Journal of Neuro-Ophthalmology, September 2008, Volume 28, Issue 3

Letters to the Editor

LETTERS TO THE EDITOR Positive Apraclonidine Test Within Two Weeks of Onset of Horner Syndrome Caused by Carotid Artery Dissection Horner syndrome, manifested by ipsilateral miosis, upper lid ptosis, and sometimes facial anhidrosis, is caused by disruption of sympathetic innervation to the eye and face (1). Lack of pupil dilation after instillation of cocaine, an indirect sympathomimetic (2), has been traditionally used to support a clinical diagnosis of Horner syndrome (1). However, cocaine has the disadvantages of high cost, poor dilating capability, and lack of ready availability (3). Topical 0.5% or 1% apraclonidine (Iopidine; Alcon, Fort Worth, TX) has recently been proposed as a substitute for cocaine in testing for Horner syndrome (4-12). Although apraclonidine is primarily an a2 agonist, it also has weak affinity for a1, the predominant receptor in the iris dilator muscle (13). Sympathetic denervation in Horner syndrome results in upregulation or increased sensitivity of a1 receptors (14). Topical apraclonidine dilates a sympa-thetically denervated iris but not a normally innervated iris. However, the latency between sympathetic damage and development of upregulated adrenergic iris receptors is uncertain. In previous reports, patients had long-standing Horner syndrome before the application of the apracloni-dine test (4-9,11,12). The shortest documented latency from occurrence of the lesion to a positive apraclonidine test is 1 month in a patient with ‘‘carotid stenosis'' (5). We report a patient who developed a Horner syndrome acutely from carotid artery dissection who had a positive apraclo-nidine test within 2 weeks of symptom onset. A 36-year-old man was ‘‘cracking his neck'' as a cus-tomary practice when he heard a loud popping sound in his neck. He immediately developed right-sided headache and right posterior neck pain. A coworker noted that the patient's right upper eyelid was droopy and that the right pupil was relatively small. Ten days after onset, he pre-sented to a hospital emergency room and was transferred to our care with a clinical presumption of right Horner syndrome. Head and neck computed tomographic angiog-raphy (CTA) and catheter-based carotid angiography (Fig. 1) showed tapered narrowing of the right internal carotid artery of 2.5 cm extending from the carotid artery bifurcation to the skull base in a configuration typical of dissection. We examined the patient 14 days after symptom onset. Visual acuity was 20/20 in both eyes. There was 1 mm of right upper lid ptosis with good levator function. In dim illumination, the pupils measured 2 mm on the right and 3 mm on the left with both pupils constricting adequately to direct light (Fig. 2). The anisocoria was more apparent in dim illumination. There was no relative affer-ent pupillary defect. Results for the remainder of the ophthalmic and neurologic examinations were normal. Thirty minutes after instillation of one drop of apraclonidine 0.5% in both eyes, the right pupil measured 5 mm and the left pupil measured 3 mm in dim illumination (Fig. 2). The right upper lid ptosis disappeared. Because our patient's manifestations of carotid artery dissection had such abrupt onset, we can accurately date the latency from the time of sympathetic damage to the performance of the apraclonidine test as being no more than 14 days. Apraclonidine testing in Horner syndrome has been reported to have been administered in 65 patients. The documented latency of a positive test after sympathetic damage ranges between 1 month and 10 years (4-12). The sensitivity of the apraclonidine test for Horner syndrome is still unknown. Among the patients tested with apraclonidine (using cocaine as the pharmacologic gold standard), two false-negative results have been reported FIG. 1. Right carotid catheter angiography shows tapered narrowing (arrow) of the right internal carotid artery consistent with dissection. J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 235 (5,8), and an additional three patients have shown reversal of the anisocoria only in bright illumination (6). One explanation for false-negative test results has been the unknown latency required for up-regulation of a1 receptors. The false-negative results occurred, however, in patients who had had clinical evidence of Horner syndrome for a minimum of 6 months. Wider studies will need to be performed to determine the shortest latency and the reliability of the apraclonidine test in the diagnosis of Horner syndrome. Brenda L. Bohnsack, MD, PhD Jared W. Parker, MD Kellogg Eye Center University of Michigan Ann Arbor, Michigan [e-mail] REFERENCES 1. Miller NR, Newman NJ, Biousse V, et al. Walsh and Hoyt's Clinical Neuro-Ophthalmology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2005:749-53. 2. Ritz MC, Cone EJ, Kuhar MJ. Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: a structure-activity study. Life Sci 1990;46:635-45. 3. Kardon R. Are we ready to replace cocaine with apraclonidine in the pharmacologic diagnosis of Horner syndrome. J Neuroophthalmol 2005;25:69-70. 4. Bacal D, Levy SR. The use of apraclonidine in the diagnosis of Horner syndrome in pediatric patients. Arch Ophthalmol 2004;122: 276-9. 5. Brown SM, Aouchiche R, Freedman KA. The utility of 0.5% apraclonidine in the diagnosis of Horner syndrome. Arch Ophthalmol 2003;121:1201-3. 6. Chen PL, Hsiao CH, Chen JT, et al. Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination. Am J Ophthalmol 2006;142:469-74. 7. Chen PL, Chen JT, Lu DW, et al. Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of Horner syndrome in pediatric patients. J Ocul Pharmacol Ther 2006;22:182-7. 8. Chu EA, Byrne PJ. Pharmacologic reversal of Horner's syndrome-related ptosis with apraclonidine. Ear Nose Throat J 2007;86:270, 273. 9. Freedman KA, Brown SM. Topical apraclonidine in the diagnosis of suspected Horner syndrome. J Neuroophthalmol 2005;25:83-5. 10. Garibaldi DC, Hindman HB, Grant MP, et al. Effect of 0.5% apraclonidine on ptosis in Horner syndrome. Ophthal Plast Reconstr Surg 2006;22:53-5. 11. Koc F, Kavuncu S, Kansu T, et al. The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis. Br J Ophthalmol 2005;89:1442-4. 12. Morales J, Brown SM, Abdul-Rahim AS, et al. Ocular effects of apraclonidine in Horner syndrome. Arch Ophthalmol 2000;118: 951-4. 13. Abrams DA, Robin AL, Pollack IP, et al. The safety and efficacy of topical 1% ALO 2145 (p-aminoclonidine hydrochloride) in normal volunteers. Arch Ophthalmol 1987;105:1205-7. 14. Ramsay DA. Dilute solutions of phenylephrine and pilocarpine in the diagnosis of disordered autonomic innervation of the iris: observa-tions in normal subjects, and in the syndromes of Horner and Holmes-Adie. J Neurol Sci 1986;73:125-34. Transient Anisocoria Caused by Aerosolized Ipratropium Bromide Exposure From an Ill-Fitting Face Mask Transient anisocoria caused by aerosolized ipra-tropium bromide from an ill-fitting face mask is apparently a well-described entity (1-7), but is still not immediately recognized. We report such an occurrence. A 52-year-old man with chronic obstructive pulmo-nary disease and depression was transferred to our institution for further management of a biliary leak due to laparoscopic cholecystectomy. Physical examination on admission showed a distended abdomen with absent bowel sounds. Twenty-four hours later, he developed acute hypercapnic respiratory failure that required noninvasive ventilation with bilevel positive airway pressure (BiPAP). During morning rounds, his right pupil was found to be fixed and dilated. No other abnormalities were noted on neurologic examination. Results of emergency brain CTwere normal. Further review disclosed that he had received nebulized albuterol and ipratropium bromide via a face mask that was attached FIG. 2. Our patient at 14 days after onset of right neck pain. A. Before instillation of 0.5% apraclonidine, the right pupil measures 2 mm and the left pupil measures 3 mm. B. Thirty minutes after instillation of 0.5% apraclonidine, the right pupil measures 5 mm and the left pupil measures 3 mm. 236 J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 Letters to the Editor to the noninvasive BiPAP ventilator. The BiPAP face mask was found to fit imperfectly and to leak to the right (Fig. 1). The anisocoria resolved within 24 hours after discontinuation of the ipratropium bromide and adjustment of the face mask. Anisocoria is an alarming physical sign, leading most of the time to an extensive neuroradiologic investigation to rule out life-threatening conditions such as cerebral neoplasm, expanding aneurysm, or intracranial bleeding (1,2). Atropine, scopolamine, and spray perfumes contain-ing belladonna are well known to cause pharmacologic pupillary dilation by direct or indirect contamination of the eye. Ipratropium bromide was not considered a cause of anisocoria until 1986 when Samaniego and Newman (3) described the first case. Most cases have since been de-scribed among children because of the difficulty in main-taining a properly fitted mask during delivery of respiratory treatments (4). Ipratropium bromide, which is used frequently as a bronchodilator in patients with bronchospasm, is a quater-nary amine derivative of atropine and a direct antagonist at muscarinic cholinergic receptors (5). Contamination of the eye from nebulized ipratropium bromide leads to asym-metric pupillary dilation by paralyzing the parasympathetic nerve endings. The anisocoria usually resolves within 48 hours of removal of the agent but sometimes may last up to 3 weeks (6) after the aerosolized bronchodilator is stopped. Other manifestations of ipratropium exposure include bilateral mydriasis, cycloplegia, blurred vision, dry eyes, and in rare cases, acute glaucoma (7). Failure of the dilated pupil to constrict after instillation of 1% of pilocarpine hydrochloride confirms the diagnosis. Administration of ipratropium bromide via a mask attached to a noninvasive BiPAP ventilator has become increasingly popular with the frequent use of noninvasive ventilation techniques. Therefore, the incidence of ipra-tropium bromide-induced anisocoria may increase. Edgard Wehbe, MD Smyrna Abou Antoun, MD Jany K. Moussa, MD Imad I. Nassif, MD Department of Internal Medicine University of Kansas School of Medicine-Wichita Wichita, Kansas [e-mail] REFERENCES 1. Goldstein JB, Biousse V, Newman NJ. Unilateral pharmacologic mydriasis in a patient with respiratory compromise. Arch Ophthalmol 1997;115:806. 2. Bisquerra RA, Botz GH, Nates JL. Ipratropium-bromide-induced acute anisocoria in the intensive care setting due to ill-fitting face masks. Respir Care 2005;50:1662-4. 3. Samaniego F, Newman LS. Migratory anisocoria-a novel clinical entity. Am Rev Respir Dis 1986;134:844. 4. Cabana MD, Johnson H, Lee CK, Helfaer M. Transient anisocoria secondary to nebulized ipratropium bromide. Clin Pediatr (Phila) 1998;37:445-7. 5. Lust K, Livingstone I. Nebulizer-induced anisocoria. Ann Intern Med 1998;128:327. 6. Jannun DR, Mickel SF. Anisocoria and aerosolized anticholinergics. Chest 1986;90:148-9. 7. Iosson N. Nebulizer-associated anisocoria. N Engl J Med 2006;354:e8. Optic Neuritis as the First Manifestation of Rheumatoid Arthritis Optic neuritis has been rarely reported in patients with rheumatoid arthritis (RA) and never as the initial manifestation in a patient who lacked any clinical evidence of RA until years later. We report a patient with optic neuritis as the initial presentation of RA. A 52-year-old woman without medical problems presented in 1988 to our hospital with sudden left eye visual loss for 3 weeks. Best-corrected visual acuity was 20/25 in the right eye and no light perception in the left eye. Optic disc swelling was present in the left eye. The right eye visual field was normal. Laboratory studies showed a normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. Normal results included tests for antinuclear antibodies (ANAs), rheumatoid factor (RF), C3, and C4. Orbit CT FIG. 1. Mydriatic right pupil in patient fitted with a face mask delivering aerosolized ipratropium bromide. Because the face mask was malpositioned, the agent leaked out toward the right eye. J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 237 Letters to the Editor J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 revealed no abnormalities. Despite oral corticosteroid treat-ment for presumed optic neuritis, visual acuity of the left eye did not recover. In 1995 she complained of poor vision of the right eye for 3 days. Best-corrected visual acuity was 20/200 in the right eye and no light perception in the left eye. The right optic disc was normal, and the left optic disc was pale. She read none of the Ishihara color plate. Automated perimetric examination revealed a nasal upper quadrant defect. Brain CT was normal (MRI was contraindicated because of residual bomb chips in her abdomen and mediastinum). ESR and CRP level were normal, the RF level was elevated and results for ANAwere positive, with normal levels of C3 and C4. Pulse therapy with methylprednisolone produced recovery to 20/20 and a normal visual field in the right eye. In 1999, she developed arthralgia and symmetrical swelling with morning stiffness over the proximal in-terphalangeal joints and carpal bones of both hands. Plain x-rays of the both hands showed periarticular swelling in the proximal interphalangeal joints and relatively osteo-porotic changes of carpal bones. She had an elevated RF level and a positive results for ANAs. RA was diagnosed according to the clinical classification criteria for RA (1). She began treatment for this condition. In 2006 she reported acute blurred vision of the right eye again for 3 days but no exacerbation of rheumatologic symptoms. Best-corrected visual acuity of the right eye was finger counting. No optic swelling of the right eye was found. Perimetry of the right eye revealed nerve fiber bundle defects. RF level and test results for ANAs were normal, but her test results were positive for anti-Ro and anti-La antibodies. Pulse therapy with methylprednisolone produced recovery of visual acuity in the right eye to 20/20 but both optic discs were now pale (Fig. 1) and visual field loss persisted. Optic neuropathy was first reported in RA in 1980 (2). Autopsy showed necrotizing vasculitis of the right posterior ciliary artery and lymphocytic vasculitis and perivasculitis of the left posterior ciliary artery (2). Approximately 25% of patients with RA have vasculitis with involvement in all sizes of veins and arteries on post-mortem examination (2). Occlusion of one of the posterior ciliary arteries or its branches produces ischemic optic neuropathy with a spectrum of changes that results in com-plete blindness or variable visual field defects (2). Milder optic nerve damage due to a vasculitic mechanism, char-acterized by demyelination, had a good response to pulse corticosteroid therapy (3). More severe and irreversible cases of optic neuropathy have caused axonal necrosis (3). In our patient, the first attack of optic neuropathy of the left eye resulted in blindness. Its features are atypical for optic neuritis and more typical of a severe ischemic process. In subsequent attacks affecting the right eye, however, vision did recover and corticosteroid treatment might have made a difference, perhaps by attenuating vasculitis. Particularly unusual in our patient is the fact that the manifestations of RA appeared 11 years after the first attack of optic neuropathy. We highlight this patient to emphasize that an underlying rheumatologic condition may be occult and that early treatment with corticosteroids of a presumed vasculitis may be vision-saving. Ying-Hua Chen, MD An-Guor Wang, MD Yen-Ching Lin, MD May-Yung Yen, MD Taipei Veterans General Hospital Taipei, Taiwan [e-mail] REFERENCES 1. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24. 2. Crompton JL, Iyer P, BeggMW. Vasculitis and ischemic optic neuropathy associated with rheumatoid arthritis. Aust J Ophthalmol 1980;8:219-30. 3. Giorgi D, Balacco Gabrieli C. Optic neuropathy in systemic lupus erythematosus and antiphospholipid syndrome (APS): clinical features, pathogenesis, review of the literature and proposed ophthalmological criteria for APS diagnosis. Clin Rheumatol 1999;18:124-131. FIG. 1. After bouts of optic neurop-athy in both eyes, the optic discs are pale bilaterally. 238 J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 Letters to the Editor Transient Third Cranial Nerve Palsy Caused by Sphenoid Sinus Aspergillosis We recently examined a patient who developed a nearly complete unilateral third cranial nerve palsy attrib-uted to sphenoid sinus aspergillosis. The unusual feature is that the palsy resolved spontaneously within 2 days. A 78-year-old retired teacher presented with the sudden onset of a ptotic right upper lid and diplopia for 1 day. There was no headache. He had hypertension and chronic renal impairment but no diabetes or head trauma. Vital signs were normal. Visual acuity was 20/40 in both eyes attributed to cataract. Intraocular pressures were 12 mm Hg in both eyes. In dim light, pupils measured 4.5 mm in the right eye and 3 mm in the left eye. The right pupil was not reactive to light; the left pupil was normally reactive. There was no afferent pupil defect. There was complete right upper lid ptosis and a complete deficit of adduction, supraduction, and infraduction of the right eye with normal incyclotorsion and abduction. Ductions of the left eye were normal. Findings from ophthalmoscopy and the rest of the neurological examination were normal. Although we recommended emergency neuroimag-ing, the patient insisted on later admission for personal reasons. Two days later, our examination showed complete resolution of all eye findings, but he reported brief episodes of syncope, mental confusion, and headache. Complete blood count showed a mild leukocytosis (10.6 103 cells/mL), and C-reactive protein was 1.37 mg/dL. Erythrocyte sedimentation rate was 35 mm/hr. Brain MRI showed a heterogeneous space-occupying lesion in the right sphenoid sinus and a soft tissue lesion in the basal cisterns and sylvian fissure with low signal intensity on precontrast T1 and enhancement on postcontrast T1. There were also a subdural effusion (Fig. 1). MRA demonstrated no aneurysm. Transsphenoidal endoscopic biopsy disclosed necrotic tissue with a pathologic diagnosis of aspergillosis (Fig. 2). The patient was given intravenous voriconazole for 3 weeks followed by oral fluconazole. Neurologic symptoms and the original MRI lesions eventually resolved (Fig. 1C). Transient third cranial nerve palsy occurs in oph-thalmoplegic migraine (1,2), pseudotumor cerebri (3,4), arteriovenous malformation (5), cryptococcal meningitis (6,7), basilar or posterior communicating artery aneurysm (8,9), and thiazide-induced glucose intolerance (10). It has not been reported in sphenoid sinus aspergillosis. The transient nature of our patient's third cranial nerve palsy is curious. A possible explanation is that the nerve was initially compressed by localized sphenoid inflammation; perhaps as the pathogen broke through the sphenoid bone and invaded the contiguous basal cistern, the tension of compression was released, allowing spontaneous resolution of the palsy but development of other neurologic deficits. Rong Kung Tsai, MD Department of Ophthalmology Buddhist Tzu Chi General Hospital Tzu Chi University Hualien, Taiwan [e-mail] Ming Shan He, MD Department of Ophthalmology Buddhist Tzu Chi General Hospital Tzu Chi University Hualien, Taiwan Chung Lung Cheu, MD Department of Neurosurgery Buddhist Tzu Chi General Hospital Tzu Chi University Hualien, Taiwan Min Muh Sheu, MD Department of Ophthalmology Buddhist Tzu Chi General Hospital Tzu Chi University Hualien, Taiwan FIG. 1. Pretreatment postcontrast TI axial (A) and coronal (B) MRI shows enhancing soft tissue lesions with low central signal intensity in both sylvian fissures, the prepontine cistern, and the right sphenoid sinus (A, arrow). One month after sys-temic antifungal treatment, post-contrast T1 MRI (C) demonstrates mucosal thickening with enhance-ment of the sphenoid sinus mucosa (arrow) and dural enhancement with nodularity (arrowhead). J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 239 Letters to the Editor J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 REFERENCES 1. McMillan HJ, Keene DL, Jacob P, et al. Ophthalmoplegic migraine: inflammatory neuropathy with secondary migraine? Can J Neurol Sci 2007;34:349-55. 2. Levin M,Ward TN. Ophthalmoplegic migraine. Curr Pain Headache Rep 2004;8:306-9. 3. McCammon A, Kaufman HH, Sears ES. Transient oculo-motor paralysis in pseudotumor cerebri. Neurology 1981;31: 182-4. 4. Chansoria M, Agrawal A, Ganghoriya P, et al. Pseudotumor cerebri with transient oculomotor palsy. Indian J Pediatr 2005;72: 1047-8. 5. Wu G, Agrawal A, Ghanchi FD. Transient third nerve palsy in a young patient with intracranial arteriovenous malformation. Eur J Ophthalmol 2003;13:324-7. 6. Keane JR. Intermittent third nerve palsy with cryptococcal meningitis. J Clin Neuroophthalmol 1993;13:124-6. 7. Azran MS,Waljee A, Biousse V, et al. Episodic third nerve palsy with cryptococcal meningitis. Neurology 2005;64:759-60. 8. DiMario FJ Jr, Rorke LB. Transient oculomotor nerve paresis in congenital distal basilar artery aneurysm. Pediatr Neurol 1992;8: 303-6. 9. Greenspan BN, Reeves AG,. Transient partial oculomotor nerve paresis with posterior communicating artery aneurysm: a case report. J Clin Neuroophthalmol 1990;10:56-8. 10. Miller NR, Moses H. Transient oculomotor nerve palsy: associ-ation with thiazide-induced glucose intolerance. JAMA 1978;240: 1887-8. Lateral Rectus Muscle Metastasis As the Initial Manifestation of Gastric Cancer Four weeks after developing diplopia and right lateral gaze palsy, a 49-year-old man was hospitalized for deep venous thrombosis with pulmonary embolism. Neurologic examination demonstrated orbital swelling, diplopia, and reduced abduction of the right eye. On forced duction testing, there was resistance to passive movement of the right globe. Neck examination was significant for left subclavicular and submandibular adenopathies. MRI of the brain and orbit revealed diffuse enlargement of the right lateral rectus muscle (Fig. 1A) and the muscle tendon with homogenous enhancement on postcontrast images (Fig. 1B). Upper gastrointestinal tract endoscopy demonstrated moderately to poorly differenti-ated adenocarcinoma at the gastric body. Right orbital biopsy revealed poorly differentiated carcinoma consistent with a metastasis from the gastric tumor. Despite radiotherapy, the patient died of massive gastrointestinal bleeding approximately 10 weeks after onset of symptom. Orbital metastasis is uncommon, accounting for 0.07%-4.7% among patients with malignancy (1). Discrete extraocular muscle metastases constitute only 9% of orbital metastases (2). In adults, extraocular metastases originate mostly from cutaneous melanomas and breast and lung carcinomas (2,3). Only rarely do they originate from a carcinoma of the gastrointestinal tract (4). The majority of patients with metastases to extraocular muscle not only already have a diagnosis of primary malignancy at presentation (2), but also the metastasis occurs late in the course of the systemic malignancy (2). The most frequently affected extraocular muscle is the medial rectus, followed by the lateral rectus, the superior rectus, and the inferior rectus. Bilateral extraocular muscle involvement has FIG. 2. Histopathology of the sphenoid sinus tissue shows aggregates of 45 branching hyphae with septae (inset, arrowhead ) that are 2-4 mm in width, features character-istic of aspergillosis (hematoxylin and eosin stain, original magnification: 3400). FIG. 1. A. T2 axial MRI shows hyperintensity and thickening of the right lateral rectus muscle in-cluding its tendon sheath. B. Post-contrast T1 MRI shows diffuse enhancement of right lateral rectus muscle. 240 J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 Letters to the Editor been reported in 17%of patients (2). In our patient, unilateral lateral rectus metastasis was the initial presentation of adenocarcinoma at the gastric body, extending the spectrum of metastatic diseases with a gastric source. Nizar Souayah, MD Natalia Krivitskaya Department of Neurology Huey-Jen Lee, MD Department of Neuroradiology University of Medicine and Dentistry of New Jersey Newark, New Jersey [e-mail] REFERENCES 1. Geetha N, Chandralekha B, Kumar A, et al. Carcinoma of the pancreas presenting as an orbital tumor: a case report. Am J Clin Oncol 1998;21: 532-3. 2. Lacey B, Chang W, Rootman J. Nonthyroid causes of extraocular muscle disease. Surv Ophthalmol 1999;44:187-213. 3. Capone A Jr. Slamovits TL. Discrete metastasis of solid tumors to extraocular muscles. Arch Ophthalmol 1990;108:237-43. 4. Van Gelderen WF. Gastric carcinoma metastases to extraocular muscles. J Comput Assist Tomogr 1993;17:499-500. Pupillary Autonomic Neuropathy Simulating Partial Horner Syndrome in Diabetes Mellitus and Its Reversal With Control of Blood Glucose Horner syndrome, an oculosympathetic dysfunction, which is characterized by a triad of ptosis, miosis, and anhidrosis (1-3), is a rarely reported complication of diabetes (1). We describe a patient who had anisocoria with features of a Horner syndrome as an initial mani-festation of diabetes. The anisocoria and supersensitivity to topical apraclonidine resolved with the treatment of hyperglycemia. A 45-year-old woman was referred to our clinic for a weight gain of 11 kg over the previous 6 months. She had no other symptoms and was not taking any medications. She had no history of past illnesses, trauma, operations, or hospitalizations. Because of a positive family history of diabetes, she had been having her blood glucose monitored yearly for the previous 5 years. A fasting plasma glucose (FPG) concentration had been 5.4 mmol/L (97 mg/dL) 9 months earlier. On ophthalmologic examination, there was no perceptible ptosis and no iris heterochromia. There was a 2-mm anisocoria in room light with the smaller right pupil manifesting a dilation lag in dim illumination. There was no evidence of cataract or retinopathy. There was no appreciable anhidrosis. There was a reversal of baseline anisocoria 60 minutes after bilateral conjunctival instillation of 1 drop of 0.5% apraclonidine solution, with the right pupil becoming 1 mm larger than the left pupil. Results of the neurologic examination were otherwise normal. The FPG concentration was 10.5 mmol/L (189 mg/dL), triglyceride concentration was 2.8 mmol/L (248 mg/dL), and low-density lipoprotein (LDL) cholesterol concentration was 3.1 mmol/L (120 mg/dL). Repeat FPG concentration was 9.9 mmol/L (178 mg/dL) with hemo-globin (Hb) A1c of 7.3%. Serum creatinine and urinary microalbumin concentrations were within normal limits. Results of VDRL, fluorescent treponemal antibody (FTA) absorption, and tuberculin test were all negative. MRI of the head, neck, and thorax as well as ultrasonography of the neck and mammography of both breasts, did not reveal any pathologic conditions. A diagnosis of type 2 diabetes with a right ‘‘Horner pupil'' was made. She was prescribed 1000 mg metformin twice daily and was advised to lose weight through dieting and exercise. Three months later, she had lost 10 kg; her FPG concentration was 4.9 mmol/L (89 mg/dL) and her HbA1c and lipid profile were normal. The pupils were equal in size with normal reactions to light and a near target. Retesting with apraclonidine instillation demonstrated no anisocoria; the supersensitivity was gone. Diabetic autonomic neuropathy causes loss of sym-pathetic function and is associated with increased tissue sensitivity to catecholamines. Supersensitivity to catechol-amines could be due to a postsynaptic increase in sensitivity or to decreased catecholamine uptake into sympathetic nerve endings (4-6). a-Agonist-receptor interactions are coupled through the G protein complex to phospholipase C. The latter catalyzes the hydrolysis of phosphatidylinositol biphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3). These intracellular messengers, in turn, activate further specific enzymes, culminating in catechol-amine action. Also the interaction of the G protein with the receptor affects the affinity with which the receptor binds its ligand. Moreover, the effect on binding affinity depends on whether guanosine diphosphate (GDP) or guanosine triphosphate (GTP) is bound to the G protein. In diabetes, there may be a supersensitivity to a-agonists, probably owing to high activity of phospholipase C (with an increase in DAG production), which induces alterations in the membrane a-adrenergic receptors (5). Topical apraclonidine is used for reduction of intra-ocular pressure in acute angle closure glaucoma and after J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 241 Letters to the Editor J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 yttrium-aluminum-garnet (YAG) laser therapy (7-9). In this regard, the major site of pharmacologic action of apraclonidine for reduction of aqueous production is the postjunctional a 2-receptors in the ciliary body. The drug also has a weak a 1-adrenergic effect. In Horner syndrome, sympathetic denervation induces an up-regulation of a-receptors (4-6), which also unmasks the a1 effect of apraclonidine, clinically causing pupil dilation. Apracloni-dine is thus a useful medication to confirm the clinical diagnosis of Horner syndrome regardless the site of the lesion (7-9). Anisocoria with supersensitivity to topical apraclo-nidine has not been reported as an initial sign of diabetes mellitus that disappears with appropriate regulation of blood glucose. This patient is a reminder that, particularly when ipsilateral ptosis is absent, diabetic pupillary autonomic neuropathy should be considered as a cause of these phenomena before one embarks on an imaging investigation of mass lesions in the sympathetic pathway. Gholam Reza Pishdad, MD Section of Endocrinology and Metabolism Department of Internal Medicine Shiraz University of Medical Sciences Shiraz, Iran Parisa Pishdad, MD Department of Radiology Shiraz University of Medical Sciences Shiraz, Iran Reza Pishdad Shiraz Medical School Shiraz University of Medical Sciences Shiraz, Iran [e-mail] REFERENCES 1. Smith SA, Smith SE. Bilateral Horner's syndrome: detection and occurrence. J Neurol Neurosurg Psychiatry 1999;66:48-51. 2. Kong YX, Wright G, Pesudovs K, et al. Horner syndrome. Clin Exp Optom 2007;90:336-44. 3. Martin TJ. Horner's syndrome, pseudo-Horner's syndrome, and simple anisocoria. Curr Neurol Neurosci Rep 2007;7:397-406. 4. Eichler HG, Blaschke TF, Kraemer FB, et al. Responsiveness of superficial hand veins to alpha-adrenoceptor agonists in insulin-dependent diabetic patients. Clin Sci (Lond) 1992;82:163-8. 5. Cohen RA, Tesfamariam B, Weisbrod RM, et al. Adrenergic denervation in rabbits with diabetes mellitus. Am J Physiol 1990; 259:H55-61. 6. Wald M, Borda ES, Sterin-Borda L. a-Adrenergic supersensitivity and decreased number of alpha-adrenoceptors in heart from acute diabetic rats. Can J Physiol Pharmacol 1988;66:1154-60. 7. Antonio-Santos AA, Santo RN, Eggenberger ER. Pharmacological testing of anisocoria. Expert Opin Pharmacother 2005;6:2007-13. 8. Morales J, Brown SM, Abdul-Rahim AS, et al. Ocular effects of apraclonidine in Horner syndrome. Arch Ophthalmol 2000;118: 951-4. 9. Brown SM, Aouchiche R, Freedman KA. The utility of 0.5% apraclonidine in the diagnosis of Horner syndrome. Arch Ophthalmol 2003;121:1201-3. Nonarteritic Ischemic Optic Neuropathy After LASIK With Femtosecond Laser Flap Creation Non-arteritic ischemic optic neuropathy (NAION) has been reported after laser in situ keratomileusis (LASIK) performed with a microkeratome flap (1,2). Its occurrence has been attributed to the pressure elevation caused by the suction ring. The suction ring placed during hyperopic LASIK transiently elevates the intraocular pressure (IOP) to levels exceeding 65 mm Hg. We examined a 53-year-old man who developed unilateral NAION after bilateral simultaneous uncompli-cated hyperopic LASIK in which flap creation was performed using the IntraLase femtosecond laser (IntraLase Corp., Irvine, CA) with a low-pressure suction ring. To the best of our knowledge, NAION has not been reported in this setting. Preoperative refractive errors were +5.50 +0.50 3105 for the right eye and +5.25 +0.50 390 for the left eye with best-corrected visual acuities of 20/20 in both eyes. Preoperatively, IOPs were normal and family history was negative for glaucoma. The LASIK surgeon reported that results of a preoperative dilated fundus examination was unremarkable except for small optic discs and cup/disc ratios. The procedure was uneventful. In each eye, the IntraLase femtosecond laser was used to create superiorly hinged flaps of 110 mm thickness, and stromal ablation was performed. Corneal topography after LASIK surgery revealed a hyperopic LASIK ablation pattern. On the first postoperative day, best-corrected visual acuities were 20/20 in the right eye and 20/200 in the left eye. The right optic disc was normal, and the left optic disc was edematous. There was a relative afferent pupillary defect in the left eye. Visual field examination showed a dense nerve fiber bundle defect in the left eye (Fig. 1). In the two reported cases of NAION after LASIK surgery (1,2), flap creation was performed using a mechan-ical microkeratome, with an associated sudden increase in IOP to 60-70 mm Hg, followed by a rapid IOP decrease upon suction release. Our patient is unusual because during IntraLase laser treatment, the IOP did not exceed 30-40 mm Hg (3,4). The mechanism of NAION under these circumstances is unknown. 242 J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 Letters to the Editor Ahmet Maden, MD Safiye Yilmaz, MD Nazife Sefi Yurdakul, MD Department of Ophthalmology Izmir Atatu¨ rk Training and Research Hospital Izmir, Turkey [e-mail] REFERENCES 1. Bushley DM, Parmley VC, Paglen P. Visual field defect associated with laser in situ keratomileusis. Am J Ophthalmol 2000;129:668-71. 2. Cameron BD, Saffra NA, Strominger MB. Laser in situ keratomileusis-induced optic neuropathy. Ophthalmology 2001;108:660-5. 3. Juhasz T, Loesel FH, Kurtz RM et al. Corneal refractive surgery with femtosecond lasers. IEEE J Selected Topics Quantum Electron 1999;5: 902-10. 4. Principe AH, Lin DY, Small KW, Aldave AJ. Macular hemorrhage after laser in situ keratomileusis (LASIK) with femtosecond laser flap creation. Am J Ophthalmol 2004;138:657-9. FIG. 1. On postoperative day 1 after bilateral hyperopic LASIK pro-cedures with femtosecond flap cre-ation, fundus photographs (A) show left segmental optic disc edema, and visual fields (B) show a correspond-ing left eye defect. J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 243 Letters to the Editor J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 Notice: Duplicate Publication We would like to provide an explanation for the fact that our publication entitled ‘‘Wall-eyed bilateral inter-nuclear ophthalmoplegia in a patient with progressive supranuclear palsy'' published in the June 2008 issue of the Journal (1) involved the same patient as reported in another publication from our institution entitled ‘‘Progressive supranuclear palsy with wall-eyed bilateral internuclear ophthalmoplegia syndrome'' (2). We have written our paper independently, basing it mainly on the findings on electronystagmography and vestibular testing.We did not know that Dr. Matsumoto and his colleagues were going to publish the case report about the same patient. We had no intention of duplicate publication. Insufficient communication between us and Matsumoto and co-authors has brought about this matter. We have already reported the error to our institution. We are consulting with experts in our institution to develop an institutional means to prevent recurrence of this sort of mistake.We will propose neweffective rules for publication in our institution. We apologize for this matter caused by our in-sufficient communication. Munetaka Ushio, MD Shinichi Iwasaki, MD Yasuhiro Chihara, MD Toshihisa Murofushi, MD Department of Otolaryngology Graduate School of Medicine University of Tokyo Tokyo, Japan [e-mail] REFERENCES 1. Ushio M, Iwasaki S, Chihara Y, et al. Wall-eyed bilateral internuclear ophthalmoplegia in a patient with progressive supranuclear palsy. J Neuroophthal 2008;28:93-103. 2. Matsumoto H, Ohminami S, Goto J, et al. Progressive supranuclear palsy with wall-eyed bilateral internuclear ophthalmoplegia syndrome. Arch Neurol 2008;65:827-829. Reply: The Journal of Neuro-Ophthalmology accepts the apology of Drs. Ushio et al. for having unknowingly submitted for publication to this journal a case report prepared concurrently by other authors for publication in another journal. It is acceptable to present the same case material in more than one publication if it is not the principal focus of the articles and the interpretation of the findings is very different. Otherwise it is either a serious breach of ethics or a serious example of sloppiness. With the growth and increasing complexity of academic medical centers, this kind of mistake is bound to happen-and it happens often. The editorial staff of medical journals has no way to prevent it. The burden is on the investigators and their host institutions to develop a reliable communication system. Jonathan D. Trobe, MD Editor-in-Chief Journal of Neuro-Ophthalmology Ann Arbor, Michigan [e-mail] J Neuro-Ophthalmol, Vol. 28, No. 3, 2008 Notice 244 J Neuro-Ophthalmol, Vol. 28, No. 3, 2008