Journal of Neuro-Ophthalmology, June 2009, Volume 29, Issue 2

Letters to the Editor

LETTERS TO THE EDITOR Cerebral Blindness After Scorpion Sting A 40-year-old woman was stung by a scorpion on her left foot. Sharp burning pain at the bite site was followed by a high-grade fever, severe breathlessness, oliguria, and altered sensorium over a period of hours. She was rushed in an unconscious state to a critical care center where blood pressure was 90/60, and she was diagnosed with acute pulmonary edema, myocarditis, and acute renal failure (venom-induced multiorgan failure). After endotracheal intubation, she received low-dose aspirin, enalapril, and supplemental intravenous fluids. Eight hours later, on recovery of consciousness, she reported poor vision in both eyes. On examination 1 week later, visual acuity was light perception in both eyes. Anterior segments were unremarkable, including pupillary reactions. A dilated fundus examination was normal in both eyes. Limb ataxia, dysdiadochokinesis, poor tandem walking, and staccato speech could be elicited. Otherwise the findings from neurological examination appeared to be normal. Brain MRI revealed restricted diffusion in the medial occipital (Fig. 1) and occipitotemporal lobes and cerebel-lum bilaterally. Results of a coagulation profile, C3 and C4 complement, homocysteine, protein C and S, VDRL, anti-nuclear antibody (ANA), and antiphospholipid antibody were negative. Cerebrospinal fluid analysis and a color Doppler study of both carotid and vertebral arteries showed normal results. A diagnosis of cerebral and cerebellar infarction was made. No direct treatment occurred. Over 10 days, there was gradual improvement so that the patient was able to walk without support. At the 6-month follow up, visual acuity was light perception in both eyes, the only neurologic deficit. Scorpion bites affect the central nervous system in three ways: altered consciousness, seizures, and infarc-tions (1). Cerebral and/or cerebellar infarctions have been reported (2-7), with numerous mechanisms advanced to explain them: 1) an acute rise in blood pressure during the autonomic storm that ruptures unprotected or diseased vessels (2); 2) toxic myocarditis that precipitates arrhythmias that give rise to embolic stroke (2); 3) hypercoagulability (3); 4) disseminated intravascular coagulation (4); 5) vasculitis caused by venom (5); and 6) hypotension caused by myocarditis, parasympathetic overactivity, and dehydration (6). Bilateral optic neuropathy (6), transient ophthalmo-plegia (8), transient blindness (9), and myelopathy (10) FIG. 1. Diffusion brain MRI performed 10 days after the patient reported poor vision in both eyes shows restricted diffusion (high signal) in the medial occipital lobes bi-laterally, consistent with infarction. have been documented. We believe that this is the first description of persistent (and severe) cerebral visual loss after a scorpion bite. We cannot be certain of the mechanism, although hypotension seems likely. Sabyasachi Sengupta, DO Praveen Dhanapal, MBBS Ravilla D. Ravindran, MS, DO Nirmala Devi, DO Department of Neuro-Ophthalmology Aravind Eye Hospital and Post Graduate Institute of Ophthalmology Pondicherry, India [e-mail] REFERENCES 1. Amitai I, Mann G, Katzir Z, et al. Convulsions following a black scorpion (Buthus judaicus) sting. Isr J Med Sci 1981;17: 1083-4. 2. Nagaraja D, Taly AB, Naik R, et al. Scorpion sting: a rare cause of stroke in the young. NIMHANS J 1996;14:89-92. 3. Jain MK, Indurkar M, Kastwar Y et al. Myocarditis and multiple cerebral and cerebellar infarction following scorpion sting. J Assoc Physicians India 2006;54:491-2. 154 J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Letters to the Editor J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 4. Kochar DK, Singh P, Sharma BV et al. Scorpion envenoma-tion causing hemiparesis. J Assoc Physicians India 2002;50:606-7. 5. Chelliah T, Rajendran M, Daniel MK, et al. Stroke following scorpion sting. J Assoc Physicians India 1993;41:310. 6. Thacker AK, Lai R, Misra M. Scorpion bite and multiple cerebral infarcts. Neurol India 2002;50:100-2. 7. Gadwalkar SR, Bushan S, Pramod K, et al. Bilateral cerebellar infarction: a rare complication of scorpion sting. J Assoc Physicians India 2006;54:581-3. 8. Sadeghian H. Transient ophthalmoplegia following envenoma-tion by the scorpion Mesobuthus eupeus. Neurology 2003;60:346-7. 9. Roussel L. Scorpionism complicated by transient blindness: apropos of a case (in French). Med Trop (Mars) 1986;46:409-11. 10. Bharani AK, Sepaha GC. Myelopathy after scorpion sting. Arch Neurol 1984;41:1130. Atypical Central Serous Chorioretinopathy With Peripapillary Subretinal Fluid Suggesting an Optic Neuropathy I recently examined a patient with atypical features of central serous chorioretinopathy (CSC) (1) extending to the peripapillary region that mimicked the fundus findings of an optic neuropathy. A 43-year-old man presented with distorted vision in his left eye noted upon awakening that morning. He described the area of distorted vision as being slightly temporal to the center of fixation. He denied recent illness, pain on eye movements, photophobia, constitutional symp-toms, or injuries to the eye. Past medical history was unremarkable. Past ocular history was significant for moderate myopia and a well-healed left upper lid laceration from a distant injury. He took no prescription medications, including no corticosteroid formulations, and only occasionally consumed alcohol or used tobacco products. Family history was noncontributory. Uncorrected visual acuity was 20/20 in the right eye and 20/60 in the left eye. The patient had been emmetropic in the past. On this examination, visual acuity improved to 20/20 in the left eye with +1.25 sph, indicating a new hyperopic shift. Ishihara plates were correctly identified by both eyes. However, mild red desaruration was reported in the left eye. The patient reported mild micropsia with the left eye, and Amsler grid testing confirmed vertical metamorphopsia just temporal to fixation. Confrontation visual fields were full. Intraocular pressures were 16 mm Hg in both eyes. Pupils were of equal size and constricted briskly to direct light without a relative afferent pupil defect (RAPD). Extraocular movements and alignment were normal, as was biomicroscopic examination of the anterior ocular segment. Ophthalmoscopy of the right eye disclosed faint retinal pigment epithelium (RPE) mottling within the fovea as the only abnormality. In the left eye, there were foveal pigmentary alterations and subretinal fluid. The optic disc margins were blurred without pallor or hemorrhage. There was circumferential subretinal fluid around the optic disc (Fig. 1A). OCT of the left macula and peripapillary region revealed fluid under the neurosensory retina (Fig. 1B). There was no retinal thickening. Humphrey visual field 24-2 was normal in the right eye and revealed mild paracentral depression temporally in the left eye. Fluorescein angiography in the left eye revealed four pinpoint foci of hyperfluorescence at the level of the RPE exhibiting increasing leakage through the later phases of the angiogram. The optic nerve margins were blurred but there was no hyperfluorescence or leakage from the optic disc. There was no pooling of dye within the subretinal space around the optic nerve (Fig. 2). FIG. 1. Fundus photograph (A) of the left eye demonstrates optic nerve edema with a cuff of subretinal fluid surrounding the optic nerve. The macula demonstrates pigmentary alterations and evidence of subneurosensory fluid accumulation. A 6-mm horizontal optical coherence tomography (OCT) scan (B) demonstrates subretinal fluid adjacent to the optic nerve as well as in the macular region (asterisk). 155 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 Letters to the Editor encountered in optic neuropathy, may also be reported in CSC, as in this patient. David Johnson, MD Palmetto Retina Center West Columbia, South Carolina [e-mail] REFERENCES 1. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology 2002;109: 1834-7. 2. Brodsky MC. Central serous papillopathy. Br J Ophthalmol 1999; 83:878. Papilledema Caused by a Thoracic Schwannoma Increased intracranial pressure rarely occurs with spinal tumors at any level but is most common with upper cervical tumors (1). There has been no report of papilledema attributed to a thoracic schwannoma. A 54-year-old man had headaches and papilledema without other signs of nervous system dysfunction. Lumbar puncture revealed an opening pressure of 440 mm water, a protein level of 210 mg/dL, and a mild pleocytosis. Brain CT and MRI showed no abnormalities. Accordingly, we performed MRI of the spinal cord which disclosed a T2-3 intraspinal tumor (Fig. 1). Surgical removal disclosed a schwannoma. One month after the operation, there was no headache, papilledema, or neurologic deficit. The lumbar puncture was not repeated. The five previously reported cases (2-6) of intra-spinal schwannomas/neuromas and papilledema have included tumors of the cauda equina, cervical spine, and lumbar spine, but not thoracic spine. FIG. 2. Late-phase fluorescein angiography demonstrates areas of pinpoint hyperfluorescence without marked optic disc hyperfluorescence. Examination 2 months later was unchanged in the right eye. In the left eye, visual acuity had improved to 20/50, and the hyperopia and most of the subretinal fluid had disappeared. A creamy yellow-white subretinal lesion was now present immediately above the fovea. My patient exhibited CSC with subretinal fluid around the optic disc, a rarely reported set of findings in CSC. There was no evidence of optic nerve dysfunction as color vision and pupillary reactions were normal. No optic pit or optic nerve head drusen (ONHD) were seen by ophthalmoscopy, OCT, or fluorescein angiography with autofluorescence. Multiple simultaneous pinpoint leaks on fluorescein angiography are unusual in acute CSC but are not unusual in the chronic severe form of CSC called diffuse retinal pigment epitheliopathy Although multiple pinpoint leaks can also occur in Harada disease, leukemic infiltration, hypertensive retinopathy, and various inflammatory con-ditions, but there was no clinical support for these entities in our patient. Brodsky (2) described a single case labeled as central serous papillopathy. He proposed that the neurosensory detachment emanated from a discrete area of capillary leakage within a nonexcavated optic disc. Ours is an atypical case of CSC with submacular retinal edema and peripapillary edema that mimicked optic disc edema. Admitting that extension of subretinal fluid to the peripapillary area is unusual in CSC, the complaints of metamorphopsia and micropsia, in the absence of a relative afferent pupil defect, identified a retinal origin of this condition. The complaint of red desaruration, so often FIG. 1. Postcontrast T1 axial spine MRI at the T2-3 level shows an avidly enhancing intradural extramedullary mass {arrow) and displacement of the spinal cord (arrowhead). 156 © 2009 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Letters to the Editor J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 The pathogenesis of intracranial pressure elevation caused by spinal schwannomas is uncertain. It has been suggested that they may secrete protein kinase, which evokes synthesis of increased protein or that the protein represents a tumor breakdown product that interferes with absorption of cerebrospinal fluid (CSF) (7). Venous stasis caused by tumor compression of spinal or medullary venous plexuses producing an unfavorable transarachnoid villous hydrostatic pressure is another proposed mechanism that could lead to transudation of substances and further elevation of protein (8). Subarachnoid hemorrhage is described in about one-quarter of patients with spinal tumors and could be respon-sible for papilledema (9). Blockage of the CSF outflow by spinal arachnoid adhesions can also cause raised intracranial pressure (10). The spinal canal, acting as an elastic reservoir for CSF, is thought to be important in maintenance of a constant intracranial volume. By compromising this system, spinal tumors may reduce the capacity of this reservoir (11). Comprehensive spine imaging should be a part of the evaluation of a patient with papilledema who has normal brain imaging, especially if spinal fluid protein is elevated and even if there are no clinical manifestations of a spinal tumor. Xiao-jun Wu, MD Huai-rui Chen, MD Ju-xiang Chen, MD Yi-cheng Lu, MD Wei Huang, MD Department of Neurosurgery Changzheng Hospital Shanghai, People's Republic of China [e-mail] REFERENCES 1. Winn HR. Youmans Neurological Surgery. 5th ed. Philadelphia: Saunders Elsevier; 2004. 2. Guigou S, Mercie M, Blanc JL, et al. Bilateral papilledema as the manifestation of schwannoma of the cauda equina (in French). J Fr Ophtalmol 2006;29:312-8. 3. Niwa J, Suetake K, Okuyama T, et al. Cauda equina neurinoma associated with intracranial hypertension-case report (in Japanese). No To Shinkei 1991;43:1151-5. 4. Koyama T, Hanakita J, Ishikawa J, et al. Thoraco-lumbar spinal tumor asso-ciated with papilledema (in Japanese). No Shinkei Geka 1977;5:1171-80. 5. Feldmann E, Bromfield E, Navia B, et al. Hydrocephalic dementia and spinal cord tumor, report of a case and review of the literature. Arch Neurol 1986;43:714-8. 6. Sugaya M, Noguchi M, Tsutsumi Y. Neurinoma of the cauda equina associated with normal pressure hydrocephalus (in Japanese). No To Shinkei 1993;45:871-5. 7. Gardner WJ, Spitler DK, Whitten C. Increased intracranial pressure caused by increased protein content in the cerebrospinal fluid: an explanation of papilledema in certain cases of small intracranial and intraspinal tumors, and in the Guillain Barre syndrome. N Engl J Med 1954;250:932-6. 8. Beduschi A, Culumella F, Papo I. Ependimomi della cauda con stasi papillare. Chirurgia (Milano) 1955;10:310. 9. Schaltenbrand G Normal and pathological physiology of the cerebrospinal fluid circulation. Lancet 1953;1:805-8. 10. Schijman E, Zuccaro G, Monges JA. Spinal tumors and hydroceph-alus. Childs Brain 1981;8:401-5. 11. Martins AN, Wiley JK, Meyers PW. Dynamics of cerebrospinal fluid and the spinal dura mater. J Neurol Neurosurg Psychiatry 1972;35: 468-73. Anterior Ischemic Optic Neuropathy After Strabismus Surgery We report a case of nonarteritic anterior ischemic optic neuropathy (NAION) in a healthy young woman after strabismus surgery. A 26-year-old woman with no medical history underwent uneventful left medial rectus recession and lateral rectus resection for a long-standing esotropia under general anesthesia. Preoperatively, visual acuity had been 20/20 in the right eye and 20/200 in the left eye (amblyopia). Thirteen days postoperatively, she noticed loss of vision superiorly in the left eye on awakening without any other symptoms. On our examination the next day, visual acuity was 20/20 in the right eye and 20/400 in the left eye. She had a superior nerve fiber bundle (altitudinal) visual field defect on confrontation, a left relative afferent pupillary defect, and mild left optic disc swelling, mainly inferiorly (Fig. 1). The right optic disc had a normal appearance. Both discs had a cup-to-disc ratio of 0.1. All other aspects of the ophthalmic examination were normal. Results of standard laboratory tests, including a full blood cell count, serum electrolytes, erythrocyte sedimen-tation rate, C-reactive protein, thyroid function, blood glucose, and anti-nuclear, anti-mitochondrial, anti-smooth muscle, and anti-parietal cell antibodies, were normal. MRI of the brain and orbits was unremarkable. Four weeks later, visual acuity in the left eye had returned to its baseline level of 20/200, but the altitudinal FIG. 1. Fundus photography performed 1 day after onset of visual field loss shows left optic disc swelling. 157 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. the optic neuropathy and strabismus surgery were necessarily related. O. A. R. Mahroo, MB, BChir, PhD C. J. Hammond, MB, BChir, MD, FRCOphth West Kent Eye Centre Princess Royal University Hospital Farnborough Common Orpington, UK [e-mail] REFERENCES 1. McCulley TJ, Lam BL, Feuer WJ. Nonarteritic anterior ischemic optic neuropathy and surgery of the anterior segment: temporal relationship analysis. Am J Ophthalmol 2003;136:1171-1172. 2. Taban M, Lewis H, Lee MS. Nonarteritic anterior ischemic optic neuropathy and 'visual field defects' following vitrectomy: could they be related? Graefes Arch Clin Exp Ophthalmol 2007;245:600-605. 3. Taban M, Sharma MC, Lee MS. Anterior ischemic optic neuropathy after uncomplicated scleral buckling surgery. Graefes Arch Clin Exp Ophthalmol 2006;244:1370-1372. 4. Lee AG, Kohnen T, Ebner R, et al. Optic neuropathy associated with laser in situ keratomileusis. J Cataract Refract Surg 2000;26:1581-1584. 5. Retout A, Charlin JF, Brasseur G, et al. Amaurosis during surgery of strabismus: Apropos of a case. Bull Soc Ophtalmol Fr 1989;89:247-249. 6. Perez-Santonja JJ, Bueno JL, Meza J, et al. Ischemic optic neuropathy after intraocular lens implantation to correct high myopia in a phakic patient. J Cataract Refract Surg 1993;19:651-654. Transient Corneal Edema and Left Hemisphere Dysfunction in Pearson Syndrome Pearson syndrome is a rare mitochondrial disorder of infancy manifested by sideroblastic anemia, pancytopenia, exocrine pancreatic insufficiency, and variable involvement of the kidneys and liver (1). Large deletions in the mitochondrial genome lead to derangement of oxidative metabolism and a decreased mitochondrial energy supply (2). The neurologic manifestations include hypotonia, developmental delay, ataxia, and tremor (3). There are no reported ophthalmic findings. Patients who survive infancy may later develop Kearns-Sayre syndrome (KSS) (4). Persistent corneal edema attributed to endothelial dysfunction has been reported in KSS (3,5,6) and in chronic progressive external ophthalmoplegia (CPEO) (7), but transient corneal edema has not been reported in any mitochondrial disorder. We recently examined a 3-year-old girl with Pearson syndrome who developed transient corneal edema in conjunction with transient left cerebral hemispheric dysfunction manifesting as left gaze deviation and right hemiparesis. Such phenomena have not been reported previously in Pearson syndrome. Pearson syndrome was diagnosed in the patient at 12 months of age after she presented with transfusion- FIG. 2. Visual field examination performed 4 weeks after the onset of visual field loss shows a superior nerve fiber bundle defect in the field of the left eye. FIG. 3. Visual field examination performed 7 months after the onset of field loss shows minimal improvement. field defect persisted (Fig. 2). A diagnosis of left NAION was made. Six months later, field testing showed a persistent defect with some improvement (Fig. 3). NAION has been reported after anterior segment (mainly cataract) surgery (1), vitrectomy (2), scleral buckling surgery (3), and post-LASIK (4). We have found no reports of NAION occurring either immediately or after an interval following strabismus surgery, although a case of posterior ischemic optic neuropathy has been reported (5). Our patient had no risk factors for NAION apart from a low cup-to-disc ratio, and her youth makes her an unlikely candidate for spontaneous NAION. The ages of patients reported with NAION occurring at an interval after ocular surgery range from 48 to 94 (2,4). A case has been reported after intraocular lens implantation in a 33-year-old woman, but this occurred immediately after surgery rather than after an interval (6). The delayed onset of symptoms in our young patient raises the possibility of an inflammatory etiology. However, the lack of pain and normal MRI scan suggest that optic neuritis was unlikely. Given our patient's left amblyopia, we cannot exclude preexisting structural anomalies that might have increased her susceptibility to NAION. Also, from one case, we cannot conclude that 158 © 2009 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 Letters to the Editor Letters to the Editor J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 dependent sideroblastic anemia. Testing revealed a large mitochondrial DNA deletion. She later developed pancre-atic insufficiency and Fanconi renal disease. At 3 years and 9 months of age she was admitted for severe sepsis due to Salmonella infection. Before this admission, she had had no known neurologic abnormal-ities. A normal ophthalmologic examination with a pediatric ophthalmologist had occurred 1 month before admission. She required intubation, pressor support, and chest compressions for episodes of cardiac arrest. After extubation, she exhibited lingering reduced consciousness, left gaze deviation, and right hemiparesis. She failed to respond to verbal stimuli. A right extensor plantar reflex was present. Her eyes were fully deviated to the left and did not cross the midline to command, visual stimuli, or the oculocephalic maneuver. Both corneas were cloudy. Results of dilated fundus examination were unremarkable. Brain MRI obtained during this episode showed diffuse parenchymal volume loss but was otherwise unremarkable. MRI spectroscopy was not performed. Electroencephalography showed diffuse slowing but no epileptiform activity. The hemiparesis, gaze deviation, and corneal edema had resolved within 1 week. The patient was discharged in her baseline state. Stroke-like manifestations are well documented in many mitochondrial disorders, most notably the condition called mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) (8), but not in Pearson syndrome. Reversible corneal edema has not been described in any mitochondrial disorder. We presume that in our patient this ocular manifestation, together with transient cerebral hemi-spheric dysfunction, were related to an exacerbation of impaired mitochondrial function triggered by the sepsis (9) Lee et al (3) described a 3-year-old girl with Pearson syndrome who was discovered to have persistent corneal haze and early retinitis pigmentosa in conjunction with acute pancreatitis. She died 4 months later without autopsy. Chang et al (5) reported the histopathologic results on the post-mortem cornea of a patient with KSS who died at age 27 and had had persistent corneal edema since age 4. It showed edema of the epithelium with areas of bullous separation, thickening of Descemet's membrane, and absence of the endothelium and Bowman's membrane. Boonstra et al (6) reported stromal and epithelial corneal edema by biomicroscopy as the initial sign of KSS in a 6-year-old boy. At age 14, biomicroscopic examination showed endothelial edema as well. Nakagawa et al (10) described improvement of corneal edema in an 11-year-old boy with KSS during treatment with antioxidants. Brain MRI performed during stroke-like episodes in MELAS typically shows transient restricted diffusion pre-dominantly affecting gray matter (11), a feature not seen in our patient. It is possible that a later MRI would have shown abnormalities. Magnetic resonance spectroscopy or positron emission tomography, reported to show abnormalities in mitochondrial disorders in which MRI appears normal might also have marked the left hemisphere dysfunction (12,13). Anna C. Momont, MD Jonathan D. Trobe, MD Kellogg Eye Center Department of Ophthalmology and Visual Sciences University of Michigan Ann Arbor, Michigan [e-mail] REFERENCES 1. Pearson HA, Lobel JS, Kocoshis SA, et al. A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction. JPediatr 1979;95:976-84. 2. Rotig A, Cormier Y Blanche S, et al. Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J Clin Invest 1990;86:1601-8. 3. Lee HF, Lee HJ, Chi CS, et al. The neurological evolution of Pearson syndrome: case report and literature review. Eur J Paediatr Neurol 2007;11:208-14. 4. Simonsz HJ, Barlocher K, Rotig A. Kearns-Sayre's syndrome developing in a boy who survived Pearson's syndrome caused by mitochondrial DNA deletion. Doc Ophthalmol 1992;82:73-9. 5. Chang TS, Johns DR, Stark WJ, et al. Corneal decompensation in mitochondrial ophthalmoplegia plus (Kearns-Sayre) syndrome: a clinicopathologic case report. Cornea 1994;13:269-73. 6. Boonstra FN, Claerhout I, Hol FA, et al. Corneal decompensation in a boy with Kearns-Sayre syndrome. Ophthalmic Genet 2002;23:247-51. 7. Colyer MH, Bower KS, Ward TP, et al. Mitochondrial myopathy presenting with segmental corneal oedema and retrocorneal membrane. Br J Ophthalmol 2007;91:696-7. 8. Bi WL, Baehring JM, Lesser RL. Evolution of brain imaging abnormalities in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. J Neuroophthalmol 2006;26:251-6. 9. Longo N Mitochondrial encephalopathy. Neurol Clin 2003;21:817-31. 10. Nakagawa E, Osari S, Yamanouchi H, et al. Long-term therapy with cytochrome c, flavin mononucleotide and thiamine diphosphate for a patient with Kearns-Sayre syndrome. Brain Dev 1996;18:68-70. 11. Saneto RP, Friedman SD, Shaw DW. Neuroimaging of mitochondrial disease. Mitochondrion 2008;8:396-413. 12. Mathews PM, Andermann F, Silver K, et al. Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial encephalomyopathies. Neurology 1993;43:2484-90. 13. Molnar MJ, Valikovics A, Molnar S, et al. Cerebral blood flow and glucose metabolism in mitochondrial disorders. Neurology 2000;55: 544-8 Another Case of Leber Hereditary Optic Neuropathy in an Octogenarian We read with interest the articles by Dagi et al (1) and Yu-Wai-Man et al (2) in this journal, which described 81- and 75-year-old patients with clinical findings and genetic testing consistent with Leber hereditary optic neuropathy (LHON). We recently examined a patient who developed slowly progressive painless vision loss in the right eye at age 81 years. He noted that the right eye stabilized after 3 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 159 J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 Letters to the Editor months. Five months later, he developed a similar decline of vision in the left eye. He had hypertension, prostate cancer, hypercholes-terolemia, depression, and essential tremor. A deceased maternal cousin "went blind" at about the age of 60 of unknown cause. The patient had stopped smoking cigarettes 46 years earlier and drank alcohol occasionally. Our examination disclosed best-corrected visual acuities of finger counting in both eyes. (Baseline visual acuities had been 20/25 in both eyes.) Both pupils constricted sluggishly and there was a 1+ afferent pupillary defect in the right eye. Fundus examination revealed pallor of the right optic disc and mild pallor of the left optic disc. The patient denied symptoms of giant cell arteritis. Brain MRI and erythrocyte sedimentation rate, C-reactive protein, angiotensin-converting enzyme, syphilis, neuro-myelitis optica IgG serology, and vitamin B12 test results were all normal. Genetic testing for LHON revealed the 11778 mutation. The present case adds to the growing number of patients with LHON of clinical onset at an advanced age (1-3). In the proper clinical context, LHON testing even among octogenarians is a reasonable consideration for diagnosis and genetic counseling. Alejandra Decanini-Mancera, MD Andrew R. Harrison, MD Michael S. Lee, MD Department of Ophthalmology University of Minnesota Minneapolis, Minnesota [e-mail] This work was supported by an unrestricted grant from Research to Prevent Blindness. REFERENCES 1. Dagi LR, Rizzo JF 3rd, Cestari DM. Leber hereditary optic neuropathy in an octogenarian. J Neuroophthalmol 2008;28:156. 2. Yu-Wai-Man P, Bateman DE, Hudson G, et al. Leber hereditary optic neuropathy presenting in a 75-year-old man. J Neuroophthalmol 2008; 28:155. 3. Shah VA, Randhawa S, Mizen T, et al. You're too old for that. Surv Ophthalmol 2008;53:403-10. Anterior Ischemic Optic Neuropathy After Intravitreal Injection of Bevacizumab Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent widely used for intravitreal treatment of neovascular and exudative ocular diseases, is generally free of complications, but lens injury, endophthalmitis, retinal detachment, subconjunctival hemorrhage, cataract progression, acute vision loss, central retinal artery occlusion, new or progressive subretinal hemorrhages, and tears of the retinal pigment epithelium have been reported (1). We describe a case of nonarteritic ischemic optic neuropathy (NAION) after intravitreal injection of bevacizumab, a complication not heretofore reported. A 72-year-old woman presented with vision loss in her right eye from exudative age-related macular degeneration (ARMD). She had had an episode of NAION 10 years earlier in the right eye. Best-corrected visual acuity was light perception in the right eye and finger counting at 1 m in the left eye. An afferent pupillary defect was present in the right eye. Intraocular pressures were 12 mmHg in both eyes. Slit-lamp examination was unremarkable except for a nuclear cataract in both eyes. Fundus examination and retinal fluorescein angiography revealed optic disc pallor and dry ARMD in right eye and an active subfoveal choroidal neovascularization in left eye (Fig. 1). The left eye underwent an intravitreal injection of 2.5 mg/0.1 mL bevacizumab. Four weeks later, visual acuity was light perception in the right eye and finger counting at 2 m in the left eye with decreased activity of the neovascular complex. Two weeks later, she underwent an additional intravitreal injection of 2.5 mg/0.1 mL bevaci-zumab. One week after the injection, she reported visual loss in the left eye on awakening. On our examination, visual acuity was light perception in both eyes. Intraocular pressure was normal. Pupils were sluggishly reactive without afferent defect. The left optic nerve was now edematous with peripapillary hemorrhages (Fig. 2). She reported no symptoms of giant cell arteritis. Results of laboratory tests, including complete blood count, erythrocyte sedimentation rate, and serum C-reactive protein, were within the normal range. Risk factors of NAION include crowding of the optic disc, systemic hypertension, diabetes, smoking, hyperlip-idemia, and surgery (2). We propose the following possible mechanisms for NAION in our patient: 1. Impaired autoregulatory and microcirculatory mecha-nisms of optic nerve circulation due to pan-VEGF blockade. The exact mechanism responsible for blood flow autoregulation in the optic nerve remains enigmatic (3). Recent studies have shown that vascular endothelial vasoactive agents play an important role in modulating the local vascular tone and perhaps in blood flow autoregulation (3). Impaired autoregulation of the optic disc circulation by atherosclerosis, with a possible contribution from serotonin and endothelin-mediated vasospasm, may play a role in the pathogenesis of idiopathic NAION (4). Inhibition of VEGF may influence this autoregulation in the microcirculation. In addition, a sudden drop in effective VEGF concentration may be responsible for closure of normal capillaries (5). 160 © 2009 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Letters to the Editor J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 FIG. 1. Fluorescein angiography performed 14 days before intravitreal bevacizumab injection shows optic disc hypoperfusion and macular pigmentary changes in the right eye and a classic subfoveal choroidal neovascular membrane in the left eye (arrow). REFERENCES 1. Fung AE, Rosenfeld PJ, Reichel E. The International Intravitreal Bevacizumab Safety Survey: using the Internet to assess drug safety worldwide. Br J Ophthalmol 2006;90:1344-9. 2. Hayreh SS. Anterior ischemic optic neuropathy. VIII. Clinical features and pathogenesis of post-hemorrhagic amaurosis. Ophthalmology 1987;94:1488-502. 3. Hayreh SS. Blood flow in the optic nerve head and factors that may influence it. Prog Retin Eye Res 2001;20:595-624. 4. Arnold AC. Pathogenesis of nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol 2003;23:157-63. 5. Ameri H, Chader GJ, Kim JG, et al. The effects of intravitreous bevacizumab on retinal neovascular membrane and normal capillaries in rabbits. Invest Ophthalmol Vis Sci 2007;48:5708-15. 6. Tomsak RL, Render BE Anterior ischemic optic neuropathy and increased intraocular pressure. J Clin Neuroophthalmol 1989;9: 116-8. 7. Kim JE, Mantravadi Ay Hur EY, et al. Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial growth factor agents. Am J Ophthalmol 2008;146: 930^1. 8. Newman NJ, Scherer R, Langenberg P, et al. The fellow eye in NAION: report from the ischemic optic neuropathy decom-pression trial follow-up study. Am J Ophthalmol 2002;134: 317-28. 2. Transient intraocular pressure (IOP) elevation after intravitreal injection of bevacizumab. A transient increase in IOP can lead to ischemia of the optic nerve head because of a decrease in perfusion pressure (6). Elevations in IOP immediately after intravitreal injections are common (7). However, this mechanism seems less likely because NAION occurred 7 days after the injection. 3. The NAION is an incidental occurrence. The risk of fellow eye involvement in NAION is 15-24% within 5 years (8). Because our patient had an attack of NAION in right eye, she was susceptible to this event in the fellow eye. Given the widespread use of intravitreal anti-VEGF agents, a possible effect of VEGF blockade on optic nerve circulation merits further exploration. Hamid Hosseini, MD Mohammad Reza Razeghinejad, MD Poostchi Ophthalmic Research Center Shiraz University of Medical Sciences Shiraz, Iran [e-mail] FIG. 2. Fundus photography and fluorescein angiography of the left eye performed 8 days after intravitreal bevacizumab injection show disc swelling with adjacent splinter hemorrhages and blockage of the peripapillary background fluorescence. 161 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. New International Classification of Diseases (ICD-11) Needs NANOS Input We wish to invite NANOS members to contact us with their ideas about the upcoming revision of the International Classification of Diseases (ICD) (ICD-11), a project of the World Health Organization (WHO). The International Council of Ophthalmology (ICO) has formed a Task Force to work with the WHO in this revision. The ICO Task Force for ICD-11, approved to form the Topic Advisory Group (TAG) for Eye Diseases by the WHO on December 9, 2008, is presently forming work groups that will serve as the key functioning units for the review of evidence and generation of proposals. To head the work group in neuro-ophthalmology the cochairs are John Keltner, MD (Sacramento, CA) and Satoshi Kashii, MD, PhD (Osaka, Japan). The plans for ICD-11 are more extensive than those for previous revisions. The WHO intends to create a permanent Internet process involving a knowledge management and sharing portal similar to that used by the Internet encyclopedia Wikipedia. The new classifica-tion is to take advantage of modern data-processing capabilities and meet additional needs, such as those for electronic medical records. Previous classifications have not officially adopted a definition of disease. Linking ICD with standard terminologies such as the System-atized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) is one of the main aims of the revision process. We encourage readers to send comments or sug-gestions to us. Satoshi Kashii, MD, PhD Department of Ophthalmology Osaka Red Cross Hospital Osaka, Japan [e-mail] John L. Keltner, MD Sacramento, CA J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 Letters to the Editor 162 © 2009 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.