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.

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.

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.

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.

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.

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.

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.

Pediatric optic neuritis: does a prolonged course of steroids reduce relapses? A preliminary study.

BACKGROUND: Optic neuritis is an important pediatric disorder causing visual impairment. Because of the absence of pediatric-specific studies, data extrapolated from the adult-based optic neuritis treatment trial are used to guide management of pediatric patients. Recent literature promotes a prolonged course of oral steroids to prevent relapses. However, there are no published data to support this view. Patients who were recently treated in our hospital received a longer course of steroids, relative to those treated several years ago. We hypothesized that a longer course of steroids results in fewer relapses and better final visual acuity. METHODS: A retrospective analysis of 26 consecutive patients (age 4.5-19 years) treated for optic neuritis within the past 10 years was conducted. Patients received either a short course (2 weeks) or a prolonged course (more than 2 weeks) of steroids. Some patients were not treated. Mean follow-up was 70 weeks (3 weeks-10 years). Comparisons were made among the groups receiving 2 weeks of steroid treatment (16 of 26 patients) and greater than 2 weeks of steroid treatment (seven of 26 patients) to evaluate relapse rate, eventual visual acuity, and reported side effects. RESULTS: There were no significant differences in the relapse rates, reported side effects, and final visual acuity in the two treatment groups. CONCLUSIONS: In this cohort, a prolonged course of steroids was not associated with reduced relapse rate, increased side effects, or improved visual outcome. This cohort was small, but the results do not identify any reason to deviate from the common approach of optic neuritis treatment, which is 2 weeks of steroids.

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.

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.

Retinal arterial but not venous tortuosity correlates with facioscapulohumeral muscular dystrophy severity.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease beginning with facial and shoulder girdle weakness with variable progression. Exudative retinal detachment, retinal vessel irregularities on fluorescein angiography, and retinal vessel tortuosity have been found in association with FSHD. METHODS: In this retrospective study, muscle affectedness severity was rated as mild, moderate, or severe by a neurologist masked to the retinal images. Three ophthalmologists masked to disease severity graded the degree of arterial and venous tortuosity on a scale of 1 to 4. An automated method estimated an index of tortuosity for arteries and veins from color fundus photographs. Spearman rank correlation coefficients were used to describe the relationship between retinal vessel tortuosity and disease severity. RESULTS: Seven patients with an average age of 13 years (range, 7-36 years) were selected. Correlation between the subjective tortuosity for arteries, and the severity of FSHD was 0.78 (p = 0.039). The correlation coefficient for venous tortuosity was -0.06 and was not significant (p = 0.882). The correlation coefficient between the average algorithmic computer-generated tortuosity indices for arteries and FSHD severity was high (0.85, p = 0.016), but for veins it was low and not significant (0.19, p = 0.662). CONCLUSIONS: The authors of previous reports have shown retinal vascular abnormalities did not correlate to FSHD disease severity. Our results suggest a correlation between the tortuosity of arteries and the severity of disease in FSHD patients. These results suggest the tortuosity of arteries can serve as a biomarker of severity of disease in these FSHD patients, either as determined by human experts or by an automated method.

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.