Journal of Neuro-Ophthalmology, June 2010, Volume 30, Issue 2

Letters to the Editor

Progressive Optic Neuropathy in Idiopathic Intracranial Hypertension After Optic Nerve Sheath Fenestration We read with interest the article by Wilkes and Siatkowski (1) and believe that it raises several important questions concerning the pathophysiology of papilledema. Their patient had idiopathic intracranial hypertension and underwent optic nerve sheath fenestration (ONSF) because of progressive visual loss, loss of color vision, and worsening visual field defects. The patient's visual parameters initially improved after surgery, including the development of spontaneous venous pulsations (SVP), but visual sensory function subsequently deteriorated again despite normal-appearing optic discs and persistent SVPs, suggesting normal intracranial pressure (ICP). A ventriculoperitoneal shunt was placed without effect on progressive visual loss. Because the subarachnoid space (SAS) of the optic nerve (ON) contains numerous trabeculae and septa (2), it is probably incorrect to consider the SAS of the ON as one continuous cerebrospinal fluid (CSF) space that allows free flow of fluid throughout. Although an ONSF appears to be able to reduce ICP (evidenced in this case by the resolution of optic disc swelling and the appearance of SVPs), it is possible that some SAS compartments still exist that contain toxic substances in the trapped CSF. In a recent study, we found a deleterious effect of lipocalin-like prostaglandin D synthase, a substance that appears to be increased in the SAS of the ON in patients with papilledema (HE Killer, MD, unpublished data), on cultured astrocytes (3). The case reported by Wilkes and Siatkowski emphasizes that the pathophysiology of papilledema may be far more compli-cated than we used to believe (4). The use of more so-phisticated imaging techniques, such as computed tomographic cisternography, provides a dynamic view of CSF flow and ultimately may be helpful in determining the optimum treatment for patients with worsening visual function in the setting of severe papilledema. Hanspeter E. Killer, MD Department of Ophthalmology, Kantonsspital Aarau, Aarau, Switzerland Eye Institute, University of Basel, Basel, Switzerland [e-mail] Gregor P. Jaggi, MD Department of Ophthalmology, Kantonsspital Aarau, Aarau, Switzerland Neil R. Miller, MD Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland REFERENCES 1. Wilkes BN, Siatkowski RM. Progressive optic neuropathy in idiopathic intracranial hypertension after optic nerve sheath fenestration. J Neuroophthalmol. 2009;29:281-283. 2. Killer HE, Laeng HR, Flammer J, Groscurth P. Architecture of arachnoid trabeculae, pillars, and septa in the subarachnoid space of the human optic nerve: anatomy and clinical considerations. Br J Ophthalmol. 2003;87:777-781. 3. Xin X, Huber A, Meyer P, Flammer J, Neutzner A, Miller NR, Killer HE. L-PGDS (betatrace protein) inhibits astrocyte proliferation and mitochondrial ATP production in vitro. J Mol Neurosci. 2009;39:366-371. 4. Killer HE, Jaggi GP, Miller NR. Papilledema revisited: is its pathophysiology really understood? Clin Experiment Ophthalmol. 2009;37:444-447. Bisphosphonate-Induced Orbital Inflammation We read with interest the article ‘‘Another case of bisphosphonate-induced orbital inflammation'' (1). We commend the authors for a comprehensive appraisal that included detailed clinical and radiological documen-tation and establishment of a causal relationship between the offending drug and the clinical findings. However, we seek to refute the assertion that this case represents the first instance of orbital inflammation following bisphosphonate treatment of osteoporosis. We reported 3 menopausal middle-aged women taking alendronate (Fosamax; Merck, White-house Station, NJ) for osteoporosis, 2 of whom developed manifestations consistent with orbital inflammation: myositis and posterior scleritis (2). Causal association was established similarly by the temporal relation with commencement and withdrawal of the drug. Subsequent reports of orbital inflammation associated with various bisphosphonates administered for osteoporosis have appeared in the literature and online (3-5). Indeed, Killer et al: J Neuro-Ophthalmol 2010; 30: 205-206 205 Letters to the Editor Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited. some of these reports cite our original article. Most of these cases have responded well to drug withdrawal and systemic corticosteroid therapy. Of note, rechallenge with intra-venous zoledronate produced a recurrence (3). Fraunfelder et al (6) likewise observed recurrent scleritis on rechallenge with pamidronate. We believe that this association with variants of nonspecific orbital inflammation, while uncom-mon, probably occurs more frequently than is recognized or reported. A variety of ocular inflammatory manifestations are present in an idiosyncratic manner with different gen-erations and modes of administration of bisphosphonates. Since osteoporosis and autoimmune ocular diseases occur most commonly in middle-aged women, it is important that ophthalmologists are cognizant of the association of ocular and orbital inflammation with this class of drugs. Where a positive history is obtained, we urge consideration of drug withdrawal in the management plan. Joyce N. Mbekeani, FRCS, FRCOphth Albert Einstein College of Medicine, Bronx, New York Thomas L. Slamovits, MD Albert Einstein College of Medicine, Bronx, New York [e-mail] REFERENCES 1. Yang BE, Birkholz ES, Lee AG. Another case of bisphosphonate-induced orbital inflammation. J Neuroophthalmol. 2010;30:94-95. 2. Mbekeani JN, Slamovits TL, Schwartz B, Sauer H. Ocular inflammation associated with alendronate therapy. Arch Ophthalmol. 1999;117:837-838. 3. Leung S, Ashar BH, Miller RG. Bisphosphonate-associated scleritis: a case report and review. South Med J. 2005;98: 733-735. 4. Procianoy F, Procianoy E. Orbital inflammatory disease secondary to a single-dose administration of zolendronic acid for treatment of postmenopausal osteoporosis. Osteoporos Int. 2010;21:1057-1058. 5. Chang J, Soukiasian SH. Elderly woman presents with decreased vision and ocular pain. Ocular Surgery News supersite. Published online October 1, 2007. 6. Fraunfelder FW, Fraunfelder FT, Jensvold B. Scleritis and other side-effects associated with pamidronate sodium. Am J Ophthalmol. 2003;135:219-222. Response We thank Drs. Mbekeani and Slamovits for their in-terest in our article (1). As an author, one always lives in fear of receiving the news that one's literature search did not capture all prior reports. Gunter von Noorden, MD, used to caution residents that it was unlikely that anything in the modern English medical literature was truly the first report of anything as a thorough review of the German (and other non-English language) literature would likely produce a similar prior report. We appreciate Drs. Mbekeani and Slamovits bringing our oversight to our attention (2). We agree that ophthalmologists should always ask patients who present with orbital or ocular inflammation about the use of bisphosphonates. This is especially true in an era whenmany ophthalmologists may become less interested in the use of systemic medications. In obtaining a patient's history, medi-cation lists often look like the following: ‘‘some type of anti-inflammatory,'' ‘‘some lung medicine,'' ‘‘some kind of bone treatment,'' or the worst shortcut of all . . . ‘‘see list.'' Most of the time we get away with it as eye MDs, but what if that ‘‘anti-inflammatory'' is hydroxychloroquine, that ‘‘lung medicine'' ethambutol, or that ‘‘bone treatment'' is a bisphosphonate? Bo Yang, MD Andrew G. Lee, MD Houston, Texas REFERENCES 1. Yang EB, Birkholz ES, Lee AG. Another case of biphosphate-induced orbital inflammation. J Neuroophthalmol. 2010;30: 94-95. 2. Mbekeani JN, Slamovits TL, Schwartz BH, Sauer HL. Ocular inflammation associated with alendronate therapy. Arch Ophthalmol. 1999;117:837-838. 206 Mbekeani et al: J Neuro-Ophthalmol 2010; 30: 205-206 Letters to the Editor Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited.