Ocular manifestations of SARS-CoV-2: Literature review. / Manifestaciones oftalmológicas del SARS-CoV-2: Revisión de la literatura.

In this review, a summary is presented of the main reports regarding the potential ocular manifestations of the new coronavirus disease (COVID-19). Scientific evidence is based on letters to the editor, clinical cases and case series, cross-sectional, and a few longitudinal studies. To date, it includes viral conjunctivitis, immune conjunctivitis, and oculomotor palsies (OCP) due to the novel coronavirus. Retinopathy is discussed. A viral conjunctivitis outbreak can be isolated or associated with the systemic picture, mainly pulmonary, before or after the onset of respiratory symptoms. It can be both unilateral and bilateral, follicles are typical, and duration is variable between 5 and 21 days. Immune-mediated conjunctivitis consists of eye redness, together with erythroderma and fever. It appears more frequently in children, and has been associated with a «Kawasaki-like¼ disease and toxic shock syndrome. OCP can present on its own, or as part of Miller-Fisher syndrome, along with ataxia, and hyporeflexia. Ophthalmologists have a considerable risk of developing COVID-19 due to close contact with the patient, exposure to tears and eye secretions, and the use of various pieces of equipment and devices susceptible to contamination.

Clinical characterization of anti-GQ1b antibody syndrome in Korean children.

Anti-GQ1b antibody syndrome encompasses Miller Fisher syndrome and its related disorders. We retrospectively identified 11 pediatric patients (5.4-18 years old) with anti-GQ1b antibody syndrome. Diagnoses of patients included acute ophthalmoparesis (n = 6), classical Miller Fisher syndrome (n = 2), Miller Fisher syndrome/Guillain-Barré syndrome (n = 1), acute ataxic neuropathy (n = 1), and pharyngeal-cervical-brachial weakness (n = 1). Nine patients (81.8%) fully recovered. Maturational change in GQ1b antigen expression and the accessibility of anti-GQ1b antibodies might be the cause of the difference of clinical manifestations in children with anti-GQ1b antibody syndrome.

Atypical clinical manifestations of Miller Fisher syndrome.

Miller Fisher syndrome (MFS) is characterized by a clinical triad of ophthalmoplegia, ataxia, and areflexia, and is closely associated with serum anti-GQ1b antibody. Although the clinical triad is the cardinal diagnostic clue, a variety of other symptoms and signs beyond the triad have been reported. To elucidate the frequency and characteristics of atypical clinical manifestations of MFS, we recruited 38 patients with MFS and evaluated the symptoms or signs beyond the classic triad. Eleven (29%) of 38 patients had atypical clinical manifestations of MFS such as headache (n = 6), delayed facial palsy (n = 3), divergence insufficiency (n = 2), and taste impairment (n = 2). Headache was localized to the periorbital (n = 3), temporal (n = 2), or whole (n = 1) area. Only one of them showed bilateral papilledema and an elevated opening pressure in cerebrospinal fluid analysis. Delayed facial palsy developed after the other signs have reached nadir (n = 1) or started to improve (n = 2), and did not follow a pattern of descending paralysis with other cranial neuropathies. Two patients showed divergence insufficiency without external ophthalmoplegia, and another two had taste impairment over the entire tongue without the other signs of facial and glossopharyngeal nerve involvements. Our study shows that approximately 30% of MFS patients can have atypical clinical manifestations beyond the classic triad. These results reflect the broad clinical spectrum of MFS, and might be associated with the presence of additional antiganglioside antibodies besides anti-GQ1b in patients with MFS.

Characteristics of single ocular motor nerve palsy associated with anti-GQ1b antibody.

To define the prevalence and characteristics of single ocular motor nerve palsy (OMNP) associated with positive serum anti-GQ1b antibody. We performed a prospective multicenter study that recruited 82 patients with single OMNP without identifiable causes from the history and neuroimaging in six neurology clinics of university hospitals. We measured serum anti-GQ1b antibody in all participants. Twelve patients with multiple OMNP and 30 with identifiable causes served as the controls. Overall, the prevalence of anti-GQ1b antibody syndrome was 10% (8/82) in patients with single OMNP and 6% (5/78) in those with single OMNP in isolation. None of the 14 patients with OMNP with identifiable causes showed positive serum anti-GQ1b antibody. The prevalence of anti-GQ1b antibody syndrome was much higher in patients with multiple OMNP than in those with single OMNP (50% vs. 10%, p < 0.01). Patients with single OMNP and positive anti-GQ1b antibody are younger (42 ± 16 vs. 58 ± 15, p < 0.05) and had a significantly higher frequency of preceding infection (75 vs. 19%, p < 0.05) and other neurological signs (38 vs. 1%, p < 0.05) than those with negative antibody. Eight patients with single OMNP and positive serum anti-GQ1b antibody involved the abducens (n = 6), trochlear (n = 1), or oculomotor nerve (n = 1). Single OMNP accompanying other neurological signs and multiple OMNP are more likely to be associated with anti-GQ1b antibody. Anti-GQ1b antibody syndrome should be considered even in patients with single OMNP, especially when antecedent infection was associated in younger patients.

Oculomotor palsy in diabetics.

INTRODUCTION: Oculomotor palsy is one of the most frequent neuro-ophthalmologic complications of diabetic patients. It generates less interest in the literature than the other ocular manifestations. Our goal was to study the clinical, epidemiological, therapeutic and prognostic characteristics of oculomotor palsy in the diabetic. METHODS: This is a retrospective study of 24 diabetic patients with oculomotor palsy. The ophthalmological examination emphasized ocular motility. We performed an orthoptic assessment and a Hess-Lancaster test. Neuro-imaging was ordered in case of IIIrd and IVth nerve involvement, bilateral involvement, multiple ocular cranial nerve palsy or associated optic neuropathy. Treatment consisted of glucose management and alternating monocular occlusion or prisms for the diplopia. Data were entered and analyzed on SPSS 11.5 software. RESULTS: The mean age of the patients was 58.5±11.9 years. Binocular diplopia was the main symptom. The oculomotor palsy involved the VIth nerve in 50% of cases and was bilateral in two cases. Three patients also had an optic neuropathy. The mean duration of diabetes was 11.7±11 years; poorly controlled diabetes was found in 75% of cases and an association with diabetic retinopathy was noted in 56% of cases. CONCLUSIONS: Long-standing uncontrolled type 2 diabetes, hypertension, coronary artery disease, left ventricular hypertrophy, and elevated hematocrit are the most common risk factors. The VIth nerve is commonly involved. Certain characteristics of the pupillary light reflex can help to differentiate an ischemic insult from an aneurysmal injury to the IIIrd nerve.

Pattern of ocular involvement in myasthenia gravis with MuSK antibodies.

BACKGROUND: Myasthenia gravis (MG) with antibodies to the muscle-specific kinase (MuSK) has a characteristic phenotype. Ocular manifestations have not been systematically evaluated. OBJECTIVE: To investigate the features of extrinsic ocular muscle involvement in patients with MuSK-MG. METHODS: We retrospectively evaluated the prevalence, time of onset, clinical pattern and outcome of ocular symptoms in 82 patients with a clinical follow-up ≥2 years. RESULTS: Ocular manifestations were observed in 79 patients (96.4%) and were the presenting symptoms in 48 (58.5%). Intermittent diplopia with subtle ophthalmoparesis was the most common complaint, ptosis was generally symmetrical and conjugated gaze paresis occurred in 35% of the patients. Ocular manifestations responded well to prednisone and partially to symptomatic treatment. A few patients developed chronic symmetrical ophthalmoparesis, associated with persistent weakness in other muscle groups. All patients with ocular presentation progressed to generalised disease, though weakness spread to other muscle groups was considerably delayed in a few cases. CONCLUSIONS: In MG with antibodies to MuSK, ocular manifestations were as frequent as in other disease subtypes. Symmetrical ophthalmoparesis with conjugated gaze limitation was rather common and associated with low functional disability. A proportion of these patients developed chronic eye muscle paresis.

Manifestaciones neuroftalmológicas en enfermedades neuroendocrinas / Neurophthalmological findings in neuroendocrine diseases

La neuroftalmología es considerada una especialidad frontera por su vínculo con otras múltiples especialidades médicas, clínicas y quirúrgicas. Los tumores de hipófisis son de tal importancia desde el punto de vista neuroftalmológico que son tratados separadamente en casi todos los textos de la especialidad. El objetivo de la presente revisión es aproximarnos, sobre la base de los conocimientos actuales, a los hallazgos neuroftalmológicos de algunas enfermedades neuroendocrinas, haciendo hincapié en dos temas fundamentales: los adenomas hipofisarios y el síndrome de neoplasias endocrinas múltiples, y demostrar además el importante papel del neuroftalmólogo en estas dos entidades. Quedan aquí evidenciadas las variadas manifestaciones neuroftalmológicas de estas entidades neuroendocrinas, el importante cometido del oftalmólogo en el diagnóstico y el ulterior seguimiento de los pacientes con adenomas hipofisarios, así como lo decisiva que puede resultar su actuación en la identificación de los hallazgos asociados al síndrome de neoplasias endocrinas múltiples tipo 2 B(AU)

Neurophthalmology is considerate frontier speciality because of their relationships with many other medical and surgical specialities. Pituitary tumors are so important from neuro-ophthalmological point of view that they appear as special chapter in text books. Our objective in the present review is to refer the neurophthalmological finfings in two main entities: pituitary adenomas and multiple endocrine neoplasia syndromes and to establish the important role of neuro-ophthalmologist in those neuroendocrine conditions. It was proved the diversity of neurophthalmological findings in neuroendocrine entities, the important role of ophthalmologist in diagnosis and pursuance of patients with pituitary adenomas and its peremptory role in screening finding associated to 2 B type multiple endocrine neoplasia syndrome(AU)

KIF21A mutation in two Chinese families with congenital fibrosis of the extraocular muscles type 1 and 3.

Congenital fibrosis of the extraocular muscles (CFEOM) is a hereditary ocular disease and can be classified into three subtypes. The aim of the present study was to determine the genetic basis and describe the clinical phenotype of CFEOM type 1 and 3. Two Chinese families with CFEOM type 1 and 3 were identified. The patients and their family members were subjected to comprehensive ophthalmic examinations, including best­corrected visual acuity, slit­lamp examination, fundus examination, assessment of palpebral fissure size, levator function, ocular motility, and cover and forced duction tests. Genomic DNA was extracted from the leukocytes of venous blood samples collected from the two families and from 200 unrelated control subjects from the same population. Coding exons of the KIF21A gene were amplified using polymerase chain reaction analysis and sequenced directly in the two probands. The detected mutations were further analyzed in all available family members and the unrelated control subjects. A heterozygous mutation, c.2860C>T (p.R954W), in KIF21A was identified in the two families, and this was cosegregated with the presence of the diseases in the two families, however, it was absent in the 200 normal control subjects. Among the three affected family members with CFEOM1, differences were observed with regard to the presence of aberrant eye movement. The results indicated that, in the patients with CFEOM1 and CFEOM3, the disease was caused by the same KIF21A gene mutation. The KIF21A gene may be a major disease­causing gene for Chinese patients with CFEOM3. Phenotypic heterogeneity was observed in the patients with CFEOM1.

Assessment of the prevalence and risk factors of ophthalmoplegia among diabetic patients in a large national diabetes registry cohort.

BACKGROUND: There are limited data on the epidemiology and risk factors of ophthalmoplegia among diabetic patients. This study aims to determine the prevalence and important risk factors related to ophthalmoplegia among diabetic patients. METHODS: This is an observational registry-based study using the Saudi National Diabetes Registry (SNDR) database to select diabetic patients regardless of their diabetes type. A total of 64,351 Saudi diabetic patients aged more than 18 years and registered in SNDR between January 2000 and December 2010 were analyzed to identify ophthalmoplegic cases. Demographic, clinical, and biochemical parameters were studied and STROBE guidelines were used to design and report the results of this study. RESULTS: The overall prevalence of ophthalmoplegia cases was 0.32 %, further distributed into: 53.11 %, 36.36 %, and 2.8 % for cranial nerves VI, III, IV palsies respectively. Ophthalmoplegic cases were predominantly type 2 diabetic males with older age and longer diabetes duration. The most important and significant risk factors were age ≥ 45 years, diabetes duration ≥ 10 years, male gender and presence of retinopathy and nephropathy. CONCLUSIONS: Ophthalmoplegia is a rare entity associated mainly with type 2 diabetes. Clinicians have to consider its risk factors when screening or planning for prevention of this condition.

SANDO syndrome in a cohort of 107 patients with CPEO and mitochondrial DNA deletions.

OBJECTIVE: The sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) syndrome is a subgroup of mitochondrial chronic progressive external ophthalmoplegia (CPEO)-plus disorders associated with multiple mitochondrial DNA (mtDNA) deletions. There is no systematic survey on SANDO in patients with CPEO with either single or multiple large-scale mtDNA deletions. METHODS: In this retrospective analysis, we characterised the frequency, the genetic and clinical phenotype of 107 index patients with mitochondrial CPEO (n=66 patients with single and n=41 patients with multiple mtDNA deletions) and assessed these for clinical evidence of a SANDO phenotype. Patients with multiple mtDNA deletions were additionally screened for mutations in the nuclear-encoded POLG, SLC25A4, PEO1 and RRM2B genes. The clinical, histological and genetic data of 11 patients with SANDO were further analysed. RESULTS: None of the 66 patients with single, large-scale mtDNA deletions fulfilled the clinical criteria of SANDO syndrome. In contrast, 9 of 41 patients (22%) with multiple mtDNA deletions and two additional family members fulfilled the clinical criteria for SANDO. Within this subgroup, multiple mtDNA deletions were associated with the following nuclear mutations: POLG (n=6), PEO1 (n=2), unidentified (n=2). The combination of sensory ataxic neuropathy with ophthalmoparesis (SANO) was observed in 70% of patients with multiple mtDNA deletions but only in 4% with single deletions. The combination of CPEO and sensory ataxic neuropathy (SANO, incomplete SANDO) was found in 43% of patients with multiple mtDNA deletions but not in patients with single deletions. CONCLUSION: The SANDO syndrome seems to indicate a cluster of symptoms within the wide range of multisystemic symptoms associated with mitochondrial CPEO. SANO seems to be the most frequent phenotype associated with multiple mtDNA deletions in our cohort but not or is rarely associated with single, large-scale mtDNA deletions.

A comparison of benign and inflammatory manifestations of Tolosa-Hunt syndrome.

BACKGROUND: Tolosa-Hunt syndrome (THS) manifests as a benign or an inflammatory type disease. The nosography differences between these types remain to be elucidated. We aimed to analyze and compare the clinical presentations of benign and inflammatory THS. METHODS: The ward patients who presented with THS from January 1990 to May 2011 were retrospectively reviewed. THS was diagnosed according to the recommendations of the International Headache Society. RESULTS: Of the 53 THS cases (49 patients), 30 (56.6%) were classified as benign and 23 (43.4%) as inflammatory THS. There were strong similarities between the groups in terms of clinical manifestations, laboratory findings, responses to glucocorticoid treatment, and outcomes. However, patients with inflammatory THS tended to be younger (mean age, 43.4 years; P 0.05) and have optic nerve dysfunction (56.5%; P 0.05) and longer disease duration (2.3 ± 1.0 months; P 0.05) compared to those with benign THS (mean age, 56.4 years; mean disease duration, 1.6 ± 0.7 months). The patients with additional involvement of both the optic nerve and the second division of the trigeminal nerve experienced a longer disease duration ( P 0.05). Additionally, patients with orbital pseudotumors had diplopia that responded poorly to treatment with glucocorticoids ( P 0.05). High-dose (>0.5 mg/kg/day) and low-dose (≤0.5 mg/kg/day) prednisolone were equally effective in relieving symptoms in both groups ( P > 0.05). CONCLUSION: Benign and inflammatory THS were highly similar in terms of nosography. The responses to glucocorticoid treatment were generally good except in patients with orbital pseudotumors.

Incidence of pupillary involvement, course of anisocoria and ophthalmoplegia in diabetic oculomotor nerve palsy.

AIMS: To derive a reliable estimate of the frequency of pupillary involvement and to study the patterns and course of anisocoria in conjunction with ophthalmoplegia in diabetes-associated oculomotor nerve palsy. MATERIALS AND METHODS: In this prospective analytical study, standardized enrolment criteria were employed to identify 35 consecutive patients with diabetes-associated oculomotor nerve palsy who were subjected to a comprehensive ocular examination. Standardized methods were used to evaluate pupil size, shape, and reflexes. The degree of anisocoria, if present and the degree of ophthalmoplegia was recorded at each visit. RESULTS: Pupillary involvement was found to be present in 25.7% of the total number of subjects with diabetic oculomotor nerve palsy. The measure of anisocoria was < 2 mm, and pupil was variably reactive at least to some extent in all cases with pupillary involvement. Majority of patients in both the pupil-involved and pupil-spared group showed a regressive pattern of ophthalmoplegia. Ophthalmoplegia reversed much earlier and more significantly when compared to anisocoria. CONCLUSIONS: Pupillary involvement in diabetes-associated oculomotor nerve palsy occurs in about 1/4 th of all cases. Certain characteristics of the pupil help us to differentiate an ischemic insult from an aneurysmal injury to the 3 rd nerve. Ophthalmoplegia resolves much earlier than anisocoria in diabetic oculomotor nerve palsies.

Recovery of ophthalmoplegia after endovascular treatment of intracranial aneurysms.

BACKGROUND AND PURPOSE: Recovery of aneurysm induced CNP after endosaccular coiling has been reported in the literature. The aim of this study was to assess in detail the parameters that affect the outcome after endovascular treatment of ophthalmoplegic aneurysms due CNP. MATERIALS AND METHODS: Between November 1999 and March 2008, 30 consecutive patients (8 men, 22 women; mean age, 54.9 years) presenting with CNP underwent endosaccular coiling with or without additional use of stents in the parent artery. Subarachnoid hemorrhage was present in 10 patients, whereas 20 patients had unruptured aneurysms. The mean size of the aneurysms was 10 mm. Initial CNP was complete in 11 patients and partial in 19. Mean follow-up after coiling was 19 months. RESULTS: The mean interval between the onset of CNP and aneurysm embolization was 48 days. Fifteen patients (50%) had complete recovery of oculomotor function, 12 had incomplete recovery (40%), and 3 (10%) remained unchanged after treatment. In 4 aneurysms (13.3%), 1 additional embolization was performed, whereas in 4 other aneurysms, 2 additional embolization procedures were necessary. Procedure-related permanent morbidity occurred in 2 patients (6.6%). CONCLUSIONS: Endosaccular coiling is an effective and safe method for the treatment of ophthalmoplegic aneurysms. Age, neck size, and time of treatment do not seem to constitute prognostic factors with respect to CNP recovery, though patients with small aneurysms, unruptured status, and/or location in the posterior circulation showed a tendency for better outcome. The degree of initial CNP was the only statistically significant prognostic factor concerning the final outcome, resulting in better recovery, in case of incomplete initial CNP.

Painful ophthalmoplegia: a retrospective study of 23 cases.

Painful ophthalmoplegia is a rare pathologic condition caused by non-specific inflammation of the cavernous sinus, but other causes such as tumours, vasculitis, basal meningitis, neurosarcoidosis, diabetes can be responsible for the syndrome. Aim of this study is a review of the cases of painful ophthalmoplegia admitted to our Institute in the last 20 years in order to verify the incidence of symptomatic versus benign forms in a clinical case series, with particular focus on the cases in which a long term (at least 4 years) and detailed follow-up did not revealed spread of any systemic disease or other presumed causes for painful ophthalmoplegia. Twenty-three patients were retrospectively studied, 12 patients (52%) were classified as benign forms and their disease course was again evaluated and 11 cases (48%) were designated as symptomatic. The present study suggests that in the clinical practice the incidence of benign forms among the painful ophthalmoplegias is more elevate than the symptomatic ones and underlines the need of a specific nosography for benign forms.

Ophthalmoplegia with migraine in adults: is it ophthalmoplegic migraine?

OBJECTIVE: Ophthalmoplegic migraine (OM) is a rare disorder characterized by recurrent oculomotor nerve palsy in children, following migraine headaches. We report 62 adults, seen consecutively, who developed acute ophthalmoplegia with severe attacks of migraine over a 10-year (1996-2005) period. An overwhelming majority of these patients had an antecedent worsening in severity of migraine headaches, before the ophthalmoplegic attack. METHODS: Sixty-two patients, aged 15-68 years, with an acute attack of OM underwent detailed clinical, biochemical, and neuroradiological evaluation. RESULTS: There were 62 patients with 86 attacks of OM. Whereas 48 patients had a single attack, 14 had 2 or more attacks, fulfilling the International Headache Society criteria for probable and definite OM, respectively. At presentation, isolated abducens, oculomotor, and trochlear nerve involvements were seen in 35 (56.5%), 21 (33.9%), and 5 (8.1%) patients, respectively. One patient had simultaneous involvement of 3rd and 6th nerves. Fifty-one (82.3%) patients exhibited an antecedent worsening in severity of migraine, before developing ophthalmoplegia during (59/95.2%) or within 24 hours (3/4.8%) of a severe migraine attack, respectively. Detailed biochemistry and cranial neuroimaging were normal. No case had any nerve enhancement. Use of steroids hastened recovery (P < .05). CONCLUSION: We conclude: (1) OM in adults is characterized by single attacks of ophthalmoplegia in a great majority of patients; and (2) 6th nerve involvement occurs commonly. Our results indicate that moving OM to the chapter on cranial neuralgias in the second edition of the International Headache Classification may be premature, since nerve palsy occurred during a severe migraine attack in all patients.

Unusual primary manifestations of multiple sclerosis.

OBJECTIVES: The aim of this study is to describe patients with unusual symptoms that were primary manifestations of multiple sclerosis (MS). PATIENTS AND METHODS: We report 21 multiple sclerosis patients who presented unusual initial pictures (acute brachial pain n=4, headache n=6, ptosis n=1, oculomotor nerve palsy n=1, peripheral facial palsy n=1, throat pain n=1, hypoglossal nerve palsy n=1, visual field defect n=2, epilepsia n=2, and coma n=2) as the first manifestations in the absence of other obvious symptoms or signs. RESULTS: Investigations demonstrated changes highly suggestive of multiple sclerosis on magnetic resonance imaging, cerebrospinal fluid analysis and electrophysiological tests. All cases completely or partially recovered after high-dose corticosteroid therapy. These patients have been followed up for 5 years. CONCLUSION: In this study, we discuss possible correlations between clinical disturbances and neuroradiological abnormalities and show some rare or previously undescribed manifestations in multiple sclerosis.

Acute ophthalmoplegia (without ataxia) associated with anti-GQ1b antibody.

BACKGROUND: Anti-GQ1b antibody has been found in Miller Fisher syndrome (MFS), Guillain-Barré syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis (BBE), and acute ophthalmoplegia without ataxia (AO). The aim of this study was to determine the clinical features of AO associated with anti-GQ1b antibody. METHODS: We retrospectively collected 34 patients with anti-GQ1b antibody syndrome. Of these patients, 31 patients had ophthalmoplegia. The patients with ophthalmoplegia were classified into MFS (n = 13), AO (n = 11), GBS with ophthalmoplegia (n = 6), and BBE (n = 1). We analyzed clinical features and patterns of external and internal ophthalmoplegia of AO, and neuro-ophthalmologic findings were compared with those of other anti-GQ1b syndromes with ophthalmoplegia. RESULTS: AO was observed in 11 (32.4%) of the 34 patients with anti-GQ1b antibody. External ophthalmoparesis was present in all the patients and included mixed horizontal-vertical (n = 7), pure horizontal (n = 3), and pure vertical gaze palsy (n = 1). Binocular involvement was common, but unilateral ophthalmoparesis was also observed in 27.3%. Other findings included ptosis (n = 5, 45.5%) and internal ophthalmoplegia (n = 6, 54.5%). Other anti-GQ1b antibody syndromes had prominent neurologic signs including ataxia, weakness, and facial palsy in addition to ophthalmoplegia. The patterns of neuro-ophthalmologic findings did not differ between AO and other anti-GQ1b antibody syndromes with ophthalmoplegia. CONCLUSIONS: Acute ophthalmoplegia (AO) commonly occurs in anti-GQ1b antibody syndrome and manifests as various combinations of external and internal ophthalmoplegia. Internal ophthalmoplegia is fairly common and unilateral involvement may occur in AO.