, p=0.0082; CVr=0.5190, p=0.0474) and CRVO group (CRTr=0.6270, p=0.0124; CVr=0.6898, p=0.0044). In RVO patients, the GC-IPL thickness of affected eyes were significantly reduced compared with the normal follow eyes (CRVOt=4.55, p=0.006; BRVOt=4.54, p=0.004). Meanwhile, negative correlation of SEMA3A level with GC-IPL thickness was found in both BRVO group (r=-0.5906, p=0.0205) and CRVO group (r=-0.6100, p=0.0157). Semaphorin 3A level is increased in aqueous humor of RVO patients. Positive correlation of CRT as well as negative correlation of GC-IPL thickness with SEMA3A may suggest a pathological role of SEMA3A in macular oedema and ganglion cell degeneration during RVO.

Optical Coherence Tomography of the Retinal Ganglion Cell Complex in Leber’s Hereditary Optic Neuropathy and Dominant Optic Atrophy

ABSTRACTBackground: Mitochondrial optic neuropathies such as Leber’s Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA) have been shown to produce an optic neuropathy secondary to retinal ganglion cell loss with thinning of the retinal ganglion cell complex (RGCC).Methods: We performed a retrospective analysis assessing the thicknesses of the peripapillary retinal nerve fiber layer (pRNFL) along with the macular retinal ganglion cell-inner plexiform layer (RGC-IPL) using optical coherence tomography (OCT). We compared these changes among acute and chronic LHON, DOA, and normal healthy control patients.Results: Patients with chronic LHON exhibited statistically significant thinning of the RNFL in the superior, nasal, and inferior quadrants of the retina. In acute LHON, the RNFL was relatively thicker in all but the temporal quadrant when compared with respective quadrants in normal eyes; however, statistical significance was not achieved. In DOA, the RNFL was thinnest in the superior and inferior quadrants of the retina, measuring between acute and chronic LHON thickness values. In chronic LHON and DOA, both the pRNFL and RGC-IPL were significantly thinner in all four retinal quadrants relative to controls.Conclusions: This article represents the first comparative study of the RGCC between LHON and DOA. Our findings demonstrated significant thickness reductions in pRNFL and macular RGC-IPL in patients with LHON and DOA, with different specific patterns consistent with the general patterns of thinning classically observed. This study suggests the usefulness of the RGCC as a potential in vivo biomarker for assessing disease in patients with LHON and DOA.

Potential retinal biomarkers for dementia: what is new?

To summarize the current findings on clinical retinal diseases and retinal imaging changes with dementia, focusing on Alzheimer's disease. Studies observed that clinical retinal diseases such as age-related macular degeneration, open-angle glaucoma and diabetic retinopathy are related to dementia, but the associations are not entirely consistent. In terms of the retinal neuronal structure, multiple retinal neuronal layers are significantly thinner in Alzheimer's disease dementia, such as the parapapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GC-IPL). Recent studies further demonstrated that macular GC-IPL and macular RNFL are also significantly thinner in the preclinical stage of Alzheimer's disease. A thinner RNFL is also associated with a significantly increased risk of developing both cognitive decline and Alzheimer's disease dementia. In addition, studies consistently showed that retinal vascular changes are associated with poorer cognitive performance, as well as prevalent and incident Alzheimer's disease dementia. The current findings support the concept that changes in the retina, particular in retinal neuronal structure and vasculature, can reflect the status of cerebral neuronal structure and vasculature, highlighting the potential role of retinal changes as biomarkers of dementia.

Retinal vascular density evaluated by optical coherence tomography angiography in macular telangiectasia type 2.

To evaluate the retinal and choroidal vascular changes through optical coherence tomography angiography (OCTA) in patients with macular telangiectasia type 2 (MacTel 2). Our study included 20 patients (40 eyes) with MacTel 2, and age-matched and sex-matched 18 subjects (36 eyes) in the control group. Fundus color photographs, fundus autofluorescence, fundus fluorescein angiography, spectral-domain optical coherence tomography and OCTA were performed. Foveal vascular density and parafoveal vascular density (PFVD), and foveal retinal thickness and parafoveal retinal thickness, choroidal thickness (CT) and retinal ganglion cell-inner plexiform layer (GCIPL) were compared between MacTel 2 patients and normal age-matched controls. The retinal whole vascular density and PFVD of the deep plexus were significantly lower in patients with MacTel 2 than that of the control group (56.93% vs. 58.54%, p = 0.003; and 60.38% vs. 61.66%, p = 0.045). The foveal avascular zone (FAZ) of the deep plexus was significantly enlarged in patients with MacTel 2 than that of the control group (0.44 vs. 0.36, p = 0.009). There was a positive and statistically significant correlation between the FAZ of the superficial and deep plexus and CT in patients with MacTel 2. There was a positive and statistically significant correlation between retinal whole, parafoveal temporal quadrant vascular density of the superficial and deep plexus and GCIPL thickness in patients with MacTel 2. Our study demonstrated that important retinal vascular density and FAZ changes in MacTel 2 occur in the deep capillary plexus of the retina.

Optical coherence tomography in central nervous system demyelinating diseases related optic neuritis.

To compare the thickness of the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) among patients with various forms of optic neuritis (ON) and to identify whether any particular parameters or their thinning pattern can be used to distinguish the type of ON. This prospective study was conducted at the Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Thailand, between January, 2015 and December, 2016. We enlisted patients over 18 years of age with history of ON and categorized patients into 4 groups: 1) aquaporin 4 antibodies (AQP4-IgG) positive; 2) multiple sclerosis (MS); 3) myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) positive; 4) idiopathic-ON patients. Healthy controls were also included during the same study period. All patients underwent complete ophthalmological examination and spectral domain optical coherence tomography (OCT) imaging to analyze RNFL and GCIPL thickness after at least 3mo since the last episode of acute ON. The generalized estimating equation (GEE) models were used to compare the data amongst ON groups. Among 87 previous ON eyes from 57 patients (43 AQP4-IgG+ON, 17 MS-ON, 8 MOG-IgG+ON, and 19 idiopathic-ON), mean logMAR visual acuity of AQP4-IgG+ON, MS-ON, MOG-IgG+ON, and idiopathic-ON groups was 0.76±0.88, 0.12±0.25, 0.39±0.31, and 0.75±1.08, respectively. Average, superior, and inferior RNFL were significantly reduced in AQP4-IgG+ON, MOG-IgG+ON and idiopathic-ON eyes, relative to those of MS-ON. Differences were not statistically significant for RNFL or GCIPL between the AQP4-IgG+ON and MOG-IgG+ON groups, whereas visual acuity in MOG-IgG+ON was slightly, but not significantly, better (0.39 vs 0.76). Although RNFL thickness in MOG-IgG+ON was significantly reduced as compared to MS-ON, mean visual acuity and GCIPL were not different. Thinning of superior and inferior quadrants of RNFL are more commonly seen in MOG-IgG+ON and AQP4-IgG+ON. Long term visual acuity in MOG-IgG+ON is often better than AQP4-IgG+ON, whereas the structural change from OCT is comparable.

Combined Use of Retinal Nerve Fiber Layer and Ganglion Cell–Inner Plexiform Layer Event-based Progression Analysis

To evaluate patterns of glaucomatous structural progression using the combined retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) event-based progression analysis feature provided by spectral-domain optical coherence tomography (SD-OCT)'s - (GPA) software. Retrospective observational case series. Seventy-nine (79) patients were identified with open-angle glaucoma (OAG) showing clinically confirmed structural progression within a minimum 3-year follow-up period. For each eye, RNFL and GCIPL GPA data were obtained from serial SD-OCT data from 2012 to 2017. An integrated GPA map thereafter was merged by vascular landmark-guided superimposition of RNFL and GCIPL GPA event-based progression maps onto the RNFL imagery (resulting in what we call the GPA PanoMap). The GPA PanoMap progression patterns were classified as (1) RNFL-only, (2) GCIPL-only, (3) concurrent (both RNFL and GCIPL), (4) GCIPL after RNFL, and (5) RNFL after GCIPL. The locations of structural progression were classified, based on an earlier schematic model, as (1) superior vulnerability zone (SVZ), (2) papillomacular bundle (PM), (3) macular vulnerability zone (MVZ), and (4) inferoinferior portion. Structural progression patterns on the GPA PanoMap were evaluated according to the location of progression. Among the eyes with progression in the inferior hemiretina, structural progression patterns on the GPA PanoMap were evaluated according to the baseline structural damage. On the GPA PanoMap, when structural progression was located in the SVZ or inferoinferior portion, it was detected only in the RNFL area; when progression was located in the PM or MVZ, various patterns were observed, among which the concurrent pattern was the majority in both areas (43.8% and 45.6% in the PM and MVZ, respectively). Among the eyes with progression in the inferior hemiretina (n= 66), the location of progression varied but did not differ significantly according to the baseline deviation map (P= .440). The progression patterns of MVZ were significantly different among the baseline deviation map patterns (P= .023); however, all of the progression patterns of the inferoinferior portion were RNFL-only. The various progression patterns were confirmed according to the locations and baseline patterns of glaucomatous structural change on the integrated GPA map (GPA PanoMap). Combined use of RNFL and GCIPL GPA or the GPA PanoMap could be useful for determination of structural progression and understanding of its patterns in patients with glaucoma.

Discriminative power of intra-retinal layers in early multiple sclerosis using 3D OCT imaging.

To evaluate volumetric changes and discriminative power of intra-retinal layers in early-stage multiple sclerosis (MS) using a 3D optical coherence tomography (OCT) imaging method based on an in-house segmentation algorithm. 3D analysis of intra-retinal layers was performed in 71 patients with early-stage MS (mean disease duration 2.2 ± 3.5years) at baseline and 40 healthy controls (HCs). All patients underwent a follow-up OCT scan within 23 ± 9months. Patients with a clinical episode of optic neuritis (ON) more than 6months prior to study entrance were compared with patients who never experienced clinical symptoms of an ON episode (NON). Significantly decreased total retinal volume (TRV), macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL) volumes were detected in ON patients compared to NON patients (all p values < 0.05) at baseline. Each parameter on its own allowed identification of prior clinical ON based on a discriminative model (ROC analysis). Over time, TRV decreased in both ON (p = 0.013) and NON patients (p = 0.002), whereas mRNFL volume (p = 0.028) decreased only in ON and GCIPL volume (p = 0.003) decreased only in NON patients. Our 3D-OCT data demonstrated that TRV, mRNFL and GCIPL allow discrimination between ON and NON patients in a cross-sectional analysis. However, the subsequent retinal atrophy pattern diverges in the initial phase of MS: Prior ON promotes sustained axonal thinning over time indicated by mRNFL loss, whereas longitudinal measurement of GCIPL volume better depicts continuous retrograde neurodegeneration in NON patients in early-stage MS.

Normative Database and Color-code Agreement of Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-inner Plexiform Layer Thickness in a Vietnamese Population.

Evaluate the distribution and the color probability codes of the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thickness in a healthy Vietnamese population and compare them with the original color-codes provided by the Cirrus spectral domain-optical coherence tomography. This is a cross-sectional study. We recruited nonglaucomatous Vietnamese subjects and constructed a normative database for peripapillary RNFL and macular GCIPL thickness. The probability color-codes for each decade of age were calculated. We evaluated the agreement with κ coefficient between optical coherence tomography color probability codes with Cirrus built-in original normative database and the Vietnamese normative database. In total, 149 eyes of 149 subjects were included. The mean age of enrollees was 60.77 (±11.09) years, with a mean spherical equivalent of +0.65 (±1.58) D and mean axial length of 23.4 (±0.87) mm. Average RNFL thickness was 97.86 (±9.19) µm and average macular GCIPL was 82.49 (±6.09) µm. Agreement between original and adjusted normative database for RNFL was fair for average and inferior quadrant (κ=0.25 and 0.2, respectively); and good for other quadrants (range, κ=0.63 to 0.73). For macular GCIPL κ agreement ranged between 0.39 and 0.69. After adjusting with the normative Vietnamese database, the percent of yellow and red color-codes increased significantly for peripapillary RNFL thickness. Vietnamese population has a thicker RNFL in comparison with Cirrus normative database. This leads to a poor color-code agreement in average and inferior quadrant between the original and adjusted database. These findings should encourage to create a peripapillary RNFL normative database for each ethnicity.

Serial Combined Wide-Field Optical Coherence Tomography Maps for Detection of Early Glaucomatous Structural Progression

Both parapapillary and macular areas are important in determining the progression of early glaucoma. However, no attempt has been made to assess the progression of glaucoma in images that combine the 2 areas. To evaluate the potential usefulness of serial analysis of combined wide-field optical coherence tomography (OCT) maps for detection of structural progression in patients with early glaucoma. Retrospective observational study. Patients with early primary open-angle glaucoma with a minimum of 3-year follow-up involving serial spectral-domain OCT measurement were analyzed. Patients were divided into a nonprogressor group (n = 47) and a progressor group (n = 47) on the basis of serial stereo disc photography and red-free photography. Serial combined wide-field OCT maps integrating parapapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) maps were generated with the embedded software of serial spectral-domain OCT. Glaucoma specialists then assessed the structural progression detection ability of those serial wide-field OCT maps for early glaucomatous eyes and compared their sensitivity with those of RNFL and GCIPL guided progression analyses (GPAs). The diagnostic ability of the serial wide-field OCT maps for early glaucomatous structural progression. Ninety-four patients (mean [SD] age, 51.4 [12.3] years; 48 [51.1%] women; all Korean) were included. The serial wide-field OCT map analysis showed good agreement for detection of structural progression between the 2 glaucoma graders (wide-field OCT thickness map: κ = 0.649; wide-field OCT deviation map: κ = 0.833). These maps showed early glaucomatous structural progression detection abilities comparable with those of RNFL and GCIPL GPAs (sensitivities of wide-field OCT thickness map, wide-field OCT deviation map, RNFL GPA, and GCIPL GPA = 63.8%, 83.0%, 83.0%, and 66.0%, respectively, all P > .05; specificities of wide-field OCT thickness map, wide-field OCT deviation map, RNFL GPA, and GCIPL GPA = 93.6%, 95.7%, 84.8%, and 93.6%, respectively, all P > .05). The serial combined wide-field OCT maps integrating RNFL and GCIPL maps performed well in detecting structural progression in early glaucomatous eyes. Confirmation in an independent prospective study might provide greater confidence in this conclusion.

Development of Topographic Scoring System for Identifying Glaucoma in Myopic Eyes: A Spectral-Domain OCT Study

To develop a new scoring system that uses topographic diagnostic signs of spectral-domain (SD) OCT to enhance glaucoma diagnostic performance for myopic eyes and to validate the system's diagnostic ability. Cross-sectional study. A total of 517 patients (517 eyes; spherical equivalent [SE] <-1.0 diopters [D] or axial length >24.0 mm), including 175 highly myopic eyes (SE <-6.0 D or axial length >26.0 mm), were recruited and divided into 2, training (241 eyes) and validation (276 eyes) test sets. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) topographic signs were selected based on the morphologic patterns of RNFL (size, shape, location, and agreement between deviation and thickness maps) and GCIPL (size, shape, location, color tone, agreement between maps, and step sign) abnormalities indicative of higher likelihood of myopic glaucoma on deviation and thickness maps. The diagnostic score was compiled according to the sensitivity, specificity, and positive likelihood ratio (PLR) of each diagnostic sign using the training set. The area under the receiver operating characteristic curve (AUC) was plotted and compared between the OCT-provided parameters and the scoring system in the validation set. The diagnostic performance of a new scoring system as validated by AUC. Among all of the RNFL and GCIPL parameters, the presence of temporal hemifield asymmetry on the GCIPL thickness map (PLR, 5.98) showed the highest diagnostic ability, followed by location of the RNFL defect (PLR, 5.79) and color tone of the GCIPL defect (PLR, 5.04). The AUC of the topographic scoring system in myopic eyes was 0.979, which was significantly higher than those of the inferior (0.895; P < 0.001) and average (0.894; P < 0.001) RNFL thickness parameters. For highly myopic eyes, the scoring system (AUC, 0.983) also showed a higher diagnostic performance than that of the RNFL and GCIPL thickness parameters (all P < 0.001). Our scoring system including OCT topographic parameters demonstrated to be beneficial for clinicians to differentiate real glaucomatous damage from myopic healthy eyes. Our results support the value of using multitopographic OCT parameters for detecting glaucoma in myopic eyes.

A New Objective Parameter in Hydroxychloroquine-Induced Retinal Toxicity Screening Test: Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness.

This study aims to detect hydroxychloroquine (HCQ)-induced retinal toxicity at an earlier stage through the use of spectral-domain optical coherence tomography device, especially by measuring macular retinal ganglion cell-inner plexiform layer (RGC-IPL) thickness. In this study, 92 eyes of 46 Caucasian female patients (mean age 53.6±8.1 years; range 32 to 69 years) who were taking HCQ were assigned to group 1, while 80 eyes of 40 age-matched Caucasian female control subjects (mean age 56.1±10.7 years; range 34 to 71 years) were assigned to group 2. RGC-IPL thickness and retinal nerve fiber layer thickness were measured in all subjects by Cirrus high-definition optical coherence tomography model 5000 device using macular cube 512¥128 and optic disc cube 200¥200 protocols. We performed an evaluation to see if there was any difference between the measured values of the groups. The correlation between average RGC-IPL thickness measures and cumulative dose of HCQ and duration of use was analyzed. Retinal ganglion cell-inner plexiform layer of group 1 was found to be statistically thinner than that of group 2 both on average and in all segments (superior, superonasal, inferonasal, inferotemporal and superotemporal) except inferior segment when segmented (p<0.05). Additionally, a statistically significant negative correlation was found between the average RGC-IPL thickness and cumulative dose of HCQ (r= -0.371, p=0.001) as well as the duration of use (r= -0.308, p=0.006). Patients taking HCQ were found to have decreased RGC-IPL thickness at an early stage due to retinal toxicity induced by the drug. We think that measuring the RGC-IPL thickness may become an important objective in HCQ screening tests.

Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer’s disease

Inner retina in Alzheimer's Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninvasive biomarkers to diagnose AD. This cross-sectional case-control study enrolled 15 mild cognitive impairment (MCI) patients, 15 mild-moderate AD patients, and 18 cognitively normal adults. NFL and GCIPL thicknesses on optical coherence tomography (OCT) were measured using Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) and Spectralis software. We demonstrated that regional thicknesses of NFL or GCIPL on macular or nerve OCTs did not differ between groups. However, a multi-variate regression analysis identified macular areas with a significant thickening or thinning in NFL and GCIPL in MCI and AD patients. Our primary findings controvert previous reports of thinner NFL in moderate-to-severe AD. The areas of thickening of GCIPL and NFL in the macula adjacent to areas of thinning, as revealed by a more complex statistical model, suggest that NFL and GCIPL may undergo dynamic changes during AD progression.

Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis optica.

To determine the thickness of the retinal ganglion cell-inner plexiform layer (GCIPL) and the retinal nerve fiber layer (RNFL) in patients with neuromyelitis optica (NMO). We conducted a cross-sectional study that included 30 NMO patients with a total of 60 eyes. Based on the presence or absence of optic neuritis (ON), subjects were divided into either the NMO-ON group (30 eyes) or the NMO-ON contra group (10 eyes). A detailed ophthalmologic examination was performed for each group; subsequently, the GCIPL and the RNFL were measured using high-definition optical coherence tomography (OCT). In the NMO-ON group, the mean GCIPL thickness was 69.28±21.12 µm, the minimum GCIPL thickness was 66.02±10.02 µm, and the RNFL thickness were 109.33±11.23, 110.47±3.10, 64.92±12.71 and 71.21±50.22 µm in the superior, inferior, temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean GCIPL thickness was 85.12±17.09 µm, the minimum GCIPL thickness was 25.39±25.1 µm, and the RNFL thicknesses were 148.33±23.22, 126.36±23.45, 82.21±22.30 and 83.36±31.28 µm in the superior, inferior, temporal and nasal quadrants, respectively. In the control group, the mean GCIPL thickness was 86.98±22.37 µm, the minimum GCIPL thickness was 85.28±10.75 µm, and the RNFL thicknesses were 150.22±22.73, 154.79±60.23, 82.33±7.01 and 85.62±13.81 µm in the superior, inferior, temporal and nasal quadrants, respectively. The GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group (P<0.05); additionally, the RNFL was thinner in the inferior quadrant in the NMO-ON group than in the control group (P<0.05). Significant correlations were observed between the GCIPL and RNFL thickness measurements as well as between thickness measurements and the two visual field parameters of mean deviation (MD) and corrected pattern standard deviation (PSD) in the NMO-ON group (P<0.05). The thickness of the GCIPL and RNFL, as measured using OCT, may indicate optic nerve damage in patients with NMO.

Peripapillary retina nerve fiber layer thickness and macular ganglion cell layer thickness in patients with obstructive sleep apnea syndrome.

PurposeTo investigate the association of the severity of obstructive sleep apnea syndrome (OSAS) with peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GC-IPL).Materials and methodsIn this cross-sectional study, 145 patients with OSAS and 40 healthy subjects were enrolled. OSAS patients were further divided into mild (n=50), moderate (n=36), and severe (n=59) OSAS groups according to their apnea-hypopnea index (AHI) values. Spectral-domain optical coherence tomography was used to measure the peripapillary RNFL and GC-IPL thicknesses.ResultsThere was no statistical difference between the RNFL thickness in OSAS and control groups (P>0.05). Both average GC-IPL and minimum GC-IPL thicknesses were significantly lower in severe OSAS group than in healthy controls (P<0.05 for both). There was a significant negative correlation between AHI and both average GC-IPL (r=-0.232, P=0.005) and minimum GC-IPL (r=-0.233, P=0.005) thicknesses.ConclusionsOur study results suggest that although RNFL thickness did not differ significantly between OSAS and control groups, ganglion cell layer thickness in OSAS patients is much lower than in healthy population. Ganglion cell thickness showed a significant correlation with the severity of OSAS.

Optical coherence tomography indices of structural retinal pathology in schizophrenia.

Prior optical coherence tomography (OCT) studies of schizophrenia have identified thinning of retinal layers. However, findings have varied across reports, and most studies have had serious methodological limitations. To address unresolved issues, we determined whether: (1) retinal thinning in schizophrenia occurs independently of comorbid medical conditions that affect the retina; (2) thinning is independent of antipsychotic medication dose; (3) optic nerve parameters are abnormal in schizophrenia; and (4) OCT indices are related to visual and cognitive impairments common in schizophrenia. A total of 32 people with schizophrenia and 32 matched controls participated. Spectral domain OCT generated data on retinal nerve fiber layer (RNFL), macula, and ganglion cell-inner plexiform layer (GCL-IPL) thickness, in addition to cup volume and the cup-to-disc ratio at the optic nerve head. Subjects with schizophrenia also completed measures of symptoms, visual processing, and IQ. The groups did not differ on RNFL, macula, or GCL-IPL thickness. However, thinning of these layers was related to the presence of diabetes or hypertension across the sample as a whole. The schizophrenia group demonstrated enlarged cup volume and an enlarged cup-to-disc ratio in both eyes, which were unrelated to medical comorbidity, but were related to increased cognitive symptoms. Past reports of retinal thinning may be artifacts of medical comorbidity that is over-represented in schizophrenia, or other confounds. However, optic nerve head abnormalities may hold promise as biomarkers of central nervous system abnormality, including cognitive decline, in schizophrenia.

Glaucoma Diagnostic Capabilities of Foveal Avascular Zone Parameters Using Optical Coherence Tomography Angiography According to Visual Field Defect Location.

To assess the diagnostic ability of foveal avascular zone (FAZ) parameters to discriminate glaucomatous eyes with visual field defects (VFDs) in different locations (central vs. peripheral) from normal eyes. Totally, 125 participants were separated into 3 groups: normal (n=45), glaucoma with peripheral VFD (PVFD, n=45), and glaucoma with central VFD (CVFD, n=35). The FAZ area, perimeter, and circularity and parafoveal vessel density were calculated from optical coherence tomography angiography images. The diagnostic ability of the FAZ parameters and other structural parameters was determined according to glaucomatous VFD location. Associations between the FAZ parameters and central visual function were evaluated. A larger FAZ area and longer FAZ perimeter were observed in the CVFD group than in the PVFD and normal groups. The FAZ area, perimeter, and circularity were better in differentiating glaucomatous eyes with CVFDs from normal eyes [areas under the receiver operating characteristic curves (AUC), 0.78 to 0.88] than in differentiating PVFDs from normal eyes (AUC, 0.51 to 0.64). The FAZ perimeter had a similar AUC value to the circumpapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer thickness for differentiating eyes with CVFDs from normal eyes (all P>0.05, the DeLong test). The FAZ area was significantly correlated with central visual function (β=-112.7, P=0.035, multivariate linear regression). The FAZ perimeter had good diagnostic capability in differentiating glaucomatous eyes with CVFDs from normal eyes, and may be a potential diagnostic biomarker for detecting glaucomatous patients with CVFDs.

O9 Early macular atrophy at optical coherence tomography is predicted by visual evoked potentials and precedes peripapillary neurodegeneration after acute optic neuritis

Background Demyelination and axonal loss following acute optic neuritis (AON) can be respectively measured as delayed visual evoked potentials (VEPs) and as reduced thickness of retinal nerve fiber (RNFL) and ganglion cell-inner plexiform layer (GCL-IPL) at optical coherence tomography (OCT). Traditionally, atrophy of GCL and IPL, which contains cell bodies and dendrites of the ganglion cells, is measured at the macula, but can be also measured with faster peripapillary scans at the optic nerve head. We explored if, in addition to the GCL measured at the macula, GCL-IPL atrophy could be detected with peripapillary scans and its association with VEPs evolution after AON. Methods Twenty subjects with unilateral AON underwent OCT and full-field VEP at baseline in the acute phase (8 ± 6 days after onset) and after 1 month (33 ± 5 days) and 4 months (128 ± 11 days). RNFL and GCIPL were segmented from peripapillary scans, GCL from macular scans. We explored the time evolution of RNFL, GCIPL, and GCL thickness over time and their correlation with VEP latency. Results Macular GCL was significantly reduced at 1 month (34.49 ± 4.42 μ m) compared to baseline (36.31 ± 3.67 μ m; p = 0.008). Peripapillary RNFL and GCIPL reduction was instead significant only at 4 months (RNFL: 97.32 ± 16.07 μ m at baseline and 96.65 ± 16.73 μ m at 1 month vs 92.11 ± 16.98 μ m at 4 month, p = 0.023; GCIPL: 47.94 ± 3.22 μ m at baseline and 46.61 ± 4.63 μ m at 1 month vs 43.96 ± 6.65 μ m at 4 month, p = 0.005). Baseline VEP latency correlated with OCT measures both at 1 month (RNFL: r = −0.648, p = 0.001; GCIPL: r = −0.495, p = 0.019; GCL: r = −0.742, p r = −0.616, p = 0.004; GCIPL: r = −0.564, p = 0.010; GCL: r = −0.748, p Discussion After AON, macular changes seem to precede detectable atrophy at peripapillary level, even within ganglion cell layers, suggesting this region as the most suitable to track early neurodegeneration. Demyelination in the acute phase, as measured by early VEPs, is associated with subsequent neuroretinal neurodegeneration and suggests the usefulness of VEPs as early predictor of ON outcome for individualized treatment and for patients’ selection for clinical trials assessing remyelination and neuroprotective strategies.

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.