THE INTERNIST AND THE OPHTHALMOLOGIST
From Update in Medicine and Ophthalmology, presented by the University of Toronto Faculty of Medicine,
Departments of Ophthalmology and Vision Sciences, and Continuing Education
| OCULAR SIDE EFFECTS OF SYSTEMIC MEDICATION —Fritz T. Fraunfelder, MD, Professor of Ophthalmology
and Director Emeritus, Casey Eye Institute, Oregon Health and Science University, Portland
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| Erectile dysfunction medications: sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) have similar ocular
effects; sildenafil most extensively studied; at normal dose (50 mg), 4% of patients develop blue or green vision
or central haze lasting ≈30 min; prevalence increases to 40% at doses of 200 mg; conjunctival hyperemia and subconjunctival
hemorrhage also reported; some adverse effects possibly related to increased physical activity, not drug
|
 | Nonarteritic ischemic optic neuropathy (NAION): recent reports in men who took sildenafil, but relationship to drug
unknown
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| Central serous chorioretinopathy (CSR): condition seen in men, 35 to 75 yr of age, with onset 1 to 7 days after taking
sildenafil; positive rechallenge seen in several cases; 75% of cases bilateral; >50% of cases did not resolve until
drug discontinued; causal relationship still unproven; clinical implications—obtain history of sildenafil use from
patients with bilateral CSR (especially elderly men); discontinue sildenafil
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| Ocular contraindications to erectile dysfunction agents: history of NAION; history of CSR or transitory loss of vision
associated with prior use of sildenafil
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| Topiramate: approved for treatment of migraine headaches and epilepsy; prescribed off-label for insomnia and weight
loss; ocular adverse effects (certain)—acute bilateral narrow-angle glaucoma that develops within 3 to 21 days after
starting drug (patients 3.5-53 yr of age; more common in women); myopia up to 8 diopters; suprachoroidal effusions;
probable adverse effects—blepharospasm; oculogyric crisis; possible adverse effects—scleritis (injection of eye or
retinal hemorrhage from acute glaucoma more likely explanations); termination—medication must be discontinued
(peripheral iridectomy not helpful); abrupt termination associated with severe rebound; glaucoma medications quickly
restore normal pressure
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| Bisphosphonates: pamidronate (Aredia) and alendronate (Fosamax) inhibit bone resorption associated with malignancy
or menopause; pamidronate proven to cause scleritis (probably true of all bisphosphonates); patient must discontinue pamidronate
for scleritis to resolve; other known complications include uveitis and conjunctivitis; any drug that causes dry
mouth aggravates ocular sicca; episcleritis also may occur; all drugs that cause peripheral edema also cause periocular
edema
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| National Registry of Drug-Induced Ocular Side Effects: began in 1974; includes every English-language report
of any drug associated with ocular side effects; available online at www.eyedrugregistry.com
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| INFECTIOUS DISEASES —David McNeely, MD, Associate Professor of Medicine, University of Toronto, Faculty of
Medicine, Toronto, ON
|
| Herpes varicella zoster: by 16 yr of age, 97% of North Americans have antibodies for herpes varicella-zoster virus
(chickenpox); during primary infection, virus settles in dorsal root ganglia or facial sensory ganglia; reactivation results
in blistering dermopathy (shingles)
|
| Shingles: incidence increases with age, immunosuppressive illness, and organ system dysfunction; symptoms include
burning, itching, pain, and secondary infection; 10% to 12% of patients develop long-term problems; postherpetic
neuralgia (pain requiring medical intervention at 6 mo) most common; pain occurs in dermatome affected by shingles;
risk increases with severity and age at which shingles develops; 15% to 20% of patients 75 yr of age develop
postherpetic neuralgia
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| Ophthalmitis: blisters in conjunctival space associated with infections involving first or, most commonly, second branch
of fifth cranial nerve, especially if nasociliary branch involved; many patients develop keratitis or anterior chamber
disease (early antiviral treatment decreases risk)
|
| Vaccine: new exposure boosts adult immune system to maintain defenses against dormant virus; consists of live, attenuated
virus; adult version has 16 times more viral burden than pediatric vaccine; efficacy—when administered to people >60
yr of age, 5-yr incidence of active disease decreased by >50%, and incidence of postherpetic neuralgia decreased by
≈70%, compared to placebo group; vaccine also associated with lower incidence of ophthalmic complications; use—
approved in United States; approval expected soon in Canada; cost ($150/dose) elicits questions about who will pay
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| Suppurative conjunctivitis: organisms include Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus
influenzae, and Moraxella
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| Treatment recommendations: first choice—empiric therapy with quinolones (ciprofloxacin or moxifloxacin); second
choice—topical sulfacetamide or polymyxin–trimethoprim
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| Contact lens–associated suppurative conjunctivitis: infection with afermentive gram-negative rods (water-borne organisms
that may contaminate contact lens solutions); recommendations—always culture; add topical gentamicin
or tobramycin to antibiotic regimen
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| Dry eyes, diabetes, or immunosuppression: many possible pathogens, including fungi; recommendations—always
get culture; use concentrated topical cefazolin plus gentamicin or tobramycin until culture results come back
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| Chronic mucopurulent (follicular) conjunctivitis: suspect Chlamydia infection, especially in sexually active young
adults; characteristics—usually unilateral; poor response to topical antibiotics; in women, associated with chronic
mucopurulent cervicitis; in men, associated with smoldering urethritis; treatment—first choice, single large dose
of azithromycin (1 g taken orally under observation); second choice, doxycyline 100 mg bid for 2 to 3 wk; note—
follow-up testing important
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| Periorbital (preseptal) cellulitis: approach dictated by severity of presentation and host’s age and health
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| Healthy children and adults with mild disease: oral antibiotics effective; children—cefuroxime or amoxicillin–
clavulanate, or clarithromycin for patients sensitive to penicillin; adults—cephalexin, dicloxacillin; clindamycin
for penicillin-allergic patients
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| Elderly, chronically ill patients with extensive disease: long list of possible pathogens, including coliform and noncoliform
gram-negative organisms; high rate of complications (eg, sinusitis, cavernous sinus thrombosis, and bacterial
cerebritis); treatment—emergency administration of systemic antibiotics usually indicated; broad-spectrum drugs
recommended until results of blood culture known
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| THE EYELID AND SYSTEMIC DISEASE —Larry H. Allen, MD, Assistant Professor of Ophthalmology, Schulich
School of Medicine and Dentistry, University of Western Ontario, London, ON
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| Factors to consider: presenting complaint; duration; bilateral or unilateral presentation; progression; factors that improve
or exacerbate condition; individual and family medical history
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| Graves’ disease: “the great imitator” (may mimic myasthenia gravis); ocular manifestations most common in women
40 to 50 yr of age; bilateral and unilateral disease; patients often report family history of autoimmune disease; early
symptoms often relatively minor, then progress quickly; upper lid retraction most common presenting sign (white of
eye visible when patient looks down); if diagnosis uncertain, have patient return for follow-up
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| Investigations: thyroid-stimulating hormone; triiodothyronine; free thyroxine; no relationship between thyroid antibodies
and disease severity or progression; tibial dermopathy rare but suggestive of severe disease; ≈10% of patients
euthyroid; 40% of patients hyperthyroid at initial presentation; ocular signs often precede imaging findings
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| Acquired ptosis: etiologies include levator problems (most common) and neurologic problems (eg, myasthenia gravis)
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| Chronic progressive external ophthalmoplegia: patients present with ptosis, diminished ocular movement, weak orbicularis,
and poor blink; mitochondrial problem evident upon muscle biopsy; double vision uncommon
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| Other causes: myotonic dystrophy—patients have abnormal blink, weak obicularis, and may have “Christmas tree
cataract”; associated problems include dysphagia; patients lack facial expression and often balding (men and
women); ptosis often bilateral and symmetric; oculopharyngeal dystrophy—patients present with ptosis and limited
ocular movement, and often report difficulties swallowing (throat surgery may help)
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| Xanthelasma: ≈30% of cases associated with abnormalities of lipid metabolism, especially in patients <40 yr of age;
surgical excision best approach (high rate of recurrence with laser resurfacing)
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| Pemphigoid: ocular manifestations usually occur early in course of disease (first in medial canthus, leading to rounding
and loss of medial canthal angle); trichiasis and symblepharon may develop; disease also may affect naso-oral
cavity (ask patient about gum and dental problems); younger patients often have more severe symptoms
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| Amyloid: primary or secondary; local or systemic; associated with chronic disease or plasma cell dyscrasias, but exact
cause unknown; features—subconjunctival hemorrhage and bloody tears; even slight pressure causes bleeding
(makes biopsy difficult); if bilateral, suspect bleeding dyscrasia; patients often have history of breast carcinoma; early
treatment prevents scarring
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| OCULOPLASTICS UPDATE —Dr. Allen
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| Graves’ ophthalmopathy: fibroblasts—most likely target cell; differentiation to adipose cells causes production of
excess fat in orbit; glycosoaminoglycans retain fluid; cytokine release leads to inflammation and scarring; target
tissue—probably extraocular muscle; association with thyroid unclear; incidence—decreasing in North America
and western Europe, but rising in eastern Europe (likely associated with smoking); treatment issues—cigarettes
can interfere with efficacy of steroid therapy and treatment of thyroid disease; radioactive iodine also thought to aggravate
Graves’ disease (total ablation of thyroid preferred because of better long-term results)
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| Approach to therapy: thyroid stabilization for 6 mo; radioactive iodine for patients with mild thyroid inflammation;
steroids appropriate for patients with moderate inflammation; hypothyroidism requires treatment; some centers treat
all patients with radioactive iodine plus steroids for 6 to 8 wk; intravenous steroids preferred if optic nerve compressed;
orbital irradiation controversial (study results inconsistent; speaker uses radiation for severe soft tissue
problems or optic nerve compression)
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| Rosacea: tetracyclines reduce lid inflammation and bacterial count; condition frequently associated with chalazia; etiology
may be more inflammatory than infectious; speaker treats with several courses of doxycycline; steroids necessary
to control inflammation; severe cases may benefit from dexamethasone drops (6 times daily for 3-4 days) in
addition to usual regimen, but warn patient about possible risk for increased intraocular pressure
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| Floppy lid syndrome: patients usually heavy middle-aged men; ≈8% of cases associated with sleep apnea; lid tightening
may help; early signs include lash ptosis (curling lashes may keep them out of eyes)
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| ESSENTIAL PEDIATRICS —Alex V. Levin, MD, Professor of Pediatrics, Genetics, and Ophthalmology & Vision Sciences,
University of Toronto, ON
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| Vaccines: Haemophilus influenzae vaccine associated with sharp decrease in incidence and severity of disease and associated
illnesses; development of many new vaccines associated with growing public concern
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| Biologic agents: anti-tumor necrosis factor agents (etanercept, infliximab) effective for treating all types of uveitis, including
that associated with juvenile idiopathic arthritis (formerly juvenile rheumatoid arthritis); infliximab associated
with better outcomes and fewer complications, but both effective and avoid need for high-dose steroids and other toxic
agents; drawbacks—expense; administration requires either home injection or prolonged infusion in hospital; rare but
serious side effects (eg, respiratory arrest); ineffective in some patients; other agents—amniotic membrane; limbal
cell transplantation; enzyme replacement therapy
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| Molecular genetics: knowledge of genetics improves understanding of disease process, diagnostic ability, family
counseling about disease risks, and access to support groups; gene therapy controversial; ethical questions concern
prenatal counseling, confidentiality, and insurance issues
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| Bioethical issues: concept of assent (involving children in decisions about their care); predictive testing for diseases
that might be unpreventable and incurable; questions related to autonomy
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| Child abuse: American Academy of Pediatrics approved child abuse subspecialty in 2006; vigilance for shaken baby
syndrome critical; law requires physicians to report suspicious cases
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| Shaken baby syndrome: diagnostic term will change to “abusive head injury”; symptoms include retinal hemorrhage;
injuries also result from head impact while shaking
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| Neonatology: increased survival of premature infants associated with increased global incidence of retinopathy of prematurity;
treatment often challenging in emerging nations
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| International medicine: infectious disease, war, violence, and terrorism
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Educational Objectives
| The goal of this program is to describe the ophthalmologic impact of certain systemic conditions. After hearing and
assimilating this program, the listener will be able to:
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| 1. List the potential ocular side effects of commonly used medications.
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| 2. Describe the ocular manifestations of certain infectious illnesses, and how they can be managed.
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| 3. State the guidelines for antibiotic use in general ophthalmology practice.
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| 4. Discuss the effect of common systemic illnesses on eyelid function and appearance.
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| 5. Explain why ophthalmologists should be aware of current issues in pediatrics.
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Suggested Reading
[No authors listed]: Adverse drug reactions in Canada. Bisphosphonates and ocular disorders. Can Fam Physician
50:422, 2004; Alvarenga LS, Mannis MJ: Ocular rosacea. Ocul Surf 3:41, 2005; Forbes BJ et al: Inflicted
childhood neurotrauma (shaken baby syndrome): ophthalmic findings. J Pediatri Ophthalmol Strabismus 41:80,
2004; Fraunfelder FW, Fraunfelder FT: Adverse ocular drug reactions recently identified by the National Registry
of Drug-Induced Ocular Side Effects. Ophthalmology 111:1275, 2004; Fraunfelder FW, Shults T: Non-arteritic
anterior ischemic optic neuropathy, erectile dysfunction drugs, and amiodarone: is there a relationship? J
Neuroophthalmol 26:1, 2006; Karger RA et al: Prevalence of floppy eyelid syndrome in obstructive sleep apnea-
hypopnea syndrome. Ophthalmology 113:1669, 2006; Leibovitch I et al: Periocular and orbital amyloidosis: clinical
characteristics, management, and outcome. Ophthalmology 113:1657, 2006; Mah F: Bacterial conjunctivitis in
pediatrics and primary care. Pediatr Clin North Am 53 Suppl 1:7, 2006; Mitka M: FDA approves shingles vaccine:
herpes zoster vaccine targets older adults. JAMA 296:157, 2006; Oxman M et al: A vaccine to prevent herpes
zoster and postherpetic neuralgia in older adults. N Engl J Med 352:2271, 2005; Prey S et al: Treatment of ocular
cicatricial pemphigoid with tumour necrosis factor alpha antagonist etanercept. Acta Derm Venereol 87:74, 2007;
Renouf P: Immediate or delayed prescribing of antibiotics reduced duration of symptoms in acute infective conjunctivitis.
Evid Based Nurs 10:10, 2007; Santaella RM, Fraunfelder FW: Ocular adverse effects associated with
systemic medications: recognition and management. Drugs 67:75, 2007; Tynjala P et al: Infliximab and etanercept
in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis Oct 26,
2006 [Epub ahead of print].
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the faculty reported nothing to disclose.
Drs. Fraunfelder, McNeely, Allen, and Levin were recorded at Update in Medicine and Ophthalmology, held December
8-9, 2006, in Toronto, ON, and sponsored by the University of Toronto. The Audio-Digest Foundation thanks the
speakers and the sponsor for their cooperation in the production of this program.
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