Outcome of Teprotumumab Treatment for Graves Orbitopathy After Multiple Attempts at Orbital Decompression Surgery

Background: Graves’ Orbitopathy, also known as Thyroid Eye Disease (TED) is a severe ocular manifestation of Graves’ Disease. It manifests as an autoantibody mediated reaction to the thyroid hormone stimulating receptor (TSH-R), these receptors are closely linked with the insulin-like growth factor-1 receptors (IGF-1R). The TSH-R antibodies play a major role in the pathogenesis of TED. The activation of the TSH-R and IGF-1R on orbital fibroblasts and adipocytes lead to IGF-1 expression. This initiates inflammation, fibroblast proliferation and accumulation of glycosaminoglycans in the orbital tissue. Treatment modalities include glucocorticoids, orbital radiation and orbital decompressions. Recent understanding of the molecular basis of TED has resulted in targeted therapy with Teprotumumab, an inhibitory monoclonal antibody against IGF-1R. There is limited literature on the outcomes of Teprotumumab use after orbital decompression surgery. Clinical Case: 43-year-old female presented with symptoms of diplopia, periorbital pain, dry eyes and tremor. Ocular exam: Vision was correctable to 20/20 in each eye, restricted motility, bilateral lid edema, lid retraction with superior scleral show and conjunctival injection. Clinical Activity Score > 4. Diagnostic tests: TSH 0.00 undetectable (N:0.5-5.0mIU/L) FT4 3.19 (N:0.7-1.9ng/dL) TSI thyroid stimulating immunoglobulin 490% of baseline (N: 130% of baseline). Diagnosis of Graves’ disease with associated orbitopathy was made. In addition to medical management for Graves’ thyroid disease she was referred to ophthalmology. She was treated with high dose steroids for 4 weeks with no resolution of symptoms. She was then referred to an oculoplastic surgeon for bilateral orbital decompressions which resulted in mild improvement in diplopia but a residual proptosis. The decision was made to treat with teprotumumab, which had recently been FDA approved. Patient reported improved symptoms without complicating enophthalmos. Review confirmed improved proptosis on Hertel Exophthalmometry. The right eye improved from 22 mm to 16 mm and the left eye from 21 mm to 17 mm (N <20.1 mm Caucasian females) with preserved visual acuity, improved lid retraction, resolved conjunctival chemosis and decreased periorbital pain after 6 doses of Teprotumumab therapy. Conclusion: Graves’ orbitopathy can result in debilitating symptoms affecting quality of life. Targeted molecular therapy such as teprotumumab is an effective treatment even after orbital decompression. Reference: Ting, M., Ezra, D.G. Teprotumumab: a disease modifying treatment for graves’ orbitopathy. Thyroid Res13, 12 (2020). https://doi.org/10.1186/s13044-020-00086-7

Gradinego’s syndrome: atypical presentation

Gradenigo’s syndrome was first described by Giuseppe Gradenigo in 1907 when he reported a triad of symptoms consisting of unilateral periorbital pain related to trigeminal nerve involvement, diplopia due to sixth cranial nerve palsy and persistent otorrhoea, associated with otitis media with petrositis. The classical syndrome related to otitis media has become very rare after the antibiotic era. Incomplete and atypical clinical features of Gradenigo’s syndrome have been described and non infectious causes may mimic this condition. We report a case of acute petrositis in a 19 year old boy with unilateral periorbital pain, diplopia (lateral rectus palsy) in the absence of ear discharge. Careful clinical history, physical examination, including neuroimaging, is necessary to make a differential diagnosis. Appropriate management requires antibiotic treatment and possible surgical intervention.

Infratrochlear neuralgia: A prospective series of seven patients treated with infratrochlear nerve blocks

Background Infratrochlear neuralgia is a recently described painful cranial neuropathy that causes pain in the internal angle of the orbit and the medial upper eyelid, the upper bridge of the nose and/or the lacrimal caruncle. We aim to present seven new cases of infratrochlear neuralgia treated with anaesthetic nerve blocks. Methods Over an 18-month period, we prospectively identified seven cases of infratrochlear neuralgia among the patients attending the Headache Unit in a tertiary hospital. Anaesthetic blocks were performed by injecting 0.5 cc of bupivacaine 0.5% at the emergence of the nerve above the internal canthus. Results All patients were women, and the mean age was 49.1 years (standard deviation, 17.9). The pain appeared at the internal angle of the orbit and/or the medial upper eyelid in six cases, and the whole territory of the infratrochlear nerve in one case. Six patients had continuous pain and one had episodes lasting 8–24 hours. All patients showed sensory disturbances within the painful area and tenderness upon palpation of the infratrochlear nerve. Nerve blocks resulted in complete and long-lasting relief in four patients and short-lasting relief in the other three patients. Conclusions Infratrochlear neuralgia should be considered among the neuralgic causes of orbital and periorbital pain. Anaesthetic blocks may assist clinicians in the diagnosis and may also be an effective therapy.

A patient with periorbital pain: A case of isolated schwannoma of the eyebrow

<p>Schwannomas rarely occur around the orbit and they commonly arise in patients between ages 20 and 70 as unilateral masses with well-defined borders and with a rather slow growth rate. There are only a few case reports with lower and upper eyelid involvement in the English-language literature. In this report, an isolated schwannoma case with eyebrow involvement on the trajectory of the supraorbital nerve in a 24-year-old male patient is presented.</p>

Chronic Cluster Headache with an Atypical Presentation and Treatment Response

The management of cluster headache (CH) may be challenging. We report a 50-year-old male with recurrent attacks of dull and severe unilateral periorbital pain, lasting 30–45 minutes, twice a day, exclusively during sleep, and accompanied by ipsilateral rhinorrhea and lacrimation. The pain switched sides within every attack. CH treatment was initiated but the patient maintained recurrence rates compatible with chronic CH, even after increasing verapamil to 460 mg/day. Afterwards we decided to add lithium (800 mg/day). With this treatment the severity and recurrence of CH substantially decreased, despite the patient’s autonomous decision to take lithium only during the acute phase of the cluster. The exclusively alternating location and the excellent response to short cycles of lithium represent two unique features of CH.

Lacrimal neuralgia: So far, a missing cranial neuralgia

Background The lacrimal nerve supplies the lacrimal gland, the lateral upper eyelid, and a small cutaneous area adjacent to the external canthus. First division trigeminal neuralgia, supraorbital/supratrochlear neuralgia, and infraorbital neuralgia have been acknowledged as neuralgic causes of pain in the forehead and periorbit. However, the lacrimal nerve has never been identified as a source of facial pain. Here we report two cases of lacrimal neuralgia. Case reports A 66-year-old woman had continuous pain in the lateral aspect of her left superior eyelid and an adjacent area of the temple since age 64. A 33-year-old woman suffered from continuous pain in a small area next to the lateral canthus of her left eye since age 25. In both patients the superoexternal edge of the orbit was tender. In addition, sensory dysfunction could be demonstrated within the painful area. Anaesthetic blockades of the lacrimal nerve with lidocaine 2% resulted in complete but short-lasting relief. Pregabalin provided a complete response in the first patient. The second patient was refractory to various oral and topical drugs and different radiofrequency procedures, but she eventually obtained partial relief with pregabalin. Conclusions Lacrimal neuralgia should be considered among the neuralgic causes of orbital and periorbital pain.