MANAGEMENT OF ARTERITIC AION AND GIANT CELL ARTERITIS

This is a highly controversial field. For a detailed discussion of the controversies, the reasons for them and the management of giant cell arteritis, please refer to my web article on giant cell arteritis. The following regimen of treatment is the one we use.

It is universally agreed that the treatment of choice for giant cell arteritis is systemic corticosteroids. I am of the opinion that if there is a reasonable index of suspicion of giant cell arteritis in patients presenting with AION, it is essential to start high doses of systemic corticosteroid, IMMEDIATELY, as an EMERGENCY MEASURE. Do not wait for the temporal artery biopsy or its results, because by the time the biopsy is done and its results available, the patient could have lost further vision in one or both eyes. The visual loss due to arteritic AION is almost always permanent. Temporal artery biopsy should be done as soon as possible but not necessarily that very day; starting the treatment does not interfere with the biopsy results. If the biopsy result and other evidence indicate that the patient does not have giant cell arteritis, the drug can be stopped without ill effects.

The exact regimen of steroids in giant cell arteritis is highly controversial. The main issues of conflict and confusion are the dosage and duration of corticosteroid therapy required, and how to regulate steroid therapy? We have recently reviewed these and other aspects of steroid therapy in the management of giant cell arteritis,⁵⁵ and also reported findings of my 27-year planned clinical study on steroid therapy in giant cell arteritis.⁵⁵

(a) Starting dose of corticosteroid therapy: I usually start with high-dose corticosteroid therapy (80 - 120 mg of prednisone orally daily). I always explain to the patient that this aggressive treatment cannot provide a cure, but can prevent any further visual loss; that I have not seen any significant visual recovery in my large series, once an eye has lost vision.⁵⁷ It is important to stress to the patient that the treatment is essentially suppressive and not curative, and most probably life-long. All patients are maintained at the high dose of Prednisone till both the ESR and CRP have stabilized at low levels (that usually takes 2-3 weeks - CRP comes down much faster than ESR - see figure 10); after that very gradual tapering of Prednisone is started, guided by the ESR and CRP levels only.

     In the past, I usually gave 3-4 intravenous megadoses (equivalent to one gram of Prednisone) in the form of a slow intravenous drip, every 6-8 hours, and then switch to high-dose oral Prednisone. My indications for the intravenous megadose steroid therapy included: (i) development of transient visual blurring or loss (amaurosis fugax) in a patient with giant cell arteritis, (ii) complete loss of vision in one eye, and (iii) early signs of second eye involvement. However, recent analyses of the results of my studies, comparing the effectiveness of high-dose oral corticosteroids with that of intravenous megadoses corticosteroid therapy in improving vision⁵⁷ or preventing visual deterioration⁵⁶ due to giant cell arteritis, showed no evidence that intravenous megadose steroid therapy was more effective than oral therapy for either. In view of that new finding, I now advocate giving only one initial intravenous loading dose of megadose corticosteroids, followed by high-dose oral Prednisone. My indications for intravenous corticosteroid therapy in giant cell arteritis are the same as given above.

(b) How to regulate steroid therapy? I have found that the most reliable and sensitive parameters to regulate and taper down steroid therapy are the levels of ESR and CRP, and NOT systemic symptoms.^34,55 I am fully aware that rheumatologists in general advocate that alteration in the treatment should be based on the clinical picture, rather than on laboratory tests^34,55; but my experience has been that that can be dangerous, because patients may lose vision irrevocably without any clinical warning symptoms. Moreover, one in five patients with visual loss from giant cell arteritis has never had any systemic symptoms⁴⁹ (i.e. had occult giant cell arteritis). Therefore, I regularly perform both ESR and CRP at every visit . Tapering down of steroids is not indicated till both ESR and CRP have stabilized, because the disease can instantly flare up again, as shown by an immediate rise in ESR and CRP levels. The lowest level of ESR and CRP achieved provides a guideline for future management also.

(c) Maintenance dose and duration of steroid therapy: In my study^,55 the median time to reach the lowest maintenance dose of Prednisone at which the ESR and CRP stayed low and stable was 48.7 months, and the median lowest Prednisone maintenance dose achieved was 7 mg/day (interquartile range of 1 to 16 mg/day). There was no significant difference in the time to reach the lowest maintenance dose among patients with and without visual loss. My study showed that no generalization at all is possible for tapering down of Prednisone and there is no set formula because of the infinite variation between individuals. My study has shown that tapering down of steroid therapy and determining the maintenance dose is a slow, laborious, painstaking individualized job, taking months or even years. Only 10 of 145 patients in my study were able to stop the therapy and maintain stable ESR and CRP levels during a median follow-up time of 2.43 years (inter-quartile range of 1 to 6 years). I have found that the vast majority of giant cell arteritis patients need a small dose of steroid therapy for years, if not for the rest of their life.

Figure 10-A: Graph of CRP levels in 6 patients with giant cell arteritis, showing initial responses to high doses of systemic corticosteroid therapy.	Fig. 10-B: Graphic representation of the pattern of initial response of erythrocyte sedimentation rate (Westergren) to original high-dose systemic corticosteroid treatment in six patients with arteritic AION. (Reproduced from Hayreh23)
[For a larger view of image, click on the image.]	[For a larger view of image, click on the image.]

In conclusion, my study showed marked inter-individual variation among giant cell arteritis patients in: (a) the amount and duration of steroid required to control the active disease, (b) the time needed to reach a maintenance dose, (c) the maintenance dose required to keep the disease under control to prevent blindness, and (d) the total length of treatment.⁵⁵ Therefore, steroid therapy for giant cell arteritis has to be individualized. The guiding principle, obviously, is to maintain the lowest level of ESR and CRP with the lowest dose of Prednisone. I have found that most giant cell arteritis patients require a virtually life-long, very small maintenance dose, which has little or no systemic side-effects.⁵⁵ A common mistake made by physicians in these cases is to taper the steroids down rapidly to a very low dosage without doing ESR and CRP or taking into consideration their levels, and then discontinue it. There is a common belief among rheumatologists that giant cell arteritis burns itself out in a year or two, and steroids can then be tapered off unless the patient develops systemic symptoms.^34,55 As discussed above, I have found this notion to be completely wrong, and even disastrous, because repeat temporal artery biopsy has shown evidence of active disease even after 9 years of steroid therapy.^34,55 I have found that the only trustworthy and safe parameters to regulate the steroid therapy and to prevent visual loss are the levels of ESR and CRP, and nothing else.^34,55

To have the full co-operation of the patient in the management of giant cell arteritis, it is very important to explain the objectives of the treatment clearly to him/her. In my experience there is usually no useful recovery of visual function in the already involved eye.⁵⁷ The patient needs to know this right from the start, to avoid having unrealistic expectations from the aggressive steroid therapy. The primary objective of treatment is to prevent loss of vision in the fellow eye. I have found that there are a few patients who are still likely to lose further vision during the first 5 days of treatment, even when it is intensive and aggressive.⁵⁶ However, I have not had anyone lose any more vision after that, if treated properly and adequately. Thus, intensive treatment is extremely effective, and about 5 days after the start of treatment one can almost guarantee that the patient will not lose any further vision. To maintain that vision, however, maintenance treatment with adequate oral corticosteroids is absolutely essential, and that is usually lifelong.

Alternate Day Corticosteroid Therapy in Giant Cell Arteritis: There is much misunderstanding among physicians about this mode of steroid therapy, and many patients are given alternate day therapy from the start. But this mode of therapy has no place in the treatment of almost any active disease (including giant cell arteritis) and is indicated only for maintaining suppression of disease activity and prevention of flare-up. Therefore, alternate day corticosteroid therapy has no place at all in the treatment of active giant cell arteritis.

MANAGEMENT OF NON-ARTERITIC AION

Unlike giant cell arteritis, there is NO established treatment for non-arteritic AION. It is well-known that “a disease which has no treatment has many treatments”. Each new treatment is put forward as a magic bullet for a while, then found to be useless or perhaps even harmful. Patients going blind are desperate to try any treatment. Non-arteritic AION is an absolutely classical example of that phenomenon.

Over the years a number of medical and surgical treatments have been tried without much success.

1. MEDICAL TREATMENTS: The following medical treatments have been advocated:
   1. Systemic Corticosteroids: A number of reports suggest that systemic corticosteroids given during the very early stages of the disease may help to improve the visual function in some patients.^{10,11,30,36,45} In my experience this therapy does not help the majority; however, I have found definite evidence of significant visual improvement with steroids in a small group of patients, particularly those with incipient non-arteritic AION, treated early.
   2. Aspirin: is often prescribed in these patients to prevent involvement of the second eye, but our studies revealed that aspirin made no significant difference to the development of AION in the fellow eye.² This is because non-arteritic AION is NOT an embolic disorder but mainly a hypotensive disorder, as discussed above. Aspirin is indicated only occasionally when there is a definite evidence that AION is embolic in nature.
   3. Levodopa: A study claimed that levodopa improves visual function in non-arteritic AION⁶⁰; however, that study was badly flawed and had no scientific rationale for its claims.^1,35
2. SURGICAL TREATMENTS: Following surgical treatment in AION have been reported:
   1. Optic nerve sheath decompression: This procedure was first reported in 1989.⁶³ Based on my various related studies on the subject^13,24, I pointed out that this procedure had no scientific rationale in treatment of non-arteritic AION and may be harmful.²⁴ However, it became popular because desperate patients wanted something done to recover vision. Finally, a large multicenter clinical trial conducted by the National Institute of Health clearly showed that it was not effective and in fact harmful.⁵⁹ This was a classic example of a treatment without scientific rationale and even harmful.
   2. Optic neurotomy: This surgical procedure has been advocated recently for non-arteritic AION.⁶⁴ In this procedure a radial cut is made through the entire thickness of the optic nerve head; this procedure cuts not only thousands and thousands of nerve fibers in the optic nerve head but also cuts the blood vessels supplying the optic nerve head - both of which are bound to produce more loss of vision without any beneficial effect. My basic, experimental and clinical studies on the optic nerve head and its circulation and non-arteritic AION all show that this is an ill-conceived procedure, without any scientific rationale and potentially harmful. It is sadly reminiscent of the optic nerve sheath decompression procedure discussed above. Therefore, it has NO role in the treatment of non-arteritic AION.
      
      Naturally, the question arises: what can be done for patients with non-arteritic AION? The most important information for management of a disease is always provided by the natural history of a disease, i.e. what happens if no treatment is given. It is vital to know the natural history of a disease before assessing the outcome of a treatment,, so that the natural recovery of visual function is not mistaken for a beneficial effect of treatment. Natural history studies^45,59 on non-arteritic AION have shown that some patient spontaneously recover a variable amount of visual loss without any treatment, and that recovery of vision has erroneously been attributed to several treatments.
      
3. PROPHYLACTIC MEASURES: Although as yet there is no treatment available to recover the visual loss in non-arteritic AION, there are measures that may be helpful to reduce the risk of further visual loss or development of AION in the fellow eye. My studies strongly suggest the following:
   1. Reduction Of Risk Factors: As discussed above, non-arteritic AION is a multifactorial disease and many risk factors contribute to it.^30,36,40,44 I advise patients to reduce as many risk factors (discussed above) as possible to reduce their risk of developing any further episode of AION.
   2. Management of Nocturnal Arterial Hypotension: Our recent studies^{28,33,47,50,58} on nocturnal arterial hypotension or fall of blood pressure during sleep (Fig. 2), discussed above, have revealed this to be a significant risk factor in the development of non-arteritic AION. In view of this, management of nocturnal arterial hypotension seems to be important, both in the management of non-arteritic AION and in prevention of its development in the second eye. In our studies on nocturnal arterial hypotension, about 90% of our patients had no hypertension during the night because of physiological nocturnal arterial hypotension⁵⁸ (Fig. 2-A). This indicates that most hypertensive patients may not need any therapy at bedtime to control their hypertension during the night. Prescribing medication to be taken at bedtime or in the evening to lower the blood pressure during the night may be unnecessary and possibly may put the patient at risk of systemic and/or ocular complications.
      

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