Over the past 30 years, 49 articles on giant cell arteritis (GCA) have been published in the Journal of Neuro-Ophthalmology, highlighting the diverse presentations of patients, discussing controversies in diagnosis and treatment, and reviewing prognosis. GCA, although rare, is a condition that can lead to devastating visual and systemic consequences if left untreated and, therefore, it remains an important area of research in neuro-ophthalmology.
Reports have described both familial and conjugal cases of GCA, raising the possibility of environmental or geographic associations (1–3). In the 1980s, there were several accounts of Borrelia spirochetes found in temporal artery biopsies, inferring that Borrelia infection may play a role in the development of GCA (4,5). Although this association may have fallen out of favor, researchers continue to investigate the role of infectious agents in the development of the disease.
Two studies discussed the relationship between diabetes mellitus and GCA. A retrospective review of temporal artery biopsy specimens showed a lower prevalence of diabetes among patients with GCA positive biopsies, raising the questions of whether diabetes is protective in the development of GCA or leads to lower positive biopsy results (6). In contrast, large review of Medicare claims data reached the opposite conclusion that diabetes is associated with a higher risk of GCA in older patients (7).
A number of case reports and case series have been published describing the broad spectrum of clinical manifestations in patients diagnosed with GCA. These include patients with isolated third nerve palsies, bilateral sixth nerve palsies, and a third nerve palsy with ipsilateral anterior ischemic optic neuropathy (AION) (8–10). A sixth nerve palsy with an ipsilateral Horner syndrome in a patient raised the possibility of cavernous sinus inflammation secondary to GCA (11). A patient with GCA presented initially with severe throat pain, presumably from ischemia of the pharyngeal tissue due to inflammation of the branches of the external carotid artery (12). Two patients were reported to have postural vision loss secondary to GCA (13). Cases of occult GCA causing transient monocular vision loss or bilateral sequential central retinal artery occlusions keeps GCA on the differential diagnosis in patients presenting with these signs and symptoms, despite lacking typical GA complaints and having normal lab values (14–16). Less commonly reported exam findings in patients with GCA included bilateral mydriasis, anterior uveitis, and anterior segment ischemia (17–19). Siegrist streaks were described in a patient with ophthalmic artery occlusion secondary to GCA (20). GCA in a patient with systemic sclerosis cautions us that patients can have similar symptoms from more than 1 condition (21). Several studies have commented on the presence of optic nerve sheath enhancement on magnetic resonance imaging in GCA, including the unaffected contralateral optic nerve, which may guide diagnosis and further elucidate the pathophysiology of GCA (22–24). A case report of radiosensitive orbital inflammation in a patient with GCA reminds us that there are many unanswered questions in the immunopathologic process of GCA (25,26).
Certain exam findings can assist in differentiating arteritic AION from nonarteritic anterior ischemic optic neuropathy (NAION). Patients with ocular manifestations of GCA were found to have significantly lower intraocular pressure compared with patients with NAION and controls (27). A key finding of delayed choroidal filling on fluorescein angiography is highly specific for GCA (with either arteritic AION or amaurosis fugax) compared with nonarteritic AION (28).
The interpretation of blood work often plays an important role in the diagnosis of GCA. However, the erythrocyte sedimentation rate (ESR) is nonspecific and can be elevated in the setting of renal disease (29) and lowered in patients taking nonsteroidal anti-inflammatory or statin medications (30). Thrombocytosis can be a helpful adjunct marker to differentiate arteritic AION from other types of optic neuropathy (31).
Superficial temporal artery biopsy remains the “gold standard” in diagnosis of GCA. Although biopsies of at least 2 cm in length have been recommended to reduce the risk of false negative results from skip lesions, 1 retrospective review found that there was no correlation between length of biopsy and histological findings in specimens of at least 4 mm in length (32). A review of histopathological features of temporal artery biopsies also found no correlation with presenting visual or systemic symptoms, severity of vision loss or elevation in ESR (33). The debate over unilateral vs. bilateral simultaneous or sequential biopsies continues. Two articles published in 2000 reviewed the discordance rate amongst bilateral biopsies, with 1 reporting a rate of less than 2% and another higher at 13% (34,35). In an editorial review of the articles, Miller discussed the lower risk of the procedure compared with the significant risk of vision loss due to a missed diagnosis of GCA and concluded that even with a low rate of discordance, bilateral simultaneous or sequential biopsies should be considered (36). Lessell cautioned that clinical judgment is also important and that not every patient with a low likelihood of GCA needs bilateral biopsies (37). A recent large review of patients undergoing temporal artery biopsies led to a diagnostic algorithm based on specific symptoms, exam findings, and lab results, which may assist physicians in determining prebiopsy risk for GCA when evaluating patients (38).
Color Doppler ultrasound of the superficial temporal artery offers a noninvasive way to diagnose GCA, but with lower sensitivity and specificity compared with temporal artery biopsy, in addition to higher degree of examiner variability, it is not currently accepted as standard of care (39). Microembolus in the ophthalmic artery on transcranial Doppler testing was observed in a patient with arteritic AION (40).
Steroids remain the standard of care for the treatment of GCA; however, complications and recurrence can occur while on treatment. One patient was reported to have died from disseminated aspergillosis while on high-dose steroids for GCA (41). Vision loss despite escalating doses of steroids was described in another patient (42). In contrast, a 47-year-old man with a biopsy consistent with GCA was reported to have dramatic visual recovery after high-dose intravenous steroids (43). Ipsilateral recurrence of ischemic optic neuropathy was observed in patients on maintenance doses of prednisone, up to 3 years after initial diagnosis (44,45). Controversy continues on whether patients with GCA should be treated with immediate high-dose oral vs. intravenous steroids, with some consensus that a patient presenting with severe vision loss should be given at least 1 dose of intravenous steroids (46). A patient on etanercept for rheumatoid arthritis developed arteritic AION from GCA, suggesting that antitumor necrosis factor agents are not beneficial as a steroid sparing agent in GCA (47). A state-of-the-art review in 2012 discussed the immunopathology of GCA and potential future targeted therapies (48).
GCA can have devastating visual consequences, although a review of visual performance and quality of life measures in GCA patients showed no significant difference in disability between patients with and without vision loss when only 1 eye was affected (49).
Although significant progress has been made in describing the diverse manifestations of GCA and guidelines for diagnosis, many questions remain about the underlying pathophysiology. Ongoing research efforts may allow us to diagnose GCA more accurately and noninvasively before onset of visual loss and to treat affected patients with targeted, less morbid therapies.
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