Therapies, trends make waves in neuro-ophthalmology


Editor's note: This piece was written by Drs. Ko and McCulley on behalf of the North American Neuro-Ophthalmology Society (NANOS)

These are exciting times for neuro-ophthalmologists and our patients. We are refining existing therapies, and 2018 marked a time of revolutionary breakthroughs in the management of previously untreatable diseases. For instance, promising steps have been taken toward viral vector-delivered gene therapy for patients with Leber’s hereditary optic neuropathy.1,2

Additionally, not only has sleep apnea been identified as a probable risk factor for non-arteritic anterior ischemic optic neuropathy (NAION), its management has been shown to reduce the risk of second eye involvement.3,4

Each year, we are finding novel uses for optical coherence tomography (OCT), and 2018 was certainly no different. In addition to its well-established role in the assessment of patients with optic neuropathies, recent innovations include utilization of the ganglion cell layer thickness to estimate the potential for visual recovery in patients with optic nerve compression.5

A rapidly evolving and intriguing application is in the diagnosis and monitoring of patients with various forms of dementia.6

Central retinal artery occlusion

Best practices in the management of central retinal artery occlusion (CRAO) continues to be a topic of interest. Fueled largely by anecdotal accounts, trends are leaning toward treating CRAO with thrombolysis,7 and this perception is supported by a recent meta-analysis.8 But controversy remains and will likely persist until an adequately powered, prospective study sheds light.

In addition to these more-focused innovations, numerous diseases are being attacked from multiple angles. Management of multiple sclerosis and related demyelinating disease have improved by leaps and bounds.

For example, we are recognizing subsets of disease including patients with neuromyelitis optica (NMO) in whom antibodies directed against aquaporin-4 are detectable.9

More recently, a subgroup has been identified in whom harbor antibodies directed against myelin oligodendrocyte glycoprotein (MOG)10 aid in assigning prognosis and tailoring therapy. Moving forward, precision in our understanding of disease pathophysiology will enable development of targeted immunotherapy.

Targeted therapy

Concerning targeted therapy, one of the most impactful developments in clinical medicine is the commercial availability of therapeutically designed recombinant monoclonal antibodies. These antibodies are engineered to target specific antigens, most commonly on tumor or inflammatory cells.

The most well-known among these is rituximab. Targeting CD20, rituximab has found an invaluable role in the treatment of lymphoproliferative disease. With regard to neuro-ophthalmology, success with rituximab has been described in the treatment of Graves’ ophthalmopathy, demyelinative disease, and orbital inflammation.11

Teprotumumab, a monoclonal antibody targeting insulin-like growth factor I receptor (IGF-IR), has shown promise in reducing orbital involvement in patients with Graves’ disease. Data continue to be made available from an ongoing clinical trial, spearheaded by Raymond Douglas.12 Thanks to these efforts, in the near future we may be able to prevent the life-altering consequences of Graves’ ophthalmopathy.

Another recent breakthrough that may transform the management of giant cell arteritis (GCA) is the FDA approval of tocilizumab, which targets interleukin-6 (IL-6).

Results from a large, multicenter clinical trial demonstrated the benefits of tocilizumab as a steroid-sparing agent over prednisone alone.13 Although we are still finetuning tocilizumab’s optimal role in patients suffering ophthalmic involvement of GCA, these initial results are very promising.

Nordic research

The Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC) is a collaborative group of researchers-including neuro-ophthalmologists, biostatisticians, clinical trial experts, and a robust administrative team-who are supported by the National Eye Institute (NEI) of the National Institutes of Health (NIH). Results from a number of NORDIC-led projects are already available and a number of trials are either ongoing or about to initiate enrollment, including studies assessing treatment of NAION and idiopathic intracranial hypertension (IIH).

Advances in treatment of IIH

NORDIC’s most substantial contribution to date relates to the treatment of IIH.14-16 Results from a trial assessing the use of acetazolamide, labeled the Idiopathic Intracranial Hypertension Treatment Trial, continue to be published.

Beyond initial results demonstrating therapeutic benefits, this year an assessment of optic disc size and papilledema grade was released.17

The next phase is the Surgical IIH Treatment Trial (or SIGHT Trial). This study is designed to compare optic nerve sheath fenestration with cerebrospinal fluid (CSF) shunting. Enrollment to this multicenter trial will commence throughout the country in the near future. Information about this and other clinical trials are available at

Another advance in the treatment of IIH is transverse sinus stenting.18,19 There is a subset of patients with IIH with narrowing of the transverse sinus, detected with cerebral angiography. Within this group, in some patients’ intracranial pressure can be normalized with stenting of the transverse sinus.

Presently, we lack precision to identify which individuals will benefit. This is a very active area of interest and transverse sinus stenting is sure to play a valuable role in managing patients with IIH.

Most importantly, we have to figure how to best identify appropriate candidates.

Healthcare delivery

A final noteworthy achievement of the neuro-ophthalmology community is our contribution to healthcare delivery. No subspecialty in ophthalmology struggles more to meet patients’ demands. With financial pressures, cumbersome regulations, and the complexity of neuro-ophthalmic patients, our ability to provide optimal care to all in need is dependent on improving efficiency and expanding our workforce.

Some departments are adding depth to their neuro-ophthalmology divisions with the addition of optometrists, orthoptists, and physicians with duel training.20 Other innovations include providing remote screening via fundus photography.21,22 As healthcare delivery evolves, so, too, is neuro-ophthalmology.

In closing, the rapidly changing face of modern healthcare comes with challenges and opportunities.

The practice of neuro-ophthalmology is rising to the challenge and expanding like never before. This year has seen many exciting innovations, and many more are expected in the near future.


Timothy J. McCulley, MD
E: tmccull5@jhmi.eduDr. McCulley is vice chairman for clinical strategic planning; director, oculoplastic surgery and neuro-ophthalmology, and director, Oculoplastic (ASOPRS) Fellowship, Johns Hopkins University School of Medicine. He is a consultant to Genentech.

Melissa W. Ko, MD, FAAN, CPE
E: kom@upstate.eduDr. Ko is associate professor of neurology and ophthalmology, and medical director, Ambulatory Neurological Services and Infusion Center, SUNY Upstate Medical University, Syracuse, New York. She has no proprietary interest to declare.