Lecture: Ocular Complications of Medications

This lecture reviews common and rare ocular manifestations and complications of ocular and systemic medications. Class of medications or specific medications, its uses, symptoms, and most importantly, its associated ocular manifestations and complications are discussed in detail after a brief introduction about the importance of this knowledge for clinicians.

Lecturer: Dr. Sowmya Srinivas, OD, MS, ABO, FAAO, Dartmouth-Hitchcock Medical Center, New Hampshire, USA

Transcript

[Sowmya] Hello, everyone, thank you for joining me today. My name is Dr. Sowmya Srinivas. I am in clinical practice at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, USA. And I’m very excited to bring to you all, Ocular Complications of Systemic Medications. I don’t have any disclosure for this talk. Today, this course will review some common and rare ocular manifestations and/or complications of ocular and systemic medications. We’ll talk about each class of medication or a specific medicine, its uses, some of the symptoms that the patient may experience, and most importantly, its ocular manifestations and what you should know when you’re examining the patient who’s on that specific medication. Briefly, we’ll also talk about why this knowledge is so important for clinicians.

Before we begin the talk, we’ll get to our first polling question. Which is, why is it important to study the ocular complications of medications? A, the eyes have a poor blood supply and a relatively small mass? B, the eyes have a rich blood supply and a relatively large mass? C, the eyes have a rich blood supply and a relatively small mass? Or D, the eyes have a poor blood supply and a relatively large mass?

All right, so the reason why it’s important to know the ocular manifestations or complications of medications is because the eyes have a very rich blood supply and a small mass. They exhibit unusually high susceptibility to some toxic medications. These drug molecules can be present in systemic circulation, can reach the ocular structures by a uveal or retinal vasculature. Choroid, sclera, and ciliary body have these thin, fenestrated walls for direct passages. So this way, small lipid molecules can pass freely into the aqueous and also diffuse into avascular structures such as the lens, the cornea, or the trabecular meshwork.

Direct molecules that enter through the uveal circulation exit from the canal of Schlemm, ciliary body, or they can diffuse into adjacent anatomical structures. From the retinal circulation, they can re-enter the systemic circulation, their drugs can diffuse into the vitreous, or their drug can get actively transported out.

These are some sites of accumulation in the eye. Cornea’s one of them, lens is the other one, retina, and the vitreous. We’ll go over each one and why it’s important to know why the drugs may accumulate in these structures.

The duration, or the longer the drug is in the eye, increases the risk of toxicity. In the cornea, what happens is the permeable endothelium and the stromal glycosaminoglycans can bind to these drug molecules. And they lead to edema and they reduce transparency of the cornea. In the lens, the drug molecules can bind with these lens proteins and photosynthesize the lens to UV. What happens when it’s photosynthesized is they’re bound by these drug molecules and the exposed lens proteins may denature, they opacify, and obviously, they accumulate and this could lead to cataract formation.

In the retina, what happens is loss of pigmentation with accumulation of pigment-laden cells in the outer retinal layers, damage and reduce the photoreceptors. This damage to the retina, especially in the ganglion cell layer, is what we see when the drugs accumulate in the retina.

In the vitreous, what happens is there’s a slow rate of fluid exchange. Therefore, the drugs have the possibility to accumulate in the vitreous humor. These are four key sites to remember, as far as these sites for where the drug molecules can accumulate in the eye.

Melanin is a pigment and it absorbs harmful UV rays and it protects against cellular damage from UV exposure. Melanin absorbs light and it’s a free radical. So this increases the chance of damage in the uveal tract and RPE. And these are drugs, chloroquine and chlorpromazine, have an eye affinity to melanin. So where melanin is high, these potential drugs can accumulate and cause retinal toxicity. Almost all the drugs have adverse side effects. So what happens is that incidence and severity of their drug reaction actually vary by patient characteristics and also drug factors. So with advancing age the incidence is higher of adverse side effects of a particular drug. And also incidence is higher of adverse side effects with polypharmacy. Meaning the more drugs you add to the patient’s body, the more the adverse side effects for this patient.

There are three types of etiologies that we need to know as to why adverse drug reactions may occur. The first one is dose-related, the second one could be an allergic adverse drug reaction. The third one is idiopathic, meaning recently we may not know why their drug is having an adverse reaction. So we’ll get into each of these three types of etiologies next.

The first one is our dose-related etiology or cause. Dose-related means drugs are predictable and common when they have a narrow therapeutic index. Therapeutic index is when you quantitatively measure the relative safety of the drug. So when the concern comes in if a patient has imparied renal or kidney function, hepatic liver function, or if there’s another drug they’re taking, and this may cause a drug-to-drug interaction.

What happens with drug metabolism is a body’s ability to metabolize a drug correlates with our toxicity. If a patient has imparied renal or hepatic functions, there’s a decreased rate of excretion. Their drug is not readily excreted from the body and that can accumulate and cause problems if the drug accumulates to toxic levels. These toxic metabolites are formed elsewhere, like in the liver, can reach the eye through the systemic circulation or reproduce locally in ocular tissues.

The second etiology or cause for adverse reactions may be allergic. May not be dose related. Allergic responses are mostly unpredictable but they can be predicted with clinical history and skin tests. And allergic responses require prior exposure, meaning if a patient has taken the drug before. And the drugs can act as an antigen or an alert. And after the patient is sensitized, subsequent drug exposures may result in different types of allergic reactions.
And finally, the last cause of adverse reactions may be idiopathic. In other words, we may not know why the patient is having such a reaction so it may not be dose-related or allergic, and so it can be an unexpected cause. This abnormal reaction to a drug may not always have a pharmacogenetic cause. And pharmacogenetic just means it’s a branch to pharmacology, concern with the effects of genetic factors on the reactions of certain drugs.

The next piece we’re getting into is classification. How do we classify what a patient experiences when they’re on this drug? We can do it by severity. Are they having the midl reaction, a moderate, or a severe adverse reaction? And then we consider possibly discontinuing the drug. And drug reactions may not be detected until the drug is released and used widely. And it’s really important to remember that just because a particular drug is on the market does not mean that we know all the reactions. So for example, even the COVID-19 vaccine. Just because it’s now in the market and widely used means that we may not know all the side effects that potentially may be needed with that particular vaccine.

The next part of the presentation, we’ll be going into classifications of certain drugs or a specific medication, and talking about what eye problems it can cause.

That brings us to the second polling question which is, which medication can potentially cause intraoperative floppy iris syndrome? Remember that IFS results in complications during cataract surgery and it can also increase cataract surgery time and also be associated with choroidal rupture. Is it A, Tamsulosin or Flomax? Is it Hydroxychloroquine or Plaquenil? Or is it Lisinopril? Or Simvastatin? All right, excellent. That is the correct answer, it is Flomax. And we’ll talk more about that next.

Flomax falls into the Alpha 1 blocker; it is used for treatment of benign prostatic hypertrophy in men and it’s used to treat bladder problems in women. What happens in benign BPH or benign prostatic hyperplasia, is that the prostate gland enlarges. So it’s really difficult for urination because the bladder tightens up. So this particular medication is used to relax the bladder.

This is a very busy slide, but what Alpha 1 blockers do is they’re relaxing the smooth muscles that make the bladder and the prostate, making it easier to urinate. But a side effect it has is on the iris smooth muscle. So what happens is because of this relaxing nature of the medication, the pupillary dilator is weakened with the Alpha 1A blockers. And so what happens is not only is their dilator weakened, but the constriction response is pretty strong, and this leads to the fact that during cataract surgery there’s not a good dilation, which is required for successful cataract surgery. And what happens then, is that the iris billows during irrigation and it can cause intraoperative miosis. Which means there’s a lot of constriction so the pupil’s not going to dilate well. And then the iris can prolapse through the phaco or even a side incision. And it can lead to complications during cataract surgery and it can cause damage to the iris and it can also cause loss of vitreous fluid. So this is an unwanted side effect that happens to the iris smooth muscle. So this is a complication that we often see during cataract surgery.

There are ways to correct that. I don’t want to get too much into these options, but you could use iris hooks and retractor rings, or ophthalmic viscosurgical devices. Or soft shell techniques can be used to keep the dilation in place so that the cataract surgery can be performed successfully.

The next medication class we’re going to get into is amiodarone. And remember that this is used to treat serious cardiac arrhythmias. What the patients notice with this medication are green halos in vision and also reduced vision. A type of vortex keratopathy, which is these corneal deposits, that we see in a whorl-like pattern can be seen on the cornea. And with the particular medication, amiodarone, we can also see anterior capsular lens opacities, we can see multiple chalazia, and also dry eye, which we’ll talk about. Dry eye is a common symptom for many medications including amiodarone.

This is whorl keratopathy, it goes by a couple different names: vortex keratopathy, it can also be called cornea verticillata because of the way it appears on the cornea in these significant deposits in a whorl-like pattern. And remember that these will not cause any vision problems. In other words, they’re not visually significant.

That brings us to the next poll question. Which of the following medications can cause whorl or vortex keratopathy or cornea verticillata? Is it A, Chloroquine? B, Hydroxychloroquine? C, Amiodarone? D, Indomethacin? E, Tamoxifen? Is it all of the above or G, none of the above? All of the above is the correct answer and we’ll go over a mnemonic so you can remember these drugs.

All right, CHAI-T is the mnemonic. Or C-H-A-T-I, or CHAI-T. These are the following drugs that cause vortex keratopathy, so they can include everything. Chloroquine, Hydroxychloroquine, Amiodarone, which we discussed before, Indomethacin, and also Tamoxifen. These are all the drugs. Again, CHAI-T, if you remember that mnemonic, it can help you recognize what drugs can result in vortex keratopathy. And the other condition that results in vortex keratopathy is if a patient has Fabry’s disease. This is a lysosomal storage disorder. If you see a patient who’s diagnosed with Fabry’s disease, be on the lookout for vortex keratopathy. Again, remember CHAI-T as a clinical pearl for drugs that cause vortex keratopathy.

The other visually significant problem that amiodarone can cause is optic neuropathy. Remember that vortex keratopathy is not visually significant, but optic neuropathy, on the other hand, can cause problems and reduced vision. This is similar to what you would see to non-arteritic anterior ischemic neuropathy. And so this is pretty rare, happens in 1-2% of the cases, whereas whorl keratopathy happens in many more patients. And optic neuropathy, on the other hand, can be happening within a week or two after a patient starts amiodarone. Definitely be on the lookout for optic neuropathy which can cause visual problems if a patient starts this drug.

And so these are other medications that cause optic neuropathy. OCP’s are oral contraceptive pills, these are birth control pills. Digitalis is another one, so this is a heart medication used to treat congestive heart failure. Methotrexate, which is used in chemotherapy and as an immunosuppressive drug, and it can treat cancer of the blood or the bone, lung, breast, head and neck. And it could also be used to treat rheumatoid arthritis. And then a few other ones include isoniazid, it’s a tuberculosis medicine. Ethambutol, so remember that one, I saw a few questions about what ocular complication ethambutol can cause, and so it is optic neuropathy. Remember ethambutol. Streptomycin, which is an antibiotic, also used to treat tuberculosis. Chloramphenicol which is another antibiotic and sulfonamides which is antimicrobial. These are drugs to remember that cause optic neuropathy.

And again, just another slide of drugs that can cause optic neuropathy. Here it goes over each one again and heavy metal, again lead, mercury, thallium, carbon monoxide, tobacco. Certain alcohol, so methanol, ethylene glycol are some other ones that can cause optic neuropathy. And the reference for this is down below.

The next class of medications we’re going to talk about is anticholinergics. This includes antihistamines, antipsychotics, antispasmodics. Antispasmodics is a pharmaceutical drug that can suppress muscle spasms. And then you have antidepressants and also mydriatics. The symptoms to remember with ocular complications for anticholinergics, the big one is dry eye, dry mouth, and also decreased accommodation.

What this can do, also, is increase risk or worsen angle closure glaucoma in susceptible patients who have narrow angles. So again, medications that can cause secondary angle closure, things to remember for that are tricyclic antidepressants can cause angle closure. Monoamine oxidase inhibitors used to treat depression, antihistamines, and also sulfa-based drugs like Topiramate can cause angle closure, especially patients who have narrow angles.

What angle closure, as you know, might cause is a mid-dilated pupil, it causes severe red eye, pain, corneal haze, so these are all the symptoms that the patient may present with when they are having angle closure.

The next one is antihistamines. This is prescribed for allergic rhinitis or seasonal or even skin allergies. And remember that patients with narrow angle glaucoma may have an increased risk with angle closure, so this is one that can cause angle closure. Other things to remember for antihistamines can cause mydriasis, dry eye, again, keratitis sicca. And because of dry eye it can cause contact lens intolerance, reduced accommodation, and even increased IOP. Some other things to remember for antihistamines are facial dyskinesia or blepharospasms in large doses. And cetirizine, which is Zyrtec, can cause abnormal EOM contradictions and these are called oculogyric crisis, where the eye shoots up and it can cause this particular oculogyric crisis. So remember that for Zyrtec, which is an antihistamine.

Why do antihistamines cause dry eye? Because they block histamine receptors. Antihistamines. And what blocking histamine receptors do is it inhibits the glandular secretion, it reduces mucus, and also tear secretion, which is when dry eye exacerbates.

Look at this picture and that brings us to the next polling question. Which is, what is your diagnosis for this patient and why do you think this may have happened? Is it A, hyphema in the conjunctiva because the patient is on a blood thinner or valsalva? Or is it hematoma in the conjunctiva, is it because it happened because of blood thinner or valsalva? Is it C, hemorrhage in the sub-conjunctiva because of blood thinners or valsalva? Or D, hyphema in the sub-conjunctiva because of blood thinners or valsalva? Excellent, you guys got this correctly. It is a hemorrhage in the sub-conjunctiva. Subconjunctival hemorrhage.

Remember that blood thinners are used to prevent clots and they can be used to reduce strokes and heart disease. And they are usually discontinued before cataract surgery and/or eyelid surgery. And it may prolong bleeding time. Again, it may cause or even make subconjunctival hemorrhages worse. Anticoagulants can also cause retinal hemorrhages. And some studies have even found that early AMD and wet AMD with frequent aspirin use and it also increases the risk with increased aspirin consumption.

The next class we’re going to discuss is antimalarials. These are aminoquinolines, including chloroquine and hydroxychloroquine. These are used for treatment of rheumatologic conditions. And as you may know, the retinal toxicity is related to large cumulative lifetime dose over many years. This is one of the ones that may not cause problems initially for the patient, but it happens many years usually after the patient has been on these types of medications. The way this medication is dosed is initially it starts with 400 milligrams to 600 milligrams, a single dose or twice a day. And the action of hydroxychloroquine is cumulative, so it may require weeks to months, even, for maximum therapeutic effect for that patient.

This is a great resource for you, this is EyeDock, which gives you a Plaquenil risk calculator. Remember on the last slide we discussed how Plaquenil causes problems when it’s taken long term and cumulative doses. If you want a good resource to calculate what is the safe baby dose for your patient, or even calculate the cumulative dose, this is a wonderful resource. But there’s also many other calculators that you can use to use the risk factors for Plaquenil. I’ll give you an example in the upcoming slides.

Here’s the same website where you can calculate the cumulative dose that a particular patient is on.
Per the American Academy of Ophthalmology, the risk of toxicity is dependent on daily dose and duration of this medication. At recommended doses the risk of toxicity, up to five years, is under 1% and if the patient is on it for 10 years, it’s under 2%. But it raises to almost 20% if a patient is on Plaquenil after 20 years. And however, even after 20 years, a patient without toxicity only has about a 4% risk of converting in that subsequent year.

This is the patient I saw recently who was on Plaquenil for rheumatoid arthritis. She is a 68-year-old Caucasion female. She had been on Plaquenil since 2004 and she had been taking 400 milligrams per day. And her body weight was 178 pounds, which is equal to 80.7 kilograms. I used the calculator, which I gave you link for on the previous slide, and so I calculated her cumulative dosage. Because remember, Plaquenil toxicity is dependent on cumulative dosage. I plugged that in, 200 milligrams taken twice a day for 17 years total. I put 12 in and five more, it will only go up to twelve. And then you add using these plus and minus signs. So that comes out to the cumulative dosage of 2,482 grams for this patient. Remember the risk of toxicity is low if the total dose is less than 1,000 grams, but increases thereafter. Since this patient had cumulative dose of 2,482 grams, we recommended that this patient discontinue Plaquenil because the exam and early signs did show retinal toxicity. I have pictures of that next.

This is her right eye, this is her left eye. And I know it may be hard to see, but on her exam I saw a little bit of RP changes and cycling on the right macula. In other words, bull’s eye macula is what Plaquenil causes. And when you look at the OCT, it stands out. You can see the outer retinal layer disruption, particularly in the right eye. We talked about in a previous Cybersight lecture I gave about how the ellipsoid zone or the photoreceptor integrity line has to be intact, and with Plaquenil this particular layer is disrupted or damaged. And compare that to the left eye where the ellipsoid zone or the PIL/IS/OS junction, these are different names, is intact. But in her right eye, it’s subtle, but there’s disruption on the outer retinal layers of the patient’s right eye.

These are 10-2s for this same patient. We see pericentral defects, early pericentral defects in this patient’s right eye. The left eye, low test reliability so some central defects. But in the right eye I was more concerned about the pericentral defects which are classic when a patient has bull’s eye maculopathy or Plaquenil toxicity. And so based on all of this information, I called this patient’s rheumatologist and reviewed the imagining and her results of her 10-2 visual field test. And we decided that the patient should stop Plaquenil based on some early toxicity. And the patient did and so she’s on a different medication for rheumatoid arthritis now.

Obviously, this is advanced bull’s eye maculopathy. We didn’t let that particular patient of mine get to this stage. Because then that would have been much more visually significant and damaging. It’s really important to catch Plaquenil toxicity, bull’s eye maculopathy early on and again. The OCT can help us really do that and pick up any subtle changes early on so that this patient does not have to undergo the visual changes that comes with advanced stage of this disease. Again, this is a different patient with advanced, your classic textbook bull’s eye maculopathy.

And a different patient, you can see that the outer retinal layers are completely disrupted for this patient. Definitely visually significant because the IS/OS junction or the ellipsoid zone, the PIL, the photoreceptor integrity line is totally disrupted. And then I just wanted to show that to you, compare that to the patient I saw. It is slightly disrupted but certainly not as bad as this textbook case.

And so these are classic paracentral defects that we would see when Plaquenil causes toxicity in the eyes. Again, for my patient, we saw some early defects but before it got to this stage, we picked up on it and had her stop the Plaquenil. So it’s really, really important to use our technology and your knowledge of what potential problems certain medications can cause so you can intervene early on.

The next class of medications that we’re getting to are antiseizure. These are used for treatment of seizures, they’re also used for mood stabilizing indications as well. And a big one here is Topamax. And it’s prescribed off label for migraine headaches. And so the symptoms here that the patient presents with includes eye pain, headaches, nausea, vomiting, and again these are all because of angle closure. Remember acute myopia, acute angle closure glaucoma can happen and this can happen because of anterior chamber shallowing, suprachoroidal effusion, scleritis, periorbital edema, and also oculogyric crisis.

Here’s a UVM showing shallowing of the anterior chamber and also this anterior rotation of ciliary body with a closed angle, and also suprachoroidal effusion in a patient with Topamax-induced acute angle closure glaucoma. What this patient did was they stopped the medication and so then the angles opened up on ultrasound via microscopy and you can see a much deeper anterior chamber, and open angles, and there’s a resolution of suprachoroidal effusion. Again, a big thing to remember with Topamax is angle closure glaucoma.

This brings us to the poll question number five, which is, which of the following medications can typically lead to this type of cataract? Is it anti-hypertensives, is it anti-seizure medication, is it corticosteroids or Alpha 1 blockers? Which can lead to this type of cataract? Excellent. That is the correct answer, corticosteroids. And we will discuss more about corticosteroids next.

As you know, corticosteroids are used for a wide variety of conditions. And through many different routes. You can prescribe corticosteroids orally, nasally, topically, IV, IM, and also to the joints. The eyes can be affected through any route of administration although the risk increases greatest orally. For example, if it’s a nasal corticosteroid it may not cause much eye problems as opposed to if it’s an oral route of a corticosteroid. Corticosteroids, you are correct, can cause PSC or posterior subcapsular cataract, IOP increases, glaucoma and also central serous chorioretinopathy. And the risk of corticosteroids increases with chronic use. So in other words, the longer the patient is on corticosteroids, the more complications we can see in these types of patients.
This is an example of PSC cataract. And here’s a patient I saw in a case example. He’s a 49-year-old Caucasian male. And he had renal transplants, kidney transplants in 2004 and 2011 and he was on long-term oral prednisone. And he was also on dual immunosuppression with Prograf and Cellcept after these transplants. He also had a few other conditions, chronic kidney disease, high blood pressure, and these are some of the medications he was on.

And so again, a busy slide, but the main thing to note for this particular patient was in the macula. When I saw this patient, I saw RP hyperplasia, pigment mottling in both of his eyes. And it was a little bit worse in his left eye which is why his vision in that left eye was 20/40. So the RP mottling or the hyperplasia was worse in his left eye compared to his right eye. And so these are images, I know they’re difficult to see, but I do have a larger picture here. So you can see the RP hyperplasia, worse in his left eye, compared to his right eye.

And again, I gave you a hint that he was on corticosteroids for a number of years after, during the kidney transplant. And so what might have happened for this patient? Even though I saw this patient when he had these RP mottling, what he likely had was central serous chorioretinopathy. He mentioned some vision changes around the time that he was on prednisone. What likely happened was it led to central serous chorioretinopathy. Which then, what happens in acute central serous, is there’s a fluid but then what happens in chronic CSCR is that the RP turns into this hyperplasia or mottling.

Here are represented OCT images for the patient’s right eye and also his left eye. And you can appreciate how the RP layer is more disrupted in his left eye compared to his right eye. And remember that there’s this fluid initially, subretinal fluid, in acute central serous chorioretinopathy and then as the CSCR results, it results in this out of retinal layer disruption which is exactly what happened to this patient. Even though I had not seen this patient when he had the acute CSCR, it’s important to look at his history. He was on corticosteroids for many years and that tells me that he may have had CSCR from the corticosteroids many years ago. And when I saw him, he had the outer retinal layer disruption which is chronic central serous chorioretinopathy.

The next class of medication we’re going to discuss is cannabinoids. These are derivatives of the marajuana plant. And so this reduces eye pressure, IOP. And the maximum effect is usually 60-90 minutes after inhalation. And systemic side effects are also present for this and it includes postural hypotension, anxiety, euphoria, drowsiness. This is why this type of treatment is unacceptable for glaucoma. You may have had some patients asking for treatment of cannabinoids because of high eye pressure. But again because of the adverse side effects, systemic side effects, it is not acceptable for treatment of glaucoma.

The next one here is digoxin. This is our treatment for congestive heart failure and also cardiac arrhythmias. Patients with this medication complain of flickering or flashing of light, they can see colored spots, blue/yellow vision defects, this is an important one you may have read this for your board exams. Entoptic phenomenon or snowy, hazy vision, flickering lights, and also dimming of vision. And this causes retrobulbar optic neuritis. It can also cause IOP reduction because of decrease of aqueous humor. And these visual changes are reversible if the drug is discontinued.

Drugs which treat erectile dysfunction can cause ischemic optic neuropathy, so NAION. And you have to be cautious in patients who have retinitis pigmentosa, AMD, and diabetic retinopathy when you prescribe drugs that treat erectile dysfunction.

Fluoroquinolone is an antibiotic and it can cause acute retinal detachment, especially with Ciprofloxacin. Results in this four fold increase in oral fluoroquinolones and this is based on a 2012 study. And the potential question here was whether oral fluoroquinolones disrupt the collagen synthesis and can cause tendon weakness. What happens when it affects the eyes, is the weakening of the collagen tissues could potentially increase the risk of retinal detachments and this was seen about five days after starting the med. Again, these relationships we’re not sure about, but this is what one study from 2012 showed with regards to fluoroquinolones increasing the risk of retinal detachments.

Accutane/Isotretinoin is a treatment that is used for cystic acne and keratinizing dermatoses and patient’s complaints include decreased dark adaptation/nyctalopia or night blindness, reduced tolerance to contact lenses, again, because of dry eye. Reduced vision, again, ocular discomfort, blepharoconjunctivitis, lid edema, photophobia, and also reduced color vision. What Accutane causes are MGD/Meibomian gland dysfunction, blepharoconjunctivitis, corneal opacities, keratitis, dry eye, myopia, and a big one is pseudotumor cerebri.

Another medication for treatment of acne is minocycline, and this is tetracycline derivative. It’s an antibiotic. And it causes papilledema from increased intracranial pressure. Patient symptoms include headaches, neck pain, transient or even persistent loss of vision. And this usually happens weeks to months after starting the medication. And the visual field is abnormal and that is because of axonal damage from elevated intracranial pressure. The brain imaging is normal but remember that there is a high opening pressure on lumbar puncture, which indicates elevated intracranial hyper ICP. And again, there’s baseline screening required for this medication and also routine screening eye exam every three to six months because papilledema can exist, but it may not cause visual symptoms initially.

The next class is phenothiazines, so these are psychotropic agents. These are thioridazine and chlorpromazine and these are used for treatment of anxiety, depression, and also behavioral conditions. Patient symptoms for this include brown vision, decreased vision, and also nyctalopia or night blindness. And what this medication can do for the eyes is cause pigmentation of the eyelids, conjunctiva, and even cornea in large doses. And in the retina, it can cause pigmentary retinal degeneration with long term use. This is salt/pepper retinopathy and it can result in widespread loss of RP and also choriocapillaris. And with this class of medications cataracts are also something you can see as an ocular complication.

The next class is neoplastics. These include Interferon As, used for hepatitis C and also other malignancies. The ocular complications to remember for these types of medications is retinal ischemia and/or non-perfusion. It can cause optic neuritis and also dry eye.

Radiation treatment is a treatment for malignancy. And it targets cellular DNA. Important notes to remember for radiation is trichiasis, epiphora or watery, ectropion, or nasolacrimal duct obstruction. Radiation can also cause iritis, or iris and angle neovascularization. It can cause cataracts. Remember radiation retinopathy in a patient who has had radiation treatment really look for retinopathy, macular edema and also optic neuropathy.

This brings us to poll question six. What medication can typically contribute to this type of retinopathy? Is it Tamsulosin or Flomax? Tamoxifen? Tetracycline or Tylenol? Excellent, so that is the correct answer, it is Tamoxifen. This is a picture of crystalline retinopathy which can happen from Tamoxifen.
Again, remember that Tamoxifen is used for treatment for metastatic breast cancer in postmenopausal women. And the big ocular compilation for this is crystalline retinopathy. And here’s just a larger image of crystalline retinopathy.

Final poll question. What other eye complication can be caused by Tamoxifen? Is it CSR, whorl keratopathy, posterior subcapsular cataract, or glaucoma? Again, just to see if you all were paying attention so this should be an easy one. What other complications can be caused by Tamoxifen? That is correct, B is the correct answer, vortex/whorl keratopathy. Remember amiodarone, CHAI-T. C-H-A-I slash T are Tamoxifen. So that is correct.

Tetracyclines are treatment for acne and rosacea. These medications can cause idiopathic intracranial hypotension, especially with long term use. You can also see scleral pigmentation in this three to five millimeter band starting at the limbus. Tetracycline, remember, causes discoloration of growing bones or teeth. Pigmentation of various body sites including skin, nails, bone, mouth. And these skin pigmentations are reversible. If the medication is stopped, these changes can be reversed. But the eye pigmentation, which is less common, is irreversible.

TCAs, or tricyclic antidepressants, are treatment for depression. Dry eye, again, acute angle closure glaucoma and especially patients with narrow angles.
Again, important to remember all these medications that can cause acute angle closure glaucoma are TCAs, SSRIs, SNRIs, which are serotonin norepinephrine reuptake inhibitors, topical antipsychotics, and theoretically any psychiatric medication having anticholinergic effects can cause acute angle closure.
This one’s important, Gilenya or Fingolimod is used for treatment for multiple sclerosis. And this particular medication causes fingolimod-associated macular edema, so FAME. As you can see, you can see intraretinal edema in a patient who is on this medication for multiple sclerosis. Retinal hemorrhages and retinal vein occlusions can also occur. This is the paper if you’re interested in reading about it. And in most cases, this particular type of FAME or macular edema, occurs within four months of starting the treatment. So it is important to have a baseline eye exam as well as the follow up eye exam, usually three to four months after a patient starts this medication. Again, remember this for Gilenya, which is macular edema caused by this multiple sclerosis medication.
Elmiron, this is a newer ocular complication we’re learning about. This is used for treatment for interstitial cystitis that millions of Americans take. And it causes this type of pigmentary retinopathy and it was actually first recorded to cause maculopathy, just in 2018. But I think this was likely underreported because this association was not known until recently. Remember that Elmiron, again, many people take this for interstitial cystitis and it can cause pigmentary retinopathy.

This is that pigmentary retinopathy that we see. And the OCT shows these focal nodules and it happens at the level of the RPE, and it localizes with these hyper pigmented spots.

Bisphosphonates, used to treat bone density in patients with osteoporosis or Paget’s myeloma, and bone cancer. And Fosamax is prescribed for postmenapausal women to prevent calcium bone loss. Rare eye side effects can include uveitis, scleritis, or ocular and orbital inflammation. These side effects are not common and you can’t predict which patient will experience them. And these side effects are reversible. Again, if their medication is discontinued, these side effects can be reversed. Here’s a patient with episcleritis and she was on the osteoporosis medication which are bisphosphonates.

Cidofovir, is treatment for CMV retinitis in AIDS and it’s also an antiherpetic agent. It primarily causes anterior uveitis. Secondary effects include macular folds, or retinal or even choroidal detachment. Can result in permanent loss of vision.

Peripheral vascular dilators for hyperlipidemia. These medications can cause pseudo-cystoid macular edema. Usually happens in men who are between age 30 to 50. And the vision loss is reversible in one to two days after this medication is stopped.

Thyroid agents, these are treatments such as thyroxine which is not produced by the thyroid gland. It can cause pseudotumor cerebri in children with pre and peri-puberty hypothyroid. It can also cause myasthenia-like symptoms with excess hormones including diplopia, ptosis, and also paralysis of the extraocular muscles.

These are a long laundry list of medications that can cause dry eye. A lot of medications can exacerbate dry eye. Here’s a good resource. This is the link to the website for the article. And again, just some of the medications here that can aggravate dry eye.

I also had a few questions about drugs that are safe or that can be used in pregnancy. Here’s a good resource for you. The link is above. And the FDA uses these categories: A, B, C, D, and X. For example, A is controlled studies in pregnant women have not shown an increase in the risk of fetal abnormalities. Whereas X is it has demonstrated positive evidence of fetal abnormalities. Category X means that these medications should not be used in women who are pregnant or who may be pregnant.

Again, the link is here, but these are medications, as you can see, most medications are category B, C, D. And again, you can use that resource to look at this list. And again, these are drugs which you should be careful in using for pregnant women.

These are preferred drugs that you can use during pregnancy. Antibiotics include Erythromycin, Polymyxin B. Antivirals, Acyclovir and valacyclovir. Antifungal, so you can use Amphotericin, ketoconazole in pregnant women. Anti-inflammatory, you can use prednisolone. Ocular anti-hypertensives, you can use brimonidine. But it should be discontinued prior to delivery because of potential effects in neonates after birth. Again, you can use that link to access all these tables for which drugs to use during pregnancy.

I had a few questions about COVID vaccines and vision. Unfortunately, since it’s fairly new, there’s no evidence to indicate that these vaccines may have widespread effects on the eyes. Again, it’s simply not known. But I’m sure as these vaccines are given, there may be some potential ocular side effects.
With that, I want to get to the main clinical pearl for the day is always review patient’s medications and keep up to date. I know it’s a lot to remember but they’re wonderful references you can use to keep up to date on ocular complications and side effects that medications can cause. And with that, I thank you all for joining me today. Thank you for your time and I’m looking forward to answering any other questions that you may have.

Optic neuropathy with amiodarone is rare, remember that vortex keratopathy is common. Are topical antihistamines less common? Most of the antihistamines, the systemic antihistamines can cause angle closure. If Zyrtec is discontinued the changes are not permanent.

Can excessive COVID medication cause ocular mucormycosis? Again, we don’t know about COVID vaccines and any potential side effects. It is not known.
With OCPs, you can see optic neuropathy, so that results in swelling of the optic nerve in addition to many other medications that can cause optic neuropathy including, remember, Ethambutol.

The cumulative dose can be calculated using various calculators. There’s wonderful resources online. EyeDoc.com is one of them that you can use cumulative dose to calculate the risk factor for your patient.

I saw middle-aged women with the branch retinal vein occlusion one week after COVID vaccination. Could the vaccination be the cause? Again, it’s not known what ocular complications that the COVID vaccine may have. It may be coincidental. It’s just not known yet whether branch retinal vein occlusions can happen from COVID vaccines.

Are there any ocular side effects of amphotericin B given in mucormycosis? Dry eye is a common one with many medications. Remember that this could be a potential cause. A lot of the chemotherapy treatments, radiation, can cause retinopathy even dry eye. These are common ones to remember and I can give you the link and resources for these types of medications.

What other ocular medications can cause color vision defects? Remember that anything that can cause optic neuropathy because Ethambutol, for example, can cause color vision defects. For instance, any medications that affect the optic nerve can potentially cause color vision defects.
Again, COVID-19 vaccine, unknown as to what side effects it may have on the eyes.

Which course and where may one study this type of knowledge on ocular medications? I put together this talk based on a lot of research and papers and so there’s not one particular resource, but I’m happy to share a list of my resources if you wish to review the ocular complications of medications.
And with that, I’m happy to answer any other questions. Feel free to send it to Cybersight, have a wonderful rest of your day. Thank you.

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June 18, 2021

Last Updated: September 12, 2022

5 thoughts on “Lecture: Ocular Complications of Medications”

  1. This was very informative, and a good balance of clarifying acronyms and concepts, with assuming a baseline of ophthalmic knowledge.

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