Teprotumumab in Clinical Practice: Recommendations and Considerations From the OPTIC Trial Investigators.

BACKGROUND: Thyroid eye disease (TED) is a vision-threatening and debilitating condition that until very recently had no Food and Drug Administration (FDA)-approved medical therapies. Teprotumumab has recently been approved to treat TED. We aim to provide guidance for its use, based on the input of the US investigators who participated in Phase 2 and Phase 3 clinical trials. METHODS: An expert panel was convened on October 11th and November 16th of 2019. All panel members had extensive experience as investigators in the Phase 2 and/or Phase 3 clinical trials of teprotumumab. Consensus among those investigators was reached to determine patient characteristics most appropriate for teprotumumab treatment. Safety guidelines were also reviewed and agreed on. RESULTS: The authors recommend that teprotumumab be considered first-line therapy for patients with clinically significant ophthalmopathy, including those with disease duration exceeding 9 months. The clinical activity score (CAS) may be useful for longitudinal monitoring but should not be used to determine treatment eligibility. Criteria will likely be expanded after more experience with the drug. Using teprotumumab for patients with TED with substantial signs, symptoms, or morbidity without a CAS score of >4 (e.g., progressive proptosis, diplopia, and early compressive optic neuropathy) or more, could be considered. Diabetes mellitus and inflammatory bowel disease comorbidities should not be exclusionary, but stringent monitoring in these patients is recommended. Drug dosing, administration interval, and duration should adhere to the study protocol: 8 infusions, separated by 3 weeks. Patients with more severe disease may benefit from additional doses. Corticosteroids can be used before or during teprotumumab therapy. Clinical and laboratory monitoring should be consistent with good clinical practice for patients receiving teprotumumab. CONCLUSIONS: Confirming the efficacy of teprotumumab usage outside the narrow parameters of the completed clinical trials will require rigorous scientific validation. As a step in that direction, we believe its on-label usage is appropriately applied to all patients with TED with substantial symptoms or morbidity, as judged by their physician.

Teprotumumab for Thyroid-Associated Ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).

Custom Optical Coherence Tomography Parameters for Distinguishing Papilledema from Pseudopapilledema.

SIGNIFICANCE: Causes of papilledema can be life-threatening; however, distinguishing papilledema from pseudopapilledema is often challenging. The conventional optical coherence tomography (OCT) scan for assessing the optic nerve often fails to detect mild papilledema. Our study suggests that parameters derived from volumetric OCT scans can provide additional useful information for detecting papilledema. PURPOSE: Optical coherence tomography analysis of the optic nerve commonly measures retinal nerve fiber layer thickness (RNFLT) along a 1.73-mm-radius scan path. This conventional scan, however, often fails to detect mild papilledema. The purpose of this study was to evaluate additional OCT-derived measures of the optic nerve head (ONH) and peripapillary retina for differentiating papilledema (all grades and mild) from pseudopapilledema. METHODS: Cirrus OCT ONH volume scans were acquired from 21 papilledema (15 mild papilledema), 27 pseudopapilledema, and 42 control subjects. Raw scan data were exported, and total retinal thickness within Bruch's membrane opening (BMO) plus RNFLT and total retinal thickness at the following eccentricities were calculated using custom algorithms: BMO to 250, 250 to 500, 500 to 1000, and 1000 to 1500 µm. Minimum rim width was calculated, and BMO height was measured from a 4-mm Bruch's membrane reference plane centered on the BMO. RESULTS: Retinal nerve fiber layer thickness from BMO to 250 µm, minimum rim width, and BMO height had significantly greater areas under the receiver operating characteristic curve than did conventional RNFLT for differentiating mild papilledema from pseudopapilledema (P < .0001) and greater sensitivities at 95% specificity. Using cutoff values at 95% specificity, custom parameters detected 10 mild papilledema patients, and conventional RNFLT detected only 1. Bruch's membrane opening heights above the reference plane were observed in papilledema only, although many papilledema cases had a neutral or negative BMO height. CONCLUSIONS: Using OCT volumetric data, additional parameters describing peripapillary tissue thickness, neuroretinal rim thickness, and ONH position can be calculated and provide valuable measures for differentiating mild papilledema from pseudopapilledema.

Use of A-scan Ultrasound and Optical Coherence Tomography to Differentiate Papilledema From Pseudopapilledema.

SIGNIFICANCE: Differentiating papilledema from pseudopapilledema reflecting tilted/crowded optic discs or disc drusen is critical but can be challenging. Our study suggests that spectral-domain optical coherence tomography (OCT) peripapillary retinal nerve fiber layer thickness and retrobulbar optic nerve sheath diameter (ONSD) measured by A-scan ultrasound provide useful information when differentiating the two conditions. PURPOSE: To evaluate the use of A-scan ultrasound and spectral-domain OCT retinal nerve fiber layer thickness (RNFLT) in differentiating papilledema associated with idiopathic intracranial hypertension from pseudopapilledema. METHODS: Retrospective cross-sectional analysis included 23 papilledema and 28 pseudopapilledema patients. Ultrasound-measured ONSD at primary gaze, percent change in ONSD at lateral gaze (30° test), and peripapillary RNFLT were analyzed. Receiver operating characteristic curves were constructed using one eye from each subject. RESULTS: Compared with pseudopapilledema, papilledema eyes showed larger mean ONSD (5.4 ± 0.6 vs. 4.0 ± 0.3 mm, P < .0001), greater change of ONSD at lateral gaze (22.4 ± 8.4% vs. 2.8 ± 4.8%, P < .0001), and thicker retinal nerve fiber layer (219.1 ± 104.6 vs. 102.4 ± 20.1 µm, P < .0001). Optic nerve sheath diameter and 30° test had the greatest area under the receiver operating characteristic curve, 0.98 and 0.97, respectively; followed by inferior quadrant (0.90) and average RNFLT (0.87). All papilledema eyes with Frisén scale greater than grade II were accurately diagnosed by ONSD, 30° test, or OCT. In mild papilledema (Frisén scale grades I and II, n = 15), area under the receiver operating characteristic curve remained high for ONSD (0.95) and 30° test (0.93) but decreased to 0.61 to 0.71 for RNFLT. At 95% specificity, sensitivities for ONSD, 30° test, and RNFLT were 91.3%, 91.3%, and 56.5%, respectively, for the entire papilledema group and 80.0%, 86.7%, and 13.3% for the mild papilledema subgroup. CONCLUSIONS: Retinal nerve fiber layer thickness can potentially be used to detect moderate to severe papilledema. A-scan may further assist differentiation of mild papilledema from pseudopapilledema.

Reproducibility of multifocal visual evoked potential and traditional visual evoked potential in normal and multiple sclerosis eyes.

PURPOSE: To establish reproducibility of multifocal visual evoked potential (mfVEP) and traditional pattern-reversal VEP (tVEP) in normals and relapsing-remitting multiple sclerosis (RRMS). METHODS: mfVEP (60-sector dartboard) was recorded twice within a month in 40 normals and 40 RRMS patients [25 eyes with last optic neuritis (ON) ≥6 months, 34 non-ON]. mfVEP amplitude and latency (ms) were calculated as mean logSNR and median relative latency, respectively, for all 60 sectors (global) and 9 regions. tVEP was recorded (15', 60' and 120' checks) in subsets of 34 normals and 30 RRMS patients. tVEP N75-P100 amplitude (µV) and P100 latency (ms) were obtained. Reproducibility was evaluated using intraclass correlation coefficient (ICC) and test-retest variability (TRV). ICC ≥ 0.75 was considered good. RESULTS: ICCs for global and regional mfVEP were >0.80 in all groups. ICCs for tVEP were >0.75 for all except latency in ON (0.52-0.68). For mfVEP or tVEP, TRV for amplitude was similar among all groups; TRV for latency (ms) was larger in ON (5.3 for mfVEP global, 10.3 for 60' tVEP) compared with non-ON (3.1, 8.3) and normal (2.3, 5.7) (p < 0.05 for all). When tVEP was analyzed using similar methods as mfVEP (logSNR and relative latency), mfVEP global measures showed better ICC and TRV than tVEP in all groups. CONCLUSIONS: mfVEP and tVEP showed good reproducibility in normals and RRMS. TRV for mfVEP latency was larger in ON than normal or non-ON. mfVEP global latency's TRV was about half the respective values for tVEP in all groups, due to averaging of multiple responses.

Longitudinal Evaluation of Visual Function in Multiple Sclerosis.

PURPOSE: To evaluate longitudinal changes of visual function in relapsing-remitting multiple sclerosis (RRMS). METHODS: Multifocal visual evoked potential (mfVEP), contrast sensitivity (CS), and Humphrey visual fields (HVFs) were obtained at two visits (mean follow-up, 1.5 [±0.9] years) in both eyes of 57 RRMS patients (53 eyes with optic neuritis [ON]: 14 ON within 6 months of first visit [ON < 6 months] and 39 ON ≥ 6 months; 57 non-ON). Longitudinal changes were assessed using mfVEP amplitude (log signal-to-noise ratio [logSNR]), latency, CS, and HVF mean deviation based on established 95% tolerance limits of test-retest variability. RESULTS: A significant percentage of eyes in the ON < 6 months group exceeded 95% tolerance limits for mfVEP logSNR (21%, p < 0.05), latency (35%, p < 0.01), and CS (31% p < 0.001); more improved than worsened over time (14% vs. 7% for logSNR, 21% vs. 14% for latency, and 31% vs. 0% for CS). Multifocal visual evoked potential latency decreased in 11% of non-ON eyes and in 10% of eyes in the ON ≥ 6 months group, and increased in 21% and 10%, respectively (p < 0.01 for all). Latency changes correlated negatively with baseline latency (r = -0.43 and -0.45 for non-ON and ON ≥ 6 months; p = 0.0008). Although a nonsignificant percentage of non-ON and ON ≥ 6 months eyes exceeded tolerance limits for logSNR, CS, or HVF, logSNR and latency changes correlated, and both measures correlated with changes in CS (r = 0.47 to 0.79, p < 0.01). CONCLUSIONS: Multifocal visual evoked potential, particularly latency, is potentially useful for assessing neuroprotective and remyelinating strategies in RRMS.

Tracking changes over time in retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness in multiple sclerosis.

BACKGROUND: Neurodegeneration plays an important role in permanent disability in multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to determine whether progressive neurodegeneration occurs in MS eyes without clinically evident inflammation. METHODS: Retinal nerve fiver layer thickness (RNFLT) and ganglion cell-inner plexiform layer thickness (GCIPT) were measured using Cirrus optical coherence tomography (OCT) in 133 relapsing-remitting MS (RRMS) patients (149 non-optic neuritis (ON), 97 ON eyes, last ON ≥6 months). Ninety-three patients were scanned at two visits. Percentages of abnormal GCIPT vs RNFLT (<5% of machine norms) in cross-sectional data were compared. Relations between RNFLT/GCIPT and MS duration (cross-sectional) and follow-up time (longitudinal) were assessed. RESULTS: GCIPT was abnormal in more eyes than RNFLT (27% vs 16% p = 0.004 in non-ON, 82% vs 72% p = 0.007 in ON). RNFLT and GCIPT decreased with MS duration by -0.49 µm/yr (p = 0.0001) and -0.36 (p = 0.005) for non-ON; -0.52 (p = 0.003) and -0.41 (p = 0.007) for ON. RNFLT and GCIPT decreased with follow-up time by -1.49 µm/yr (p < 0.0001) and -0.53 (p = 0.004) for non-ON, -1.27 (p = 0.002) and -0.49 (p = 0.04) for ON. CONCLUSIONS: In RRMS eyes without clinically evident inflammation, progressive loss of RNFLT and GCIPT occurred, supporting the need for neuroprotection in addition to suppression of autoimmune responses and inflammation.

Neuroimaging Features of Intracranial Hypertension in Pediatric Patients With New-Onset Idiopathic Seizures, a Comparison With Patients with Confirmed Diagnosis of Idiopathic Intracranial Hypertension: A Preliminary Study.

CONCLUSION: A cutoff value of 6.0 mm for optic nerve sheath dilation may be used as a screening imaging marker to suspect elevated opening pressure with specificity of 88% in pediatric patients with new-onset idiopathic seizures.

Comparison of multifocal visual evoked potential, standard automated perimetry and optical coherence tomography in assessing visual pathway in multiple sclerosis patients.

BACKGROUND: Multifocal visual evoked potentials (mfVEP) measure local response amplitude and latency in the field of vision. OBJECTIVE: To compare the sensitivity of mfVEP, Humphrey visual field (HVF) and optical coherence tomography (OCT) in detecting visual abnormality in multiple sclerosis (MS) patients. METHODS: mfVEP, HVF, and OCT (retinal nerve fiber layer [RNFL]) were performed in 47 MS-ON eyes (last optic neuritis [ON] attack >or=6 months prior) and 65 MS-no-ON eyes without ON history. Criteria to define an eye as abnormal were: (1) mfVEP amplitude/latency - either amplitude or latency probability plots meeting cluster criteria with 95% specificity; (2) mfVEP amplitude or latency alone (specificity: 97% and 98%, respectively); and (3) HVF and OCT, mean deviation and RNFL thickness meeting p < 0.05, respectively. RESULTS: MfVEP (amplitude/latency) identified more abnormality in MS-ON eyes (89%) than HVF (72%), OCT (62%), mfVEP amplitude (66%) or latency (67%) alone. Eighteen percent of MS-no-ON eyes were abnormal for both mfVEP (amplitude/latency) and HVF compared with 8% with OCT. Agreement between tests ranged from 60% to 79%. mfVEP (amplitude/latency) categorized an additional 15% of MS-ON eyes as abnormal compared with HVF and OCT combined. CONCLUSIONS: mfVEP, which detects both demyelination (increased latency) and neural degeneration (reduced amplitude), revealed more abnormality than HVF or OCT in MS patients.

Neuro-ophthalmologic complications and manifestations of upper and lower motor neuron facial paresis.

The facial nerve (cranial nerve VII) courses a long pathway beginning in the precentral gyrus and ending at the facial muscles, lacrimal and salivary glands, and structures of the inner ear. Lesions along this pathway, clinically divided into upper and lower motor neuron lesions, present with unique characteristics that assist the physician in identifying the lesion site. The sequelae particularly of peripheral CN VII palsies, may result in significant and chronic damage to the cornea that may be challenging for the physician and patient.

Comparison of optical coherence tomography and scanning laser polarimetry measurements in patients with multiple sclerosis.

PURPOSE: To compare optical coherence tomography (OCT) and scanning laser polarimetry (GDx) measurements of the retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) patients with and without optic neuritis (ON). METHODS: OCT and GDx were performed on 68 MS patients. Qualifying eyes were divided into two groups: 51 eyes with an ON history > or =6 months before (ON eyes) and 65 eyes with no history of ON (non-ON eyes). Several GDx and OCT parameters and criteria were used to define an eye as abnormal, for example, GDx nerve fiber indicator (NFI) >20 or 30, OCT average RNFL thickness, and GDx temporal-superior-nasal-inferior-temporal average (TSNIT) below 5 or 1% of the normative database of the instruments. Agreement between OCT and GDx parameters was reported as percent of observed agreement, along with the AC1 statistic. Linear regression analyses were used to examine the relationship between OCT average RNFL thickness and GDx NFI and TSNIT. RESULTS: All OCT and GDx measurements showed significantly more RNFL damage in ON than in non-ON eyes. Agreement between OCT and GDx parameters ranged from 69 to 90% (AC1 0.37 to 0.81) in ON eyes and 52 to 91% (AC1 = 0.21 to 0.90) in non-ON eyes. Best agreement was observed between OCT average RNFL thickness (p < 0.01) and NFI (>30) in ON eyes (90%, AC1 = 0.81) and between OCT average RNFL thickness (p < 0.01) and GDx TSNIT average (p < 0.01) in non-ON eyes (91%, AC1 = 0.90). In ON eyes, the OCT average RNFL thickness showed good linear correlation with NFI (R = 0.69, p < 0.0001) and TSNIT (R = 0.55, p < 0.0001). CONCLUSIONS: OCT and GDx show good agreement and can be useful in detecting RNFL loss in MS/ON eyes.

Assessing visual pathway function in multiple sclerosis patients with multifocal visual evoked potentials.

Multifocal visual evoked potentials provide a topographic measure of visual response amplitude and latency. The objective of this study was to evaluate the sensitivity and specificity of the multifocal visual evoked potential technique in detecting visual abnormalities in patients with multiple sclerosis. Multifocal visual evoked potentials were recorded from 74 patients with multiple sclerosis with history of optic neuritis (MS-ON, n = 74 eyes) or without (MS-no-ON, n = 71 eyes), and 50 normal subjects (controls, n = 100 eyes) using a 60-sector pattern reversal dartboard stimulus (VERIS). Amplitude and latency for each sector were compared with normative data and assigned probabilities. Size and location of clusters of adjacent abnormal sectors (p < 0.05) were examined. Mean response amplitudes were (+/- SE) 0.39 +/- 0.02, 0.53 +/- 0.02, and 0.60 +/- 0.01 for MS-ON, MS-no-ON, and control groups, respectively, with significant differences between all groups (p < 0.0001). Mean latencies (ms; +/-SE relative to normative data) were 12.7 +/- 1.3 (MS-ON), 4.3 +/- 1.1 (MS-no-ON), and 0.3 +/- 0.4 (controls); group differences again significant (p < 0.0001). Half the MS-ON eyes had clusters larger than five sectors compared with 13% in MS-no-ON and 2% in controls. Abnormal sectors were distributed diffusely, although the largest cluster was smaller than 15 sectors in two-thirds of MS-ON eyes. Cluster criteria combining amplitude and latency showed an area of 0.96 under the receiver operating characteristic curve, yielding a criterion with 91% sensitivity and 95% specificity. We conclude that the multifocal visual evoked potential provides high sensitivity and specificity in detecting abnormalities in visual function in multiple sclerosis patients.

Multifocal visual evoked potentials and contrast sensitivity correlate with ganglion cell-inner plexiform layer thickness in multiple sclerosis.

OBJECTIVE: To examine the relationship between optical coherence tomography (OCT) macular ganglion cell-inner plexiform layer thickness (GCIPLT), peripapillary retinal nerve fiber layer thickness (RNFLT) and visual function in relapsing-remitting multiple sclerosis (RRMS). METHODS: Cirrus OCT, VERIS 60-sector multifocal visual evoked potential (mfVEP) and Pelli-Robson contrast sensitivity (CS) were obtained for 53 eyes with last optic neuritis (ON) > 6 months and 105 non-ON eyes in 90 patients. One eye (43 ON, 73 non-ON) was used for correlations when both had the same history. Global (G, 60 sectors) and central 5.6° (C, 24 sectors) mfVEP amplitude and latency were calculated as mean logSNR and median latency. RESULTS: Eyes showing abnormal mfVEP (amplitude or latency) vs OCT (GCIPLT or RNFLT) was 77% vs 69% (p = 0.33) in ON, 45% vs 22% (p < 0.0005) in non-ON. In ON and non-ON, mfVEP measures and CS correlated with GCIPLT and RNFLT (r = -0.24 to 0.78, p = 0.03-0.0001). In ON, mfVEP amplitude (C,G) correlated better with GCIPLT (r = 0.78, 0.76) than RNFLT (r = 0.43, 0.58; p < 0.001, 0.01). CONCLUSIONS: MfVEP measures and CS correlated well with GCIPLT and RNFLT in ON and non-ON. MfVEP amplitudes were more highly correlated with GCIPLT than RNFLT in ON. MfVEP detected significantly more defects than OCT in non-ON. SIGNIFICANCE: GCIPLT, mfVEP and CS provide useful measures of optic nerve integrity in RRMS.

Retinal toxicity secondary to Plaquenil therapy.

BACKGROUND: Hydroxychloroquine sulfate (Plaquenil; Sanofi-Aventis, Bridgewater, New Jersey) is an antimalarial agent, which is sometimes used for the treatment of certain autoimmune disorders. Its use has been associated with ocular side effects; the most concerning is toxic maculopathy. CASE REPORT: A 71-year-old arthritic white woman requested a second opinion regarding retinal Plaquenil toxicity. The patients history was significant for seronegative rheumatoid arthritis diagnosed 6 years prior. She had taken Plaquenil 400 mg a day for about 5 years but had discontinued the drug 6 months before when bilateral central scotomas were first noted. At the consultation visit, her visual acuities were 20/20 in both eyes. SITA-Standard 10-2 disclosed a dense scotoma with 4 degrees of central sparing in each eye. Fundus examination found retinal pigment epithelium changes bilaterally; no "bulls eye" retinopathy was observed. CONCLUSION: Withdrawal of the medication is the only effective treatment for Plaquenil toxicity and, even then, the toxic effects may progress because of the slow clearance of the drug. Though controversy exists regarding screening recommendations, a baseline ophthalmic examination should be performed on all patients before initiating Plaquenil. If a patient is considered low risk, examinations can be scheduled annually. For high-risk patients, 6-month progress visits are strongly recommended.

The relationship between visual field and retinal nerve fiber layer measurements in patients with multiple sclerosis.

PURPOSE: To investigate the relationship between visual function, measured by standard automated perimetry (SAP), and retinal nerve fiber layer (RNFL) thickness, measured by optical coherence tomography (OCT), in patients with multiple sclerosis (MS). METHODS: SAP and RNFL thickness were measured in patients with MS in 28 eyes with the last optic neuritis (ON) >or=6 months prior (ON group) and 33 eyes without ON history (non-ON group). Abnormal overall or quadrant RNFL thickness was defined by measured values below 5% of the norm. A whole visual field or a sector of the field was classified as abnormal by using cluster criteria on total-deviation plots. Agreement between SAP and OCT results in classifying eyes/sectors was presented as a percentage of observed agreement, along with the AC1 statistic, which corrects for chance agreement. Regression analyses were performed relating several SAP parameters and RNFL thickness in the ON group. RESULTS: ON eyes showed more loss of visual sensitivity (MD, P = 0.02) and more loss of RNFL thickness (P < 0.0001) than did non-ON eyes. SAP and OCT agreed in 86% (AC1 = 0.78) of eyes and 69% (AC1 = 0.38) of sectors in the ON group and 61% (AC1 = 0.33) of eyes and 66% (AC1 = 0.48) of sectors in the non-ON group. Overall RNFL thickness was related to MD (dB) by a simple exponential function (R(2) = 0.48), supporting a linear relationship between these measures when both are expressed on linear scales. Absolute Pearson correlation coefficients for overall RNFL thickness and several SAP parameters ranged from 0.51 to 0.69. CONCLUSIONS: Good agreement between SAP and OCT was found in ON eyes but not in non-ON eyes or in individual sectors in either group. The findings in this study provide further support for the utility of combining structural and functional testing in clinical research on patients with MS, as well as in future neuroprotection trials for which the anterior visual pathways in patients with MS and optic neuritis may be used as a model.

Surgical Resection of an Optic Nerve Sheath Meningioma: Relevance of Endoscopic Endonasal Approaches to the Optic Canal.

Optic nerve sheath meningiomas (ONSMs) account for less than 2% of meningiomas and 1.7% of orbital tumors. Although rare, the management of these tumors is important as unilateral blindness often results in untreated cases. Radiotherapy has emerged as the preferred treatment. However, therapies for ONSMs are controversial due to the variable natural history of the disease and limitations of surgical and radiotherapy options. A 60-year-old woman presented with monocular left diminished color perception and blurred vision. Magnetic resonance imaging demonstrated a homogenously enhancing 5-mm left optic nerve mass with evidence of nerve compression. Conservative management was advised. However, 1 month after diagnosis her visual acuity deteriorated further. Because of the small focal location of the tumor within the optic canal, surgery was considered. Given the tumor's location inferomedial to the optic nerve, an endoscopic endonasal approach to the optic canal was performed. This patient recovered fully with resolution of visual symptoms immediately following surgery. Postoperative imaging 24 hours after surgery demonstrated gross total resection of the tumor; 1 year postoperatively the patient has a normal ophthalmologic examination. This report highlights the value of endoscopic endonasal approaches in the management of select optic canal pathology, otherwise inaccessible via transcranial approaches.

Compressive optic neuropathy after use of oxidized regenerated cellulose in orbital surgery: review of complications, prophylaxis, and treatment.

PURPOSE: We report 2 cases of compressive optic neuropathy after use of oxidized regenerated cellulose (ORC) in orbital surgery. To our knowledge, no complications have been reported previously after use of this material in orbital surgery. We also review the complications related to its retention at operative sites outside the orbit and recommend precautions to avoid them. DESIGN: Retrospective interventional case reports. PARTICIPANTS: Two patients with compressive optic neuropathy after use of ORC in orbital surgery. METHODS: Case reports from 2 different clinics and review of the English scientific literature. MAIN OUTCOME MEASURES: Best-corrected visual acuity, extraocular motility, proptosis, and chemosis. RESULTS: One patient underwent orbital exploration and biopsy of an orbital tumor, and the second had repair of an orbital floor fracture. Postoperatively, both presented with chemosis, ophthalmoplegia, and progressive loss of vision. Orbital imaging revealed a retrobulbar soft-tissue density compatible with hematoma. Repeat orbital exploration revealed the soft-tissue mass to be swollen ORC. CONCLUSIONS: Retained intraorbital ORC may cause a compartment syndrome and should be suspected in postoperative patients with orbital symptoms. When ORC is used around the optic nerve, it should be removed after hemostasis is achieved.

Clinical Validation of a Transcranial Doppler-Based Noninvasive Intracranial Pressure Meter: A Prospective Cross-Sectional Study.

BACKGROUND: Noninvasive intracranial pressure (ICP) measurement would represent a major advance for patients with neurological problems. The Vittamed ICP meter is an ultrasound-based device reported to have high agreement with lumbar puncture cerebrospinal fluid (CSF) pressure measurement. However, previous studies included mostly patients with normal levels of ICP. The purpose of our study was to perform an independent clinical validation study of a transcranial Doppler-based noninvasive ICP meter in patients anticipated to have a wide range of ICP. METHODS: In a prospective cross-sectional design, we simultaneously measured ICP with the Vittamed device and the invasive lumbar CSF pressure. The operator of each procedure was blinded to the result of the other method. Data were analyzed using Bland-Altman plots, Pearson correlation coefficients, and receiver operator characteristic curves. RESULTS: Twenty-four independent paired measurements of Vittamed and lumbar CSF pressure were obtained; with mean absolute difference between paired measures of 4.5 mmHg (standard deviation 3.1). The 95% limits of agreement were -10.5 to +11.0. The systematic bias (mean of paired differences) was negligible at 0.25 mmHg. The sensitivity, specificity, and area under the curve for ICP >20 mmHg were 0.73, 0.77, and 0.71, respectively. CONCLUSIONS: The Vittamed ICP meter had fair agreement with lumbar CSF pressure measurement. The wide limits of agreement would preclude using this version of the device as a stand-alone method for ICP determination, but may be useful if combined with other ICP screening methods. Ongoing improvements to the Vittamed hardware and software may lead to improvements in accuracy and clinical utility of this device.

Her vision was tied down.

A 50-year-old female presented with progressive painless vision loss in the left eye and was subsequently diagnosed to have a pituitary macroadenoma, consistent with a prolactinoma, which was compressing the chiasm primarily on the left and involving the left cavernous sinus. She was treated with oral bromocriptine, resulting in marked shrinkage of the tumor and significant visual field recovery. Subsequently, she again began noting progressive vision loss in both eyes and was initially thought to have pituitary tumor regrowth. Repeat brain MRI, however, showed chiasmal prolapse with inferior tethering into an empty sella. Surgical fat padding to reposition the chiasm resulted in visual improvement with a different visual field pattern in the left eye. The clinical manifestations and etiopathogenesis of the empty sella syndrome are discussed.

Screening for cognitive impairment in older adults attending an eye clinic.

PURPOSE: We conducted a cross-sectional study examining potentially modifiable factors associated with cognitive impairments (mild or severe) in older whites, African Americans and Hispanics attending an outpatient eye clinic. METHODS: In-clinic interviews and physical examinations assessed social, demographic and health information from 100 consecutive Hispanic, African-American and white adults aged > or = 55. Our primary outcome was presence of any cognitive impairment (mild or severe) using the St. Louis University Mental Status Examination (SLUMS) scale. RESULTS: Of the 100 subjects, 65 screened positive for cognitive impairments on the SLUMS cognitive instrument: 46 with mild cognitive impairment and 19 with severe impairment (possible dementia). African-American and Hispanic adults (nonwhites) were significantly more likely to have cognitive impairment compared to white adults (OR 2.80: 95% CI = 1.05-7.44), independent of age, years of education and systolic blood pressure. Subjects with diabetes also had increased odds of cognitive impairments (OR 3.28, 95% CI = 1.21-8.90) even after adjusting for relevant confounders. There was a nonsignificant trend between visual acuity impairment and cognitive impairment (p = 0.059). CONCLUSIONS: Sixty-five percent of adults aged > or = 55 attending the eye clinic screened positive for cognitive impairments, with higher rates among nonwhites and adults living with diabetes.