A Case of Atypical Leber Hereditary Optic Neuropathy With Slow, Symmetrical Progression Over Three Years

Letters to the Editor interferon-alpha: a case report and literature review. J Pediatr Hematol Oncol. 2010;32:579-584. 3. Cramer SL, Wei S, Merrow AC, Pressey JG. Gorham-Stout disease successfully treated with sirolimus and zoledronic acid therapy. J Pediatr Hematol Oncol. 2016;38:e129-e132. 4. Nazarian GK, Gebarski SS, Niparko JK. Cranial lymphangiomatosis causing CSF otorrhea and recurrent meningitis: CT features. J Comput Assist Tomogr. 1990;14:121-123. 5. Cushing SL, Ishak G, Perkins JA, Rubinstein JT. Gorham-Stout syndrome of the petrous apex causing chronic cerebrospinal fluid leak. Otol Neurotol. 2010;31:789-792. 6. Hernández-Marqués C, González AS, Ortega FC, Alvarez-Coca J, Cerda SS, Lechón FC, Cuadillero DA. Gorham-Stout disease and cerebrospinal fluid otorrhea. Pediatr Neurosurg. 2011;47:299-302. 7. Morimoto N, Ogiwara H, Miyazaki O, Kitamuara M, Nishina S, Nakazawa A, Maekawa T, Morota N. Gorham-Stout syndrome affecting the temporal bone with cerebrospinal fluid leakage. Int J Pediatr Otorhinolaryngol. 2013;77:1596-1600. 8. Molina EJS, Niederstadt T, Ruland V, Kayser G, Stummer W, Ewelt C, Rössler J. Cerebrospinal fluid leakage in Gorham-Stout disease due to dura mater involvement after progression of an osteolytic lesion in the thoracic spine. J Neurosurg Spine. 2014;21:956-960. A Case of Atypical Leber Hereditary Optic Neuropathy With Slow, Symmetrical Progression Over Three Years with each eye. Pupillary reactions, slit-lamp examination, intraocular pressures, and ophthalmoscopy were normal. One year later, she complained of progressive, painless vision loss in both eyes. Acuity was now 20/40 bilaterally, the patient identified 2 Ishihara color plates with each eye, kinetic perimetry demonstrated cecocentral scotomas bilaterally, and ophthalmoscopy revealed temporal pallor of both optic discs. Optical coherence tomography (OCT) showed significant thinning of the retinal nerve fiber layer (RNFL) in both eyes (Fig. 1A). Genetic testing showed an mtDNA nucleotide 11778 point mutation. Postcontrast orbital MRI was normal. Two years after the first visit, visual acuity was 20/70 bilaterally and the patient could still identify 2 Ishihara color plates with each eye. The optic discs remained pale temporarily, whereas OCT showed further RNFL thinning in both eyes. The average RNFL thickness had decreased from 54 to 49 mm in the right eye and from 56 to 46 mm in the left eye (Fig. 1B). T here have been a number of interesting letters to the Journal of Neuro-Ophthalmology dealing with Leber hereditary optic neuropathy (LHON) (1,2). We would like to add the case of a patient with LHON who experienced slow, symmetrical disease progression over 3 years. A 24-year-old Korean woman reported mildly decreased vision in both eyes over 1 year. Her medical, ocular, and neurological histories were unremarkable. She took no medications nor did she smoke or drink alcohol. Her father and sister were healthy and had no vision-related problems; however, her mother exhibited dyschromatopsia. Visual acuity in both eyes was 20/30, and the patient identified 3 Ishihara color plates FIG. 1. Optical coherence tomography shows progressive thinning of the RNFL from 1 (A) to 2 (B) years after initial presentation. RNFL, retinal nerve fiber layer. Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 419-425 421 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor Although the reason for the slow deterioration of vision in our patient is unclear, we suggest 3 possibilities. First, under metabolic conditions causing stress such as respiratory complex 1 dysfunction in LHON, the retinal ganglion cells may have been able to increase their mitochondrial copy number to compensate for insufficient ATP synthesis. Conceivably, our patient was able to upregulate her mitochondrial biogenesis against acute or subacute vision deterioration that occurs in LHON. Second, estrogens may have a protective effect against retinal ganglion cell damage in women with LHON mutations. It has been reported that LHON cybrids treated with 17b-estradiol demonstrated a significant reduction in reactive oxygen species levels and more efficient mitochondrial biogenesis (3-5). Retinal ganglion cell bodies, which are selectively damaged in patients with LHON, have a high concentration of estrogen receptors. This evidence suggests that the neuroprotective effect of estrogen may have played a role in the clinical course of our patient. Finally, we could not find any clinical or environmental factors known to trigger vision loss in our patient, so possibly this led to a slow decline in vision rather than one of abrupt onset. We are unaware of any similar reports of visual loss in patients with LHON occurring over many years. Our case emphasizes that the presentation and progression of LHON are variable, and clinicians should be aware of this clinical course. Bo Young Chun, MD, PhD Department of Ophthalmology, School of Medicine, Kyungpook National University, Daegu, Korea Department of Ophthalmology, Kyungpook National University Hospital, Daegu, Korea Brain Science & Engineering Institute, School of Medicine, Why Therapeutic Compliance in Optic Neuritis Deserves to be More Than Just a Footnote W e read with interest the Point Counter-Point by Morrow and Ko (1) discussing the use of oral corticosteroids to treat demyelinating optic neuritis. Despite their differences, both authors agreed, and we concur, that the treatment of typical optic neuritis with high-dose oral corticosteroids (at least 1,000-mg prednisone equivalents) is noninferior to intravenous methylprednisolone (IV-MP) (1,000 mg), and that there is no evidence of benefit and some evidence of risk with lower-dose corticosteroids. Both authors outlined and evaluated the relevant studies and 422 Kyungpook National University, Daegu, Korea Dai Woo Kim, MD, PhD Department of Ophthalmology, School of Medicine, Kyungpook National University, Daegu, Korea Department of Ophthalmology, Kyungpook National University Hospital, Daegu, Korea Byeong Jae Son, MD, PhD Department of Ophthalmology, Kyungpook National University Hospital, Daegu, Korea The authors report no conflicts of interest. REFERENCES 1. Ohden KL, Tang PH, Liley CC, Lee MS. Atypical Leber hereditary optic neuropathy: 18-year interval between eyes. J Neuroophthalmol. 2016;36:304-307. 2. Jorstad OK, Odegaard EM, Heimdal KR, Kerty E. Leber hereditary optic neuropathy caused by mitochondrial DNA 40663T˃C point mutation and its response to idebenone treatment. J Neuroophthalmol. 2018;38:129-131. 3. Yu-Wai-Man P. Therapeutic approaches to inherited optic neuropathies. Semin Neurol. 2015;35:578-586. 4. Pfeiffer ML, Hashemi N, Foroozan R, Lee AG. Late-onset Leber hereditary optic neuropathy. Clin Exp Ophthalmol. 2013;41:690-693. 5. Giordano C, Montopoli M, Perli E, Orlandi M, Fantin M, Ross-Cisneros FN, Caparrotta L, Martinuzzi A, Ragazzi E, Gheli A, Sadun AA, d'Amati G, Carelli V. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy. Brain. 2011;134:220-234. available evidence base, however, neither considered the crucial issue of therapeutic compliance. One major advantage of intravenous administration of any drug is that there can be little doubt that the patient is, indeed, receiving treatment. By contrast, with oral administration, unless patients take their medication in front of a witness (e.g., as is often required with methadone in the treatment of opioid dependence), drug intake cannot be guaranteed. Approximately 50% of patients do not take their medication as prescribed (2), and the likelihood of noncompliance is generally increased when there are wellknown and undesirable side effects, as is the case with corticosteroids. It is, therefore, likely that some patients prescribed oral corticosteroids may only take them initially, or at a reduced dose. The risk of noncompliance is Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 419-425 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.