Older man referred for persistent bilateral optic disc swelling
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A 77-year-old man was referred to the neuro-ophthalmology clinic at Tufts/New England Eye Center for bilateral optic nerve swelling.
Six months prior, the patient had reportedly sought evaluation from an outside neuro-ophthalmologist due to intermittent binocular double vision and fatigue, with no other symptoms. During this assessment, the patient exhibited a positive ice test and was consequently diagnosed with ocular myasthenia gravis. He was started on pyridostigmine, which effectively managed his double vision.
Source: Omar Abu-Qamar, MD, MMSc, and Yosbelkys Martin-Paez, MD
One month later, he presented to another outside ophthalmologist, reporting gradual bilateral peripheral vision loss over the past 1.5 years. It was unclear from the patient’s history whether this had been discussed with the initial provider, and limited records were available for review. His examination at this time was notable for relatively preserved central vision, but there was bilateral optic disc edema more pronounced in the left eye and peripheral restriction on automated visual field testing (Figure 1). An extensive workup was performed, including blood tests and lumbar puncture (LP), which revealed unremarkable CBC, CMP, TSH and CSF studies. His opening pressure was 26 cm H2O. An MRI/MRV of the head and neck revealed no masses or thrombosis, but it showed a hypoplastic left transverse sinus, sigmoid sinus and left inferior jugular vein. There were no prior MRI scans available for comparison, limiting definitive conclusions on whether these findings represented a congenital variant.
Given the bilateral optic disc swelling and a borderline elevated opening pressure on LP, a diagnosis of idiopathic intracranial hypertension (IIH) was established, and treatment with acetazolamide was initiated. The patient was evaluated by neurology, which suspected that his IIH was related to starting mirtazapine just before presentation. When the patient returned for follow-up with the referring provider several months later, the presence of persistent optic disc edema prompted referral to our neuro-ophthalmology clinic.
His medical history was significant for Graves’ disease (status post radioactive iodine ablation), non-metastatic melanoma of the skin, hyperlipidemia, benign prostatic hyperplasia and depression. His ocular history was significant for ocular myasthenia gravis, bilateral chronic conjunctivitis, amblyopia in the left eye (with baseline visual acuity of 20/70) and pseudophakia of both eyes.
His medications included acetazolamide 250 mg twice daily, pyridostigmine 60 mg daily, olopatadine, preservative-free artificial tears, levothyroxine, alfuzosin, finasteride, lovastatin, aspirin and bupropion. His family history was noncontributory, and his social history was positive for occasional vaping and alcohol use.
Examination
Upon presentation to Tufts, the patient’s main complaint was persistent decreased peripheral vision in both eyes, as well as chronic bilateral redness with itchiness that had partially responded to olopatadine and artificial tears.
On examination, visual acuity was 20/30 in the right eye and 20/200 in the left eye (with no improvement with pinhole). IOP was 13 mm Hg in both eyes. The pupils were round and reactive, with a trace relative afferent pupillary defect in the left eye. He had full color vision in both eyes. He had minimal limitation in abduction bilaterally, but ocular motility was otherwise full. His sensorimotor examination further demonstrated a comitant esotropia of 12 prism diopters to 14 prism diopters at distance, with a right hypertropia worse with right gaze and upgaze. Hertel exophthalmometry was symmetric at 26 mm on both sides. Anterior segment exam was significant for trace to 1+ conjunctival injection and posterior chamber IOLs bilaterally. Posterior segment exam was notable for optic disc edema worse in the left eye with a small cup-to-disc ratio in both eyes.
Imaging
Color fundus photos of both eyes showed a nasally elevated right optic disc, 360° of elevation without obscuration of the vessels of the left optic disc and a small cup-to-disc ratio in both eyes (Figure 2). OCT of the macula was normal in both eyes (Figure 3). OCT of the optic nerve showed edema worse in the left eye with peripheral restriction in both eyes on visual fields (Figure 4). Fluorescein angiography showed disc staining of both eyes with possible late trace leakage in the left eye, as well as subtle chorioretinal folds adjacent to the right optic disc (Figure 5).
What is your diagnosis?
Optic disc swelling
In this male patient aged older than 60 years, the combination of multiple vascular risk factors, crowded optic nerves, absence of associated symptoms or typical MRI findings of elevated intracranial pressure, and lack of progression of his disc edema over several months suggested that his optic disc swelling may have been more likely attributed to nonarteritic ischemic optic neuropathy (NAION) rather than elevated intracranial pressure. However, the peripapillary chorioretinal folds noted in the right eye were atypical of NAION and can be suggestive of a compressive lesion, therefore prompting heightened concern. Despite the initial MRI report indicating no abnormalities, the images were not available for review to confirm. Consequently, a repeat MRI of the brain and orbits was ordered, acetazolamide was discontinued, and a follow-up appointment was scheduled for 3 weeks’ time.
On follow-up, the patient was subjectively and objectively stable. MRI revealed symmetric expansile appearance of the extraocular muscles with relative sparing of the tendinous insertions and associated proptosis, most compatible with thyroid eye disease (Figure 6). Further investigations were undertaken, uncovering an elevated level of thyroid stimulating antibodies at 409 (reference range, less than 140), along with significantly increased thyrotropin receptor antibodies exceeding 40 (reference range, less than 2). Thyroglobulin antibodies, T3, T4, TSH, CBC and CMP remained within normal ranges.
Upon obtaining the initial MRI scan from 5 months prior for review, similar findings were identified, further corroborating the diagnosis of thyroid eye disease (Figure 7).
Discussion
Thyroid eye disease (TED), also known as Graves’ orbitopathy, is an autoimmune condition characterized by inflammation and swelling of the orbital tissues surrounding the eyes. It commonly occurs in individuals with hyperthyroidism, particularly due to Graves’ disease. TED can lead to various ocular manifestations, including eyelid retraction, proptosis, double vision and ocular discomfort. In about 5% to 7% of all TED cases, compression of the optic nerve can occur due to the swelling of the orbital tissues, resulting in compressive optic neuropathy. This compression can lead to vision loss or visual disturbances if left untreated.
Traditional understanding of TED delineates two distinct phases: an initial active, progressive phase characterized by inflammation lasting approximately 1 to 3years, followed by an inactive fibrotic phase. Medical management has generally been reserved for active disease, and surgical management is utilized during the inactive phase. A recent exciting new shift in TED management is the introduction of teprotumumab, a monoclonal antibody that targets insulin-like growth factor-1 receptor. Teprotumumab can be used as a single therapy for the primary treatment of compressive optic neuropathy in mild cases and in conjunction with surgical decompression and/or high-dose steroids in more severe cases.
Clinical course
Our patient had a clinical activity score of 5 to 6 (eyelid swelling, eyelid erythema, conjunctival injection, chemosis and inflammation of the caruncle, decrease in visual acuity of less than one Snellen line in the left eye), indicating active inflammatory disease. After discussion with the patient and oculoplastics and neuro-ophthalmology services, it was determined that the risks associated with steroids and/or surgical decompression outweighed the benefits in this particular patient, and a shared decision was made to start teprotumumab infusion. Given the workup and findings, his prior symptoms of intermittent binocular diplopia were thought to be related to thyroid eye disease rather than ocular myasthenia, and his pyridostigmine was stopped.
After completing eight infusions of teprotumumab, the patient had significant improvement in his symptoms. At his most recent examination in November 2023, his best corrected visual acuity was 20/25 in the right eye and 20/80 in the left eye (near his baseline). He had full extraocular motility. The optic nerve swelling had resolved, and the peripheral restriction on his visual field testing had resolved (Figure 8).
Conclusion
This case underscores the importance of remaining open-minded to changing the diagnosis, especially when clinical presentations seem incongruent. It emphasizes the importance of not allowing preconceived notions or biases about a patient’s existing diagnosis to cloud judgment. Additionally, this case serves as a compelling illustration of the significant therapeutic advancements offered by teprotumumab as a stand-alone treatment for compressive optic neuropathy, even in severe cases in which the risks associated with high-dose steroids or surgery are elevated. Timely detection and intervention are paramount in preventing permanent vision loss and effectively managing the complexities associated with TED.
- References:
- Douglas RS, et al. J Neuroophthalmol. 2022;doi:10.1097/WNO.
- Jain AP, et al. Clin Exp Ophthalmol. 2021;doi:10.1111/ceo.13899.
- Kazim M, et al. Br J Ophthalmol. 2000;doi:10.1136/bjo.84.6.600.
- Rundle FF, et al. Clin Sci. 1945;5(3-4):177-194.
- For more information:
- Edited by Jonathan T. Caranfa, MD, PharmD, and Angell Shi, MD, of New England Eye Center, Tufts University School of Medicine. They can be reached at jcaranfa@tuftsmedicalcenter.org and ashi@tuftsmedicalcenter.org.
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