Orbital granulomatosis with polyangiitis masquerading as invasive fungal sinusitis.

A 55-year-old man presented with unilateral orbital inflammation and no light perception vision. Imaging revealed infiltrative enhancement of the optic nerve, orbit, and intracranial tissue. The case was suspicious for invasive fungal disease, but ultimate workup and orbital biopsy revealed granulomatosis with polyangiitis. The patient's inflammation resolved with corticosteroid and rituximab therapy. Granulomatosis with polyangiitis is a systemic vasculitis that can mimic a number of orbital pathologies.

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.

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.

Bilateral optic neuropathy associated with lorlatinib monotherapy for ALK-positive metastatic lung adenocarcinoma.

Purpose: This report details the characteristics of a case of bilateral optic neuropathy during treatment with oral lorlatinib for ALK-positive metastatic adenocarcinoma of the lung. Observations: A 57-year-old woman with metastatic adenocarcinoma of the lung receiving treatment with lorlatinib presented to the ophthalmology urgent care with bilateral loss of vision that had progressed to no light perception over the previous 2 weeks. She was hospitalized for an extensive autoimmune, infectious, neoplastic, and paraneoplastic workup, which revealed enhancement of both optic nerves extending up to the optic chiasm and an area of restricted diffusion in the splenium of the corpus callosum on MRI. Lorlatinib was discontinued by her oncologist and she received treatment with five days of pulse-dose intravenous solumedrol as well as five days of plasmapheresis with gradual improvement in her vision. In follow-up, her vision had improved to 20/40 and 20/30. Conclusion and importance: There have been few reports describing vision loss associated with lorlatinib, an ALK/ROS1 targeted tyrosine kinase inhibitor used to treat metastatic lung adenocarcinoma. This report details the characteristics of a case of bilateral retrobulbar optic neuropathy as well as the treatment and recovery of such a case. Further exploration is needed in order to improve our understanding of the pathogenesis of this rare but potentially devastating adverse effect.

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.

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.

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.

Adduction-Induced Strain on the Optic Nerve in Primary Open Angle Glaucoma at Normal Intraocular Pressure.

PURPOSE/AIM: The optic nerve (ON) becomes taut during adduction beyond ~26° in healthy people and patients with primary open angle glaucoma (POAG), but only retracts the globe in POAG. We used magnetic resonance imaging (MRI) to investigate this difference. MATERIALS AND METHODS: MRI was obtained in 2-mm quasi-coronal planes in central gaze, and smaller (~23-25°) and larger (~30-31°) adduction and abduction in 21 controls and 12 POAG subjects whose intraocular pressure never exceeded 21 mmHg. ON cross-sections were analyzed from the globe to 10 mm posteriorly. Area centroids were used to calculate ON path lengths and changes in cross-sections to calculate elongation assuming volume conservation. RESULTS: For both groups, ON path was nearly straight (<102.5% of minimum path) in smaller adduction, with minimal further straightening in larger adduction. ON length was redundant in abduction, exceeding 103% of minimum path for both groups. For normals, the ON elongated 0.4 ± 0.5 mm from central gaze to smaller adduction, and 0.4 ± 0.5 mm further from smaller to larger adduction. For POAG subjects, the ON did not elongate on average from central gaze to smaller adduction and only 0.2 ± 0.4 mm from smaller to larger adduction (P = .045 vs normals). Both groups demonstrated minimal ON elongation not exceeding 0.25 mm from central gaze to smaller and larger abduction. The globe retracted significantly more during large adduction in POAG subjects than normals (0.6 ± 0.7 mm vs 0.2 ± 0.5 mm, P = .027), without appreciable retraction in abduction. For each mm increase in globe axial length, ON elongation in large adduction similarly increased by 0.2 mm in each group. CONCLUSIONS: The normal ON stretches to absorb force and avert globe retraction in adduction. In POAG with mild to severe visual field loss, the relatively inelastic ON tethers and retracts the globe during adduction beyond ~26°, transfering stress to the optic disc that could contribute to progressive neuropathy during repeated eye movements.

Facial numbness in the ophthalmology clinic. A portentous sign.

AIM: To report a case series of 14 patients presenting with facial numbness primarily to the ophthalmology clinic. METHODS: All patients presenting with facial numbness to the ophthalmology clinic at the University of California, Los Angeles, were reviewed for study entry between 1993 and the present. Patients with a history of trauma or surgery were excluded. RESULTS: Fourteen patients (eight females and six males) presented to the ophthalmology clinic with numbness. Nine patients (64%) presented primarily with numbness. This symptom was associated with mortality (57%) and significant morbidity. The most common cause was neoplastic pathology (n = 10, 71%), with perineural spread from squamous cell carcinoma being the most common (five cases, 36%). The remaining cases were related to infection (n = 4, 29%). CONCLUSIONS: Most of the patients presenting to our service with numbness eventually died due to their condition. Given the poor prognosis of the patients in our case series, numbness of the face may be a portentous sign and therefore warrants a thorough examination with close follow up.

Orbital Fat Volume After Treatment with Topical Prostaglandin Agonists.

Purpose: Topical prostaglandin analogs (PGAs) are common treatment for primary open-angle glaucoma (POAG) but reportedly may cause adnexal fat atrophy. We asked if patients with POAG treated with PGAs have abnormalities in orbital fat volume (OFV). Methods: We studied 23 subjects with POAG who had never experienced intraocular pressure (IOP) exceeding 21 mm Hg and were treated long term with PGAs, in comparison with 21 age-matched controls. Orbital volume, non-fat orbital tissue volume, and OFV were measured using high-resolution magnetic resonance imaging. Results: Subjects with POAG had been treated with PGAs for 39 ± 19 months (SD) and were all treated within the 4 months preceding study. In the region from trochlea to orbital apex, OFV in POAG was significantly less at 9.8 ± 1.9 mL than in the control subjects at 11.1 ± 1.3 mL (P = 0.019). However, between the globe-optic nerve junction (GONJ) and trochlea, OFV was similar in both groups. Width and cross sectional area of the bony orbit were significantly smaller in POAG than in controls (P < 0.0001). Posterior to the GONJ, the average orbital cross-sectional area was 68.2 mm2 smaller, and the orbital width averaged 1.5 mm smaller throughout the orbit, in patients with POAG than in controls. Conclusions: Patients with POAG who have been treated with PGAs have lower overall OFV than controls, but OFV in the anterior orbit is similar in both groups. Lower overall OFV in POAG may be a primary association of this disorder with a horizontally narrower bony orbit, which may be a risk factor for POAG at nonelevated IOPs.

Optic Nerve Traction During Adduction in Open Angle Glaucoma with Normal versus Elevated Intraocular Pressure.

Purpose/Aim: We used magnetic resonance imaging (MRI) to investigate effects of intraocular pressure (IOP), race, and other factors on optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in open angle glaucoma (OAG).Materials and Methods: Thirty-five patients with OAG (26 with maximal untreated IOP ≤21 mmHg, 9 with IOP >21mmHg) and 48 controls underwent axial and quasi-coronal MRI in central gaze and large (27-33°) abduction and adduction. Some underwent MRI at smaller ductions (21-28°). Effects of presence vs. absence of OAG; within OAG whether maximum IOP level was ≤21 mmHg vs. >21 mmHg; adduction angle; race; age; and gender on ON path length and globe translation were analyzed using generalized estimating equations to account for possible intereye correlations of individual subjects.Results: Average visual field mean deviation (±standard error of mean, SEM) was -8.2 ± 1.2 dB in OAG with normal IOP, and -6.1 ± 1.4 in high IOP. In central gaze, ON path in OAG was significantly more redundant than in controls but in both groups the ON became significantly and almost equally straighter in small (~21°) or large (~27°) adduction than in central gaze. With progressive adduction only, globes retracted in OAG (P < 0.005) but not in controls; this was only weakly related to globe size and not to IOP elevation. Globe retraction in adduction was significant only in OAG, and in that group was significantly greater in Asian than white patients (P < 0.02).Conclusions: Although ON tethering in adduction is normal, progressive adduction is associated with abnormal globe retraction in OAG regardless of IOP level. This phenomenon is more prominent in Asians who have OAG. Traction in adduction may cause repetitive strain injury to the ON and peripapillary sclera, thus contributing to the optic neuropathy of glaucoma independent of IOP.

Phosphene perceptions and safety of chronic visual cortex stimulation in a blind subject.

Stimulation of primary visual cortices has the potential to restore some degree of vision to blind individuals. Developing safe and reliable visual cortical prostheses requires assessment of the long-term stability, feasibility, and safety of generating stimulation-evoked perceptions.A NeuroPace responsive neurostimulation system was implanted in a blind individual with an 8-year history of bare light perception, and stimulation-evoked phosphenes were evaluated over 19 months (41 test sessions). Electrical stimulation was delivered via two four-contact subdural electrode strips implanted over the right medial occipital cortex. Current and charge thresholds for eliciting visual perception (phosphenes) were measured, as were the shape, size, location, and intensity of the phosphenes. Adverse events were also assessed.Stimulation of all contacts resulted in phosphene perception. Phosphenes appeared completely or partially in the left hemifield. Stimulation of the electrodes below the calcarine sulcus elicited phosphenes in the superior hemifield and vice versa. Changing the stimulation parameters of frequency, pulse width, and burst duration affected current thresholds for eliciting phosphenes, and increasing the amplitude or frequency of stimulation resulted in brighter perceptions. While stimulation thresholds decreased between an average of 5% and 12% after 19 months, spatial mapping of phosphenes remained consistent over time. Although no serious adverse events were observed, the subject experienced mild headaches and dizziness in three instances, symptoms that did not persist for more than a few hours and for which no clinical intervention was required.Using an off-the-shelf neurostimulator, the authors were able to reliably generate phosphenes in different areas of the visual field over 19 months with no serious adverse events, providing preliminary proof of feasibility and safety to proceed with visual epicortical prosthetic clinical trials. Moreover, they systematically explored the relationship between stimulation parameters and phosphene thresholds and discovered the direct relation of perception thresholds based on primary visual cortex (V1) neuronal population excitation thresholds.

Progression of asymptomatic optic disc swelling to non-arteritic anterior ischaemic optic neuropathy.

BACKGROUND: The time of onset of optic disc swelling in non-arteritic anterior ischaemic optic neuropathy (NAION) is not known, and it is commonly assumed to arise simultaneously with vision loss. Our goal is to report the presence and persistence of optic disc swelling without initial vision loss and its subsequent evolution to typical, symptomatic NAION. METHODS: Clinical case series of patients with optic disc swelling and normal visual acuity and visual fields at initial presentation who progressed to have vision loss typical of NAION. All subjects underwent automated perimetry, disc photography and optic coherence tomography and/or fluorescein angiography to evaluate optic nerve function and perfusion. RESULTS: Four patients were found to have sectoral or diffuse optic disc swelling without visual acuity or visual field loss; the fellow eye of all four had either current or prior NAION or a 'disc at risk' configuration. Over several weeks of clinical surveillance, each patient experienced sudden onset of visual field and/or visual acuity loss typical for NAION. CONCLUSIONS: Current treatment options for NAION once vision loss occurs are limited and may not alter the natural history of the disorder. Subjects with NAION may have disc swelling for 2-10 weeks prior to the occurrence of visual loss, and with the development of new therapeutic agents, treatment at the time of observed disc swelling could prevent vision loss from NAION.