Lecture: Ocular Side Effects of Common Oral Medication

DR. RETT: Hey, everyone. My name’s Doug Rett. I’m the chief of optometry at VA Boston. I’m in Boston, Massachusetts. There’s about a foot of snow on the ground. I hope it’s warm where you are. I wanted to talk — I’ll share my screen. I wanted to talk today about ocular side effects in common oral medications. I’m happy to be asked to come speak with everybody. I think it’s my third Orbis webinar. I enjoy doing it. It’s a global audience. I chose these medications to speak about because I think they’re very common and ubiquitous worldwide and they’re very commonly prescribed. And so, therefore like common side effects. But I think that the most important reason why I chose these topics is because it’s an interesting mechanism of action that all of these drugs have on the eye. I think and they can teach us a lot about the eye themselves. I think it’s important to recognize that these drugs have these ocular side effects. But it’s another thing to understand the mechanism of action. So, that’s what we’ll talk about today. The side effects from oral medications that happen all over your body. But we have to admit that the side effects in the eye seem to happen a little more commonly. And so, why might that be? The eye is unique in several ways. In the eye, the most densely vascularized tissue exists, that’s the choriocapillaris in the maculas. And the most densely innervated, that’s the cornea. The eye is small, it’s fragile. It’s small — it’s crowded. There’s several conditions that we’ll talk about today that happen just simply because everything in the eye is so crammed together that if things change because of side effects, it creates a snowball immune effect. That’s a form of immune privilege in the eye, there’s simply a lot to go wrong. We’ll have about 45 minutes of talk, I’ll talk for about 45 minutes and then do about 15 minutes of Q&A. I can’t get to every medication, but get to as quickly as I can. The chat function is disabled, but the Q&A is enabled. If you have questions, put them in the Q&A, and at the end of the talk I’ll get to them.
The first topic is hydroxychloroquine. I’ll try to stick to the generic names. Hydroxychloroquine, and the mother medication, chloroquine, is used all over the world for malaria treatment. It’s the preferred treatment for lupus right now. And in America, it’s commonly prescribed for rheumatoid, sarcoid, and other inflammatory conditions. But it creates a toxicity that I think a lot of us know about. It creates a bullseye or a ring-shaped retinopathy around the fovea. It’s worse with chloroquine, as we know, and better with hydroxychloroquine. It’s still a non-negotiable percentage in terms of retinopathy and hydroxychloroquine. After I started, Michael Marmor and his colleagues came out with screening for patients with chloroquine and hydroxychloroquine. It changed the way we saw patients the next day. We read this article and what should be happening and should be going on with our patients and changed the way we worked with these patients. In if ’02, the 10-2 visual field. Nine years later in 2011, introduced three things, it introduced the concept of a cumulative dose, which is when the patient reaches 1,000 grams, the risk of retinopathy increases dramatically. When and when you’re taking the standard dose, this dose was reached at 7.5 years. And using the ideal weight as opposed to the real weight. For patients who are perhaps obesity but short have less of a risk. And then patients who are of a regular weight but taller. And introduced the novel concept of spectral domain OCT and using OCT to screen for toxicity. And then again, five years later, Michael Marmor and his group at AAO revised their recommendations and made more changes. Away from using ideal weight. The concept seemed to be confusing for certain clinicians. It leaned more on the OCT and added fundal fluorescence as a screening tool for these patients. And introduced the concept of patients of different ethnicity have different sized bullseyes and rings of their toxicity. And specifically mentioned patients of East Asian ethnicity with a larger diameter ring, and others with a tighter diameter ring around their fovea. Imagine my surprise when I was reading journals last — I think it was a couple months ago, and I found that the group came out with recommendations yet again. This article is only a couple months old. I wanted to lead off today’s talk speaking about it. Because I think some of our audience might not have read this yet. Jeez, it hasn’t been that long since they revised it, but it’s been nine years since they revised it. If anything, they come out with recommendations every nine years. Let’s dig into the new recommendations for hydroxychloroquine screening. It’s broken down into different sections. Each slide will be a different section. The mechanism of action for the nature of toxicity is still not yet known. But we know the damage is to the outer retina and the photoreceptors. As an aside, I’ll use my mouse here, there’s differences of opinion on what terminology to use when describing landmarks on the OCT. But five or more than five years ago now a group tried to come up with consensus definitions on nomenclature and specifically nomenclature for these four lines in the outer retina. I’ll refer to these, and I hope everybody else will, it’s nice to be on the same page globally and use the same nomenclature in line is the external limiting membrane. It defines where the neurosensory retina ends. The second line is the ellipsoid zone, which is the first portion of the photoreceptors. This third line is the interdigitation zone, where the photoreceptors interdigitated with RPE. The third is the RPE. It’s labeled RPE-Bruch’s membrane complex, you can’t see the Bruch’s membrane when it’s on the OCT, just when it’s detached. They just say RPE-Bruch’s membrane complex. There’s four lines, and the first time you see early damage in toxicity is the outer nuclear layer. Skip to the end, and you can see what happens after 18 years. And after 15 years, and this picture is from the article. Here you can see the outer nuclear layer, this darker band in this color. And it’s thinned in this area. And then one year later, it’s almost completely gone and you have the interdigitation zone starting to become thinner in this area. You have to admit it’s much thicker and brighter, hyper-reflective, and thinner and dimmer. After 18 years. Not that long, all within a three year period. This patient went from being barely effected to completely gone. And outer retina is gone, photoreceptors is gone, and it’s just bare RPE in this area. That’s what happens with the toxicity. It does nothing and then everything relatively quickly. Patterns of disease, and again, goes back to what I mentioned about different ethnicities having different diameter bullseyes. And identifies and many more studies have been done in these last nine years and identified patients of Indian, Middle East, and European ethnicity to have a bullseye that it described as perifoveal. And then it describes at extra-macular patients of northeast and southeast Eastern ethnicity with a larger diameter. See on the next slide. Patients with the closest distribution to the fovea itself, theoretically would be the most concerning and the most debilitating. But I think, you know, it’s one thing to, you know, if we were in school to memorize this slide and know which ethnicity is which diameter bullseye, but the article, at least this section of the article ends with this quote, a moderate percentage of patients from each group will show a contrary or mixed pattern. The important takeaway is it can be any diameter bullseye. An astute clinician needs to look for it in general. Don’t focus on this patient is this ethnicity, look for this area, just look for it every why where., in the pole, and look for it everywhere if your patient is taking hydroxychloroquine. And the perifoveal, the smaller distribution on the left, and the larger distribution on the right. Dosage recommendations. It’s been known for years or perhaps decades that the patient should not go over 5 milligrams per kilogram. That’s in real weight. Just know that the typical dose for taking this is 200 milligrams twice a day. If your patient weighs more than 80 kilograms, 176 pounds. If they’re less than that, and taking the standard dose, then your patient is taking too high of a dose. The tricky thing is they only come in 200 milligram tablets. So, the prescriber will often tell the patient to break it in half. You can see the picture on one of the first slides, those tabs were kind of barbell-shaped and they’re relatively easy to break. The toxicity is not necessarily a toxicity over a tern day, but it’s over a certain cumulative dose. You can take a full dose Monday through Thursday and take half of a tablet on the rest of the days of the week and be okay. It’s more like a cumulative dose in your system. And so that’s how they’ll do it. But, you know, you can tell a patient to skip a dose every Saturday and Sunday. Or take half of a dose half the week. But what the patient actually does is a different animal itself and if we see patients, if you’re in the audience seeing patients, you know that patients don’t always necessarily do what they’re supposed to do. If you see a patient on hydroxychloroquine, ask what doses they’re taking and might surprise you how high a dose they’re taking. Doses near 6 milligram per kilogram markedly accelerate risk. And there’s patients taking 10 milligrams per kilogram developing toxicity within two years where typically it takes over ten. I think this is all — frankly a lot of the topics we’re going to talk about are bummers and make you paranoid. But it’s a safe drug. If you’re using the direct dose, it’s a very safe drug. There are risks for toxicity. But I like this quote and I’ve said this to patient, that even after using hydroxychloroquine for 20 years, the incremental risk in the next year of you getting toxicity is still less than 5% if you’re taking the proper dose. And so just to kind of put it in perspective. Even if your cumulative dose does exceed that 1,000 grams, it’s unlikely you’ll get toxicity. Risk factors of toxicity, we talked about the dose. Renal disease. Makes sense. Increase the circulating level of the drug, almost acting like you’re taking a higher dose. Gender is no risk factor, liver disease has no risk factor. Tamoxifen use has a risk factor. That has a side effect of maculopathy. They found not ring maculopathy, but a different kind of maculopathy. They found they have an adverse metabolic synergy, which is a horrible thing to have. But this risk factor of two different types of maculopathy creates a higher risk in general. Patients taking tamoxifen, usually for breast cancer, should not take hydroxychloroquine. There’s no data to argue that macular disease like age-related macular degeneration or vitelliform macular degeneration would increase your risk of hydroxychloroquine toxicity. But it’s a contraindication to treatment. If they have pre-existing maculopathy, they should be considered for a different medication. The big change that happened in the article from a couple months ago is how they determined what tests they recommend eye care practitioners use to screen their patients. And they separated all of our tests out into primary tests, secondary tests or not recommended tests. And the only tests considered primary are spectral-domain OCT and fundus autofluorescence. We’ve talked about the spectral-domain OCT. Fundal autofluorescence, specifically asks for wide-pattern, and depends on the make and model of your OCT machine. But achieve around a 50 to 55 degree arc of visual field when you’re looking for this toxicity. Know that some patients have that wide diameter bullseye. And taking a tight autofluorescence, might only hit the middle of the bullseye and miss the bullseye itself. So, it recommended — academy recommended spectral-doe main OCT for all patients on Plaquenil, and do wide on all of your patients. And if you see unusual things on either of those tests, then you can order a visual field. For the same reasons like we talked about for the wide field autofluorescence, it recommends a wide field or a regular field, a 24-2. Specifically the 24-2C because it has these central spots. I was always taught to do 10-2s on these patients, but again, you might miss president wide diameter bullseyes in a 10-2. It also mentioned multifocal ERGs as a secondary test. Not recommended, a fundus exam. Why can’t I do a fundus exam? It’s not like you shouldn’t do a fundus exam. But know with the naked eye, with the human eye, ebb the slit lamp, you’re not able to detect changes in the retina like an OCT or autofluorescence would. By the time you detect it on a fundus exam it’s too late. The final recommendation and take-away, baseline exam when they start, fundoscopy, OCT, widefield. And look for lupus retinopathy if they’re taking it for lupus, and pre-existing maculopathy. And educate the patient, five years I’m going to see you every year and start doing tests and until you stop taking the medication to make sure you’re not suffering from side effects. And after five years, start the annual exams, OCT and widefield fundus autofluorescence. That’s it for Plaquenil. Next medication is ethambutol. Prescribed worldwide, usually for tuberculosis. Prescribed for my mycobacterial infection. Because they’re negatives of each other almost. They’re maps indicating where tuberculosis is endemic, and MAC is endemic, mycobacterial avium complex. They’re calling it MAC because they’re combining avian species that cause infection. They’re all infectious by inhalation and stubborn to treat and require months-long therapy because the infection is so deep in the lungs. Let’s talk about how ethambutol can create toxicity. Ethambutol works on these infections because it inhibits an enzyme that’s needed in the mycobacterium on the cell call. And the metals you are chelating and you are worried about zinc and copper. And there’s the PMG, papillomacular bundle. That’s where the high energy neurons and high mitochondria are in all of our neurons. If you’re starting to key late copper, you’re damaging the neurons and decreasing the function of that. Typically with toxicity from ethambutol, it’s a central detect. It also chelates zinc, damaging ganglion cells. It’s an optic neuropathy. But it’s a retrobulbar optic neuropathy which we’ll talk about in the next slide. And the World Health Organization estimates every year 9 million more cases of tuberculosis worldwide. Half are given ethambutol. If you estimate 1 to 2% prevalence, 100,000 cases of ethambutol every year. Something to screen for and look for. The toxicity is dose-dependent. You see the percentage risk at certain doses listed here and you see how it’s correlated to factors that are correlated with better outcome. It’s also secreted by the kidneys. So, renal disease increases your risk just like hydroxychloroquine does. Ethambutol optic neuropathy, it causes a painless, bilateral, symmetric and retrobulbar optic neuropathy. I was told that in retrobulbar optic neuropathy, the phrase is the patient can’t see anything and the doctor can’t see anything. Typically with optic neuropathy, looking for a swollen nerve. It grabs your attention. But in the retrobulbar optic neuropathy, you have to go with more of a history and the case presentation. You really have to be looking at the medication list in situations like EON optic neuropathy. This is a classic visual field. Again, it’s the PM bundle that’s damaged. You’ll get central defects. Especially on the temporal side of the visual field, inside the opt irk nerve and the macula. Patients have loss of central visual acuity, central visual field and color vision problems again because it’s optic neuropathy. You won’t get an APD typically. APD is almost always measured relative to the other eye. If you have a bilateral and symmetric optic neuropathy, you won’t get an APD. The pupils might be sluggish. Optic nerve swelling is not common. What should we do for patients who are on ethambutol? Because it’s such a serious risk and not that uncommon if we’re talking about these percentages of risks that are dose-dependent you know need to see these patients at baseline. Screen out any patients who already have a pre-existing optic neuropathy, and then see them monthly during the treatment. And each month you’re going to look at their visual acuity, visual fields, and color vision. At the baseline and then at each month. It also writes the tests that you can do that are not mandatory with the VEP. Again, multifocal ERG. And it urges caution with an OCT, it’s a retrobulbar condition. When you’re measuring the optic nerve of the OCT, you’re measuring the very anterior part of it, right? Maybe acutely, you might see a little bit of thickening on the optic nerve OCT, and then chronically, you might see a little bit of thinning. But again, you have a risk of being reassured if you’re doing the OCT and finding it normal that the patient is normal, where there’s really damage retrobulbar optic nerve. Use OCT with caution. The only treatment for ethambutol optic neuropathy is discontinuing the medication. Recovery does happen after you discontinue, but it’s referred to as an incomplete recovery. The average improvement is two lines better. Something to consider, but is not proven, if they’re at risk or on ethambutol, they could dose high dose copper and high dose zinc, toxicity is because of copper and zinc. It stands to increase the dose of copper and zinc, but it’s not looked at. It’s just interesting studies that people have looked at. That’s ethambutol. Another for common treatment for tuberculosis is rifampin. Part of the common cocktail given for TB patients. This is something I had to ask, trivia question, besides lacrimal system damage, what can cause reddish-orange tears. I thought it was a tumor or damage to the lacrimal gland, but if it’s reddish or orange, it’s rifampin. This happens in 100% of the patients who take rifampin. And I would be very concerned if this happened to me. It’s something that’s benign. It goes away 100% of the time. It’s never been permanent. And hopefully something that the prescribing provider does tell your patient. But if they are taking it and cam to you, you should reassure them that it’s okay. It’s an interesting way to see that the patient is compliant if you’re a TB doctor, you try to make the patient cry during their exam and you can see if they’re taking their rifampin medication. Mechanism is not known next topic is erectile dysfunction. These ED meds are some of the most commonly prescribed medicines, bar none, over the whole world. I’ve listed them here, three most common ED meds. Inhibit phospho di esterase type-5. We don’t care about that, but we care about phospho diesterase type 6, and that’s here. If you’re inhibiting P DE type 5, this is pounds in vascular smooth muscle, it inhibits arterial — and allows the engorgement of blood. It has an admittedly weak, but co-inhibition of PDE-6. When you accidently inhibit PDE-6, you can have problems with the photo transduction and problems with the optic nerve. A very well common — a commonly known side effect to these ED meds is a bluish tint in your vision, which we call cyanopsia. It’s long documented that PDE-5 inhibitors cause this, and it’s proven that those actively having this side effect underwent ERG studies and showed that there was actual changes in the optic nerve while they were having this. It’s something that you reassure your patients. I don’t think any patient should be contraindicated from taking DPE-5 inhibitors because of this cyanopsia. It’s short-lived and never found to be permanent. Patients should be contraindicated if they have certain forms of retinitis pigmentosa. There are some kinds that cause Bartholomew indications in the gene that codes for PDE-6. This would imply that if you inhibit PDE-5 for ED, you’ll weakly inhibit PDE-6, and that will decrease the retinal function in your patients with RP. This is shown to be proven in mice studies. It hasn’t been proven in human studies. So, I’ve considered telling my RP patients to not take erectile dysfunction medications because of this reason. There’s just so much to risk for patients who have RP. Sometimes hanging on by a thread and they don’t need any further risk of decrease in retinal function. But by far the most commonly talked about side effect or risk factor with ED meds in the eye is non-arteritic anterior ischemic optic neuropathy or NAION. When you read any serious scientific article about NAION and these medications, the word you hear is “Controversial.” I’ll try to explain both sides of it here. The main controversy stems from these cases coming out of patients having NAION after taking ED meds. But the simple fact that the risk factors for erectile dysfunction overlap the risk factors for NAION almost completely. So, it’s really hard to separate out this causal relationship versus just a correlation with these medications. I’ll try and explain both sides. One of the problems is when you’re talking about NAION, we still don’t know exactly the cause of NAION. But we do know that nocturnal hypotension plays a role in it. It stands to reason that most of the time you’re taking these PDE-5 inhibitors at night. At night the systemic blood pressure is reduced. And these further reduce our blood pressure. It stands to reason if you’re on the border of getting NAION and take this medication to further lower your systemic blood pressure at night, ergo you would be a little bit more at risk of having NAION. And there are many cases, in some case serious, of patients diagnosed with NAION within 24 hours of taking one of these medications. But again, the risk factors overlap. But some of these case reports are children who are taking these medications for pulmonary hypertension and you have to admit that these children don’t typically have the risk factors for erectile dysfunction. But all of the studies — well, all of the papers and articles that are written are all case reports and case series. You have to admit this is the lowest form of evidence-based medicine. None of them explicitly test for an association between the exposure and the outcome, no controls. They’re really just case reports. And arguing against a relationship between these medications has the overlapping risk factors that I talked about. And then the sheer fact that there’s so many patients who are taking these medications. They are, like I said before, some of the most commonly prescribed medications in the whole world. 6 million prescriptions written for ED meds in the US alone just last year. With all of these patients taking these medications, you have to admit, you would think that you would see a higher incidence of NAION than we do. And so most all studies that look at this concluded there is no compelling evidence to suggest that PDE-5 inhibitors are associated with a higher incidence of NAION. But typically the recommendations that I would give and what I give to my patients is that because NAION can be so serious, if you have a history of NAION in one eye, then I think that’s a contraindication to take these medications in general. And then like I said, if you have a history of retinitis pigmentosa, you should not be taking these medications. But anyone else, there’s no real justification for stopping these medications. Talk about the bluish hue in the vision, and if they have transient vision loss to come in right away, but other than that, I would leave it at that. And curiously, you would saw, almost all of these case reports have been with Viagra and tadalafil, and fewer in others and none reported with Levitra. Anticholinergics. In America is one of the only countries that has direct-to-consumer advertising — that will allow pharmaceutical companies to advertise on television. And almost all of these commercials are half side effects and they almost always mention glaucoma. I think as eye care providers we should talk about this risk and this connection because patients will ask us about this as well. These are anticholinergic medications, talk about the cholinergic system. It uses the neurotransmitter acetylcholine to control the central and autonomic nervous systems. The way it works in the CNS is generates wakefulness and alertness. These systems we’re talking about which inhibit cholinergic system cause drowsiness. The autonomic nervous system is responsible for resting and digesting. These medications are prescribed for things like bladder and bowel incontinent. There are cholinergic receptors all over our body. And the causes the usefulness of these medications are all over our body also. In the eye, really focusing on the iris sphincter, the ciliary body, and the lacrimal gland. These medications, there’s — what’s the word? Mnemonic that you learn in school. That you have to think about when prescribing anticholinergics, can’t see, can’t pee, can’t spit, can’t poop. The most commonly prescribed anticholinergic in the US is Benadryl, which is diphenhydramine. It’s in many allergy medications. It dries you out. Can’t spit. Just kind of like a drying thing. Whether it’s your eyes or your mouth or your nose. And also, it’s in a lot of over the counter sleep medications. Because, again, it decreases your wakefulness or alertness. It makes you drowsy. Oxybutynin secondly most commonly described in America, typically for bladder incontinent. Anticholinergics are commonly prescribed antidepressants. Cyclically prescribed and we have switched to a lot of serotonin reuptake inhibitors. And still some are — and SSRIs do have anticholinergic properties. But minimally so. Paxil has the greatest anticholinergic effect. When we’re talking about the risk of anticholinergic medications in the eye, typically what we’re talking about is this mid-dilation state that these medications can give you. And like we’ll talk about in the next slide, this can increase your risk of pupillary block and angle closure. But it’s really a very minimal risk. And we’re talking about — all we’re talking about is inhibiting the iris sphincter, causing it to dilate a little bit, and changing the position where the iris hits the lens and then maybe theoretically causing problems in the outflow of the aqueous humor. So, I’ve put up on this slide the most commonly prescribed antidepressants. On the left is the United States, on the left is the United Kingdom. You can see there’s similarities, but differences. And I’ve placed stars on each of these medications about what — where you found case reports for pupillary block and are where there have been case reports for ciliary body displacement. And you can see for the tricyclic antidepressants, it’s typically pupillary block. And for the SSRIs and is the SNRIs it’s typically ciliary body displacement. Let’s talk about each of those. Two different mechanisms of action where these meds can cause problems with angle modify closure. The picture on the left is a picture describing pupillary block in closed angle glaucoma. And again, we talked about in anticholinergic medications, you’re slightly dilating the pupil. And it could stand to reason that in a patient who has pre-existing narrow angles, you moving or the drug moving the position of the iris could cause problems. A lot of us on the call know that the position of the iris that is most risk of creating angle closures is mid-dilated position. Where the tip of the iris has the strongest content — contact, I should say — with the most anterior part of the lens. And so if you have a patient with a very thick lens with a cataract and put the edge of the iris right at that mid-dilated spot, you could create an adhesion to the lens, creating aqueous humor, and Bombay and closing the angle as we all know about. This is exceedingly, vanishingly low risk factor in anticholinergic met indications. And the sheer volume of patients taking Benadryl and taking anticholinergic medicines for whatever reasons and the sheer lack of angle closure that we see just shows that it’s a theoretical risk and not a real risk. But I think what a real risk is, is some of these medications that have choroidal effusion or uveal effusion creating narrow angles of closure. That’s a completely different mechanism of action. Here, the picture on the right shows a normal flow of aqueous humor. And the picture on the left shows a topiramate-induced choroidal effusion and angle closure. What the artist is trying to illustrate is a swelling of the ciliary body. When it swells, it — and pushes anterior. This pushes the lens anterior and pushes the iris anterior into the cornea, closing the angle and creating an angle closure. When you treat the first type, when you treat pupillary block, the solution is very easy. You just equalize the pressure between the anterior chamber and the posterior chamber. And the easiest way to do that it so blast a hole in the iris with the laser. Do an LPI, and the problem is solved. If you do an LPI in uveal effusion, you’re not going to solve anything. It’s not the pressure differentiation that’s causing the problem, it’s the swelling and lifting up anteriorly and closing everything. Lazier is not going to help it, the only thing that can help is to stop the offending agent. It behooves you to look at patient’s medications. You will start lowering the pressure and getting the patient LPI to relieve that. But if you don’t take a couple seconds and look at the med list, you’re going to maybe miss that the patient is on to — or on a high-dose anticholinergic medication. The cause is not necessarily pupillary block, but the block is choroidal effusion. What do you? Stop the offending agent like I talked about. Give drops like in angle closure. Give steroids, they shrink the ciliary body and lets the whole lens, iris, diaphragm shift back, and cycloplegics, not to block, but they have the same effect of rotating the lens iris diaphragm posteriorly. And remember when you’re giving IOP medications, remember the Pilo paradox. It’s a cholinergic kind of medicine. If you have an anticholinergic problem, give pilocarpine, but it has a paradoxical effect of causing the ciliary body to shift anteriorly. So, stay away from pilocarpine in these cases. There are several case reports of this. I’ve seen cases of topiramate-induced angle closure. There’s Lexapro, the first someone an SSRI. And sumatriptan and others are for migraines. And you’ll see this a lot. Topiramate, that’s the top. And sumatriptan is not far behind. I’m going to skip this slide and go into the next and last medication. Acne medications. There’s two meds that I wanted to talk about. The first one is doxycycline. Doxy is used all over the body. I use it in my patients for ocular rosacea. But it’s also worldwide the most common oral medication used for inflammatory acne. It works by decreasing the bacterial load in skin follicles. But its side effects are something we should know if we’re prescribing it for inflammatory acne, or ocular oh rosacea or gland dystrophy. It causes what can be somewhat severe sun sensitivity. I mentioned how it’s snowing here in Boston. This is the perfect time to prescribe doxycycline for your patients. Where the risk of sunlight and sunburn and sun damage is less. If you are prescribing doxycycline and the patient is about to go on holiday to a beach vacation or it’s the summer months where you live, tell them about the risk of sun damage, sunburns and then therefore skin cancer. They will them to — while they’re on it — to stay out of the sun as best they can. or wear a high level of SPF sunscreen. Doxycycline also causes nausea. Tell your patients to take it with food. And it’s contra indicated in children, causes staining of the teeth. But the real acne medication that I wanted to talk about was Accutane or isotretinoin. This is the most commonly prescribed oral med for severe or cystic acne. It works by decreasing the content of sebaceous glands, the production of sebum. But it has a massive amount of side effects. It’s strictly contraindicated in pregnancy for the risk of birth defects. Raises your triglycerides, bone toxicity, robs with skin and eyes. Like a lot of the medications we talked about is dose-dependent. The most common dose is half a milligram per kilogram per day. And stop when you reach a cumulative dose of 120 milligrams per kilogram. If you are taking 1 milligram per kilogram, you have a 98% experience of side effects. Even when a low dose, you have a non-zero chance of side effects. It works with acne, but let’s talk about the ocular side effects. I have here a picture. Take a look at this picture. In your rod photoreceptors there are rhodopsins. And in the cone photoreceptors, there are cone opsins. And walk you through this. It can cause night blindness and color vision. In our eyes, we need rhodopsin for — and retinol is crucial to make rhodopsin and isotretinoin inhibits synthesis of retinal. It’s related to retinal, just Vitamin A, essentially, right? If your patients are on Accutane, ask them about this. And if they’re experiencing this, you might talk to the prescribing provider about decreasing the dose of this. Because it can be serious. And the ocular surface it problem has the most side effects. Because it works by decreasing sebum on the skin, right? But what are meibomian glands other than just large, sebaceous glands. 0.8 milligrams per kilogram, 66% of patients develop dry eye. Because their tear film evaporates more because they don’t have the layer of the glands. It’s not just a typical evaporative dry eye complaints, decrease in corneal sensitivity if it’s severe enough and a decrease in diameter and density of the sub-basilar neural plexus. And if it can be long-term. When you lose the sub-basilar neural plexus of the cornea, these can be long-term side effects, like in exposure with pepper spray. Consider this like pepper spray to the eye. What you can do? Stop the treatment if the symptoms are too severe. But every patient who is on isotretinoin should take artificial tears. And consider omega 3 fatty acids. And careen out patients with corneal disease. Anyone with any corneal disease should not be taking this medication. Especially things like corneal transplant. That’s the last slide. In conclusion, I’ve — I mentioned this several times during the talk, but we’re all very busy. Some of us see a ton of patients each day, and it’s very easy, I think, to give the patient an eye exam, focus on glasses, focus on vision, and then move on to the next patient and not take the time to click on their medication list or really look at their medication list. And so many medications have side effects. And so many of those medications have side effects in the eyes. But you’re not going to remember all of them. But I think the more you attend lectures like this, the more you read about ocular side effects, the more it’s going to stick in. Maybe you won’t remember everything about what I said today, but you’ll remember those meds. And nose meds that he mention have had some kind of side effect. Let me look them up. Don’t be afraid to look up medication side effects in front of the patient. I don’t think the patients expect us to know every medication prescribed in the world and the side effects. I think the patient would be happy that you’re taking the time check that they’re okay. Even if your patient is not experiencing symptoms, verbalize to them the symptoms to look out for if and when they start experiencing those side effects, they come in sooner rather than later and you can catch it sooner and when in doubt, especially a new clinician, for anything, side effects or anything, if you’re on the fence, is this a side effect? Is it not? Is this disease or something else? Bring the patient back sooner. Make a decision one way or another, but if you’re not confident on it, just bring the patient back. Never be afraid. Okay. I’m three minutes over. But that’s not so bad. I’m gonna stop sharing and we’ll go to the Q&A. Okay. First question. What are the most common ocular side effects associated with oral medications? How can oral medications affect the eyes? What’s the important eye care professionals to review a patient’s medication history and are ocular side effects from oral medications reversible? Good questions. I like to think that I answered all of those questions. And in fact, some of these questions, there’s just so many ocular side effects to oral medications, right? Like I said before, like I can’t talk about all of them in 45 minutes. But I like to think that I talked about a decent amount of them. Okay. Next question. From the same person. How can corticosteroids cause ocular complications? Early detection, ocular side effects. I’ll talk about the first one about corticosteroids. I didn’t mention corticosteroids, but obviously they have tons of side effects. The reason I didn’t mention that, that’s pretty well studied. I didn’t find anything new or interesting about it. To answer your question, the two big side effects that you can have with oral steroids are cataracts and glaucoma. Steroids cause — can cause people’s intraocular pressure to increase when they’re on them. And so you’re at risk factor for glaucoma is high. It doesn’t do it immediately. Some of these medications we talked about today have immediate side effects. Steroids take at least several weeks to raise your intraocular pressure. And the same thing for cataracts. You’re not going to immediately get cataracts if you take them for months. But on long dose steroids, your risk of cataracts increase. Next question. I think I answered that one. Interesting… this question at 9:09 was from Pablo Almiron. Sorry, I’m trying to read the questions but they keep changing. What are the long-term effects of using dexamethasone is and tobramycin. That has little side effects. A drying out, minimal drying out. Dexamethasone a steroid. Same as oral steroids. I shouldn’t say high risk of glaucoma. But a risk of increasing your intraocular pressure and glaucoma. Dexamethasone and tobramycin is one of the most commonly prescribed, and it’s a nice combination antibiotic and steroid to give to patient with red eyes. I would feel very comfortable. I prescribe it all the time and don’t worry about glaucoma. But for more than a month, I bring the patient back and keep working them up to make sure I’m not causing their intraocular pressure to increase. At 9:10, Tahir blurring of vision or change of in re, for example, after the use of antidepressants, kindly discuss. I blurring of vision, changing of vision with antidepressants has to do with changing the dilation of the iris sphincter. Just like when your pupils are dilated. And the refraction can change when you cause that anterior shift in the lens iris diaphragm can create myopia. This large shift in refractive air, and myopic change in drugs like topiramate, it can be common. All right. Going through the questions. How to screen — this question is from Dan at 9:23 in the morning. I shouldn’t say the time. We’re all in different time zones. How to screen for ethambutol toxicity in pre-verbal children? Excellent question. Color vision and performing a visual field. Perhaps you could get a visual field on a pre-verbal child, but probably not. Visual acuity you can get on pre-verbal child. But whenever you have a patient like this, whether it’s a child or an adult, someone you just can’t communicate with, your object of tests are the best bet in things like pupils would be very important here. I mentioned in ethambutol that you’ll see sluggish pupils. Don’t look for an APD in pupils but have sluggish pupils. A child should have quick reflex. If the mom thinks they’re asking strange and now suddenly their pupils are sluggish and they’re on ethambutol, but that’s good to look for. Scrolling back up. Looking for the questions. How to eliminate ethambutol toxicity? The only way to eliminate it is to stop the ethambutol and hope that it comes back. A question from anonymous: How old you differentiate ethambutol toxicity in diabetic patients receiving Anti-VEGF for macular edema? How to monitor what advice should be given? It’s an excellent question. But there are two different things. Diabetic patients can get macular edema like you talked about, and the injections, but that’s in the macula, and the ethambutol toxicity is in the optic nerve so just look in different spots for them. Scrolling down. This question is from — I recently had a lot of cataract patients with benign prostate hypertrophy. I suspect one of the meds is causing it, any thoughts? I do not any that any of the BPH medications have much of a risk of cataracts. I think, again, like we talked about in some of these cases, they’re really overlapping conditions. Who gets BPH? Usually older men. Who gets cataracts? Usually older people. And I would probably just leave it at that. Of course there’s lots of different ways to treat them, prostate problems. Maybe one of them is steroids. And steroids are associated with increased cataracts. But I think in general there’s not much connection between those medications this question is from — are there any — oh, I lost it again. Are there any ocular side effects hypertensive medications. Jeez, there’s so many hypertensive medications I’m having to scroll through them in my brain. My number one answer is, no with a caveat that if you decrease the blood pressure too much or too quickly, you can have problems. And you can have problems to the optic nerve and you can create, like I talked about, in the erectile dysfunction medication an NAION, ischemic neuropathy, antihypertensive medications are perfectly safe in the eye, unless the blood pressure drops too low. I’m gonna start with the bottom from read these questions. It’s easy for per to scroll up from the bottom. This question is from — does contact lens — do contact lenses also pose some side effects in the eyes? Sure, tons of side effects. Think about a contact lens, it’s simply a piece of plastic that you put over your cornea. The cornea doesn’t have any blood vessels in it, it gets oxygen from the atmosphere. Put plastic over it, and the cornea is dry because it’s starved of oxygen.
Let’s see. Any role of VEP in ethambutol toxicity in screening in pre-verbal children? You probably mentioned it as I was saying. It’s an excellent question. I don’t a lot of experience with VEP or multi-focal ERG. Those are tests that the patient has to sit there. As long as they can sit there and behave, you can do VEP or multifocal ERG in those cases. That’s a great point. I’m scrolling through. It’s frustrating, starting to read it and missed .
What roles to doxycycline play in long-standing — especially in patients who do not want to undergo surgery? This is a great question and I’ll answer it two different ways. I prescribed doxycycline to patients who have hordeolum and lid problems all the time. The role of doxycycline in these patients is to decrease the bacterial component on the ocular surface in the eyelids. It’s get into the glands and creating an infection and creating an acute hordeolum. If you can decrease the bacterial load, you can decrease what’s inflaming the gland and decrease the incidence and risk. You mentioned long-standing chalazion. That’s different. Once a hordeolum is no longer acutely inflamed, it becomes calcified and a chalazion. It’s about the scar tissue stuck in the meibomian gland and the eyelid. The only way to get it out is time and hope it gets out or surgery. But decrease in the bacterial load is not going to help anything. Good questions. More questions about corticosteroids. I think I answered those. This question from anonymous, when do we as ophthalmologists intervene and suggest dose changes of medication? Especially in macular risk? I think this is a fantastic question. It’s 10:00 so I’ll make this the last question. I think you should never hesitate to advocate for your patient. And there’s so many specialties in medicine, but one of the things that I like the most about eye care is that nobody really knows much about the eye. And if you flip that question a different way, everybody in medicine is relying on you to tell them what to do about the eye. And everybody in medicine, from podiatry to dentists to infectious disease to primary care physicians call care very much about the vision and they don’t want their patient to go blind. It’s one thing if the patient has acid reflux or if they have cavities or something like that, but if they’re losing their vision, if a medication that me, a dentist, is prescribing and is causing someone to lose their vision, I would take that extremely seriously. And so your question about when should we be changing the dose, I would recommend never hesitate to call, write — depending on how the urgency of the situation. But speak to the provider who is prescribing the medication to the patient. And tell them what you see. And tell them, especially if it’s macular disease like you write in the question, about the urgency and the risk of serious vision loss happening to this patient. And I would imagine that prescribing provider will be the first to say, like, okay, let me find some other medication to use because I don’t want to — I don’t want to risk this side effect happening. And so the thing that I would urge all of you is you — is to empower you to say that you know the best about the eye and you have the best interest — your patient’s best interest at heart. And just speak up. I think if anyone came to you with a question about the eye, you would be very happy to answer for the patient and very helpful. You want to be as helpful as possible to the doctor and to the patient. And you should do the same thing as an eye doctor. Never hesitate to advocate for your patient and to reach out. It takes a little bit longer to make a phone call or to send an email. But I think it’s very worth it and our patients need us to do that. All right. It’s past 10 so I should probably let everybody go. But I really appreciate being asked to speak to the group Phillip enjoy these and I hope you enjoyed it, too. So, thank you.