Side Effects of Medications

Question 1

Amiodarone. What is it?

Answer 1

<ul> <li>Medication used to control heart rhythm disturbances</li> <li>Ophthalmic side effect: whorl opacities in cornea (cornea verticillata)</li> <li>Usually does not disturb vision </li> <li><a>Ischemic optic neuropathy</a> linked to amiodarone use, but evidence of causation weak</li> </ul>

Question 2

Amiodarone. How does it appear?

Answer 2

<ul> <li>Patients usually have no visual symptoms</li> <li>May rarely report mildly blurred vision or haloes </li> <li><a>Curved golden brown or gray-white lines</a> originate below center of cornea in both eyes </li> <li>Visible to naked eye but better seen with slit lamp </li> <li>Corneal whorls are subepithelial phospholipid deposits </li> </ul>

Question 3

Amiodarone. What else looks like it?

Answer 3

<ul> <li>Fabry disease: glycolipidosis caused by deficiency of the alpha-galactosidase A, but... </li> <li>Patients with Fabry disease have characteristic visceral and vascular manifestations </li> </ul>

Question 4

Amiodarone. How do you manage it?

Answer 4

<ul> <li>Be aware that these deposits are signature of amiodarone use but have no other medical importance</li> <li>Be aware that medical literature links ischemic optic neuropathy to amiodarone use, so if patient has only one sighted eye, consult ophthalmologist about prescribing amiodarone</li> <li>If patient develops sudden vision loss, refer to ophthalmologist to rule out ischemic optic neuropathy</li> </ul>

Question 5

Amiodarone. What will happen?

Answer 5

<ul> <li>Corneal whorls appear within months of starting medication and disappear within months of stopping it</li> <li>Litigation has occurred against physician prescribers of amiodarone, alleging that this medication causes ischemic optic neuropathy, but evidence not convincing</li> </ul>

Question 6

Anticholinergics. What is it?

Answer 6

<ul> <li>Systemically-administered medications used to treat gastric distress, spastic bladder, and side effects of anti-psychotic medications</li> <li>Most common ophthalmic side effect: loss of accommodation ("iatrogenic <a>presbyopia</a>")</li> <li>Loss of accommodation results from paralysis of ciliary muscle</li> <li>Topical installation (but not systemic use) may rarely provoke <a>angle-closure glaucoma</a></li> </ul>

Question 7

Anticholinergics. How does it appear?

Answer 7

<ul> <li>Blurred vision at reading distance in patients aged under 55 years</li> <li>Slightly dilated pupils that constrict weakly to bright light</li> <li>Elevated intraocular pressure if <a>angle-closure glaucoma</a> has occurred </li> </ul>

Question 8

Anticholinergics. What else looks like it?

Answer 8

<ul> <li>Anticholinergics accidentally or deliberately instilled in eyes, but they cause more widely dilated pupils that will not constrict to bright light </li> <li>Common offenders: scopolamine patch for seasickness, aerosolized medications for respiratory secretions, plant substances, or cycloplegic eye drops (atropine, homatropine, scopolamine, cyclopentolate, tropicamide)</li> <li>Systemic dysautonomias can mimic effects of anticholinergic medications</li></ul>

Question 9

Anticholinergics. How do you manage it?

Answer 9

<ul> <li>Anticipate loss of accommodation and warn patients that reading glasses may be necessary</li> <li>Recognize that dilated pupils may result from accidental contact and cause unnecessary alarm, especially in patients on respiratory therapy </li> <li>Recognize that unacknowledged instillation of anticholinergic medications may be part of factitious illness</li> </ul>

Question 10

Anticholinergics. What will happen?

Answer 10

<ul> <li>Blurred vision at reading distance can be fully corrected with glasses</li> </ul>

Question 11

Bisphosphonates. What is it?

Answer 11

<ul> <li>Medications that inhibit bone resorption and are used to prevent osteoporosis</li> <li>Most commonly used medications: pamidronate, alendronate, risedronate</li> <li>Most common ophthalmic side effects: <a>acute conjunctivitis</a>, <a>anterior uveitis</a>, orbital myositis, <a>episcleritis</a>, <a>scleritis</a> within days to weeks of starting medication </li> </ul>

Question 12

Bisphosphonates. How does it appear?

Answer 12

<ul> <li>Eye pain</li> <li>Blurred and double vision</li> <li>Red eye</li> <li>Lid swelling</li> <li>Proptosis</li> </ul>

Question 13

Bisphosphonates. What else looks like it?

Answer 13

<ul> <li><a>Orbital cellulitis</a></li> <li><a>Idiopathic orbital inflammation</a></li> <li><a>Graves disease</a></li> <li><a>Conjunctivitis</a></li> <li><a>Episcleritis</a></li> <li><a>Scleritis</a></li> </ul>

Question 14

Bisphosphonates. How do you manage it?

Answer 14

<ul> <li>Anticipate these ophthalmic manifestations </li> <li>Refer to ophthalmologist urgently</li> </ul>

Question 15

Bisphosphonates. What will happen?

Answer 15

<ul> <li>Discontinuing medication brings about recovery, but...</li> <li>Treatment with topical or oral corticosteroid or nonsteroidal anti-inflammatory drug (NSAID) often needed to hasten relief </li> </ul>

Question 16

Chloroquine and Hydroxychloroquine. What is it?

Answer 16

<ul> <li>Chloroquine prevents malaria</li> <li>Hydroxychloroquine treats rheumatic illnesses</li> <li>Most common ophthalmic side effect: damage to retinal pigment epithelium, causing irreversible vision loss</li> <li>Retinal toxicity uncommon with chloroquine and even less common with hydroxychloroquine as long as proper dose limits observed</li> <li>Ophthalmologic monitoring protects against severe toxicity</li> </ul>

Question 17

Chloroquine and Hydroxychloroquine. How does it appear?

Answer 17

<ul> <li>Blurred vision in both eyes</li> <li>Pericentral scotomas on special visual fields </li> <li>Fading of orange color of retina around fovea ("<a>bull’s eye maculopathy</a>"), appearing well after visual symptoms begin</li> <li>Optical coherence tomography and multifocal electroretinography may reveal abnormalities before they are visible with ophthalmoscope and perhaps even before patient develops symptoms</li> </ul>

Question 18

Chloroquine and Hydroxychloroquine. What else looks like it?

Answer 18

<ul> <li>Genetically-determined storage diseases</li> <li>Healed choroiditis</li> </ul>

Question 19

Chloroquine and Hydroxychloroquine. How do you manage it?

Answer 19

<ul><li>Have patients treated with chloroquine undergo baseline ophthalmic examination and be monitored by ophthalmologist every 3-6 months after starting it </li> <li>Have patients treated with hydroxychloroquine undergo baseline ophthalmic examination and be monitored yearly starting at 5 years of medication use </li><li>Keep chloroquine daily dose at <u><</u>3 mg/kg/day and cumulative dose at <u><</u>460 gm to reduce chances of retinopathy </li> <li>Keep hydroxychloroquine daily dose at <u><</u>5.0mg/kg/day and cumulative dose at <u><</u>1000gm to reduce chances of retinopathy </li> <li>Recognize that patients with renal failure are at unusually high risk of retinal toxicity </li> <li>Stop medication at first suggestion of retinal toxicity </li> </ul>

Question 20

Chloroquine and Hydroxychloroquine. What will happen?

Answer 20

<ul> <li>Chloroquine and hydroxychloroquine retinopathy rare if recommended dose limits followed </li> <li>Once visual symptoms develop, they cannot be reversed, and may worsen even if medication stopped</li> <li>Monitoring with visual fields, optical coherence tomography, and electroretinography allows earlier detection of toxicity and may prevent disabling vision loss</li> </ul>

Question 21

Cyclosporine. What is it?

Answer 21

<ul> <li>Calcineurin inhibitor (includes tacrolimus and sirolimus) that fights organ transplant rejection and autoimmune disorders </li> <li>Most common ophthalmic side effect: posterior reversible encephalopathy syndrome (PRES) producing binocular vision loss</li> <li>Caused by toxicity to vascular endothelium and high blood pressure, which provoke vascular leakage into brain</li> <li>Damage greatest in distribution of posterior cerebral artery</li> </ul>

Question 22

Cyclosporine. How does it appear?

Answer 22

<ul> <li>Acute or subacute onset of visual impairment</li> <li>Unilateral or bilateral homonymous hemianopia</li> <li>Normal eye examination </li> <li>Confusional state</li> <li>Headache</li> <li>Seizures</li> <li>High blood pressure</li> <li><a>High T2/FLAIR MRI signal</a> concentrated around visual cortex</li> <li>No abnormalities on <a>diffusion-weighted MRI</a></li></ul>

Question 23

Cyclosporine. What else looks like it?

Answer 23

<ul> <li>Stroke</li> <li>Hypertensive encephalopathy</li> <li>Reversible cerebal vasoconstriction (Call-Fleming) syndrome</li> <li>Non-convulsive status epilepticus</li> <li>Dural venous sinus thrombosis</li> <li>Encephalitis</li> <li>Posterior ischemic optic neuropathy</li> <li>Occult retinopathy</li> <li>Pituitary apoplexy</li> </ul>

Question 24

Cyclosporine. How do you manage it?

Answer 24

<ul> <li>Anticipate this common side effect </li> <li>Refer urgently to ophthalmologist or emergency room</li> </ul>

Question 25

Cyclosporine. What will happen?

Answer 25

<ul> <li>Medication must be promptly discontinued and blood pressure lowered </li> <li>These measures will lead to recovery within days, but...</li> <li>If PRES has persisted for too long, stroke may occur, producing permanent occipital blindness, so...</li> <li>Diagnosis is urgent!</li> </ul>

Question 26

Deferoxamine. What is it?

Answer 26

<ul> <li>Medication that binds iron and treats iron overload occurring after frequent blood transfusions</li> <li>Most common ophthalmic side effect: damage to retinal pigment epithelium, photoreceptors, retinal ganglion cells</li> </ul>

Question 27

Deferoxamine. How does it appear?

Answer 27

<ul> <li>Patient complains of impaired visual acuity, visual field, night vision, color vision</li> <li>Symptoms develop after acute or chronic administration of deferoxamine</li> <li>Ophthalmoscopy normal at symptom onset</li> <li>Ophthalmoscopy later shows fine retinal speckled pigmentation or pale optic discs </li> <li>Once ophthalmoscopic signs have appeared, visual dysfunction may be irreversible even if medication stopped</li> <li>Electroretinography detects abnormalities before ophthalmoscopy </li> </ul>

Question 28

Deferoxamine. What else looks like it?

Answer 28

<ul> <li>Hereditary photoreceptor dystrophy ("<a>retinitis pigmentosa</a>")</li> <li>Toxicity from thioridazine </li> <li><a>Congenital rubella syndrome</a></li> </ul>

Question 29

Deferoxamine. How do you manage it?

Answer 29

<ul> <li>Refer patients for baseline ophthalmological examination before starting medication </li> <li>Refer for reexamination every three months while on treatment</li> <li>Refer promptly for reexamination if patient develops visual symptoms</li> </ul>

Question 30

Deferoxamine. What will happen?

Answer 30

<ul> <li>If toxicity diagnosed early, visual loss may be reversible or non-disabling </li> <li>Medication must be stopped at diagnosis of ocular toxicity and later resumed at lower dose or replaced with alternative iron chelator, depending on visual manifestations</li> </ul>

Question 31

Ethambutol. What is it?

Answer 31

<ul> <li>Medication used to treat mycobacterial diseases, including tuberculosis</li> <li>Most common ophthalmic side effect: bilateral optic neuropathy</li> <li>Optic neuropathy develops in 2% to 5% treated with more than 15mg/kg/day, and in up to 25% treated with more than 25mg/kg/day</li> </ul>

Question 32

Ethambutol. How does it appear?

Answer 32

<ul> <li>Slowly progressive visual loss in both eyes, appearing within 3 months of starting medication</li> <li>Reduced visual acuity in both eyes</li> <li>Central scotomas on visual field testing</li> <li>Reduced color vision </li> <li>Ophthalmoscopy normal at first, later disclosing mildly <a>pale optic discs</a> at their temporal portions</li> </ul>

Question 33

Ethambutol. What else looks like it?

Answer 33

<ul> <li>May be mistaken for cataract or uncorrected refractive error</li> <li>Other optic neuropathies</li> </ul>

Question 34

Ethambutol. How do you manage it?

Answer 34

<ul> <li>Refer patient for baseline eye examination </li> <li>Repeat ophthalmic examinations every 3 months while patient being treated</li> <li>Avoid daily doses of greater than 15mg/kg especially in those with impaired kidney function</li> <li>Discontinue medication promptly if optic neuropathy discovered</li> </ul>

Question 35

Ethambutol. What will happen?

Answer 35

<ul> <li>Visual loss irreversible and may worsen after medication discontinued, so...</li> <li>Early detection critical to preserve vision</li> <li>Delayed diagnosis common because visual loss symmetrical, very slowly progressive, and painless</li> </ul>

Question 36

Minocycline. What is it?

Answer 36

<ul> <li>Antibiotic derived from tetracycline used against wide variety of bacteria</li> <li>Treats refractory acne vulgaris</li> <li>Most common ophthalmic side effect: papilledema (from increased intracranial pressure) </li> </ul>

Question 37

Minocycline. How does it appear?

Answer 37

<ul> <li>Headache, neck pain, transient or persistent loss of vision, and...</li> <li>Loss of vision even WITHOUT headache or other symptoms</li> <li>Symptoms begin within weeks to months after starting standard doses of minocycline</li> <li>Swollen optic discs (<a>papilledema</a>)</li> <li>Visual fields abnormal, reflecting axonal damage from chronically elevated intracranial pressure</li> <li>Brain imaging normal</li> <li>Lumbar puncture discloses high opening pressure and normal cerebrospinal constituents </li> </ul>

Question 38

Minocycline. What else looks like it?

Answer 38

<ul> <li>Isotretinoin-induced increased intracranial pressure</li> <li>Idiopathic intracranial hypertension (pseudotumor cerebri)</li> <li>Brain tumor</li> <li>Meningitis</li> <li>Hydrocephalus</li> <li>Optic neuritis</li><li>Ischemic optic neuropathy in giant cell arteritis</li> <li>Compressive or infiltrative optic neuropathy from cancer</li> </ul>

Question 39

Minocycline. How do you manage it?

Answer 39

<ul> <li>Refer promptly to ophthalmologist any patient with visual symptoms and/or headache who is using minocycline</li> <li>Consider baseline ophthalmologic screening and routine screening every 3-6 months because papilledema can exist at first without causing visual symptoms </li> </ul>

Question 40

Minocycline. What will happen?

Answer 40

<ul> <li>Vision loss may be delayed because axonal damage in papilledema proceeds slowly and initially spares visual acuity</li> <li>Vision loss reversible if papilledema detected early</li> <li>Vision loss permanent and disabling if papilledema detected late </li> </ul>

Question 41

Prednisone. What is it?

Answer 41

<ul> <li>Corticosteroid used to treat inflammatory conditions</li> <li>Most common ophthalmic side effect: posterior subcapsular cataract, developing in 25% of patients who use prednisone 15 mg/day for 1 year or more, or equivalent doses of other corticosteroids</li> </ul>

Question 42

Prednisone. How does it appear?

Answer 42

<ul> <li>Slowly progressive visual loss in both eyes, but may be asymmetric in two eyes</li> <li><a>Opacity</a> on posterior portion of crystalline lens, usually visible only with ophthalmoscope or slit lamp biomicroscope</li> </ul>

Question 43

Prednisone. What else looks like it?

Answer 43

<ul> <li><a>Cataract</a> as part of aging, intraocular inflammation, eye trauma</li> <li><a>Refractive error</a>, retinal or <a>visual pathway</a> disorder</li> </ul>

Question 44

Prednisone. How do you manage it?

Answer 44

<ul> <li>Warn patients that cataract is likely complication of chronic prednisone use</li> <li>Refer patients who report visual impairment and are using prednisone chronically</li> </ul>

Question 45

Prednisone. What will happen?

Answer 45

<ul><li>Discontinuing prednisone does not reverse cataract but may halt its progression </li> <li>Cataract extraction has high chance of restoring vision provided there are no other causes of vision loss</li> </ul>

Question 46

Sildenafil. What is it?

Answer 46

<ul><li>Phosphodiesterase inhibitor used to treat erectile dysfunction or prolong normal erection</li> <li>Most common ophthalmic side effect: temporary alteration in vision, presumed to be effect on retinal photoreceptors or their connections</li> <li>Possible ophthalmic side effect: ischemic optic neuropathy</li><li>Ophthalmic side effects reported for all phosphodiesterase inhibitors</li> </ul>

Question 47

Sildenafil. How does it appear?

Answer 47

<ul> <li>Blurred, bright, dim, blue discoloration of vision starting within 30 minutes of taking medication and ceasing within hours</li> <li>Sudden, persistent loss of vision occurring within 24 hours of medication use, associated with swollen optic disc and <a>afferent pupil defect</a> in <a>ischemic optic neuropathy</a></li> </ul>

Question 48

Sildenafil. What else looks like it?

Answer 48

<ul> <li>Temporary alteration in vision has no other explanation</li> <li>Persistent vision loss may be caused by <a>ischemic optic neuropathy</a> unrelated to phosphodiesterase inhibitor use, non-ischemic optic neuropathy, or retinopathy </li> </ul>

Question 49

Sildenafil. How do you manage it?

Answer 49

<ul><li>Reassure patient that alteration in vision common, temporary, and benign </li> <li>Refer to ophthalmologist urgently any patient with persistent vision loss occurring within day of using medication</li> <li>Warn users that ischemic optic neuropathy has been associated with phosphodiesterase inhibitor use and discourage its use in those with only one sighted eye</li> </ul>

Question 50

Sildenafil. What will happen?

Answer 50

<ul> <li>Discoloration of vision always temporary, may recur with repeated phosphodiesterase inhibitor use, but causes no permanent vision impairment</li> <li>Ischemic optic neuropathy causes irreversible and untreatable vision loss </li> </ul>

Question 51

Tamoxifen. What is it?

Answer 51

<ul><li>Medication used to treat some forms of breast cancer </li> <li>Most common ophthalmic side effect: accumulation of white crystalline deposits around fovea</li> <li>Less common ophthalmic side effect: blurred vision from cystoid macular edema mostly in patients treated with 120mg twice daily and after cumulative dose of 100gm</li> </ul>

Question 52

Tamoxifen. How does it appear?

Answer 52

<ul> <li>Perifoveal <a>white crystalline deposits</a></li> <li>Blurred vision</li> <li>Cystoid macular edema</li> </ul>

Question 53

Tamoxifen. What else looks like it?

Answer 53

<ul> <li>Macular hard exudates in <a>diabetes mellitus</a></li> <li>Hereditary maculopathy</li> <li>Cystoid macular edema of other causes </li> </ul>

Question 54

Tamoxifen. How do you manage it?

Answer 54

<ul> <li>Perform baseline ophthalmic examination if treatment with high doses is anticipated</li> <li>Refer patient with visual symptoms </li> <li>Discontinue medication if tamoxifen retinopathy confirmed</li> </ul>

Question 55

Tamoxifen. What will happen?

Answer 55

<ul> <li>Visual loss usually reversible </li> <li>Crystalline deposits sometimes reversible</li> </ul>

Question 56

Tamsulosin. What is it?

Answer 56

<ul> <li>Selective alpha-1A antagonist used to treat symptoms in benign prostatic hypertrophy</li> <li>Most common ophthalmic side effect: floppy iris syndrome</li> </ul>

Question 57

Tamsulosin. How does it appear?

Answer 57

<ul><li>Dome-shaped anterior displacement of iris</li><li>Prolapse of iris during cataract surgery, requiring special measures to prevent surgical complications</li> <li>Occurs in up to 60% of patients </li> </ul>

Question 58

Tamsulosin. What else looks like it?

Answer 58

<ul> <li>Nothing</li> </ul>

Question 59

Tamsulosin. How do you manage it?

Answer 59

<ul> <li>Discontinue medication within week of anticipated intraocular surgery</li> </ul>

Question 60

Tamsulosin. What will happen?

Answer 60

<ul> <li>Floppy iris syndrome must be anticipated by cataract surgeon to avoid complications</li> <li>Special maneuvers usually allow safe lens extraction</li> </ul>

Question 61

Topiramate. What is it?

Answer 61

<ul> <li>Medication used to treat seizures and migraine </li> <li>Most common ophthalmic side effect: angle-closure glaucoma caused by edema of the ciliary body</li><li>Incidence of this side effect estimated at 2%</li></ul>

Question 62

Topiramate. How does it appear?

Answer 62

<ul> <li>Sudden eye pain</li> <li>Blurred vision</li> <li>Red eye with <a>ciliary flush</a></li> <li>Hazy cornea</li> <li>Shallow anterior chamber (note that <a>iris surface nearly touches peripheral cornea</a>); compare to <a>normal depth of anterior chamber</a></li> <li><a>Angle-closure</a> well shown on ultrasound; compare to <a>normal anterior chamber depth</a></li></ul>

Question 63

Topiramate. What else looks like it?

Answer 63

<ul> <li><a>Angle-closure glaucoma</a> of other cause</li> <li><a>Anterior uveitis</a></li> </ul>

Question 64

Topiramate. How do you manage it?

Answer 64

<ul> <li> Avoid prescribing topiramate if ophthalmologist has documented that patient has narrow anterior chamber angle</li> <li> Refer emergently to ophthalmologist any patient with acute eye pain or visual symptoms who is taking topiramate</li> <li> Discontinue topiramate if angle closure glaucoma is confirmed </li></ul>

Question 65

Topiramate. What will happen?

Answer 65

<ul> <li>Intraocular pressure must be lowered promptly with aqueous suppressants, cycloplegia, topical corticosteroids</li> <li>Peripheral iridectomy, standard approach to angle closure glaucoma not caused by topiramate, does not work here</li> <li>Permanent vision loss has resulted from angle closure precipitated by topiramate even when diagnosis and treatment are undertaken promptly </li></ul>

Question 66

Vigabatrin. What is it?

Answer 66

<ul> <li> Anti-epileptic agent used mainly for refractory childhood seizure disorder called infantile spasms</li> <li> Most such children are cognitively impaired </li> <li>Ophthalmic side effect: visual field constriction </li> <li>Attributed to effect of excess neurotransmitter GABA on retinal photoreceptors and ganglion cells </li></ul>

Question 67

Vigabatrin. How does it appear?

Answer 67

<ul> <li>Children do not report symptoms because they are neurologically impaired and vision deficits are subtle</li> <li> Ophthalmoscopy normal unless damage advanced</li><li>Visual field constriction and optic disc pallor indicate advanced damage</li> <li>Electroretinography may disclose abnormalities</li></ul>

Question 68

Vigabatrin. What else looks like it?

Answer 68

<ul> <li><a>Genetic retinal dystrophies</a></li></ul>

Question 69

Vigabatrin. How do you manage it?

Answer 69

<ul> <li>Try not to exceed daily dose of 100mg/kg</li> <li> Withdraw this medication if ineffective </li> <li>FDA requires that children undergo baseline and serial ophthalmic examinations, but </li> <li>These children not able to cooperate for visual function testing or electroretinography, so... </li> <li>Serial ophthalmoscopy may be only way to monitor for retinal toxicity, yet... </li> <li>Ophthalmoscopy insensitive to toxicity </li></ul>

Question 70

Vigabatrin. What will happen?

Answer 70

<ul> <li>Peripheral visual field loss may occur but unlikely to be disabling, and... </li> <li>Visual field loss may be reasonable trade-off for seizure control </li></ul>