Accuracy of Diagnostic Imaging Modalities for Classifying Pediatric Eyes as Papilledema Versus Pseudopapilledema.

PURPOSE: To identify the most accurate diagnostic imaging modality for classifying pediatric eyes as papilledema (PE) or pseudopapilledema (PPE). DESIGN: Prospective observational study. SUBJECTS: Nineteen children between the ages of 5 and 18 years were recruited. Five children (10 eyes) with PE, 11 children (19 eyes) with PPE owing to suspected buried optic disc drusen (ODD), and 3 children (6 eyes) with PPE owing to superficial ODD were included. METHODS: All subjects underwent imaging with B-scan ultrasonography, fundus photography, autofluorescence, fluorescein angiography (FA), optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL), and volumetric OCT scans through the optic nerve head with standard spectral-domain (SD OCT) and enhanced depth imaging (EDI OCT) settings. Images were read by 3 masked neuro-ophthalmologists, and the final image interpretation was based on 2 of 3 reads. Image interpretations were compared with clinical diagnosis to calculate accuracy and misinterpretation rates of each imaging modality. MAIN OUTCOME MEASURES: Accuracy of each imaging technique for classifying eyes as PE or PPE, and misinterpretation rates of each imaging modality for PE and PPE. RESULTS: Fluorescein angiography had the highest accuracy (97%, 34 of 35 eyes, 95% confidence interval 92%-100%) for classifying an eye as PE or PPE. FA of eyes with PE showed leakage of the optic nerve, whereas eyes with suspected buried ODD demonstrated no hyperfluorescence, and eyes with superficial ODD showed nodular staining. Other modalities had substantial likelihood (30%-70%) of misinterpretation of PE as PPE. CONCLUSIONS: The best imaging technique for correctly classifying pediatric eyes as PPE or PE is FA. Other imaging modalities, if used in isolation, are more likely to lead to misinterpretation of PE as PPE, which could potentially result in failure to identify a life-threatening disorder causing elevated intracranial pressure and papilledema.

The 14th Hoyt Lecture: Ischemic Optic Neuropathy: The Evolving Profile, 1966-2015.

Since the first English language description by Miller and Smith in 1966 of ischemic optic neuropathy as a distinct ophthalmic syndrome, a long series of studies has refined the clinical profile to what we consider to be accurate today. From the specifics of pathogenesis to the clinical appearance to the effect of therapy, the basic tenets of diagnosis and management have evolved over 5 decades. What we thought we knew about the following topics has changed: location of vasculopathy; incidence; age at onset; optic disc appearance; risk factors for development; natural history; rate of fellow eye involvement; ischemia as an all-or-none phenomenon; and treatment. A look back at these discoveries shows both how far we have come and how far we have to go in managing this disorder.

Trauma-Associated Leber Hereditary Optic Neuropathy.

A 19-year-old man developed visual loss in the left eye 1 day following a martial arts kick to the head. Vision worsened over a week, when visual loss was noted in the right eye without further trauma. The fundus was initially normal, but visual field testing showed temporal depression right eye with diffuse depression left eye, and traumatic chiasmopathy was suspected. Magnetic resonance imaging (MRI) of the brain demonstrated an enlarged chiasm with intrinsic signal abnormality, but no enhancement. Treatment with intravenous corticosteroids and hyperbaric oxygen therapy did not result in visual improvement. Ancillary testing for atypical optic neuritis was negative, but testing for LHON was positive for the 11778 mutation. This case raises the question of trauma as a precipitating factor for LHON and illustrates the rare occurrence of intrinsic signal abnormalities of the chiasm in this disorder.

Aggressive Low-Grade Optic Nerve Glioma in Adults.

Primary optic nerve gliomas are most commonly benign pilocytic astrocytomas (World Health Organization [WHO] Grade I) occurring in childhood and following an indolent course. Malignant optic gliomas occur in adulthood and follow an extremely aggressive course, with rapid infiltration of the chiasm, blindness, and death typically within months. A third category of optic glioma, occurring in adulthood, histopathologically benign (WHO Grade I-II) but following an aggressive course, has been rarely reported. The authors describe clinical and histopathologic features of clinically aggressive but histopathologically benign optic nerve gliomas of adulthood. Retrospective review of cases of biopsy-proven optic nerve glioma in the neuro-ophthalmology division of the Jules Stein Eye Institute from 1990 to 2011 was carried out. Cases following an aggressive course were selected for review of clinical, neuroradiologic, and histopathologic features. Three cases were selected for detailed study. Ages ranged from 31 to 45 years. All were initially diagnosed with optic nerve inflammation or benign neoplasm based on clinical and neuroradiologic features, but all suffered neuroradiologic extension and rapid deterioration of vision in the affected eye to no light perception over 3-8 weeks. Optic nerve biopsies were undertaken for the suspicion of malignancy. Features ranged from WHO Grade I (pilocytic astrocytoma, ganglioglioma) in two cases, to WHO Grade II in one case (diffuse astrocytoma, histopathologically benign, but associated with aggressive features such as high p53 [13-21%] and Ki-67 [40%]). The diffuse astrocytoma case subsequently developed extensive intracranial extension suspicious for malignant transformation. These findings indicate that benign optic nerve glioma in adults may be initially misdiagnosed as inflammation, be clinically aggressive, and require excision to prevent further intracranial involvement.

Managing idiopathic intracranial hypertension in the eye clinic.

Idiopathic intracranial hypertension (IIH) is a neuro-ophthalmological condition characterised by a raised intracranial pressure and papilloedema that causes disabling headaches. The main risk factors of female sex and living with obesity have been known for some time, however the knowledge of the underlying pathophysiology is evolving. Papilloedema can impact the visual function, and the majority of people are offered acetazolamide. Those with sight threatening disease need urgent management, though there is little high quality evidence to recommend any particular surgical intervention. Headache treatment is an unmet clinical need and simple medication overuse advice has the potential to reduce the chronification of migraine-like headaches. IIH is emerging as a systemic metabolic disease distinct from people living with obesity alone. While weight loss is the main stay of disease modifying therapy this is challenging to access and many healthcare professionals that manage the condition have no formal training or accessible pathways for weight management. The aim of this "how to do it" article is to present the latest advances in knowledge of IIH that we pragmatically included in routine clinical care for people living with the condition.

Nonarteritic anterior ischemic optic neuropathy and obstructive sleep apnea.

BACKGROUND: To evaluate the obstructive sleep apnea syndrome (OSAS) in patients with nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: We recruited 27 patients with NAION and 27 age-matched and sex-matched controls who also were similar for systemic risk factors such as diabetes mellitus, hypertension, and hypercholesterolemia. All patients and controls underwent overnight polysomnography for the diagnosis of OSAS and calculation of apnea-hypopnea index (AHI). RESULTS: Patients and controls were statistically similar in terms of age, sex, gender, smoking, systemic risk factors, neck circumference, and body mass index. The subjects with AHI ≥ 20 were accepted as OSAS. Fifteen of 27 patients (55.6%) with NAION and 6 of 27 controls (22.2%) had OSAS (P < 0.05). CONCLUSION: The prevalence of OSAS was higher in patients with NAION, and the difference between patient and control groups was statistically significant (P < 0.05). This result supports prior series suggesting the association between NAION and OSAS.

Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks.

PURPOSE: To evaluate the effectiveness of plasma exchange (PLEX) for optic neuritis (ON). METHODS: We conducted an international multicenter retrospective study evaluating the outcomes of ON following PLEX. Outcomes were compared to raw data from the Optic Neuritis Treatment Trial (ONTT) using a matched subset. RESULTS: A total of 395 ON attack treated with PLEX from 317 patients were evaluated. The median age was 37 years (range 9-75), and 71% were female. Causes of ON included multiple sclerosis (108), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) (92), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) (75), seronegative-NMOSD (34), idiopathic (83), and other (3). Median time from onset of vision loss to PLEX was 2.6 weeks (interquartile range [IQR], 1.4-4.0). Median visual acuity (VA) at the time of PLEX was count fingers (IQR, 20/200-hand motion), and median final VA was 20/25 (IQR, 20/20-20/60) with no differences among etiologies except MOGAD-ON, which had better outcomes. In 81 (20.5%) ON attacks, the final VA was 20/200 or worse. Patients with poor outcomes were older (P = .002), had worse VA at the time of PLEX (P < .001), and longer delay to PLEX (P < .001). In comparison with the ONTT subset with severe corticosteroid-unresponsive ON, a final VA of worse than 20/40 occurred in 6 of 50 (12%) PLEX-treated ON vs 7 of 19 (37%) from the ONTT treated with intravenous methylprednisolone without PLEX (P = .04). CONCLUSION: Most ON attacks improved with PLEX, and outcomes were better than attacks with similar severity in the ONTT. The presence of severe vision loss at nadir, older age, and longer delay to PLEX predicted a worse outcome whereas MOGAD-ON had a more favorable prognosis. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Fluorescein angiographic identification of optic disc drusen with and without optic disc edema.

BACKGROUND: The fluorescein angiographic criteria for differentiating optic disc drusen (ODD) from optic disc edema have been unclear. We designed a study to identify distinguishing angiographic features of each and to apply them to cases where both drusen and edema were present. METHODS: A computer search was performed for cases evaluated in a university academic neuro-ophthalmology consultative practice and coded as ODD; all cases were reviewed, and those with fluorescein angiography were selected for further study. Cases were classified as either buried or surface ODD. Ten cases with papilledema were selected for comparison. Eight cases of coexistent drusen and edema were identified. Autofluorescence, early leakage, early blockage, early and late nodular staining, late peripapillary staining, and late leakage were tabulated. RESULTS: Two hundred sixteen cases of ODD were identified; 62 (116 eyes) had adequate fluorescein angiography for study. Twenty-three eyes were classified as surface ODD; 90% demonstrated early nodular staining of the disc, with late nodular staining in 90% and late circumferential peripapillary staining in 22%; autofluorescence was visible in 93% with preinjection photography. Eighty-three eyes were classified as buried ODD; 25% demonstrated early nodular staining, with late nodular staining in 29% and late circumferential peripapillary staining in 80%; autofluorescence was visible in 12% of those with preinjection photography. In 9 eyes, buried ODD were present with superimposed true edema. In these eyes, early dye leakage, late nodular hyperfluorescence, and late leakage were present. CONCLUSION: Early and late fluorescein angiographic features reliably distinguish ODD from edema and may be particularly useful when the conditions coexist.

Details and outcomes of a large cohort of MOG-IgG associated optic neuritis.

BACKGROUND: The goal of this study was to examine the temporal relationship of eye pain to visual loss and investigate whether timing of steroid treatment affects the rate and extent of visual recovery in optic neuritis (ON) from MOG-IgG associated disease (MOGAD) in a large cohort of MOGAD patients with ON. METHODS: This is a multicenter, retrospective cohort study of consecutive MOGAD patients with ON attacks seen from 2017 to 2021 fulfilling the following criteria: (1) clinical history of ON; (2) MOG-IgG seropositivity. ON attacks were evaluated for presence/duration of eye pain, nadir of vision loss, time to intravenous methylprednisolone (IVMP) treatment, time to recovery, and final visual outcomes. RESULTS: There were 107 patients with 140 attacks treated with IVMP and details on timing of treatment and outcomes. Eye pain was present in 125/140 (89%) attacks with pain onset a median of 3 days (range, 0 to 20) prior to vision loss. Among 46 ON attacks treated with IVMP within 2 days of onset of vision loss, median time to recovery was 4 days (range, 0 to 103) compared to 15 days (range, 0 to 365) in 94 ON attacks treated after 2 days (p = 0.004). Those treated within 2 days had less severe VA loss at time of treatment (median LogMAR VA 0.48, range, 0.1 to 3) compared to those treated after 2 days (median LogMAR VA 1.7, range, 0 to 3; p < 0.001), and were more likely to have a VA outcome of 20/40 or better (98% vs 83%, p = 0.01). After adjustment for the initial VA at time of treatment, the differences in final VA were no longer significantly different (p = 0.14). In addition, some patients were documented to recover without steroid treatment. CONCLUSION: This study suggests that pain precedes vision loss in the majority of ON attacks and early steroids may lead to better outcomes in MOG-IgG ON, but some patients can recover without steroid treatment. Prospective randomized clinical trials are required to confirm these findings.

OCT retinal nerve fiber layer thickness differentiates acute optic neuritis from MOG antibody-associated disease and Multiple Sclerosis: RNFL thickening in acute optic neuritis from MOGAD vs MS.

BACKGROUND: Optic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities. METHODS: This was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS. RESULTS: Sixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range [IQR]: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93-113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17-105) and 7.5 µm (IQR: 1-18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening. CONCLUSION: OCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials.

Incidence of nonarteritic anterior ischemic optic neuropathy: increased risk among diabetic patients.

OBJECTIVE: Previous studies have identified a higher prevalence of diabetes mellitus (DM) among patient cohorts with nonarteritic anterior ischemic optic neuropathy (NAION). We sought to determine the development of incident NAION among a group of newly diagnosed patients with DM and to estimate the incidence of NAION among the elderly. DESIGN: Medicare 5% database study. PARTICIPANTS: A total of 25 515 patients with DM and an equal number of age- and gender-matched nondiabetic patients. METHODS: Query of Medicare 5% claims files identified patients with a new diagnosis of DM in 1994. A randomly selected control group was created using 1-to-1 propensity score matching. Patients with a diagnosis of giant cell arteritis, preexisting DM, and age 68 years or older or >95 years were excluded. Patients with DM and controls were followed for the development of NAION over the following 4745 days. MAIN OUTCOME MEASURES: Incidence of NAION among patients with and without DM. RESULTS: In each group, 85% were white, 11% were black, and 4% were other race. Patients were aged 76.4 years, and 40% were male. Mean follow-up was 7.6 years. In the diabetes group, 188 individuals developed NAION (0.7%) compared with 131 individuals (0.5%; P < 0.01) in the control group. In unadjusted Cox regression analysis, having DM was associated with a 43% increased risk (hazard ratio [HR]: 1.431; 95% confidence interval [CI], 1.145-1.789) of developing NAION. After adjusting for other covariates, the risk of developing NAION among individuals with DM was reduced to 40% (HR 1.397; 95% CI, 1.115-1.750). Male gender increased an individual's risk of developing NAION by 32% (HR 1.319; 95% CI, 1.052-1.654). No other covariate was statistically significantly associated with developing NAION. The annual incidence of NAION was 82 per 100 000 persons. CONCLUSIONS: Diabetes mellitus significantly increased the risk of the diagnosis NAION. The incidence of NAION among patients aged more than 67 years may be higher than previously reported.

Bitemporal visual field defects in ethambutol-induced optic neuropathy.

BACKGROUND: Ethambutol-induced optic neuropathy is well documented and most frequently associated with central or cecocentral scotomas. We designed a study to characterize the subset of patients who exhibit bitemporal visual field defects. METHODS: A computer search was performed for patients evaluated in a university academic neuro-ophthalmology consultative practice to identify those with the diagnosis of ethambutol-induced optic neuropathy. Clinical features were tabulated, including dose and duration of ethambutol use, time to onset of visual loss, initial and follow-up visual acuities, automated perimetry, optic disc appearance, and MRI features. Assessments for bitemporal visual field defect with alignment on vertical midline and for visual improvement after discontinuing ethambutol were performed. RESULTS: Nineteen cases of ethambutol-induced optic neuropathy were identified; All but 2 eyes demonstrated visual field defects worse in the temporal fields, most with margination along the vertical midline with superimposed central or cecocentral scotomas. Six cases (12 eyes) showed bitemporal defects with such margination without superimposed scotomas. Median time to onset of visual loss was 6.0 months. Visual improvement occurred (of 17 cases with data available) by at least 3 Snellen lines in 17 of 34 eyes (50%); mean visual acuity improvement was 3.74 lines (median, 3.0). Visual improvement by at least 3.0 decibels (dB) mean deviation (MD) on automated perimetry occurred in 27 of 34 eyes (79%); mean improvement in MD was 7.82 dB (median, 7.86). Median follow-up was 8.0 months. None had MRI abnormality in the chiasmal region. CONCLUSION: Bitemporal visual field defects are common in ethambutol-induced optic neuropathy. The pattern may mimic chiasmal compression, and neuroimaging is required. It may reflect susceptibility to toxicity of chiasmal crossing fibers.