Optic Neuropathy and Myelopathy in a Teenager With Biotinidase Deficiency.

ABSTRACT: A 19-year-old man presented with 3 years of gradually progressive, painless vision loss in both eyes. The ophthalmic examination showed bilateral diminished visual acuity, dyschromatopsia, and temporal optic nerve pallor. The neurological examination was consistent with a mild myelopathy with decreased pin-prick sensation starting at T6-T7 and descending through the lower extremities. Hyperreflexia was also present in the lower more than upper extremities. Infectious, inflammatory, and nutritional serum workup and cerebrospinal fluid analysis were both unrevealing. MRI of the brain and spinal cord showed abnormal T2 hyperintensity of the fornix, corpus callosum, optic nerves, and lateral columns of the cervical and thoracic spine, with diffusion restriction in the inferior-posterior corpus callosum and fornix. Biotinidase serum enzyme activity was tested and showed a decreased level of activity. Biotinidase gene testing showed a homozygous pathogenic variant, c.424C>A (p.P142T), confirming the diagnosis of biotinidase deficiency and prompting oral biotin supplementation. Three months after starting treatment, the patient's visual acuity, color vision, visual fields, and MRI spine abnormalities all improved significantly. Biotinidase deficiency is an important diagnostic consideration in patients with unexplained optic neuropathy and/or myelopathy.

Linezolid optic neuropathy.

PURPOSE OF REVIEW: In this article, we reviewed 67 reported cases of linezolid optic neuropathy and describe the common characteristics and expectations for recovery with an emphasis on recent findings in the literature. RECENT FINDINGS: Linezolid classically causes a reversible, duration-dependent optic neuropathy. However, in our review, we found only 66.7% of patients recovered complete visual function. Vision loss most commonly affected visual acuity followed by visual field and color vision. We also found patients taking higher doses of linezolid experienced full recovery less often, suggesting a dose-dependent component of linezolid optic neuropathy. Linezolid use has increased in frequency and duration, especially in the treatment of drug-resistant tuberculosis, and data indicate that these patients experience lower rates of complete vision recovery compared with patients taking linezolid for other indications. SUMMARY: Linezolid is an effective medication for treating drug-resistant infections; however, it may result in optic neuropathy. It is reasonable for patients on linezolid to undergo screening examinations, especially those on higher doses or for prolonged duration of therapy.

MRI Signal Intensity Varies Along the Course of the Normal Optic Nerve.

BACKGROUND: MRI can help distinguish various causes of optic neuropathy including optic neuritis. Importantly, neuromyelitis optica spectrum disorder (NMOSD) has a propensity to cause enhancement of the prechiasmatic optic nerves. To determine whether the prechiasmatic optic nerve (PC-ON) demonstrates a different intensity from the midorbital optic nerve (MO-ON) on MRI among patients without optic neuropathy. METHODS: Data were retrospectively obtained from 75 patients who underwent brain MRI for an ocular motor nerve palsy between January 2005 and April 2021. Inclusion criteria were patients aged 18 years or older with visual acuities of at least 20/25 and no evidence of optic neuropathy on neuro-ophthalmic examination. A total of 67 right eyes and 68 left eyes were assessed. A neuroradiologist performed quantitative intensity measurements of the MO-ON and PC-ON on precontrast and postcontrast T1 axial images. Normal-appearing temporalis muscle intensity was also measured and used as a reference to calculate an intensity ratio to calibrate across images. RESULTS: The mean PC-ON intensity ratio was significantly higher than the MO-ON intensity ratio on both precontrast (19.6%, P < 0.01) and postcontrast images (14.2%, P < 0.01). Age, gender, and laterality did not independently affect measurements. CONCLUSIONS: The prechiasmatic optic nerve shows brighter intensity ratios on both precontrast and postcontrast T1 images than the midorbital optic nerve among normal optic nerves. Clinicians should recognize this subtle signal discrepancy when assessing patients with presumed optic neuropathy.

Bilateral Simultaneous Nonarteritic Anterior Ischemic Optic Neuropathy: Demographics, Risk Factors, and Visual Outcomes.

BACKGROUND: Although nonarteritic anterior ischemic optic neuropathy is a well-known cause of vision loss, it typically presents unilaterally. Simultaneous, bilateral nonarteritic anterior ischemic optic neuropathy (sNAION) is rare and poorly studied in comparison. This study seeks to characterize the clinical features and risk factors of patients with sNAION compared with unilateral NAION (uNAION). METHODS: In this retrospective case-control study, we reviewed 76 eyes (38 patients) with sNAION and 38 eyes (38 patients) with uNAION (controls) from 4 academic institutions examined between 2009 and 2020. Demographic information, medical history, medication use, symptom course, paraclinical evaluation, and visual outcomes were collected for all patients. RESULTS: No significant differences were observed in demographics, comorbidities and their treatments, and medication usage between sNAION and uNAION patients. sNAION patients were more likely to undergo an investigative work-up with erythrocyte sedimentation rate measurement ( P = 0.0061), temporal artery biopsy ( P = 0.013), lumbar puncture ( P = 0.013), and MRI ( P < 0.0001). There were no significant differences between the 2 groups for visual acuity, mean visual field deviation, peripapillary retinal nerve fiber layer thickness, or ganglion cell-inner plexiform layer thickness at presentation, nor at final visit for those with ≥3 months of follow-up. The sNAION eyes with ≥3 months of follow-up had a smaller cup-to-disc ratio (CDR) at final visit ( P = 0.033). Ten patients presented with incipient NAION, of which 9 suffered vision loss by final visit. CONCLUSION: Aside from CDR differences, the risk factor profile and visual outcomes of sNAION patients seem similar to those of uNAION patients, suggesting similar pathophysiology.

Ganglion Cell Layer Thickness Variance Using SPECTRALIS Optical Coherence Tomography.

BACKGROUND: To determine the normal variance of the mean macular ganglion cell layer (GCL) volume among subjects without significant ocular pathology using SPECTRALIS optical coherence tomography (OCT). METHODS: Fifty subjects underwent a baseline scan using SPECTRALIS OCT followed by 2 more studies with (reg-ON) and without (reg-OFF) eye registration all taken at the same session. The mean GCL volume was measured using built-in SPECTRALIS software. Eyes with macular pathology were excluded. The reproducibility of the measurements of the GCL volume was evaluated with Bland-Altman plots and limits of agreement, intraclass correlation coefficient (ICC), and the coefficient of repeatability (CR). RESULTS: A total of 98 eyes met criteria for the analysis. The mean GCL volume difference was 0.0002 ± 0.029 and -0.0005 ± 0.035 mm 3 for scans 1 versus 2 (baseline vs reg-ON) and 3 (baseline vs reg-OFF), respectively. The ICCs were 0.985 and 0.977 for the baseline vs reg-ON and reg-OFF groups. The CR for baseline vs reg-ON was 0.056 while CR for baseline vs reg-OFF was 0.069. Ninety percent of eyes fell within 0.04 mm 3 of test-retest reliability. CONCLUSIONS: Our model found a predictable threshold of 0.07 mm 3 or less for SPECTRALIS OCT mean GCL volume variance, which did not significantly change with eye registration in eyes without macular pathology. Clinicians may also consider a threshold of 0.04 mm 3 when determining stable vs progressive changes in mean GCL volume using this device.

Delayed-Onset Inflammatory Optic Nerve Sheath Mass and Perineuritis Following Cessation of Ipilimumab and Nivolumab Therapy.

A 65-year-old male presented with headaches and painless episodes of unilateral vision loss. He had a history of renal cell carcinoma, in remission following surgery and immunotherapy with ipilimumab and nivolumab, discontinued 2 years and 3 months before presentation, respectively. MRI revealed an optic nerve sheath mass and perineuritis. After 1 month of corticosteroid therapy, there was a robust clinical and radiographic response, which relapsed dramatically following cessation. An optic nerve sheath biopsy showed chronic mild inflammation, and extensive work-up for alternative etiologies of orbital inflammation was negative. Following a prolonged taper of corticosteroids, he demonstrated complete response. In the setting of ocular immune privilege, ophthalmic immune-related adverse events (irAE) are rare, although multifarious. While on-treatment irAE are well-characterized, posttreatment irAE have become increasingly recognized across multiple organ systems. We report a case of a delayed-onset inflammatory optic nerve sheath mass and perineuritis after cessation of immunotherapy.

Downbeat nystagmus: a clinical review of diagnosis and management.

PURPOSE OF REVIEW: This review will extensively cover the clinical manifestations, causes, diagnostic evaluation, and management strategies of downbeat nystagmus (DBN). RECENT FINDINGS: Historically, MRI to assess for structural lesions at the cervicomedullary junction has been the primary diagnostic test in the evaluation of DBN since the 1980s. In recent years, there is increasing awareness of nonstructural causes of DBN including gluten ataxia, nutritional deficiencies, and paraneoplastic syndromes, among others. Medical management with aminopyridines has become first-line therapy in addition to disease-specific therapies. SUMMARY: DBN is a common form of acquired nystagmus and the differential diagnosis remains broad, including both benign and potentially fatal causes. For practical purposes, the causes can be categorized as structural vs. nonstructural with MRI as the ideal, initial diagnostic study to differentiate the two. General therapeutic options include pharmacotherapy to enhance Purkinje cell function, strabismus surgery or prisms to shift null points, and behavioural changes. Disease-specific treatment is necessarily broad, though a significant proportion of patients will be idiopathic.

Increased Intracranial Pressure Without Hydrocephalus Associated With Spinal Cord Tumor: Literature Review.

ABSTRACT: Spinal cord tumors (SCTs) may rarely cause increased intracranial pressure without hydrocephalus (IICPWH). A review of the English literature published after 1970 revealed 29 cases of IICPWH secondary to SCT. The following data were acquired: demographics, tumor characteristics, ophthalmic and neurological manifestations, and cerebral spinal fluid (CSF) features. We summarize the existing literature regarding various theories of pathophysiology, spinal imaging recommendations, and treatment modalities used in managing such patients. Patients with papilledema who also have neurological signs or symptoms of myelopathy or elevated CSF protein particularly in the setting of an atypical demographic for pseudotumor cerebri should raise a suspicion for a spinal tumor and prompt further investigation with a spinal MRI.

Gadoxetate Disodium-Enhanced Imaging of Gradenigo Syndrome in End-Stage Renal Disease.

ABSTRACT: A 65-year-old man with end-stage renal disease on peritoneal dialysis was admitted for new onset binocular double vision, failure to thrive, and debilitating right-sided headaches. Medical history was significant for tympanomastoidectomy for polymicrobial mastoiditis and treatment with IV antibiotics. MRI brain without contrast was read by radiology initially as showing expected postsurgical changes; however, given patient's history of mastoiditis infection, there was a high clinical suspicion for Gradenigo syndrome. MRI brain was repeated with gadoxetate contrast to minimize the risk of nephrogenic systemic fibrosis (NSF) in a patient with severe renal disease and this revealed an intracranial empyema involving both the trigeminal and abducens nerves confirming the diagnosis of Gradenigo syndrome. This case presented a diagnostic challenge because of suboptimal visualization on initial nonenhanced MRI. Gadoxetate was chosen because of its unique properties including high hepatobiliary excretion making it a safer form of gadolinium-based contrast agent that may not have the potential to precipitate NSF.

Managing Photophobia with the Utilisation of Smart Light Bulbs.

Photophobia can affect a person's quality of life. We present a case of idiopathic photophobia that was successfully managed with smart light bulbs that allowed the patient to participate in daily activities. Smart light can complement other treatment options including tinted lenses. In conclusion, smart light is a novel way of treating photophobia and should be considered by clinicians.

Ocular myasthenia gravis: updates on an elusive target.

PURPOSE OF REVIEW: Ocular myasthenia gravis (OMG) is a complex condition with heterogenous phenotypes and ill-defined diagnostic criteria. Understanding concomitant risk factors and autoimmune serology can help inform prognosis for generalization and guide treatment. RECENT FINDINGS: Although antibodies to acetylcholine receptors or muscle-specific kinase likely increase risk of generalization, they are less frequent in OMG. Patients without either antibody tend to have a milder disease process and often have variable antibodies to other end-plate proteins such as LRP4, agrin, or cortactin. The treatment of OMG begins with pyridostigmine and is supplemented by oral prednisone if treatment-resistant or high risk for generalization. Variable oral prednisone regimens have been used with success and further immunosuppression may be best achieved with mycophenolate mofetil and azathioprine. Checkpoint inhibitor-induced myasthenia gravis is increasingly recognized and likely has high rates of mortality associated with myocarditis. SUMMARY: Our understanding of OMG and its variable phenotypes continues to evolve. Autoantibody testing increasingly provides valuable diagnostic and prognostic information. Despite these improvements, a lack of quality treatment trials creates significant challenges for evidence-based management guidelines.

Eye pain in the white and quiet eye.

PURPOSE OF REVIEW: Eye pain is one of the most common presenting symptoms in ophthalmology. It can range from bothersome to debilitating for patients, and it can be vexing for clinicians, especially in the white and quiet eye. The purpose of this review is to provide updates of recent literature regarding eye pain and to communicate our current understanding regarding the evaluation and management of conditions that cause eye pain with a relatively normal examination. RECENT FINDINGS: This review concerns recent literature regarding eye pain in the white and quiet eye. It is arranged by cause of pain and discusses dry eye syndrome, recurrent corneal erosion, postrefractive surgical pain, eye strain, intermittent angle closure, benign essential blepharospasm, trochleodynia, trochleitis and trochlear headache, and posterior scleritis. SUMMARY: Eye pain in the white and quiet eye remains a difficult-to-navigate topic for practitioners. However, a careful history and focused physical examination can elucidate the diagnosis in many cases. Recent updates to the literature have advanced our knowledge of how to identify and treat the underlying causes of eye pain.

Thyroid eye disease presenting with superior rectus/levator complex enlargement.

Purpose: To describe the demographic and clinical characteristics of patients with thyroid eye disease (TED) who present with predominate superior rectus/levator complex involvement.Methods: A multi-institutional retrospective review was performed to identify patients with TED who presented with superior isolated or predominate rectus/levator involvement. Baseline and subsequent visits were reviewed to characterize the clinical course.Results: Nineteen patients were identified. All patients had imaging demonstrating an enlarged levator/superior rectus complex. At presentation, the mean clinical activity score (CAS) was 2.1 (range: 0-5). Nineteen (100%) patients had proptosis on the affected side. Lid abnormalities, including upper/lower eyelid retraction and ptosis were higher on affected side compared to the unaffected side. Eleven (58%) patients had vertical misalignment. Mean thyroid stimulating immunoglobulin (TSI) was 3.7 (range: 1-7.1). Mean follow-up time was 18 months (range: 0-60 months). At last follow-up, the mean CAS was 1.3 (range 0-5). Ten (53%) patients had proptosis. Eleven (58%) patients had vertical misalignment. Repeat imaging in eight patients showed interval enlargement of other extraocular muscles.Conclusions: The presentation of TED with superior rectus/levator complex enlargement may be under-appreciated. Orbital imaging, as well as laboratory evaluation, may help support a diagnosis of TED. In the setting of abnormal TSI and/or thyrotropin receptor antibody, presence of upper eyelid retraction, and an otherwise unremarkable laboratory and systemic evaluation, a presumptive diagnosis of TED may be made, and the patient can be followed closely, as he/she is likely to develop involvement of other extraocular muscles, consistent with a more typical presentation of TED.

Retrospective, Multicenter Comparison of the Clinical Presentation of Patients Presenting With Diplopia From Giant Cell Arteritis vs Other Causes.

BACKGROUND: Although giant cell arteritis (GCA) is a well-known cause of transient and permanent vision loss, diplopia as a presenting symptom of this condition is uncommon. We compared symptoms and signs of patients presenting with diplopia from GCA to those from other causes. METHODS: This was a multicenter, retrospective study comparing the clinical characteristics of patients presenting with diplopia from GCA with age-matched controls. Demographic information, review of symptoms, ophthalmic examination, and laboratory data of biopsy-proven patients with GCA were compared with those of age-matched controls presenting with diplopia. RESULTS: A total of 27 patients presented with diplopia from GCA, 19 with constant diplopia, and 8 with transient diplopia. All patients with constant diplopia from GCA were matched with 67 control subjects who had diplopia from other etiologies. Patients with GCA were more likely to describe other accompanying visual symptoms (58% vs 25%, P = 0.008), a greater number of systemic GCA symptoms (3.5, GCA vs 0.6, controls, P < 0.001) such as headache (94% [17/18] vs 39% [23/67]; P < 0.001), jaw claudication (80% [12/15] vs 0% [0/36]; P < 0.001), and scalp tenderness (44% [7/16] vs 7% [3/43]; P < 0.001). Ocular ischemic lesions (26% vs 1%, P < 0.001) were also common in patients with diplopia from GCA. Inflammatory markers were elevated significantly in patients with GCA vs controls (erythrocyte sedimentation rate: 91% [10/11] vs 12% [3/25], P < 0.001; C-reactive protein: 89% [8/9] vs 11% [2/19], P < 0.001). CONCLUSIONS: GCA is a rare but serious cause of diplopia among older adults and must be differentiated from other more common benign etiologies. Our study suggests that most patients with diplopia from GCA have concerning systemic symptoms and/or elevated inflammatory markers that should trigger further work-up. Moreover, careful ophthalmoscopic examination should be performed to look for presence of ocular ischemic lesions in older patients presenting with acute diplopia.

Idiopathic Intracranial Hypertension in a Mother and Pre-pubertal Twins.

Idiopathic intracranial hypertension is a syndrome of elevated intracranial pressure without an identifiable cause. The majority of cases appear to be sporadic, and incidence is highest in obese women of childbearing age. The role of genetics in the pathophysiology of the disease is unclear, and familial cases are rare. We report a familial occurrence in a mother and her twin, 5-year-old sons.

Optic Nerve Head Drusen: The Relationship Between Intraocular Pressure and Optic Nerve Structure and Function.

OBJECTIVE: To determine whether at the time of diagnosis, the intraocular pressure (IOP) in patients with optic nerve head drusen (ONHD) correlates with the perimetric mean deviation (PMD) and the mean retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT). METHODS: This retrospective chart review included adults with ONHD from 2 academic medical centers. Inclusion criteria were age older than 18 years, definitive diagnosis of ONHD, measurement of IOP, and an automated visual field (VF) within 3 months of diagnosis. Exclusion criteria were unreliable VFs, use of IOP-lowering therapy, and visually significant ocular comorbidities. Data were collected from the initial visit. Age, IOP, method of diagnosis of ONHD, mean RNFL thickness, and PMD were recorded. Multiple and logistic regression models were used to control for potential confounders in statistical analyses. RESULTS: Chart review identified 623 patients, of which 146 patients met inclusion criteria. Mean age was 44.2 years (range: 19-82 years). Average PMD of 236 eyes was -5.22 dB (range, -31.2 to +1.21 dB). Mean IOP was 15.7 mm Hg (range: 6-24 mm Hg). Forty eyes (16.9%) underwent RNFL measurement using OCT; mean RNFL thickness was 79.9 µm (range: 43-117 µm). There was no statistically significant association between IOP and PMD (P = 0.13) or RNFL thickness (P = 0.65). Eyes with ocular hypertension tended to have less depressed PMD than those without (P= 0.031). Stratified analyses of visible and buried subgroups yielded similar results. CONCLUSIONS: Lowering IOP in patients with ONHD has been proposed as a means to prevent progression of optic neuropathy. Our study demonstrated that among predominately normotensive eyes, higher IOP was not associated with greater VF loss or thinner RNFL at the time of presentation. This suggests that lowering IOP may not be beneficial in preventing visual loss in normotensive eyes with ONHD.

Carboplatin-associated Cranial Neuropathy.

Carboplatin is a platinum-based chemotherapeutic agent used for the treatment of many solid tumors. Peripheral neuropathy is a common side effect; but, to our knowledge, ocular motor cranial neuropathies have not been reported in the literature. We describe a case of persistent third and fourth nerve palsies after systemic administration of intra-arterial carboplatin for glioblastoma multiforme. Neither nerve regained function after carboplatin was stopped.

Brown Syndrome Following Upper Eyelid Ptosis Repair.

Brown syndrome is characterised by impaired supraduction worse in adduction due to a restricted superior oblique tendon passing through the trochlea. A few reports have previously described Brown syndrome after upper eyelid surgery, including blepharoplasty and ptosis repair. The authors describe two additional cases of Brown syndrome following ptosis repair. The first case is a 65-year-old woman with new-onset vertical binocular diplopia following bilateral levator advancement surgery. Ocular motility examination demonstrated moderate impairment of elevation in adduction. The second case is a 35-year-old woman who presented with new-onset intermittent binocular diplopia following right upper lid ptosis repair. Examination revealed large vertical fusional amplitudes and a large left intermittent hyperphoria in an alignment pattern consistent with Brown syndrome. Despite presenting after surgery, these cases differ in mechanism. The first case likely occurred due to intraoperative impairment of the superior oblique tendon sheath or trochlea, whereas the second case represented an unmasking of a long-standing, previous vertical strabismus that was consistent with a Brown syndrome pattern.