Targeted antibody testing and therapy offers new options for ophthalmologists
Reviewed by Kimberly M. Winges, MD
Neuro-ophthalmology is experiencing an exciting growth in diagnostic and treatment options, especially with targeted antibody testing and therapy, according to Kimberly Winges, MD, who discussed some of the most recent available treatments in the subspecialty.
Winges is an associate professor of ophthalmology and neurology at Casey Eye Institute at Oregon Health & Science University in Portland, and assistant chief of surgery at the Veterans Administration Portland Health Care System in Oregon.
New therapies and diagnostics
Tocilizumab (Actemra, Genentech) for giant cell arteritis (GCA).
Patients with GCA now have access to the first FDA-approved treatment for the disease.
This is noteworthy because GCA is the most common form of vasculitis affecting adults over age 50, and historically, steroids with all their unfavorable adverse effects have been the only treatment.
“This drug is a sea change in GCA treatment,” Winges said.
⎯Tocilizumab is an anti–interleukin 6 receptor antibody that reduces B-cell activation, acute phase reactants, and differentiation of T-helper cells, she explained.
The approval in May 2017 was based on the results of the GiACTA trial (NCT01791153),1 in which dosing was weekly or every other week along with a 26-week prednisone taper. The regimen was superior to steroids alone.
Winges recommends tocilizumab as both a first-line therapy and second-line therapy in cases with poor high-dose steroid tolerance.
⎯Teprotumumab (Tepezza, Horizon Therapeutics) for thyroid eye disease (TED). Teprotumumab, approved by the FDA in January 2020, is the first therapy for TED.
The drug blocks the insulin-like growth factor (IGF)-1 receptor antibody of the thyroid stimulating hormone receptor/IGF-1 receptor complex and prevents fibroblast stimulation, according to Winges.
“Teprotumumab is showing promise in reducing all aspects of thyroid orbitopathy, including optic neuropathy, and not just proptosis, which was the primary outcome measure in the phase 2 and 3 clinical trials,” she explained.
The results of these promising trials have been released and there are more forthcoming that look at other features of the disease.2
⎯Test for anti–myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) antibody–associated disease (AD). Physicians faced with patients suspected of having atypical optic neuritis have a new diagnostic tool: the anti-MOG antibody test.
This can be ordered from the Mayo Clinic laboratory and other commercial laboratories and includes neuromyelitis optica (NMO) in the panel.
Some physicians may be concerned about bilateral disease, optic neuritis in the presence of obvious marked disc edema, longitudinal optic nerve enhancement on magnetic resonance images, and/or their pediatric patients.
Winges said the test is almost always performed as it can help counsel treatment and prognosis, which is more favorable in the MOGAD group than the NMO group.3
⎯Test for aquaporin-4 chloride channel antibody.4 Physicians have another diagnostic test at their fingertips when NMO is suspected.
Patients may have bilateral severe optic neuropathy with longitudinal optic nerve enhancement, longitudinal cervical spine lesions, relapsing course, or involvement of the optic chiasm and other central nervous system structures such as the area postrema. NMO is more common in women.
The test is available from Mayo Clinic and other commercial laboratories. Importantly, in this very severe disease, steroids are not the treatment choice; plasmapheresis and intravenous immunoglobulin therapies are initiated quickly in patients who have no improvement with steroids after a 5-day course or in whom an NMO diagnosis is immediately suspected based on clinical history, Winges explained.
⎯Oral megadose steroids. When treating patients with typical optic neuritis, these drugs are as efficacious as intravenous steroids. The bioequivalent dose of 1250 mg taken orally is equivalent to 1000 mg administered intravenously.
“This treatment is now acceptable based on current findings,”5 Winges said. This is especially appealing for adherent, insightful patients with no access to an infusion center.
Related: A new tool to treat TED
⎯Stroke treatment for branch retinal artery occlusion and central retinal artery occlusion(BRAO, CRAO). Winges explained that retinal artery occlusions are defined as embolic strokes based on a new classification by the American Heart Association and American Stroke Association.6
Patients should be sent to the emergency department for a stroke work-up.
“Many stroke centers will consider CRAO acute reperfusion therapies, which are being investigated in several ongoing international clinical trials,” she concluded. “It is not just steroids anymore. But when it is, we have more options. Test for MOGAD/NMO on all atypical optic neuritis patients. Remember that new retinal artery occlusions require an acute stroke work-up.”
Kimberly M. Winges, MD
This article is adapted from Winges’ presentation at the Women in Ophthalmology 2021 Summer Symposium. She has no financial interest in this subject matter.
1. Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377(4):317-328. doi:10.1056/NEJMoa1613849
2. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382(4):341-352. doi:10.1056/NEJMoa1910434
3. Chen JJ, Pittock SJ, Flanagan EP, Lennon VA, Bhatti MT. Optic neuritis in the era of biomarkers. Surv Ophthalmol. 2020;65(1):12-17. doi:10.1016/j.survophthal.2019.08.001
4. Abel A, McClelland C, Lee MS. Critical review: typical and atypical optic neuritis. Surv Ophthalmol. 2019;64(6):770-779. doi:10.1016/j.survophthal.2019.06.001
5. Morrow SA, Fraser JA, Day C, et al. Effect of treating acute optic neuritis with bioequivalent oral vs intravenous corticosteroids: a randomized clinical trial. JAMA Neurol. 2018;75(6):690-696. doi:10.1001/jamaneurol.2018.0024
6. Mac Grory B, Schrag M, Biousse V, et al; American Heart Association Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; Council on Peripheral Vascular Disease. Management of central retinal artery occlusion: a scientific statement from the American Heart Association. Stroke. 2021;52(6):e282-e94. doi:10.1161/STR.0000000000000366