Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.

PURPOSE: Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. METHODS: This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. RESULTS: Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. CONCLUSIONS: Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

Unilateral Fourth Nerve Palsy due to Presumed Metastatic Melanoma.

ABSTRACT: An 81-year-old man with a history of metastatic melanoma presented with sudden onset of painless, binocular vertical diplopia. The clinical examination was consistent with a right fourth nerve palsy. An MRI of the head revealed a mass dorsal to the right tectum at the level of the inferior colliculus. An MRI just 4 months prior did not show a lesion in that location. An MRA of the head did not show an aneurysm. This is a rare case of an isolated fourth nerve palsy believed to be due to metastatic melanoma compressing the nerve along the dorsal midbrain.

Zygomatic dental implant induced orbital fracture and inferior oblique trauma.

A 51-year-old female underwent four upper zygomatic dental implants (ZI) and one upper and four lower conventional implants. Immediately postoperatively, the patient had pain and diplopia upon manual elevation of the edematous eyelid. Panoramic x-ray showed a malpositioned right upper ZI, requiring removal of the right upper ZI the following day. The patient had delayed referral to ophthalmology one month later for persistent diplopia. Computed tomography scan and magnetic resonance imaging demonstrated a right inferolateral fracture with fibrosis surrounding the inferior oblique muscle. Clinical exam showed right lower eyelid retraction, right hypotropia, and inability to elevate in adduction, consistent with a right inferior oblique paresis. Surgical exploration revealed incarceration of lid and orbital tissue into the fracture. After repositioning of the prolapsed tissue, a high-density porous polyethylene implant was placed for fracture repair. The inferior fornix was reconstructed with amniotic membrane and 5-fluorouracil was injected into the scar tissue. Six months later, the patient underwent strabismus surgery with resolution of symptoms.

Idiopathic Unilateral Enlargement of the Extraocular Muscles in an Infant.

A 6-month-old boy presented with a unilateral motility deficit of the right eye in all fields of gaze. Neuroimaging revealed unilateral enlargement of the medial, lateral, and inferior rectus muscles with sparing of the tendons. An evaluation for thyroid eye disease, idiopathic orbital inflammation, myositis, inflammatory and neoplastic infiltration of the muscle, vascular anomalies, and metastatic neuroblastoma was unrevealing. Biopsy of the muscle revealed normal architecture with an absence of inflammation, infiltration, or fibrosis. A review of the literature reveals the exceptionally rare nature of this finding. While the authors cannot rule out an atypical case of congenital euthyroid eye disease, this constellation of findings is not consistent with thyroid eye disease and may represent previously described cases of idiopathic enlargement of the extraocular muscles.

Ocular Neuromyotonia Noted after Recent Botulinum Toxin Injection for Sixth Nerve Palsy Following Resection of a Posterior Fossa Skull Base Meningioma.

A 56-year-old female complained of diplopia immediately after surgical excision of a recurrent left skull base tuberculum meningioma. She was found to have a left sixth nerve palsy, which was subsequently treated with botulinum toxin injection to the medial rectus muscle. Three months post injection, the patient had partial recovery of the sixth nerve palsy and new-onset ocular neuromyotonia.

Differentiating mild papilledema and buried optic nerve head drusen using spectral domain optical coherence tomography.

PURPOSE: To evaluate the clinical utility of spectral domain optical coherence tomography (SD-OCT) in differentiating mild papilledema from buried optic nerve head drusen (ONHD). DESIGN: Comparative case series. PARTICIPANTS: Sixteen eyes of 9 patients with ultrasound-proven buried ONHD, 12 eyes of 6 patients with less than or equal to Frisén grade 2 papilledema owing to idiopathic intracranial hypertension. Two normal fellow eyes of patients with buried ONHD were included. METHODS: A raster scan of the optic nerve and analysis of the retinal nerve fiber layer (RNFL) thickness was performed on each eye using SD-OCT. Eight eyes underwent enhanced depth imaging SD-OCT. Images were assessed qualitatively and quantitatively to identify differentiating features between buried ONHD and papilledema. Five clinicians trained with a tutorial and masked to the underlying diagnosis independently reviewed the SD-OCT images of each eye to determine the diagnosis. MAIN OUTCOME MEASURES: Differences in RNFL thickness in each quadrant between the 2 groups and diagnostic accuracy of 5 independent clinicians based on the SD-OCT images alone. RESULTS: We found no difference in RNFL thickness between buried ONHD and papilledema in any of the 4 quadrants. Diagnostic accuracy among the readers was low and ranged from 50% to 64%. The kappa coefficient of agreement among the readers was 0.35 (95% confidence interval, 0.19-0.54). CONCLUSIONS: We found that SD-OCT is not clinically reliable in differentiating buried ONHD and mild papilledema.

Ventriculoperitoneal shunt as a treatment of visual loss in idiopathic intracranial hypertension.

BACKGROUND: The aims of this study were to evaluate visual function outcomes in idiopathic intracranial hypertension (IIH) patients who underwent ventriculoperitoneal (VP) shunt for visual loss and to determine a VP shunt survival curve over time. METHODS: A retrospective medical record review was performed of all new IIH patients first evaluated at our institution who underwent VP shunt placement over a 7-year period (2004-2010). There were 2 primary outcome measures: the first being visual acuity (VA) and the second being shunt survival. Patients who received VP shunt for visual loss were included in the visual outcome analysis, and all patients who received VP shunt for any reason were included in the shunt survival analysis. RESULTS: Of the 338 new patients with IIH, 19 patients (6%) met the inclusion criteria and 17 underwent VP shunt for visual loss and 2 for headaches. Average follow-up was 21.2 months (range, 5-1,342 days). Of the 17 patients who had VP shunt for visual loss, 5 patients had optic nerve sheath fenestration (ONSF) surgery before VP shunt, and 1 patient had bilateral ONSF surgery after VP shunt. Median VA before shunt was 20/200 in the worse eye (range, 20/20 to NLP) and 20/40 in the better eye (20/20 to HM). Median VA after shunt was 20/60 in the worse eye (20/20 to lumboperitoneal) and 20/30 in the better eye (20/20 to 20/800). The improvement in VA was statistically significant in both worse eyes (P = 0.002, Wilcoxon signed-rank test) and better eyes (P = 0.028). The mean automated visual field (AVF) mean deviation (MD) of available AVFs before shunt was 223.36 dB (range, 233.38 to 27.01 dB) for the worse eye (n = 11) and 219.66 dB (230.11 to 25.91 dB) for the better eye (n = 11). Mean AVF MD deviation of available AVFs after shunt was 220.68 dB (232.13 to 23.97 dB) for the worse eye (n = 11) and 216.35 dB (232.13 to 21.00 dB) for the better eye (n = 11): this improvement was not significant (P = 0.27, P = 0.26, respectively). Independent masked record reviews by 3 neuro-ophthalmologists showed that 9 (53%) patients improved, 5 (29%) unchanged, 1 (6%) worsened, and 2 (12%) were indeterminate. Kaplan-Meier analysis showed a persistent steady decrease of functioning VP shunts over the entire period of 36 months with 80%, 65%, and 48% of VP shunts functioning without replacement, removal, or revision at 12, 24, and 36 months, respectively. CONCLUSION: VP shunts improve or stabilize most IIH patients presenting with severe progressive visual loss or those with visual loss refractive to medical treatment and ONSF. Survival analysis shows persistent decrease of functioning shunts over time.

Transient optic perineuritis as the initial presentation of central nervous system involvement by pre-B cell lymphocytic leukemia.

A 20-year-old man with a history of pre-B cell acute lymphocytic leukemia (ALL) presented with optic perineuritis of the right eye while undergoing chemotherapy. Evaluation failed to reveal an infectious or neoplastic cause, and the patient improved with oral corticosteroid treatment. He returned 10 weeks later with complete loss of vision in the right eye. Optic nerve biopsy revealed leukemic infiltration of the optic nerve, and the patient was treated for central nervous system (CNS) relapse of ALL. Transient optic perineuritis may be the initial manifestation of CNS involvement of pre-B cell ALL.

Neuro-ophthalmic manifestations of fungal disease associated with posthurricane environment.

BACKGROUND: Allergic fungal sinusitis (AFS) is thought to represent an immunologic response to exposure to dematiaceous fungi. These fungi are known to cause disease more frequently in hot and humid climates and seasons. METHODS: Three patients presented with unusual manifestations of fungal disease after exposure to environments recently affected by hurricanes. RESULTS: Two patients had AFS, 1 with gradual painless visual loss from an AFS mass extending into the suprasellar region and 1 with orbital apex syndrome. Another patient had invasive fungal disease and developed orbital apex syndrome. CONCLUSIONS: These cases underscore the importance of clinical recognition of fungal disease in patients with sinus, orbital, or skull base involvement as well as its potential for causing permanent visual loss. This report suggests a potential association between fungal disease and tropical storm exposure.

Bilateral oculomotor synkinesis following Miller Fisher syndrome.

A 64-year-old female presented with ptosis, ophthalmoplegia, ataxia, and weakness. She was diagnosed with Miller Fisher syndrome (MFS) and was treated with plasmapheresis. Six months later, she developed bilateral oculomotor synkinesis, suggesting aberrant regeneration. The pathogenesis of MFS is reviewed in light of this unusual finding.

Metastatic paraganglioma presenting as ajunctional scotoma.

PURPOSE: To report a unique case of metastatic paraganglioma presenting as a junctional scotoma. OBSERVATIONS: A 38-year-old Caucasian man with a history of abdominal paraganglioma presented with minimally blurred vision 20/25 visual acuity in the left eye. The patient was found to have a junctional scotoma upon visual field testing. Cranial MRI revealed a large peri-clival mass compressing the pre-chiasmal optic nerves and other loci of metastatic disease. Intracranial masses, including metastases, can present with a relatively intact central acuity and nonspecific visual symptoms. CONCLUSIONS AND IMPORTANCE: To the best of our knowledge, this is the first report of metastatic paraganglioma causing a junctional scotoma. In cases with junctional scotoma, careful neuro-ophthalmic assessment and imaging are of paramount importance, even in patients with excellent visual acuity.

Morning glory disc anomaly associated with moyamoya disease and pituitary stalk duplication.

Purpose: We report a case of a 10-year-old with Moring glory disc anomaly (MGDA) associated with Moyamoya disease and pituitary stalk duplication. Observations: A 10-year-old Asian child presented with decreased vision in the right eye and bilateral nystagmus. Both dilated fundus exam and magnetic resonance imaging (MRI) of the orbit confirmed MGDA of the right eye. MRI of the brain demonstrated duplication of the pituitary stalk. Magnetic resonance angiography (MRA) of the brain revealed bilateral severe narrowing (greater on the right side) of the distal supraclinoid internal carotid arteries with bilateral reconstitution at the carotid terminus and prominent collaterals, suggestive of Moyamoya disease. Conclusions: Patients with MGDA should undergo neuroimaging due to the associated central nervous system (CNS) anomalies.

Neuro-ophthalmic disease and optical coherence tomography: glaucoma look-alikes.

PURPOSE OF REVIEW: The use of optical coherence tomography (OCT)-measured retinal nerve fiber layer (RNFL) thickness in neuro-ophthalmic disease has grown since its first use in glaucoma and retinal diseases. OCT-measured RNFL in nonglaucomatous optic neuropathies shows thinning, which may mimic those seen in glaucoma. This article aims to provide insight regarding the use of OCT in nonglaucomatous optic neuropathies and sheds light on common patterns of RNFL loss in different nonglaucomatous optic neuropathies. RECENT FINDINGS: RNFL thinning is most likely to occur in the temporal peripapillary quadrant than in other quadrants in nonglaucomatous optic neuropathies. The pattern of RNFL thinning in ischemic optic neuropathy and optic nerve head drusen is more likely to mimic the pattern found in glaucoma due to the superior and inferior quadrant predilection. OCT-measured RNFL thickness in Alzheimer's disease reveals thinning superiorly and inferiorly, whereas superior and temporal thinning is seen in Parkinson's disease. The thinning observed in neurodegenerative diseases is believed to be multifactorial including causes such as axonal degeneration and retrograde degeneration. However, more studies are needed to further study these changes. SUMMARY: OCT is a valuable tool in evaluating the peripapillary RNFL in both glaucomatous and nonglaucomatous optic neuropathies. This technology may be used for both research and clinical purposes to assess disease progression in optic neuropathies and diseases that affect the central nervous system. OCT-measured RNFL thickness remains complimentary to the clinical examination skills in the evaluation of nonglaucomatous optic neuropathies.