| OCR Text |
Show Letters to the Editor Intravitreal Triamcinolone Acetonide Injection in a Rodent Model of Anterior Ischemic Optic Neuropathy: Comment I read with great interest the recent article from Pereira et al (1) which detailed a trial of an intravitreal triamcinolone acetate (IVTA) injection in the rodent model of anterior ischemic optic neuropathy (rNAION). The group demonstrated no significant difference between the IVTA group and controls. I suggest that significant differences in the pathophysiology of the rNAION model and human nonarteritic ischemic neuropathy, NAION, make this model challenging for testing the therapeutic potential of steroids. The rNAION model establishes optic nerve ischemia using intravenous rose bengal and subsequent laser; Pereira et al used 532-nm diode laser to cause selective ischemia of the optic nerve head (ONH). This rNAION model does demonstrate many functional and histological similarities with NAION (2). Histological analysis of the ONH in the rNAION model demonstrates a significant reduction in the filling of optic nerve capillaries. This ischemic lesion results in a protracted optic disc swelling, demonstrated with biomicroscopic images here (2). The rNAION model should be thought of as a homolog to end-stage NAION, irreversible ONH ischemia, and cell loss. It is for this reason that steroids are unlikely to have a therapeutic effect. Much of the pathophysiology of NAION remains in question, but it is undoubtedly a multifactorial process that manifests as small vessel circulatory insufficiency of the ONH (3). It is believed that this vascular insufficiency, at least in its beginnings, is transient (4). ONH edema and a subsequent compartment syndrome are likely to play a role in exacerbating the ischemia with smaller and more crowded optic nerves being particularly vulnerable (3). Furthermore, ONH edema has been shown to precede visual loss in NAION (4). Rather than viewing ONH edema as a downstream effect of ON infarction, as it is in rNAION, one must consider it part of the initial pathophysiology and therefore a potential therapeutic target. The role of IVTA in the treatment of NAION remains controversial. Studies to date using IVTA have been small; however, some groups have shown modest benefits (5). The evidence for oral steroids is more robust (5). The proposed Intravitreal Triamcinolone Acetonide Injection in a Rodent Model of Anterior Ischemic Optic Neuropathy: Response W e would like to thank Dr. Harvey for his interest in our study titled “Intravitreal triamcinolone acetonide injection in a rodent model of anterior ischemic optic neuropathy” (1). He points out the limitations of using a rodent model to Letters to the Editor: J Neuro-Ophthalmol 2019; 39: 545-547 mechanism of action of steroids is to speed up the resolution of ONH edema and thus re-establish ONH blood supply (5). If true, this mechanism of action makes the rNAION model used in the study by Pereira et al a challenging choice. The structural damage caused to the ONH capillaries in the rNAION model is likely irreversible. ONH ischemia will ensue, despite reestablishment of blood supply to these vessels. Furthermore, ONH edema in the rNAION model resolves by 5 days, compared with the much longer time course seen in humans (2). This suggests significant differences in the role ONH edema plays in the pathophysiology of the disease in rNAION and NAION. NAION is a poorly understood and severe optic neuropathy for which we have few therapeutic options. One of the difficulties with NAION research in humans is its rapid progression, which makes the therapeutic window extremely small. For this reason, animal models present an exciting opportunity to test potential treatments. However, the rNAION model may represent a choice that has challenges for investigating the therapeutic potential of steroids in NAION. Joshua P. Harvey, MA (Oxon), BM, BCh Ophthalmology Department, King's College Hospital, London, United Kingdom The author reports no conflicts of interest. REFERENCES 1. Pereira LS, Ávila MP, Salustiano LX, Paula AC, Arnhold E, McCulley TJ. Intravitreal triamcinolone acetonide injection in a rodent model of anterior ischemic optic neuropathy. J Neuroophthalmol. 2018;38:561–565. 2. Bernstein SL, Johnson MA, Miller NR. Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models. Prog Retin Eye Res. 2011;30:167–187. 3. Arnold AC. Pathogenesis of nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2003;23:157–163. 4. Hayreh SS, Zimmerman MB. Incipient nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 2007;114:1763–1772. 5. Atkins EJ, Bruce BB, Newman NJ, Biousse V. Treatment of nonarteritic anterior ischemic optic neuropathy. Surv Ophthalmol. 2010;55:47–63. investigate anterior ischemic optic neuropathy (AION). We are in agreement that animal models will always fall short of studying human disease. However, they are often the most appropriate first step. There is no question that rodents have different responses to tissue injury than do primates. We also agree that, unlike AION in humans, the current animal models of AION, both rodent and nonhuman primate, are potentially different from human AION. With all animal models, we know 545 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
