Pellegrini et al-"Reply to: Paracentral Acute Middle Maculopathy as a Manifestation of Giant Cell Arteritis": Response

Letters to the Editor Comment to: “Ahuja AS et al: Paracentral Acute Middle Maculopathy as a Manifestation of Giant Cell Arteritis” strongly hints at the presence of an underlying systemic disorder, GCA being at the top of this list in the elderly population. Francesco Pellegrini, MD Ophthalmology Department, “Santo Spirito” Hospital, Pescara, Italy W e enjoyed reading the paper by Ahuja AS et al entitled: “Paracentral Acute Middle Maculopathy as a Manifestation of Giant Cell Arteritis” (1). In their interesting paper, Ahuja and coworkers described 2 cases of Paracentral Acute Middle Maculopathy (PAMM), a focal retinal ischemic disorder of the inner nuclear layer, in which a definite diagnosis of giant cell arteritis (GCA) was later done through temporal artery biopsy (TAB). The first patient presented optical coherence tomography (OCT) findings suggestive of PAMM associated to cotton wool spots, whereas in the second case, PAMM was found in association with optic disc edema and peripapillary hemorrhage. They state that their “series is the first in which PAMM has been described in biopsy-proven GCA.” We would like to point out that in 2018 we already reported 2 cases of PAMM in biopsy-proven GCA (2). Among 53 eyes of 53 patients with cilioretinal artery occlusion (CILRAO), we found 2 patients with PAMM in whom TAB confirmed the suspect of GCA. As for Ahuja et al' cases, we also found PAMM not as an isolated finding, but associated to other manifestations of retinal ischemia, namely CILRAO. The clinical value of Ahuja and coworkers' paper, however, remains unchanged. In fact, they correctly highlighted the importance of obtaining OCT imaging in patients with retinal ischemia. They also correctly pointed out that the identification of ischemia affecting 2 separate vascular beds Pellegrini et al—“Reply to: Paracentral Acute Middle Maculopathy as a Manifestation of Giant Cell Arteritis”: Response W e appreciate the interest of Pellegrini et al in our recent article, “Paracentral Acute Middle Maculopathy as a Manifestation of Giant Cell Arteritis” (1), and we are glad that they agree with our conclusions about the utility of identifying multifocal ischemia on spectraldomain optical coherence tomography (SD-OCT) as a red flag for the possibility of giant cell arteritis (GCA). We would, however, like to respond to their assertion that paracentral acute middle maculopathy (PAMM) as a manifestation of biopsy-proven GCA was described in their previous publication on the topic of cilioretinal artery occlusions (2). Their large retrospective series of 53 cases of cilioretinal artery occlusion is very informative and offers striking SD-OCT images of PAMM in the distribution of Letters to the Editor: J Neuro-Ophthalmol 2022; 42: e533-e538 Emanuela Interlandi, MD, PhD Ophthalmology Department, “Ospedale del Mare,” Naples, Italy Francesco Pichi, MD Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates The authors report no conflicts of interest. REFERENCES 1. Ahuja AS, El-Dairi MA, Hadziahmetovic M, Gospe SM III. Paracentral acute middle maculopathy as a manifestation of giant Cell arteritis. J Neuroophthalmol. 2021;41:e153– e156. 2. Pichi F, Fragiotta S, Freund KB, Au A, Lembo A, Nucci P, Sebastiani S, Gutierrez Hernandez JC, Interlandi E, Pellegrini F, Dolz-Marco R, Gallego-Pinazo R, Orellana-Rios J, Adatia FA, Munro M, Abboud EB, Ghazi N, Cunha Souza E, Amer R, Neri P, Sarraf D. Cilioretinal artery hypoperfusion and its association with paracentral acute middle maculopathy. Br J Ophthalmol. 2019;103:1137–1145. the cilioretinal artery. However, in their article, the authors report that it is their 51 non–GCA-related cases that demonstrate PAMM on SD-OCT, manifesting as a hyperreflective band in the inner nuclear layer with variable extension into the inner plexiform layer, but no involvement of the inner-most retinal layers. Conversely, in their 2 cases of cilioretinal artery occlusions in patients with biopsyproven GCA, the SD-OCT images demonstrate infarction of the middle and inner retina together; this is akin to what would be seen in a typical central retinal artery occlusion, where all but the outer-most retinal layers are hyperreflective and thickened. In fact, in their Discussion, the authors explicitly state that in their 2 cases of complete occlusion of the cilioretinal artery in the setting of GCA, ‟PAMM lesions were not identified with SD-OCT.” Ultimately, any claim to the first identification of PAMM as a manifestation of GCA is of less importance than the understanding that this pathological feature demands urgent and thorough workup to identify underlying etiologies that may put patients at risk of further vision loss. e533 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor Abhimanyu S. Ahuja, BS Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida Mays A. El-Dairi, MD Majda Hadziahmetovic, MD Sidney M. Gospe, III, MD, PhD Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina Comments on Tocilicizumab Use in Giant Cell Arteritis W e read with interest the recent Point–Counterpoint discussion regarding the use of tocilizumab in giant cell arteritis (GCA) by Gordon and Sadun. We have encountered many patients with GCA in our practice in the past few years who were initiated on therapy with tocilizumab within weeks of their diagnosis. The evidence cited for this practice is always the Giant-Cell Arteritis Actemra (GiACTA) study, published in the New England Journal of Medicine in 2017, the same study on which Gordon and Sadun base their main conclusions (1). However, we would like to raise a number of critical points regarding the study methodology that were not discussed. First, the inclusion criteria for GiACTA trial did not specify that participants should have a new diagnosis of GCA. Thus, patients were enrolled in the study if they had a new diagnosis of GCA within past 6 weeks or had a refractory (nonremitting or refractory relapsing) GCA, with evidence of active disease within 6 weeks of study onset while they were treated with 20–60 mg of daily oral prednisone. Of the 251 enrolled patients, half (52%) had relapsing disease. The mean disease duration at baseline in each of the 4 study arms was reported as: 307 6 564, 258 6 501, 365 6 570, and 255 6 436 days. These data by themselves are very confusing: when reporting data with bimodal distribution of disease duration, SD is not a useful measure. If half of the enrolled patients had disease diagnosed within 6 weeks of enrollment yet the mean number of days from the onset of diagnosis was minimum 255 days for all groups, the second group (those who were not diagnosed within 6 weeks of disease onset) would have had GCA for many months (over 2 years in many cases) before being enrolled in this trial. We know that most patients with GCA should be weaned off steroids completely within 12–18 months from the time of their diagnosis (2) and European League Against e534 The authors report no conflicts of interest. REFERENCES 1. Ahuja AS, El-Dairi MA, Hadziahmetovic M, Gospe SM III. Paracentral acute middle maculopathy as a manifestation of giant cell arteritis. J Neuroophthalmol. 2021;41:e153–e156. 2. Pichi F, Fragiotta S, Freund KB, Au A, Lembo A, Nucci P, Sebastiani S, Gutierrez Hernandez JC, Interlandi E, Pellegrini F, Dolz-Marco R, Gallego-Pinazo R, Orellana-Rios J, Adatia FA, Munro M, Abboud EB, Ghazi N, Cunha Souza E, Amer R, Neri P, Sarraf D. Cilioretinal artery hypoperfusion and its association with paracentral acute middle maculopathy. Br J Ophthalmol. 2019;103:1137–1145. Rheumatism recommends tapering prednisone to a target of 15–20 mg daily within 2–3 months and 5 mg or less after 1 year (3). Thus, at least half of the patients enrolled in GiACTA should have already been weaned off the steroids completely. On top of that, only 62% of patients in the GiACTA study had biopsy-proven GCA, with the remaining patients diagnosed using evidence of large vessel vasculitis on any of the following modalities: traditional angiography, computed tomography or magnetic resonance angiography or positron-emission tomography. Findings of inflammation and vessel wall abnormalities on these studies are not specific to GCA and are often subtle and difficult to interpret. The first set of formal guidelines on the use of imaging in large vessel vasculitis were not published until 2018 (4), 5 years after the start of the GiACTA trial. In this document, computed tomography and positron-emission tomography are not recommended for diagnosis of cranial GCA and for magnetic resonance imaging, specific sequences to be used are outlined the need for an expert interpreter is recognized. Thus, it is possible that at least some participants included in GiACTA study had a diagnosis other than GCA. Finally, the definition of a disease flare is critical to determining the efficacy and steroid-sparing benefit of tocilizumab and in GiACTA flare was “. . .Determined by the investigator and defined as the recurrence of signs or symptoms of GCA and/or ESR $30 mm/hour attributable to GCA.” Disease flares in GCA are most commonly characterized by headache and polymyalgia rheumatica symptoms. Ischemic complications such as permanent vision loss are very rare in relapsing disease (5–7). This makes the diagnosis of a flare challenging and subjective and GiACTA study definition means that a patient with any vague complaint could have been considered as having a disease flare and treated with steroids for a dose and duration determined by the individual investigator. Also, erythrocyte sedimentation rate of 30 mm/hour would be within the range of normal for any patient over 60 years. In neuro-ophthalmology Letters to the Editor: J Neuro-Ophthalmol 2022; 42: e533-e538 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.