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Show Progressive Postoperative Visual Loss in Idiopathic Intracranial Hypertension With Extremely Elevated ICP Wilkes and Siatkowski (1) recently reported a 16-year-old girl with idiopathic intracranial hypertension (IIH) who underwent uncomplicated bilateral optic nerve sheath fenestration (ONSF) for worsening vision despite maximal medical therapy. Postoperatively, she continued to lose vision, deteriorating from 20/25, right eye, and 20/40, left eye, on postoperative day 4 to 20/100 in both eyes at postoperative day 14. Repeat lumbar puncture revealed an opening pressure of 65 cm H2O. A ventriculoperitoneal (VP) shunt was performed, but progressive visual loss ensued, to the 20/200 level in each eye at the most recent visit. It was pos-tulated that in patients with IIH with very high intracranial pressure (ICP), abnormal cerebrospinal fluid (CSF) flow producing a compartmentalization syndrome, as described by Killer et al (2), may preclude a good response to ONSF and/or VP shunt. We recently encountered a similar case of an obese 11-year-old girl with IIH and an opening CSF pressure of .50 cm H2O. She was initially treated with acetazol-amide at an outside facility and 5 days later presented to us. Examination revealed marked chronic papilledema with macular exudates and visual acuities of 20/100, right eye, and 20/20, left eye, with profound generalized visual field constriction. Also, she had a right facial and bilateral abducens nerve palsies. The patient was treated with intravenous solumedrol and acetazolamide and scheduled for bilateral ONSF in approximately 24 hours. Preoperative visual acuities were 20/800, right eye, and 20/50, left eye. One day following uncomplicated surgery, vision was stable in each eye, and on postoperative day 6, visual fields showed persistent generalized constriction and visual acuities were 20/250, right eye, and 20/60, left eye. Two weeks later, she saw her pediatrician because of decreased visual acuity in the right eye but was not seen by an ophthalmologist. Lumbar puncture revealed an opening pressure of 55 cm H2O. The patient underwent VP shunt on postoperative day 14. Eleven days after VP shunt, visual acuity was light per-ception, right eye, and 20/60, left eye. Dilated fundus ex-amination showed residual optic disc swelling in both eyes with optic atrophy. Opening pressure on lumbar puncture was 16 cm H2O. Three months after VP shunt, vision measured light perception, right eye, and 20/600, left eye. Dilated fundus examination showed sharp and flat discs with diffuse pallor. The patient described here and the one previously reported (1) are similar in that they both underwent uncomplicated ONSF, had high ICP (above 55 cm H2O) after ONSF with progressive visual loss, and subsequently underwent VP shunting after which visual acuity continued to decline. Killer et al (2) have reported patients with IIH who underwent ONSF but had persistent papilledema, even after subsequent VP shunting. They suggested that a pos-sible impedance of flow exists between the subarachnoid space of the optic nerve and the intracranial space, specu-lating that CSF flow may not be bidirectional due to the high pressure (2). Patients with extreme elevations of ICP after ONSF who do not respond to interventions to de-compress the optic nerve may have a compartmentalization syndrome sequestering the subarachnoid space and the optic nerve and represent a subgroup of patients with IIH prone to profound visual loss. Beck and Greenberg (3) described 5 patients with papilledema secondary to intracranial tumors who became blind immediately following decompressive craniotomy. They postulated that lowering the ICP altered local vaso-regulatory factors within the optic nerve, reducing perfusion to the ophthalmic artery and prelaminar optic nerve. Any concomitant drop in the systemic blood pressure could exacerbate optic nerve blood flow already compromised by the elevated subarachnoid space pressure. In addition to medically lowering ICP preoperatively, they recommended constant monitoring of blood pressure during surgery in attempt to prevent visual loss after surgery in high-risk patients with papilledema and visual field defects (3). Neither patient described here had periods of hypotension either intra- or postoperatively. Although most patients with IIH and significant visual loss undergo successful ONSF, some patients may continue to have progressive loss of vision postoperatively. The temporal profile of this visual loss is not consistent with complications from surgery or with abrupt intraoperative reduction of ICP or systemic blood pressure. Our cases suggest that patients with IIH and extremely elevated (.50 cm water) ICP may require more aggressive intervention in order to minimize vision loss. Such patients need strict monitoring of vision and ICP after ONSF. Further reduction of vision after 386 Linden and Siatkowski: J Neuro-Ophthalmol 2010; 30: 386-390 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. uncomplicated surgery should prompt repeat lumbar puncture. If these patients have persistent and extreme el-evation of ICP after ONSF, urgent VP shunt placement should be performed to protect remaining vision, with appropriate preoperative medical lowering of ICP and in-traoperative monitoring of systemic blood pressure. Julie A. Linden, BA R. Michael Siatkowski, MD Dean McGee Eye Institute University of Oklahoma Oklahoma City, Oklahoma rmichael-siatkowski@dmei.org REFERENCES 1. Wilkes BN, Siatkowski RM. Progressive optic neuropathy in idiopathic intracranial hypertension after optic nerve sheath fenestration. J Neuroopthalmol. 2009;29: 281-283. 2. Killer HE, Jaggi GP, Flammer J, Miller NR, Huber AR, Mironov A. Cerebrospinal fluid dynamics between intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional? Brain. 2007;130:514-520. 3. Beck RW, Greenberg HS. Post-decompression optic neuropathy. J Neurosurg. 1985;63:196-199. Long-Term Survivor of Paraneoplastic Optic Neuropathy Small cell lung cancer carries a very poor long-term prognosis. In a survey performed at the Mayo Clinic from 1997 to 2003, the 5-year survival rate was only 9% (1). In addition, to our knowledge, the longest published survival duration for paraneoplastic optic neuropathy secondary to small cell lung cancer has been 8 years (2). We wish to provide an update on a patient previously reported by one of us (A.G.L.) in this Journal in 1998 (3) who returned 14 years later without evidence of tumor recurrence and believed to be in clinical remission. The earlier detection of the tumor from her neuro-ophthalmologic examination followed by timely systemic treatment may have contributed to her favorable outcome. To the best of our knowledge, she is the longest survivor of paraneoplastic optic neuropathy secondary to small cell lung cancer. At the time of her diagnosis, she underwent surgery, chemotherapy, and radiation therapy and was believed to be in remission at the last follow-up. The patient, a 73-year-old white woman, was last seen in the neuro-ophthalmology clinic on July 20, 2010. She was complaining of blurred vision in the left eye that had worsened since sustaining a fall on March 1, 2010. She was seen by her neurologist who obtained a brain MRI that showed no focal lesions. Best-corrected visual acuity was 20/30 in the right eye and 20/40 in the left eye without a relative afferent pupillary defect. Ishihara color plate testing was intact in both eyes, and she was orthotropic on cover-uncover testing. Confrontation visual fields were full. Ocular motility was full with normal pursuit and saccades. There was no nystagmus or cerebellar eye signs. Slit-lamp examination revealed no uveitis and cataracts that were consistent with the patient's level of vision. Ophthalmoscopy was normal and automated visual fields revealed nonspecific peripheral depression bilaterally. Over the years, the patient has been seen regularly by her oncologist and determined to be stable. Chest CT performed inMarch 2010 showed no evidence of recurrent or metastatic disease. The patient returned to TheMethodist Hospital after 10 years of follow-up to specifically report on her progress and survival from small cell carcinoma of the lung. Derrick Pau, MD Sushma Yalamanchili, MD Department of Ophthalmology, The Methodist Hospital Houston, Texas Andrew G. Lee, MD Department of Ophthalmology, The Methodist Hospital Houston, Texas Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medical College New York, New York Department of Ophthalmology, University of Iowa Hospitals and Clinics Iowa City, Iowa Department of Ophthalmology, UTMB-Galveston Galveston, Texas REFERENCES 1. Yang P, AllenMS, AubryMC, Wampfler JA,Marks RS, Edell ES, Thibodeau S, Adjei AA, Jett J, Deschamps C. Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. Chest. 2005;128:452-462. 2. Cross SA, Salomao DR, Parisi JE, Kryzer TJ, Bradley EA, Mines JA, Lam BL, Lennon VA. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol. 2003;54:38-50. 3. Luiz JE, Lee AG, Keltner JL, Thirkill CE, Lai EC. Paraneoplastic optic neuropathy and autoantibody production in small-cell carcinoma of the lung. J Neuroophthalmol. 1998;18: 178-181. Pau et al: J Neuro-Ophthalmol 2010; 30: 386-390 387 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Role of Steroid Therapy in Nonarteritic Anterior Ischemic Optic Neuropathy Iwas interested to read the comments by Drs Lee and Biousse (1) in ‘‘Point Counter-Point,'' dealing with steroid therapy in nonarteritic anterior ischemic optic neuropathy (NA-AION). The impetus for this discussion came from my prospective ‘‘patient randomized'' study on the subject (2). That report showed that when patients with NA-AION were treated, according to the steroid therapy protocol in the study, 69.8% (95% confidence interval [CI], 57.3%-79.9%) of eyes with initial visual acuity of 20/70 or worse, seen within 2 weeks of onset, experienced visual acuity improvement compared to 40.5% (95% CI, 29.2%- 52.9%) in the untreated group (odds ratio of improvement: 3.39; 95% CI, 1.62-7.11; P = 0.001). Among those seen within 2 weeks of NA-AION onset, with moderate-to-severe initial visual field defect, there was improvement in 40.1% (95% CI, 33.1%-47.5%) of the treated group and 24.5% (95% CI, 17.7%-32.9%) of the untreated group (odds ratio: 2.06; 95% CI, 1.24-3.40; P = 0.005). Neuro-ophthalmologists, however, are of the opinion that steroid therapy has no role in the treatment of NA-AION, as I have learned from multiple e-mails, letters, and telephone calls from patients with NA-AION who have been told by neuro-ophthalmologists that steroid therapy will not benefit them and that there is no known treatment available. I feel impeled to defend my study's findings and conclusions, respond to criticism, and place the role of steroid therapy in NA-AION in proper perspective. This is vital because there has not previously been any effective treatment for NA-AION, and this study provides hope to these patients. 1. Scientific rationale for visual improvement with steroid therapy in NA-AION. Primary and secondary changes in the optic nerve head (ONH) produce optic disc edema in NA-AION (2). The primary change is ischemic axoplasmic flow stasis; vascular changes and fluid leakage (as shown by fluorescein angi-ography initially in NA-AION) occur secondarily. There is good evidence that steroid therapy reduces capillary per-meability. A large study showed that systemic steroid therapy given within 2 weeks after the onset of NA-AION resulted in significantly (P = 0.0006) faster resolution of optic disc edema in treated than in untreated cases (3). The most likely scenario to explain the beneficial effect of steroid therapy on visual outcome in NA-AION, as discussed in detail in my article (2), seems to be as follows: The faster resolution of optic disc edema with steroid therapy compared to the untreated patients ! Progressive decrease of compression of the capillaries in the ONH ! Improved circulation in the ONH ! Improved function of the sur-viving hypoxic axons. There is a possibility that the steroids may also have additional beneficial effects such as inhibition of damage by free radicals. Therefore, in NA-AION, steroid therapy DOES have a scientifically valid rationale. 2. There was no conventional randomization in this study. Lacking extramural funding, I decided on a prospective ‘‘patient choice'' controlled study instead of the ‘‘conven-tional randomized study''-the next best choice. Every patient with NA-AION seen in my clinic was given a free and informed ‘‘patient choice.'' The crucial criterion for any ‘‘conventional randomiza-tion'' is to have treated and untreated groups at baseline comparable in demographic and clinical characteristics. In my study, that was the case. 1. In the study, 51% voluntarily opted for systemic steroid therapy and 49% opted for no treatment. Thus, the numbers of patients in the treated and untreated groups were similar. 2. There was no significant difference between the 2 groups in visual acuity, visual fields, and systemic diseases, except that patients who opted for treat-ment were slightly younger (59.2 vs 62.0 years) and had a lower prevalence of arterial hypertension (34% vs 43%).To determine if those factors influenced the visual outcome, they were accounted for in the statistical analysis by including them as covariates in the logistic regression model-they made no difference in visual outcome (age, P = 0.8; hypertension, P = 0.6). Contrary to the assertion in Point Counter-Point, there was no difference in the frequency of diabetes or other vascular risk factors between the 2 groups. The assertion by Biousse et al (4) that the statistical analysis given above does not rule out a higher prevalence of systemic diseases in the untreated group compared with the treated group, contradicts standard scientific practice. 3. The data were not collected in a masked fashion. The following are proofs of the collected data that had no bias: 1. Visual acuity: Our results exactly mirrored those of the Ischemic Optic Neuropathy Decompression Trial, a randomized and masked study (5). In that study, in the untreated eyes seen within 2 weeks 388 Hayreh: J Neuro-Ophthalmol 2010; 30: 386-390 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. after the onset of NA-AION with visual acuity of 20/70 or worse, the visual acuity improved in 43% of the untreated eyes. In my study, in an exactly identical group of patients with NA-AION, in the untreated group, the visual acuity improved in 41% of the untreated eyes. In both studies, the visual acuity improved up to 6 months. This is the most convincing proof that the visual acuity data in my study were unbiased. 2. Visual fields: These were plotted by perimetrists who were unaware of the diagnosis. The fields were graded by 3 neuro-ophthalmologists, in-dependently, in a masked fashion, without any knowledge of the patients' diagnosis. Three additional factors have played an important role in the controversy of using steroids in the treatment of NA-AION: 1. As stated in Point Counter-Point: ‘‘A number of well-designed studies in the neurologic literature have shown that steroid do not improve outcome of patients with acute arterial or venous cerebral ischemia.'' There is a fundamental problem with this argument. Cerebral stroke is a thromboem-bolic disorder. Steroid therapy has no role in such a situation. In contrast, we have scientifically valid evidence that NA-AION is primarily a hypotensive disorder in the majority of cases, with much less severe ischemic damage (6-8), and not a throm-boembolic disorder. Thus, the 2 diseases are totally unrelated pathogenetically and in their manage-ment (7). To equate NA-AION and stroke is a fundamental mistake. 2. It seems that one major reason for the controversy on NA-AION management is the lack of in-depth understanding of its pathogenesis. I have discussed the pathogenesis of NA-AION elsewhere at length (7,8) and concluded that available evidence shows that ‘‘the pathogenesis of NA-AION is complex but not, as often stated, unknown.'' 3. Many physicians are uncomfortable treating pa-tients, particularly the elderly, with high-dose steroid therapy. For more than 45 years, I have treated several thousand patients with high-dose steroid therapy for a variety of ophthalmic diseases. Based on my clinical practice, I find that steroids can be used safely, provided patients are followed closely and meticulously. I realize that my findings challenge conventional wisdom in the management of NA-AION. I urge my colleagues to look at this study with unbiased and open minds, in the interest of helping these desperate patients. Given the visual devastation of NA-AION, our patients deserve nothing less! Sohan Singh Hayreh, MD, MS, PhD, DSc, FRCS, FRCOphth(Hon) Department of Ophthalmology & Visual Sciences College of Medicine, University of Iowa Iowa City, IA sohan-hayreh@uiowa.edu REFERENCES 1. Lee AG, Biousse V. Should steroid be offered to patients with nonarteritic anterior ischemic optic neuropathy? J Neuroophthalmol. 2010;30:193-198. 2. Hayreh SS, Zimmerman MB. Non-arteritic anterior ischemic optic neuropathy: role of systemic corticosteroid therapy. Graefes Arch Clin Exp Ophthalmol. 2008;246:1029-1046. 3. Hayreh SS, Zimmerman MB. Optic disc edema in non-arteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2007;245:1107-1121. 4. Biousse V, Bruce BB, Newman NJ. Non-arteritic anterior ischemic optic neuropathy: role of systemic corticosteroid therapy. Surv Ophthalmol. 2010;55:400-401. 5. Ischemic Optic Neuropathy Decompression Trial Research Group. Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. JAMA. 1995;273:625-632. 6. Hayreh SS, Podhajsky PA, Zimmerman B. Non-arteritic anterior ischemic optic neuropathy-time of onset of visual loss. Am J Ophthalmol. 1997;124:641-647. 7. Hayreh SS. Ischemic optic neuropathy. Prog Retin Eye Res. 2009;28:34-62. 8. Hayreh SS. Acute ischemic disorders of the optic nerve: pathogenesis, clinical manifestations and management. Ophthalmol Clin North Am. 1996;9:407-442. Ptosis in Pompe Disease: Common Genetic Background in Infantile and Adult Series Yanovitch et al (1) reported a patient with nonclassic infantile Pompe disease, who developed ‘‘slowly pro-gressive, variable, bilateral ptosis'' at the onset of myopathic signs at an age of 9 months. Ptosis slowly progressed through the adolescence along with the progression of skeletal and respiratory muscle weakness. At the age of 13 years, the patient started enzyme replacement therapy (ERT), which failed to produce any change either of the degree of ptosis Ravaglia et al: J Neuro-Ophthalmol 2010; 30: 386-390 389 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. or of the skeletal muscle function. When ERT dosage was doubled, both ptosis and skeletal muscle weakness improved. In infantile Pompe disease, the development of ptosis has not been described previously. Literature data are limited to 4 reports concerning adults, recently reviewed by Yanovitch et al (2): a total of 7 patients (6 women), 6 of 7 with unilateral ptosis, are described. Mutation analysis was available for 5 of 7 cases. All had the IVS13T-G mutation in 1 allele, and the second mutation led to complete loss of alpha-glucosidase activity, which is typically found in infantile-onset disease: the 525delT in 2 patients; delExon18 in 2 patients; and Trp516Stop in 1 patient (see Pompemutation database: http:// www.pompecenter.nl/en/?Molecular_aspects:Mutations). In the same publication (2), the authors reported the development of bilateral ptosis in 4 of 30 ERT-treated infant patients, who survived beyond the first years of life. This figure is remarkably high (13%) compared to the seemingly rare occurrence of ptosis in late-onset Pompe disease. The effectiveness of ERT on ptosis is unknown. In our cohort of 28 patients with late-onset disease, only 1 patient, carrying the 525delT mutation, had bilateral severe ptosis. After 3 years of ERT, despite improvement in walking and respiratory function, the patient still shows severe bilateral ptosis. We do not know about the treatment outcome of the 4 patients with Pompe disease described by Groen et al (3), but we suspect that a positive response would have been considered worth reporting. Based on our own experience and that reported by Yanovitch et al (1), we can draw the following conclusions: 1. Ptosis has a higher prevalence and is more severe in children than in adults with Pompe disease. All the reported infantile cases showed bilateral ptosis, while bilateral ptosis has been reported in only 1 adult (the remainder showing unilateral involvement). 2. The above clinical finding is consistent with the ob-servation that the mutations detected in adult patients with ptosis (in addition to the IVS13T-G) are those typically found in the infantile disease. Ptosis was previously unrecognized in the infantile form because of the shortened lifespan of these patients. This suggests that ERT has altered the natural history of the infantile form, leading to the development of additional disease complications such as hearing loss, cognitive dysfunc-tion, and ptosis. When observed in adults, ptosis is a sentinel sign of a more severe genotype, thus possibly reflecting a more severe disease course. 3. Regardless of the age of the patient, and unlike other disease manifestations (eg, impairment of skeletal muscle strength and respiratory involvement), ptosis seems not to respond to ERT at standard dosages. The lack of response characterized the patient described by Yanovich et al (1) (in whom other disease manifestations also were resistant to treatment) as well as our patient (otherwise a re-sponder). We do not know whether this lack of im-provement of ptosis may be due to a different fiber type composition of the levator muscles compared to skeletal muscles, including the contribution of smooth muscle fibers, or to additional CNS dysfunction (affecting, for instance, the third cranial nerve nuclei in the midbrain). Sabrina Ravaglia, MD, PhD Paola Bini, MD Department of Neurological Sciences University of Pavia, Pavia, Italy sabrina.ravaglia@mondino.it Kolsoum Saeidi Garaghani, MD Cesare Danesino, MD, PhD Institute of Medical Genetics University of Pavia, Pavia, Italy REFERENCES 1. Yanovitch TL, Casey R, Banugaria SG, Kishnani PS. Improvement of bilateral ptosis on higher dose enzyme replacement therapy in Pompe disease. J Neuroophthalmol. 2010;30:165-166. 2. Yanovitch TL, Banugaria SG, Proia AD, Kishnani PS. Clinical and histologic ocular findings in Pompe disease. J Pediatr Ophthalmol Strabismus. 2010;47:34-40. doi: 10.3928/ 01913913-20100106-08. 3. Groen WB, Leen WG, Vos AM, Cruysberg JR, van Doorn PA, van Engelen BG. Ptosis as a feature of late-onset glycogenosis type II. Neurology. 2006;67:2261-2262. 390 Ravaglia et al: J Neuro-Ophthalmol 2010; 30: 386-390 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |