Pediatric Neuro-Ophthalmology: Coming of Age

Editorial Pediatric Neuro-Ophthalmology: Coming of Age Grant T. Liu, MD P ediatric neuro-ophthalmology is distinct from adult neuro-ophthalmology because the examination, disorders, and treatment issues are different. The goal of this supplement is to review the most recent advances regarding the diagnosis and management of selected congenital and acquired pediatric neuro-ophthalmic disorders. Pediatric neuro-ophthalmology has come a long way. I first heard the term "pediatric neuro-ophthalmology" when I was a medical student at Columbia University in the late 1980s. A neurology resident with whom I was working proclaimed that he was going to pursue pediatric neuro-ophthalmology as a career. I did not even know it was a subspecialty-I had never heard of it, and there was no faculty member at Columbia at the time who called himself or herself a pediatric neuro-ophthalmologist. To my knowledge and for unclear reasons, however, this resident pursued another subspecialty. Toward the end of my adult neurology residency in Boston in the early 1990s, once I had committed to neuro-ophthalmology as a career, I started seeking postfellowship faculty opportunities. I truly enjoyed my pediatric neurology rotations, so I approached the chief of ophthalmology at Boston Children's Hospital to ask if there was a need for a pediatric neuro-ophthalmologist in the practice there. He said that there was no need. The discussion was very brief. Soon after that, seemingly out of the blue, Steve Galetta, MD, contacted me about working at the University of Pennsylvania in 1993, and he said my job at Penn would include seeing adults but also becoming the first on-site pediatric neuro-ophthalmologist at the adjacent Children's Hospital of Philadelphia. The chief of pediatric ophthalmology there at the time questioned the need for a pediatric neuro-ophthalmologist, but the chiefs of pediatric neurology, neurosurgery, and neuro-oncology felt otherwise. In particular, the late Dr. Peter Berman, then the chief of pediatric neurology, allayed any doubts. He said, "Grant, just get started, and the patients will be there." He was right. Today, there are over 2,000 pediatric neuro-ophthalmic visits per year at the Children's Hospital of Philadelphia. Over 2 decades, the practice became too busy for just 1 person with an increasingly larger demand for outpatient appointments and inpatient consults. I realized I needed help. So in 2015, Robert Avery, DO, who completed his fellowship at Penn in 2010, returned from Washington, DC to join me as the second pediatric neuro-ophthalmologist at the Children's Hospital of Philadelphia. Brodsky, Hamed, and Baker's book entitled, "Pediatric Neuro-ophthalmology" (1996, Springer) help solidify the subspecialty and give it legitimacy. I remember early in my career how excited I was to absorb the pearls provided in the chapters on congenital optic disc anomalies, optic disc swelling in children, and nystagmus in infancy and childhood, among many others. Michael Brodsky, MD, subsequently wrote the successful and authoritative second (2010, Springer) and third editions (2016, Springer) on his own (oh, my goodness!). Because he was one of the first widely-recognized pediatric neuro-ophthalmologists, in addition to his incredible knowledge and thoughtfulness, (and not because of his age!) many of us consider Mike Brodsky to be the elder statesman of pediatric neuroophthalmology. The timing is right for a pediatric neuro-ophthalmology supplement for the Journal of NeuroOphthalmology (JNO). Tremendous scientific and clinical advancements have been made in the conditions covered here. I asked many of my pediatric neuro-ophthalmic, neurologic, and oncologic colleagues to contribute to these reviews in their fields of expertise, and I would like to thank them Neuro-Ophthalmology Service, Division of Ophthalmology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Division of NeuroOphthalmology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; and Departments of Neurology and Ophthalmology, the Perelman School of Medicine, the University of Pennsylvania, Philadelphia, Pennsylvania. The author reports no conflicts of interest. Address correspondence to Grant T. Liu, MD, Division of Neuro-Ophthalmology, 3400 Spruce Street, Philadelphia, PA 19104; E-mail: [e-mail] Liu: J Neuro-Ophthalmol 2017; 37(Suppl): S1-S3 S1 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Editorial for their effort, time, and dedication. I would also like to thank Lanning Kline, MD for giving us the opportunity to bring the JNO readership up to date on these topics. At the October 2016 Joint American Academy of Ophthalmology (AAO)-American Academy of Pediatric Ophthalmology and Strabismus (AAPOS) Symposium entitled, "Pediatric Neuro-ophthalmology: Kids are not little adults," Gena Heidary, MD gave a wonderful presentation entitled "Neurodegenerative diseases you do not want to miss." These disorders are rare but, nonetheless, interesting for most neuro-ophthalmologists, who sometimes are called on to examine or follow children with these conditions. Dr. Kline suggested I ask Dr. Heidary to use her talk for the basis of a review on "Neuro-Ophthalmic Manifestations of Pediatric Neurodegenerative Disease." Dr. Heidary thoughtfully separates afferent from efferent neuroophthalmic abnormalities in her cases and informative tables. Her review provides much new information as she highlights not just the neuro-ophthalmic findings of these disorders but also the genetic mutations associated with them. I agree with Dr. Heidary's prediction that, "In the future, we may more actively be involved in cases where gene therapies may be available for the treatment of some of the of these disorders." In fact, the future is now, as gene therapies have already been used successfully to treat some leukodystrophies (1). In the next review, Mark Borchert, MD and colleagues provide an informative update on the latest in pediatric optic neuritis. In addition, Amy Waldman, MD, a pediatric neurologist at the Children's Hospital of Philadelphia with an expertise in pediatric demyelinating diseases, collaborated on the article. She has published extensively on pediatric optic neuritis, optical coherence tomography (OCT), and multiple sclerosis. Her influence can be seen clearly in Table 1 of the review, which outlines the spectrum of inflammatory diseases that can be associated with optic neuritis. The multitude of conditions will be new information to most neuro-ophthalmologists. While the relationship between optic neuritis and neuromyelitis optica spectrum disorders and pediatric MS is known to most neuro-ophthalmologists, entities such as recurrent optic neuritis associated with anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies and relapsing optic neuritis associated with acute disseminated encephalomyelitis are likely unfamiliar. Although assays for anti-MOG antibodies are not yet commercially available in the United States, the authors review their implications in pediatric optic neuritis and other demyelinating diseases. Over the past 20 years, there have been paradigm shifts in the approach and management of optic pathway gliomas in neurofibromatosis Type 1 (NF1). Optic pathway gliomas are now considered tumors (2). In the past, decisions to treat and responses to therapies were based primarily on radiographic size of the glioma. Today more modern management as outlined by Listernick et al (3) S2 relies more on changes in visual acuity (4,5), which is the major morbidity of these lesions. There is more collaboration between pediatric neuro-ophthalmologists, neuro-oncologists, and NF1-ologists (6). This is highlighted by the update on management of optic pathway gliomas by Peter de Blank, MD, and colleagues. In addition to recommendations for surveillance and treatment indications in patients with NF type 1 and optic pathway gliomas, new information is provided on biomarkers of vision including OCT and diffusion tensor imaging. These tools assist clinicians in the assessment of visual status in children who do not cooperate with standard visual acuity tests. There have been similar advances in pediatric pseudotumor cerebri syndrome, and Paul Phillips, MD, and Claire Sheldon, MD, provide a comprehensive review of this topic. There is new information on the cerebrospinal fluid opening pressure reference range for children (7), updated classification and diagnostic criteria (8), and of anthropometrics of children with this condition (9). Similarities and difference between adults and children, pathophysiology, MRI abnormalities, monitoring of visual function, and use of OCT also are discussed. The field of pediatric neuro-ophthalmology is thriving, and pediatric neuro-ophthalmologists are now in demand. Today, in contrast to 25 years ago, most academic pediatric ophthalmology services throughout the United States have embraced a subspecialty model. Many disorders have become too complex for general pediatric ophthalmologists to manage alone. For instance, here at the Children's Hospital of Philadelphia there are subspecialists in pediatric uveitis, medical and surgical retina, retinal genetics, oculoplastics, and neuro-ophthalmology. There are now many pediatric neuro-ophthalmologists at major medical centers throughout the country. Most, but not all, have been dually trained in both neuro-ophthalmology and either pediatric ophthalmology or pediatric neurology. Pediatric neuro-ophthalmologists also are more organized with formation of the Consortium of Pediatric Neuro-Ophthalmologists (CPNO) in 2014. Members of the CPNO meet at the annual North American NeuroOphthalmology Society (NANOS) meeting to discuss multicenter studies. Its mission statement is to promote and advance pediatric neuro-ophthalmology by 1) enhancing the ability of pediatric neuro-ophthalmologists to perform multi-center studies; 2) providing a forum for discussing research and clinical topics; and 3) creating a sense of community to those specializing in pediatric neuro-ophthalmology. Collaborative studies in pediatric pseudotumor cerebri syndrome, pediatric optic neuritis, and NF1-related optic pathway gliomas in part grew out of the CPNO. After I served as director for 2 years, Mark Borchert, MD, is now leading the group. Simmons Lessell, MD, used to have a drawing on his office wall from William Hoyt, MD, in which the latter was drawn playing a harp. To paraphrase Dr. Hoyt's accompanying Liu: J Neuro-Ophthalmol 2017; 37(Suppl): S1-S3 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Editorial message, "A pediatric neuro-ophthalmologist is like a harpist. Every orchestra needs one, just not all the time." REFERENCES 1. Penati R, Fumagalli F, Calbi V, Bernardo ME, Aiuta A. Gene therapy for lysosomal storage disorders: recent advances for metachromatic leukodystrophy and mucopolysaccaridosis I. J Inherit Metab Dis. 2017;40:543-554. 2. Liu GT, Katowitz JA, Rorke-Adams LB, Fisher MJ. Optic pathway gliomas: neoplasms, not hamartomas. JAMA Ophthalmol. 2013;131:646-650. 3. Listernick R, Ferner RE, Liu GT, Gutmann DH. Optic pathway gliomas in neurofibromatosis-1: controversies and recommendations. Ann Neurol. 2007;61:189-198. 4. Avery RA, Ferner RE, Listernick R, Fisher MJ, Gutmann DH, Liu GT. Visual acuity in children with low grade gliomas of the visual pathway: implications for patient care and clinical research. J Neurooncol. 2012;110:1-7. Liu: J Neuro-Ophthalmol 2017; 37(Suppl): S1-S3 5. Fisher MJ, Avery R, Allen J, Ardern-Holmes A, Bilaniuk L, Ferner R, Gutmann D, Listernick R, Martin S, Ullrich N, Liu GT. Functional outcomes for neurofibromatosis type 1-associated optic pathway glioma clinical trials. Neurology. 2013;81(suppl): S15-S24. 6. Avery RA, Fisher MJ, Liu GT. Optic pathway gliomas. J Neuro Ophthalmology. 2011;31:269-278. 7. Avery RA, Shah SS, Licht DJ, Seiden JA, Huh JW, Boswinkel J, Ruppe MD, Chew A, Mistry RD, Liu GT. Reference range of cerebrospinal fluid opening pressure in children undergoing diagnostic lumbar puncture. N Engl J Med. 2010;363:891-893. 8. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81:1-7. 9. Sheldon CA, Paley GL, Xiao R, Kesler A, Eyal O, Ko MW, Boisvert CJ, Avery RA, Salpietro V, Phillips PH, Heidary G, McCormack SE, Liu GT. Pediatric idiopathic intracranial hypertension: age, gender, and anthropometric features at diagnosis in a large, retrospective, multisite cohort. Ophthalmology. 2016;123:2424-2431. S3 Copyright © North American Neuro-Ophthalmology Society. 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