Variability Within Optic Nerve Optical Coherence Tomography Measurements Distinguishes Papilledema From Pseudopapilledema.

BACKGROUND: To report a linear risk score obtained using clock-hour optical coherence tomography (OCT) data from papilledema and pseudopapilledema nerves that differentiates between the 2 diagnoses with high sensitivity and specificity. METHODS: Patients presenting to a single neuro-ophthalmologist with papilledema or pseudopapilledema were included for a retrospective review. The absolute consecutive difference in OCT retinal nerve fiber layer (RNFL) thickness between adjacent clock hours and the mean magnitude of thickness for clock hours 1-12 were compared between the 2 groups using mixed-effect models adjusting for age and clock hour with a random intercept for subjects and eyes (nested within subject). The area under the curve (AUC) for the receiver operating characteristics curve and a separate calibration curve was used to evaluate potential clinical usage. RESULTS: Forty-four eyes with papilledema and 72 eyes with pseudopapilledema, 36 of whom had optic nerve drusen met criteria. The papilledema group had a higher mean RNFL thickness (papilledema = 163 ± 68 µm, pseudopapilledema = 82 ± 22 µm, P < 0.001). The papilledema groups also had more variability between consecutive clock hours (papilledema = 57 ± 20 µm, pseudopapilledema = 26 ± 11 µm, P < 0.001). A linear combination of each patient's averaged values separated the 2 groups with an AUC of 98.4% (95% CI 95.5%-100%) with an optimized sensitivity of 88.9% and specificity of 95.5% as well as good calibration (mean absolute error = 0.015). CONCLUSIONS: Patients with papilledema have higher intrinsic variability and magnitude within their OCT, and this finding reliably distinguishes them from those with pseudopapilledema.

Third nerve palsy as the initial manifestation of giant cell arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is rarely reported as a cause of third nerve palsy. We describe the presentation and course of patients with third nerve palsy as the sole initial ocular manifestation of GCA. METHODS: Retrospective chart review of patients with third nerve palsy as the presenting sign of GCA. Symptoms, signs, and inflammatory marker levels at presentation and on follow-up were analyzed. All patients had imaging of the brain and circle of Willis, to exclude a compressive or inflammatory lesion, and had a temporal artery biopsy showing granulomatous arteritis. RESULTS: Four patients (aged 63-82) were identified and included. One patient had a complete third nerve palsy with pupil involvement, whereas the other 3 had third nerve palsies without pupil involvement. Three patients had ipsilateral periorbital/brow pain, and the other patient had temporal headache. Two patients reported no systemic symptoms of GCA but had elevated inflammatory markers. One patient had normal inflammatory markers but reported systemic symptoms of GCA. All patients had rapid improvement in symptoms and signs after high-dose oral prednisone was started with all showing complete recovery within weeks. CONCLUSIONS: GCA can rarely present with acute painful third nerve palsy, mimicking the presentation of a microvascular cause. The third nerve palsy often improves rapidly after steroid treatment is started. The presence of GCA symptoms or elevated inflammatory markers in a patient older than 50 years with an acute third nerve palsy should prompt initiation of high-dose steroid treatment and temporal artery biopsy.

Diagnostic features of retinal nerve fiber layer rotation in skew deviation using optical coherence tomography.

A 41-year-old woman with skew deviation had cyclotorsion of both eyes. This resulted in a falsely low probability plot of retinal nerve fiber layer thickness in adjacent clock hours on optical coherence tomography (OCT) due to displacement of the retinal nerve fiber layer peaks. Ocular cyclotorsion may cause misinterpretation of OCT probability plots. OCT retinal nerve fiber layer plots also may be used to objectively quantify the degree of ocular cyclotorsion.

Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced 'PANIC' attack.

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish 'PANIC', thereby 'left-shifting' severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this disease. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon SARS-CoV-2 triggered 'PANIC Attack'. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons which could be leveraged to more effectively prepare for the next challenge to global health.

Part I. SARS-CoV-2 triggered 'PANIC' attack in severe COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constrained our freedom of movement. This respiratory tract infection is nefarious in how it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the delicate yet irreplaceable alveoli that are responsible for the loading of oxygen upon red cell hemoglobin for use by all of the body's tissues. In most symptomatic individuals, the disease is a mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a disease course characterized by a cataclysmic set of immune activation responses that can culminate in the diffuse and irreversible obliteration of the distal alveoli, leading to a virtual collapse of the gas-exchange apparatus. Here, in Part I of a duology on the characterization and potential treatment for COVID-19, we define severe COVID-19 as a consequence of the ability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to trigger what we now designate for the first time as a 'Prolific Activation of a Network-Immune-Inflammatory Crisis', or 'PANIC' Attack, in the alveolar tree. In Part II we describe an immunotherapeutic hypothesis worthy of the organization of a randomized clinical trial in order to ascertain whether a repurposed, generic, inexpensive, and widely available agent is capable of abolishing 'PANIC'; thereby preventing or mitigating severe COVID-19, with monumental ramifications for world health, and the global pandemic that continues to threaten it.

Current pharmacologic testing for Horner syndrome.

First described in 1727, Horner syndrome occurs from injury to one of the three neurons in the oculosympathetic pathway. Its presence can be confirmed with pharmacologic testing, traditionally including cocaine testing with hydroxyamphetamine localization. More recently, apraclonidine testing has become a viable alternative in some practices. Concern has been raised regarding the possibility of false-negative results with apraclonidine testing as well as the safety of its use in young children.

Intracranial hypertension in systemic lupus erythematosus.

PURPOSE: Intracranial hypertension (IH) mimicking pseudotumor cerebri (i.e., idiopathic IH) has been reported in individuals with systemic lupus erythematosus (SLE) since the 1960s. Although various mechanisms have been proposed (e.g., venous thrombosis, medication side effect, and immunologic or inflammatory disease) none have been proven to be causal. METHODS: Retrospective chart review of patients with IH and SLE at a single tertiary care institution. RESULTS: In a cohort of IIH patients the percentage of patients in our study with SLE was 1% (4 in 410). Three out of the four patients had serologic evidence for a hypercoagulable state but only one had cerebral venous sinus thrombosis. Two patients had onset or worsening of IH in close temporal relationship to steroid withdrawal. The course, treatment, and prognosis of our patients with SLE and intracranial hypertension did not differ significantly from our clinical experience with IIH or with the published natural history data for IIH. CONCLUSIONS: The association of SLE and IH may occur more than by chance alone. Steroid withdrawal in the treatment of the SLE may be a predisposing or precipitating factor in the development of IH in these patients rather than the inflammatory effects of SLE per se. The hypercoagulable state in some patients with SLE may also produce cerebral venous sinus thrombosis as an additional potential mechanism of IH.

Contact lens strategies for the patient with dry eye.

Dry eye is the most common reason for contact lens (CL) discontinuation, and the patient with pre-existing dry eye presents particular challenges to the CL fitter. Poor tear film quality/stability, oxygen deprivation, lens deposits, and adverse reactions to CL solutions all contribute to dry eye, and lid disease, allergies, environmental factors, and medications can further hamper successful CL wear by the patient with dry eye. Health and comfort of the ocular surface is affected by the water content, ionicity, oxygen permeability, and modulus of elasticity of the lens, as well as by surface characteristics, such as protein, lipid, and mucin deposition; protein adsorption; and wettability. The choice of CL cleaning solutions with regard to action, cytotoxicity, and biocompatibility are as important as the choice of the CL itself. With appropriate management of the lid, meibomian gland, and ocular surface conditions that produce dry eye, careful selection of lenses and solutions, and vigilant follow-up, successful CL wear should be achievable for the dry eye patient.

Visual loss due to Wernicke syndrome following gastric bypass.

PURPOSE: To report a case of Wernicke encephalopathy after gastric bypass surgery resulting in vision loss, ophthalmoplegia, and ataxia, all of which reversed with a single dose of IV thiamine. METHODS: Observational case report. RESULTS: A 34-year-old woman presented with decreased vision and intermittent diplopia after gastric bypass surgery. She was found to have bilateral limitation of horizontal gaze, decreased vision with bilateral central scotoma and mild disc edema OU. Her cranial magnetic resonance imaging (MRI) was normal. A presumptive diagnosis of Wernicke encephalopathy was made. The patient was admitted, and a single dose of IV thiamine reversed the ophthalmoplegia and vision loss within 24 hours. CONCLUSION: Wernicke encephalopathy should be considered in patients with vision loss after gastric bypass surgery. The classic triad of confusion, ataxia, and ophthalmoplegia may not be present and, although uncommon, the findings of optic disc edema and vision loss should not deter the clinician from making the diagnosis. Replacement thiamine if given promptly may rapidly reverse the findings.

Optic disc edema with adjacent cilioretinal artery occlusion in a male with ulcerative colitis.

OBJECTIVE: To report a case of optic disc edema with adjacent retinal ischemia in ulcerative colitis. DESIGN: Photo essay. CASE REPORT: A 36-year-old white man presented with visual loss OD. Past medical history was significant for ulcerative colitis. The patient had suffered presumed non-arteritic anterior ischemic optic neuropathy OS one year prior to the episode OD. Ophthalmoscopic exam showed optic disc edema associated with an area of adjacent retinal ischemia that was confirmed on fluorescein angiography OD. An extensive evaluation for infectious, inflammatory, vasculitic, and hypercoagulable etiologies was negative. The presumptive diagnosis of ulcerative colitis-related ischemic optic neuropathy with simultaneous retinal ischemia was made. The patient was treated with antiplatelet therapy and the vision stabilized but did not recover. CONCLUSION: To our knowledge, this is the first report in the English language literature of a simultaneous ischemic event involving the optic nerve and the adjacent retina in a patient with ulcerative colitis.

Cotton wool spots associated with interferon beta-1 alpha therapy.

PURPOSE: To describe a case of cotton wool spots associated with interferon beta-1a treatment. METHODS: Observational case report. RESULTS: A 40-year-old man with a history of multiple sclerosis was on interferon beta-1a. He presented with cotton wool spots on fundus exam, which resolved and then recurred all while on therapy. Interferon was discontinued after the second episode and again the cotton wool spots resolved. Upon restarting the interferon, no further cotton wool spots have recurred. CONCLUSION: To our knowledge this represents only the third case of interferon beta-1a associated cotton wool patches and the first in the English-language ophthalmic literature. Unlike interferon alpha therapy, interferon beta 1-a retinopathy is presumed to be extremely rare and more common etiologies for cotton wool spots should be excluded in these patients. Given this limited number of cases versus the relatively frequent use of interferon beta-1a in the management of multiple sclerosis, no conclusions regarding causality or screening can be made but the issue probably deserves further study.

Rapid regression of retinochoroidal venous collaterals following optic nerve sheath fenestration in idiopathic intracranial hypertension.

A woman with idiopathic intracranial hypertension (IIH) experienced rapid regression of retinochoroidal venous collaterals ("optociliary shunt vessels") following optic nerve sheath fenestration. The presence of these vessels is a nonspecific sign of chronic retinal venous compression in patients with optic disc edema including IIH.

Syringohydromyelia in association with syringobulbia and syringocephaly: case report.

The authors present the case of a 14-year-old boy with holocord syringohydromyelia extending into the brainstem, cerebral peduncle, internal capsule, and cerebral cortex. At the posterior fossa exploration, an opaque thickened arachnoid with occlusion of the foramen of Magendie was encountered. Careful documentation of postoperative regression of the syringocephaly, syringobulbia, and syringohydromyelia was made. The pathophysiology is discussed.

Description and validation of a structured simulation curriculum for strabismus surgery.

PURPOSE: To describe and validate a Web-based structured simulation curriculum of strabismus surgery for residents in training using noncadaveric eye models. METHODS: A pre- and posttest of cognitive skills, objective wet laboratory structured assessment of technique, and summative global evaluation form were implemented as part of a systematic ophthalmology wet lab (OWL) curriculum. Strabismus techniques were taught using a structured simulation method on noncadaveric models of eyes. Likert scale questionnaires were administered to assess the comfort level with strabismus surgery of residents before and after participation in the wet laboratory. Statistical analysis was performed using the paired t test. RESULTS: Seven residents participated in the curriculum. Average test scores improved from 65% to 91% (P = 0.0002). Resident comfort level improved from an average score (assessed by Likert scale of 1-5) with standard deviation of 2.6 ± 1.0 to 4.3 ± 0.5 for passing scleral sutures (P = 0.0008), of 2.6 ± 0.5 to 4.3 ± 0.5 for isolating and suturing muscles (P = 0.00004), and of 2.7 ± 1.0 to 4.6 ± 0.5 for comfort with naming instruments (P = 0.0007). CONCLUSIONS: In this study of 7 residents, knowledge and comfort level with strabismus surgery statistically improved with a structured simulation curriculum.

Causes and Prognosis of Visual Acuity Loss at the Time of Initial Presentation in Idiopathic Intracranial Hypertension.

PURPOSE: To determine the etiology and prognosis of visual acuity loss in idiopathic intracranial hypertension (IIH) at presentation and to provide objective measures to predict visual outcome. METHODS: A retrospective review of 660 patients with IIH (2009-2013) identified 31 patients (4.7%) with 48 eyes having best-corrected visual acuity (BCVA) of 20/25 or worse on initial presentation. Fundus photography, optical coherence tomography (OCT) of the optic disc and macula, and perimetry were used to determine the causes and prognosis of vision loss. Segmentation of the macula OCT was performed using the Iowa Reference Algorithm to determine the retinal ganglion cell-inner plexiform layer complex (GCL-IPL) thickness. RESULTS: Outer retinal changes alone caused decreased BCVA at initial presentation in 22 eyes (46%): subretinal fluid in 16, chorioretinal folds in 5, and peripapillary choroidal neovascularization in 1. The vision loss was reversible except for some eyes with chorioretinal folds. Optic neuropathy alone caused decreased BCVA in 10 eyes (21%) and coexisting outer retinal changes and optic neuropathy caused decreased BCVA in 16 eyes (33%). A GCL-IPL thickness less than or equal to 70 µm at initial presentation or progressive thinning of greater than or equal to 10 µm within 2 to 3 weeks compared with baseline correlated with poor visual outcome. CONCLUSIONS: Visual acuity loss in IIH can be caused by both outer retinal changes and optic neuropathy. Vision loss from outer retinal changes is mostly reversible. The outcome of patients with coexisting outer retinal changes and optic neuropathy or optic neuropathy alone depends on the degree of optic neuropathy, which can be predicted by the GCL-IPL thickness.

Risk factors for poor visual outcome in patients with idiopathic intracranial hypertension.

OBJECTIVES: Determine potential risk factors for progressive visual field loss in the Idiopathic Intracranial Hypertension Treatment Trial, a randomized placebo-controlled trial of acetazolamide in patients with idiopathic intracranial hypertension and mild visual loss concurrently receiving a low sodium, weight reduction diet. METHODS: Logistic regression and classification tree analyses were used to evaluate potential risk factors for protocol-defined treatment failure (>2 dB perimetric mean deviation [PMD] change in patients with baseline PMD -2 to -3.5 dB or >3 dB PMD change with baseline PMD -3.5 to -7 dB). RESULTS: Seven participants (6 on diet plus placebo) met criteria for treatment failure. The odds ratio for patients with grades III to V papilledema vs those with grades I and II was 8.66 (95% confidence interval [CI] 1.65-∞, p = 0.025). A 1-unit decrease in the number of letters correct on the ETDRS (Early Treatment Diabetic Retinopathy Study) chart at baseline was associated with an increase in the odds of treatment failure by a factor of 1.16 (95% CI 1.04-1.30, p = 0.005). Compared with female participants, the odds ratio for male participants was 26.21 (95% CI 1.61-433.00, p = 0.02). The odds of treatment failure were 10.59 times higher (95% CI 1.63-116.83, p = 0.010) for patients with >30 transient visual obscurations per month vs those with ≤30 per month. CONCLUSIONS: Male patients, those with high-grade papilledema, and those with decreased visual acuity at baseline were more likely to experience treatment failure. All but one of these patients were treated with diet alone. These patients should be monitored closely and be considered for aggressive treatment of their idiopathic intracranial hypertension.

Comparison of the clinical expression of retinitis pigmentosa associated with rhodopsin mutations at codon 347 and codon 23.

PURPOSE: To examine the difference in expression of retinitis pigmentosa from mutations at codon 23 and codon 347 or rhodopsin; to report a novel mutation in rhodopsin. METHODS: Goldmann perimetry (solid angle of I4e isopter) and electroretinographic amplitudes (square root transform of a response ratio) were analyzed for 24 patients with mutations at codon 347 (15 with Pro347Ala, 2 with Pro347Gln, 6 with Pro347Leu, and 1 with a novel Pro347Cys change) and 41 patients with mutations at codon 23 (6 with Pro23Ala; 35 with Pro23His). RESULTS: When all patients with mutations at codons 347 and 23 were compared, loss of visual fields was significantly worse in patients with codon 347 changes (P =.0003). Only rod responses of the electroretinograms were significantly different between the two groups (P =.048). Specific comparison of Pro347Ala with Pro23Ala using regression analysis demonstrated significant differences in severity between codon 23 and codon 347 patients for b-wave amplitudes of rod (P =.0069), cone (P =.039) and maximum combined response (P =.049). The solid angle of the I4e isopter was also significantly different (P =.025) between the groups after controlling for age. Modeling age by group for Pro347Ala comparison produced an R(2) of.44. CONCLUSION: We reconfirmed that rhodopsin-related retinitis pigmentosa from mutations involving codon 347 produces a more severe phenotype than that involving codon 23. Accurate modeling of disease was shown to be possible by incorporating the effects of a patient's age and specific genotype. Therefore, both of these variables must be considered in prognostic counseling and subject recruitment for future therapeutic trials.