Ophthalmic manifestations of giant cell arteritis

Ophthalmic manifestations of giant cell arteritis Abstract GCA, the most common systemic arteritis, affects medium-sized and larger extradural arteries that have the internal elastic lamina. Involvement of the ophthalmic artery and its branches results in visual loss, which is often complete but is usually painless. Visual loss may be monocular or binocular developing simultaneously or sequentially. Rarely, it stems from occipital lobe infarct that result in homonymous hemianopia, a visual field defect involving the two identical halves (right or left) of the visual fields of both eyes. Visual hallucinations and diplopia are less common. All visual symptoms, including those that are transient, require urgent ophthalmological evaluation and treatment with high-dose glucocorticoids to avoid permanent visual loss. giant cell arteritis, visual loss, visual hallucinations, ischaemic optic neuropathy, retinal artery occlusion, occipital infarct, diplopia, glucocorticoids Rheumatology key messages All acute ophthalmic manifestations of GCA are emergencies, given the risk of permanent visual loss. The importance of premonitory symptoms in GCA, including transient monocular vision loss, visual hallucinations and diplopia, is frequently unrecognized. High-dose glucocorticoids are the mainstay of initial treatment of GCA patients with visual symptoms. Introduction GCA can disrupt vision by causing ischaemia of either the afferent or the efferent visual pathways [1]. The former produces visual loss, whereas the latter produces double vision. All acute ophthalmic manifestations of GCA are emergencies, given the risk for progressive and permanent damage. Arteritic anterior ischaemic optic neuropathy (AAION), which often is severe and irreversible, is the most common cause of GCA-associated blindness [2]. GCA is characterized by granulomatous inflammation that results in narrowing or occlusion of medium-sized and larger extradural arteries that have the internal elastic lamina [3]. In the orbit, GCA-induced vasculitis has a predilection for the ophthalmic artery and its branches, including most importantly the posterior ciliary arteries (PCAs) and the central retinal artery (Fig. 1). The PCAs perfuse the choroid, which nourishes the photoreceptors in the outer third of the retina and the optic nerve head [4]. The central retinal artery provides blood to the inner two-thirds of the retina, which includes the retinal ganglion cells, the axons of which form the optic nerve. The ophthalmic artery also provides blood to the extraocular muscles and the vasa nervorum of the ocular motor nerves. Ischaemia of these structures causes ophthalmoparesis and diplopia [1]. Giant cell arteritis also can affect extracranial and intracranial blood vessels and produce homonymous loss of the visual field (i.e. loss of vision to the same side of each eye) due to stroke in the occipital cortex. Fig. 1 View largeDownload slide Blood supply to the optic nerve and the posterior segment of the eye The blood supply to the optic nerve and the eye comes from the branches of the ophthalmic artery. Long branches of posterior ciliary arteries perfuse the choroid, which nourishes the outer third of the retina containing photoreceptors. The short branches of posterior ciliary arteries create an anastomotic arterial circle (the circle of Zinn-Haller) that provides blood supply to the optic nerve head (anterior part of the optic nerve). The posterior part of the optic nerve is supplied by the small branches of the ophthalmic artery. The inner two-thirds of the retina receives its blood supply from the central retinal artery and its branches (branch retinal arteries). From Biousse V and Newman NJ. Ischemic optic neuropathies. N Engl J Med 2015;372:2428–36. Copyright © (2015) Reprinted with permission from Massachusetts Medical Society. Fig. 1 View largeDownload slide Blood supply to the optic nerve and the posterior segment of the eye The blood supply to the optic nerve and the eye comes from the branches of the ophthalmic artery. Long branches of posterior ciliary arteries perfuse the choroid, which nourishes the outer third of the retina containing photoreceptors. The short branches of posterior ciliary arteries create an anastomotic arterial circle (the circle of Zinn-Haller) that provides blood supply to the optic nerve head (anterior part of the optic nerve). The posterior part of the optic nerve is supplied by the small branches of the ophthalmic artery. The inner two-thirds of the retina receives its blood supply from the central retinal artery and its branches (branch retinal arteries). From Biousse V and Newman NJ. Ischemic optic neuropathies. N Engl J Med 2015;372:2428–36. Copyright © (2015) Reprinted with permission from Massachusetts Medical Society. Afferent manifestations The reported incidence of visual symptoms in GCA ranges widely, from 12 to 70% (Table 1) [1, 5–27], with lower numbers being reported in large population-based studies (as opposed to clinic-based studies) and in studies conducted after the introduction of the glucocorticoids [26]. Factors associated with visual loss include lower levels of inflammatory markers, prior stroke and peripheral vascular disease [28]. Table 1 Large retrospective studies describing visual morbidity in patients with GCA Source  Study population  Time period  Sample size/number of women enrolled (% of women)  Biopsy-positive, n (%)  Visual symptoms (including TMVL and diplopia), n (%)  Permanent visual loss, n (%)  TMVL/solated TMVL, n  Diplopia and/or ophthalmoplegia, n (%)  Course of efferent abnormalities  AION, n  CRAO, n  CLRAO, n  BRAO, n  PION, n  Other ocular pathologies  Cortical visual loss, n  [5]  GCA, Mayo Clinic, MN, USA  –1956  122/64 (52)  74 (60)  41 of 74 (55)  28 of 74 (38)  12 of 74/8 of 74  11 of 74 (15)  NR  23 of 74 (reported together w/PION; AION 34 eyes, PION 4 eyes)  1 of 74  NR  NR  See AION  Two with ischaemic retinopathy  NR  [6]  Biopsy-proven GCA, United Birmingham Hospitals, UK  1948–62  72/39 (54)  NA  49 (68)  40 (56)  8/5  14 (2 with ptosis; 19%)  Transient  Papilloedema in majority of cases w/visual loss  NR  NR  NR  NR  NR  NR  [7]  Biopsy-proven GCA, Chelmsford Group of Hospitals, UK  1965–72  36/21 (58)  36 of 42 biopsied (86)  8 of 36 (22)  3 of 36 (8)  Unclear/3 of 36  1 of 36 (3)  Transient  NR  NR  NR  NR  NR  NR  NR  [8]  GCA, Olmsted County, MN, USA  1950–74  42/33 (79)  38 of 38 (100)  17 (40)  8 (20)  5/NR  5 (12)  NR  NR  NR  NR  NR  NR  NR  NR  [9]  Biopsy-proven GCA, Lothian Region, UK  1964–77  136/101 (74)  NA  93 (68)  81 (60)  12/6  6 (4)  Transient  66 of 81  15 of 81  NR  NR  NR  NR  NR  [10]  Biopsy-proven GCA, Royal Adelaide Hospital, Australia  1973–78  25/18 (72)  NA  17 (68)  4 (16)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [11]  GCA, two hospitals in Goteborg, Sweden  1973–75  126/85 (67)  74 (59)  15 of 126 (12)  9 of 126 (7), 6 of 74 (8)  2/2  4 of 126 (3)  Transient  8 of 126 or 5 of 74  1 with retinal stroke  NR  NR  NR  NR  NR  [12]  Biopsy-proven GCA, two hospitals in London, UK  1968–78  90/64 (71)  NA  55 (61)  44 (49)  NR  11 (12)  Transient  38  4  0  1  NR  NR  1  [13]  Biopsy-proven GCA, Mayo Clinic, MN, USA  1981–83  166/128 (77)  NA  35 (21)  14 (8)  17/15  3 (2)  NR  NR  NR  NR  NR  NR  NR  2  [14]  GCA, Mayo Clinic, MN, USA  1980–84  245/185 (76)  204 of 231 (88)  52 (21)  34 of 245 (14), 25 of 204 (12)  16 of 245/12 of 245  6 of 245 (2)  Transient  24 of 245  7 of 245  NR  NR  1 of 245  1 of 245 with macular haemorrhages  1 of 245  [15]  GCA, Iceland  1984–90  133/94 (70)  125 (94)  19 (14)  1 (0.75)  3/3  2 (1.5)  NR  NR  NR  NR  NR  NR  NR  NR  [16]  Visual symptoms and biopsy-proven GCA, Bascom Palmer Eye Institute, FL, USA  1980–93  45/31 (69)  NA  All patients  41/45 (91), 63 eyes  8/3  7 (16)  NR  55 of 63 eyes  3 of 63 eyes  NR  3 of 63 eyes  2 of 63 eyes  4 of 63 eyes with choroidal infarction;3 of 63 eyes with optic atrophy  NR  [17]  Biopsy-proven GCA and available FA, Hôpital Ophthalmique Jules Gonin, Switzerland  1977–94  47/33 (70)  NA  33 (70)  25 of 30 (83)  12 of 30/5 of 30  6 (13)  CN palsies in 4, persistent ophthalmoplegia in 2  22 (6 AION + CLRAO)  7 with CRAO/ BRAO  7 (6 CLRAO + AION, 1 CLRAO + CRAO)  7 with CRAO/ BRAO  NR  Choroidal ischaemia associated with other abnormalities  NR  [18]  Biopsy-proven GCA, Hospital Clinic i Provincial, Spain  1980–95  146/102 (70)  NA  23 (16)  23 (16)  7/0  2 (1)  NR  18 (1 AION + CRAO)  1  NR  1  NR  Three without funduscopic exam  NR  [19]  Biopsy-proven GCA, three hospitals in Spain  1975–96  239/133 (56)  NA  69 (29)  34 (14)  40/25  16 (7)  Transient in 11  30  2  NR  NR  1  NR  1  [20]  Biopsy-proven GCA, three hospitals in Barcelona, Spain  1980–96  200/141 (70)  NA  Unclear (>38)  28 (14)  20/NR  11 (5.5)  Transient in 9, persistent ophthalmoplegia in 2  23 (1 AION + CRAO)  1  NR  1  1 ? (normal funduscopic exam)  Three without funduscopic exam  NR  [1]  Biopsy-proven GCA, University of Iowa Hospitals and Clinics, IA, USA  1973–95  170/123 (72)  NA  85 (50)  83 (49)  26, 33 eyes/12 of 33 eyes  5 (3)  Transient  69  12  12 of 55 patients with FA  NR  6  One with ocular ischaemia  NR  [21]  Biopsy-proven GCA, Hospital Xeral-Calde, Spain  1981–98  161/79 (49)  NA  42 (26)  24 (15)  23/11  9 (6)  CN palsies in 3  22  2  NR  NR  NR  NR  1  [22]  GCA, Dupuyren Hospital, France  1978–2000  174/109 (63)  147 (88)  48 of 174 (28)  23 of 174 (13)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [23]  GCA, four hospitals in Jerusalem, Israel  1980–2000  175/110 (63)  152 (87)  48 (27)  32 (18)  <14 (reported together with TIA)/NR  3  Transient  26  6  NR  NR  NR  NR  NR  [24]  Biopsy-proven GCA, Santa Maria Nuova Hospital, Italy  1986–2002  136/102 (75)  NA  41 (30)  26 (19)  15/13  6 (4)  Transient  24  2  NR  NR  NR  NR  NR  [25]  Biopsy-proven GCA, Hospital Xeral-Calde, Spain  1981–2005  255/139 (55)  NA  57 (22)  32 (16)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [26]  GCA, Olmsted County, MN, USA  1950–2004  204/163 (80)  177 of 192 (92)  47 of 204 (23)  18 (9)  7/NR  11 (5)  NR  17  2  NR  NR  NR  Two with non- specific changes  NR  [27]  GCA, Olmsted County, MN, USA  1950–2009  245/178 (79)  NR  NR  20 (8.2)  NR  NR  NR  17 (1 AION + CLRAO, 1 AION + CRAO)  4  1  NR  NR  NR  NR  Source  Study population  Time period  Sample size/number of women enrolled (% of women)  Biopsy-positive, n (%)  Visual symptoms (including TMVL and diplopia), n (%)  Permanent visual loss, n (%)  TMVL/solated TMVL, n  Diplopia and/or ophthalmoplegia, n (%)  Course of efferent abnormalities  AION, n  CRAO, n  CLRAO, n  BRAO, n  PION, n  Other ocular pathologies  Cortical visual loss, n  [5]  GCA, Mayo Clinic, MN, USA  –1956  122/64 (52)  74 (60)  41 of 74 (55)  28 of 74 (38)  12 of 74/8 of 74  11 of 74 (15)  NR  23 of 74 (reported together w/PION; AION 34 eyes, PION 4 eyes)  1 of 74  NR  NR  See AION  Two with ischaemic retinopathy  NR  [6]  Biopsy-proven GCA, United Birmingham Hospitals, UK  1948–62  72/39 (54)  NA  49 (68)  40 (56)  8/5  14 (2 with ptosis; 19%)  Transient  Papilloedema in majority of cases w/visual loss  NR  NR  NR  NR  NR  NR  [7]  Biopsy-proven GCA, Chelmsford Group of Hospitals, UK  1965–72  36/21 (58)  36 of 42 biopsied (86)  8 of 36 (22)  3 of 36 (8)  Unclear/3 of 36  1 of 36 (3)  Transient  NR  NR  NR  NR  NR  NR  NR  [8]  GCA, Olmsted County, MN, USA  1950–74  42/33 (79)  38 of 38 (100)  17 (40)  8 (20)  5/NR  5 (12)  NR  NR  NR  NR  NR  NR  NR  NR  [9]  Biopsy-proven GCA, Lothian Region, UK  1964–77  136/101 (74)  NA  93 (68)  81 (60)  12/6  6 (4)  Transient  66 of 81  15 of 81  NR  NR  NR  NR  NR  [10]  Biopsy-proven GCA, Royal Adelaide Hospital, Australia  1973–78  25/18 (72)  NA  17 (68)  4 (16)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [11]  GCA, two hospitals in Goteborg, Sweden  1973–75  126/85 (67)  74 (59)  15 of 126 (12)  9 of 126 (7), 6 of 74 (8)  2/2  4 of 126 (3)  Transient  8 of 126 or 5 of 74  1 with retinal stroke  NR  NR  NR  NR  NR  [12]  Biopsy-proven GCA, two hospitals in London, UK  1968–78  90/64 (71)  NA  55 (61)  44 (49)  NR  11 (12)  Transient  38  4  0  1  NR  NR  1  [13]  Biopsy-proven GCA, Mayo Clinic, MN, USA  1981–83  166/128 (77)  NA  35 (21)  14 (8)  17/15  3 (2)  NR  NR  NR  NR  NR  NR  NR  2  [14]  GCA, Mayo Clinic, MN, USA  1980–84  245/185 (76)  204 of 231 (88)  52 (21)  34 of 245 (14), 25 of 204 (12)  16 of 245/12 of 245  6 of 245 (2)  Transient  24 of 245  7 of 245  NR  NR  1 of 245  1 of 245 with macular haemorrhages  1 of 245  [15]  GCA, Iceland  1984–90  133/94 (70)  125 (94)  19 (14)  1 (0.75)  3/3  2 (1.5)  NR  NR  NR  NR  NR  NR  NR  NR  [16]  Visual symptoms and biopsy-proven GCA, Bascom Palmer Eye Institute, FL, USA  1980–93  45/31 (69)  NA  All patients  41/45 (91), 63 eyes  8/3  7 (16)  NR  55 of 63 eyes  3 of 63 eyes  NR  3 of 63 eyes  2 of 63 eyes  4 of 63 eyes with choroidal infarction;3 of 63 eyes with optic atrophy  NR  [17]  Biopsy-proven GCA and available FA, Hôpital Ophthalmique Jules Gonin, Switzerland  1977–94  47/33 (70)  NA  33 (70)  25 of 30 (83)  12 of 30/5 of 30  6 (13)  CN palsies in 4, persistent ophthalmoplegia in 2  22 (6 AION + CLRAO)  7 with CRAO/ BRAO  7 (6 CLRAO + AION, 1 CLRAO + CRAO)  7 with CRAO/ BRAO  NR  Choroidal ischaemia associated with other abnormalities  NR  [18]  Biopsy-proven GCA, Hospital Clinic i Provincial, Spain  1980–95  146/102 (70)  NA  23 (16)  23 (16)  7/0  2 (1)  NR  18 (1 AION + CRAO)  1  NR  1  NR  Three without funduscopic exam  NR  [19]  Biopsy-proven GCA, three hospitals in Spain  1975–96  239/133 (56)  NA  69 (29)  34 (14)  40/25  16 (7)  Transient in 11  30  2  NR  NR  1  NR  1  [20]  Biopsy-proven GCA, three hospitals in Barcelona, Spain  1980–96  200/141 (70)  NA  Unclear (>38)  28 (14)  20/NR  11 (5.5)  Transient in 9, persistent ophthalmoplegia in 2  23 (1 AION + CRAO)  1  NR  1  1 ? (normal funduscopic exam)  Three without funduscopic exam  NR  [1]  Biopsy-proven GCA, University of Iowa Hospitals and Clinics, IA, USA  1973–95  170/123 (72)  NA  85 (50)  83 (49)  26, 33 eyes/12 of 33 eyes  5 (3)  Transient  69  12  12 of 55 patients with FA  NR  6  One with ocular ischaemia  NR  [21]  Biopsy-proven GCA, Hospital Xeral-Calde, Spain  1981–98  161/79 (49)  NA  42 (26)  24 (15)  23/11  9 (6)  CN palsies in 3  22  2  NR  NR  NR  NR  1  [22]  GCA, Dupuyren Hospital, France  1978–2000  174/109 (63)  147 (88)  48 of 174 (28)  23 of 174 (13)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [23]  GCA, four hospitals in Jerusalem, Israel  1980–2000  175/110 (63)  152 (87)  48 (27)  32 (18)  <14 (reported together with TIA)/NR  3  Transient  26  6  NR  NR  NR  NR  NR  [24]  Biopsy-proven GCA, Santa Maria Nuova Hospital, Italy  1986–2002  136/102 (75)  NA  41 (30)  26 (19)  15/13  6 (4)  Transient  24  2  NR  NR  NR  NR  NR  [25]  Biopsy-proven GCA, Hospital Xeral-Calde, Spain  1981–2005  255/139 (55)  NA  57 (22)  32 (16)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [26]  GCA, Olmsted County, MN, USA  1950–2004  204/163 (80)  177 of 192 (92)  47 of 204 (23)  18 (9)  7/NR  11 (5)  NR  17  2  NR  NR  NR  Two with non- specific changes  NR  [27]  GCA, Olmsted County, MN, USA  1950–2009  245/178 (79)  NR  NR  20 (8.2)  NR  NR  NR  17 (1 AION + CLRAO, 1 AION + CRAO)  4  1  NR  NR  NR  NR  AION: anterior ischaemic optic neuropathy; BRAO: branch retinal artery occlusion; CLRAO: cilioretinal artery occlusion; CN, cranial nerve; CRAO: central retinal artery occlusion; FA: fluorescein angiography; NA: not available; NR: not reported; PION: posterior ischaemic optic neuropathy; TIA: transient ischaemic attack; TMVL: transient monocular visual loss. Permanent vision loss Of patients with permanent vision loss, 8–28% report premonitory transient monocular vision loss (TMVL) [1, 17]. More than 10% of patients report pain at the time of visual loss [1, 16]. Notably, about 20% of patients with GCA-induced visual loss do not have any systemic symptoms of the disease, which makes it challenging to recognize the diagnosis [29]. Bilateral vision loss, either simultaneous or sequential, occurs in 20–62% of patients, which emphasizes the need for prompt diagnosis and treatment [16, 30]. Patients who become blind because of GCA usually (80–90% of the time) experience arteritic ischaemic optic neuropathy (AION; Table 1) [1, 16, 30, 31]. Patients may also present with evidence of both optic nerve head and retinal ischaemia, which in an older patient is virtually diagnostic of GCA. Occipital lobe infarction is quite uncommon [14], and branch retinal artery occlusions are rare, given the general understanding that they are not primarily involved in the inflammatory process because they lack the internal elastic lamina [32]. The visual loss is severe, and the prognosis following loss of vision from GCA is poor. The severity of visual loss reflects both the loss of central visual acuity (VA) and the loss of visual field. VA is a measure of the ability to spatially distinguish two points in space, and generally refers to central acuity, which reflects the maximum ability to resolve spatial detail as enabled by the foveal outflow pathway from the retina to the brain. VA has been historically measured using Snellen eye charts with lines of letters of different sizes. The charts are read at a fixed distance, and each line of letters on the chart has a corresponding VA. VA worse than 20/800 is evaluated at a fixed distance of 2 ft (0.6 m) and graded as counting fingers, hand motion, light perception and no light perception [33]. The final median VA in one study of patients with GCA-associated visual loss was counting fingers [31], and <40% of patients retained a VA of better than 20/200 [30]. Even with prompt glucocorticoid therapy, the VA of most patients does not change, and in some patients it may worsen, presumably because the treatment was too late or insufficient to stop or reverse the ischaemic process. On the other hand, a small percentage of patients may experience some visual improvement. One study of 32 patients with visual loss from biopsy-proven GCA reported improvement in VA of two or more Snellen lines in 13%, although without concomitant improvement in the visual field [34]. However, the typical scenario is more grim. For instance, one study of 34 patients with visual loss from GCA documented visual deterioration in 27% of eyes within the first week despite treatment with high-dose intravenous corticosteroids [31]. Fifteen per cent of the eyes showed an improvement of VA by two or more Snellen lines within the first month, but only 5% had corresponding improvement in the visual field. In addition, the improvement in visual function was attributed to eccentric viewing rather than a true rescue of the neurovisual pathway. Another study of 84 patients with biopsy-proven GCA showed improvement in both VA of two or more Snellen lines and central visual field in only 4% of patients, with an additional six patients showing a similar improvement in VA without improvement in the central visual field [30]. AION AION is the most common ocular manifestation of GCA (Table 1). The ischaemia to the optic nerve most frequently occurs near the junction of the optic nerve to the eye and produces oedema of the optic nerve head during the acute phase. This presentation is thus known as AAION. Ischaemia that occurs more distally along the optic nerve in the so-called retrobulbar segment causes blindness without swelling of the optic nerve during the acute phase. This presentation, which is much less common, is referred to as arteritic posterior ischaemic optic neuropathy (APION or PION). Either form of ischaemic optic neuropathy must be distinguished from the much more common non-arteritic form of anterior ischaemic optic neuropathy (NAION), which almost always occurs anteriorly and presents with optic nerve head oedema. To assist in this clinical distinction, one searches for clues of an active inflammatory process, which often produces some combination of headache, jaw claudication and constitutional symptoms. A history of PMR should raise the suspicion that new-onset blindness may be secondary to GCA, but some patients with GCA-induced blindness are otherwise asymptomatic and also may have normal inflammatory markers. Thus, one must always have a high index of suspicion that visual loss caused by an optic neuropathy in older patients may be due to GCA. Any older patient with this type of visual loss should undergo laboratory studies that include a complete blood count (to explore for an unexplained anaemia or elevated platelet count), ESR and CRP. As discussed below, even a moderate suspicion that blindness might be secondary to GCA should prompt urgent intervention in an attempt to prevent further visual loss. In the acute phase, AAION produces a pale appearance of the optic nerve head in addition to the oedema (Fig. 2A). This combination of pallor and oedema of the optic nerve head during the acute phase is unusual, since ischaemia caused by the much more common NAION produces oedema of the nerve head in the acute phase and pallor in the chronic phase. With AAION, the pallor of the nerve head becomes even more apparent as the oedema resolves and loss of the retinal ganglion cell axons that form the optic nerve develops (Fig. 2B). In some patients, the more aggressive arteritic process can cause late cupping of the optic nerve head, in distinction to the non-arteritic form (NAION) in which the optic nerve cups are characteristically small. As such, a presentation of ischaemic optic neuropathy in one eye and a relatively large optic nerve head cup in the fellow eye should at least raise a suspicion of GCA. Fig. 2 View largeDownload slide Colour fundus photographs of two patients with AION The right and left eyes are shown on the left- and right-hand sides of the images, respectively. (A) Fundi of a patient who presented with acute bilateral visual loss from giant cell arteritis. There is bilateral optic nerve head oedema, which is ‘pallid’ in the left eye. The left eye also demonstrated cotton wool spots (arrows), which reflect ischaemia of the retina. (B) Bilateral optic disc pallor with cupping as late sequela of AION. AION: arteritic ischaemic optic neuropathy. Fig. 2 View largeDownload slide Colour fundus photographs of two patients with AION The right and left eyes are shown on the left- and right-hand sides of the images, respectively. (A) Fundi of a patient who presented with acute bilateral visual loss from giant cell arteritis. There is bilateral optic nerve head oedema, which is ‘pallid’ in the left eye. The left eye also demonstrated cotton wool spots (arrows), which reflect ischaemia of the retina. (B) Bilateral optic disc pallor with cupping as late sequela of AION. AION: arteritic ischaemic optic neuropathy. As mentioned earlier, ischaemia of the retrobulbar portion of the optic nerve in arteritic posterior ischaemic optic neuropathy does not produce a change in the appearance of the optic nerve head during the acute phase. In the late stage, optic nerve pallor becomes evident, as would be true for any disorder that causes significant damage to the optic nerve fibres. Central retinal artery occlusion Arteritic central retinal artery occlusion (CRAO) also causes profound visual loss, more than is typically seen with non-arteritic CRAO, AION or PION from any cause [32]. The earliest and most subtle funduscopic finding of any CRAO is a blunting of choroidal pigmentary detail in the macula caused by retinal oedema. In hours or within a day, the classic cherry-red spot becomes evident, as does box-carring of blood flow within retinal vessels and retinal arterial attenuation (Fig. 3). In a typical CRAO, whether caused by an embolus or arteritis, a cherry-red spot develops around the fovea; this finding is the result of visual contrast between the oedematous retina surrounding the fovea and retained choroidal perfusion under the retina. When the central retinal artery and ophthalmic artery are both involved, the cherry-red spot may not be as evident because of reduced perfusion of the choroid, with loss of the redness that creates the classic cherry-like appearance of a CRAO. Fig. 3 View largeDownload slide Colour fundus photographs of acute visual loss from CRAO in the right eye The right and left eyes are shown on the left- and right-hand sides, respectively. A cherry-red spot (arrow), segmentation or box-carring of blood flow within retinal vessels (arrowheads) and attenuation of retinal arteries are demonstrated. CRAO: central retinal artery occlusion. Fig. 3 View largeDownload slide Colour fundus photographs of acute visual loss from CRAO in the right eye The right and left eyes are shown on the left- and right-hand sides, respectively. A cherry-red spot (arrow), segmentation or box-carring of blood flow within retinal vessels (arrowheads) and attenuation of retinal arteries are demonstrated. CRAO: central retinal artery occlusion. Cilioretinal artery occlusion Cilioretinal arteries are anatomic variants found in about 25% of the population. These arteries supply the retina even though they arise out of the ciliary circulation, either from the peripapillary choroid or directly from a short PCA. A cilioretinal artery provides nourishment to some portion of the nasal aspect of the macula. In the context of a CRAO, the presence of a cilioretinal artery is protective and tends to allow sparing of a small region of central vision. However, patients with a cilioretinal artery occlusion caused by arteritis tend to fare less well visually, given that the arteritis also often produces a concomitant AION or CRAO (Table 1) [32]. Occipital lobe infarct Ischaemic stroke of the occipital lobe occurs in up to 7% of patients, although this is high compared with our own experience [13, 35]. Similarly, GCA accounts for only a very small percentage of all ischaemic strokes—only 0.15% at our institution (I. Vodopivec and J. F. Rizzo III, personal communication). The incidence of GCA-related stroke in patients older than 50 years has been reported to be 0.76/100 000/year (95% CI: 0, 2.47), with a slightly higher (1.36/100 000/year) risk in men (95% CI: 0, 3.63) and a slightly lower (0.33/100 000/year) risk in women (95% CI: 0, 1.45) [35], which is about 250-fold lower than the overall annual incidence of adult, first-ever, hospital-ascertained stroke of 189/100 000/year noted in 2005 [36]. Transient monocular vision loss Among the general population of older adults, TMVL is usually caused by emboli arising from atherosclerotic plaques. TMVL also occurs with arteritis, and is reported by 8–30% of patients with GCA-induced visual symptoms (Table 1). Premonitory TMVL can occur with incipient retinal or optic nerve ischaemia, although it is more common with the former. TMVL may also occur much more insidiously as a result of borderline perfusion of the retina caused by the ischaemic ocular syndrome. This disorder is usually a result of severe stenosis of the external and internal carotid arteries, which gradually reduces perfusion to both the anterior and posterior segments of the eye. The latter places the retina in a tenuous metabolic state, which can induce recurrent episodes of very brief (i.e. lasting seconds) amaurosis precipitated by exposure to bright light. Such events may occur repeatedly throughout the day, with a much greater frequency and shorter duration than TMVL caused by emboli. Blindness in the ischaemic ocular syndrome is the result of ischaemia of the photoreceptors, which are the most numerous and metabolically demanding cell types in the retina. In GCA, the pathogenic mechanism of the ischaemic ocular syndrome differs from the atherosclerotic form in that GCA can cause pervasive inflammation of orbital arteries, which can have the same ischaemic consequence for the end organ as more proximal atherosclerotic stenosis. The ischaemic ocular syndrome, especially from GCA, is often not diagnosed because it usually presents insidiously, unlike the typical apoplectic visual loss that occurs from ischaemia of the optic nerve or inner retina. Ischaemic ocular syndrome can also cause a red eye, owing to ischaemia of the anterior segment of the eye, which can be misdiagnosed as conjunctivitis. Iritis is often present, though this finding cannot be recognized without a slit lamp examination. Unlike other forms of visual loss from GCA, the ocular ischaemic syndrome responds readily to corticosteroids, and the transient fluctuations of vision may cease without permanent loss of vision. Visual hallucinations Photopsias (i.e. perception of brief flashes of light) are reported by some patients in the acute phase of either the retinal or optic nerve ischaemia. Should permanent visual loss occur, patients may also develop chronic visual hallucinations, often of well-formed images, including perceptions of small people, flowers, animals, etc. This type of hallucination, often referred to as Charles Bonnet syndrome, is believed to result from ‘release’ of activity of the primary visual cortex, which no longer receives its normal afferent input from the eye(s). Charles Bonnet syndrome is common, but is often underdiagnosed [16, 37]. It is advisable to explore with patients the possibility that they are experiencing Charles Bonnet syndrome, since older patients often assume that the hallucinations are the consequence of early dementia or mental illness. Patients are typically reassured that the hallucinations are the result of visual loss. Interestingly, Charles Bonnet syndrome can develop even in patients with relatively mild visual loss. Efferent manifestations Diplopia Diplopia is reported by 1–19% of patients with GCA (Table 1), although our experience is that it is experienced by fewer than 5% of patients with GCA. Diplopia can result from ischaemia of any segment of the ocular motor system, including the brainstem, ocular motor nerves or extraocular muscles. Diplopia is most commonly secondary to a sixth nerve palsy, although a third nerve, or more rarely, a fourth nerve palsy may occur as well with GCA, sometimes as the herald event. Diplopia from GCA can also arise as a manifestation of a brainstem stroke, in which case it is referred to as a skew deviation. Unlike vision loss, diplopia in GCA is typically transient [1], especially when the ocular motor nerves are involved (Table 1), although permanent strabismus can occur as well. Diagnostic evaluation Ophthalmological examination A detailed examination that includes an assessment of VA, colour vision, pupillary function (especially whether a relative afferent pupillary defect is present), ocular motility, intraocular pressures, the anterior segment (with a slit lamp examination) and the posterior segment (with dilated funduscopy) should be performed in any patient with suspected GCA. Possible funduscopic findings include pallid oedema of the optic nerve head and signs of retinal ischaemia, including cotton wool spots (Fig. 2A). In patients with visual loss and testable vision, an examination of the visual fields (typically with automated perimetry) should be performed. Without such testing, loss of visual field may not be recognized by the patient, especially when there is significant visual loss in the fellow eye but retained central vision in the seemingly unaffected eye. Given the high risk of progressive and sequential visual loss, it is important to obtain the most complete assessment of visual function possible during the acute presentation. Fluorescein angiography Suspected GCA may be evaluated with fluorescein angiography, which can demonstrate delay of perfusion and hypoperfusion of either choroid, retina or both (Fig. 4) [38, 39]. A large swathe of choroidal hypoperfusion is highly suggestive of GCA, and should prompt consideration of prompt corticosteroid therapy, especially if patients are experiencing only transient episodes of visual loss. This type of choroidal hypoperfusion is not a feature of NAION. Fig. 4 View largeDownload slide Fluorescein angiography of the left eye Patches of choroidal hypoperfusion are demonstrated (asterisks). The optic nerve head is outlined by yellow arrows. Fig. 4 View largeDownload slide Fluorescein angiography of the left eye Patches of choroidal hypoperfusion are demonstrated (asterisks). The optic nerve head is outlined by yellow arrows. Neuroimaging Neuroimaging is generally normal in patients with GCA. However, some patients with GCA may have non-specific orbital enhancement or enhancement of the optic nerve, chiasm or perineural sheath as signs of inflammation (Fig. 5) [40]. In one study, mural inflammation of the ophthalmic artery in contrast-enhanced, fat-saturated, T1-weighted sequences acquired on 3 T MRI was observed in almost 50% of patients with GCA [41]. In the proper clinical scenario, this finding can suggest a diagnosis of GCA but should not preclude obtaining a biopsy of the temporal artery in an attempt to obtain histological confirmation of the diagnosis. We have not recognized this MRI to be as useful as that report suggested, perhaps because we do not usually obtain an MRI in patients who are suspected of having GCA if the presenting features are fairly typical. However, neuroimaging should generally be obtained in patients with blindness if the aetiology is uncertain, especially because some patients may have an infectious disease, such as fungal sinusitis, that would worsen if treated with corticosteroids. Fig. 5 View largeDownload slide MRI of the orbits in a patient with GCA Coronal and axial contrast-enhanced T1-weighted fat-suppressed magnetic resonance imaging of the orbits demonstrating enhancement of the optic nerve sheaths (arrows). Fig. 5 View largeDownload slide MRI of the orbits in a patient with GCA Coronal and axial contrast-enhanced T1-weighted fat-suppressed magnetic resonance imaging of the orbits demonstrating enhancement of the optic nerve sheaths (arrows). Treatment The advent of the use of corticosteroids in GCA had an immediate and profound salutary benefit for patients [42]. Although there is no doubt that glucocorticoids are effective in the management of GCA, it is also clear that side effects, some of which can be medically serious and even life threatening, commonly occur, given the prolonged course of therapy that typically is required or at least used. Side effects from long-term use of prednisone occur even with careful medical management and with attentive patients who present as requested for follow-up exams. There has been substantial debate and variation on the preferred starting dose and duration of treatment with corticosteroids. The majority of patients with GCA are managed by internists and rheumatologists who tend to use lower starting doses of prednisone (40–60 mg/day) than neuro-ophthalmologists. This approach works well for most patients, although neuro-ophthalmologists are consulted when patients on these lower starting doses experience blindness. Whatever the preference, glucocorticoids must be administered promptly once the diagnosis of GCA is strongly suspected, although it is important to appreciate that there is no adequate evidence-based guidance of a preferred dosing regimen for glucocorticoid therapy alone. As glucocorticoid therapy is introduced, it is critical to be aware that the rare group of patients who present with blindness and signs and symptoms of GCA may harbour an infection (e.g. bacterial endocarditis, fungal sinusitis). As such, there must always be vigilance about these risks, since glucocorticoid therapy could have disastrous consequences. Regardless of the dosing preferences among subspecialists, any patient with acute visual loss or stroke should receive glucocorticoids immediately because of the risk of severe, progressive and permanent deficits. The primary purpose of glucocorticoids in this setting is prevention of new ischaemic events, including visual loss in the fellow eye, rather than visual recovery in the affected eye. For patients with acute visual loss in one eye and either symptoms or signs of ischaemia in the second eye, we tend to initiate treatment with a 3-day course of intravenous pulse methylprednisolone (at a dose of 500–1000 mg daily) because of its rapid onset of action. Thereafter, the patient is switched to high-dose (100–120 mg/day) oral prednisone. For patients without visual loss or with visual loss that is confined to one eye, our practice has been to initiate treatment with oral glucocorticoids, with a starting dose of 80–120 mg/day. In general, our approach is to use this dose for 3–4 days (depending upon the clinical course), then decrease gradually to 30 mg/day by the end of the third or fourth week. We typically treat patients with progressively lower doses for 12–18 months. If the pre-treatment ESR or CRP was elevated, sequential tests should be obtained to guide the taper once the dose is relatively low, perhaps 15 mg/day or less. It is rare for patients to experience blindness after an initial period of effective treatment followed by a taper to ∼15 mg. All dosing should be given once daily, as patients can be at risk of blindness if prednisone is switched to alternate-day dosing. At 10–15 mg/day, the taper can generally be reduced by 2.5-mg increments, assuming that the patient does not have symptoms suggestive of adrenal insufficiency and has a normal morning cortisol level. The one exception to this guideline is for patients who also have PMR, as they frequently can become symptomatic even with a 1 mg per day reduction in prednisone. If the index of suspicion for GCA is low, treatment with glucocorticoids may not be needed, although in such cases it is reassuring to obtain a negative temporal artery biopsy. Glucocorticoid treatment will not affect the results of temporal artery biopsy if the biopsy is performed within a week or so of beginning therapy [43]. Because of its antithrombotic and anti-inflammatory properties and favourable side effect profile, low-dose aspirin has been commonly used as an adjunctive treatment in GCA. It should be noted, however, that there have been no randomized controlled trials evaluating the role of aspirin for the prevention of ischaemic complications [44], and data from several retrospective studies have been conflicting [22, 45–50]. A recent landmark study demonstrated the benefit of tocilizumab administered weekly or every other week in the treatment of GCA [51, 52]. This study provided convincing evidence of a steroid-sparing benefit of tocilizumab, which should improve the long-term risk–benefit profile for treating GCA. This study was not designed to assess the effect of tocilizumab and its dosing regimens on vision complications. The investigators, however, reported that one patient in the group that received tocilizumab every other week had AAION and vision loss that resolved after treatment with glucocorticoids. It is, therefore, important that clinicians managing patients with GCA maintain persistent vigilance for ophthalmic manifestations. Future studies addressing the efficacy of tocilizumab with respect to prevention of ophthalmic complications in patients with GCA are required. 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Ophthalmic manifestations of giant cell arteritis

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Abstract

Abstract GCA, the most common systemic arteritis, affects medium-sized and larger extradural arteries that have the internal elastic lamina. Involvement of the ophthalmic artery and its branches results in visual loss, which is often complete but is usually painless. Visual loss may be monocular or binocular developing simultaneously or sequentially. Rarely, it stems from occipital lobe infarct that result in homonymous hemianopia, a visual field defect involving the two identical halves (right or left) of the visual fields of both eyes. Visual hallucinations and diplopia are less common. All visual symptoms, including those that are transient, require urgent ophthalmological evaluation and treatment with high-dose glucocorticoids to avoid permanent visual loss. giant cell arteritis, visual loss, visual hallucinations, ischaemic optic neuropathy, retinal artery occlusion, occipital infarct, diplopia, glucocorticoids Rheumatology key messages All acute ophthalmic manifestations of GCA are emergencies, given the risk of permanent visual loss. The importance of premonitory symptoms in GCA, including transient monocular vision loss, visual hallucinations and diplopia, is frequently unrecognized. High-dose glucocorticoids are the mainstay of initial treatment of GCA patients with visual symptoms. Introduction GCA can disrupt vision by causing ischaemia of either the afferent or the efferent visual pathways [1]. The former produces visual loss, whereas the latter produces double vision. All acute ophthalmic manifestations of GCA are emergencies, given the risk for progressive and permanent damage. Arteritic anterior ischaemic optic neuropathy (AAION), which often is severe and irreversible, is the most common cause of GCA-associated blindness [2]. GCA is characterized by granulomatous inflammation that results in narrowing or occlusion of medium-sized and larger extradural arteries that have the internal elastic lamina [3]. In the orbit, GCA-induced vasculitis has a predilection for the ophthalmic artery and its branches, including most importantly the posterior ciliary arteries (PCAs) and the central retinal artery (Fig. 1). The PCAs perfuse the choroid, which nourishes the photoreceptors in the outer third of the retina and the optic nerve head [4]. The central retinal artery provides blood to the inner two-thirds of the retina, which includes the retinal ganglion cells, the axons of which form the optic nerve. The ophthalmic artery also provides blood to the extraocular muscles and the vasa nervorum of the ocular motor nerves. Ischaemia of these structures causes ophthalmoparesis and diplopia [1]. Giant cell arteritis also can affect extracranial and intracranial blood vessels and produce homonymous loss of the visual field (i.e. loss of vision to the same side of each eye) due to stroke in the occipital cortex. Fig. 1 View largeDownload slide Blood supply to the optic nerve and the posterior segment of the eye The blood supply to the optic nerve and the eye comes from the branches of the ophthalmic artery. Long branches of posterior ciliary arteries perfuse the choroid, which nourishes the outer third of the retina containing photoreceptors. The short branches of posterior ciliary arteries create an anastomotic arterial circle (the circle of Zinn-Haller) that provides blood supply to the optic nerve head (anterior part of the optic nerve). The posterior part of the optic nerve is supplied by the small branches of the ophthalmic artery. The inner two-thirds of the retina receives its blood supply from the central retinal artery and its branches (branch retinal arteries). From Biousse V and Newman NJ. Ischemic optic neuropathies. N Engl J Med 2015;372:2428–36. Copyright © (2015) Reprinted with permission from Massachusetts Medical Society. Fig. 1 View largeDownload slide Blood supply to the optic nerve and the posterior segment of the eye The blood supply to the optic nerve and the eye comes from the branches of the ophthalmic artery. Long branches of posterior ciliary arteries perfuse the choroid, which nourishes the outer third of the retina containing photoreceptors. The short branches of posterior ciliary arteries create an anastomotic arterial circle (the circle of Zinn-Haller) that provides blood supply to the optic nerve head (anterior part of the optic nerve). The posterior part of the optic nerve is supplied by the small branches of the ophthalmic artery. The inner two-thirds of the retina receives its blood supply from the central retinal artery and its branches (branch retinal arteries). From Biousse V and Newman NJ. Ischemic optic neuropathies. N Engl J Med 2015;372:2428–36. Copyright © (2015) Reprinted with permission from Massachusetts Medical Society. Afferent manifestations The reported incidence of visual symptoms in GCA ranges widely, from 12 to 70% (Table 1) [1, 5–27], with lower numbers being reported in large population-based studies (as opposed to clinic-based studies) and in studies conducted after the introduction of the glucocorticoids [26]. Factors associated with visual loss include lower levels of inflammatory markers, prior stroke and peripheral vascular disease [28]. Table 1 Large retrospective studies describing visual morbidity in patients with GCA Source  Study population  Time period  Sample size/number of women enrolled (% of women)  Biopsy-positive, n (%)  Visual symptoms (including TMVL and diplopia), n (%)  Permanent visual loss, n (%)  TMVL/solated TMVL, n  Diplopia and/or ophthalmoplegia, n (%)  Course of efferent abnormalities  AION, n  CRAO, n  CLRAO, n  BRAO, n  PION, n  Other ocular pathologies  Cortical visual loss, n  [5]  GCA, Mayo Clinic, MN, USA  –1956  122/64 (52)  74 (60)  41 of 74 (55)  28 of 74 (38)  12 of 74/8 of 74  11 of 74 (15)  NR  23 of 74 (reported together w/PION; AION 34 eyes, PION 4 eyes)  1 of 74  NR  NR  See AION  Two with ischaemic retinopathy  NR  [6]  Biopsy-proven GCA, United Birmingham Hospitals, UK  1948–62  72/39 (54)  NA  49 (68)  40 (56)  8/5  14 (2 with ptosis; 19%)  Transient  Papilloedema in majority of cases w/visual loss  NR  NR  NR  NR  NR  NR  [7]  Biopsy-proven GCA, Chelmsford Group of Hospitals, UK  1965–72  36/21 (58)  36 of 42 biopsied (86)  8 of 36 (22)  3 of 36 (8)  Unclear/3 of 36  1 of 36 (3)  Transient  NR  NR  NR  NR  NR  NR  NR  [8]  GCA, Olmsted County, MN, USA  1950–74  42/33 (79)  38 of 38 (100)  17 (40)  8 (20)  5/NR  5 (12)  NR  NR  NR  NR  NR  NR  NR  NR  [9]  Biopsy-proven GCA, Lothian Region, UK  1964–77  136/101 (74)  NA  93 (68)  81 (60)  12/6  6 (4)  Transient  66 of 81  15 of 81  NR  NR  NR  NR  NR  [10]  Biopsy-proven GCA, Royal Adelaide Hospital, Australia  1973–78  25/18 (72)  NA  17 (68)  4 (16)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [11]  GCA, two hospitals in Goteborg, Sweden  1973–75  126/85 (67)  74 (59)  15 of 126 (12)  9 of 126 (7), 6 of 74 (8)  2/2  4 of 126 (3)  Transient  8 of 126 or 5 of 74  1 with retinal stroke  NR  NR  NR  NR  NR  [12]  Biopsy-proven GCA, two hospitals in London, UK  1968–78  90/64 (71)  NA  55 (61)  44 (49)  NR  11 (12)  Transient  38  4  0  1  NR  NR  1  [13]  Biopsy-proven GCA, Mayo Clinic, MN, USA  1981–83  166/128 (77)  NA  35 (21)  14 (8)  17/15  3 (2)  NR  NR  NR  NR  NR  NR  NR  2  [14]  GCA, Mayo Clinic, MN, USA  1980–84  245/185 (76)  204 of 231 (88)  52 (21)  34 of 245 (14), 25 of 204 (12)  16 of 245/12 of 245  6 of 245 (2)  Transient  24 of 245  7 of 245  NR  NR  1 of 245  1 of 245 with macular haemorrhages  1 of 245  [15]  GCA, Iceland  1984–90  133/94 (70)  125 (94)  19 (14)  1 (0.75)  3/3  2 (1.5)  NR  NR  NR  NR  NR  NR  NR  NR  [16]  Visual symptoms and biopsy-proven GCA, Bascom Palmer Eye Institute, FL, USA  1980–93  45/31 (69)  NA  All patients  41/45 (91), 63 eyes  8/3  7 (16)  NR  55 of 63 eyes  3 of 63 eyes  NR  3 of 63 eyes  2 of 63 eyes  4 of 63 eyes with choroidal infarction;3 of 63 eyes with optic atrophy  NR  [17]  Biopsy-proven GCA and available FA, Hôpital Ophthalmique Jules Gonin, Switzerland  1977–94  47/33 (70)  NA  33 (70)  25 of 30 (83)  12 of 30/5 of 30  6 (13)  CN palsies in 4, persistent ophthalmoplegia in 2  22 (6 AION + CLRAO)  7 with CRAO/ BRAO  7 (6 CLRAO + AION, 1 CLRAO + CRAO)  7 with CRAO/ BRAO  NR  Choroidal ischaemia associated with other abnormalities  NR  [18]  Biopsy-proven GCA, Hospital Clinic i Provincial, Spain  1980–95  146/102 (70)  NA  23 (16)  23 (16)  7/0  2 (1)  NR  18 (1 AION + CRAO)  1  NR  1  NR  Three without funduscopic exam  NR  [19]  Biopsy-proven GCA, three hospitals in Spain  1975–96  239/133 (56)  NA  69 (29)  34 (14)  40/25  16 (7)  Transient in 11  30  2  NR  NR  1  NR  1  [20]  Biopsy-proven GCA, three hospitals in Barcelona, Spain  1980–96  200/141 (70)  NA  Unclear (>38)  28 (14)  20/NR  11 (5.5)  Transient in 9, persistent ophthalmoplegia in 2  23 (1 AION + CRAO)  1  NR  1  1 ? (normal funduscopic exam)  Three without funduscopic exam  NR  [1]  Biopsy-proven GCA, University of Iowa Hospitals and Clinics, IA, USA  1973–95  170/123 (72)  NA  85 (50)  83 (49)  26, 33 eyes/12 of 33 eyes  5 (3)  Transient  69  12  12 of 55 patients with FA  NR  6  One with ocular ischaemia  NR  [21]  Biopsy-proven GCA, Hospital Xeral-Calde, Spain  1981–98  161/79 (49)  NA  42 (26)  24 (15)  23/11  9 (6)  CN palsies in 3  22  2  NR  NR  NR  NR  1  [22]  GCA, Dupuyren Hospital, France  1978–2000  174/109 (63)  147 (88)  48 of 174 (28)  23 of 174 (13)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [23]  GCA, four hospitals in Jerusalem, Israel  1980–2000  175/110 (63)  152 (87)  48 (27)  32 (18)  <14 (reported together with TIA)/NR  3  Transient  26  6  NR  NR  NR  NR  NR  [24]  Biopsy-proven GCA, Santa Maria Nuova Hospital, Italy  1986–2002  136/102 (75)  NA  41 (30)  26 (19)  15/13  6 (4)  Transient  24  2  NR  NR  NR  NR  NR  [25]  Biopsy-proven GCA, Hospital Xeral-Calde, Spain  1981–2005  255/139 (55)  NA  57 (22)  32 (16)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [26]  GCA, Olmsted County, MN, USA  1950–2004  204/163 (80)  177 of 192 (92)  47 of 204 (23)  18 (9)  7/NR  11 (5)  NR  17  2  NR  NR  NR  Two with non- specific changes  NR  [27]  GCA, Olmsted County, MN, USA  1950–2009  245/178 (79)  NR  NR  20 (8.2)  NR  NR  NR  17 (1 AION + CLRAO, 1 AION + CRAO)  4  1  NR  NR  NR  NR  Source  Study population  Time period  Sample size/number of women enrolled (% of women)  Biopsy-positive, n (%)  Visual symptoms (including TMVL and diplopia), n (%)  Permanent visual loss, n (%)  TMVL/solated TMVL, n  Diplopia and/or ophthalmoplegia, n (%)  Course of efferent abnormalities  AION, n  CRAO, n  CLRAO, n  BRAO, n  PION, n  Other ocular pathologies  Cortical visual loss, n  [5]  GCA, Mayo Clinic, MN, USA  –1956  122/64 (52)  74 (60)  41 of 74 (55)  28 of 74 (38)  12 of 74/8 of 74  11 of 74 (15)  NR  23 of 74 (reported together w/PION; AION 34 eyes, PION 4 eyes)  1 of 74  NR  NR  See AION  Two with ischaemic retinopathy  NR  [6]  Biopsy-proven GCA, United Birmingham Hospitals, UK  1948–62  72/39 (54)  NA  49 (68)  40 (56)  8/5  14 (2 with ptosis; 19%)  Transient  Papilloedema in majority of cases w/visual loss  NR  NR  NR  NR  NR  NR  [7]  Biopsy-proven GCA, Chelmsford Group of Hospitals, UK  1965–72  36/21 (58)  36 of 42 biopsied (86)  8 of 36 (22)  3 of 36 (8)  Unclear/3 of 36  1 of 36 (3)  Transient  NR  NR  NR  NR  NR  NR  NR  [8]  GCA, Olmsted County, MN, USA  1950–74  42/33 (79)  38 of 38 (100)  17 (40)  8 (20)  5/NR  5 (12)  NR  NR  NR  NR  NR  NR  NR  NR  [9]  Biopsy-proven GCA, Lothian Region, UK  1964–77  136/101 (74)  NA  93 (68)  81 (60)  12/6  6 (4)  Transient  66 of 81  15 of 81  NR  NR  NR  NR  NR  [10]  Biopsy-proven GCA, Royal Adelaide Hospital, Australia  1973–78  25/18 (72)  NA  17 (68)  4 (16)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [11]  GCA, two hospitals in Goteborg, Sweden  1973–75  126/85 (67)  74 (59)  15 of 126 (12)  9 of 126 (7), 6 of 74 (8)  2/2  4 of 126 (3)  Transient  8 of 126 or 5 of 74  1 with retinal stroke  NR  NR  NR  NR  NR  [12]  Biopsy-proven GCA, two hospitals in London, UK  1968–78  90/64 (71)  NA  55 (61)  44 (49)  NR  11 (12)  Transient  38  4  0  1  NR  NR  1  [13]  Biopsy-proven GCA, Mayo Clinic, MN, USA  1981–83  166/128 (77)  NA  35 (21)  14 (8)  17/15  3 (2)  NR  NR  NR  NR  NR  NR  NR  2  [14]  GCA, Mayo Clinic, MN, USA  1980–84  245/185 (76)  204 of 231 (88)  52 (21)  34 of 245 (14), 25 of 204 (12)  16 of 245/12 of 245  6 of 245 (2)  Transient  24 of 245  7 of 245  NR  NR  1 of 245  1 of 245 with macular haemorrhages  1 of 245  [15]  GCA, Iceland  1984–90  133/94 (70)  125 (94)  19 (14)  1 (0.75)  3/3  2 (1.5)  NR  NR  NR  NR  NR  NR  NR  NR  [16]  Visual symptoms and biopsy-proven GCA, Bascom Palmer Eye Institute, FL, USA  1980–93  45/31 (69)  NA  All patients  41/45 (91), 63 eyes  8/3  7 (16)  NR  55 of 63 eyes  3 of 63 eyes  NR  3 of 63 eyes  2 of 63 eyes  4 of 63 eyes with choroidal infarction;3 of 63 eyes with optic atrophy  NR  [17]  Biopsy-proven GCA and available FA, Hôpital Ophthalmique Jules Gonin, Switzerland  1977–94  47/33 (70)  NA  33 (70)  25 of 30 (83)  12 of 30/5 of 30  6 (13)  CN palsies in 4, persistent ophthalmoplegia in 2  22 (6 AION + CLRAO)  7 with CRAO/ BRAO  7 (6 CLRAO + AION, 1 CLRAO + CRAO)  7 with CRAO/ BRAO  NR  Choroidal ischaemia associated with other abnormalities  NR  [18]  Biopsy-proven GCA, Hospital Clinic i Provincial, Spain  1980–95  146/102 (70)  NA  23 (16)  23 (16)  7/0  2 (1)  NR  18 (1 AION + CRAO)  1  NR  1  NR  Three without funduscopic exam  NR  [19]  Biopsy-proven GCA, three hospitals in Spain  1975–96  239/133 (56)  NA  69 (29)  34 (14)  40/25  16 (7)  Transient in 11  30  2  NR  NR  1  NR  1  [20]  Biopsy-proven GCA, three hospitals in Barcelona, Spain  1980–96  200/141 (70)  NA  Unclear (>38)  28 (14)  20/NR  11 (5.5)  Transient in 9, persistent ophthalmoplegia in 2  23 (1 AION + CRAO)  1  NR  1  1 ? (normal funduscopic exam)  Three without funduscopic exam  NR  [1]  Biopsy-proven GCA, University of Iowa Hospitals and Clinics, IA, USA  1973–95  170/123 (72)  NA  85 (50)  83 (49)  26, 33 eyes/12 of 33 eyes  5 (3)  Transient  69  12  12 of 55 patients with FA  NR  6  One with ocular ischaemia  NR  [21]  Biopsy-proven GCA, Hospital Xeral-Calde, Spain  1981–98  161/79 (49)  NA  42 (26)  24 (15)  23/11  9 (6)  CN palsies in 3  22  2  NR  NR  NR  NR  1  [22]  GCA, Dupuyren Hospital, France  1978–2000  174/109 (63)  147 (88)  48 of 174 (28)  23 of 174 (13)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [23]  GCA, four hospitals in Jerusalem, Israel  1980–2000  175/110 (63)  152 (87)  48 (27)  32 (18)  <14 (reported together with TIA)/NR  3  Transient  26  6  NR  NR  NR  NR  NR  [24]  Biopsy-proven GCA, Santa Maria Nuova Hospital, Italy  1986–2002  136/102 (75)  NA  41 (30)  26 (19)  15/13  6 (4)  Transient  24  2  NR  NR  NR  NR  NR  [25]  Biopsy-proven GCA, Hospital Xeral-Calde, Spain  1981–2005  255/139 (55)  NA  57 (22)  32 (16)  NR  NR  NR  NR  NR  NR  NR  NR  NR  NR  [26]  GCA, Olmsted County, MN, USA  1950–2004  204/163 (80)  177 of 192 (92)  47 of 204 (23)  18 (9)  7/NR  11 (5)  NR  17  2  NR  NR  NR  Two with non- specific changes  NR  [27]  GCA, Olmsted County, MN, USA  1950–2009  245/178 (79)  NR  NR  20 (8.2)  NR  NR  NR  17 (1 AION + CLRAO, 1 AION + CRAO)  4  1  NR  NR  NR  NR  AION: anterior ischaemic optic neuropathy; BRAO: branch retinal artery occlusion; CLRAO: cilioretinal artery occlusion; CN, cranial nerve; CRAO: central retinal artery occlusion; FA: fluorescein angiography; NA: not available; NR: not reported; PION: posterior ischaemic optic neuropathy; TIA: transient ischaemic attack; TMVL: transient monocular visual loss. Permanent vision loss Of patients with permanent vision loss, 8–28% report premonitory transient monocular vision loss (TMVL) [1, 17]. More than 10% of patients report pain at the time of visual loss [1, 16]. Notably, about 20% of patients with GCA-induced visual loss do not have any systemic symptoms of the disease, which makes it challenging to recognize the diagnosis [29]. Bilateral vision loss, either simultaneous or sequential, occurs in 20–62% of patients, which emphasizes the need for prompt diagnosis and treatment [16, 30]. Patients who become blind because of GCA usually (80–90% of the time) experience arteritic ischaemic optic neuropathy (AION; Table 1) [1, 16, 30, 31]. Patients may also present with evidence of both optic nerve head and retinal ischaemia, which in an older patient is virtually diagnostic of GCA. Occipital lobe infarction is quite uncommon [14], and branch retinal artery occlusions are rare, given the general understanding that they are not primarily involved in the inflammatory process because they lack the internal elastic lamina [32]. The visual loss is severe, and the prognosis following loss of vision from GCA is poor. The severity of visual loss reflects both the loss of central visual acuity (VA) and the loss of visual field. VA is a measure of the ability to spatially distinguish two points in space, and generally refers to central acuity, which reflects the maximum ability to resolve spatial detail as enabled by the foveal outflow pathway from the retina to the brain. VA has been historically measured using Snellen eye charts with lines of letters of different sizes. The charts are read at a fixed distance, and each line of letters on the chart has a corresponding VA. VA worse than 20/800 is evaluated at a fixed distance of 2 ft (0.6 m) and graded as counting fingers, hand motion, light perception and no light perception [33]. The final median VA in one study of patients with GCA-associated visual loss was counting fingers [31], and <40% of patients retained a VA of better than 20/200 [30]. Even with prompt glucocorticoid therapy, the VA of most patients does not change, and in some patients it may worsen, presumably because the treatment was too late or insufficient to stop or reverse the ischaemic process. On the other hand, a small percentage of patients may experience some visual improvement. One study of 32 patients with visual loss from biopsy-proven GCA reported improvement in VA of two or more Snellen lines in 13%, although without concomitant improvement in the visual field [34]. However, the typical scenario is more grim. For instance, one study of 34 patients with visual loss from GCA documented visual deterioration in 27% of eyes within the first week despite treatment with high-dose intravenous corticosteroids [31]. Fifteen per cent of the eyes showed an improvement of VA by two or more Snellen lines within the first month, but only 5% had corresponding improvement in the visual field. In addition, the improvement in visual function was attributed to eccentric viewing rather than a true rescue of the neurovisual pathway. Another study of 84 patients with biopsy-proven GCA showed improvement in both VA of two or more Snellen lines and central visual field in only 4% of patients, with an additional six patients showing a similar improvement in VA without improvement in the central visual field [30]. AION AION is the most common ocular manifestation of GCA (Table 1). The ischaemia to the optic nerve most frequently occurs near the junction of the optic nerve to the eye and produces oedema of the optic nerve head during the acute phase. This presentation is thus known as AAION. Ischaemia that occurs more distally along the optic nerve in the so-called retrobulbar segment causes blindness without swelling of the optic nerve during the acute phase. This presentation, which is much less common, is referred to as arteritic posterior ischaemic optic neuropathy (APION or PION). Either form of ischaemic optic neuropathy must be distinguished from the much more common non-arteritic form of anterior ischaemic optic neuropathy (NAION), which almost always occurs anteriorly and presents with optic nerve head oedema. To assist in this clinical distinction, one searches for clues of an active inflammatory process, which often produces some combination of headache, jaw claudication and constitutional symptoms. A history of PMR should raise the suspicion that new-onset blindness may be secondary to GCA, but some patients with GCA-induced blindness are otherwise asymptomatic and also may have normal inflammatory markers. Thus, one must always have a high index of suspicion that visual loss caused by an optic neuropathy in older patients may be due to GCA. Any older patient with this type of visual loss should undergo laboratory studies that include a complete blood count (to explore for an unexplained anaemia or elevated platelet count), ESR and CRP. As discussed below, even a moderate suspicion that blindness might be secondary to GCA should prompt urgent intervention in an attempt to prevent further visual loss. In the acute phase, AAION produces a pale appearance of the optic nerve head in addition to the oedema (Fig. 2A). This combination of pallor and oedema of the optic nerve head during the acute phase is unusual, since ischaemia caused by the much more common NAION produces oedema of the nerve head in the acute phase and pallor in the chronic phase. With AAION, the pallor of the nerve head becomes even more apparent as the oedema resolves and loss of the retinal ganglion cell axons that form the optic nerve develops (Fig. 2B). In some patients, the more aggressive arteritic process can cause late cupping of the optic nerve head, in distinction to the non-arteritic form (NAION) in which the optic nerve cups are characteristically small. As such, a presentation of ischaemic optic neuropathy in one eye and a relatively large optic nerve head cup in the fellow eye should at least raise a suspicion of GCA. Fig. 2 View largeDownload slide Colour fundus photographs of two patients with AION The right and left eyes are shown on the left- and right-hand sides of the images, respectively. (A) Fundi of a patient who presented with acute bilateral visual loss from giant cell arteritis. There is bilateral optic nerve head oedema, which is ‘pallid’ in the left eye. The left eye also demonstrated cotton wool spots (arrows), which reflect ischaemia of the retina. (B) Bilateral optic disc pallor with cupping as late sequela of AION. AION: arteritic ischaemic optic neuropathy. Fig. 2 View largeDownload slide Colour fundus photographs of two patients with AION The right and left eyes are shown on the left- and right-hand sides of the images, respectively. (A) Fundi of a patient who presented with acute bilateral visual loss from giant cell arteritis. There is bilateral optic nerve head oedema, which is ‘pallid’ in the left eye. The left eye also demonstrated cotton wool spots (arrows), which reflect ischaemia of the retina. (B) Bilateral optic disc pallor with cupping as late sequela of AION. AION: arteritic ischaemic optic neuropathy. As mentioned earlier, ischaemia of the retrobulbar portion of the optic nerve in arteritic posterior ischaemic optic neuropathy does not produce a change in the appearance of the optic nerve head during the acute phase. In the late stage, optic nerve pallor becomes evident, as would be true for any disorder that causes significant damage to the optic nerve fibres. Central retinal artery occlusion Arteritic central retinal artery occlusion (CRAO) also causes profound visual loss, more than is typically seen with non-arteritic CRAO, AION or PION from any cause [32]. The earliest and most subtle funduscopic finding of any CRAO is a blunting of choroidal pigmentary detail in the macula caused by retinal oedema. In hours or within a day, the classic cherry-red spot becomes evident, as does box-carring of blood flow within retinal vessels and retinal arterial attenuation (Fig. 3). In a typical CRAO, whether caused by an embolus or arteritis, a cherry-red spot develops around the fovea; this finding is the result of visual contrast between the oedematous retina surrounding the fovea and retained choroidal perfusion under the retina. When the central retinal artery and ophthalmic artery are both involved, the cherry-red spot may not be as evident because of reduced perfusion of the choroid, with loss of the redness that creates the classic cherry-like appearance of a CRAO. Fig. 3 View largeDownload slide Colour fundus photographs of acute visual loss from CRAO in the right eye The right and left eyes are shown on the left- and right-hand sides, respectively. A cherry-red spot (arrow), segmentation or box-carring of blood flow within retinal vessels (arrowheads) and attenuation of retinal arteries are demonstrated. CRAO: central retinal artery occlusion. Fig. 3 View largeDownload slide Colour fundus photographs of acute visual loss from CRAO in the right eye The right and left eyes are shown on the left- and right-hand sides, respectively. A cherry-red spot (arrow), segmentation or box-carring of blood flow within retinal vessels (arrowheads) and attenuation of retinal arteries are demonstrated. CRAO: central retinal artery occlusion. Cilioretinal artery occlusion Cilioretinal arteries are anatomic variants found in about 25% of the population. These arteries supply the retina even though they arise out of the ciliary circulation, either from the peripapillary choroid or directly from a short PCA. A cilioretinal artery provides nourishment to some portion of the nasal aspect of the macula. In the context of a CRAO, the presence of a cilioretinal artery is protective and tends to allow sparing of a small region of central vision. However, patients with a cilioretinal artery occlusion caused by arteritis tend to fare less well visually, given that the arteritis also often produces a concomitant AION or CRAO (Table 1) [32]. Occipital lobe infarct Ischaemic stroke of the occipital lobe occurs in up to 7% of patients, although this is high compared with our own experience [13, 35]. Similarly, GCA accounts for only a very small percentage of all ischaemic strokes—only 0.15% at our institution (I. Vodopivec and J. F. Rizzo III, personal communication). The incidence of GCA-related stroke in patients older than 50 years has been reported to be 0.76/100 000/year (95% CI: 0, 2.47), with a slightly higher (1.36/100 000/year) risk in men (95% CI: 0, 3.63) and a slightly lower (0.33/100 000/year) risk in women (95% CI: 0, 1.45) [35], which is about 250-fold lower than the overall annual incidence of adult, first-ever, hospital-ascertained stroke of 189/100 000/year noted in 2005 [36]. Transient monocular vision loss Among the general population of older adults, TMVL is usually caused by emboli arising from atherosclerotic plaques. TMVL also occurs with arteritis, and is reported by 8–30% of patients with GCA-induced visual symptoms (Table 1). Premonitory TMVL can occur with incipient retinal or optic nerve ischaemia, although it is more common with the former. TMVL may also occur much more insidiously as a result of borderline perfusion of the retina caused by the ischaemic ocular syndrome. This disorder is usually a result of severe stenosis of the external and internal carotid arteries, which gradually reduces perfusion to both the anterior and posterior segments of the eye. The latter places the retina in a tenuous metabolic state, which can induce recurrent episodes of very brief (i.e. lasting seconds) amaurosis precipitated by exposure to bright light. Such events may occur repeatedly throughout the day, with a much greater frequency and shorter duration than TMVL caused by emboli. Blindness in the ischaemic ocular syndrome is the result of ischaemia of the photoreceptors, which are the most numerous and metabolically demanding cell types in the retina. In GCA, the pathogenic mechanism of the ischaemic ocular syndrome differs from the atherosclerotic form in that GCA can cause pervasive inflammation of orbital arteries, which can have the same ischaemic consequence for the end organ as more proximal atherosclerotic stenosis. The ischaemic ocular syndrome, especially from GCA, is often not diagnosed because it usually presents insidiously, unlike the typical apoplectic visual loss that occurs from ischaemia of the optic nerve or inner retina. Ischaemic ocular syndrome can also cause a red eye, owing to ischaemia of the anterior segment of the eye, which can be misdiagnosed as conjunctivitis. Iritis is often present, though this finding cannot be recognized without a slit lamp examination. Unlike other forms of visual loss from GCA, the ocular ischaemic syndrome responds readily to corticosteroids, and the transient fluctuations of vision may cease without permanent loss of vision. Visual hallucinations Photopsias (i.e. perception of brief flashes of light) are reported by some patients in the acute phase of either the retinal or optic nerve ischaemia. Should permanent visual loss occur, patients may also develop chronic visual hallucinations, often of well-formed images, including perceptions of small people, flowers, animals, etc. This type of hallucination, often referred to as Charles Bonnet syndrome, is believed to result from ‘release’ of activity of the primary visual cortex, which no longer receives its normal afferent input from the eye(s). Charles Bonnet syndrome is common, but is often underdiagnosed [16, 37]. It is advisable to explore with patients the possibility that they are experiencing Charles Bonnet syndrome, since older patients often assume that the hallucinations are the consequence of early dementia or mental illness. Patients are typically reassured that the hallucinations are the result of visual loss. Interestingly, Charles Bonnet syndrome can develop even in patients with relatively mild visual loss. Efferent manifestations Diplopia Diplopia is reported by 1–19% of patients with GCA (Table 1), although our experience is that it is experienced by fewer than 5% of patients with GCA. Diplopia can result from ischaemia of any segment of the ocular motor system, including the brainstem, ocular motor nerves or extraocular muscles. Diplopia is most commonly secondary to a sixth nerve palsy, although a third nerve, or more rarely, a fourth nerve palsy may occur as well with GCA, sometimes as the herald event. Diplopia from GCA can also arise as a manifestation of a brainstem stroke, in which case it is referred to as a skew deviation. Unlike vision loss, diplopia in GCA is typically transient [1], especially when the ocular motor nerves are involved (Table 1), although permanent strabismus can occur as well. Diagnostic evaluation Ophthalmological examination A detailed examination that includes an assessment of VA, colour vision, pupillary function (especially whether a relative afferent pupillary defect is present), ocular motility, intraocular pressures, the anterior segment (with a slit lamp examination) and the posterior segment (with dilated funduscopy) should be performed in any patient with suspected GCA. Possible funduscopic findings include pallid oedema of the optic nerve head and signs of retinal ischaemia, including cotton wool spots (Fig. 2A). In patients with visual loss and testable vision, an examination of the visual fields (typically with automated perimetry) should be performed. Without such testing, loss of visual field may not be recognized by the patient, especially when there is significant visual loss in the fellow eye but retained central vision in the seemingly unaffected eye. Given the high risk of progressive and sequential visual loss, it is important to obtain the most complete assessment of visual function possible during the acute presentation. Fluorescein angiography Suspected GCA may be evaluated with fluorescein angiography, which can demonstrate delay of perfusion and hypoperfusion of either choroid, retina or both (Fig. 4) [38, 39]. A large swathe of choroidal hypoperfusion is highly suggestive of GCA, and should prompt consideration of prompt corticosteroid therapy, especially if patients are experiencing only transient episodes of visual loss. This type of choroidal hypoperfusion is not a feature of NAION. Fig. 4 View largeDownload slide Fluorescein angiography of the left eye Patches of choroidal hypoperfusion are demonstrated (asterisks). The optic nerve head is outlined by yellow arrows. Fig. 4 View largeDownload slide Fluorescein angiography of the left eye Patches of choroidal hypoperfusion are demonstrated (asterisks). The optic nerve head is outlined by yellow arrows. Neuroimaging Neuroimaging is generally normal in patients with GCA. However, some patients with GCA may have non-specific orbital enhancement or enhancement of the optic nerve, chiasm or perineural sheath as signs of inflammation (Fig. 5) [40]. In one study, mural inflammation of the ophthalmic artery in contrast-enhanced, fat-saturated, T1-weighted sequences acquired on 3 T MRI was observed in almost 50% of patients with GCA [41]. In the proper clinical scenario, this finding can suggest a diagnosis of GCA but should not preclude obtaining a biopsy of the temporal artery in an attempt to obtain histological confirmation of the diagnosis. We have not recognized this MRI to be as useful as that report suggested, perhaps because we do not usually obtain an MRI in patients who are suspected of having GCA if the presenting features are fairly typical. However, neuroimaging should generally be obtained in patients with blindness if the aetiology is uncertain, especially because some patients may have an infectious disease, such as fungal sinusitis, that would worsen if treated with corticosteroids. Fig. 5 View largeDownload slide MRI of the orbits in a patient with GCA Coronal and axial contrast-enhanced T1-weighted fat-suppressed magnetic resonance imaging of the orbits demonstrating enhancement of the optic nerve sheaths (arrows). Fig. 5 View largeDownload slide MRI of the orbits in a patient with GCA Coronal and axial contrast-enhanced T1-weighted fat-suppressed magnetic resonance imaging of the orbits demonstrating enhancement of the optic nerve sheaths (arrows). Treatment The advent of the use of corticosteroids in GCA had an immediate and profound salutary benefit for patients [42]. Although there is no doubt that glucocorticoids are effective in the management of GCA, it is also clear that side effects, some of which can be medically serious and even life threatening, commonly occur, given the prolonged course of therapy that typically is required or at least used. Side effects from long-term use of prednisone occur even with careful medical management and with attentive patients who present as requested for follow-up exams. There has been substantial debate and variation on the preferred starting dose and duration of treatment with corticosteroids. The majority of patients with GCA are managed by internists and rheumatologists who tend to use lower starting doses of prednisone (40–60 mg/day) than neuro-ophthalmologists. This approach works well for most patients, although neuro-ophthalmologists are consulted when patients on these lower starting doses experience blindness. Whatever the preference, glucocorticoids must be administered promptly once the diagnosis of GCA is strongly suspected, although it is important to appreciate that there is no adequate evidence-based guidance of a preferred dosing regimen for glucocorticoid therapy alone. As glucocorticoid therapy is introduced, it is critical to be aware that the rare group of patients who present with blindness and signs and symptoms of GCA may harbour an infection (e.g. bacterial endocarditis, fungal sinusitis). As such, there must always be vigilance about these risks, since glucocorticoid therapy could have disastrous consequences. Regardless of the dosing preferences among subspecialists, any patient with acute visual loss or stroke should receive glucocorticoids immediately because of the risk of severe, progressive and permanent deficits. The primary purpose of glucocorticoids in this setting is prevention of new ischaemic events, including visual loss in the fellow eye, rather than visual recovery in the affected eye. For patients with acute visual loss in one eye and either symptoms or signs of ischaemia in the second eye, we tend to initiate treatment with a 3-day course of intravenous pulse methylprednisolone (at a dose of 500–1000 mg daily) because of its rapid onset of action. Thereafter, the patient is switched to high-dose (100–120 mg/day) oral prednisone. For patients without visual loss or with visual loss that is confined to one eye, our practice has been to initiate treatment with oral glucocorticoids, with a starting dose of 80–120 mg/day. In general, our approach is to use this dose for 3–4 days (depending upon the clinical course), then decrease gradually to 30 mg/day by the end of the third or fourth week. We typically treat patients with progressively lower doses for 12–18 months. If the pre-treatment ESR or CRP was elevated, sequential tests should be obtained to guide the taper once the dose is relatively low, perhaps 15 mg/day or less. It is rare for patients to experience blindness after an initial period of effective treatment followed by a taper to ∼15 mg. All dosing should be given once daily, as patients can be at risk of blindness if prednisone is switched to alternate-day dosing. At 10–15 mg/day, the taper can generally be reduced by 2.5-mg increments, assuming that the patient does not have symptoms suggestive of adrenal insufficiency and has a normal morning cortisol level. The one exception to this guideline is for patients who also have PMR, as they frequently can become symptomatic even with a 1 mg per day reduction in prednisone. If the index of suspicion for GCA is low, treatment with glucocorticoids may not be needed, although in such cases it is reassuring to obtain a negative temporal artery biopsy. Glucocorticoid treatment will not affect the results of temporal artery biopsy if the biopsy is performed within a week or so of beginning therapy [43]. Because of its antithrombotic and anti-inflammatory properties and favourable side effect profile, low-dose aspirin has been commonly used as an adjunctive treatment in GCA. It should be noted, however, that there have been no randomized controlled trials evaluating the role of aspirin for the prevention of ischaemic complications [44], and data from several retrospective studies have been conflicting [22, 45–50]. A recent landmark study demonstrated the benefit of tocilizumab administered weekly or every other week in the treatment of GCA [51, 52]. This study provided convincing evidence of a steroid-sparing benefit of tocilizumab, which should improve the long-term risk–benefit profile for treating GCA. This study was not designed to assess the effect of tocilizumab and its dosing regimens on vision complications. The investigators, however, reported that one patient in the group that received tocilizumab every other week had AAION and vision loss that resolved after treatment with glucocorticoids. It is, therefore, important that clinicians managing patients with GCA maintain persistent vigilance for ophthalmic manifestations. Future studies addressing the efficacy of tocilizumab with respect to prevention of ophthalmic complications in patients with GCA are required. 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RheumatologyOxford University Press

Published: Feb 1, 2018

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