| OCR Text |
Show Journal of Neuro- Ophthalmology 18( 1): 30- 31, 1998. 1998 Lippincott- Raven Publishers, Philadelphia Late- Onset Leber's Hereditary Optic Neuropathy E. Todd Ajax, M. D., and Randy Kardon, M. D., Ph. D. Progressive, sequential visual loss in the left and then right eye was reported in a 73- year- old male over three months. The presence of a family history of visual loss and the lack of other-findings in association with bilateral cecocentral scotomata led to a diagnosis of new onset Leber's hereditary optic neuropathy, confirmed by the presence of a mutation at the 11778 position. This case illustrates that Leber's hereditary optic neuropathy may manifest late in life. Leber's hereditary optic neuropathy is a well-recognized genetic disorder with several point mutations on the mitochondrial genome known to be associated with this condition ( 1- 5). The significance of some of these mutations is uncertain, but three of these mutations at positions 11778, 14484, and 3960 are pathogenic. These mutations lead to amino acid substitutions in highly conserved regions of mitochondrial protein complexes. The most common mutations result in reduced complex- 1 activity. These mutations may not cause visual symptoms until a threshold is reached through a continued decline in energy production or an exposure to Manuscript accepted 7/ 2/ 97. From the Departments of Neurology ( E. T. J.) and Ophthalmology, Division of Neuro- Ophthalmology ( R. K.), University of Iowa Hospitals and Clinics, Iowa City, Iowa, U. S. A. Address correspondence and reprint requests to Dr. R. Kardon, Department of Ophthalmology ( Pomerantz Family Pavillion), University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, U. S. A. a toxic or metabolic stress within the optic nerve. Approximately 80% of the time, the disease affects men in their 20s. Uncommonly, however, men and women may be affected past the fifth decade. We recently diagnosed Leber's optic neuropathy in a 73- year- old gentleman with a 3- month history of gradually declining vision. Initially, this began in his left eye, but his right eye was affected within a month. He noticed it when reading and looking at faces, and described it as looking through a " hazy fog." He had difficulty distinguishing colors and contrasts in fabrics. He felt that the visual loss was progressing rapidly and that his vision was declining " nearly daily." His visual acuity 2 weeks after the onset of his difficulties was 20/ 40 OD and 20/ 200 OS. Approximately a month later, his visual acuity was 20/ 100 OD and count- fingers vision OS. When he was evaluated by our neuro- ophthalmology service months after the onset of symptoms, he was able to count fingers at 6 feet OU and had central red desaturation in both eyes. Funduscopic examination demonstrated temporal pallor of the optic discs ( Fig. 1) with a cup- to- disc ratio of 0.2. There was no relative afferent pupillary defect. Bilateral cecocentral scotomas were noted on kinetic visual field testing ( Fig. 2), and a magnetic resonance image of the orbits and a fluorescein angiogram were unremarkable. He had smoked a pipe for 40 years, but denied cigarette smoking or alcohol use. There was no history of other toxic exposures or metabolic stresses. His vitamin B12, folate, and Venereal Disease Research Laboratory test levels were normal. He reported that a FIG. 1. Fundus photograph of the right optic nerve ( left) and left optic nerve ( right) on presentation showing only temporal pallor. 30 LEBER'S HEREDITARY OPTIC NEUROPATHY 31 IM ( Ml.. i- is- n _*_. .- {. I * I * * jjfL mi fun. ••• I. l l i l k l - ... ...^ ( JJS- flif FIG. 2. Right and left kinetic visual fields ( Goldmann) showing bilateral cecocentral scotomata. great- grandfather had " eye problems." His sister went blind at the age of 36, although an evaluation reported that her " peripheral vision" was intact. The visual loss was attributed to arachnoiditis, and lysis of adhesions was performed that reportedly aborted further progression. Her son also developed central visual loss at the age of 27, which was attributed to heavy alcohol use and was treated with vitamin B, 2 and multivitamins. His visual loss continued to progress, and he is now legally blind. Because of his family history and the lack of a clear cause for his visual loss, a screen for Leber's hereditary optic neuropathy was performed and revealed the presence of the 11778 mutation. We were unable to determine any coexisting metabolic or nutritional factors that may have predisposed this patient to develop optic neuropathy at this late age. However, he appears to be the oldest individual reported to have developed progressive visual failure from this mutation. Our review of the literature indicates the oldest reported patient to date was 72, with a majority of cases presenting in their 20s. This and other atypical late- onset cases are associated with a poorer prognosis for visual recovery. Our case illustrates the importance of keeping this diagnosis in mind even in the elderly population, especially in the setting of a suggestive family history and the lack of more common etiologies of optic neuropathy. Acknowledgment: R. K. is a recipient of the Research to Prevent Blindness Lew R. Wasserman Merit Award. This study was also supported by an unrestricted grant from Research to Prevent Blindness, New York, NY. REFERENCES 1. Harding AE, Sweeney MG, Govan GG, Riordan- Eva P. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am J Hum Genet 1995; 57: 77- 95. 2. Oostra RI, Bolhuis PA, Wijburg FA, Zonn- Enda G. Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome. J Med Genet 1994; 31: 280- 6. 3. Nikoskelainen EK, Huoponen K, Juvonen V, et al. Ophthalmologic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology 1996; 103: 504- 14. 4. Riordan- Eva P, Sanders MD, Govan GG, et al. The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain 1995; 118: 319- 37. 5. Zhu D, Economou EP, Antonarakis SE, Maumenee 1H. Mitochondrial DNA mutations and heteroplasmy in type I Leber hereditary optic neuropathy. Am J Med Genet 1992; 42: 173- 9. J Neuro- Ophlhalmol. Vol. IS, No. I. 1998 |
