Treatment of Acute Visual Loss in Giant Cell Arteritis

A 76 year-old Caucasian woman presents to her ophthalmologist with acute visual loss in her right eye. She has a medical history of hypertension well-controlled with one medication, diet-controlled borderline diabetes mellitus, hysterectomy, and cholecystectomy. She takes one aspirin 81 mg per day. She is mildly overweight and denies smoking or drinking alcohol. She had cataract extractions in both eyes 10 years previously, and she only wears reading glasses. One day ago, she noticed a “shadow” in her right eye while vision seemed normal in the left eye. Her ophthalmologist documented visual acuities of hand motion in the right eye and 20/25 in the left eye. Color vision was normal in the left eye. There was a large right relative afferent pupillary defect. Fundus examination showed diffuse, pallid right optic disc edema with attenuated arteries and a few cotton wool spots in the peripapillary area. In the left eye, the optic nerve was normal with a cup-to-disc ratio of 0.3, with mild retinal arterial attenuation and a few macular drusen. Suspicious that the patient may have arteritic ischemic optic neuropathy (AION), the ophthalmologist obtained an erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which came back “very high” the following morning. The patient denied headache, scalp tenderness, jaw claudication or diplopia, but mentioned an episode of blurry vision in the right eye 2 days before permanent visual loss. The diagnosis of arteritic-AION secondary to giant cell arteritis (GCA) was considered very likely. Aware of your expertise in GCA, the ophthalmologist calls the following day upon reviewing the laboratory results, asking whether the patient should be sent to the local hospital for high-dose intravenous (IV) methylprednisolone or rather begin treatment with oral prednisone 1 mg/kg per day. What do you recommend and why? IV corticosteroids are not more effective than oral corticosteroids to treat patients with acute visual loss secondary to GCA. Oral steroids should be given to GCA patients with acute visual loss: Sohan Singh Hayreh, MD, MS, PhD, DSc, FRCS, FRCOphth (Hon) First of all, I would like to comment on the management of the narrated case, by the referring ophthalmologist. It is stated: “he obtained ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein), which came back “very high” the following morning.” Having dealt with giant cell arteritis (GCA) cases for more than 40 years, I am very concerned about this statement for the following 2 reasons. The ophthalmologist described ESR and CRP as “very high.” When a referring physician tells me that the ESR and/or CRP are “normal”, “high,” or “very high”, I always ask for the exact values, because these descriptive terms are subjective and meaningless in the management of a case of GCA. The ophthalmologist reported that ESR and CRP came back “very high” the “following morning.” Kearns (1) rightly stressed that GCA “ranks as the prime medical emergency in ophthalmology, there being no other disease in which the prevention of blindness depends so much on prompt recognition and early treatment.” To wait for the ESR and CRP results until “the following morning” is unacceptable, in my opinion. I do not let my patients leave the clinic until I have the results, which I get within 1–1½ hours—CRP much earlier than ESR. If those tests indicate the possibility of GCA, then I immediately start the patient on high-dose corticosteroid therapy to prevent visual loss or further visual loss. This is an emergency and there is NO safe period between diagnosis and start of corticosteroid therapy to prevent visual loss. Role of IV vs oral corticosteroid therapy in prevention of visual loss due to GCA The primary concern in the management of GCA is visual loss. I have reviewed the conflicting literature on this subject (2). The use of IV vs oral corticosteroids in the management of GCA has been reported, but these studies are mostly based on only a few patients (3–8). In addition, progressive visual loss has been described in GCA, despite corticosteroid therapy (IV or oral) (6,7,9). I investigated the question whether IV megadose corticosteroid therapy was more effective than oral therapy in the prevention of visual loss (2). A total of 144 consecutive patients fulfilled the criteria for the study. All patients had temporal artery biopsy positive for GCA. At their first visit, 53 patients had no visual loss, whereas 91 had a variable degree of visual loss in one or both eyes. Initially, 96 patients were treated by high-dose (80–120 mg) oral prednisone only and 48 with IV megadose of corticosteroid therapy; the treatment regimen for IV therapy was usually 150 mg dexamethasone every 8 hours for 1–3 days, followed by high-dose oral prednisone. During the initial stages of the study, because of the prevalent impression that IV therapy was better than the oral therapy, IV treatment was generally given to patients with visual loss and also to some patients without visual loss. Later on, with greater experience, my criteria for initial IV therapy became: 1) history of amaurosis fugax but no visual loss; 2) complete or marked loss of vision (judged by both visual acuity and visual fields) in one eye; and 3) early signs of involvement of the second eye. Tapering of the oral corticosteroid therapy was done very gradually, guided only by the levels of ESR and CRP (10). The results of this study showed that 13% of those on IV corticosteroid therapy had visual deterioration compared with 3% on oral corticosteroid therapy. This indicated that IV megadose corticosteroid therapy was no more effective than oral therapy in preventing visual deterioration. The following GCA case with positive temporal artery biopsy is an instructive example. A 78-year-old Caucasian man noticed blurred vision in the left eye when he awoke one morning, which progressively worsened during the day (Day 1). That day his ophthalmologist recorded visual acuity of hand motions in the left eye and normal acuity in the right eye. On the second day (Day 2) he was seen in my clinic, with visual acuity of hand motions in a temporal island of visual field in the left eye and 20/20 in the right eye. Fundus examination revealed chalky white left optic disc swelling (classic finding of arteritic AION (11)), and a normal right fundus. He was admitted to hospital and immediately started on IV dexamethasone 150 mg every 8 hours. Beginning on Day 3, he was switched to 120 mg oral prednisone daily. Vision in both eyes was stable until Day 6 (while still in hospital), when he awoke with visual acuity of counting fingers at 2½ feet in the right eye and light perception in the left eye. The right optic disc now had chalky white swelling. IV dexamethasone 150 mg was again started immediately and repeated every 6 hours 4 times that day. The following morning (Day 7), his visual acuity was hand motions in the right eye and no light perception in the left eye. So, despite IV megadose corticosteroid therapy, the patient suffered progressive visual loss in both eyes. For that reason, I felt that IV corticosteroid therapy was not helping him, so he was switched to 120 mg prednisone orally. On Day 8, visual acuity in the right eye was bare light perception and in the left it no light perception. On Day 9, it was no light perception in both eyes and remained unchanged on follow-up. Despite intensive IV and oral corticosteroid therapy, there was relentless visual deterioration in both eyes. Role of IV vs oral corticosteroid therapy in visual improvement in visual loss due to GCA A review of the literature reveals disagreement on the effect of IV vs oral corticosteroid therapy on visual improvement in GCA. The majority of the reported patients with visual loss due to GCA in these studies initially were started on IV corticosteroids, followed by oral therapy. Some authors (3,12,13) claimed that IV corticosteroid therapy improved vision (based on only a total of 4 anecdotal cases). These 3 reports (3,12,13) require comment. In 2 cases (12,13), improved visual acuity without concomitant improvement in visual fields probably represented the patients' learning to fixate eccentrically (see below). The report by Matzkin et al (3) illustrates another problem with visual improvement during corticosteroid therapy in GCA. These authors reported visual improvement with megadose IV methylprednisolone in 2 eyes diagnosed with “central retinal artery occlusion.” My review of these cases offers a different interpretation. One of the 2 eyes had a cilioretinal artery occlusion and NOT central retinal artery occlusion. Our natural history study of 61 eyes with cilioretinal arterial occlusion showed marked spontaneous improvement in visual acuity (14). Similarly, our natural history study of 260 eyes with central retinal artery occlusion showed evidence of spontaneous improvement in visual acuity (15). It seems that the improvement in visual acuity claimed by Matzkin et al (3) in 2 cases simply represented natural history rather than the effect of the megadose IV methylprednisolone. Clearkin (16,17), on review of reports in the literature that have claimed visual improvement with IV megadose corticosteroid therapy, rightly pointed out that these claims were not justified and concluded that oral therapy is safer and just as efficacious. I agree with these conclusions. Liu et al (5) retrospectively reviewed the records of 41 GCA patients with visual loss. IV methylprednisolone was given to 25 patients, while the rest received oral prednisone alone. These authors reported that in the 41 patients with visual loss, there was visual improvement in 39% after IV treatment vs 28% on oral therapy. They claimed that “visual loss due to giant cell arteritis had a 34% chance for some improvement in visual function after corticosteroid treatment”; however, this is not supported by other prospective studies (see below). In view of this controversy, we investigated the usefulness of IV vs oral systemic corticosteroid therapy in visual improvement in 84 consecutive patients with visual loss due to biopsy-proven GCA (18). The regimen of IV and oral corticosteroid therapy was the same as described above. Visual loss was due to arteritic AION (91%), central retinal artery occlusion (10.5%), cilioretinal artery occlusion (10%), and/or posterior ischemic optic neuropathy (4%) alone or in various combinations. Visual improvement was seen in 7% of 41 patients treated initially with IV corticosteroids vs 5% of 43 patients treated with oral corticosteroids (P = 0.672). This study did not support IV megadose corticosteroid therapy as being more effective than oral therapy in leading to visual of patients with visual improvement in both visual acuity and fields vs those with no improvement a (P = between of visual loss and start of therapy in the improved The early diagnosis and start of corticosteroid therapy a better chance of visual only of eyes with visual loss due to GCA improvement in both visual acuity and central visual field and Similarly, et al in a of consecutive biopsy-proven GCA patients, that only 5% had improvement in both visual acuity and visual These 2 studies the finding of Liu et al (5) that 34% of patients had improvement in visual function after corticosteroid It is to that reported in visual not always visual as by my various studies and by visual improvement improvement in both visual acuity and central visual in visual acuity without improvement in the central visual usually the learning to better by My studies in GCA patients no in between IV vs high-dose oral corticosteroid therapy in the prevention or improvement of visual loss on my my for corticosteroid therapy in GCA are as (10). For patients, with or without vision loss, I initially begin with a of at mg oral prednisone in the following 3 1) A history of amaurosis fugax but no visual loss; amaurosis fugax is an of visual loss. 2) or marked (judged by both visual acuity and visual the loss of vision in one eye. 3) signs of involvement of the second eye. In these it is to to levels of corticosteroid in the as as Oral corticosteroid therapy takes some to levels in the in these patients, I initially one megadose of IV corticosteroid an and immediately start the patient on at mg oral prednisone daily. What I have my in with GCA patients the 4 is that it is to the to the at and not I it is to out that about a I was diagnosed with GCA, without loss of My ESR was normal usually about 10 and CRP was with a positive temporal artery I to be treated the I had treated my patients because the treatment is for it is also for I my physician to start me immediately on mg oral prednisone daily. this treatment my ESR to 8 and CRP to mg within 3 I no visual I have been my guided by the levels of ESR and CRP (10). In light of this my for the management of the patient in question is as The patient had vision in the eye. this patient in one of my 3 that complete or marked loss of vision in one eye. One has to to the of visual loss in the eye. as I would initially her one megadose of IV corticosteroids and immediately start her on mg prednisone daily. I would the of her therapy based only on the levels of ESR and CRP (10). IV steroids should be given to GCA patients with acute visual loss: Visual loss is the of GCA and was in of patients with GCA before the of corticosteroid treatment Despite the use of corticosteroids in the visual loss may still in of patients GCA a of arteritis with ischemic as visual loss and large arteritis and artery and leading to and and a systemic with and with and systemic studies have treatment by GCA studies treatment for GCA are by the patient which by and in have generally more treatment for of than studies and those by for may use oral prednisone to treat while use high-dose IV methylprednisolone to treat patients with acute visual loss or The of GCA and the visual of a diagnosis and treatment of this a medical emergency in recognition and management of GCA still In a study of GCA patients in the to diagnosis to was This the rate of visual in a of hours in treatment seen in the case is and the of therapy is probably more than the or of a patient has vision in one eye, the of visual loss in the eye is within hours to days (10). treatment by hours not only the of visual improvement but also the patient at for eye which in more than of the visual of arteritic AION is treatment with steroids in some visual and complete visual There is that corticosteroids are the of treatment for GCA and should be immediately and with the of and disease preventing further visual loss in the eye, preventing visual loss in the eye, and vision The initial of and of therapy are still of but upon the for visual loss What the literature tells Oral prednisone is the therapy for GCA in The initial to GCA in the mg per day in a of patients with GCA or but with signs and to more than mg per day in a with or visual loss (10). during the of these reports GCA with and reports patients with visual loss and GCA. no for initial of the majority of patients to a of 1 mg/kg per day of mg per day are given to patients with visual or IV methylprednisolone is therapy when vision is at studies have IV therapy in GCA, 2 of which were prospective 1). The study by et al showed no for a of IV methylprednisolone mg) in at 1 et al that a of IV methylprednisolone at a much of mg/kg per day more oral prednisone than and also the at the of therapy in this study only in the of the et al IV steroids in with biopsy-proven GCA and or visual improvement of visual acuity in more patients treated with IV steroids compared with oral steroids alone. A study by et al did not of high-dose IV but the patients were not and the of patients treated with IV steroids to have greater vision loss at as were those reported by et al of intravenous methylprednisolone for the of corticosteroid no the systemic of GCA and hours to days in patients of visual loss is much in only of eyes Visual when it is with and visual field There not to be in terms of visual based on whether patients IV steroids initially or whether are treated with oral steroids alone. when treatment is within hours of visual loss, of patients have visual improvement compared with the of patients after a in treatment This better visual when steroids are early after visual loss has been documented in other studies case reports also improvement of visual function in patients high-dose IV methylprednisolone it is to of visual in giant cell arteritis patients treated with treatment with high-dose corticosteroids, both oral and vision loss or of vision loss may usually within the first days of treatment there are reports of GCA patients progressively vision while on oral and then with high-dose IV and reported a of visual deterioration in patients high-dose IV methylprednisolone 6 of 48 than in those treated with oral steroids 3 of that high-dose IV steroids are to those patients with or visual loss at the of a more of GCA with IV steroids I always recommend IV steroids for patients with acute visual loss and GCA for the following It is to steroids as as when GCA is I the patient my to the IV methylprednisolone be started This is much more than an and patient with a for oral prednisone. It also patient with The GCA is by with and have with These which may to in are by to the When a patient is seen a few days after visual loss and is on oral prednisone or not have visual oral steroids are IV steroids me to the patient to the hospital for at 48 hours. as and diabetes the of of A to hospital that IV steroids are and other medical are It as temporal artery and in some of and and patient use and prevention of The patient is usually hospital after 3 days of IV with a for oral prednisone and to prevent and other of a and and have a more effect when IV rather than orally. This is IV therapy is oral in a of systemic acute and other and systemic their function in by to in the cell the are to the and in the or of the of and/or In addition, the with These of are as and be seen as early as after as to which are in to a of mg oral results in of IV methylprednisolone at greater than mg may by In addition, IV methylprednisolone has a of than oral and may have greater and This is in the initial treatment of ischemic of GCA visual loss. IV of methylprednisolone are generally greater than 10 mg/kg a of mg is and given for 3 days prednisone This was in with evidence It has been that mg per day may be as effective as 1 per day for systemic and a also be considered for GCA, in patients with or diabetes IV high-dose methylprednisolone seems to be as as oral prednisone. It the of and but use may to a of total the patient to of therapy In of GCA are to corticosteroid therapy. high-dose steroids as as after the of visual loss is to prevent further visual loss, prevent visual loss in the eye, and IV methylprednisolone at a of mg per day is a and safe to treat GCA patients and should be in patients with acute visual loss. This statement is in with the the of and the of 3) of the initial and of steroids to treat GCA Sohan Singh Hayreh, MD, MS, PhD, DSc, FRCS, FRCOphth (Hon) I studies on various of GCA for 40 years as a of the prospective studies on by the of the comment by that my studies were is not One has to be in claims of visual improvement with IV corticosteroid therapy vs oral therapy based simply on visual acuity My various studies on visual have that there is a improvement in central visual better visual acuity alone simply a patient learning to better by In light of this I the in 2 et al in their review were to on both therapy and visual acuity in only patients with visual patients treated with IV methylprednisolone and with oral prednisone. There was no in the visual acuity between the 2 (P = They that those were treated within hours had better chance of visual improvement but the regimen did not the visual In the studies by et al and et al there was no visual field improvement to improved visual acuity The study by et al had other as In the prospective study by et al only 5% of GCA patients had improvement in both visual acuity and visual field when treated with IV corticosteroid therapy. Similarly, in our prospective study only showed improvement in both visual acuity and visual that our study did not of high-dose IV steroids because the of patients treated with IV steroids to have visual loss at This is by the that visual improvement in our study patients, and in that of et patients, 40 was that and The report of visual improvement in 34% of GCA patients by Liu et al (5) was based only on visual and that results of high-dose IV methylprednisolone treatment of patients with visual loss GCA were to the results of treatment with oral corticosteroid therapy. et al no evidence that IV methylprednisolone was better than oral therapy. et al a study and visual improvement based only on visual acuity and the authors stated: steroids may a greater of improvement compared with oral prospective intravenous with oral is to these The study by et al to be in in to visual and of GCA. In that study, patients received a of IV methylprednisolone oral prednisone and received only oral prednisone. The oral prednisone was 40 mg the was every 2 to then by to 10 and by 1 mg every 2 visual acuity was My studies that this treatment regimen was to prevent visual loss in GCA. It is not that in the oral there were which also a GCA patient at for visual loss. There were no at in my There is not a large study that has better visual improvement with IV corticosteroid therapy compared with oral corticosteroid therapy. has much literature about the management of GCA. I have stressed and have different on GCA with patients with while GCA patients with visual loss or patients with GCA may vision without or systemic For the GCA is a disease with for the it is a disease with systemic with medical et al have given a regimen of corticosteroid therapy in GCA, which may be to but is to prevent visual loss. Similarly, et al as a of corticosteroid therapy that is to prevent visual loss, as is in their My studies have that a regimen is to prevent visual loss. There is marked in the and of corticosteroid therapy to GCA and prevent visual loss. corticosteroid therapy to be guided by systemic which is not effective to prevent visual loss of ESR and CRP are the only to treatment in GCA. that GCA out in 2 years and there is no to corticosteroid therapy. I have seen patients corticosteroid therapy, then a patient to hospital for of intravenous as also was done by et al et al and by the of there is no study that an is to to patients for 3 days is not justified in my also that that and in some cases and the of and In my experience, and are in GCA and I no for a patient for of and I have not admitted a GCA patient to the hospital in In the of and the of and IV is I have when IV corticosteroid therapy is one IV as an In my not only is an and to the it is a medical I agree with the in the patient is that the ophthalmologist until the day to the results of the ESR and CRP and not therapy A in treatment is still within the of for visual and the patient is at very for vision in the eye and for loss of vision in the eye. This is despite I still would not to recommend of IV methylprednisolone or mg) and to hospital for and further as above. I am to that one initial of IV methylprednisolone in this to levels of Hayreh, I would then the patient in the hospital for 2 more days and the of IV methylprednisolone so that the patient mg of methylprednisolone per day for 3 days before being on 1 mg/kg per day of oral prednisone. I am that did not visual his comment is to this case and this I would have with oral prednisone as an This that despite different the management of GCA patients with acute visual loss, and I agree that patients with acute visual loss should be treated with at one of high-dose IV not just oral