Intravitreal Triamcinolone Acetonide Injection in a Rodent Model of Anterior Ischemic Optic Neuropathy: Response.

Abstract

We 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 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 exactly when damage occurred; however, with humans, we do not know when damage began—only when symptoms were first detected. Positive studies are of most value. If drug studies in rodents and other lower animals (e.g., rodents, rabbits, and hamsters) work, then we have a basis on which to test drugs in nonhuman primates or, in some cases, directly in humans. However, if they do not work, we still do not know with certainty that they would not work in humans. Such negative studies do have value in that they serve as essential building blocks, providing direction for future studies and at times justification for funding. Dr. Harvey voices several specific concerns. He asserts that laser-induced optic AION should be viewed as “a homolog” to end-stage AION. This presumption may or may not be accurate. But, even if accurate, our findings would still suggest that steroids lack benefit at this stage of disease, which may be at or shortly after appreciation of visual symptoms. He further argues that edema may play a role in the pathophysiology of AION, at different phases of the disease, and in some cases, preceding infarction. This likely is correct, and it is possible that steroids could have benefit in a subset of patients, specifically those with progressive axonal ischemia related to secondary compartmental compression. As we stated in our discussion section, we agree that our findings do not negate the possibility that steroids may have benefit in all or possibly a subset of human patients. In closing, we agree with Dr. Harvey that findings in a rodent model of AION far from perfectly parallel human disease. However, it would be unwise to assume animal studies such as this are entirely without value. They are, in many cases, the most appropriate initial step. We maintain that our data are sufficient to exclude a significant impact of intravitreal triamcinolone, with a final intravitreal concentration of 1 mg/mL, on retinal ganglion cells number in rodent eyes with nonarteritic ischemic optic neuropathy (NAION). Our findings do not exclude the possibility that anti-inflammatory therapy may be beneficial in all or in subsets of human patients with NAION. A detailed account of our study's limitations and implications comprises the bulk of the discussion section of the article (1). We are hopeful that these data will benefit future the design of more focused studies.