A challenging differential diagnosis - Leber's Hereditary Optic Neuropathy.

Leber's hereditary optic neuropathy (LHON) is the most common maternally inherited disease linked to mitochondrial DNA (mtDNA). The patients present with subacute asymmetric bilateral vision loss. Approximately 95% of the LHON cases are caused by m.3460G>A (MTND1), m.11778G>A (MTND4), and m.14484T>C (MTND6) mutations. The hallmark of hereditary optic neuropathies determined by mitochondrial dysfunction is the vulnerability and degeneration of retinal ganglion cells (RGC). We present the case of a 28-year-old man who came to our clinic complaining of a subacute decrease in visual acuity of his left eye. From his medical history, we found out that one month before he had the same symptoms in the right eye. From the family history, we noted that an uncle has had vision problems since childhood. We carried out complete blood tests, including specific antibodies for autoimmune and infectious diseases. Laboratory tests and MRI were within normal limits. A blood test of the mtDNA showed the presence of 11778 G>A mutation on the mtND6 gene. The medical history, the fundus appearance, the OCT, and the paraclinical investigations, made us diagnose our patient with Leber's hereditary optic neuropathy. As soon as possible, we began the treatment with systemic idebenone, 900 mg/day. We examined the patient 2, 6, and 10 weeks after initiating the treatment. Abbreviations: LHON = Leber's Hereditary Optic Neuropathy, mtDNA = mitochondrial DNA, VA = visual acuity, RE = right eye, LE = left eye, OCT = Optical coherence tomography, pRNFL = peripapillary retinal nerve fiber layer, GCL = retinal ganglion cells layer, MRI = magnetic resonance imaging, VEP = visual evoked potentials, VEP IT = VEP implicit time, VEP A = VEP amplitude.

The macular retinal ganglion cell layer as a biomarker for diagnosis and prognosis in multiple sclerosis: A deep learning approach.

PURPOSE: The macular ganglion cell layer (mGCL) is a strong potential biomarker of axonal degeneration in multiple sclerosis (MS). For this reason, this study aims to develop a computer-aided method to facilitate diagnosis and prognosis in MS. METHODS: This paper combines a cross-sectional study of 72 MS patients and 30 healthy control subjects for diagnosis and a 10-year longitudinal study of the same MS patients for the prediction of disability progression, during which the mGCL was measured using optical coherence tomography (OCT). Deep neural networks were used as an automatic classifier. RESULTS: For MS diagnosis, greatest accuracy (90.3%) was achieved using 17 features as inputs. The neural network architecture comprised the input layer, two hidden layers and the output layer with softmax activation. For the prediction of disability progression 8 years later, accuracy of 81.9% was achieved with a neural network comprising two hidden layers and 400 epochs. CONCLUSION: We present evidence that by applying deep learning techniques to clinical and mGCL thickness data it is possible to identify MS and predict the course of the disease. This approach potentially constitutes a non-invasive, low-cost, easy-to-implement and effective method.

Multimodal analysis in symptomatic MIDD-associated retinopathy. A case report and literature review.

Purpose: To present results of contemporary multimodal ophthalmic imaging in a case of maternally inherited diabetes and deafness (MIDD) and a literature review of MIDD. Methods: A case of a 47-year-old female with diabetes mellitus, severe insulin resistance, familial lipodystrohy, deafness and increasing problems with vision is reported. A full ophthalmic examination was done, including best corrected visual acuity (BCVA, LogMAR), funduscopy, and imaging studies: optical coherence tomography (OCT), OCT angiography (OCT-A), fundus autofloresence (FAF), visual fields (HVF) 10-2 , electrophysiology (EP) and genetic testing were performed. Literature available on the topic was reviewed. Results: BCVA was 0.06 LogMAR in the right eye and 0.1 LogMAR in the left. Funduscopy revealed atrophy (AT) and pigmentary changes but no diabetic retinopathy. HVF confirmed corresponding defects. The imaging and diagnostic tests showed the following abnormalities: FAF: hypoautofluoresence in areas of AT and mottled appearance in the macular and peripapillary area; OCT: attenuation of outer retinal layers and retinal pigment epithelium (RPE) in the AT; OCT-A: thinning of the deep capillary plexus and choriocapillaris; EP: abnormalities on full field electroretinogram (ERG), 30 Hz flicker and single cone flash response; multifocal ERG: reduced responses; genetic testing: A-to-G transition mutation at position 3243 of the mitochondrial genome, typical for MIDD. After one year OCT ganglion cell analysis showed loss of thickness. Conclusions: Genetic testing should be considered in diabetic patients with pigmentary retinopathy. Imaging studies and diagnostic testing showed structural and functional retinal changes, confined to the macula and progressive in nature.

LCM-Seq for Retinal Cell Layer-Specific Responses During Optic Nerve Regeneration.

LCM-seq is a powerful tool for gene expression analysis from individual or groups of cells that can be spatially isolated. Within the visual system, retinal ganglion cells (RGCs), the cells that connect the eye to the brain through the optic nerve, reside in the retinal ganglion cell layer of the retina. This well-defined location provides a unique opportunity to harvest RNA by laser capture microdissection (LCM) from a highly enriched cell population. Using this method, it is possible to explore transcriptome-wide changes in gene expression following optic nerve injury. In the zebrafish model, this method can be used to identify molecular events driving successful optic nerve regeneration in contrast to mammals that fail to regenerate axons in the central nervous system. Here we provide a method for LCM from the different retinal layers of zebrafish following optic nerve injury and during the process of optic nerve regeneration. Purified RNA from this protocol is sufficient for RNA-seq or other downstream analysis.

Caffeine and the Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: Findings from Clinical and Experimental Studies.

The aim of this study was to assess the potential benefits of caffeine intake in protecting against the development of diabetic retinopathy (DR) in subjects with type 2 diabetes (T2D). Furthermore, we tested the effect of topical administration of caffeine on the early stages of DR in an experimental model of DR. In the cross-sectional study, a total of 144 subjects with DR and 147 individuals without DR were assessed. DR was assessed by an experienced ophthalmologist. A validated food frequency questionnaire (FFQ) was administered. In the experimental model, a total of 20 mice were included. One drop (5 µL) of caffeine (5 mg/mL) (n = 10) or vehicle (5 µL PBS, pH 7.4) (n = 10) was randomly administered directly onto the superior corneal surface twice daily for two weeks in each eye. Glial activation and retinal vascular permeability were assessed using standard methods. In the cross-sectional study in humans, the adjusted-multivariable model showed that a moderate and high (Q2 and Q4) caffeine intake had a protective effect of DR (odds ratio (95% confidence interval) = 0.35 (0.16-0.78); p = 0.011 and 0.35 (0.16-0.77); p = 0.010, respectively). In the experimental model, the administration of caffeine did not improve either reactive gliosis or retinal vascular permeability. Our results suggest a dose-dependent protective effect of caffeine in the development of DR, while the potential benefits of antioxidants in coffee and tea should also be considered. Further research is needed to establish the benefits and mechanisms of caffeinated beverages in the development of DR.

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

INTRODUCTION: 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. CASE DESCRIPTION: 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. CONCLUSION: 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.

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

PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Evaluation of the Correlation between Regional Retinal Ganglion Cell Damage and Visual Field Sensitivity in Patients with Advanced Glaucoma.

(1) Background: to investigate the correlation between structural (retinal ganglion cells and retinal nerve fibers) and functional alterations analyzed point-by-point in the central 10 degrees of the visual field of patients with advanced glaucoma using Humphrey 10-2 visual field tests. (2) Methods: Single-center prospective cohort study carried on from October 2018 to February 2019 at the Croix-Rousse hospital, Lyon, France. The primary outcome measure was the point-by-point correlation between retinal sensitivity (Humphrey 10-2) and retinal ganglion cell complex (GCC) thickness. (3) Results: 29 eyes of 27 patients were examined. Of these, 15 eyes had a mean deviation (MD) less than −20 dB. There were statistically significant linear relationships between GCC thickness and 10-2 visual field sensitivity for several points in the lower part of the visual field, with lower retinal sensitivity being associated with thicker GCC layers. There were no strong linear relationships or statistically significant correlations in the other regions of the visual field. For the patients with MD < −20 dB, there were statistically significant linear relationships between GCC thickness and 10-2 visual field sensitivity for several points in the superior nasal region. Retinal sensitivity was not correlated with retinal nerve fibre layer thickness. (4) Conclusions: In this study of patients with advanced glaucoma, GCC thickness was linearly associated with 10-2 visual field sensitivity in certain regions, negatively for patients with less-severe glaucoma. The initial thickening raises questions about the apoptosis mechanism, while the thinning observed in the most severe cases is consistent with the ganglion cell death identified on visual field tests.

Retinal ganglion cell layer thickness and volume measured by OCT changes with age, sex, and axial length in a healthy population.

BACKGROUND: The ganglion cell layer (GCL) measurements with Optical Coherence Tomography (OCT) are important for both ophthalmologists and neurologists because of their association with many ophthalmic and neurological diseases. Different factors can affect these measurements, such as brain pathologies, ocular axial length (AL) as well as age and sex. Studies conducted to measure the GCL have overlooked many of these factors. The purpose of this study is to examine the effect of age, sex, and AL on normal retinal GCL thickness and volume in a healthy population without any neurological diseases. METHODS: A prospective cross-sectional study was designed to measure GCL thickness and total volume with OCT with automated segmentation and manual correction where needed. Visual acuity, AL, and autorefraction were also measured. A mixed linear model was used to determine the association of the effect of the various parameters on the GCL thickness and volume. RESULTS: One hundred and sixteen eyes of 60 subjects (12-76 years of age, 55% female) were examined of which 77% had 0 ± 2 D of spherical equivalent, and mean axial length was 23.86 mm. About 25% of the OCT-automated GCL measurements required manual correction. GCL thickness did not differ in similar anatomic regions in right and left eyes (P > 0.05). GCL volume was greater in males relative to females after adjustment for age and axial length (1.13 ± 0.07 mm3 for males vs 1.09 ± 0.09 mm3 for females; P = 0.031). GCL thickness differed between males and females in the inner retinal ring (P = 0.025) but not in the outer ring (P = 0.66). GCL volume declined with age (P = 0.031) but not after adjustment for sex and axial length (P = 0.138). GCL volume declined with longer axial length after adjustment for age and sex (P = 0.048). CONCLUSION: Age, sex and axial length should be taken into consideration when measuring the GCL thickness and volume with OCT. Automated OCT segmentation should be reviewed for manual adjustments.

Detecting glaucoma with only OCT: Implications for the clinic, research, screening, and AI development.

A method for detecting glaucoma based only on optical coherence tomography (OCT) is of potential value for routine clinical decisions, for inclusion criteria for research studies and trials, for large-scale clinical screening, as well as for the development of artificial intelligence (AI) decision models. Recent work suggests that the OCT probability (p-) maps, also known as deviation maps, can play a key role in an OCT-based method. However, artifacts seen on the p-maps of healthy control eyes can resemble patterns of damage due to glaucoma. We document in section 2 that these glaucoma-like artifacts are relatively common and are probably due to normal anatomical variations in healthy eyes. We also introduce a simple anatomical artifact model based upon known anatomical variations to help distinguish these artifacts from actual glaucomatous damage. In section 3, we apply this model to an OCT-based method for detecting glaucoma that starts with an examination of the retinal nerve fiber layer (RNFL) p-map. While this method requires a judgment by the clinician, sections 4 and 5 describe automated methods that do not. In section 4, the simple model helps explain the relatively poor performance of commonly employed summary statistics, including circumpapillary RNFL thickness. In section 5, the model helps account for the success of an AI deep learning model, which in turn validates our focus on the RNFL p-map. Finally, in section 6 we consider the implications of OCT-based methods for the clinic, research, screening, and the development of AI models.

Laser Capture Microdissection-Based RNA Microsequencing Reveals Optic Nerve Crush-Related Early mRNA Alterations in Retinal Ganglion Cell Layer.

Purpose: To establish a method of laser capture microdissection (LCM) and RNA microsequencing for exploring optic nerve crush (ONC)-related early mRNA alterations in retinal ganglion cell (RGC) layer. Methods: An LCM protocol was developed using retinal tissue sections to obtain high-quality RNA for microsequencing. Cells in the RGC layer were collected by laser pressure catapulting (LPC) using a PALM Zeiss UV LCM system. The effect of section thickness and slide type on tissue capture success and RNA yield and the integrity after LCM were evaluated. The optimal LCM protocol was used to explore ONC-related early mRNA alterations in the RGC layer. Candidate genes were validated by real-time polymerase chain reaction of the RGC layer tissue dissected by "cut and LPC" using the same LCM system. Results: We successfully established an optimal LCM protocol using 30-µm-thick retinal tissue sections mounted on glass slides and laser pressure catapulting (LPC) to collect cells in the RGC layer and to obtain high-quality RNA for microsequencing. On the basis of our protocol, we identified 8744 differentially expressed genes that were involved in ONC-related early mRNA alterations in the RGC layer. Candidate genes included Atf3, Lgals3, LOC102551701, Plaur, Tmem140, and Maml1. Conclusions: The LCM-based single-cell RNA sequencing allowed a new sight into the early mRNA changes of RGCs highlighting new molecules associated to ONC. Translational Relevance: This technique will be helpful for more accurate transcriptome analysis of clinical pathological samples of ophthalmology and provide important reference for the discovery of new pathological diagnosis indicators and drug development targets.

Thickness of individual layers at the macula and associated factors: the Beijing Eye Study 2011.

BACKGROUND: Diagnosis and follow-up of retinal diseases may be improved if the thickness of the various retinal layers, in addition to the total retinal thickness, is taken into account. Here we measured the thickness of the macular retinal layers in a population-based study group to assess the normative values and their associations. METHODS: Using spectral-domain optical coherence tomographic images (Spectralis®, wavelength: 870 nm; Heidelberg Engineering Co, Heidelberg, Germany), we measured the thickness of the macular retinal layers in participants of the population-based Beijing Eye Study without ocular diseases and without systematic diseases, such as arterial hypertension, hyperlipidemia, diabetes mellitus, cardiovascular diseases, previous myocardial infarction, cerebral trauma and stroke. Segmentation and measurement of the retinal layers was performed automatically in each of the horizontal scans. RESULTS: The study included 384 subjects (mean age:60.0 ± 8.0 years). The mean thickness of the whole retina, outer plexiform layer, outer nuclear layer,retinal pigment epithelium, inner retinal layer and photoreceptor layer was 259.8 ± 18.9 µm, 19.4 ± 3.9 µm, 93.4 ± 9.6 µm, 17.6 ± 1.9 µm, 169.8 ± 18.6 µm, and 90.0 ± 4.2 µm, respectively. In multivariable analysis, the thickness of the foveola and of all retinal layers in the foveal, parafoveal and perifoveal region decreased with older age (all P < 0.05), except for the thickness of the parafoveal outer plexiform layer which increased with age. Men as compared to women had higher thickness measurements of the photoreceptor layer and outer nuclear layer in all areas, and of all layers between the retinal nerve fiber layer and inner nuclear layer in the parafoveal area (all P < 0.05). The associations between the macular retinal layers thickness and axial length were not consistent. The inner plexiform layer was thicker, and the ganglion cell layer and inner nuclear layer were thinner, in the temporal areas than in the nasal areas, CONCLUSIONS: The associations between decreasing thickness of most retinal layers with older age and the correlation of a higher thickness of some retinal layers with male gender may clinically be taken into account.

Retinal Ganglion Cell Layer Thicknesses and Visual Functions in Patients with Bilateral Temporal Optic Atrophy

PURPOSE: To investigate correlations between macular retinal ganglion cell (RGC) layer thickness and best-corrected visual acuity (BCVA) and visual field parameters in patients with bilateral temporal optic atrophy.METHODS: Thirty eyes of 15 patients with bilateral temporal optic atrophy and 30 eyes of 15 normal subjects that were age- and sex-matched were included in the study. We measured the thicknesses of the RGC layers of posterior poles using optical coherence tomography volume scanning. The RGC layer was divided into nine zones based on the Early Treatment of Diabetic Retinopathy Study baseline. Possible correlations of the RGC layer with the BCVA and visual field parameters were determined.RESULTS: The RGC layer thickness was significantly thinner in all patients compared to those in the control group (p = 0.001). The RGC layer thicknesses in the inner superior, inner temporal, inner inferior, and inner nasal areas were significantly correlated with the BCVA (r = −0.650, r = −0.626, r = −0.616, and r = −0.636, respectively; p = 0.000). The RGC layer thicknesses in the outer superior, outer temporal, outer inferior, and outer nasal areas were significantly correlated with the mean deviation of the visual field test (r = 0.470, r = 0.349, r = 0.496, and r = 0.469, respectively; p < 0.05).CONCLUSIONS: In patients with bilateral temporal optic atrophy, the RGC layer thickness in the medial region was correlated with the BCVA, and the RGC layer thickness in the lateral region was correlated with the mean deviation of the visual field test.

The impact of ganglion cell layer cysts in diabetic macular oedema treated with anti-vascular endothelial growth factor.

PURPOSE: To investigate the prevalence and impact of ganglion cell layer cysts (GCLC) in patients with diabetic macular oedema (DME) under continuous anti-vascular endothelial growth factor (VEGF) therapy. METHODS: The clinical findings and spectral domain optical coherence devices of baseline visits and follow-up after 12-24 and 36 months of DME patients under continuous anti-VEGF therapy were retrospectively collected and analysed for the impact of GCLC cysts. Previously established prognostic parameters were also assessed. RESULTS: A total of 110 eyes of 110 DME patients (mean age 64 ± 10 years) were included. At baseline, 17% eyes had GCLC. With GCLC, the best-corrected visual acuity (BCVA) improvement was in mean 8.4 ± 2.4 Early-Treatment-Diabetic-Retinopathy-Study (ETDRS) letters less over the course of 36 months compared to the group lacking GCLC (p = 0.0009). Eyes with GCLC showed 68 ± 23.4 µm less central retinal thickness (CRT) decrease than eyes lacking GCLC (p < 0.0001). In the linear mixed effect models including external limiting membrane disruption, disintegration of inner retinal layer and epiretinal membrane, GCLC remained a statistical significant factor for the outcome parameter CRT, but missed statistical significance for BCVA. CONCLUSION: Ganglion cell layer cysts (GCLC) seem to impact outcome in DME in patients receiving long-term treatment. This prognostic factor warrants further evaluation in the context of already well-established outcome parameters.

Structural impairment patterns in peripapillary retinal fiber layer and retinal ganglion cell layer in mitochondrial optic neuropathies.

AIM: To evaluate the structural injure patterns in peripapillary retinal fiber layer (pRNFL), retinal ganglion cell layer (RGCL) and their correlations to visual function in various mitochondrial optic neuropathies (MON) to offer help to their differential diagnosis. METHODS: Totally 32 MON patients (60 eyes) were recruited within 6mo after clinical onsets, including 20 Leber hereditary optic neuropathy (LHON) patients (37 eyes), 12 ethambutol-induced optic neuropathy (EON) patients (23 eyes), and 41 age-gender matched healthy controls (HC, 82 eyes). All subjects had pRNFL and RGCL examinations with optic coherence tomography (OCT) and visual function tests. RESULTS: In the early stages of MON, the temporal pRNFL thickness decreased (66.09±22.57 µm), but increased in other quadrants, compared to HC (76.95±14.81 µm). The other quadrants remaining stable for LHON and EON patients besides the second hour sector of pRNFL thickness reduced and the temporal pRNFL decreased (56.78±15.87 µm) for EON. Total macular thickness in MON reduced remarkably (279.25±18.90 µm; P=0.015), which mainly occurring in the inner circle (3 mm diameter of circle) and the nasal temporal sectors in the outer circle (5.5 mm diameter of circle), in contrast to those in HC. RGCL thickness reduced in each sector of the macula (61.90±8.73 µm; P≤0.001). It strongly showed the correlationship of best corrected visual acuity (R=0.50, P=0.0003) and visual field injury (R=0.54, P=0.0002) in MON patients. CONCLUSION: OCT is a potential tool for detecting structural alterations in the optic nerves of various MON. Different types of MON may have different damage patterns.

Injuries to the Immature Optic Radiation Show Correlated Thinning of the Macular Ganglion Cell Layer.

Injuries to the immature optic radiation (OR) are associated with thinning of the retinal nerve fiber layer and corresponding visual field (VF) defects. The aim of the current study was to seek evidence for causal retrograde trans-synaptic degeneration by exploring the correspondence between the localization and extension of the injury to the OR and the structure of the macular ganglion cell complex, and the relation to VF function. Seven adults (age range 18-35) with visual dysfunction secondary to white-matter damage of immaturity and six healthy adults (age range 22-33) underwent magnetic resonance imaging (MRI). Fiber tractography was used to generate the geniculate projections to the dorsal and ventral striate cortex, delineated by retinotopic functional MRI mapping. The structure of the macular ganglion cell complex was measured with optical coherence tomography. The tractography showed overlaps between the dorsal and ventral geniculo-striate projections. However, in four patients with inferior VF defects, the dorsal projections were to a large extent traversing the space normally solely occupied by ventral projections. This is consistent with structural changes to the OR and suggests of re-organization upon injury. Diffusion parameters were significantly different between patients and controls, and most pronounced in the dorsal geniculo-striate projections, with a pattern indicating primary injury. The macular ganglion cell complex was significantly thinner in the patients and most pronounced in the superior sectors; a pattern particularly evident in the four patients with inferior VF defects. The ratio of the mean thickness of the macular ganglion cell complex in the superior and inferior sectors significantly correlated with the axial and mean diffusivities in the contra- and ipsilateral dorsal striate projections. The results suggest a causal link between injuries to the superior portion of the immature OR and secondary thinning in the macular ganglion cell complex, resulting in inferior VF defects.

Evaluation of retinal nerve fibre layer, ganglion cell layer and choroidal thickness with optical coherence tomography in migraine patients: a case-control study.

BACKGROUND: Evaluation of retinal nerve fibre layer (RNFL), ganglion cell layer (GCL) and choroidal thickness (CT) with optical coherence tomography (OCT) in chronic migraine patients, to compare with healthy controls. MATERIAL AND METHOD: Ninety-four eyes of 47 chronic migraine patients (Group 1) and 68 eyes of 34 healthy individuals (Group 2) were included in this prospective case-control study. The right and left eyes were separately evaluated. Mean peripapillary RNFL thicknesses, mean GCL measured from superior and inferior quadrants, and mean CT were measured at three different regions (central, 500 µm nasal and temporal region of the fovea). RESULTS: There was no statistically significant differences in RNFL between the two groups (p > 0.05), while CT values were significantly higher and GCL values were significantly lower in chronic migraine groups (p < 0.05). There were no statistically significant differences between migraine duration, frequency and length of attacks, presence of aura, relation to menstrual cycle, white matter lesions in cranial magnetic resonance imaging and RNFL, GCL and CT (p > 0.05). DISCUSSION: In this study, we observed chronic migraine disease does not have any effect on peripapillary RNFL thickness; however, increases in CT and decreases in GCL thickness were observed in migraine patients.

The c-jun N-terminal kinase plays a key role in ocular degenerative changes in a mouse model of Alzheimer disease suggesting a correlation between ocular and brain pathologies.

Recently a range of ocular manifestations such as retinal and lens amyloid-beta accumulation and retinal nerve fiber layer loss have been proposed as potential biomarkers in Alzheimer disease (AD). The TgCRND8 mouse model of AD exhibits age-dependent amyloid ß (Aß) oligomers accumulation and cognitive defects, amyloid plaques and hyperphosphorylated Tau deposition and inflammation. We proved the correlation between ocular pathologies and AD, observing increased levels of p-APP and p-Tau, accumulation of Aß oligomers in the retina, eye, and optic nerve. The accumulation of amyloid markers was significantly stronger in the retinal ganglion cell (RGC) layer, suggesting that RGC might be more susceptible to degeneration. We detected a thinning of the RGC layer as well as RGC death in the retina of TgCRND8 mice, by using a combination of Optical Coherence Tomography (OCT), immunofluorescence, immunohistochemistry and Western blotting techniques. We proved for the first time the key role of C-Jun N-terminal Kinase (JNK) in the ocular degeneration. In support of this, the administration of the JNK inhibitor, D-JNKI1, was able to counteract the Aß and p-Tau accumulation in the retina of TgCRND8 mice, and consequently reduce RGCs loss. These results confirm that degenerative changes in the retina/eye of AD mouse model mirrors the events observed in the brain parenchyma. Ocular changes can be detected by non-invasive imaging techniques, such as OCT, to study and test different therapeutic strategies against degenerative events associated to AD.

Trans-synaptic Retrograde Degeneration Following Hemispherectomy in Childhood.

Trans-synaptic retrograde degeneration (TRD) in the human visual system has been established. However there are few studies demonstrating macular thinning of the Retinal Ganglion cell Layer and/or Inner Plexiform layer (RGCL-IPL), corresponding to an acquired homonymous hemianopia. We report a 17 year old with a homonymous hemianopia, secondary to a hemispherectomy for intractable epilepsy. Three years following hemispherectomy, Optical Coherence Tomography (OCT) revealed evidence of TRD, corresponding to his complete homonymous hemianopia. Macular maps of the RGCL-IPL thickness provides useful additional information to measurements of optic nerve Retinal Nerve Fibre Layer Thickness (RNFL) in identifying TRD in acquired homonymous hemianopia.

Does Retinal Neurodegeneration Seen in Diabetic Patients Begin in the Insulin Resistance Stage?

OBJECTIVES: To investigate whether retinal neurodegeneration and impairment in contrast sensitivity (CS), which have been demonstrated to begin in diabetic patients before the presence of signs of diabetic retinal vasculopathy, also occur in the stage of insulin resistance. MATERIALS AND METHODS: The average, minimum and sectoral (inferior, superior, inferonasal, superonasal, inferotemporal and superotemporal) thicknesses of the ganglion cell-inner plexiform layer (GCIPL) measured using optical coherence tomography were compared between an insulin-resistant group and control group in order to evaluate the presence of retinal neurodegeneration. The CS of the two groups was also compared according to the logarithmic values measured at spatial frequencies of 1.5, 3, 6, 12 and 18 cycles per degree in photopic light using functional acuity contrast test (FACT). RESULTS: Twenty-five eyes of 25 patients with insulin resistance (insulin resistant group) and 25 eyes of 25 healthy subjects (control group) were included in this study. There were no statistically significant differences between the two groups in any of the spatial frequencies in the FACT. The mean average GCIPL thickness and mean GCIPL thickness in the inferotemporal sector were significantly less in the insulin-resistant group when compared with the control group (mean average GCIPL thicknesses in the insulin-resistant and control groups were 83.6±4.7 µm and 86.7±3.7 µm respectively, p=0.01; mean inferotemporal GCIPL thicknesses in the insulin-resistant and control groups were 83±6.0 µm and 86.7±4.6 µm respectively, p=0.02). CONCLUSION: Although it may not lead to functional visual impairment such as CS loss, the retinal neurodegeneration seen in diabetic patients may begin in the insulin resistance stage.