Search

Background: Increasing incidence of idiopathic intracranial hypertension (IIH), overreported radiologic signs of intracranial hypertension, difficult access to outpatient neuro-ophthalmology services, poor insurance coverage, and medicolegal concerns have lowered the threshold for emergency department (ED) visits for "papilledema." Our objective was to examine referral patterns and outcomes of neuro-ophthalmology ED and inpatient consultations for concern for papilledema. Methods: At one university-based quaternary care center, all adults referred for "papilledema" over one year underwent a standardized ED "papilledema protocol." We collected patient demographics, final diagnoses, and referral patterns. Results: Over 1 year, 153 consecutive patients were referred for concern for papilledema. After papilledema protocol, 89 of 153 patients (58%) had bilateral optic disc edema, among whom 89% (79/89) had papilledema (intracranial hypertension). Of the 38 of 153 (25%) consultations for suspected disorder of intracranial pressure without previous fundus examination (Group 1), 74% (28/38) did not have optic disc edema, 21% (8/38) had papilledema, and 5% (2/38) had other causes of bilateral disc edema. Of the 89 of 153 (58%) consultations for presumed papilledema seen on fundus examination (Group 2), 58% (66/89) had confirmed papilledema, 17% (15/89) had pseudopapilledema, and 9% (8/89) had other causes of bilateral optic disc edema. Of the 26 of 153 (17%) patients with known IIH (Group 3), 5 had papilledema and 4 required urgent intervention. The most common diagnosis was IIH (58/79). Compared with IIH, patients with secondary causes of intracranial hypertension were older (P = 0.002), men (P < 0.001), not obese (P < 0.001), and more likely to have neurologic symptoms (P = 0.002). Conclusions: Inpatient and ED consultations for "papilledema" are increasing. Of the 153 ED and inpatient neuro-ophthalmology consultations seen for "papilledema" over 1 year, one-third of patients with optic disc edema of unknown cause before presentation to our ED had new vision- or life-threatening disease, supporting the need for prompt identification and evaluation of optic disc edema in the ED. In the face of limited access to neuro-ophthalmologists, this study supports the need for emergency department access to expert eye-care evaluation or ocular fundus camera for prompt identification of optic disc edema and standardized evaluation for neurologic emergencies. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Optic disc drusen (ODD) represent an important differential diagnosis of papilledema caused by intracranial hypertension, but their distinction may be difficult in clinical practice. The aim of this study was to train, validate, and test a dedicated deep learning system (DLS) for binary classification of ODD vs papilledema (including various subgroups within each category), on conventional mydriatic digital ocular fundus photographs collected in a large international multiethnic population. Methods: This retrospective study included 4,508 color fundus images in 2,180 patients from 30 neuro-ophthalmology centers (19 countries) participating in the Brain and Optic Nerve Study with Artificial Intelligence (BONSAI) Group. For training and internal validation, we used 857 ODD images and 3,230 papilledema images, in 1,959 patients. External testing was performed on an independent data set (221 patients), including 207 images with ODD (96 visible and 111 buried), provided by 3 centers of the Optic Disc Drusen Studies Consortium, and 214 images of papilledema (92 mild-to-moderate and 122 severe) from a previously validated study. Results: The DLS could accurately distinguish between all ODD and papilledema (all severities included): area under the receiver operating characteristic curve (AUC) 0.97 (95% confidence interval [CI], 0.96–0.98), accuracy 90.5% (95% CI, 88.0%–92.9%), sensitivity 86.0% (95% CI, 82.1%–90.1%), and specificity 94.9% (95% CI, 92.3%–97.6%). The performance of the DLS remained high for discrimination of buried ODD from mild-to-moderate papilledema: AUC 0.93 (95% CI, 0.90–0.96), accuracy 84.2% (95% CI, 80.2%–88.6%), sensitivity 78.4% (95% CI, 72.2%–84.7%), and specificity 91.3% (95% CI, 87.0%–96.4%). Conclusions: A dedicated DLS can accurately distinguish between ODD and papilledema caused by intracranial hypertension, even when considering buried ODD vs mild-to-moderate papilledema. [ABSTRACT FROM AUTHOR]

evaluate patients with acute vision loss and are often the first to diagnose a central retinal artery occlusion (CRAO). How quickly these patients present to the optometrist, are diagnosed, and referred for evaluation are major factors influencing the possibility of acute therapeutic intervention. Our aim was to survey the U.S. optometric community to determine current optometric practice patterns for management of CRAO. Methods: An anonymous seven-question survey was emailed in 2020 to the 5,101 members of the American Academy of Optometry and the 26,502 members of the American Optometric Association. Results: Of 31,603 optometrists who were sent the survey, 1,926 responded (6.1%). Most respondents (1,392/1,919, 72.5%) worked in an optometrypredominant outpatient clinic and were less than 30 minutes from a certified stroke center (1,481/1,923, 77.0%). Ninety-eight percent (1,884/1,922) of respondents had diagnosed less than 5 CRAOs in the previous year, and 1,000/1,922 (52.0%) had not diagnosed a CRAO in the prior year. Of the optometrists who diagnosed at least one CRAO in the previous year, 661/922 (71.7%) evaluated these patients more than 4 hours after the onset of vision loss. Optometrists who diagnosed a CRAO or branch retinal artery occlusion referred patients to an emergency department (ED) affiliated with a certified stroke center (844/1,917, 44.0%), an outpatient ophthalmology clinic (764/1,917, 39.9%), an ED without a stroke center (250/1,917, 13.0%), an outpatient neurology clinic (20/1,917, 1.0%), or other (39/1,917, 2.0%); most (22/ 39, 56.4%) who responded "other" would refer to a primary care physician. Conclusions: Optometrists are likely the first providers to evaluate patients with acute vision loss, including from a retinal artery occlusion. However, only 6.1% of optometrists responded to our survey despite 2 reminder emails, likely reflecting the lack of exposure to acute retinal artery occlusions, and a potential lack of interest of optometrists in participating in research. Of the optometrists who reported evaluating a CRAO in the previous year, less than 29% saw the patient within 4 hours of vision loss. In addition, a large portion of optometrists are referring acute CRAO patients to outpatient ophthalmology clinics, delaying appropriate acute management. Therefore, it is imperative that optometrists and ophthalmologists are educated to view acute retinal arterial ischemia as an acute stroke and urgently refer these patients to an ED affiliated with a stroke center. The delay in patient presentation and these referral patterns make future clinical trials for acute CRAO challenging. [ABSTRACT FROM AUTHOR]

Background: MRI abnormalities are common in optic neuropathies, especially on dedicated orbital imaging. In acute optic neuritis, optic nerve T2-hyperintensity associated with optic nerve contrast enhancement is the typical imaging finding. In chronic optic neuropathies, optic nerve T2-hyperintensity and atrophy are regularly seen. Isolated optic nerve T2-hyperintensity is often erroneously presumed to reflect optic neuritis, frequently prompting unnecessary investigations and neuro-ophthalmology consultations. Our goal was to determine the significance of optic nerve/chiasm T2-hyperintensity and/or atrophy on MRI. Methods: Retrospective study of consecutive patients who underwent brain/orbital MRI with/without contrast at our institution between July 1, 2019, and June 6, 2022. Patients with optic nerve/chiasm T2-hyperintensity and/or atrophy were included. Medical records were reviewed to determine the etiology of the T2-hyperintensity and/or atrophy. Results: Four hundred seventy-seven patients (698 eyes) were included [mean age 52 years (SD ±18 years); 57% women]. Of the 364 of 698 eyes with optic nerve/chiasm T2-hyperintensity without atrophy, the causes were compressive (104), inflammatory (103), multifactorial (49), glaucoma (21), normal (19), and other (68); of the 219 of 698 eyes with optic nerve/chiasm T2-hyperintensity and atrophy, the causes were compressive (57), multifactorial (40), inflammatory (38), glaucoma (33), normal (7), and other (44); of the 115 of 698 eyes with optic nerve/chiasm atrophy without T2-hyperintensity, the causes were glaucoma (34), multifactorial (21), inflammatory (13), compressive (11), normal (10), and other (26). Thirty-six eyes with optic nerve/chiasm T2-hyperintensity or atrophy did not have evidence of optic neuropathy or retinopathy on ophthalmologic examination, and 17 eyes had clinical evidence of severe retinopathy without primary optic neuropathy. Conclusions: Optic nerve T2-hyperintensity or atrophy can be found with any cause of optic neuropathy and with severe chronic retinopathy. These MRI findings should not automatically prompt optic neuritis diagnosis, workup, and treatment, and caution is advised regarding their use in the diagnostic criteria for multiple sclerosis. Cases of incidentally found MRI optic nerve T2-hyperintensity and/or atrophy without a known underlying optic neuropathy or severe retinopathy are rare. Such patients should receive an ophthalmologic examination before further investigations. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: The examination of the optic nerve head (optic disc) is mandatory in patients with headache, hypertension, or any neurological symptoms, yet it is rarely or poorly performed in general clinics. We recently developed a brain and optic nerve study with artificial intelligence-deep learning system (BONSAI-DLS) capable of accurately detecting optic disc abnormalities including papilledema (swelling due to elevated intracranial pressure) on digital fundus photographs with a comparable classification performance to expert neuro-ophthalmologists, but its performance compared to first-line clinicians remains unknown. Methods: In this international, cross-sectional multicenter study, the DLS, trained on 14,341 fundus photographs, was tested on a retrospectively collected convenience sample of 800 photographs (400 normal optic discs, 201 papilledema and 199 other abnormalities) from 454 patients with a robust ground truth diagnosis provided by the referring expert neuro-ophthalmologists. The areas under the receiver-operating-characteristic curves were calculated for the BONSAI-DLS. Error rates, accuracy, sensitivity, and specificity of the algorithm were compared with those of 30 clinicians with or without ophthalmic training (6 general ophthalmologists, 6 optometrists, 6 neurologists, 6 internists, 6 emergency department [ED] physicians) who graded the same testing set of images. Results: With an error rate of 15.3%, the DLS outperformed all clinicians (average error rates 24.4%, 24.8%, 38.2%, 44.8%, 47.9% for general ophthalmologists, optometrists, neurologists, internists and ED physicians, respectively) in the overall classification of optic disc appearance. The DLS displayed significantly higher accuracies than 100%, 86.7% and 93.3% of clinicians (n = 30) for the classification of papilledema, normal, and other disc abnormalities, respectively. Conclusions: The performance of the BONSAI-DLS to classify optic discs on fundus photographs was superior to that of clinicians with or without ophthalmic training. A trained DLS may offer valuable diagnostic aid to clinicians from various clinical settings for the screening of optic disc abnormalities harboring potentially sight- or life-threatening neurological conditions. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Radiologic findings of intracranial hypertension (RAD-IH) are common in idiopathic intracranial hypertension (IIH) patients. Paralleling the increasing rates of obesity, the burden of IIH is growing. Urgent neuro-ophthalmology consultations for possible IIH in patients with incidentally detected RAD-IH are increasing, with many patients receiving unnecessary lumbar punctures (LPs) and treatments. This retrospective observational study aimed to determine the prevalence of neuro-ophthalmology consultations for RAD-IH, rate of funduscopic examination by referring providers, prevalence of papilledema, outcomes after neuro-ophthalmic evaluation, and rates of misdiagnosis. Methods: Records of 1,262 consecutive new patients seen in one neuro-ophthalmology clinic from January 2019 to January 2020 were reviewed. We identified patients who were: 1) referred with concern for IIH because of findings of RAD-IH; 2) referred for "papilledema"; 3) referred with a diagnosis of IIH; and 4) referred for spontaneous cranial cerebrospinal fluid (CSF) leaks. In addition to basic demographic profiles for all groups, detailed information was collected for patients referred solely for RAD-IH, including referral patterns, prior history of IIH, previous LPs, prior medical or surgical treatment(s), risk factors for increased intracranial pressure (ICP), presenting symptoms, radiologic features observed on neuroimaging, and final disposition. When available, the neuroimaging was reviewed by an expert neuroradiologist. Results: Of 1,262 consecutive new patients, 66 (5%) were referred specifically for RAD-IH; most referrals came from neurologists (58%); 8/66 (12%) patients had papilledema; 16/66 (24%) patients had prior LP and 13/66 (20%) were already treated based on MRI findings; and 22/66 (33%) patients had ≤2 RAD-IH. Only 34/66 (52%) of patients referred for RAD-IH had prior funduscopic examinations. We confirmed papilledema in 26/82 (32%) patients referred for "papilledema." Only 29/83 (35%) patients referred with a diagnosis of IIH had active papilledema, and 3/16 (19%) patients with spontaneous CSF leaks had papilledema. In total, 247/1,262 (20%) new patients were referred to our clinic over 1 year with concern for IIH, among whom only 66 (27%) were confirmed to have active IIH with papilledema. Conclusions: One in 5 new patient referrals seen in our neuro-ophthalmology clinic were referred because of concern for increased ICP, but only 1/4 had active papilledema. Most patients referred for isolated RAD-IH do not have papilledema, many having undergone unnecessary LPs and treatments. The burden of these "rule-out IIH" consultations is overwhelming and will only continue to increase with the concurrent rise of obesity and IIH, straining the already limited neuro-ophthalmologic resources available in the US. [ABSTRACT FROM AUTHOR]

Background: The Neurological Pupil index (NPi) provides a quantitative assessment of pupil reactivity and may have prognostic value in patients with subarachnoid hemorrhage (SAH). We aimed to explore associations between the NPi and clinical outcomes in patients with SAH. Methods: A retrospective analysis of 79 consecutive patients with acute SAH. Age, sex, Acute Physiology and Chronic Health Evaluation-II score, and respiratory failure and NPi in each eye were recorded at admission. The primary outcomes included death and poor clinical outcome (defined as inpatient death, care withdrawal, or discharge Glasgow Outcome Score <4). Groups were compared using the Fisher exact test, and predictive models developed with fast-and-frugal trees (FFTs). Results: A total of 53 patients were included: 21 (40%) had poor clinical outcomes and 2 (4%) died. Univariate analysis found that only APACHE-II score (P < 0.001) and respiratory failure (P = 0.04) were significantly associated with poor clinical outcomes. NPi was lower among patients with poor clinical outcomes (mean 4.3 in the right eye and 4.2 in the left eye) vs those without (mean 4.5 in the right eye and 4.5 in the left eye), but neither was significant. However, the most accurate FFTs for death and poor clinical outcome included NPi after accounting for age in the death FFT and APACHE-II score in the poor outcome FFT (sensitivity [sn] = 100%, specificity [sp] = 94%, and accuracy (ac) = 94% in a model for death; sn = 100%, sp = 50%, and ac = 70%) in a model for poor clinical outcome. Conclusions: Our study supports the NPi as a useful prognostic marker for poor outcomes in acute SAH after accounting for age and APACHE-II score. [ABSTRACT FROM AUTHOR]

Background: Unilateral isolated optic disc edema (UIODE) represents a challenging clinical presentation that frequently precipitates an extensive diagnostic work-up. Patients without an apparent diagnosis despite appropriate investigations are often categorized as having "papillophlebitis," an entity that is poorly defined in the existing literature. Our aim was to describe the characteristics of a series of patients with paucisymptomatic UIODE, determine the optimal diagnostic approach to such cases, and clarify the clinical features of presumed papillophlebitis. Methods: We retrospectively identified 29 patients with UIODE who were seen by neuro-ophthalmologists at a single center between 2005 and 2019. Each patient presented with isolated, unilateral disc edema that was either entirely asymptomatic or associated with minimal visual symptoms. Patients underwent a comprehensive neuro-ophthalmic evaluation and several ophthalmic and systemic investigations. Data from the initial visit and all subsequent clinical visits were collected, including patient demographics, examination findings, and details of the diagnostic work-up. Results: Our 29 patients with UIODE were found to have a variety of underlying diagnoses including unilateral papilledema due to idiopathic intracranial hypertension (10 patients), optic nerve sheath meningioma (5), incipient nonarteritic anterior ischemic neuropathy (4), vitreopapillary traction (3), orbital masses (2), a peripapillary choroidal neovascular membrane (1), and presumed papillophlebitis (4). The duration of disc edema varied considerably based on the etiology, but most patients had favorable visual outcomes. Conclusions: A systematic approach to the evaluation of UIODE, combined with long-term follow-up, led to a definite diagnosis in a majority of patients, with only 4 patients presumed to have papillophlebitis, a diagnosis the actual existence of which remains controversial. [ABSTRACT FROM AUTHOR]

Background: A relationship between idiopathic intracranial hypertension and spontaneous skull base cerebrospinal fluid (CSF) leaks has been proposed, by which CSF leak decreases intracranial pressure (ICP) and masks the symptoms and signs of elevated ICP. These patients are at risk of developing papilledema, symptoms of elevated ICP, or a recurrent CSF leak after CSF leak repair. The objective of this study was to assess whether radiographic signs of raised ICP on preoperative magnetic resonance or computed venography (MRI or CTV) are predictors of postoperative papilledema, recurrence of CSF leak, or need for CSF shunt surgery. Methods: We performed a retrospective review of systematically collected demographics, fundus examination, and presurgical brain MRI and magnetic resonance venography/computed tomography venography (MRV/CTV) in patients seen at 1 institution between 2013 and 2019 with spontaneous skull base CSF leak repair. Patients were divided into 2 groups depending on whether they developed papilledema, recurrent CSF leak, or required CSF shunting (Group 1) or not (Group 2). Results: Fifty-seven patients were included, among whom 19 were in Group 1. There was no difference in demographic characteristics or clinical features between patients in Group 1 and Group 2. Controlling for other imaging features, bilateral transverse venous sinus stenosis (TVSS) on preoperative imaging increased the odds of being in Group 1 by 4.2 times (95% confidence interval [CI], 1.04–21.2, P = 0.04), optic nerve tortuosity decreased the odds of being in Group 1 by 8.3 times (95% CI: 1.4–74.6, P = 0.02). Conclusion: Imaging of the intracranial venous system with MRV or CTV is warranted before repair of spontaneous CSF leak, as bilateral TVSS is an independent risk factor for postoperative papilledema, CSF leak recurrence, or need for a CSF shunting procedure. [ABSTRACT FROM AUTHOR]

Background: The tortuosity of the optic nerve can be quantified radiologically by measuring the angle of optic nerve deformation (the "optic nerve angle" [ONA]). In patients with idiopathic intracranial hypertension (IIH), lowering the intracranial pressure (ICP) to a normal range by lumbar puncture leads to straightening of the optic nerve and an increase in the measured sagittal ONA on MRI. It is uncertain whether there is any correlation between ONA and cerebrospinal fluid (CSF) opening pressure or visual function. Methods: Retrospective study of patients with and without IIH who had MRI of the brain followed by lumbar puncture with CSF opening pressure within 24 hours of MRI. Before LP and within 24 hours of MRI of the brain, all patients with IIH had neuro-ophthalmologic assessment including visual acuity, Humphrey Visual Field (HVF), and fundus photography. Sagittal ONA was measured on multiplanar T2-SPACE images on a DICOM viewer. Papilledema on the fundus photographs was graded using the Frisén scale. Results: Fifty-four patients with IIH and 30 unmatched controls were included. The IIH group was 6.3 years younger (95% CI 2.4–10.3, P = 0.002), had 8.7 kg/m2 higher body mass index (4.9–12.5, P < 0.001), and 26.3% more women (P = 0.011) compared with controls. In both eyes, the ONA was significantly smaller in patients with IIH by 12° compared with controls (7°–17°, P < 0.00001). In the IIH group, no correlation between ONA and the CSF opening pressure was present in either eye (right eye r = 0.19, P = 0.15; left eye r = 0.18, P = 0.19) The ONA did not correlate with logarithm of the minimum angle of resolution visual acuity (right eye r = 0.26, P = 0.063; left eye r = 0.15, P = 0.27), HVF mean deviation (right eye r = 0.0059, P = 0.97; left eye r = −0.069, P = 0.63), or Frisén grade (Spearman's rho right eye 0.058, P = 0.67; left eye 0.14, P = 0.30). Conclusions: The ONA is significantly smaller in patients with IIH compared to controls, but does not correlate with CSF opening pressure, severity of papilledema, or visual function. The ONA may be useful in identifying patients with raised ICP, but not necessarily those with a poor visual prognosis. [ABSTRACT FROM AUTHOR]

Background: Central retinal artery occlusion (CRAO) is a medical emergency, and patients who present acutely should be immediately referred to the nearest stroke center. We evaluated practice patterns for CRAO management at one academic center over the last decade. Methods: This was a retrospective study on all adult patients diagnosed with a CRAO seen at one tertiary hospital and outpatient clinic affiliated with a comprehensive stroke center ("our institution") from 2010 to 2020. Our electronic medical records were searched for CRAO diagnoses, and patient medical records were reviewed. The exclusion criteria were incorrect diagnosis, unclear diagnosis, historical CRAO, or satellite clinic location. Demographics, distance and time to presentation to our institution, number and type of prior providers seen, diagnostic tests performed, and treatments provided were collected. Summary statistics of median, mean, and frequency were calculated and reported with measures of variance (interquartile range [IQR], ranges). F, Tukey, and Fisher exact tests were used for comparisons. Results: We included 181 patients with a diagnosis of CRAO (80 [44.2%] women; median age 69 years [range 20–101]). The median distance from patient's home to our institution was 27.8 miles (IQR 15.5–57.4; range 2.4–930). The median time from visual loss to presentation at our institution was 144 hours (IQR 23–442 hours, range 0.5–2,920) from 2010 to 2013, 72 hours (IQR 10.5–372 hours, range 0–13,140) from 2014 to 2016, and 48 hours (IQR 7–180 hours, range 0–8,030) from 2017 to 2020 (P = 0.07). 91/181 (50%) patients presented to an outpatient provider. 73/181 (40%) presented to an emergency department. Eighty-six percent presented within 1 week of visual loss onset, and rates of comprehensive inpatient evaluation for acute CRAO improved from 44% in 2010–2013 to 82% in 2017–2020 (P < 0.01). Conclusions: Patients with CRAO often present late and only after evaluation by multiple outpatient providers. Improvement has occurred over the past decade, but delays underscore the barriers to performing clinical trials evaluating very acute treatments for CRAO. Educational interventions for healthcare providers and patients are necessary. [ABSTRACT FROM AUTHOR]

• Fundus photography in the emergency department accelerates the diagnosis of retinal ischemia. • Optical coherence tomography of the retina is a powerful tool to detect early retinal ischemia. • An eye stroke protocol allows for rapid intervention for patients with acute retinal ischemia. • Education is needed so that acute vision loss patients present to the emergency department promptly. Visual outcomes of acute central and branch retinal artery occlusions (CRAO/BRAO) are poor and acute treatment options are limited by delayed diagnosis. In the hyper-acute setting, the ocular fundus may appear "normal", making recognition challenging, but is facilitated by retinal optical coherence tomography (OCT), which is seldom available in emergency departments (ED). We evaluated the use of non-mydriatic ocular fundus photographs (NMFP) combined with OCT to facilitate ultra-rapid remote diagnosis and stroke alert for patients with acute vision loss presenting to the ED. Prospective evaluation of all CRAO/BRAO between 06/06/2023-06/06/2024 who had NMFP-OCT in our general ED affiliated with a stroke center. Over 1 year, 22 patients were diagnosed with CRAO, 4 with BRAO. Five patients presented within 4.5 hours of vision loss onset, 6 within 4.5 to ≤12 hours and 15 within >12 to 24 hours. On average, NMFP-OCT was performed within 141 minutes of presentation to the ED (range 27- 422 minutes). Diagnosis of acute RAO was made remotely with NMFP-OCT within 4.5 hours in 4 patients, 2 of whom received intravenous thrombolysis. Of the 9 patients with NMFP-OCT within 12 hours of symptom onset, 5 patients had subtle retinal whitening on color fundus photograph, but all had OCT inner retinal hyper-reflectivity/edema. Implementation of NMFP-OCT in a general ED enables rapid remote diagnosis of CRAO/BRAO and facilitates initiation of an eye stroke protocol in acute patients. OCT complements color fundus photography and provides greater diagnostic accuracy in hyperacute cases with near-normal appearing ocular fundi. [ABSTRACT FROM AUTHOR]

Objective: This report presents a cross-sectional analysis of the baseline characteristics of subjects with Leber hereditary optic neuropathy enrolled in the gene therapy trials RESCUE and REVERSE, to illustrate the evolution of visual parameters over the first year after vision loss. Methods: RESCUE and REVERSE were 2 phase III clinical trials designed to assess the efficacy of rAAV2/2-ND4 gene therapy in ND4-LHON subjects. At enrollment, subjects had vision loss for ≤6 months in RESCUE, and between 6 and 12 months in REVERSE. Functional visual parameters (best-corrected visual acuity [BCVA], contrast sensitivity [CS], and Humphrey Visual Field [HVF]) and structural parameters assessed by spectral-domain optical coherence tomography were analyzed in both cohorts before treatment. The cross-sectional analysis of functional and anatomic parameters included the baseline values collected in all eyes at 2 different visits (Screening and Inclusion). Results: Seventy-six subjects were included in total, 39 in RESCUE and 37 in REVERSE. Mean BCVA was significantly worse in RESCUE subjects compared with REVERSE subjects (1.29 and 1.61 LogMAR respectively, P = 0.0029). Similarly, mean CS and HVF were significantly more impaired in REVERSE vs RESCUE subjects (P < 0.005). The cross-sectional analysis showed that the monthly decrease in BCVA, ganglion cell layer macular volume, and retinal nerve fiber layer thickness was much more pronounced in the first 6 months after onset (+0.24 LogMAR, -0.06 mm³, and -6.00 mm respectively) than between 6 and 12 months after onset (+0.02 LogMAR, -0.01 mm³, and -0.43 µm respectively). Conclusion: LHON progresses rapidly in the first months following onset during the subacute phase, followed by relative stabilization during the dynamic phase. [ABSTRACT FROM AUTHOR]

Background: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of sub-jects treated in the RESCUE and REVERSE trials. Methods: In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a period of up to 52 months after onset of vision loss. A locally estimated scatterplot smoothing regression model was used to analyze changes in BCVA over time. Vision-related quality of life was reported using the visual function questionnaire-25 (VFQ-25). Results: The population of MT-ND4 subjects enrolled in RESTORE was representative of the combined cohorts of RESCUE and REVERSE for mean age (35.1 years) and gender distribution (79% males). There was a progressive and sustained improvement of BCVA up to 52 months after the onset of vision loss. The final mean BCVA was 1.26 logarithm of the minimal angle of resolution 48 months after the onset of vision loss. The mean VFQ-25 composite score increased by 7 points compared with baseline. Conclusion: The treatment effect of lenadogene nolparvovec on BCVA and vision-related quality of life observed 96 weeks (2 years) after treatment in RESCUE and REVERSE was sustained at 3 years in RESTORE, with a maximum follow-up of 52 months (4.3 years) after the onset of vision loss. [ABSTRACT FROM AUTHOR]

Vision problems from giant cell arteritis (GCA) can be difficult to diagnose as patients may present with vision loss in the absence of systemic symptoms, have other comorbidities that affect inflammatory blood markers, or have other ocular diagnoses. We present 3 cases illustrating this point including a patient with advanced glaucoma with worsening vision from posterior ischemic optic neuropathy from GCA, a patient with arteritic anterior ischemic optic neuropathy (AAION) erroneously diagnosed as optic neuritis without elevated inflammatory blood markers due to corticosteroid use, and a patient with AAION and a history of nonarteritic anterior ischemic optic neuropathy in her fellow eye and untreated obstructive sleep apnea. GCA should be kept in the differential diagnosis for patients over 50 years of age even if they carry other ocular diagnoses. Temporal artery biopsy remains the gold standard for GCA diagnosis and is often required in equivocal cases. [ABSTRACT FROM AUTHOR]

Background: Diagnostic error is prevalent and costly, occurring in up to 15% of US medical encounters and affecting up to 5% of the US population. One-third of malpractice payments are related to diagnostic error. A complex and specialized diagnostic process makes neuroophthalmologic conditions particularly vulnerable to diagnostic error. Evidence Acquisition: English-language literature on diagnostic errors in neuro-ophthalmology and neurology was identified through electronic search of PubMed and Google Scholar and hand search. Results: Studies investigating diagnostic error of neuroophthalmologic conditions have revealed misdiagnosis rates as high as 60%–70% before evaluation by a neuroophthalmology specialist, resulting in unnecessary tests and treatments. Correct performance and interpretation of the physical examination, appropriate ordering and interpretation of neuroimaging tests, and generation of a differential diagnosis were identified as pitfalls in the diagnostic process. Most studies did not directly assess patient harms or financial costs of diagnostic error. Conclusions: As an emerging field, diagnostic error in neuroophthalmology offers rich opportunities for further research and improvement of quality of care. [ABSTRACT FROM AUTHOR]

Background: The association between spontaneous skull base cerebrospinal fluid (CSF) leaks and idiopathic intracranial hypertension (IIH) has been suggested, but its significance remains unclear. Objective: To estimate the prevalence of IIH in spontaneous skull base CSF leak patients. Methods: Systematic collection of demographics, neuro-ophthalmic and magnetic resonance imaging evaluation of spontaneous skull base CSF leak patients seen pre- and post-leak repair in one neuro-ophthalmology service. Patients with preexisting IIH were diagnosed with definite IIH if adequate documentation was provided; otherwise, they were categorized with presumed IIH. Classic radiographic signs of intracranial hypertension and bilateral transverse venous sinus stenosis were recorded. Results: Thirty six patients were included (age [interquartile range]: 50 [45;54] years; 94% women; body mass index: 36.8 [30.5;39.9] kg/m2), among whom six (16.7%, [95% confidence interval, CI]: [6.4;32.8]) had a preexisting diagnosis of definite or presumed IIH. Of the remaining 30 patients, four (13.3%, 95%CI: [3.8;30.7]) had optic nerve head changes suggesting previously undiagnosed IIH, while one was newly diagnosed with definite IIH at initial consultation. One out of 29 patients with normal findings of the optic nerve head at presentation developed new onset papilledema following surgery (3.4%, 95%CI: [0.1;17.8]) and was ultimately diagnosed with definite IIH. Overall, the prevalence of definite IIH was 19.4% (95%CI: [8.2;36.0]). Conclusion: Striking demographic overlap exists between IIH patients and those with spontaneous CSF leak. Definite IIH was present in approximately 20% of our patients. However, its true prevalence is likely higher than identified by using classic criteria. We therefore hypothesize that an active CSF leak serves as an auto-diversion for CSF, thereby "treating" the intracranial hypertension and eliminating characteristic signs and symptoms at initial presentation. [ABSTRACT FROM AUTHOR]

Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited bilaterally blinding optic neuropathy, predominantly affecting otherwise healthy young individuals, mostly men. The visual prognosis is generally poor, with most patients worsening to at least 20/200 visual acuity. The m.11778G.A(MTND4) mitochondrial DNA mutation is the most common cause of LHON and is associated with poor outcomes and limited potential for meaningful visual recovery. Treatments for LHON are limited, and clinical trials are hampered by inadequate data regarding the natural history of visual loss and recovery. In this article, we review the current literature specifically related to visual function of LHON patients with the m.11778G.A mutation. Evidence acquisition: Literature review was performed using MEDLINE through PubMed, Cochrane Reviews Library, and Orpha.net with search terms of "Leber hereditary optic neuropathy,""LHON,""ND4,""G11778A,""visual acuity," "nadir,""natural history," and "registry." All English- language, peer-reviewed publications with study cohorts of at least 5 LHON patients with the molecularly confirmed m.11778G.A mutation were included. Results: Meta-analysis of 12 retrospective and 3 prospective studies provided visual function information on 695 LHON patients with the m.11778G.A mutation, 100 (14.4%) of whom were reported to have "recovered" some vision, although definitions of "recovery" varied among studies and idebenone use could not always be excluded. When incorporating age at onset of visual loss into the analyses, and specifically addressing those patients aged 15 years or older, meaningful visual recovery occurred in 23 of 204 (11.3%) patients. A younger age at onset, especially less than 12 years, portends a better visual prognosis and a different natural history of visual loss progression and recovery than in adults. Conclusions: The classic presentation of LHON patients with the m.11778G.A mutation of severe visual loss with rare or poor recovery from nadir still holds true for most affected individuals. Among patients 15 years and older, recovery of meaningful vision likely occurs in less than 20% of patients, irrespective of how recovery is defined, and ultimate visual acuities of better than 20/200 are rare. Adequate prospective studies with sufficient sample sizes of genotypically homogeneous untreated LHON patients stratified by age, immediately enrolled when symptomatic, followed regularly for adequate periods of time with consistent measures of visual function, and analyzed with a standard definition of visual improvement are unfortunately lacking. Future clinical trials for LHON will require more standardized reporting of the natural history of this disorder. [ABSTRACT FROM AUTHOR]

Background: Neuro-ophthalmologists specialize in complex, urgent, vision- and life-threatening problems, diagnostic dilemmas, and management of complex work-ups. Access is currently limited by the relatively small number of neuro-ophthalmologists, and consequently, patients may be affected by incorrect or delayed diagnosis. The objective of this study is to analyze referral patterns to neuroophthalmologists, characterize rates of misdiagnoses and delayed diagnoses in patients ultimately referred, and delineate outcomes after neuro-ophthalmologic evaluation. Methods: Retrospective chart review of 300 new patients seen over 45 randomly chosen days between June 2011 and June 2015 in one tertiary care neuro-ophthalmology clinic. Demographics, distance traveled, time between onset and neuro-ophthalmology consultation (NOC), time between appointment request and NOC, number and types of providers seen before referral, unnecessary tests before referral, referral diagnoses, final diagnoses, and impact of the NOC on outcome were collected. Results: Patients traveled a median of 36.5 miles (interquartile range [IQR]: 20--85). Median time from symptom onset was 210 days (IQR: 70--1,100). Median time from referral to NOC was 34 days (IQR: 7--86), with peaks at one week (urgent requests) and 13 weeks (routine requests). Median number of previous providers seen was 2 (IQR: 2--4; range:0--10), and 102 patients (34%) had seen multiple providers within the same specialty before referral. Patients were most commonly referred for NOC by ophthalmologists (41% of referrals). Eighty-one percent (242/300) of referrals to neuro-ophthalmology were appropriate referrals. Of the 300 patients referred, 247 (82%) were complex or very complex; 119 (40%) were misdiagnosed; 147 (49%) were at least partially misdiagnosed; and 22 (7%) had unknown diagnoses. Women were more likely to be at least partially misdiagnosed--108 of 188 (57%) vs 39 of 112 (35%) of men (P, 0.001). Mismanagement or delay in care occurred in 85 (28%), unnecessary tests in 56 (19%), unnecessary consultations in 64 (22%), and imaging misinterpretation in 16 (5%). Neuro-ophthalmologists played a major role in directing treatment, such as preserving vision, preventing life-threatening complications, or avoiding harmful treatment in 62 (21%) patients. Conclusions: Most referrals to neuro-ophthalmologists are appropriate, but many are delayed. Misdiagnosis before referral is common. Neuro-ophthalmologists often prevent vision- and life-threatening complications. [ABSTRACT FROM AUTHOR]

Background: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. Methods: Open-label, multicenter, retrospective, non-controlled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. Results: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. Conclusions: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone. [ABSTRACT FROM AUTHOR]

Background: Acute nonarteritic central retinal artery occlusion (CRAO) is an eye stroke with poor visual prognosis and no proven effective therapies. Given advances in acute stroke care, thrombolysis in CRAO merits critical re-examination. We review the evidence for intravenous (IV) and intra-arterial (IA) tissue plasminogen activator (tPA) in CRAO management. Evidence Acquisition: MEDLINE, Scopus, and Cochrane online databases were systematically searched from 1960 to present, for reports of acute IV or IA therapy with alteplase or tenecteplase in nonarteritic CRAO patients. English language case reports, case series, interventional studies, or randomized controlled trials were included. The study type, age and number of subjects, the regimen administered, the time since symptoms' onset, visual outcome, and safety reports were noted. Results: Use of IV thrombolysis with alteplase was reported in 7 articles encompassing 111 patients, with 54% of them receiving IV tPA within 4.5 hours of symptom onset, and none developing symptomatic intracranial or ocular hemorrhage. Six studies described IA alteplase administration, with only 18 of a total of 134 patients (13.4%) treated within the first 6 hours after visual loss. The reported adverse events were minimal. Visual outcomes post-IV and IA thrombolysis were heterogeneously reported; however, most studies demonstrated benefit of the respective reperfusion therapies when administered very early. We found no reports of tenecteplase administration in CRAO. Conclusions: In 2020, nonarteritic CRAO patients should theoretically receive the same thrombolytic therapies, in the same time window, as patients with acute cerebral ischemia. Eye stroke and teleeye stroke code encounters must include an expert ophthalmologic evaluation to confirm the correct diagnosis and to evaluate for ocular signs that may help guide IV tPA administration or IA management. Future research should focus on developing feasible retinal penumbra imaging studies that, similar to cerebral tissue viability or perfusion imaging, can be incorporated into the thrombolysis decision-making algorithm. [ABSTRACT FROM AUTHOR]

Background: Idiopathic intracranial hypertension (IIH) mostly affects overweight and obese women. Severe obesity is associated with poorer visual outcomes in IIH, and weight gain can precipitate IIH and increase the risk of recurrence. Conversely, weight loss can decrease intracranial pressure and is an effective IIH treatment. Therefore, accurate monitoring of weight and body mass index (BMI) is important to help guide the management of IIH patients. Our goal was to compare estimated and measured BMI among patients with presumed IIH and non-IIH controls to determine whether these vital signs should be systematically measured when evaluating patients for IIH. Methods: A retrospective chart review was performed of consecutive patients with reported and measured weight and height seen in one ophthalmology-based neuroophthalmology clinic for IIH between January 2, 2018 and September 10, 2018. Patients with IIH or presumed IIH were compared to non-IIH controls, matched according to age (±5 years), BMI (±5 kg/m2 unless $40 kg/m2), sex, and race. Patients with confirmed IIH were asked to selfreport their weight when seen in follow-up and they were weighed to compare their self-reported vs measured percent weight change. Results: We included 379 subjects (140 patients; 239 controls) among whom 75 of the IIH patients were matched to non-IIH controls. Patients with presumed or definite IIH accurately estimated their height and generally underestimated their weight by a median of 1.8 kg (4 lb), resulting in a median BMI underestimate of 0.9 kg/m2. There was no difference in BMI underestimation when comparing presumed or definite IIH patients to matched non-IIH controls while controlling for insurance status, smoking, diabetes, and vascular disease (P = 0.66). As BMI increased, all subjects underestimated their BMI more (by 0.9% per 10 measured BMI unit increase), when controlling for age, sex, and race (P, 0.003). Sixteen confirmed IIH patients were seen in follow-up. At initial neuro-ophthalmology consultation, these subjects underestimated their weight by a mean of 3.2%. At last follow-up they underestimated their weight by only 1.2% (P = 0.03). Conclusions: There was no evidence that IIH or presumed IIH patients had a different perception of their weight than non-IIH controls at initial neuro-ophthalmology consultation. Both patients and matched controls tended to underestimate their weight by the same amount, resulting in an overall BMI underestimation of approximately 1% per 10 measured BMI unit increase. Heavier subjects tended to underestimate their body weight and resultant BMI more, and IIH patients tended to estimate their weight more accurately at follow-up. Our results emphasize the need to systematically objectively measure the weight of presumed IIH patients seen in an ophthalmology clinic. [ABSTRACT FROM AUTHOR]

Background: The association between cerebrospinal fluid (CSF) leaks at the skull base and raised intracranial pressure (ICP) has been reported since the 1960s. It has been suggested that spontaneous CSF leaks might represent a variant of idiopathic intracranial hypertension (IIH). We review the evidence regarding the association between spontaneous CSF leaks and IIH, and the role of ICP in the pathophysiology of nontraumatic skull base defects. We also discuss the management of ICP in the setting of CSF leaks and IIH. Evidence Acquisition: References were identified by searches of PubMed from 1955 to September 2018 with the terms "idiopathic intracranial hypertension" and "cerebrospinal fluid leak." Additional references were identified using the terms "pseudotumor cerebri," "intracranial hypertension," "benign intracranial hypertension," and by hand search of relevant articles. Results: A CSF leak entails the egress of CSF from the subarachnoid spaces of the skull base into the surrounding cavitary structures. Striking overlaps exist regarding demographic, clinical, and radiological characteristics between IIH patients and those with spontaneous CSF leaks, suggesting that some (if not most) of these patients have IIH. However, determining whether a patient with spontaneous CSF leak may have IIH may be difficult, as signs and symptoms of raised ICP may be obviated by the leak. The pathophysiology is unknown but might stem from progressive erosion of the thin bone of the skull base by persistent pulsatile high CSF pressure. Currently, there is no consensus regarding the management of ICP after spontaneous CSF leak repair when IIH is suspected. Conclusions: IIH is becoming more widely recognized as a cause of spontaneous CSF leaks, but the causal relationship remains poorly characterized. Systematic evaluation and follow-up of patients with spontaneous CSF leaks by neuro-ophthalmologists will help clarify the relation between IIH and spontaneous CSF leaks. [ABSTRACT FROM AUTHOR]