Retinal Ganglion Cell Layer Research Articles

Silent Information Regulator T1 in Aqueous Humor of Patients with Age-Related Macular Degeneration

Purpose: The purpose of this study is to compare the aqueous humor level of Silent Information Regulator T1 (SIRT1) between patients with Age-related Macular Degeneration (AMD) and cataract patients. Materials and Methods: Aqueous humor level of SIRT1 was measured by enzyme-linked immunosorbent assay in 13 patients with wet-type AMD (n=13, AMD group) and 13 patients with cataracts (cataract group). In addition, the thickness of each retinal layer was determined by optical coherence tomography. Results: The aqueous humor level of SIRT1 was significantly lower in the AMD group than in the cataract group (p=0.007). In the AMD group, the SIRT1 level was positively correlated with the thickness of the retinal ganglion cell layer (r=0.31) and the inner nuclear layer (r=0.76). Conclusion: The aqueous level of SIRT1 decreased as the ganglion cell layer and inner nuclear layer became thinner, suggesting that reduction of SIRT1 activity might be involved in the pathogenesis of this disease.

Cell - Vessel Mismatch in Glaucoma: Correlation of Ganglion Cell Layer Soma and Capillary Densities.

PurposeThe purpose of this study was to characterize the relationship between retinal ganglion cell layer (GCL) soma density and capillary density in glaucomatous eyes.MethodsSix glaucoma subjects with known hemifield defects and 6 age-matched controls were imaged with adaptive optics – optical coherence tomography (AO-OCT) at 6 locations: 3 degrees, 6 degrees, and 12 degrees temporal to the fovea above and below the midline. GCL soma density and capillary density were measured at each location. Coefficients of determination (pseudo R2) and slopes between GCL soma and capillary density were determined from mixed-effects regressions and were compared between glaucoma and control subjects, between more and less affected hemifield in subjects with glaucoma, and between subjects with early and moderate glaucoma, both in a local, bivariate model and then a global, multivariable model controlling for eccentricity and soma size.ResultsThe global correlation between GCL soma and capillary density was stronger in control versus subjects with glaucoma (R2 = 0.59 vs. 0.22), less versus more affected hemifields (R2 = 0.55 vs. 0.01), and subjects with early versus moderate glaucoma subjects (R2 = 0.44 vs. 0.18). When controlling for eccentricity and soma size, we noted an inverse soma-capillary density local relationship in subjects with glaucoma (−388 ± 190 cells/mm2 per 1% change in capillary density, P = 0.046) and more affected hemifields (−602 ± 257 cells/mm2 per 1% change in capillary density, P = 0.03).ConclusionsAn inverted soma-capillary density local relationship in areas affected by glaucoma potentially explains weaker global correlations observed between GCL soma and capillary density, suggesting cell–vessel mismatch is associated with the disease.

Changes in retinal multilayer thickness and vascular network of patients with Alzheimer\u2019s disease

BackgroundRetinal biomarkers of Alzheimer’s disease (AD) have been extensively investigated in recent decades. Retinal nervous and vascular parameters can reflect brain conditions, and they can facilitate early diagnosis of AD.ObjectiveOur study aimed to evaluate the difference in retinal neuro-layer thickness and vascular parameters of patients with AD and healthy controls (HCs).MethodsNon-invasive optical coherence tomography angiography (OCTA) was used to determine the combined thickness of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), as well as the full retinal thickness (FRT). The vascular branching (VB), vascular curvature (VC), and vascular density (VD) for AD and HC groups were also obtained. The Mini-Mental State Examination (MMSE) was used to evaluate the cognitive performance of all the participants. After obtaining all the parameters, two-way analysis of variance (ANOVA) was used to compare the mean values of all the retinal parameters of the patients with AD and the HCs. Pearson's correlation was used to test the association between retinal parameters, MMSE scores, and vascular parameters.ResultsSeventy-eight eyes from 39 participants (19 AD and 20 HC; male, 52.6% in AD and 45.0% in HC; mean [standard deviation] age of 73.79 [7.22] years in AD and 74.35 [6.07] years in HC) were included for the analysis. The average RNFL + GCL thickness (106.32 ± 7.34 μm), FRTs of the four quadrants (290.35 ± 13.05 μm of inferior quadrant, 294.68 ± 9.37 μm of superior quadrant, 302.97 ± 6.52 μm of nasal quadrant, 286.02 ± 13.74 μm of temporal quadrant), and retinal VD (0.0148 ± 0.003) of patients with AD, compared with the HCs, were significantly reduced (p < 0.05). Retinal thickness was significantly correlated with the MMSE scores (p < 0.05). Meanwhile, retinal VD was significantly correlated with the average RNFL + GCL thickness (r2 = 0.2146, p < 0.01). When the vascular parameters were considered, the sensitivity of the AD diagnosis was increased from 0.874 to 0.892.ConclusionOur study suggested that the patients with AD, compared with age-matched HCs, had significantly reduced RNFL + GCL thickness and vascular density. These reductions correlated with the cognitive performance of the participants. By combining nerve and vessel parameters, the diagnosis of AD can be improved using OCTA technology.Trail registration Name of the registry: Chinese Clinical Trail Registry, Trial registration number: ChiCTR2000035243, Date of registration: Aug. 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx

The Effectiveness of Binocular Virtual Reality Training on Repairing Visual Field Defect of Glaucoma.

Visual field defect caused by glaucoma seriously affects the quality of life of patients, and clinically, this type of visual field defect has been considered to be irreversible. The aim of this study is to use binocular virtual reality training (VR training) to repair visual field defect in glaucoma patients, improve the quality of life of patients, and provide a new therapeutic strategy for the rehabilitation of glaucoma. Seventy glaucoma patients (median 56, range 15-84 years) were recruited and divided into control and training groups. Fifty-four patients' data were analyzed. The training group (n = 30) received binocular VR training for 3 months. The control group (n = 24) maintained the conventional treatment without any other intervention. Their visual field index (VFI) and mean defect (MD), and retinal nerve fiber layer average thickness (RNFL) and ganglion cell layer average thickness (GCL) average thickness before training and during followup were analyzed. In the training group, the VFI value (Z = 3.277; p = 0.001) and MD value (Z = 3.913; p < 0.0001) were significantly improved after 1 month of training. After 3 months of training, the VFI value (Z = 3.761; p < 0.0001) and MD value (Z = 3.133; p = 0.002) were significantly improved. There was no significant difference with the changes of average thickness of RNFL (p = 0.350) and GCL average (p = 0.383) after 3 months of training; whereas in the control group, except for a further reduction in GCL average thickness (Z = 3.158; p = 0.002) compared with the baseline data, the other followup data were not statistically significant compared with the baseline data. Our data suggested that binocular VR training can significantly improve the visual field defect of glaucoma patients but warrants further study with large sample size. Clinical Trail registration number: ChiCTR1900027909.

Creation of a New Explosive Injury Equipment to Induce a Rabbit Animal Model of Closed Globe Blast Injury via Gas Shock.

To establish a rabbit animal model of closed globe blast injury with an application of self-developed explosive injury equipment, we tend to explore the anatomic and pathological changes of eyes under different gas pressure. The device comprises of high-pressure air source compression pump, air channel, and gas shock. There were 36 healthy bluish blue rabbits exposed to one of five blast pressures (500, 1,000, 1,500, 2,000, and 5,000 Kpa). Slit lamp microscope, B-mode ultrasonography, fundus photography, optical coherence tomography (OCT), and intraocular pressure (IOP) examination were performed at 0-, 1-, 3-, and 7-days post exposure, while gross histopathology was assessed with H&E stain at 7 days. The contralateral eyes and non-blast exposed rabbits were used as controls. Definitive evidence of closed globe blast injury was obtained. Corneal edema and hyphema were observed in the models under all pressures with no full-thickness globe injury, or lens rupture, as the severity was pressure independent. There was no obvious retinal abnormality on B ultrasound or OCT scan, while light vitreous hemorrhage, commotio retinae, and heavy retinal pigmentation presented on one eye, respectively, in the eyes exposed to 5,000 Kpa. Increased retinal thickness with disorganizations on the retinal ganglion cell (RGC) layer and RGC apoptosis in groups under higher pressure (>500 Kpa). IOP of injured eyes were statistically decreased at day 1 and 7 post injury (p < 0.05). Conclusively, the rabbit animal model induced by self-developed equipment could mimic the clinical features of closed ocular blast injury successfully that was feasible and easy to operate. This will be a new rabbit animal model for investigating mechanisms and new therapeutic interventions of closed globe blast injury in the future.

Diagnostic accuracy of total macular and ganglion cell layer thickness in differentiating different stages of glaucoma: an SD-OCT study

Purpose: To determine the diagnostic accuracy of mean macular retinal thickness (mRT) and macular ganglion cell layer (mGCL) thickness measured by Spectralis spectral-domain optical coherence tomography (SD-OCT) posterior pole thickness map (PPTM) in differentiating between normal and glaucoma eyes of different severity.Study design: Cross-sectional study.Methods: All subjects were divided into normal and glaucoma groups according to the visual fields-based Glaucoma Staging System. They underwent slit-lamp examination, Humphrey visual field test, and SD-OCT (PPTM) imaging. mRT and mGCL thickness measurements were recorded. Analysis of variance with the least significant difference post hoc test was used for pairwise comparison. Ability to discriminate between normal eyes and those with differing severity of glaucoma was assessed using the area under the receiver operating characteristic curve (AUROC).Results: A total of 201 eyes from 201 subjects were enrolled in this study. The mean glaucoma was 290.2 ± 12.1 μm, 270.1 ± 17.0 μm, and 259.1 ± 15.0 μm, respectively. Mean mGCL thickness for the corresponding three groups was 32.3 ± 2.8 μm, 27.6 ± 3.3 μm and 22.2 ± 3.8μm, respectively. AUROC analysis showed excellent diagnostic discrimination between glaucoma and normal subjects for mRT (AUC: 0.90) and mGCL thickness (AUC: 0.92). The cut-off value of mRT was 274.9 μm (90% sensitivity, 75% specificity) and of mGCL thickness was 27.9 μm (93% sensitivity, 74% specificity). The discrimination ability performance of mRT and mGCL thickness deteriorated with increasing severity of glaucoma with mGCL thickness (AUC: 0.67–0.87) performing slightly better than mRT for all grades (AUC: 0.58–0.71).Conclusions: mRT and mGCL thickness measurement on PPTM showed great sensitivity and specificity to discern between normal and glaucomatous subjects. The discrimination ability of mRT and mGCL thickness, however, decreases with increasing grade of glaucoma. We believe SD-OCT PPTM offers an alternative imaging method to detect early glaucoma.

Microvascular Breakdown Due to Retinal Neurodegeneration in Ataxias.

Neurodegenerative ataxias are devastating disorders of the cerebellum and spinal cord, accompanied by death of retinal ganglion cells, leading to relentlessly progressive decline of motor coordination and permanent disability. Retinal microvascular affection has not yet been determined. The aim of this study is to assess whether retinal microvascular alterations occur and, if so, whether they are concurrent with or follow cell death in the retina in neurodegenerative diseases. This study involves the cross-sectional observational study of 43 patients with ataxia and 43 controls enrolled from August 1, 2018, to September 30, 2020. The extent of ataxia was determined by the Scale for the Assessment and Rating of Ataxia. Changes in retinal vasculature were examined by optical coherence tomography angiography (OCT-A) and retinal cell and fiber density by OCT in ataxias concurrently. When comparing the ataxia cohort with healthy subjects, ataxia patients exhibited reduced vessel density in the radial peripapillary capillary (RPC) network (P=0.005), capillary density inside the optic nerve head (cdONH) (P < 0.001), nasal superficial vascular plexus (P=0.03) as well as reduced ganglion cell layer (GCL) volume (P=0.04), and temporal peripapillary retinal nerve fiber layer thickness (P=0.04). Mixed effect analysis modeling laterality confirmed these findings. These findings demonstrate a distinct pattern of concurrent changes in vessel density of the retinal superficial vascular complex, encompassing the superficial vascular plexus, RPC network and cdONH, and retinal GCL volume, providing new insights into the ongoing degeneration in ataxias. Our findings may have relevance for design of novel therapeutic approaches for ataxias and possibly other neurodegenerative diseases.

Optic neuritis in Asian type opticospinal multiple sclerosis (OSMS-ON) in a non-Asian population: A functional-structural paradox

BackgroundBiomarkers have improved the classification of autoimmune inflammatory disorders, including optic neuritis (ON) as a frequent presentation of multiple sclerosis, neuromyelitis spectrum disorders, MOG antibody-related disease (MOGAD), and opticospinal multiple sclerosis (OSMS). The phenotype of OSMS in non-Asian populations is less well known. ObjectiveWe investigated the clinical features and prognosis of OSMS–ON in a Brazilian cohort. MethodsThis was a single-center cohort study of patients from Rio de Janeiro (Brazil) with OSMS. All individuals were MOG- and AQP4-seronegative, clinically diagnosed with ON, and had magnetic resonance imaging-confirmed transverse myelitis (TM). Subjects and healthy controls (HCs) were assessed for visual acuity (logMAR VA), automated perimetry mean deviation (MD), intraocular pressure, and spectral-domain optical coherence tomography (OCT), followed by automated retinal layer segmentation of the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (mGCIPL). Receiver operator characteristic curves were plotted and the area under the curve (AUC) was calculated for group comparisons of retinal asymmetry of the pRNFL and mGCIPL. ResultsThe 30 patients with OSMS were predominantly female and white. The mean age was 48 years (range 20–70 years). Unilateral ON was the index event in 83.3% of patients. Over the average 18-year follow-up period, there were 89 relapses of ON. In individuals with OSMS, the average VA was 0.07±0.14 in the right eye (RE) and 0.13±0.30 in the left eye (LE). The MD was −5.37±5.88 dB and −5.23±3.34 dB for the RE and LE, respectively. There was a significant cumulative loss of VA (p = 0.0003) and MD (p = 0.0001) with a higher number of recurrent episodes. Atrophy of the pRNFL thickness was significant in OSMS (RE, 78.62 ± 16.01 µm; LE, 79.86 ± 13.79 µm) relative to the HC group (RE, 98.87 ± 10.68 µm; LE, 97.87 ± 10.85 µm, p = 0.0001). Likewise, there was significant mGCIPL atrophy in patients with OSMS (RE, 74.96 ± 14.46 µm; LE, 73.88 ± 13.79 µm) relative to the HC group (RE, 90.50 ± 6.74 µm; LE, 90.41± 6.89 µm; p = 0.0001). Retinal asymmetry, inter-eye percentage, and absolute differences accurately separated patients with unilateral ON from HCs (AUC=0.89 and AUC=0.85, respectively). ConclusionA structural-functional paradox was found in OSMS with a high diagnostic value for a novel metric based on retinal asymmetry. The functional visual outcome are excellent despite significant structural damage to the inner retinal layers in patients with a high ON relapse rate and long-term bilateral sequential involvement.

Age-related changes in the rhesus macaque eye

PurposeTo assess age-related changes in the rhesus macaque eye and evaluate them to corresponding human age-related eye disease. MethodsData from eye exams and imaging tests including intraocular pressure (IOP), lens thickness, axial length, and retinal optical coherence tomography (OCT) images were evaluated from 142 individuals and statistically analyzed for age-related changes. Quantitative autofluorescence (qAF) was measured as was the presence of macular lesions as related to age. ResultsAges of the 142 rhesus macaques ranged from 0.7 to 29 years (mean = 16.4 years, stdev = 7.5 years). Anterior segment measurements such as IOP, lens thickness, and axial length were acquired. Advanced retinal imaging in the form of optical coherence tomography and qAF were obtained. Quantitative assessments were made and variations by age groups were analyzed to compare with established age-related changes in human eyes. Quantitative analysis of data revealed age-related increase in intraocular pressure (0.165 mm Hg per increase in year of age), ocular biometry (lens thickness 7.2 μm per increase in year of age; and axial length 52.8 μm per increase in year of age), and presence of macular lesions. Age-related changes in thicknesses of retinal layers on OCT were observed and quantified, showing decreased thickness of the retinal ganglion cell layer and inner nuclear layer, and increased thickness of photoreceptor outer segment and choroidal layers. Age was correlated with increased qAF by 1.021 autofluorescence units per increase in year of age. ConclusionsThe rhesus macaque has age-related ocular changes similar to humans. IOP increases with age while retinal ganglion cell layer thickness decreases. Macular lesions develop in some aged animals. Our findings support the concept that rhesus macaques may be useful for the study of important age-related diseases such as glaucoma, macular diseases, and cone disorders, and for development of therapies for these diseases.

Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies

Retinal ganglion cell (RGC) death occurs after optic nerve injury due to acute trauma or chronic degenerative conditions such as optic neuropathies (e.g., glaucoma). Currently, there are no effective therapies to prevent permanent vision loss resulting from RGC death, underlining the need for research on the pathogenesis of RGC disorders. Modeling human RGC/optic nerve diseases in non-human primates is ideal because of their similarity to humans, but has practical limitations including high cost and ethical considerations. In addition, many retinal degenerative disorders are age-related making the study in primate models prohibitively slow. For these reasons, mice and rats are commonly used to model RGC injuries. However, as nocturnal mammals, these rodents have retinal structures that differ from primates - possessing less than one-tenth of the RGCs found in the primate retina. Here we report the diurnal thirteen-lined ground squirrel (TLGS) as an alternative model. Compared to other rodent models, the number and distribution of RGCs in the TLGS retina are closer to primates. The TLGS retina possesses ~600,000 RGCs with the highest density along the equatorial retina matching the location of the highest cone density (visual streak). TLGS and primate retinas also share a similar interlocking pattern between RGC axons and astrocyte processes in the retina nerve fiber layer (RNFL). In addition, using TLGS we establish a new partial optic nerve injury model that precisely controls the extent of injury while sparing a portion of the retina as an ideal internal control for investigating the pathophysiology of axon degeneration and RGC death. Moreover, in vivo optical coherence tomography (OCT) imaging and ex vivo microscopic examinations of the retina in optic nerve injured TLGS confirm RGC loss precedes proximal axon degeneration, recapitulating human pathology. Thus, the TLGS retina is an excellent model, for translational research in neurodegeneration and therapeutic neuroprotection.This study characterizes the composition of the retinal ganglion cell (RGC) layer and the distribution of RGCs in the cone-dominant ground squirrel retina. The RGC density and the anatomical features of axon-astrocyte interaction in the ground squirrel resemble primates, rendering it an excellent alternative model for RGC neurodegeneration and neuroprotection.

Afferent Visual Manifestations of Traumatic Brain Injury

Traumatic brain injury (TBI) causes structural and functional damage to the central nervous system including the visual pathway. Defects in the afferent visual pathways affect visual function and in severe cases cause complete visual loss. Visual dysfunction is detectable by structural and functional ophthalmic examinations that are routine in the eye clinic, including examination of the pupillary light reflex and optical coherence tomography (OCT). Assessment of pupillary light reflex is a non-invasive assessment combining afferent and efferent visual function. While a assessment using a flashlight is relatively insensitive, automated pupillometry has 95% specificity and 78.1% sensitivity in detecting TBI-related visual and cerebral dysfunction with an area under the curve of 0.69-0.78. OCT may also serve as a noninvasive biomarker of TBI severity, demonstrating changes in the retinal ganglion cell layer and nerve fiber layer throughout the range of TBI severity even in the absence of visual symptoms. This review discusses the impact of TBI on visual structure and function.

Red Light Irradiation In Vivo Upregulates DJ-1 in the Retinal Ganglion Cell Layer and Protects against Axotomy-Related Dendritic Pruning.

Retinal ganglion cells (RGCs) undergo dendritic pruning in a variety of neurodegenerative diseases, including glaucoma and autosomal dominant optic atrophy (ADOA). Axotomising RGCs by severing the optic nerve generates an acute model of RGC dendropathy, which can be utilized to assess the therapeutic potential of treatments for RGC degeneration. Photobiomodulation (PBM) with red light provided neuroprotection to RGCs when administered ex vivo to wild-type retinal explants. In the current study, we used aged (13–15-month-old) wild-type and heterozygous B6;C3-Opa1Q285STOP (Opa1+/−) mice, a model of ADOA exhibiting RGC dendropathy. These mice were pre-treated with 4 J/cm2 of 670 nm light for five consecutive days before the eyes were enucleated and the retinas flat-mounted into explant cultures for 0-, 8- or 16-h ex vivo. RGCs were imaged by confocal microscopy, and their dendritic architecture was quantified by Sholl analysis. In vivo 670 nm light pretreatment inhibited the RGC dendropathy observed in untreated wild-type retinas over 16 h ex vivo and inhibited dendropathy in ON-center RGCs in wild-type but not Opa1+/− retinas. Immunohistochemistry revealed that aged Opa1+/− RGCs exhibited increased nitrosative damage alongside significantly lower activation of NF-κB and upregulation of DJ-1. PBM restored NF-κB activation in Opa1+/− RGCs and enhanced DJ-1 expression in both genotypes, indicating a potential molecular mechanism priming the retina to resist future oxidative insult. These data support the potential of PBM as a treatment for diseases involving RGC degeneration.

Retinal nerve fibre layer and ganglion cell layer changes in children who recovered from COVID-19: a cohort study

ObjectiveTo investigate the optic nerve and macular parameters of children who recovered from COVID-19 compared with healthy children using optical coherence tomography (OCT).DesignCohort study.SettingHospital Clinico San Carlos, Madrid.PatientsChildren between 6...

Retinal and choroidal thickness measurements in obstructive sleep apnea: impacts of continuous positive airway pressure treatment.

To examine retinal and choroidal thicknesses in individuals with obstructive sleep apnea (OSA) and determine the impacts of continuous positive airway pressure (CPAP) treatment. Prospective follow-up study conducted at a university hospital. 40 patients with OSA, 28 treated with CPAP, and 12 untreated, were enrolled immediately after diagnosis and graded according to the apnea hypopnea index (AHI) determined in an overnight polysomnography. Inclusion criteria were a new diagnosis of OSA and CPAP indicated. Participants underwent a full ophthalmologic examination including optical coherence tomography (OCT) at the peripapillary, macular, and choroidal levels and the same examination 3months later. Outcome measures were peripapillary retinal nerve fiber layer (RNFL), total retinal (TRT), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), photoreceptor layer (PL), and choroidal thicknesses. At 3months, RGCL thickness was reduced at the inner nasal macula segment in the no-CPAP group (P = 0.016). In + CPAP, increases were produced in RNFL thickness (5/6 segments) and TRT (7/ 9 segments), while choroidal thinning was observed temporally (P = 0.003). At baseline, positive correlation was detected between choroidal thickness and AHI (r = 0.352, P = 0.005) and between IPL thickness (7/9 segments) and AHI (r = 0.414, P < 0.001). Initial retinal and choroidal thickening was followed by RGCL thinning over 3months. In patients receiving CPAP, we observed no thinning of any retinal layer and normalization of choroidal thickness.

Reproducibility of Retinal Nerve Fiber Layer and Macular Ganglion Cell Layer Thickness Measurements by Optical Coherence Tomography in Myopic Eyes.

In myopic eyes, reproducibility of circumpapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer thickness measurement by optical coherence tomography (OCT) showed excellent reproducibility except for the temporal quadrant RNFL thickness measurement. The aim of this study was to evaluate the long-term reproducibility of circumpapillary RNFL and macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements using OCT in myopic eyes. Sixty-five eyes with moderate-to-high myopia (spherical equivalent <-3.0 D, myopia group) and 53 eyes with low-to-no myopia (spherical equivalent ≥-3.0 D, control group) without ocular disorders, such as glaucoma or retinal diseases, were included. Three serial OCT scans recorded at 1-year intervals were analyzed. Reproducibility was evaluated using within-subject SD (Sw), coefficient of variation (CVw), and intraclass correlation coefficient (ICC). Mean±SD refractive error was -0.30±0.80 and -6.26±2.45 D for control and myopia groups, respectively. The myopia group had thinner superior, inferior, and nasal quadrant RNFL, thicker temporal quadrant RNFL, and thinner GCIPL than the control group (P<0.05), except for the minimum and superotemporal GCIPL thicknesses (P>0.05). The myopia group had lower reproducibility in temporal quadrant RNFL thickness (Sw, 2.57 μm; CVw 3.27%; ICC, 0.979) than the control group (Sw, 1.80 μm; CVw 2.59%; ICC, 0.989), whereas in other sectors of RNFL and all GCIPL parameters, comparable reproducibility was observed between the 2 groups. Long-term reproducibility of RNFL and GCIPL thickness measurements in moderate-to-high myopia was comparable to that of low-to-no myopia, except RNFL thickness in the temporal quadrant. These findings should be considered when detecting RNFL and GCIPL changes.

Long-Term Effects of a Photodisruptive Laser-Induced Traumatic Neuropathy Model.

PurposeTo create a mouse traumatic optic neuropathy (TON) model that is reproducible, reliable, and easy to manipulate with high specificity to retinal ganglion cell (RGC) layer and no mortality. The model will be useful for understanding the pathophysiology of retinal ganglion cell death and for testing neuroprotective therapeutics.MethodsAn Nd:YAG laser was used to generate focal photodisruptive retinal damage. Noninvasive in vivo ophthalmologic imaging technologies such as optical coherence tomography (OCT) and confocal laser scanning ophthalmoscopy (CSLO) were used to longitudinally track the retinal nerve fiber layer (RNFL) thickness and RGC number change, respectively. Immunostaining and pattern electroretinography (PERG) were also used to evaluate structure and functional change after laser injury.ResultsOur ND:YAG laser generates a concussive photodisruptive laser shockwave force which induces focal RGC death in the targeted area. We observed a correlative decrease in RGCs number, RNFL, and PERG function of RGC in the laser zone. The pattern of RNFL thinning and RGC soma loss correlates with the pattern and amount of fluorescence loss on OCT and CSLO images, respectively. The ND:YAG laser does not cause any damage to other layers in the retina nor any side effects including changes in intraocular pressure, corneal edema, and calcification or mortality (which has been observed in other TON models).ConclusionsWe have created a new and novel RGC TON death model that confers no mortality and produces a quantifiable decrease in RGC number and function. The laser targeted regions of the retina correlate with both in vivo imaging by OCT and CSLO and histologically with regions of RGC loss without ophthalmic side effects.Translational RelevanceThis laser-based TON injury model is simple to implement, is reproducible, and is useful for determining the molecular and cellular pathophysiology of TON and RGC death and for testing neuroprotective therapeutics.

Structural and Functional Correlations in Patients with Advanced Stages of Primary Open-Angle Glaucoma

Purpose: To study the correlations in the diagnosis of patients with advanced stages of primary open-angle glaucoma (POAG) using data from electroretinography and optical coherence tomography (OCT) of the retina.Methods. The study was performed in two clinical subgroups of patients (35 people, 55 eyes) with stages II and III POAG and the age-matched control group (28 healthy people, 32 eyes). The thickness of the ganglion cell complex (GCC), including the retinal nerve fiber layer (RNFL), the retinal ganglion cell layer (RGC), and the inner plexiform layer (INL) in the macular region, was assessed in nine segments. Correlation analysis of morphometric parameters of GCC in advanced POAG was performed with data from previously performed electroretinography: the transient pattern-ERG (T-PERG), stationary pattern-ERG (S-PERG), and photopic negative response (PhNR).Results. Statistically significant (p &lt; 0.01) thinning of all layers of the GCC was revealed in all studied sectors. Significant (p &lt; 0.05) differences in all morphometric characteristics were recorded between the two subgroups. In patients of the 1st subgroup, the greatest differences in morphological parameters from the control group’s values were noted in the lower, upper parafoveal sectors of the RGC layer, as well as in the temporal perifoveolar quadrant. In the 2nd subgroup, significant changes in the thickness of the inner retina layers were recorded for the upper and lower peripheral sectors of the RNFL and the temporal para- and peripheral quadrants of the RGC layer. In the study of morphological-functional relationships, the most significant correlations were revealed for the parameters of S-PERG. The amplitude of S-PERG directly correlated with the thickness of RNFL in the nasal sector of the perifovea (r = 0.86; p &lt; 0.01) in the 1st subgroup of patients and the thickness of the RGC in the nasal sector of the perifovea in the 2nd subgroup (r = 0.84; p &lt; 0.01). Moderate relationships were revealed between the N95/P50 T-PERG index and the RNFL thickness in the upper sector of the perifovea (r = 0.46; p &lt; 0.05), the peak N95 T-PERG latency, and the RNFL thickness in the upper sector of the perifovea (r = –0.43; p &lt; 0.05) in patients of the 1st subgroup. In patients of the 2nd subgroup, there was a correlation between the amplitude of N95 T-PERG and the thickness of the RGC in the lower sector of the perifovea (r = –0.42; p &lt; 0.01), the peak latency of N95, and the thickness of the RNFL in the upper sector of the parafovea (r = –0.31; p &lt; 0.05). A direct correlation was established between the PhNR amplitude from the baseline and the thickness of the RGC layer in the perifovea’s temporal sector (r = 0.72; p &lt; 0.01) in patients with stage II POAG. The PhNR amplitude from the b-wave peak in patients with stage III POAG correlated with the RNFL thickness in the perifovea’s nasal sector (r = 0.51; p &lt; 0.01).Conclusion. Specific patterns of morphological-functional changes in the parameters of the retina’s inner layers in patients with advanced POAG are presented, which can be used as clinical markers in determining an individual therapeutic strategy.

Bruch Membrane Opening Minimum Rim Width in Neuromyelitis Optica.

Optical coherence tomography (OCT) analyzes the neurodegeneration in neuromyelitis optica (NMO) and multiple sclerosis (MS) and quantifies optical atrophy. The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness are decreased, and this structural change is correlated with visual function of patients, including contrast vision and visual field deviation. The main objective of this study was to evaluate the Bruch membrane opening minimum rim width (BMO) of the patients with NMO. We studied the thickness of the BMO by OCT, in patients with NMO (n = 25; 34 eyes), MS (n = 50; 70 eyes), and a control group (n = 51; 100 eyes). The study evaluated the structure-function relationship with the correlation between OCT and visual function: Visual acuity, Pelli-Robson score, Sloan 2.5 and 1.25, color vision, standard automated perimetry (SAP), and frequency-doubling technology perimetry (FDT). The average thickness of BMO was significantly reduced in NMO and MS with or without a history of optic neuritis (ON). Significant thinning of the average, nasal, and inferonasal BMO in the absence of ON in NMO was found compared with controls (P = 0.022, 0.006, and 0.026, respectively). BMO was strongly correlated with Pelli-Robson score (P < 0.001), Sloan 2.5 (P < 0.001), and mean deviation of SAP and FDT (P = 0.004). The sectorial study found a high correlation between the BMO and the corresponding sector of the visual field. The BMO thickness is decreased after ON in NMO and MS. This study showed an improved ability of BMO over RNFL and GCL to detect infraclinical impairment in patients with NMO without a history of optic neuropathy. Like the RNFL and GCL, BMO is well correlated with visual function, including contrast vision and visual field deviation.

Thinning of the inner and outer retinal layers, including the ganglion cell layer and photoreceptor layers, in obstructive sleep apnea and hypopnea syndrome unrelated to the disease severity.

The aim of this study was to analyze the segmented layers of the macula in patients with obstructive sleep apnea and hypopnea syndrome (OSAS) using spectral domain optical coherence tomography (SD-OCT). This single-center, cross-sectional study included 31 OSAS patients and 31 age- and gender-matched control subjects. SD-OCT and overnight polysomnography were performed on all participants. The OSAS patients were categorized according to disease severity (mild, moderate, severe). The groups were compared in respect of each segmented macular layer through the use of segmentation software on SD-OCT. Total retinal thickness (RT), peripapillary retina nerve fiber layer (pRNFL) thickness, central corneal thickness (CCT) and intraocular pressure (IOP) values were also compared between the groups. Mean CCT (p:0.015) and nasal pRNFL values (p:0.042) were lower and mean IOP was higher (p:0.018) in OSAS patients than in the control group. The statistical analysis revealed significantly thinner total RT, inner retinal layers (IRL), outer retinal layers (ORL), photoreceptor layers (PRL) and ganglion cell layer (GCL) thicknesses in the OSAS groups compared to healthy subjects. No significant differences were found between the three OSAS subgroups in all segmented macular layers and pRNFL measurements. The results of this study showed relatively thinner nasal pRNFL, total RT, IRL, ORL, PRL and GCL layers in OSAS patients compared to healthy subjects. Moreover, this thinning of the segmented layers was unrelated to disease severity.

Structural and functional correlations in the pre-perimetric and the initial stages of glaucomatous optic neuropathy

Purpose:to study morphological and functional relationships in the early and preclinical diagnosis of glaucomatous optical neuropathy based on optical coherence tomography (OCT) of the retina and the data of electrophysiological research. Material and methods. Two clinical groups: (I) 35 patients (60 eyes) aged 49–70 (ave. 58.0 ± 5.3 yrs) with suspected glaucoma and (II) 21 patients (30 eyes) aged 46-68 (ave. 61.0 ± 4.8 yrs) with initial primary open-angle glaucoma (POAG), and a comparison group consisting of 36 relativelyhealthy subjects (41 eyes) aged 54–70 (ave. 62.0 ± 4.5 yrs), were subjected to spectral OCT by OСT Spectralis (Heidelberg Engineering, Germany). The thickness of the peripapillary layer of retinal nerve fibers (pRNFL), the minimum rim width (MRW), and the thickness of theretinal layers in the macular region that make up the ganglion cell complex (GCC) were evaluated. Spearman correlation analysis was used to identify correlations between OCT and electroretinography (ERG) data. Results.In patients with suspected glaucoma, changes in the parameters of transient pattern-ERG correlated with RNFL thinning in the macular region, inner plexiform layer (IPL), and ganglion cell layer(GCL) in the parafoveal area. In patients with initial glaucoma, changes in the retinal GCL were detected for the upper, lower, and temporal quadrants, while the nasal and central quadrants remained intact in all three GCC layers (RNFL, GCL, and IPL). In patients with suspected glaucoma, no statistically significant changes in the thickness of the pRNFL as compared with the norm were detected. Yet the MRW differed significantly from the comparison group. The highest number of correlations was found between the parameters of the ERGs and the thickness of the pRNFL. In patients with the initial stage of POAG, there was a significant increase in the thickness of RNFL in the temporal quadrant of the paramacular region. In our opinion, this phenomenon may be associated with the development of reactive gliosis being thereaction of neuroglia in response to changes in vascular and/or dystrophic homeostasis. Conclusion.Specific combinations of changes in the structural parameters of the retina and optic nerve head and the temporal and amplitude indices of the PERG and phototopic negative response have been found, justifying their use as combined markers of early and preclinical diagnosis of POAG.