Does Nocturnal Hypotension Play a Causal Role in Nonarteritic Anterior Ischemic Optic Neuropathy?: Response

Letters to the Editor Does Nocturnal Hypotension Play a Causal Role in Nonarteritic Anterior Ischemic Optic Neuropathy?: Response I appreciate the opportunity to respond to Dr. Hayreh's comments. I have tremendous respect for his research studies, and I completely agree with him that the pathogenesis of nonarteritic anterior ischemic optic neuropathy (NAION) is multifactorial. However, I believe that there are certain areas in which the data he presents do not adequately support his conclusions. The nocturnal hypotension theory is one of those areas. I will address his comments point by point. First, regarding a control group in studies of nocturnal hypotension: a study to assess whether subjects with NAION had an exaggerated nocturnal dip in blood pressure would ideally compare those subjects to a control group with a similar profile, to measure the difference in nocturnal dips between the 2 groups. To state that it is "impossible to have a valid control group" is to suggest that every factor must be matched in comparisons, and this is simply not true. In this instance, a comparison would not require that groups be matched for disc morphology or other factors unrelated to blood pressure that might be involved in pathogenesis; it is aimed at only 1 feature and, therefore, only aspects which might affect that feature need to be matched. The study by Landau et al (1) accomplished this and found no difference between the 2 groups for levels of nocturnal hypotension. Although Dr. Hayreh et al (2) claims that he uncovered "flaws in that study which invalidate its conclusions," this claim was refuted by Dr. Landau et al (3). The lack of control subjects makes it difficult to interpret Dr. Hayreh's conclusions that nocturnal hypotension is related to pathogenesis of NAION, to progressive visual field loss in NAION, to ipsilateral recurrence in NAION, and more, because nowhere does he define what the term "nocturnal hypotension" means in these settings. Nocturnal hypotension is a normal finding. Does he mean that abnormally low nocturnal blood pressure is the factor? If so, then how does he define abnormal if he does not compare measured levels in subjects with NAION to controls? His statement that "patients with nocturnal hypotension, compared to those without it, had a significant association with progression of visual field deterioration in NA-AION," is misleading. He did not compare patients with nocturnal hypotension to those without it. He compared levels of nocturnal hypotension in various subject groups. The data indicating lower nocturnal blood pressure readings in certain categories of NAION are of interest, but they do not constitute evidence that nocturnal hypotension is pathogenetic, even in the multifactorial schema that he proposes. 352 Regarding the itemized responses: 1. As I mentioned in my review, Dr. Hayreh's methodology for blood pressure measurements differed from most other investigators' techniques, and was therefore not directly comparable. Whether his method of measurement is superior is a matter of opinion. My comment was simply meant to indicate that they were not comparable, and therefore a clear assessment of whether the levels he measured were out of the normal range established by other large scale population studies was not possible. 2. Dr. Hayreh and I are in agreement here regarding the concept that the use of antihypertensive therapy at night certainly might produce an exaggerated nocturnal dip which could override the optic nerve circulation autoregulatory system and potentiate ischemia. I concur in recommending reduction of nighttime medication where possible. Avoiding the more severe levels of hypotension induced by medication (or severe blood loss) certainly seems reasonable. This does not, however, imply that levels seen without these factors are significant in the development of NAION. 3. My statement regarding the broader base of interviewers reflects the research axiom that the use of multiple observers in varied population groups may reduce observational bias from a single observer and population group. However, one could argue that even the lower 42% figure detected in the Ischemic Optic Neuropathy Decompression Trial is substantial, and that becoming aware of the visual loss on awakening is relatively common in patients with NAION. Whether this has anything to do with nocturnal hypotension is purely speculative. 4. My point in this statement (which actually read ". . .a nocturnal dip level that would increase risk. . .") was to refute the idea presented in the debate format by Dr. Cestari that 24-hour blood pressure monitoring might be useful in routine management of patients with NAION. It seems that Dr. Hayreh is actually agreeing with me here that the specific level of nocturnal hypotension would not be useful in management. 5. Even if we accept the nocturnal hypotension theory here, it has nothing to do with whether altering blood pressure would have any effect on the occurrence or course of NAION. There are no data available regarding this question. 6. Dr. Hayreh and I certainly agree that NAION is an ischemic disorder and that its pathogenesis is complex. But despite his claim to have clearly demonstrated the pathogenetic features, many aspects remain unclear: the precise location of the vasculopathy; the role of autoregulation; the role of vasospasm; the precise mechanism by which the "crowded disc" contributes; and, as pertains to this letter, the role of nocturnal hypotension. It certainly is reasonable to consider this factor as Letters to the Editor: J Neuro-Ophthalmol 2017; 37: 347-353 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor a contributor to hypoperfusion, but to date I do not believe the evidence is convincing. Anthony C. Arnold, MD Stein Eye Institute, UCLA Department of Ophthalmology, Los Angeles, California The author reports no conflicts of interest. REFERENCES 1. Landau K, Winterkorn JMS, Mailloux LU, Vetter W, Napolitano B. 24-hour blood pressure monitoring in patients with anterior ischemic optic neuropathy. Arch Ophthalmol. 1996;114:570-575. 2. Hayreh SS, Zimmerman MB, Podhajsky P, Alward WL. Nonarteritic anterior ischemic optic neuropathy: role of nocturnal hypotension (letter). Arch Ophthalmol. 1997;115:942-943. 3. Landau K, Winterkorn JMS, Napolitano B. Nonarteritic anterior ischemic optic neuropathy: role of nocturnal hypotension (reply to letter). Arch Ophthalmol. 1997;115:943-945. Retraction Intracranial Displacement of the Eye After Blunt Trauma: Retraction In the December 2009 issue of the Journal of Neuro-Ophthalmology, the article "Intracranial Displacement of the Eye After Blunt Trauma" appearing on page 311 is retracted. Upon the advice of the Deputy Director of Research Affairs at Tabriz University of Medical Science, Tehran, Iran the journal has decided to retract the paper on the following grounds: Following an investigation by Tabriz University, it was determined by that institution that "None of the authors of [the] paper had direct scientific or treatment link to the reported case." The doctors actually involved in the original patient treatment brought the ethical breach to the attention of Tabriz University. Following a thorough investigation at Tabriz University it was concluded fraud through inappropriate authorship had been committed. Tabriz University as a consequence of that investigation asked the Journal of Neuro-Ophthalmology to retract the case report published in 2009. REFERENCE Miabi Z, Nezami N, Midia M, Midia R. Intracranial displacement of the eye after blunt trauma. J Neuroophthalmol 2009;29:311 Letters to the Editor: J Neuro-Ophthalmol 2017; 37: 347-353 353 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.