Neuro-ophthalmological Diseases Research Articles

Vision loss related to COVID-19 infection: A case series of atypical optic neuritis

The Covid-19 outbreak, which was declared a global pandemic, has affected large human populations in many countries since March 2020. Although SARS-CoV-2 is a respiratory infection agent, various neurological syndromes, ranging from mild to severe, that may be associated with COVID-19 have been reported. Acute onset vision loss, optic neuritis (ON), cranial neuropathies, and Miller Fisher syndrome have been reported as covid 19-associated neuroophthalmological diseases. Objectives: In this case series, we aim to describe the clinical features of ON associated with COVID-19.

Neuro-ophthalmological diseases masquerading as glaucoma in the Optical Coherence Tomography era: A case series

Neuro-ophthalmological diseases masquerading as glaucoma in the Optical Coherence Tomography era: A case series

Reserch progress of neuro-ophthalmic manifestations of coronavirus disease 2019

Currently, coronavirus disease 2019 (COVID-19) is still widely prevalent around the world, leading to a major threat to the global public health. COVID-19 mainly involves the respiratory system, but extrapulmonary manifestations including that of the nervous system also exist in the setting of COVID-19. Misdiagnosis and delayed treatment of the disease may easily cause when ocular, especially neuro-ophthalmological symptoms are the first symptoms in early COVID-19, as the neuroophthalmological manifestations are rarely reported. First-line clinicians need to ask about not only respiratory symptoms such as fever, cough and sore throat, but also diplopia, impaired vision, eye motion pain, abnormal gait or other neurological deficits at the first reception, as these extrapulmonary manifestations are often signs of serious infection. The neuroophthalmological manifestations and possible underlying etiology of COVID-19 were summarized in this review, hoping to provide an early identification and effective treatment of COVID-19 for clinicians. More extensive studies are needed in the future to confirm the causal relationship between COVID-19 and neuroophthalmological disease to provide a sufficient basis for a comprehensive understanding of COVID-19. Copyright © 2021 by the Chinese Medical Association.

Neuro-ophthalmic manifestations of Susac syndrome.

This review discusses general features and organ-specific presentations of Susac syndrome as well as diagnosis and treatment. Latest literature regarding demographics, new diagnostic modalities such as optical coherence tomography and treatment options for Susac syndrome are discussed in detail in this review, summarizing the most recent updated information. Susac syndrome is a rare, underdiagnosed, and often misdiagnosed disease that can lead to severe complications such as deafness, vision loss, dementia, and death. It involves the central nervous system and may mimic other neurological and neuro-ophthalmological diseases.

Utilization of Visual Acuity Retroilluminated Charts for the Assessment of Afferent Visual System Dysfunction in a Pediatric Neuroimmunology Population

Visual acuity has been a significant outcome measure in clinical trials for patients suffering from neuro-ophthalmological diseases and multiple sclerosis; however, there are limited data on the comparison of various testing strategies in pediatric patients with these disorders. Clinical trials using vision as an outcome could include a variety of tools to assess the acuity, including 2-m and 4-m standardized retroilluminated charts. We investigated the difference in Early Treatment Diabetic Retinopathy Study (ETDRS) scores obtained using 2-m and 4-m charts, as well as the impact of optic neuritis, use of vision correction, age, and gender on visual acuity data from 71 patients with pediatric neuroimmunological conditions in a cross-sectional study. We determine that the ETDRS letter scores obtained using 4-m charts are on average 3.43 points less (P = 0.0034) when testing monocular ETDRS letter scores and on average 4.14 points less (P = 0.0008) when testing binocular ETDRS letter scores, relative to that obtained using the 2-m charts. However, we find that when performing monocular testing, optic neuritis in the eye being tested did not result in a statistically significant difference between 2-m and 4-m ETDRS letter scores. Although visual acuity charts are formatted by the distance, there are significant differences in the number of letters correctly identified between 2-m and 4-m charts. Although the differences may not impact the clinical acuity, research protocols should consider these differences before collapsing data across disparate studies.

Deep Learning and Transfer Learning for Optic Disc Laterality Detection: Implications for Machine Learning in Neuro-Ophthalmology.

Deep learning (DL) has demonstrated human expert levels of performance for medical image classification in a wide array of medical fields, including ophthalmology. In this article, we present the results of our DL system designed to determine optic disc laterality, right eye vs left eye, in the presence of both normal and abnormal optic discs. Using transfer learning, we modified the ResNet-152 deep convolutional neural network (DCNN), pretrained on ImageNet, to determine the optic disc laterality. After a 5-fold cross-validation, we generated receiver operating characteristic curves and corresponding area under the curve (AUC) values to evaluate performance. The data set consisted of 576 color fundus photographs (51% right and 49% left). Both 30° photographs centered on the optic disc (63%) and photographs with varying degree of optic disc centration and/or wider field of view (37%) were included. Both normal (27%) and abnormal (73%) optic discs were included. Various neuro-ophthalmological diseases were represented, such as, but not limited to, atrophy, anterior ischemic optic neuropathy, hypoplasia, and papilledema. Using 5-fold cross-validation (70% training; 10% validation; 20% testing), our DCNN for classifying right vs left optic disc achieved an average AUC of 0.999 (±0.002) with optimal threshold values, yielding an average accuracy of 98.78% (±1.52%), sensitivity of 98.60% (±1.72%), and specificity of 98.97% (±1.38%). When tested against a separate data set for external validation, our 5-fold cross-validation model achieved the following average performance: AUC 0.996 (±0.005), accuracy 97.2% (±2.0%), sensitivity 96.4% (±4.3%), and specificity 98.0% (±2.2%). Small data sets can be used to develop high-performing DL systems for semantic labeling of neuro-ophthalmology images, specifically in distinguishing between right and left optic discs, even in the presence of neuro-ophthalmological pathologies. Although this may seem like an elementary task, this study demonstrates the power of transfer learning and provides an example of a DCNN that can help curate large medical image databases for machine-learning purposes and facilitate ophthalmologist workflow by automatically labeling images according to laterality.

THICKNESSES OF CENTRAL MACULAR, RETINAL NERVE FIBER, AND GANGLION CELL INNER PLEXIFORM LAYERS IN PATIENTS WITH HYPERTENSION.

To compare retinal thickness between patients with chronic hypertension without retinopathy, hypertensive retinopathy, Keith-Wagener-Barker Grade IV status, and normal controls using spectral domain optical coherence tomography. In this retrospective study, we analyzed patients who visited our retinal clinic from January 2013 to February 2016. Of those included, 58 eyes of 58 patients were in the healthy control group (Group A), 37 eyes of 37 patients were in the chronic hypertension without retinopathy group (disease duration of at least 10 years; Group B), and 31 eyes of 31 patients with relieved hypertensive retinopathy (Grade IV hypertensive retinopathy a year or more ago but no longer had hypertensive retinopathy at the time of the study; Group C). The thicknesses of the central macula, retinal nerve fiber layer (RNFL), and ganglion cell inner plexiform layer (GCIPL) were measured by spectral domain optical coherence tomography in each group. The average thicknesses of the central macula, RNFL, and GCIPL layers were lower in Group B than in Group A (P < 0.001, 0.001, and <0.001, respectively). The thicknesses of the three layers were lower in Group C than in Group B (P < 0.001, <0.001, and <0.001, respectively). Of the three groups, the average thicknesses of the central macula, RNFL, and GCIPL were lowest in the Group C (P < 0.001, <0.001, and <0.001, respectively). The central macula, RNFL, and GCIPL in Group B were significantly thinner than those of healthy eyes, and these retinal changes were more prominent in Group C. Thus, the effects of retinal changes associated with hypertension should be considered when analyzing the thicknesses of the central macular, RNFL, and GCIPL layers in patients with ocular disorders, including retinal, glaucoma, and neuro-ophthalmological diseases.

Effect of Botulinum toxin Aapplication in neuro-ophtalmologic indications on Schirmerstest and tears osmolarity.

Botulinum toxin type A(BT-A) is used in the treatment of neuro-ophthalmologic disorders such as essential blepharospasm and facial hemispasm for more than 20 years. Although the long-term effect of repeated application of the BT-Awas confirmed, the BT-Aeffect on tears production and retention is not clear. In our work we investigated whether applied BT-Ain patients with blepharospasm and hemifacial spasm affect tears production. Tears quality was measured with Schirmersand tear osmolarity test during neuro-ophthalmologic diseases treatment, which was evaluated before and 14 days after application of BT-A(Botox inj, Allergan, Irvine, USA) into the orbicularis oculi muscle. BT-Adoses of 16-18 Uwith unilateral and 32 to 36 Ubilateral applications were used. The mean tear production in Schirmerstest before BT-Aapplication was 8.38 ± 0.63 mm, and 2 weeks after BT-Aapplication was 7.12 ± 0,6 mm (n = 50). Tear osmolarity was 305.4 ± 9.2 mOsm before BT-Aapplication, and 2 weeks after BT-Aapplication it was 305.2 ± 8,6 mOsm (n = 13). We found significant difference between two groups in tear quantity (p &lt; 0.012), but not quality (p &gt; 0.05). Application of the BT-Areduced the amount of tears measured by Schirmerstest. These results confirm rational basis of the empirical clinical experience where an artificial tears substitution is recommended for patients with neuro-ophthalmologic disorders treated by BT-A.

Decoding PERG: A neuro-ophthalmic retinal ganglion cell function review.

Currently, the clinical evaluation of neuro-ophthalmologic diseases are mainly focused on identifying stages where structural or functional damage occur. Recognition of retinal ganglion cell (RGC) functional patterns as well as monitoring RGC dysfunction can be performed using steady-state pattern electroretinogram (PERG). The analysis of the amplitude and latency shift aid on providing information on early damage or monitoring of the RGC, allowing for prompt clinical intervention and management modification, potentially changing the natural history of the disease. The purpose of this article is to review the latest findings in PERG, in early manifest glaucoma, non arteritic ischemic optic neuropathy, multiple sclerosis with unilateral recovered optic neuritis and its fellow eyes. The steady-state PERG responses provide new and early specific information in neuro-ophthalmic diseases affecting the inner retina. Steady state PERG presents specific amplitude and latency outcomes based on the neuro-ophthalmic disease affecting the inner retina, allowing early recognition of changes at the level of RGC and the degree of RGC dysfunction. In addition, PERG alterations may be induced in healthy subjects as well as susceptible eyes using different stress tests such as head down tilting or water drinking tests.

25-NEI VFQ in ophthalmological patients

Objective: To compare the vision-targeted health related quality of life (HRQOL) between neuro-ophthalmological patients and other eye diseases by the National Eye Institute 25-Item Visual Function Questionnaire. Methods: Cross sectional study with a control group and patients with the following pathologies: primary open-angle glaucoma (POAG), diabetic retinopathy (DR), age-related macular degeneration (ARMD), non-arteritic ischemic optic neuropathy (NAION), intracranial hypertension (IH), optic neuritis (ON), ptosis and cataract. Results: All comparisons of the subscales scores among the control group and the patient groups were statistically significant (p&lt;0.05) except for “ocular pain” (p=0.160), “social functioning” (p=0.052) and “peripheral vision” (p=0.112). The control group had the best scores across all dimensions of the NEI VFQ-25. Interestingly, the ARMD and cataract groups presented the best and worst total scores of NEI VFQ-25, respectively. The lowest subscales scores were found in the cataract, in the NAION/ON, and in the POAG groups. Finally, the comparison between the NAION/ON/IH patients and the other eye diseases did not show statistical significance in any subscale. Conclusion: The NEI VFQ-25 showed the impact of various eye conditions in vision-targeted HRQOL, and no difference was measured between neuro-ophthalmological patients and other eye diseases.

Stable Microsaccades and Microsaccade-Induced Global Alpha Band Phase Reset Across the Life Span.

To understand the effect of aging on microsaccade functions and brain physiologic responses, we quantified microsaccades and their physiologic correlates (including their interaction with alpha band brain oscillation) in normal subjects of different ages. Twenty-two normally sighted young (18 to 29 years), 22 middle-aged (31 to 55 years), and 22 elderly subjects (56 to 77 years) participated in this cross-sectional study. Dense array EEG and high-resolution eye-tracking data were simultaneously recorded during a fixation task. We quantified microsaccade features, spike potential (SP), microsaccadic lambda response (MLR) and microsaccade-related spectral perturbation (ERSP), and intertrial coherence (ITC) in the alpha and beta frequency bands and compared them between three age groups. After microsaccade onset, (1) alpha band ERSP increased (100 to 150 ms) occipitally and ITC increased (150 to 220 ms) globally in the brain; (2) low beta ITC increased (150 to 220 ms) in occipital and central regions and peaked (0 to 50 ms) in frontal region; and (3) high beta ITC increased (0 to 50 ms) globally with no beta band ERSP changes. Microsaccade features, the latency and amplitude of SP and MLR, and microsaccade-related temporal-spectral power and synchronization dynamics were all stable across different age groups. Microsaccades are well preserved in aging and can be used as reference points for studying neurodegenerative or neuro-ophthalmologic diseases where the oculomotor system is affected. Microsaccade-induced alpha band activity is a potential biomarker to better understand and monitor these diseases, and we propose that microsaccades trigger "cortical refreshment" by resetting alpha band phase globally to prepare (sensitize) the brain for subsequent visual processing.

Autoimmunity in uveitis.

Recent insights into the pathogenesis of immune-mediated diseases proposed a new classification, which includes autoimmune and auto-inflammatory diseases. The prevalence of specific autoimmune and auto-inflammatory diseases in uveitis and/or scleritis is not yet known. In this study, we examine the presence of systemic immune-mediated diseases in patients with uveitis and/or scleritis and put a special emphasis on autoimmune disorders by reporting on their clinical manifestations and visual prognosis. In this retrospective study, we reviewed data of 1327 patients presenting with uveitis and/or scleritis between January 2010 and July 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. All patients with noninfectious uveitis and/or scleritis were classified according to novel criteria for immune-mediated diseases. Various clinical data, including visual acuity (VA), of patients with uveitis of autoimmune origin were registered during 5-year follow-up. The origin of uveitis was in 5% (62/1327) autoimmune, in 15% (197/1327) auto-inflammatory and in 14% (180/1327) mixed autoimmune/auto-inflammatory. Patients with classical autoimmune connective tissue disease (N=17) suffered mostly from rheumatoid arthritis and granulomatosis with polyangiitis and exhibited predominantly scleritis (53%). After 5years of follow-up, none of the eyes of these patients developed legal blindness (VA of <0.1). The VA in patients with uveitis associated with autoimmune neuro-ophthalmological diseases (multiple sclerosis and neuromyelitis optica; N=27) remained stable over time. Uveitis and scleritis of autoimmune origin were observed in 5% of the total series. The term autoimmune uveitis should not be used as a synonym for intraocular inflammation of noninfectious origin.

Changes in thickness of central macula and retinal nerve fibre layer in severe hypertensive retinopathy: a 1-year longitudinal study.

To analyse the longitudinal changes in the thickness of the central macula and retinal nerve fibre layer (RNFL) in patients with hypertensive retinopathy (HTNR) using spectral-domain optical coherence tomography (SD-OCT). This was a prospective cohort study. We studied 18 eyes of patients with HTNR of grade IV who had been followed up for more than 1year, and 36 normal eyes (without any relevant medical history; the control group). Antihypertensive treatment successfully normalized the blood pressure of HTNR patients. The RNFL thickness and that of the central macula of HTNR patients were measured using a Cirrus HD-OCT instrument, and compared with those of the control group. At 12months of follow-up, the mean thickness of the RNFL and central macula was significantly lower in the HTNR group than in the control group (the RNFL was measured first, and then the central macular thickness (CMT): 77.4±9.1 and 233.8±30.8μm versus 94.1±7.8 and 256.3± 28.1μm, respectively; p<0.05). With time, the RNFL thickness and CMT became significantly less than that at the initial diagnosis (p<0.05). Severe HTNR causes a decrease in the thickness of the RNFL and central macula over time. Therefore, the impact of retinal changes associated with systemic diseases such as hypertension should be considered in analysing the thicknesses of the RNFL and central macula in ocular disorders, including retina, glaucoma and neuro-ophthalmologic diseases.

Neuromyelitis Optica Spectrum Disorder: Disease Course and Long-Term Visual Outcome.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that classically manifests as attacks of optic neuritis (ON) and transverse myelitis (TM). The prevalence, course, and severity of NMOSD vary considerably. Few studies report the neuro-ophthalmologic disease course and visual outcome. We sought to describe the course and long-term visual outcome in a cohort of NMOSD patients treated in a single tertiary referral center. The database was searched for all patients with NMOSD who were treated in our center from 2005 to 2014. Data collected included detailed visual outcome, grade of final visual disability, neuroimaging, and results of optical coherence tomography. Details on relapses, acute episodes, and maintenance therapies were recorded. Of the 12 patients with NMOSD who were followed for a mean duration of 9.06 years, 10 (83%) were women. Mean age at presentation was 33.90 ± 16.94 years. Patients with acute attacks were treated with high-dose intravenous methylprednisolone and offered immunosuppressive maintenance. ON occurred in 18 eyes of 12 patients, with a cumulative total of 37 ON episodes. At the end of the follow-up period, no patient had become legally blind and only 1 patient had lost her driver's license. Pain associated with acute ON was common (83%), whereas optic disc edema was a rare finding in our patient cohort (6%). In this retrospective series of 12 patients with NMOSD, followed for a mean of 9.06 years, acute-phase treatment was given within 8 days of relapse, followed by maintenance therapy. Functional visual outcome, as measured by the World Health Organization/International Classification of Diseases, Tenth Revision visual disability scale was better than reported in previous studies and driver's license was preserved in 11 of 12 patients. Pain accompanied 83% of ON attacks and may not aid differentiating multiple sclerosis from NMOSD-related ON.

Peripapillary retinal nerve fiber layer thickness in patients with iron deficiency anemia.

Purpose:To evaluate the effect of iron deficiency anemia (IDA) on peripapillary retinal nerve fiber layer (RNFL) thickness with optical coherence tomography (OCT).Materials and Methods:102 female patients who had IDA (hemoglobin <12 g/dl, serum transferrin saturation <15%, serum iron <50 μg/dl, and serum ferritin <15 μg/dl) were enrolled in the study. Optic disc and RNFL parameters obtained by Cirrus high-definition OCT 4000 were compared with those of 49 age and sex-matched nonanemic individuals. The time between blood analysis and OCT measurements was 3.14 ± 5.6 (range, 0–28) days in the anemia group, and 3.5 ± 6.7 (range, 0–27) days in the control group (P = 0.76).Results:Average ages of 102 patients and 49 control subjects were 35.76 ± 10.112 (range, 18–66) years, and 36.08 ± 8.416 (range, 19–57) years (P = 0.850), respectively. The average RNFL thickness was 94.67 ± 9.380 in the anemia group, and 100.22 ± 9.12 in the control group (P = 0.001). Temporal, nasal, and lower quadrant average RNFL thicknesses of IDA group were thinner than the control group (P = 0.001, P = 0.013, P = 0.008). Upper quadrant RNFL thicknesses in IDA and control groups were similar. Correlation analysis revealed positive correlation between mean RNFL thickness and hemoglobin (r = 0.273), iron (r = 0.177), ferritin (r = 0.163), and transferrin saturations (r = 0.185), while a negative correlation was found between total iron binding capacity (r = −0.199) and mean RNFL thickness.Conclusions:Peripapillary RNFL thickness measured by OCT is thinner in adult female patients with IDA. It may have a significant influence on the management of many disorders such as glaucoma and neuro-ophthalmological diseases.

Research status on the epidemiological characteristics of optic neuritis

Optic neuritis(ON) is one of common neuro-ophthalmologic diseases which cause vision loss in young and middle-aged population. There are obvious differences in the incidence and the epidemiological characteristics among different countries and regions. A number of studies on ON have been carried out at home and abroad. In China, it is still lack of multi-center, prospective, large sample epidemiological studies so far. This paper reviews the epidemiological characteristics of ON through the related domestic and overseas literatures.

Disminución de la agudeza visual

The decrease in visual acuity is a common symptom of many ophthalmologic and neuro-ophthalmologic diseases. The origin of the disease may be located anywhere along the entire visual pathway, from the optic nerves backward to the visual cortex. In order to guide the diagnosis and thus avoiding unnecessary complementary diagnostic tests, careful medical history and complete ocular examination must be performed. Diseases presenting decreased visual acuity must be identified and assessed urgently by ophthalmologists and/or neurologists because visual and life prognosis of some of them are directly related to the rapidity with which appropriate treatment is instituted.

CCFDN-Syndrome (Congenital Cataracts, Facial Dysmorphism and Neuropathy): Characterization and Case Report

Preface: CCFDN-syndrome is a rare and complex neuro-ophthalmologic disease occurring almost exclusively in ethnic groups of Romanies. Primary symptoms are congenital cataract and microphthalmia and/or microcornea and a neuropathy with hypo- or demyelinization and progressive course. Facial abnormalities are common as well as a mild developmental delay. Further attributes are dwarfism and hypotrophy, mild hypogonadism, cerebral and spinal atrophy, osteoporosis and others, the disease pattern is variable. Attention should be paid to disposition for rhabdomyolysis during or following viral infectious diseases.

神経眼科疾患の治療評価に対するDiplometの使用経験

【目的】様々な眼球運動障害を伴う神経眼科疾患の治療評価に対するDiplometの有用性を検討した。【対象と方法】4例について後ろ向きにDiplomet、Maddox rodとプリズムを用いた眼位検査、眼球運動写真撮影にて検討した。【結果】症例1：51歳女性。多発性硬化症による右外転神経麻痺を生じ、ステロイドパルス治療後、外転神経麻痺は改善した。症例2：54歳女性。Churg-Strauss症候群による眼窩炎症症候群で右眼内転制限、外下転制限を生じた。ステロイドパルス治療後、眼球運動障害は改善した。症例3：22歳女性。SLEに伴う側頭葉出血にて頭蓋内圧の上昇を生じ、左眼外転神経麻痺をきたした。頭蓋内圧減圧治療後、外転神経麻痺は改善した。症例4：14歳女性。蝶形骨異形成による拍動性眼球突出により、内斜視及び左上斜視を生じた。脳神経外科にて蝶形骨形成術後、新たな眼球運動障害は出現せず、眼位の改善を示した。全ての症例においてDiplometで同様の経過が記録確認できた。【結論】Diplometは様々な神経眼科疾患の眼球運動障害において、年齢・原因疾患を問わず、治療前後の眼位・眼球運動障害を測定、記録可能であった。治療前後の評価にDiplometは有用であると思われた。

Optic neuritis

Optic neuritis is a frequent neuro-ophthalmological disease in which the diagnosis can be based on just a few symptoms and findings. It is not only important to differentiate from other optic nerve disorders but also to recognise special types of optic neuritis, which is mostly only possible during the course of the disease. This article presents a review of the current state in diagnosis and therapy from the authors' personal point of view.