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Changes in neurosciences portend changes in neuro-ophthalmology
At the OSN Section Editor Summit, Barrett Katz, MD, MBA, discussed some reported neuro-ophthalmic manifestations of commonly used agents.
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If you think about what is happening these days in ophthalmology generally, with compelling science driving new retina drugs to market and previously untreatable diseases seeing much investment in time and energy, you might wonder: “If neuro-ophthalmology is the most cognitive of subspecialties, where is the cutting-edge research and advances one might expect of it? Where is the creativity? Where is the innovation? Where is the change?”
You are not alone. We as a field have been largely absent from the translational research seen in some other subspecialties of ophthalmology. That said, I think neuroscience’s time has come in ophthalmology.
By this, I mean that we will see in the next handful of years a reshuffling of the medical subspecialties in ophthalmology, such that neuro-ophthalmology will be taking a seat at the table of advances – more than it does now – and that the science and practice of each of our subspecialties will converge.
 Barrett Katz |
Indeed, the differences between retina and neuro-ophthalmology will be fewer; the overlap between glaucoma and neuro-ophthalmology will increase.
As our sophistication progresses, we recognize that the retina includes the nerve fiber layer – axions of the ganglion cell – so our distinction between retinal and neuro-ophthalmologic disease is artificial.
We ought to accept that neuroscience and practitioners in neuro-ophthalmology have as much claim on the axons of the optic nerve as the retina subspecialists – even before they get to the scleral canal.
Indeed, they have as much claim, as perhaps, the glaucoma community. Remember, glaucoma is just another optic neuropathy. And as we think about retina in creative ways, we can conceptualize retinal detachment as a neurosensory disease, one which, perhaps, may offer a useful model for studying neuroprotection.
Neuro-ophthalmology will participate in new pharmacologic innovation, including treatments for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke), Leber’s hereditary optic neuropathy, optic neuritis and anterior ischemic optic neuropathy (AION).
Ophthalmology has caught the attention of entrepreneurs, and orphan diseases of ours will benefit. And as we participate in this progress of intervention, we too will participate in the adverse events of such therapies. And we are, already.
We are seeing iatrogenic dysfunction in neuro-ophthalmology practice from the use of certain medications used systemically by our colleagues — amiodarone, erectile dysfunction agents, alpha interferon therapies, statins and tumor necrosis factor inhibition.
Amiodarone
Well known systemic complications of amiodarone involve the thyroid and the peripheral nerve. Less known ocular side effects may exist. We are not referring to the superficial corneal changes that all such patients get. We are talking about acute visual loss associated with a swollen disc, dyschromatopsia and a change in visual field suggestive of an optic neuropathy. The disc edema subsides, although the visual loss typically remains.
The purported optic neuropathy of amiodarone sounds very much like AION. You might think it is simply the co-occurrence of non-arteritic AION (N-AION) in an elderly population treated for cardiovascular dysfunction. Yet you have to allow for the possibility that it is a different subset of AIONs, one that looks a little differently than garden variety N-AION. It is a bit insidious in its onset, and it not uncommonly occurs bilaterally, as you would expect of a toxic optic neuropathy. And the disc edema persists longer, too.
Alpha interferon therapy and statins
A second systemic intervention with potential neuro-ophthalmic sequelae is seen with alpha interferon, a naturally occurring glycoprotein secreted by immune cells. This has known anti-viral, anti-tumor and anti-angiogenic influences, and has been used in hepatitis, malignancies, dendritic keratitis, cicatricial pemphigoid, sub-retinal neovascularization, iris neovascularization and post-filtering surgeries.
And yet it is associated with recognized vascular changes of the eye. These include a vascular retinopathy and seem also to include an AION-like picture, one reminiscent of optic neuritis and perhaps even asymptomatic disc edema.
The third drug category of drugs whose complications we are seeing in our practices are the statins, which are wildly successful inhibitors of hydroxy-methyl-glutaryl-CoA reductase, widely used to lower cholesterol. These have known systemic myotoxicity.
Patients have voiced complaints of achiness in their muscles and joints. Yet statins are now recognized to cause a myasthenia gravis-like syndrome presenting to the ophthalmologist with ocular motility disturbance.
Erectile dysfunction drugs and TNF inhibitors
A fourth group of agents include those for erectile dysfunction: Viagra (sildenafil, Pfizer), Levitra (vardenafil, Bayer) and Cialis (tadalafil, Eli Lilly). These are phosphodiasterase-5 (PED-5) inhibitors recently suggested to be associated with another AION-like syndrome, that is, an acute optic neuropathy associated with disc edema, leading to visual loss.
Although a definite association is still controversial, the absence of any proof to its occurrence is not proof of its absence. Indeed, the U.S. Food and Drug Administration has offered some recommendations for label changes on erectile dysfunction drugs to alert practitioners to the possibility of an associated optic neuropathy.
There is controversy in associating these agents and AION-like syndromes, and any association may be present only among men with hypertension or previous myocardial infarction. Too, there is the chance that PED-5 inhibitors but increase the risk of N-AION in this group of patients. In any event, practitioners need to know about the discussion of such a potential association.
The last group of drugs to mention is the TNF inhibitors. These are cytokines derived from macrophages and known to stimulate the inflammatory processes — perhaps also playing a role in multiple sclerosis.
TNF inhibitory therapy is now used with Remicade (infliximab, Centocor), Enbrel (etanercept, Amgen/Wyeth), Humira (adalimumab, Abbott Laboratories) and Lenercept (Genentech/Roche). It is used in treatment of rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylosis and psoriasis.
In ophthalmology, we occasionally employ it in uveitis, giant cell arteritis, Behçet’s disease and sarcoid. It is known to cause sensory neuropathy, acute confusional state, meningitis, Guillain-Barre syndrome and cranial nerve palsy. Recently, TNF inhibitory therapy has been shown to cause a multiple sclerosis-like syndrome in certain patients.
So practitioners need to know about these alleged associations because they may prove to be real, and even now, should be part of any discussion of our patients on these agents, or about to be on these agents. And as future pharmacotherapies in neuro-ophthalmology emerge, we will be participants in their risks, as well as their benefits. Stay tuned.
For more information:
- Barrett Katz, MD, MBA, can be reached at Fovea Pharmaceuticals, 12 rue Jean-Antoine de Baif, 75013 Paris, France; 011-33-1-44-16-42-49; fax: 011-33-1-44-16-42-40; e-mail: katz@fovea-pharma.com.