Retinal Ganglion Cell Layer Research Articles

Ganglion Cell and Retinal Nerve Fiver Layers Correlated with Time Disease of Bipolar Disorder Using 64 Cell Grid OCT Tool

ABSTRACT Purpose of the study: To assess the ability of the new Spectralis Optical Coherence Tomography (OCT) Posterior Pole protocol to detect degeneration of the inner retinal layers in patients with bipolar disorder (BD) and to assess the correlation between the neuroretinal thickness and disease duration. Materials and Methods Twenty-five eyes of 25 patients with bipolar disorder and 74 eyes of 74 healthy controls underwent retinal measurements of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness. Measurements were obtained using the Spectralis-OCT device with the new Posterior Pole protocol which assesses the macular area by analyzing retinal thickness in a grid of 64 (8*8) cells. Results Significant differences (p < 0.05) in RNFL and GCL thickness were found between BD patients and healthy controls, in parafoveal and perifoveal cells respectively. Significant inverse correlations were found between RNFL and GCL thinning at their thickest location and the duration of bipolar disorder. Several predictive variables were observed with a binary logistic regression for the presence/absence of BD: cell 1.3 RNFL (p = 0.028) and GCL in cells 7.8 (p = 0.012), 2.7 (p = 0.043) and 1.3 (p = 0.047). Conclusion Posterior Pole OCT protocol is a useful tool to assess changes in the inner retinal layers in bipolar disorder. These observed changes, especially those affecting the GCL, may be associated with disease evolution and may be predictive of the presence of the disease. OCT data could potentially be a useful tool for clinicians to diagnose and monitor BD patients.

Oligoclonal IgM bands in the cerebrospinal fluid of patients with relapsing MS to inform long-term MS disability

Background: Prognostic markers are needed to guide multiple sclerosis (MS) management in the context of large availability of disease-modifying drugs (DMDs). Objective: To investigate the role of cerebrospinal fluid (CSF) markers to inform long-term MS outcomes. Methods: Demographic features, IgM index, oligoclonal IgM bands (OCMB), lipid-specific OCMB, CSF neurofilament light chain protein levels, expanded disability status scale (EDSS), relapses and DMD use over the study period and peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer (GCIPL) thicknesses in non-optic neuritis eyes (end of follow-up) were collected from relapsing MS (RMS) patients with CSF obtained ⩽2 years after MS onset prospectively followed at the Hospital Clinic of Barcelona. We assessed associations between CSF markers and MS outcomes using multivariable models. Results: A total of 89 patients (71 females; median 32.9 years of age) followed over a median of 9.6 years were included. OCMB were associated with a 33% increase in the annualized relapse rate (ARR; p = 0.06), higher odds for high-efficacy DMDs use (OR = 4.8; 95% CI = (1.5, 16.1)), thinner pRNFL (β = −4.4; 95% CI = (−8.6, −0.2)) and GCIPL (β = −2.9; 95% CI = (−5.9, +0.05)), and higher rates to EDSS ⩾ 3.0 (HR = 4.4; 95% CI = (1.6, 11.8)) and EDSS ⩾ 4.0 (HR = 5.4; 95% CI = (1.1, 27.1)). No overall associations were found for other CSF markers. Conclusion: The presence of OCMB was associated with unfavorable long-term outcomes. OCMB should be determined in RMS to inform long-term prognosis.

Optical Coherence Tomography Revealing Ganglion Cell Loss in Idiopathic Normal Pressure Hydrocephalus

Although there may theoretically be a disturbance in the eye or the visual pathways due to abnormal cerebrospinal fluid (CSF) dynamics in idiopathic normal pressure hydrocephalus (iNPH), it has not been studied systemically. Optical coherence tomography (OCT) is a noninvasive, reproducible procedure for quantitative and qualitative analysis of retinal morphology. OCT was used to study the eye fundus before and after a CSF tap test in patients with iNPH compared with healthy individuals (HIs). Twelve patients with iNPH (6 females and 6 males) with a median age of 76 years (64-84 years) and 21 HIs (11 females and 10 males) with a median age of 73 years (64-79 years) were included. The patients underwent neurological, cognitive, and physiotherapeutic evaluation. Brain magnetic resonance imaging, CSF tap test via lumbar puncture, and subsequently CSF analysis were performed. OCT was performed before and after CSF removal. HIs underwent OCT once. The patients had significantly reduced retinal ganglion cell layer thickness 71 μm (56-81 μm) compared with the HIs, 79.5 μm (72-90 μm) (P = 0.001), but no significant changes were observed before or after the CSF tap test. All patients improved in motor function in a 10-m walk test after the CSF tap test. The median CSF pressure was 15 and 1 cm H2O, respectively, before and after lumbar puncture with removal of median 43.5 mL CSF. This pilot study shows OCT findings that differ from HIs and implies a rational for becoming a valuable tool in the diagnosis of iNPH. Further studies are warranted to elucidate the pathology of the retina in iNPH.

Transplanted embryonic retinal stem cells have the potential to repair the injured retina in mice

BackgroundStem cell transplantation has been reported as one of the promising strategies to treat retinal degenerative diseases. But, the application and the role of retina stem cells (RSCs) in the treatment of patients with retinal degenerative diseases have not been fully revealed. This study aimed to investigate the potential role of transplantation of the embryo-derived RSCs into the vitreous cavity in repairing the damaged retina in mice.MethodsRSCs were isolated from Kunming mice E17 embryonic retina and ciliary body tissues, and labeled with 5-bromo-2’-deoxyuridin (BrdU). Retinal optic nerve crush injury was induced in left eyes in male Kunming mice by ring clamping the optic nerve. The 6th -generation of BrdU-labeled RSCs were transplanted into the damaged retina by the intravitreal injection, and saline injected eyes were used as the control. Hematoxylin and eosin histological staining, and BrdU, Nestin and Pax6 immunostaining were performed. Electroretinogram (ERG) was used for assessing the electrical activity of the retina.ResultsEmbryo-derived RSCs were identified by the positive stains of Pax6 and Nestin. BrdU incorporation was detected in the majority of RSCs. The damaged retina showed cellular nuclear disintegration and fragmentation in the retinal tissue which progressed over the periods of clamping time, and decreased amplitudes of a and b waves in ERG. In the damaged retina with RSCs transplantation, the positive staining for BrdU, Pax6 and Nestin were revealed on the retinal surface. Notably, RSCs migrated into the retinal ganglion cell layer and inner nuclear. Transplanted RSCs significantly elevated the amplitudes of a waves in retina injured eyes.ConclusionsEmbryonic RSCs have similar characteristics to neural stem cells. Transplantation of RSCs by intravitreal injection would be able to repair the damaged retina.

Folic Acid Fortification Prevents Morphological and Behavioral Consequences of X-Ray Exposure During Neurulation.

Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.

Global optical coherence tomography measures for detecting the progression of glaucoma have fundamental flaws

ObjectiveTo understand the problems involved in using global OCT measures for detecting progression in early glaucoma.Subjects/MethodsEyes from 76 patients and 28 healthy controls (HC) had a least two OCT scans at least 1 year apart. To determine the 95% confidence intervals (CI), 151 eyes (49 HC and 102 patients) had at least two scans within 6 months. All eyes had 24-2 mean deviation ≥-6dB. The average (global) thicknesses of the circumpapillary retinal nerve fibre layer (cRNFL), GONH, and of the retinal ganglion cell layer plus inner plexiform layer (RGCLP), Gmac, were calculated. Using quantile regression, the 95% CI intervals were determined. Eyes outside the CIs were classified as “progressors.” For a reference standard (RS), four experts evaluated OCT and VF information.ResultsCompared to the RS, 31 of the 76 (40.8%) patient eyes were identified as progressors (RS-P), and 45 patient, and all 28 HC, eyes as nonprogressors (RS-NP). The metrics missed (false negative, FN) 15 (48%) (GONH) and 9 (29%) (Gmac) of the 31 RS-P. Further, GONH and/or Gmac falsely identified (false positive, FP) 10 (22.2%) of 45 patient RS-NP eyes and 7 (25%) of the 28 HC eyes as progressing. Post-hoc analysis identified three reasons (segmentation, centring, and local damage) for these errors.ConclusionsGlobal metrics lead to FPs and FNs because of problems inherent in OCT scanning (segmentation and centring), and to FNs because they can miss local damage. These problems are difficult, if not impossible, to correct, and raise concerns about the advisability of using GONH and Gmac for detecting progression.

Short-Term Effects of Photodynamic Therapy on Segmentation of Retinal Layers in Central Serous Chorioretinopathy.

Background:The present study aims to evaluate the effect of photodynamic therapy (PDT) on the thickness of segmentation layers of the retina in cases with central serous chorioretinopathy (CSCR).Materials and Methods:This was a prospective, observational study on cases with CSCR who were candidates for PDT therapy. All patients had undergone at least 1 month of conservative management without satisfactory resolution. PDT was carried out according to the safe half-dose therapy scheme. Spectral-domain optical coherence tomography was employed to evaluate the changes in morphology and segmentation of retinal layers. Patients were followed up for 3 months.Results:Twenty-seven cases (18 males and 9 females) were included. Age of the patients varied from 39 to 59 years (mean: 46.61 ± 12.48 years). Cases were followed for 92.17 ± 3.28 days. Sixteen cases had functional and anatomical improvement by the treatment. Changes in overall retinal (377.39 ± 61.36 to 323.61 ± 71.36; P = 0.004) and all outer retinal segmentation layers including outer plexiform layer (34.93 ± 10.07 to 29.25 ± 6.12; P = 0.008), outer nuclear layer (63.52 ± 30.44 to 46.44 ± 20.62; P = 0.017), and retinal pigment epithelium (40.66 ± 37.73 to 23.78 ± 29.33; P = 0.016) were statistically significant. On the contrary, inner retinal segmentation layers, especially retinal ganglion cell (RGC) layer (38.29 ± 16.63 to 37.26 ± 16.18; P = 0.387), remained statistically unchanged.Conclusion:We postulate that PDT alleviates outer retinal edema where fluid accumulation occurs mostly, whereas it does not alter inner retinal and especially RGC layer. These findings may indicate that short-term atrophy of the inner retina did not occur following PDT and may point toward safety of this method for cases with CSCR.

Comparison of diagnostic ability of standard automated perimetry, short wavelength automated perimetry, retinal nerve fiber layer thickness analysis and ganglion cell layer thickness analysis in early detection of glaucoma.

Purpose:The aim of this study was to compare the diagnostic ability of macular ganglion cell layer (GCL) analysis using spectral domain optical coherence tomography against retinal nerve fiber layer analysis (RNFL), short-wavelength automated perimetry (SWAP), and standard automated perimetry (SAP) in early detection of glaucoma.Methods:Participants fulfilling the inclusion criteria were consecutively enrolled from the glaucoma clinic of tertiary care eye hospital in Western India from November 2015 to October 2016. The subjects underwent a detailed evaluation by trained glaucoma specialists. On suspicion of glaucoma, the patients underwent SAP, SWAP, and SD-OCT for GCL and RNFL analysis.Results:There were 91 patients in total of which experts classified 54 eyes into GON and 37 eyes into nonglaucomatous group. Sensitivity of SAP (42.59%) was significantly lower (P < 0.05) than that of average GCL thickness (79.63%) and average RNFL thickness (72.22%). Specificity and positive LR of SWAP (97.3% and 19.19, respectively) and SAP (94.6% and 7.88, respectively) were greater than those of GCL (81.08% and 4.21) and RNFL (67.57% and 2.23) parameters. Negative LR of average GCL thickness (0.25) was superior to that of average RNFL thickness (0.411), SWAP (0.495), and SAP (0.607).Conclusion:Macular GCL parameters perform better than RNFL parameters in patients with early glaucomatous damage. There is superior ability of SWAP over SAP in detecting glaucomatous changes in glaucoma suspect group. GCL thickness analysis has higher sensitivity and negative likelihood ratio, whereas SWAP had higher specificity and positive likelihood ratio. Thus, combining both tests can lead to better diagnostic ability for early glaucomatous damage.

Automated macular segmentation in compressive optic neuropathy and glaucomatous optic neuropathy

PurposeCompressive optic neuropathy (CON) can sometimes mimic glaucomatous optic neuropathy (GON), leading to inadequate management. Our purpose was to compare the macular area of patients with CON and GON to healthy controls (HC) and to determine if the macula area was able to distinguish between CON and GON.MethodsRetrospective, observational, cross‐sectional study, enrolling 70 patients (22 patients with CON, 25 with GON and 23 HC). Subjects were matched by age (median of 61 [±11.6]), and one eye was randomly selected. Spectral‐domain optical coherence tomography (SD‐OCT) images were generated using the Spectralis® OCT device (Heidelberg, Germany). An automated algorithm was used to segment the macular retina into nine layers and evaluate the thickness of each layer in the foveal, inner, and outer Early Treatment Diabetic Retinopathy Study (ETDRS) subfield rings. Data were compared across all study groups using Kruskal‐Wallis test, followed by pairwise comparisons for each duo. The resulting p‐values were adjusted using the Bonferroni correction and significance level was set at 0.05.ResultsHC had thicker inner retinal layer (IRL) compared with GON and CON (p &lt; 0.05). Global retinal thickness was significantly thinner in the inner superior (IS) and inner nasal (IN) subfields in CON compared with GON (p &lt; 0.05). The IRL is thinner in CON, specifically in the inner and outer nasal subfields, compared to GON. The IN subfield was thinner in the retinal nerve fibre, ganglion cell and inner plexiform layers (IPL) in CON compared with GON (p &lt; 0.05). No differences were found on the inner nuclear, outer plexiform, outer nuclear and outer retinal layers between groups.ConclusionsOur findings suggest that IRL is thinner in both CON and GON, and the IN subfield is specially affected in CON compared with GON. Despite not being our primary outcome, our results suggest that, compared to HC, layer neurodegeneration in both CON and GON affects mainly the inner layers and that does not extend to layers external to IPL. In conclusion, evaluation of the macular segmented layers damage, by SD‐OCT, may be a useful add‐on tool in the differential diagnosis between these two entities, when their manifestations overlap.

To compare and correlate visual field changes detected by perimetry with retinal nerve fiber layer and ganglion cell layer thickness observed using spectral domain optical coherence tomography in primary open angle glaucoma

To compare and correlate visual field changes detected by perimetry with retinal nerve fiber layer and ganglion cell layer thickness observed using spectral domain optical coherence tomography in primary open angle glaucoma

Evaluation of Macular Thickness, Retinal Nerve Fiber Layer and Ganglion Cell Layer Thickness in Patients among Type 2 Diabetes Mellitus Using Optical Coherence Tomography.

Background:Vascular abnormalities and microvasculopathy are one of the widely accepted factors of diabetic retinopathy (DR). Retinal Neuronal dysfunction and neurodegeneration are also important components in the pathogenesis of DR. However recent investigations show neurodegenerative alterations before the appearance of microvascular changes in patients having DR.Aims and Objectives:(1) To measure the macular thickness, retinal nerve fiber layer thickness, and ganglion cell complex thickness among patients with type 2 diabetes mellitus using optical coherence tomography. (2) To compare the macular thickness, retinal nerve fiber layer thickness and ganglion cell complex thickness in type 2 diabetic patients with and without DR with normal controls using optical coherence tomography.Materials and Methods:Thirty Patients with type 2 diabetes mellitus without DR, 30 having mild and moderate DR and 30 healthy normals are taken considering the inclusion and exclusion criteria. Macular thickness, retinal nerve fiber layer (RNFL) thickness, ganglion cell layer-inner plexiform layer (GCL-IPL) thickness was measured in each individual and it was compared using one way ANOVA test, post hoc test and Pearson correlation was performed to evaluate the linear correlation between variables and calculated P < 0.05 was regarded as its significance.Results:The average RNFL thickness was 90.27 ± 5.57 and 107.7 ± 5.32 um in diabetic patients and controls respectively (P < 0.001). Furthermore, for two different groups of diabetic patients, the average RNFL thickness was 89.92 ± 6.62 um in the no DR group and 78.6 ± 3.93 in the DR group (P = 0.339). The average GCL-IPL thickness was 82.65 ± 2.25 um and 92.10 ± 2.41 um in diabetic patients and controls, respectively (P < 0.001). Furthermore, for two different groups of diabetic patients, the average GCL-IPL thickness was 82.22 ± 2.11 um in the no DR group and 71.55 ± 2.34 in the DR group (P = 0.535). The average macular thickness was 238.03 ± 4.42 and 277.9 ± 5.85 um in diabetic patients and controls, respectively (P < 0.001). Furthermore, for two different groups of diabetic patients, the average macular thickness was 236.56 ± 4.10 um in the no DR group and 242.8 ± 4.95 um in the DR group (P = 0.585).Conclusion:There was a statistically significant reduction of mean RNFL, GCL-IPL and macular thickness in type 2 diabetic patients with no DR compared with a homogenous control group indicating neuroretinal changes occur before vascular changes of DR.

Acute monocular oligemia in a patient with migraine with aura demonstrated using OCT-angiography: A case report.

Migraine is one of the most common causes of transient visual loss. Optical coherence tomography angiography (OCTA) provides fast and non-invasive imaging of the retinal vessels. We report one case of monocular retinal oligemia demonstrated using OCTA during a migraine attack with aura. A 27-year-old man with a previous history of migraine with visual aura was seen in the emergency room due to acute left hemicranial pain with positive visual symptoms in his right eye. The patient reported a blue stain in his right eye. Optical coherence tomography angiography (OCT-A) showed an extensive area of hypoperfusion in the macular region of his right eye. Forty-eight hours later visual symptoms had improved and the OCT-A showed a significant reduction in the area of hypoperfusion. Seven days later the patient was asymptomatic and retinal perfusion had returned to normal values. Monocular involvement suggests that these retinal vascular changes are independent from cerebral vascular changes, supporting the hypothesis of selective retinal ganglion cell layer spreading depression as the possible cause of some cases of retinal migraine.

Retinal hypoxia after experimental subarachnoid hemorrhage

Background and PurposeThe patients who survive subarachnoid hemorrhage (SAH) often have long-term neurological complications. There are no reports about the pathological change of retina after SAH. MethodsAn experimental model of SAH was established by injecting autologous blood into the prechiasmatic cistern of Sprague-Dawley rats. Hematoxylin and eosin (HE) staining was performed to show the alternation of morphology in retina after SAH. To detect the retinal new vessels (NVs), CD31 was labelled by immunofluorescence and immunohistochemistry. The time-course expressions of vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1α (HIF-1 α) was also revealed by Western blot analysis. ResultsA clear reduction of retinal ganglion cells (RGCs) was noticed after SAH. The immunofluorescence and immunohistochemical staining of CD31 reveals a large number of NVs in RGC layer after SAH compared with the normal controls. The level of VEGF-A in the retina after SAH was increased and peaked at 12h and 14 d. The expression of HIF-1α in the retina increased as early as 3 h after SAH, reached a peak at 12 h after SAH. ConclusionsThe results showed that SAH induced the retina hypoxia resulting in the reduction of RGCs, increase of NVs and activation of NVs related HIF-1α/VEGF-A pathway.

Enhanced Delivery of siRNA to Retinal Ganglion Cells by Intravitreal Lipid Nanoparticles of Positive Charge.

RNAi therapy has been developed and explored for treating retinal conditions since last decades. The progression of retinal diseases including the age-related macular degeneration and glaucoma is associated with the malfunction of specific retinal cells. Therefore, to deliver therapeutic RNAi to selective retinal tissues with desired gene downregulation is crucial for the treatment of retinal diseases via RNAi therapy. Lipid-based nanoparticles are potent delivery vectors for RNAi therapeutics to achieve high gene silencing efficiency. The surface charge has been demonstrated to affect the intraocular behaviors and retinal distribution of intravitreally administered lipid nanoparticles (LNPs), which could subsequently affect the gene knockdown efficiency in specific retinal layers. Here, we evaluated three charged LNPs for their ability to deliver siRNA and facilitate gene downregulation both in vitro and in vivo. LNPs with different surface charges ranging from neutral to positive (5-34 mV) were successfully formulated. All types of charged LNPs managed gene knockdown in both mammalian cell line and primary neurons. At 48 h post intravitreal injection, neutral LNPs (6.2 mV) and mildly positive LNPs (15.9 mV) mediated limited retinal gene suppression (<10%) and the more positive LNPs (31.2 mV) led to ∼25% gene suppression in the retinal ganglion cell (RGC) layer. No gene silencing in the retinal pigmented epithelium layer was facilitated by any LNPs independent of the charges. In summary, this study has shown that positive LNPs with an optimized charge managed specific gene downregulation in the RGC layer. These RNAi carriers hold potential for the treatment of RGC-associated retinal diseases.

The Influence of Axial Length Upon the Retinal Ganglion Cell Layer of the Human Eye.

PurposeVariation in retinal thickness with eye size complicates efforts to estimate retinal ganglion cell number from optical coherence tomography (OCT) measures. We examined the relationship among axial length, the thickness and volume of the ganglion cell layer (GCL), and the size of the optic chiasm.MethodsWe used OCT to measure GCL thickness over 50 degrees of the horizontal meridian in 50 healthy participants with a wide range of axial lengths. Using a model eye informed by individual biometry, we converted GCL thickness to tissue volume per square degree. We also measured the volume of the optic chiasm for 40 participants using magnetic resonance imaging (MRI).ResultsThere is a positive relationship between GCL tissue volume and axial length. Given prior psychophysical results, we conclude that increased axial length is associated with increased retinal ganglion cell size, decreased cell packing, or both. We characterize how retinal ganglion cell tissue varies systematically in volume and spatial distribution as a function of axial length. This model allows us to remove the effect of axial length from individual difference measures of GCL volume. We find that variation in this adjusted GCL volume correlates well with the size of the optic chiasm.ConclusionsOur results provide the volume of ganglion cell tissue in the retina, adjusted for the presumed effects of axial length upon ganglion cell size and/or packing. The resulting volume measure accounts for individual differences in the size of the optic chiasm, supporting its use to characterize the post-retinal visual pathway.Translational RelevanceVariations in ametropia can confound clinical measures of retinal features. We present a framework within which the thickness and volume of retinal structures can be measured and corrected for the effects of axial length.

Frequency of retinal changes in patients with COVID-19: an observational study

In order to enter cells, SARS-CoV-2 virus uses the angiotensin-converting enzyme 2 receptor that is also expressed in retina.Aim.Determination of the frequency and nature of retinal changes, evaluation of visual functions in patients who have got over COVID-19.Materials and methods.This observational research includes 31 patients aged from 28 to 79 that got over COVID-19 (with severity according to computed tomography (CT): 1–3) in the period from 15 to 40 days before the research. Standard ophthalmological examination and optical coherence tomography (OCT) were performed; visual acuity measurement and threshold static perimetry were used to assess visual functions.Results.Pathology of the ocular surface wasn’t detected. Ophthalmoscopy revealed retinal changes in only one patient. At OCT, 27 (87%) patients proved to have de novo changes in the retinal neuroepithelium at the level of the internal plexiform layer and the retinal ganglion cell layer in the form of hyper-reflective polymorphic foci with clear borders; 18 (67%) patients had monocular lesions. The maximum corrected visual acuity didn’t differ from the previously defined one; no violations of retinal light sensitivity were detected. No association was found between the severity of CT lung changes and retinal changes. The detected retinal changes weren’t associated with symptoms of anosmia (hyposmia) and ageusia. OCT repeated after 12–15 days showed no dynamics of hyperreflective foci: they remained unchanged in their shape, echogenicity and size.Conclusion.De novo changes in retinal neuroepithelium at the level of the inner plexiform layer and the retinal ganglion cell layer were detected according to OCT data in 87% of patients who had undergone COVID-19. Anatomical changes in the retina weren’t manifested by functional visual disturbances. There is no association of retinal changes with lesions of I and IX cranial nerve pairs.

Comparative lipidomic analysis of mammalian retinal ganglion cells and M\xfcller glia in situ and in vitro using High-Resolution Imaging Mass Spectrometry

In order to better understand retinal physiology, alterations to which underlie some ocular diseases, we set out to establish the lipid signature of two fundamental cell types in the retina, Müller Glia and Retinal Ganglion Cells (RGCs). Moreover, we compared the lipid signature of these cells in sections (in situ), as well as after culturing the cells and isolating their cell membranes (in vitro). The lipidome of Müller glia and RGCs was analyzed in porcine retinal sections using Matrix Assisted Laser Desorption Ionization Imaging Mass Spectrometry (MALDI-IMS). Isolated membranes, as well as whole cells from primary cell cultures of RGCs and Müller glia, were printed onto glass slides using a non-contact microarrayer (Nano Plotter), and a LTQ-Orbitrap XL analyzer was used to scan the samples in negative ion mode, thereafter identifying the RGCs and Müller cells immunohistochemically. The spectra acquired were aligned and normalized against the total ion current, and a statistical analysis was carried out to select the lipids specific to each cell type in the retinal sections and microarrays. The peaks of interest were identified by MS/MS analysis. A cluster analysis of the MS spectra obtained from the retinal sections identified regions containing RGCs and Müller glia, as confirmed by immunohistochemistry in the same sections. The relative density of certain lipids differed significantly (p-value ≤ 0.05) between the areas containing Müller glia and RGCs. Likewise, different densities of lipids were evident between the RGC and Müller glia cultures in vitro. Finally, a comparative analysis of the lipid profiles in the retinal sections and microarrays identified six peaks that corresponded to a collection of 10 lipids characteristic of retinal cells. These lipids were identified by MS/MS. The analyses performed on the RGC layer of the retina, on RGCs in culture and using cell membrane microarrays of RGCs indicate that the lipid composition of the retina detected in sections is preserved in primary cell cultures. Specific lipid species were found in RGCs and Müller glia, allowing both cell types to be identified by a lipid fingerprint. Further studies into these specific lipids and of their behavior in pathological conditions may well help identify novel therapeutic targets for ocular diseases.

Retinal vascularity, nerve fiber, and ganglion cell layer thickness in thyroid eye disease on optical coherence tomography angiography

ABSTRACT Purpose To compare the retinal vascularity, peripapillary vascularity, nerve fiber layer thickness and ganglion cell layer thickness between active, inactive thyroid eye disease (TED) and healthy eyes. Methods Retrospective comparative cross-sectional cohort study. Patients with TED, active and inactive on the VISA score, and healthy eyes were included. All patients underwent optical coherence tomography angiography with detailed demographic and clinical data capture. Using automated software, retinal and peripapillary vascularity index, nerve fiber layer thickness, and ganglion cell layer thickness were calculated and were compared between the groups. Results Twenty-four eyes with active TED, 102 eyes with inactive TED and 52 healthy eyes were included. Independent sample t test was used to compare parametric data and Mann-Whitney test to compare non-parametric data. The age and gender were comparable across groups. The peripapillary vascularity index (26.82 ± 4.13 versus 34.92 ± 5.08, p = .002) and the macular vascularity index (20.32 ± 2.5 versus 31.21 ± 3.89, p < .0001) were reduced in active TED eyes versus inactive eyes. Macular vascularity index was comparable in the inactive versus the healthy eyes. The RNFL thickness was increased in the active TED eyes versus the inactive eyes (45.11 ± 18.3 versus 35.55 ± 7, p = .03) and active versus healthy eyes (45.11 ± 18.3 versus 36.28 ± 7.89, p = .03). Ganglion cell layer thickness between all three groups was comparable. Conclusion Decrease in peripapillary and macular vascular density and increase in RNFL thickness are seen in active TED compared to inactive TED and healthy eyes. In disease inactivity, these parameters are comparable to healthy eyes.

Characteristics of Japanese patients with Leber's hereditary optic neuropathy and idebenone trial: a prospective, interventional, non-comparative study.

Leber's hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients. Prospective, interventional, non-comparative study in patients with definite LHON diagnosis, under trial registration number UMIN000017939. Fifty-seven patients received 900 mg/day idebenone for 24 weeks. We measured baseline best-corrected visual acuity, visual fields, critical fusion frequency and retinal ganglion cell layer complex thickness; we assessed efficacy at 24 and 48 weeks, and safety throughout. Patients were predominantly male (91.2%) and most had an mt.11778G>A mutation (94.7%). All patients tolerated idebenone therapy well. Data from the 51 mt.11778 patients were compared with their baseline data. At 48 weeks, significant improvement in best-corrected visual acuity was observed in 17 patients (33.3%). Furthermore, 25.5% of patients showed improvements in visual fields and 33.3% in critical fusion frequency. However, retinal ganglion cell layer complex thickness was significantly reduced. Among patients who started idebenone >1 year after disease onset, visual improvement was found in 12 (38.7%). Among patients who developed LHON before 19 years of age, visual improvement was found in 11 (42.3%). Idebenone's potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.

Longitudinal changes in the macula and optic nerve in familial dysautonomia.

Familial Dysautonomia (FD) disease, lacks a useful biomarker for clinical monitoring. In this longitudinal study we characterized the structural changes in the macula, peripapillary and the optic nerve head (ONH) regions in subjects with FD. Data was consecutively collected from subjects attending the FD clinic between 2012 and 2019. All subjects were imaged with spectral-domain Optical Coherence Tomography (OCT). Global and sectoral measurements of mean retinal nerve fiber layer (RNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness, and ONH parameters of rim area, average cup-to-disc (C:D) ratio, and cup volume were used for the analysis. The best fit models (linear, quadratic and broken stick linear model) were used to describe the longitudinal change in each of the parameters. 91 subjects (149 eyes) with FD of ages 5-56years were included in the analysis. The rate of change for average RNFL and average GCIPL thicknesses were significant before reaching a plateau at the age of 26.2 for RNFL and 24.8 for GCIPL (- 0.861µm/year (95% CI - 1.026, - 0.693) and - 0.553µm/year (95% CI - 0.645, - 0.461), respectively). Significant linear rate of progression was noted for all ONH parameters, except for a subset of subjects (24%), with no cupping that did not show progression in any of the ONH parameters. The rapidly declining RNFL and GCIPL can explain the progressive visual impairment previously reported in these subjects. Among all structural parameters, ONH parameters might be most suitable for longitudinal follow-up, in eyes with a measurable cup.