Figure 1
![Uveitis, optic perineuritis (OPN) and peripheral ulcerative keratitis (PUK) associated with myelin oligodendrocyte glycoprotein antibodies. Case 3 had bilateral optic disc swelling on examination (a). Case 4 had unilateral right optic disc swelling associated with retinal folds and Paton's lines (arrows) (b). Visual field testing on his initial presentation revealed dense peripheral constriction with relative central sparing, in a pattern characteristic of OPN (c). His magnetic resonance imaging demonstrated perineural gadolinium enhancement (arrow) surrounding the optic nerve (d) (coronal T1 fat suppressed post-gadolinium image), as well as involvement of the full length of the right optic nerve and enhancement of the perineural sheath and intraconal fat (arrow) (e) (axial T1 fat suppressed postgadolinium image). He re-presented with unilateral left eye conjunctival injection during an episode of PUK (f). [Colour figure can be viewed at wileyonlinelibra ry.com]](profile/Mina_Ghaly2/publication/331055600/figure/fig1/AS:864897227317248@1583218976328/Uveitis-optic-perineuritis-OPN-and-peripheral-ulcerative-keratitis-PUK-associated.png)
Uveitis, optic perineuritis (OPN) and peripheral ulcerative keratitis (PUK) associated with myelin oligodendrocyte glycoprotein antibodies. Case 3 had bilateral optic disc swelling on examination (a). Case 4 had unilateral right optic disc swelling associated with retinal folds and Paton's lines (arrows) (b). Visual field testing on his initial presentation revealed dense peripheral constriction with relative central sparing, in a pattern characteristic of OPN (c). His magnetic resonance imaging demonstrated perineural gadolinium enhancement (arrow) surrounding the optic nerve (d) (coronal T1 fat suppressed post-gadolinium image), as well as involvement of the full length of the right optic nerve and enhancement of the perineural sheath and intraconal fat (arrow) (e) (axial T1 fat suppressed postgadolinium image). He re-presented with unilateral left eye conjunctival injection during an episode of PUK (f). [Colour figure can be viewed at wileyonlinelibra ry.com]
Source publication
Background
Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been identified in both children and adults with demyelination, with a strong association with bilateral or recurrent optic neuritis (ON). However, the full clinical spectrum of this newly described condition is unknown. We sought to describe non‐ON inflammatory ophthalmologica...
Context in source publication
Context 1
... clinical characterization of these four patients is outlined in Table 1 and Fig. 1, and detailed in Appendix S1. Three patients had five episodes of uveitis (recurrent in one patient with three episodes and monophasic in two patients). Uveitis was bilateral at onset in all three patients and associated with bilateral ON at first presentation in two patients, but not in the third. The first presentation of uveitis was ...
Citations
... Chen et al. [57] found that visual acuity tended to worsen for a median of four days from onset before reaching nadir in MOG-ON. It is important to note, however, that visual acuity can rarely be normal in MOGAD, in the case of optic perineuritis with sparing of the optic nerve itself [63,64]. ...
... Aside from ON, various other ophthalmic presentations have also been reported in association with MOGAD. These include serum MOG IgG reported in association with uveitis [63,65], peripheral ulcerative keratitis [63], acute macular neuroretinopathy [66], serous retinal detachment [67], venous stasis retinopathy [68], pre-retinal macular haemorrhage [69], orbital inflammatory syndrome [70] and orbital apex syndrome [71]. Nearly all cases were accompanied by intercurrent, typical MOG-ON, with retinal and orbital manifestations believed to be secondary to the spread of adjacent inflammation and oedema from the optic nerve and nerve head. ...
... Aside from ON, various other ophthalmic presentations have also been reported in association with MOGAD. These include serum MOG IgG reported in association with uveitis [63,65], peripheral ulcerative keratitis [63], acute macular neuroretinopathy [66], serous retinal detachment [67], venous stasis retinopathy [68], pre-retinal macular haemorrhage [69], orbital inflammatory syndrome [70] and orbital apex syndrome [71]. Nearly all cases were accompanied by intercurrent, typical MOG-ON, with retinal and orbital manifestations believed to be secondary to the spread of adjacent inflammation and oedema from the optic nerve and nerve head. ...
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder, distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MOGAD most frequently presents with optic neuritis (MOG-ON), often with characteristic clinical and radiological features. Bilateral involvement, disc swelling clinically and radiologically, and longitudinally extensive optic nerve hyperintensity with associated optic perineuritis on MRI are key characteristics that can help distinguish MOG-ON from optic neuritis due to other aetiologies. The detection of serum MOG immunoglobulin G utilising a live cell-based assay in a patient with a compatible clinical phenotype is highly specific for the diagnosis of MOGAD. This review will highlight the key clinical and radiological features which expedite diagnosis, as well as ancillary investigations such as visual fields, visual evoked potentials and cerebrospinal fluid analysis, which may be less discriminatory. Optical coherence tomography can identify optic nerve swelling acutely, and atrophy chronically, and may transpire to have utility as a diagnostic and prognostic biomarker. MOG-ON appears to be largely responsive to corticosteroids, which are often the mainstay of acute management. However, relapses are common in patients in whom follow-up is prolonged, often in the context of early or rapid corticosteroid tapering. Establishing optimal acute therapy, the role of maintenance steroid-sparing immunotherapy for long-term relapse prevention, and identifying predictors of relapsing disease remain key research priorities in MOG-ON.
... However, it is not clear whether anti-MOG antibodies are the cause of the clinical findings in these cases [12]. In a recent review, a total of 11 cases of aseptic meningitis and leptomeningeal enhancement associated with MOG antibodies were identified, of which five had no demyelinating lesions [56]. A small number of unclassifiable phenotypes have also been reported. ...
Over the last two decades, immunoglobulin G (IgG) antibodies against myelin oligodendrocyte glycoprotein (MOG), previously thought to be a biomarker of multiple sclerosis (MS), have been shown to cause a distinct disease called MOG antibody-associated disease (MOGAD). MOGAD accounts for approximately one-third of all demyelinating syndromes in children and is the second most common central nervous system (CNS) demyelinating disease after MS. The diagnosis is made by detecting anti-MOG IgG antibodies against the natural MOG antigen, in the presence of compatible clinical and neuroradiological features. However, due to controversies in the methodologies for detecting anti-MOG antibodies and their diagnostic cutoff values, as well as the expanding clinical spectrum, accurate diagnosis may be challenging, at least in a subset of patients. Clinical presentations of MOGAD vary by age; the highest rates are seen in acute disseminated encephalomyelitis in younger children and optic neuritis, myelitis, or brainstem symptoms in older children. Although it was previously thought to be a milder demyelinating disorder and to have a monophasic course in the majority of patients, recent studies have shown that relapses occur in about half of the patients and sequelae develop in a significant proportion of them, especially in those with persistently high antibody titers, leukodystrophy-like magnetic resonance imaging (MRI) lesions, and spinal cord involvement. However, due to the monophasic course in about half of the patients, long-term treatment is not recommended after the first clinical episode but is recommended for patients who experience relapse. Accurate and early diagnosis of MOGAD is essential for proper management and better outcome. This review covers the challenges in the diagnosis of MOGAD in children.
... Conditions include cicatricial pemphigoid [23], trichiasis, keratoconjunctivitis sicca, rosacea blepharitis, dermatologic causes like hidradenitis supparativa [43], poorly fitting contact lenses, and exposure keratopathy. Other items on the differential include culturenegative infectious keratitis, leukemia [44][45][46], indolent systemic infections (e.g., bartonella) [47], Vitamin A deficiency [48], inflammatory bowel disease, anti-myelin oligodendrocyte disease [49,50], sarcoidosis [51][52][53], and autoimmune hepatitis [40]. Recent case reports have focused on new descriptions of medication-associated PUK, such as rituximab [54], tocilizumab [55], dupilumab [56], COVID vaccine [57], checkpoint inhibitors [58,59], and miltefosine [60]. ...
Purpose of Review
This study aimed to discuss an updated, evidence-supported, stepwise approach to the diagnosis and treatment of peripheral ulcerative keratitis (PUK).
Recent Findings
PUK conventionally describes a rapidly progressive, crescent-shaped, peripheral, and inflammatory corneal melt. Undertreated PUK may lead to vision loss and premature mortality. A comprehensive approach includes diagnosis, short-term treatment, long-term treatment, and surgical considerations. Diagnosis is based on clinical findings. Next, the clinician should pursue an underlying etiology with a meticulous workup, including careful consideration of microbial keratitis. Common causes are rheumatoid arthritis, microbial keratitis, systemic necrotizing vasculitis (such as granulomatosis with polyangiitis), and collagen vascular disease (such as systemic lupus erythematosus). For short-term management of noninfectious PUK, therapy involves intensive anti-inflammatory therapy with corticosteroids. Adjunctive therapies such as conjunctival resection, amnionic membrane transplantation, and topical cyclosporine are also discussed. Recurrence commonly occurs, sometimes months to years later. Recurrence is a major source of premature vision loss. Additionally, smoldering disease activity seems to confer a risk of early mortality. Therefore, we recommend starting or escalating immunomodulatory therapy patients in most patients with sight-threatening, steroid-responsive, noninfectious PUK, especially (but not limited to) those with systemic features or a corneal graft.
Summary
PUK is a sight-threatening condition that requires a short-term and long-term view of the disease. Multidisciplinary collaboration with other physicians is crucial to achieve optimal outcomes.
... New diagnostic criteria and a new classification of optic neuritis are required. The need has arisen as a result of several advances: (1) the precision of autoantibodyrelated diagnosis has increased; 1-3 (2) epidemiological data have confirmed that optic neuritis is associated with more disorders and that the prevalence of optic neuritis subgroups is geographically more heterogeneous than was previously thought; 4,5 (3) the accuracy of neuro imaging to identify optic neuritis subgroups has improved; 6,7 (4) the value of retinal optical coherence tomography (OCT) for diagnosis and monitoring has become apparent; 8,9 and (5) more treatment options have become available for patients with optic neuritis. [10][11][12][13][14][15] Despite the improved diagnostic potential, 35 of 38 studies of OCT in patients with optic neuritis included in a 2017 meta-analysis did not use peerreviewed diagnostic criteria for optic neuritis. ...
There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.
... Optic perineuritis is characterized by the 'tram-track' sign on axial views and the 'doughnut' sign on coronal views. This pattern, with or without uveitis, can also be seen in MOG antibody-associated disease (Ramanathan et al., 2019). Dedicated ophthalmic imaging may also reveal compressive or infiltrative lesions at the orbital apex in cases of sarcoidosis (Arun et al., 2020). ...
Neurosarcoidosis is an important diagnosis to exclude in the work-up for suspected multiple sclerosis (MS). The distinction between the two conditions is usually possible due to characteristic clinical manifestations, magnetic resonance imaging (MRI) findings, and the results of other supportive investigations such as CT-PET. Definitive diagnosis can be made by histopathological examination, but this is not always practical. Misdiagnosis can occur when the clinical characteristics and MRI findings of both conditions overlap. Those patients with characteristic findings of MS but extraneural histopathological evidence of sarcoidosis are a particularly difficult diagnostic group. Diagnostic clarity is essential to inform treatment, especially as certain treatments for one disorder can exacerbate the other. This article summarises the clinical, laboratory and radiological findings that aid the clinician in distinguishing between the two conditions. It also discusses the literature and potential for sarcoidosis and MS to co-exist in some patients, and how to approach the treatment of these “overlap” patients.
... Some rare ophthalmologic manifestations of MOGAD, such as acute macular neuroretinopathy associated with acute ON, have been reported (32) . In addition, cases of ON associated with uveitis (33) , ON associated with macular star (34) , bilateral ON associated with bilateral serous detachment of the macula (35) , and ischemic optic neuropathy associated with diffuse orbital inflammation (36) have also been reported. The clinical spectrum of MOGAD is likely to further expand over the coming years. ...
Myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated optic neuritis has been established as a new entity of immune-mediated optic neuropathy. Patients usually present with recurrent optic neuritis, often bilaterally with initially severe vision loss and optic disc edema. However, in contrast to aquaporin 4-IgG-seropositive neuromyelitis optica spectrum disorder, visual recovery tends to be more favorable, with good response to steroid treatment. Another important differential diagnosis of myelin oligodendrocyte glycoprotein-IgG--associated optic neuritis is multiple sclerosis. Close monitoring for signs of relapse and long-term immunosuppression may be considered to maintain optimal visual function. The diagnosis can be made on the basis of the presence of a specific, usually serological, antibody against myelin oligodendrocyte glycoprotein (IgG; cell-based assay), and a demyelinating event (optic neuritis, myelitis, brainstem syndrome, or cortical lesions with seizures). The clinical spectrum of this newly recognized inflammatory demyelinating disease is expanding rapidly. We briefly review the epidemiological characteristics, clinical manifestations, diagnostic considerations, and treatment options of myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis.
Keywords:
Myelin oligodendrocyte glycoprotein; Multiple sclerosis; Neuromyelitis optica; Optic neuritis
... Equivocal patients were re-blinded and independently retested. To avoid bias between assays, and in absence of diagnostic criteria for MOG Ab-associated disorders, sensitivity and specificity were determined using two groups of patients: monophasic and relapsing disorders with reported MOG Ab-association (such as ADEM, ON, BON, LETM) [23,26,46,48,49,52,70], and monophasic and relapsing disorders with not yet reported MOG Abassociation and disorders not associated with MOG Ab (MS, CIS other than ON, and general medical and noninflammatory neurological disorders) [23,26,49,52,70]. ...
Background
Myelin oligodendrocyte glycoprotein antibodies (MOG Ab) are essential in the diagnosis of MOG Ab–associated disease (MOGAD). Live cell-based assays (CBAs) are the gold standard for MOG Ab detection with improved sensitivity and specificity over fixed CBAs. A number of testing centers have used flow cytometry for its high throughput and quantitative utility. Presently, there is increasing demand to translate these research-based methods into an accredited routine diagnostic setting.
Methods
A flow cytometry live CBA was used to detect MOG Ab in patients with demyelination. Serostatuses were compared between a research-based assay and a streamlined diagnostic assay. Inter-laboratory validation of the streamlined assay was performed in an accredited diagnostic laboratory. Further streamlining was performed by introducing a borderline serostatus range and reducing the number of controls used to determine the positivity threshold.
Results
High serostatus agreement (98%–100%) was observed between streamlined and research-based assays. Intra- and inter-assay imprecision was improved in the streamlined assay (mean intra- and inter-assay CV = 7.3% and 27.8%, respectively) compared to the research-based assay (mean intra- and inter-assay CV = 11.8% and 33.6%, respectively). Borderline positive and clear positive serostatuses were associated with confirmed phenotypes typical of MOGAD. Compared to using 24 controls, robust serostatus classification was observed when using 13 controls without compromising analytical performance (93%–98.5% agreement).
Conclusions
Flow cytometry live CBAs show robust utility in determining MOG Ab serostatus. Streamlining and standardizing use of this assay for diagnostics would improve the accuracy and reliability of routine testing to aid diagnosis and treatment of patients with demyelination.
... MOGAD is usually associated with optic neuritis and/or myelitis [185] but several cases of uveitis have been recently described [186]. In our case, the appearance of the cerebellar peduncle lesion and the absence of intrathecal synthesis of immunoglobulins are ...
... MOGAD is usually associated with optic neuritis and/or myelitis [185] but several cases of uveitis have been recently described [186]. In our case, the appearance of the cerebellar peduncle lesion and the absence of intrathecal synthesis of immunoglobulins are highly suggestive of this diagnosis. ...
Sarcoidosis is a systemic granulomatous disease of unknown cause characterized by a wide variety of presentations. Its diagnosis is based on three major criteria: a clinical presentation compatible with sarcoidosis, the presence of non-necrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. Many conditions may mimic a sarcoid-like granulomatous reaction. These conditions include infections, neoplasms, immunodeficiencies, and drug-induced diseases. Moreover, patients with sarcoidosis are at risk of developing opportunistic infections or lymphoma. Reliably confirming the diagnosis of sarcoidosis and better identifying new events are major clinical problems in daily practice. To address such issues, we present seven emblematic cases, seen in our department, over a ten-year period along with a literature review about case reports of conditions misdiagnosed as sarcoidosis.
... In turn, recurrent often bilateral painful optic neuritis (ON) with optic nerve perineuritis and optic disc swelling as well as myelitis of the lower spinal cord are found to be indicative for MOG-AD. [13][14][15][16][17] By using enzyme linked immunosorbent assay (ELISA) and Westernblot (WB) as detection methods, MOG-Ab have been found in patients with other neurological disorders including multiple sclerosis, stroke and polyneuropathy as well as in viral (HSV, EBV) or autoimmune encephalitis (anti-NMDAR) several years ago. 10,12,[18][19][20][21][22] To date, detection of MOG-Ab by ELISA, WB or fixed cell-based assay are known to be less specific. ...
Background
Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is recognized as a distinct nosological entity. IgG antibodies against MOG (MOG-Ab) overlap with neuromyelitis optica spectrum disorders (NMOSD) phenotype in adults. However, an increasing number of clinical phenotypes have been reported to be associated with MOG-Ab.
Objective
To investigate the seroprevalence of MOG-Ab under consideration of demographics, disease entities and time course in a large cohort of unselected neurological patients.
Methods
Blood samples of 2.107 consecutive adult neurologic patients admitted to our department between 2016-2017 were tested for MOG-Ab using a cell-based assay. MOG-Ab persistence was analyzed in follow-up samples. External validation was performed in two independent laboratories.
Results
We found MOG-Ab in 25 of 2.107 (1.2%) patients. High antibody ratios were mostly associated with NMOSD and MOG-AD phenotype (5/25). Low ratios occurred in a wide range of neurological diseases, predominantly in other demyelinating CNS diseases (5/25) and stroke (6/25). MOG-Ab persistence over time was not confined to NMOSD and MOG-AD phenotype.
Conclusion
The present study demonstrates the occurrence of MOG-Ab in a wide range of neurological diseases. Only high MOG-Ab ratios were associated with a defined clinical phenotype, but low MOG-Ab ratios were not. The diagnostic value of low MOG-Ab is thus highly limited.
... Any lesion of the optic nerves may be more common in NMOSD than in MS [55]. Optic perineuritis may be of particular value in distinguishing NMOSD and MS from other autoimmune causes of optic neuritis [61] including MOGAD [62]. ...
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system (CNS) associated with antibodies to aquaporin-4 (AQP4) which has distinct clinical, radiological and pathological features, but also has some overlap with multiple sclerosis and MOG-antibody associated disease. Early recognition of NMOSD is important because of differing responses to both acute and preventive therapy. Magnetic resonance (MR) imaging has proven essential in this process. Key MR imaging clues to the diagnosis of NMOSD are longitudinally extensive lesions of the optic nerve (more than half the length) and spinal cord (3 or more vertebral segments), bilateral optic nerve lesions and lesions of the optic chiasm, area postrema, floor of the IV ventricle, periaqueductal grey matter, hypothalamus and walls of the III ventricle. Other NMOSD specific lesions are denoted by their unique morphology: heterogeneous lesions of the corpus callosum, “cloud-like” Gd-enhancing white matter lesions and “bright spotty” lesions of the spinal cord. Other lesions described in NMOSD, including linear periventricular periependymal lesions and patch subcortical white matter lesions, may be less specific. The use of advanced MR imaging techniques is yielding further useful information about focal degeneration of the thalamus and optic radiation in NMOSD and suggests that paramagnetic rim patterns and changes in normal appearing white matter are specific to MS. MR imaging is crucial in the early recognition of NMOSD and in directing testing for AQP4 antibodies and guiding immediate acute treatment decisions. Increasingly MR imaging is playing a role in diagnosing seronegative cases of NMOSD.
