| Affiliation |
(AGL) Chairman, Department of Ophthalmology, The Methodist Hospital, Houston, Texas; Professor of Ophthalmology, Weill Cornell Medicine, New York City, New York; (MM) Class of 2023, Baylor College of Medicine, Houston, Texas |
| Transcript |
So you're asked to talk a little bit about steroids, and the first thing is, I like to refer to the steroids as glucocorticoids. Because as you know, steroid is a very lay description of what this actually is, and if you use this term glucocorticoid, you're telling me you're not talking about the mineralocorticoid activity of the steroids, and it will remind you about the side effects which are on the glucose side. So, when we're dealing with glucocorticoid therapy in neuro-ophthalmology, the most common indication that we are using it for is giant cell arteritis. So, patients who have giant cell arteritis need to have glucocorticoids - normally if they have vision loss, we're going to give IV or high dose oral. I prefer intravenous because it gets the levels up faster. And normally we're going to choose methylprednisolone, as opposed to our colleagues in neurosurgery who very much like dexamethasone (Decadron). So, for me, the rationale for using prednisone in the PO (oral) state and methylprednisolone intravenously are, the mechanisms of actions for glucocorticoids on giant cell arteritis and all of our inflammatory diseases in neuro-ophthalmology rely upon both genomic and non-genomic effects of corticosteroids. And what I mean by that is, binding of the glucocorticoid to the membrane occurs in most genomic and non-genomic effects. Binding after the membrane into the nucleus leads to mRNA, so we have translation of proteins: either proteins to suppress the immune system, or proteins to accelerate it. So, we can repress - trans repression, pro-inflammatory molecules - and we can trans activate - anti-inflammatory molecules. And those are the genomic effects, and those genomic effects take hours to days to get going. And they reach a saturation point very quickly in terms of the genomic effects on the DNA. So, the things that we are using intravenous for are the non-genomic effects. We want the genomic effects, but the non-genomic effects really don't kick in until moderate to high doses. And so, when we have non-genomic effects, these non-genomic effects are affecting membranes - membrane stabilization - and directly acting on the pro inflammatory cascade in immune disease. So if I've got a patient is going blind with giant cell I want to get the levels up high so that I can get the non-genomic effects, including the membrane stabilization effects, of the nerve protection, and then we're going to maintain them on a dose that will maintain the genomic effects, which is the mRNA-DNA driven trans repression or trans activation of Pro and anti-inflammatory molecules. So, the choice is going to be based on potency and route. So, hydrocortisone is kind of the standard number-one potency. For prednisone and methylprednisolone, four is their potency relative to a one on hydrocortisone. But these synthetic molecules are going to have a lot less mineralocorticoid activities, so that's why neurosurgery chooses dexamethasone, and we choose methylprednisolone to maximize the glucocorticoid immunosuppressive effects and minimize the mineralocorticoid effects that are going to be inherent in any kind of steroid. And so, for giant cell arteritis, we're really talking about high dose intravenous if you've got vision loss, or high dose oral if you don't have vision loss and that is our main indication in neuro-ophthalmology for corticosteroids. Now we have some other secondary indications. So, for example, optic neuritis, or neuromyelitis optica, or MOG (myelin oligodendrocytic glycoprotein), those also need intravenous steroids. For the same reason - we're trying to achieve a total effect that is more non-genomic than genomic effect - we want that level to be high, and that dose has to be high, and the round has to be intravenous, and that's called 'pulse.' So, we give patients pulse therapy when we're trying to treat something acute, and we need high levels, and we need those non-genomic effects really quickly because the patient is no-light perception or light perception region. So that's NMO and MOG, and any inflammatory process where we can use the immuno-suppressive effects of glucocorticoids, whether that's uveitis or sarcoidosis or ANCA or lupus, all of those our go-to is going to be methylprednisolone, and in the acute setting pulse intravenous methylprednisolone. So: optic neuritis, GCA, lupus NMO, MOG, everyone's getting pulse 1,000 milligrams intravenous methylprednisolone, followed by oral taper with prednisone. The less used indications like traumatic optic neuropathy and non-arteritic anterior ischemic optic neuropathy are controversial and we will not be covering those. So in summary, you need to know that glucocorticoid is what I prefer to call steroids to differentiate the mineralocorticoid effect, that I like intravenous methylprednisolone and oral prednisone for post therapy for the bad things in neuro-op (the "three-letter words" GCA, NMO, MOG), pulse intravenous because we want to drive both genomic and non-genomic effects of the corticosteroid. And you should know that we are not using the relative potency (hydrocortisone one, prednisone and methylprednisolone four) to drive the decision making. As opposed to neurosurgery where they are using dexamethasone/Decadron for pretty much everything, we prefer intravenous methylprednisolone. |
