Viagra and vision loss

You’ll go blind! so the joke goes. It turns out that Viagra, Cialis etc… are alleged to be involved with vision loss in some patients which is something that we predicted might happen a few years ago. My wife told me this morning that this issue is finally starting to make it around to the popular media, but I first heard about this possibility several years ago when my mentor and I were talking about phototransduction and phosphodiesterase inhibitors.

The mechanism for vision loss that everyone is talking about is called non-arteritic anterior ischemic optic neuropathy and can occur in men who have diabetes or heart disease, which are two conditions that typically can lead to impotence and therefore may cause these same patients to seek out assistance. This of course is why drugs like this are prescription drugs and should be carefully monitored and administered by physicians.

However, this form of blindness is not what I am concerned about and I think these are two separate issues that perhaps are being missed by the community as a whole. Viagra, Cialis and Levitra are “selective” phosphodiesterase inhibitors. I put that in quotes, because they apparently are not that selective and have some degree of overlap with another phosophodiesterase involved in vision. Specifically, there is a 10:1 selectivity ratio for PDE-5 over that of the closely related PDE-6 enzyme that we will get to in a minute. So the intended mechanism for these drugs is: Sexual arousal leads to increased parasympathetic activity which results in production of nitric oxide (NO). NO activates the enzyme guanylate cyclase which increases cGMP concentrations. cGMP acts by dilating the smooth muscles in blood vessels which results in increased blood flow and…..enlargement. Normally, cGMP is then degraded by the enzyme phosphodiesterase5 (PDE-5) and in the absence of maintained NO synthesis, vasodilation is reduced, reversing the whole process. These drugs work on PDE-5, preventing its inactivation which results in a prolonged activity of PDE-5 and therefore, prolonged vasodilation. The problem is with this lack of selectivity issue. As discussed above, these drugs also inhibit a closely related phosophodiesterase enzyme, phosphodiesterase6 (PDE-6) which is found in the retina and plays an important role in the normal visual transduction cascade.

In vision, cGMP will keep Na+ channels open in the membranes of your photoreceptors. Photons when they hit the photoreceptors, are absorbed by another molecule called 11-cis retinal which causes a conformational change to a trans retinal form. Activated rhodopsin at this point catalyzes the conversion of GDP to GTP which then activates the transducin protein. Transducin contains multiple subunits including an alpha subunit which breaks off when activated. The activated alpha subunit breaks away from the beta and gamma subunits of transducin and then “pulls away” the inhibitor from PDE-6. At this point PDE-6 then converts cGMP to 5’GMP whereupon the reduced cGMP levels allow for Na+ channel closure. If Viagra inhibits PDE-6, the channels in photoreceptors are constitutively open which means they never shut down.

This explanation over coffee this morning Led my wife, H to quip: “wow, so you pop a rod and you pop rods!”, which was not entirely true, but it was sufficiently funny for me to almost launch my latte out of my nose.

Seriously though, there are certainly visual alterations reported with the use of these drugs including vision with a blue tint, difficulty distinguishing between blue and green light and light sensitivity. In fact, pilots are prohibited by the FAA from flying within 12 hours of using Viagra. These of course are short term problems, but there are issues that should cause some concern. Notably, there are defects in PDE subunits that are associated with a form of retinal degeneration called retinitis pigmentosa or RP (the group of diseases that much of my doctoral dissertation was about). Additionally, there are defects in the cGMP gated cation channels that are also associated with RP. If the biology and pharmacology of these drugs mimic the issues that are functionally related to aberrant activity of these diseased proteins, then we may have a problem.

28 Replies to “Viagra and vision loss”

  1. Thank you for the post. You’ve provided more info than I could get from the manufacturer, pharmacist, and doctor. Of course my pharmacist and doctor are limited to what info they get from the manufacturer as well. I’ve very much wanted to try this class of drug for my own ED. I’m only 50 and would like to remain sexually active. Unfortunately I have RP, am “legally blind” and still haven’t been able to get an accurate risk/benefit estimation. If you have any more info on this issue I’d like to get it to my doctor to follow up.

  2. Thank you for the comment Mike.

    First off, I should note that I am a research scientist and not a physician and that any information on my blog entry should not necessarily be construed as clinically relevant, or medical advice, especially as it is not my area of expertise. Furthermore, it is pure conjecture based on my understanding of the molecular processes of phosphodiesterase and the isoforms of PDE in retina. However that said, I stand by what is written there.

    Unfortunately, I have not really followed the literature since writing that blog entry (dated 2005) and cannot advise on the issue other than to say that after spending a couple of hours in a literature search this evening, I find nothing new on the issue and in fact, some disagreement over the actual effects of ED drugs on the photoreceptors. I cannot really say whether or not Viagra and other ED drugs have an effect on or accelerates retinal degeneration as I have not done those studies, but have been thinking of actually starting a small investigative study. I suspect that like anything taken in moderation it would be OK, but I should leave that decision up to you and your physician.

    Our work in RP has been focused on characterizing what happens to the retina during the disease process and most recently, we are involved in developing and testing some new drugs that we hope will have some efficacy in limiting retinal cell death in both RP and AMD. An appropriate assay of drugs is somewhat dependent upon developing new models of RP and that is another effort that is just about to pay off.

    Right now however… science funding is under intense competition for limited resources and as such, we do not have any current treatments to delay or reverse the changes in the retina. But we are passionate and working very hard on curing blindness.

  3. If you have any more information on RP and Viagra, plese post it here, been looking for, and not finding much help, what a horrible thing to have to choose between, what a cruel fate, lol! If you could post any web sites on the subject it would be greatly appreciated.
    Thanks so much…

  4. I will absolutely post information here if I run into it. I don’t necessarily think that it is a huge risk, but like most things in life, things done in moderation likely will not hurt you.

  5. Hey thanks to you all particularly B W Jones for your research into RP (I have RP) I also have ED and have been prescribed Viagra by my doctor. He obviously forgot I had RP or didn’t read who shouldn’t be prescribed Viagra as it says clearly on the information enclosed that RP sufferers should not take it. That is obviously Pfizer covering for their lack of research into this possible problem with their product & RP sufferers. I will keep an eye (no pun intended) on this blog & hope to read more if and when it is available. Take care, Shane, Navan, Ireland.

  6. Hey Shane, does the insert really contraindicate viagra for people with RP? That would be new and very interesting.

    I’ll absolutely keep this updated with anything new I learn or hear.

    Best regards,

  7. Hey Steve,

    Yeah, I’ve seen that study and while I respect the results, it was a very short term study (~48hrs) while the effects on retinal degeneration take years. As I said, any short term usage is probably just fine, but I worry about longer term implications.

  8. If your hypothesis is correct, the common pathway for all RPs resulting in vision loss should be PDE 6. If all RPs have subnormal PDE6 , then you have hit the big jackpot. Because theoretically by reverse bioengineering, PDE6 can be artificially synthesized or drugs to block the breakdown of PDE6 can be research.

    1. Hey Edmund,

      Thanks for the comment. Actually, there are many, many causes of RP, only a certain percentage of which have defects in the PDE pathways. Other forms of RP are caused by mis-trafficked rhodopsin or by defects in the retinal pigment epithelium cells or by packing abnormalities of opsins in the photoreceptors. So, a single “silver bullet” is not going to solve all instances of RP.

  9. Thanks for the post. It was a good review for me after optometry school. I definitely enjoyed your wife’s comment. I have a patient asking about vision and viagra. Any good resources for NAION and viagra?

  10. I came here within an hour of re-reading the insert of a tablet called Satisfils a sildenafil form ‘on promotion’ which the pharmacist gave me free as well this time as a bonus! I got a funny eye feeling, and was later not made to feel better by the phrase ‘hereditary degenerative retinal disorders’ since my father developed a mild glacoma after hitting sixty.

    Well the writing is now on the wall whatever the disease and whatever the name the sildenafil bears. – Moderato!!

  11. Hi,

    Today I got prescribed Viagra by my physician, and when I read the insert I got a bit scared and started browsing the net.

    The insert states that you should not use Viagra if you have some specific rare hereditary eye-sickness (like retinitis pigmentosa).

    I don’t have retinitis pigmentosa, but I do have congenital stationary night blindness (CSNB), and that illness is sometimes mentioned as being in the same group of illnesses.

    I couldn’t find anything on Viagra when having CSNB, the only thing I found was a warning from 2003 to be cautious.

    Do you know if there’s any news on this?

    Thanks!

  12. I am a 56 year old physician, one year post radical prostatectomy for minimal ca ( psa 1.4, Gleason 3+3, capsule intact; 1 of 16 cores positive )but with 10 year history of ED. I have minimally elevated systolic BP for about 1 year. No Hyperlipidemia, Diabetes or any other medical conditions. No opthalmologist has ever commented on my optic nerve including a friend who is a retina surgeon. Prior to surgery I took Viagra when it was released around 1997. Not long after I experienced several episodes of Scotomata lasting about 30 minutes and occurring within 12-18 hours of taking Viagra. Nothing permanent. I switched to Cialis which I have to take regularly since surgery with no repeat of these symptoms. I have no answers or suggestions other than for possibly some slight difference in their chemical composition even though their method of action is similar. As for dossage I take the highest dose of Cialis-20 mg. and the scotomata occurred at both 50mg and 100mg dosages of Viagra.

  13. I am 70. My eye lense is -6,-7. I had to undergo chrio surgery ( freezing) for my retina 25 years back, and then again recently lazer treatment for small holes that had developed on sides of one eye. I used viagra only once, it worked but at that time I suffered blue and green light problem for about one hour. I do not feel any other eye problem. The viagra worked otherwise. Could you comment on my eye condition. Was it due to viagra?

    1. The blue and green light problem is a pretty common side effect of Viagra and similar drugs from what I understand. I can’t/won’t give any medical advice here, but don’t think the chromatic shift in visual perception is dangerous. Contact your personal physician for guidance on this issue.

  14. Hi,

    I’m not sure if it is due to my moderate use of cialis, but I have developed what appears to be sparkles in a certain part of my vision. It only occurs in particular light such as looking at the sky and in particular when it is overcast. It also moves with my eyes as I look around. If I am inside I can’t see it or if I look away from the sky it isn’t there. I have seen the ophthalmologist. And he says my eye is healthy. I’ve been to a neuro surgeon and he is at a loss also. I do have floaters but its different to that. have had MRI scans, no strokes etc, and all is healthy. Any ideas?

    1. Hey Simon,

      Again, I cannot administer any medical advice from this blog.

      There are lots of things that it could be from optical issues with the floaters or cataract like deposits in the lens (all of us have them) to ocular migrane like presentations. I’d suggest working with your ophthalmologist further if they continue to bother you.

      1. Hey thanks, I understand you can’t give medical advice and repect that. I’m just trying to get ideas so I can work with the specialists. Take it easy.

        Regards
        Simon

  15. Sparkles (like seeing stars) in the eye field of vision can be a symptom of low blood pressure. I tried 5 mg Cialis -just one pill – the one time – and 3 hours later at bed time I experienced those sparkles and a severe loss of night vision. The sparkles went away within a day, the night vision slowly returned over a week however I think I still have some residual loss of night vision. Scared the cr** out of me. I would rather have my night vision than. …. Well you know. A full physical and eye checkup found nothing wrong.

    1. Did your night vision ever fully come back?
      I started taking a 5mg cialis here and there over the course of this year and last, I’ve took a bit over a 100 mg total if I had to guess. My night vision seems much worse than I remember. Very frightening. I also have sparkly/staticy vision in certain light that I never used to have. I really noticed my night vision worsen a day or so after the last one I took, which was a little over a week ago. Will never take one again

  16. PharmD here, was curious as to how PDE-inhibitors caused blindness – AWESOME explanation. Love the “selective” for PDE-5 Inhib – too often receptor selectivity is more about marketing than pharmacology (anticholinergics for bladder incontinence oxybutynin, tolterodine, solifenacin, et al). Thanks for putting this together, especially 10+ years ago.

    1. Hey Cole,

      Interesting question. It is thought that the mechanism is mutation leading to PDE dysfunction, leading to failure of cGMP hydrolysis. How that induced cell death is another question.

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