Retinal Ganglion Cell Layer Thickness Research Articles

Variability of relationship between inner-retinal structural changes and visual dysfunction in optic neuropathy

Optical coherence tomography (OCT) displays the retinal nerve fiber layer (RNFL) or macular ganglion cell and inner plexiform layer (GCIPL) thickness below 1st percentile in red color. This finding generally indicates severe inner-retinal structural changes and suggests poor visual function. Nevertheless, some individuals show preserved visual function despite these circumstances. This study aimed to identify the correlation between best-corrected visual acuity (BCVA) and inner-retinal thickness based on OCT parameters in various optic neuropathy patients with extremely low RNFL/GCIPL thickness, and determine the limitation of OCT for predicting visual function in these patients. 131 patients were included in the study. The mean BCVA in logMAR was 0.55 ± 0.70 with a broad range from − 0.18 to 3.00. Among the OCT parameters, temporal GCIPL (r = − 0.412) and average GCIPL (r = − 0.366) exhibited the higher correlations with BCVA. Etiological comparisons of optic neuropathies revealed significantly lower BCVA in LHON (all p < 0.05). Idiopathic optic neuritis (ON) and MOGAD exhibited better and narrower BCVA distributions compared to the other optic neuropathies. OCT had limited utility in reflecting BCVA, notwithstanding significant inner-retinal thinning after optic nerve injuries. Caution is needed in interpreting OCT findings, especially as they relate to the etiology of optic neuropathy.

Changes in Retinal Ganglion Cell (RGC) and Retinal Nerve Fiber Layer (RNFL) Thickness in Children with Type 1 Diabetes Mellitus at Dr. M. Djamil General Hospital, Padang, Indonesia

Background: Type 1 diabetes mellitus (DM) is a chronic metabolic disorder that causes hyperglycemia and increases the risk of morbidity and mortality. Diabetic retinopathy, a microvascular complication that often occurs in DM patients, can cause visual impairment and even blindness. Regular eye examinations are important for early detection of diabetic retinopathy. Optical coherence tomography (OCT) is a non-invasive method that can be used to measure the thickness of retinal layers, including RGC and RNFL. It is thought that thinning of the retinal layer can be a sensitive biomarker in detecting diabetic retinopathy in type 1 DM patients. This study aims to determine changes in RGC and RNFL thickness in children with type 1 DM. Methods: This cross-sectional design analytical observational study was conducted at the eye polyclinic of Dr. M. Djamil General Hospital Padang in November 2023-March 2024. A total of 46 eyes from 46 people, divided into two groups: the type 1 DM group and the control group, were recruited in this study. RGC thickness was measured using AS-OCT GC-IPL thickness analysis and RNFL with optic disc RNFL thickness analysis. Data analysis was carried out using the unpaired T-test. Results: The results showed RGC depletion in the type 1 DM group (RGC 83.48 ± 3.75) compared to the control group (RGC 86.70 ± 4.87) with a value of p = 0.016 (p &lt; 0.05). There was no statistical difference in RNFL thickness between the type 1 DM group (RNFL 102 ± 11.80) and the control group (RNFL 100.96 ± 10.97) with a value of p = 0.581 (p&gt; 0.05). Conclusion: This study found RGC thinning in type 1 DM patients, but did not find differences in RNFL thickness between the two groups. This RGC depletion is thought to be caused by apoptosis of retinal neuronal cells due to chronic hyperglycemia. Examination of RGC thickness with OCT can be developed as an early detection of diabetic retinopathy in children with type 1 DM.

Ripa-56 protects retinal ganglion cells in glutamate-induced retinal excitotoxic model of glaucoma

Glaucoma is a prevalent cause of blindness globally, characterized by the progressive degeneration of retinal ganglion cells (RGCs). Among various factors, glutamate excitotoxicity stands out as a significant contributor of RGCs loss in glaucoma. Our study focused on Ripa-56 and its protective effect against NMDA-induced retinal damage in mice, aiming to delve into the potential underlying mechanism. The R28 cells were categorized into four groups: glutamate (Glu), Glu + Ripa-56, Ripa-56 and Control group. After 24 h of treatment, cell death was assessed by PI / Hoechst staining. Mitochondrial membrane potential changes, apoptosis and reactive oxygen species (ROS) production were analyzed using flow cytometry. The alterations in the expression of RIP-1, p-MLKL, Bcl-2, BAX, Caspase-3, Gpx4 and SLC7A11 were examined using western blot analysis. C57BL/6j mice were randomly divided into NMDA, NMDA + Ripa-56, Ripa-56 and control groups. Histological changes in the retina were evaluated using hematoxylin and eosin (H&E) staining. RGCs survival and the protein expression changes of RIP-1, Caspase-3, Bcl-2, Gpx4 and SLC7A11 were observed using immunofluorescence. Ripa-56 exhibited a significant reduction in the levels of RIP-1, p-MLKL, Caspase-3, and BAX induced by glutamate, while promoting the expression of Bcl-2, Gpx-4, and SLC7A1 in the Ripa-56-treated group. In our study, using an NMDA-induced normal tension glaucoma mice model, we employed immunofluorescence and H&E staining to observe that Ripa-56 treatment effectively ameliorated retinal ganglion cell loss, mitigating the decrease in retinal ganglion cell layer and bipolar cell layer thickness caused by NMDA. In this study, we have observed that Ripa-56 possesses remarkable anti- necroptotic, anti-apoptotic and anti-ferroptosis properties. It demonstrates the ability to combat not only glutamate-induced excitotoxicity in R28 cells, but also NMDA-induced retinal excitotoxicity in mice. Therefore, Ripa-56 could be used as a potential retinal protective agent.

AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype–Phenotype Characterization Compared to OPA1 Patients

PurposeHeterozygous mutations in AFG3L2 gene (encoding a mitochondrial protease indirectly reflecting on OPA1 cleavage) and ACO2 gene (encoding the mitochondrial enzyme aconitase) are associated to isolated forms of Dominant Optic Atrophy (DOA). We aimed at describing their neuro-ophthalmological phenotype as compared with classic OPA1-related DOA. DesignCross-sectional study. MethodsThe following neuro-ophthalmological parameters were collected: Log MAR visual acuity (VA), color vision, mean deviation and foveal threshold at visual fields, average and sectorial retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness at optic coherence tomography. ACO2 and AFG3L2 patients were compared with an age- and gender-matched group of OPA1 patients with 1:2 ratio. All eyes were analysed using Clustered Wilcoxon rank sum test using Rosner-Glynn-Lee method. Results44 eyes from 23 ACO2 and 26 eyes from 13 AFG3L2 patients were compared with 143 eyes from 72 OPA1 patients. All cases presented with bilateral temporal-predominant optic atrophy with various degree of visual impairment. Comparison between AFG3L2 and OPA1 failed to reveal any significant difference. ACO2 patients compared to both AFG3L2 and OPA1 presented overall higher values of nasal RNFL thickness (p=0.029, p=0.023), average (p=0.012, p=0.0007) and sectorial GCL thickness. These results were confirmed also comparing separately affected and subclinical patients. ConclusionsClinically, DOA remains a fairly homogeneous entity despite the growing genetic heterogeneity. ACO2 seems associated to an overall better preservation of retinal ganglion cells, probably depending on the different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2, which is involved in OPA1 processing and resulted virtually indistinguishable from classic OPA1-DOA.

Neuropsychological and Clinical Correlations of Optical Coherence Tomography Findings in Patients with Schizophrenia

Objective: There are increasing studies examining retinal fiber layer (RNFL) and ganglion cell layer (GCL) thinning in patients with schizophrenia. However, the results are controversial, and clinical and cognitive reflections of these findings remain unclear. With this study, we aim to examine retinal abnormalities and establish correlations with cognitive and clinical parameters.&#x0D; Methods: In this cross-sectional study, we examined 29 patients with schizophrenia and 13 age and gender-matched healthy controls. All participants underwent psychometric assessment, neuropsychological tests, and optical coherence tomography (OCT) measurements. The retinal fiber layer and ganglion cell layer thickness were used as retinal parameters.&#x0D; Results: Five patients dropped out during the OCT measurement process, 24 patients with schizophrenia and nine healthy controls were included in the analysis. There was no statistically significant difference between groups in measuring retinal nerve fiber layer or ganglion cell layer thicknesses. The verbal fluency test score negatively correlated with left RNFL superior ( ρ – .422, p

MicroRNA-93 promotes the pathogenesis of glaucoma by inhibiting matrix metalloproteinases as well as up-regulating extracellular matrix and Rho/ROCK signaling pathways

ObjectiveTo investigate the effect and potential molecular mechanism of microRNA-93 (miR-93) on retinal ganglion cells (RGCs) apoptosis as well as retinal damage in acute glaucoma mice. MethodsRGCs apoptosis were induced by oxygen-glucose deprivation and reperfusion (OGD/R). The pro-apoptotic effect of miR-93 was evaluated by transfecting miR-93 mimics or miR-93 inhibitor into OGD/R-induced RGCs. The viability and apoptosis of RGCs were determined by MTT assay and flow cytometry. Mouse model of acute glaucoma were successfully induced via high intraocular pressure (IOP), and then these model animals were randomly divided into vehicle group, miR-93 mimics group or miR-93 inhibitor group (n = 10), using healthy mice as normal control. Histopathologic changes of retinal tissue were evaluated by Hematoxylin and Eosin (H&E) staining method. Moreover, cell counts of retinal ganglion cell layer and mean thickness of different layers were also determined. Quantitative real-time PCR (qPCR) and western blotting analysis were used to detect the mRNA and protein expression levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs) and Rho/ROCK signaling pathway. ResultsmiR-93 mimics significantly decreased or promoted the viability and apoptosis of OGD/R-induced RGCs, respectively. In addition, miR-93 mimics significantly exacerbated the degree of retinal tissue damage in mice with acute glaucoma, which was accompanied by a decrease in the number of ganglion cell layer (GCL) cells and the thickness of different tissue layers. Moreover, miR-93 mimics significantly increased IOP in mice with acute glaucoma. Significantly, miR-93 inhibitors significantly reversed the above changes. In addition, results of Western blot analysis showed that miR-93 mimics increased and decreased the expression of ECM-associated and MMP-associated proteins, respectively, by activating the Rho/ROCK signaling pathway. In contrast, miR-93 significantly decreased and increased the expression of ECM-associated and MMP-associated proteins, and suppressed the expression of Rho/ROCK signaling pathway-related proteins. ConclusionmiR-93 can promote the development of glaucoma by activating Rho/ROCK signaling pathway to mediate the accumulation of ECM-related proteins as well as the down-regulation of MMP-related proteins.

Retinal Microvasculature Image Analysis Using Optical Coherence Tomography Angiography in Patients with Post-COVID-19 Syndrome.

Several optical coherence tomography angiography (OCT-A) studies have demonstrated retinal microvascular changes in patients post-SARS-CoV-2 infection, reflecting retinal-systemic microvasculature homology. Post-COVID-19 syndrome (PCS) entails persistent symptoms following SARS-CoV-2 infection. In this study, we investigated the retinal microvasculature in PCS patients using OCT-angiography and analysed the macular retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thickness via spectral domain-OCT (SD-OCT). Conducted at the Manchester Royal Eye Hospital, UK, this cross-sectional study compared 40 PCS participants with 40 healthy controls, who underwent ophthalmic assessments, SD-OCT, and OCT-A imaging. OCT-A images from the superficial capillary plexus (SCP) were analysed using an in-house specialised software, OCT-A vascular image analysis (OCTAVIA), measuring the mean large vessel and capillary intensity, vessel density, ischaemia areas, and foveal avascular zone (FAZ) area and circularity. RNFL and GCL thickness was measured using the OCT machine's software. Retinal evaluations occurred at an average of 15.2 ± 6.9 months post SARS-CoV-2 infection in PCS participants. Our findings revealed no significant differences between the PCS and control groups in the OCT-A parameters or RNFL and GCL thicknesses, indicating that no long-term damage ensued in the vascular bed or retinal layers within our cohort, providing a degree of reassurance for PCS patients.

Evaluation of multiple sclerosis severity using a new OCT tool.

To assess the ability of a new posterior pole protocol to detect areas with significant differences in retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness in patients with multiple sclerosis versus healthy control subjects; in addition, to assess the correlation between RNFL and GCL thickness, disease duration, and the Expanded Disability Status Scale (EDSS). We analyzed 66 eyes of healthy control subjects and 100 eyes of remitting-relapsing multiple sclerosis (RR-MS) patients. Double analysis based on first clinical symptom onset (CSO) and conversion to clinically definite MS (CDMS) was performed. The RR-MS group was divided into subgroups by CSO and CDMS year: CSO-1 (≤ 5 years) and CSO-2 (≥ 6 years), and CDMS-1 (≤ 5 years) and CDMS-2 (≥ 6 years). Significant differences in RNFL and GCL thickness were found between the RR-MS group and the healthy controls and between the CSO and CDMS subgroups and in both layers. Moderate to strong correlations were found between RNFL and GCL thickness and CSO and CDMS. Furthermore, we observed a strong correlation with EDSS 1 year after the OCT examination. The posterior pole protocol is a useful tool for assessing MS and can reveal differences even in early stages of the disease. RNFL thickness shows a strong correlation with disability status, while GCL thickness correlates better with disease duration.

Retinal structure and visual pathway function at school age in children born extremely preterm: a population-based study

BackgroundChildren born extremely preterm (gestational age < 28 weeks) show reduced visual function even without any cerebral or ophthalmological neonatal diagnosis. In this study, we aimed to assess the retinal structure with optical coherence tomography (OCT) and visual function with pattern-reversal visual evoked potentials (PR-VEPs) in a geographically defined population-based cohort of school-aged children born extremely preterm. Moreover, we aimed to explore the association between measures of retinal structure and visual pathway function in this cohort.MethodsAll children born extremely preterm from 2006–2011 (n = 65) in Central Norway were invited to participate. Thirty-six children (55%) with a median age of 13 years (range = 10–16) were examined with OCT, OCT-angiography (OCT-A), and PR-VEPs. The foveal avascular zone (FAZ) and circularity, central macular vascular density, and flow were measured on OCT-A images. Central retinal thickness, circumpapillary retinal nerve fibre layer (RNFL) and inner plexiform ganglion cell layer (IPGCL) thickness were measured on OCT images. The N70-P100 peak-to-peak amplitude and N70 and P100 latencies were assessed from PR-VEPs.ResultsParticipants displayed abnormal retinal structure and P100 latencies (≥ 2 SD) compared to reference populations. Moreover, there was a negative correlation between P100 latency in large checks and RNFL (r = -.54, p = .003) and IPGCL (r = -.41, p = .003) thickness. The FAZ was smaller (p = .003), macular vascular density (p = .006) and flow were higher (p = .004), and RNFL (p = .006) and IPGCL (p = .014) were thinner in participants with ROP (n = 7).ConclusionChildren born extremely preterm without preterm brain injury sequelae have signs of persistent immaturity of retinal vasculature and neuroretinal layers. Thinner neuroretinal layers are associated with delayed P100 latency, prompting further exploration of the visual pathway development in preterms.

A Randomized Prospective Trial Comparing Repository Corticotropin Injection and Intravenous Methylprednisolone for Neuroprotection in Acute Optic Neuritis.

Repository corticotrophin injection (RCI, Acthar Gel) and intravenous methylprednisolone (IVMP) improve the rate but not the extent of visual recovery following acute optic neuritis. RCI has adrenal-stimulating and melanocortin receptor-stimulating properties that may endow it with unique anti-inflammatory properties relative to IVMP. Individuals with acute optic neuritis of less than 2 weeks duration were prospectively enrolled and randomized 1:1 to receive either RCI or IVMP. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer thickness (GC + IPL) were serially evaluated by OCT. In addition, patient-reported outcomes (PROs) for changes in fatigue, mood, visual function, depression, and quality of life (QOL) were measured, and high and low contrast visual acuity were recorded. Thirty-seven subjects were enrolled (19 RCI; 18 IVMP); the average time from symptom to treatment was 8.8 days. At 6 months, there was no difference in the primary outcome: loss of average pRNFL thickness in the affected eye (RCI vs IVMP: -13.1 vs -11.7 µm, P = 0.88) 6 months after randomization. Additional outcomes also showed no difference between treatment groups: 6-month attenuation of GC + IPL thickness (RCI vs IVMP: -13.8 vs -12.0 µm, P = 0.58) and frequency of pRNFL swelling at 1 month (RCI vs IVMP: 63% vs 72%, P = 0.73) and 3 months (RCI vs IVMP: 26% vs 31%, P = 0.99). Both treatments resulted in improvement in visual function and PROs. Treatment of acute optic neuritis with RCI or IVMP produced no clinically meaningful differences in optic nerve structure or visual function.

Evaluation of Retinal Nerve Fiber Layer and Macular Ganglion Cell Layer Thickness in Relation to Optic Disc Size.

To investigate whether optic nerve ganglion cell amount is dependent on optic disc size, this trial analyzes the correlation between Bruch's membrane opening area (BMOA) and retinal nerve fiber layer (RNFL) thickness as well as macular ganglion cell layer thickness (mGCLT). Additionally, differences in RNFL and mGCLT regarding various optic disc cohorts are evaluated. This retrospective, monocentric study included 501 healthy eyes of 287 patients from the University Hospital Münster, Germany, who received macular and optic disc optical coherence tomography (OCT) scans. Rank correlation coefficients for clustered data were calculated to investigate the relationship between BMOA and thickness values of respective retinal layers. Furthermore, these values were compared between different optic disc groups based on BMOA. Statistical analysis did not reveal a significant correlation between BMOA and RNFL thickness, nor between BMOA and mGCLT. However, groupwise analysis showed global RNFL to be significantly decreased in small and large discs in comparison to medium discs. This was not observed for global mGCLT. This study extends existing normative data for mGCLT taking optic disc size into account. While the ganglion cell amount represented by the RNFL and mGCLT seemed independent of BMOA, mGCLT was superior to global RNFL in displaying optic nerve integrity in very small and very large optic discs.

SAkuraBONSAI: Protocol design of a novel, prospective study to explore clinical, imaging, and biomarker outcomes in patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorder receiving open-label satralizumab.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD. SAkuraBONSAI will evaluate clinical disease activity measures, patient-reported outcomes (PROs), pharmacokinetics, and safety of satralizumab in AQP4-IgG+ NMOSD. Correlations between imaging markers (magnetic resonance imaging [MRI] and optical coherence tomography [OCT]) and blood and cerebrospinal fluid (CSF) biomarkers will be investigated. SAkuraBONSAI is a prospective, open-label, multicenter, international, Phase 4 study that will enroll approximately 100 adults (18-74 years) with AQP4-IgG+ NMOSD. This study includes two patient cohorts: newly diagnosed, treatment-naïve patients (Cohort 1; n = 60); and inadequate responders to recent (<6 months) rituximab infusion (Cohort 2; n = 40). Satralizumab monotherapy (120 mg) will be administered subcutaneously at Weeks 0, 2, 4, and Q4W thereafter for a total of 92 weeks. Disease activity related to relapses (proportion relapse-free, annualized relapse rate, time to relapse, and relapse severity), disability progression (Expanded Disability Status Scale), cognition (Symbol Digit Modalities Test), and ophthalmological changes (visual acuity; National Eye Institute Visual Function Questionnaire-25) will all be assessed. Peri-papillary retinal nerve fiber layer and ganglion cell complex thickness will be monitored using advanced OCT (retinal nerve fiber layer and ganglion cell plus inner plexiform layer thickness). Lesion activity and atrophy will be monitored by MRI. Pharmacokinetics, PROs, and blood and CSF mechanistic biomarkers will be assessed regularly. Safety outcomes include the incidence and severity of adverse events. SAkuraBONSAI will incorporate comprehensive imaging, fluid biomarker, and clinical assessments in patients with AQP4-IgG+ NMOSD. SAkuraBONSAI will provide new insights into the mechanism of action of satralizumab in NMOSD, while offering the opportunity to identify clinically relevant neurological, immunological, and imaging markers.

Assessment of Retinal Nerve Fiber Layer (RNFL) and Retinal Ganglion Cell Layer (RGCL) Thickness in Radiologically Isolated Syndrome (RIS)

Background: Three-thirds of people with radiologically isolated syndrome (RIS) develop multiple sclerosis (MS) within five years following their first brain magnetic resonance imaging (MRI). Subclinical applications of optical coherence tomography (OCT) include measuring the thickness of different retinal layers and monitoring the progression of visual pathway atrophy and neurodegeneration in relation to the progress of the entire brain. Objectives: Our OCT study was conducted in individuals with RIS to evaluate the thickness of the macular retinal nerve fiber layer (mRNFL) and the retinal ganglion cell layer (RGCL). Methods: In this study, 22 patients with RIS and 23 healthy individuals healthy control (HC) were enrolled. The control group and the RIS subjects underwent retinal imaging with OCT. Results: Total mRNFL thickness was 110.34 ± 13.71 μm in the RIS patients and 112.10 ± 11.23 μm in the HC group. Regional analysis of the mRNFL showed that the difference in thickness was more prominent in the superior quadrant. In regards to ganglion cell layer (GCL)++ thickness, the RIS and HCs population showed statistically significant differences in the nasal (P = 0.041), inferior (P = 0.040), and superior (P = 0.045) quadrants. The nasal (P = 0.041) quadrant showed the highest reduction in thickness compared to other regions of the GCL++. Meanwhile, no significant reduction was seen in GCL+ thickness (P-value &gt; 0.05). When the thickness of the retinal layer of the right eye was compared to that of the left eye of the RIS group, no statistically significant differences were found (P-value &gt; 0.05). Conclusions: Compared to the control group, the RIS group had a lower mean thickness of mRNFL and GCL++, indicating retinal neuroaxonal loss.

Examination of Inner Retinal Layers in Unilateral Wet Age-Related Macular Degeneration Treated with Anti-VEGF, Compared to Fellow Untreated Eyes.

The main aim of this study was to characterize the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness in the macular area eyes affected by wet age-related macular degeneration (wAMD) treated with anti-VEGF and compare the results with the control of fellow untreated eyes affected by early stages of dry age-related macular degeneration (dAMD). Additionally, we aimed to estimate if the number of injections received and other factors, including age, best-corrected visual acuity (BCVA), or sex, may affect the differences in the obtained measurements of retinal nerve fiber layer thickness. We prospectively included 106 eyes of 53 patients with unilateral wet age-related macular degeneration. The fellow eyes with non-advanced dry age-related macular degeneration served as a control group in a cross-sectional study. RNFL and GCL in the macular region were evaluated using optical coherence tomography, with outcomes expressed as differences in the thickness of both examined layers between the study and control groups. We found thinner GCL in wAMD vs. dAMD (p < 0.001). In turn, the RNFL layer did not show any statistically significant differences between the two groups (p = 0.409). Similarly, we found a statistically significant correlation between the number of injections and the layer thickness (p = 0.106). Among all assessed parameters, age over 73 was the only factor significantly affecting the thickness of the retinal nerve fiber layer in both groups (p = 0.042). The morphology of the inner layers of the retina in dry and wet AMD seems to differ, possibly due to differences in the etiopathogenesis of these two forms of the disease. In our study, the retinal ganglion cell layer was thinner in the treated vs. fellow eye (with dry AMD), while the nerve fiber layer was not significantly different between the groups. The number of anti-VEGF injections had no effect on the thickness of the macular nerve fiber layer.

Analysis of Retinal Structure and Electrophysiological Function in Visual Snow Syndrome: An Exploratory Case Series.

Visual snow (VS) is a rare but distressing phenomenon of persistent granular or pixelated visual distortions that may occur in isolation or as a component of visual snow syndrome (VSS). The current understanding of VS pathogenesis, including the role of retinal involvement structurally and functionally, is limited. The objective of this study is to investigate retinal structural and electrophysiological abnormalities in VS. This retrospective case series included 8 subjects (7 with VSS and 1 with isolated VS). Patients with other ocular and neurologic diseases were excluded. Data were assessed from automated perimetry, optical coherence tomography (OCT), visual evoked potential (VEP), and full-field electroretinography (ffERG) testing. The VEP and ffERG data of visual snow subjects were compared with age- and sex-matched control subjects for statistical significance. The mean age of the cohort was 29.4 years (SD = ±5.3) with 50% gender split. The mean age of VS onset was 24.2 years (SD = ±3.8). All subjects had normal visual acuity, color vision, brain MRI, automated perimetry, OCT parameters (peripapillary retinal nerve fiber layer and macular ganglion cell layer thickness), and P100 and N135 wave pattern on VEP. Compared with controls, VS subjects had a greater mean b-wave amplitude in response to light-adapted 3.0 stimuli ( t test; P = 0.035 right eye and P = 0.072 left eye), greater mean light-adapted 3.0 flicker amplitude ( t test; P = 0.028 right eye P = 0.166 left eye) and greater b-wave amplitude in response to dark-adapted 10.0 stimuli ( t test; P = 0.102 right eye; P = 0.017 left eye) on ERG. Patients with VS and VSS have normal retinal structure, but abnormal electrophysiology compared with control subjects. The increased b-wave and flicker amplitudes observed with ffERG suggest increased responsiveness of the rod and cone photoreceptors and may contribute to VS pathophysiology.

Role of optical coherence tomography in diagnosis of Alzheimer's disease

AbstractPurpose: To evaluate changes in visual function and anatomical structures in the neuroretina of patients diagnosed with Alzheimer's disease (AD) in comparison with healthy controls.Methods: A total of 25 eyes of 13 AD patients and 80 eyes of 40 healthy subjects were analysed. Best corrected visual acuity (BCVA) was assessed in different contrast situations (100%, 2.5%, 1.25%) with ETDRS chart (Early Treatment Diabetic Retinopathy Study). Also, retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thickness were analysed using Spectralis and Triton optical coherence tomography (OCT), globally and by sectors, both in peripapillary and macular area.Results: A statistically significant decrease was found in BCVA in AD patients in comparison with controls (p &lt; 0.001), specifically in 100% and 1.25% contrast charts. Regarding structural analysis, a significant reduction in retinal thickness was found in AD patients in comparison with controls. Global thickness was found to be significantly thinner in peripapillary retina in Triton OCT (p &lt; 0.001). In a similar way, macular GCL, both in Triton and Spectralis OCT, showed a significant thinning (p &lt; 0.001) in global and sectorial analysis. RNFL showed a significant tendency towards thinning, but specifically in infero‐temporal sector of macular area in Spectralis OCT (p &lt; 0.001).Conclusions: The neurodegeneration that AD produces to the brain affects the retina in a parallel way, and that can be objectified by measuring BCVA parameters and thickness measurements in OCT. Compared to healthy controls, AD has a significant thinning in several neuroretinal layers, which can be considered a potential diagnostic tool considering that OCT is a quick, reproducible, non‐invasive test.

Evaluation of severity and time disease using new optical coherence tomography tool in multiple sclersosis patients

AbstractPurpose: To assess the ability of Posterior Pole new protocol in optical coherence tomography (OCT) to detect areas with significant differences on retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thicknesses in patients with multiple sclerosis (MS) versus healthy controls; in addition, to assess the correlation between RNFL and GCL thicknesses, disease duration and the Expanded Disability Status Scale (EDSS).Methods: We analysed 64 eyes of healthy controls and 100 eyes of remitting–relapsing multiple sclerosis (RR‐MS) patients by OCT Posterior Pole protocol. Analysis based on clinically definite time point (CDMS) dividing patients in two subgroups [CDMS‐1 (≤5 years) and CDMS‐2 (≥6 years)].Results: Significant differences in RNFL and GCL were found between RR‐MS group and healthy controls, and also for each CDMS subgroups on both layers. Moderate to strong correlations were found between RNFL and GCL thicknesses and CDSM; furthermore, we observed a strong correlation with EDSS 1 year after OCT exam.Conclusions: Posterior Pole protocol is a useful tool to assess MS; it can reveal differences even in early stages of the disease. RNFL thicknesses demonstrate strong correlation with disability status, while GCL correlates better with time of disease.

Neuroprotection in ophthalmology. Targets in the most frequent diseases. A clinician's point of view

AbstractObjectives: To briefly review the most frequent ocular diseases in which a neuroprotective treatment would be needed and to present the results of a translational research based on the neuroprotective capacities of allogeneic bone marrow‐derived mesenchymal stem cells (MSCs) in an ocular disease that currently lacks treatment, the non‐arteritic acute anterior ischemic optic neuropathy. (NA‐AION) considered as an infarct of the optic nerve head.Methods: After extensive preclinical evaluation of safety in rabbits, a prospective, non‐randomized, phase II clinical trial (Eudra CT number 2016–003029‐40 and ClinicalTrials.gov NCT03173638) was approved. Five patients with acute unilateral NA‐AION diagnosed within the first 2 weeks after symptom onset were included. After informed consent, patients received an intravitreal injection of 0.05 ml containing 150 μl of isotonic medium composed of Ringer's lactate, 0.5% human albumin, and 5 mM glucose, with a cell concentration of 1.5 × 106 cells/ml. The injection was administered using a 25‐gauge needle via the pars plana after topical anaesthesia. Patients were followed on days 1, 7, 30, 90, 180 and 1 year after injection. Safety was defined as the absence of an inflammatory reaction. The best‐corrected visual acuity, visual evoked potentials (VEP) and retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thicknesses were measured.Results: No patients had signs of intraocular inflammation at any time. An epiretinal membrane (ERM) developed in one patient. One phakic patient had a retrolental aggregate that did not progress to cataract. Four patients had visual improvement and three had increased amplitudes on the VEP recordings after treatment. The RNFL and GCL thicknesses decreased significantly in parallel with the visible papillary atrophy that developed during the follow‐up period.Conclusions: Despite development of an ERM in one patient and a possible cellular deposit in the retrolental space, the functional results are encouraging. A larger multicentre study of treated patients that includes a control group is currently running. The paracrine capacities of allergenic MSCs should be more extensively investigated in the clinic, taking advantage of their non‐immunogenicity, their ease of obtaining and their apparent safety.Financial support: Funded by Strategic Action in Health of the Institute of Health Carlos III (PIC18/00018), the Department of Regional Health of the Castilla y Léon Government (GRS 1928/A/19), and the Department of Education of the Castilla y León Regional Government (Grant VA077P17).

Impact of intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell and nerve fibre layer thickness in Neovascular age-related macular degeneration.

To compare the effects of monotherapy with intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell layer (RGCL) and retinal nerve fibre layer (RNFL) in patients with naïve neovascular age-related macular degeneration (nAMD). This is a retrospective cohort study with three-groups comparison. 83 patients and 97 eyes on continuous monotherapy with an intravitreal anti-vascular endothelial growth factor (anti-VEGF) were followed for 24 months and divided into three groups according to anti-VEGF (aflibercept: 25 eyes, ranibizumab: 34 eyes, bevacizumab: 38 eyes). Main outcome measures included: RGCL and RNFL thickness, best corrected visual acuity (BCVA), central macular thickness (CMT), macular volume (MV) and the presence of intraretinal fluids (IRF), subretinal fluids (SRF) and retinal pigment epithelial atrophy (RPE-atrophy). All outcome measures were recorded at the time of the first injection, 1 and 2 years after treatment and compared longitudinally and between groups. The mean age was 79 ± 7 years. The RGCL thickness, MV, CMT and the presence of IRF and SRF decreased significantly within all three medication groups (p < 0.05 for all) with no significant difference between groups over the 2-year follow-up period (p > 0.10 for all). The decrease in RNFL thickness was not significant within or between the groups after a 2-year follow-up (p > 0.055 for all). RPE-atrophy increased significantly after 2 years in all three groups (p < 0.028 for all) with no significant difference between groups at all three time points (p > 0.307 for all). BCVA was comparable between the three groups over the 2-year follow-up period (p > 0.22 for all). Monotherapy with intravitreal aflibercept, bevacizumab and ranibizumab was associated with comparable significant decreases in RGCL thickness, CMT, MV, IRF and SRF in naïve nAMD patients during the first 2 years of treatment. Furthermore, no significant differences either in BCVA or RNFL thickness were observed between the three intravitreal anti-VEFGs during the first 2 years of treatment.

Treatment of nonarteritic anterior ischemic optic neuropathy with an endothelin antagonist: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy)—a multicentre randomised controlled trial protocol

BackgroundNonarteritic anterior ischemic optic neuropathy (NAAION) is a major cause of blindness in individuals over 50 years of age, with no available effective treatment. The oral dual endothelin receptor antagonist, bosentan, increases retinal optic nerve head blood flow in healthy humans and glaucoma patients. The objective of this trial is to assess the efficacy of bosentan administered at the acute stage in improving outcomes in NAAION patients.MethodsENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy) is a phase III, interventional, prospective, multicentre, placebo-controlled randomised double-blind clinical trial. The primary outcome is change in the visual field mean deviation (MD) at 3 months (Humphrey 30-2 SITA standard programme). Secondary outcomes include MD and visual acuity changes up to 24 months, changes in peripapillary retinal nerve fibre and macular ganglion cell layer thickness in the affected eye, as measured by optical coherence tomography, rate of NAAION bilateralisation at 2 years, and quality-of-life. Patients over 50 years of age presenting with typical NAAION of recent onset (less than 21 days) are randomly assigned to either 125 mg oral bosentan or placebo, twice a day, during 8 weeks. Besides visits during the treatment phase, patients attend follow-up visits at 2, 3, 6, 12 and 24 months. The inclusion of patients began in August 2015 at five French University hospital ophthalmology departments and two specialised ophthalmology centres. It is planned to include 86 patients in this trial. To date we have included 72 patients and 49 have completed the full follow-up process.DiscussionAn endothelin receptor antagonist is a potential approach to improving the anatomical and functional prognosis of patients with NAAION. This multicentre double-blind randomised controlled trial is an opportunity to assess (1) the effect of bosentan on the structure and function of the optic nerve in NAAION, at 3 months, (2) the effect of bosentan on the bilateralisation rate at 24 months and (3) the tolerance profile of bosentan in this population.Trial registrationClinicalTrials.gov NCT02377271. Registered on March 3, 2015.