We thank Dr. Hayreh for sharing his comments on our study. Dr. Hayreh's illustrious academic career elevated him to the status of a thought leader in many ocular vascular diseases, such as retinal vein occlusion, retinal artery occlusion, ischemic optic neuropathy, and giant cell arteritis (GCA). With such credentials, it can be a daunting task to provide a rebuttal to some of his criticisms, but we do so with great respect and admiration.
Dr. Hayreh invokes the findings from his article published in 1997 (prospectively performed from 1973 to 1994) (1) to compare and contrast the results to our study (2). We will respond in a structured fashion and discuss each point made in the order presented in his letter.
Pathology Electronic Database
As should be done in all reports, we discussed the limitations of our study, which included a lack of complete clinical and paraclinical information in the medical records of some patients. Such shortcomings are often the situation in many retrospective studies. Even in Dr. Hayreh's prospective study, C-reactive protein (CRP) values were not available for all patients.
We used the Department of Pathology electronic database to identify patients who had been evaluated for GCA at Duke University Medical Center based on the results of temporal artery biopsy (TAB). We chose to use this data set because it allowed us to capture for analysis as many patients as possible who underwent a TAB from the entire medical center and not just from the Department of Ophthalmology. In comparison, it seems to be somewhat of a unique situation that at the University of Iowa Hospitals and Clinics, all TABs were performed by ophthalmologists during the period of Dr. Hayreh's study.
Length of Temporal Artery Specimen, Serial Sectioning, and Previous Corticosteroid Therapy
We agree with Dr. Hayreh's statement that length of the temporal artery specimen and serial sectioning are important to eliminate “skip areas.” We also agree that the optimal length of a TAB should be at least 1 inch. To explain the variation in the length of TAB in our study, it should be kept in mind that there were not only multiple ophthalmologists who performed the TAB but also surgeons from other specialties (otolaryngology, neurosurgery, vascular surgery, and general surgery). However, we did not find that a longer TAB was associated with a higher rate of a positive TAB (mean biopsy length, 21.6 ± 4.1 mm for a negative TAB vs 21.6 ± 6.8 mm for a positive TAB; P = 0.49).
Our Department of Pathology performs “step sections” (“levels”) when processing TABs. Although not as thorough as serial sections, which would require examining hundreds of slides from each biopsy, we consider our technique more than adequate to avoid skip areas and minimize false-negative results. Regarding previous corticosteroid therapy, we examined each TAB for features of treated or healed arteritis.
Prevalence of Systemic Signs and Symptoms
We have no reason to disagree with the odds ratios that were published by Dr. Hayreh because “numbers do not lie.” However, given the different study design and methodologies used between the 2 studies, the argument could be made that such a comparison is akin to comparing “apples to oranges” and not “apples to apples.” We stand by the results of our study because the “numbers do not lie,” but with the caveat that our study had limitations, in particular that it was a retrospective chart review and that we did not compare our findings to normal controls.
Headache
Table 3 of Dr. Hayreh's article indicates that headaches were present in 55.7% of TAB-positive patients and 45.5% of TAB-negative patients (P = 0.084). However, the location (temporal, frontal, etc.), type (sharp, dull, pounding, etc.), and time course (acute, subacute, or chronic) of the headaches are not described.
Evaluate for Alternative Diagnosis
Based on our algorithm, we state that if the patient has only 1 positive finding of the 7 listed, an alternative diagnosis should be sought. Dr. Hayreh suggests that jaw claudication in and of itself (i.e., normal erythrocyte sedimentation rate [ESR], normal CRP, normal platelet count, no neck pain, no scalp tenderness, and no constitutional or systemic symptoms) should be an indication for performing a TAB in a patient more than 50 years. However, we were unable to determine how many of his 106 patients with a positive TAB had jaw claudication as their only manifestation of GCA. Furthermore, Dr. Hayreh states “However, when we considered a multivariate logistic regression model that included ESR and age, the only significant systemic symptoms were jaw claudication and neck pain (mostly in the occipital and back parts of the neck).” This implies that jaw claudication and neck pain were indicators of a positive biopsy, independent of ESR and age.
Hematological Tests
We would like to reiterate what we wrote regarding hematological tests: “Having any isolated laboratory value elevated (ESR, CRP, or platelet count) was not associated with a positive TAB; however, when 2 or more inflammatory markers were elevated, the RR was 3.4 (P < 0.0001) (23/25 patients with elevated platelet count also had a high ESR, and 63/76 patients with a high CRP also had high ESR). An increase in ESR, CRP, and platelet count was present in 11 of 77 patients (14.7%) and was not associated with positive TAB. Two patients with positive TAB had normal ESR, CRP, and platelet counts.”
We acknowledge differences in the results of our study compared to the study of Dr. Hayreh, but because of the different study design, demographic/geographic/genetic cohort profile, and period of the studies, it is not reasonable to just dismiss such differences in favor of one study over another. It is more important to understand why these discrepancies exist between the 2 studies, without just insinuating it is simply inaccurate or wrong because it is not in alignment with previously published results.
Giant Cell Arteritis is an Ophthalmic Emergency
Based on clinical evidence and clinical experience, it is abundantly clear that GCA is a heterogeneous disease in terms of clinical presentation, clinical manifestations, and inflammatory markers. Because the stakes are so high, in terms of not only visual loss but also systemic morbidity and mortality, it is crucial that the diagnosis of GCA be made correctly and promptly. The nidus of our study was to attempt to create an easy-to-use diagnostic algorithm for clinicians to use when trying to decide on whether to proceed with a TAB or not. In no way does our algorithm claim to have 100% sensitivity in detecting GCA. Because of the variable phenotypic expression of GCA and the fact that there can be no systemic symptoms (occult GCA) and normal inflammatory markers (CRP and ESR), the decision to perform a TAB should be made on a case-by-case basis.
We take issue with Dr. Hayreh for dismissing our study results and stating that readers should be skeptical of “many” of our conclusions. We believe that the decision to perform a TAB should not be based on just 1 clinical or laboratory finding but rather integrating all data to increase the yield of obtaining a positive TAB and preventing unnecessary TABs. We stand by our study and will let the reader determine the validity of the results and the utility of our algorithm.
REFERENCES
1. Hayreh SS, Podhajsky PA, Raman R, Zimmerman B. Giant cell arteritis: validity and reliability of various diagnostic criteria. Am J Ophthalmol. 1997;123:285–296.
2. El-Dairi MA, Chang L, Proia AD, Cummings TJ, Stinnett SS, Bhatti MT. Diagnostic algorithm for patients with suspected giant cell arteritis. J Neuroophthalmol. 2015;35:246–253.
