1. Describe the concept of professionalism, especially as it pertains to medical ethics.

2. Discuss some of the major ethical challenges ophthalmologists may encounter.

3. Determine when off-label use of systemic corticosteroids is appropriate.

4. Explain the role of magnetic resonance imaging in the work-up of patients with optic neuritis, and explain why it is important to refer such patients to a specialist.

5. Request that the radiologist develop an imaging protocol for patients suspected of having Horner syndrome.

Ethics in Retinal Practice
Nancy M. Holekamp, MD, Associate Professor of Clinical Ophthalmology, Washington University School of Medicine, and Partner, Barnes Retina Institute, St. Louis, MO

Professionalism: requires adherence to profession’s ethical standards

Challenges: conflicts of interest (eg, fee-for-service medicine); decreasing reimbursement; advertising, competition; commercial relationships (industry ties); emerging technologies; research vs patient care; complementary and alternative medicine; return-on-investment (ROI) issues; consulting in clinical investigations

Conflicts of interest: American Academy of Ophthalmology (AAO) Code of Ethics states that “a conflict of interest exists when professional judgment concerning the well-being of the patient has a reasonable chance of being influenced by other interests of the provider”; professionals must place patients’ interests above their own; being on salary diminishes conflict inherent in fee-for-service medicine

Characteristics of professionalism: self-regulating; concerned with specialized, large body of knowledge (potential exists for exploiting people who lack that knowledge); fiduciary responsibility to patient takes precedence over profit; recognition of dependence of those seeking services; instilling trust between provider and those seeking services

Ethical issues: fee-for-service medicine (eg, do not have patient undergo unnecessary procedure simply to receive additional fee); charging reasonable fees; keeping abreast of alternative treatments that do or do not work; practicing evidence-based medicine; truth-telling, honesty (not specifically mentioned in AAO Code of Ethics); avoidance of “belief-based medicine” (believing a certain treatment is superior to others with no supporting evidence); understanding difference between clinical practice and research (mutually exclusive; collecting case studies for publication constitutes research); importance of obtaining full-informed consent (patients have right to know when they are receiving anything other than standard of care)

Practice of medicine vs research: practice of medicine—interventions designed solely to enhance well-being of patient; research—activity designed to test hypothesis, permit conclusions to be drawn, and contribute to knowledge; requires special informed consent, approval from the human studies committee of the Institutional Research Board, and investigational new drug exemption from United States Food and Drug Administration (FDA)

Commercial relationships: physician’s fiduciary responsibility is to patient and patient care; concern justified when company limits access to a drug; fiduciary responsibility of pharmaceutical industry is to shareholders; physicians must fight for patients’ interests; business ethic inappropriate and insufficient; never supersedes medical ethic

Ethics of treating age-related macular degeneration (AMD): concern arose when Genentech announced it would no longer sell bevacizumab (Avastin) to compounding pharmacies; level 1 evidence from large randomized clinical trials (RCTs) now suggests that anti-vascular endothelial growth factor (anti-VEGF) therapy is new standard of care for most types of exudative AMD; however, those trials used ranibizumab (Lucentis; also made by Genentech); standard of care defined as “what a reasonable physician in your area would do in a similar situation”; bevacizumab widely used to treat AMD, despite lack of FDA approval for that purpose; full informed consent might consist of telling patient that ranibizumab extremely expensive and may require multiple injections; bevacizumab not developed for AMD and not tested in clinical trials, but used safely and effectively in thousands of patients and is much less expensive; physician responsible for obtaining informed consent

Ambulatory surgery centers: introduce potential financial conflict of interest when owned by medical practice; should disclose interest to patient before surgery

Learning curve: always inform patients when performing new procedure for first time, or if experience with procedure is limited

Recommendations: serve patient’s best interests first; provide complete informed consent and document everything; commit to evidence-based medicine; keep abreast of latest developments; for nonvalidated procedures, generate rigorous scientific data via appropriate pathways (ie, clinical trials); charge reasonable fees

Controversies in Neuro-Ophthalmology
Andrew G. Lee, MD, Professor of Ophthalmology, Neurology, and Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City

Steroid use

Graves’ disease: periocular administration of steroid decreases risk for systemic side effects associated with oral or intravenous (IV) administration; according to prospective multicenter study of 41 patients with Graves’disease, 20 mg peribulbar triamcinolone associated with decrease in double vision and volumetric reduction in size of extraocular muscles; however, manufacturer has recommended against periocular administration, due to risk of entering central retinal artery, leading to blindness; make sure patient signs informed consent form before using; IV administration associated with rare fatalities; speaker offers steroids to people with Graves’ophthalmopathy if eye red, hot, and swollen; long-term use associated with side effects, but tapering associated with symptom recurrence

Temporal arteritis: no evidence supports use of IV steroids; speaker administers IV steroids if 1) patient monocular and vision loss transient (amaurosis fugax; steroids diminish arteritic phase in attempt to prevent thrombotic phase), 2) vision loss bilateral, instantaneous, rapidly sequential, or severe (20/220 or worse), or 3) problem has occurred within previous 24 hr; recommendations not evidence-based; litmus test—“what would you do on yourself, or your grandmother?”; some data suggest patients who receive loading pulse of IV methylprednisolone need shorter course of oral steroids; for patients with vision loss due to temporal arteritis, recommended minimum dose of oral steroids is 1 to 1.5 mg/kg (higher than doses used in rheumatology)

Steroid-sparing agents: elderly people given steroids develop significant side effects (bone loss, hypertension, hyperglycemia); speaker recommends regular monitoring by patient’s internist, including baseline and follow- up bone density studies; patient should take vitamin D and calcium supplements; methotrexate recommended as first-line steroid-sparing agent for patients who develop side effects; evidence for other agents anecdotal

Optic neuritis and multiple sclerosis risk

Optic Neuritis Treatment Trial: published in 1992; survey data show that at least one-third of practicing ophthalmologists and neurologists do not follow evidence-based treatment guidelines that were based on findings of that trial; takes 10 to 15 yr for information from literature to be adopted into practice by 50% of physicians; magnetic resonance imaging (MRI) can determine risk for demyelinating disease (multiple sclerosis [MS]; look for periventricular white matter lesions); if case typical (young [usually female] patient; acute onset; vision loss; pain on eye movement; normal disc; afferent defect plus other evidence of optic neuropathy), no laboratory studies necessary; MRI sufficient; in trial, IV steroids hastened recovery compared to placebo, but even patients who received nothing eventually recovered; conventional doses of oral steroids increased rate of new attacks; conclusion—do nothing, and refer patient to specialist; do not prescribe oral steroids

Treatments for MS: interferon beta-1a (Avonex)—compared to placebo, significantly reduced likelihood of developing clinically definitive MS 36 mo after initial event (ie, fewer lesions on MRI); however, cost for interferon beta-1a (and equivalent interferons) $12,000 to $13,000/yr for rest of patient’s life; with interferon, MRI outcome measures better than clinical outcome measures; studies using different interferon preparations produce similar results; take-home messages—order MRI for optic neuritis patients, not for diagnosis, but to determine prognosis for MS (do not order computed tomography [CT]); IV steroids therapeutic option for optic neuritis, “but choosing nothing is reasonable”; warn optic neuritis patient of risk for MS, or refer to someone who will warn them; normal MRI does not mean patient will not develop optic neuritis (in one study, 22% of patients with normal MRI developed MS within 10 yr); however, many lesions on MRI not definitive proof that patient will develop MS; general ophthalmologist should not advise patient on his or her risk of developing MS (specialist can better determine which patients are best candidates for drug, since not all will need it); MS risk for patient with disc edema much less than MS risk for typical patient; atypical features that suggest causes other than demyelinating disease—no light perception (suggests sarcoidosis or other inflammatory cause); no pain; severe disc edema (360o of swelling); most patients with optic neuritis have minimal to mild hyperemia, with no hemorrhages, exudates, or cotton-wool patches; photograph optic nerve for documentation

Treatment controversy: since immunomodulator expensive, selection of most appropriate candidates important; interferon beta-1a does not cure MS, it only reduces the frequency and severity of relapses, and prolongs time to development of clinically definitive MS; cost efficacy and long-term effects on disability currently under investigation; bottom line—obtain MRI and refer patient to specialist who can provide best estimate of MS risk

Results of Optic Neuritis Treatment Trial: IV steroids delay development of clinically definitive MS; patients randomized to receive IV steroids, oral placebo, or conventional doses of oral steroids; IV steroids reduced rate of clinically definitive MS at yr 2; however, by yr 3, effect had worn off; by yr 5, rate of clinically definitive MS the same in all 3 groups; controversy—whether to administer follow-up pulses of IV steroids every few years (answer unknown); study not designed to address that question; occupational concerns valid reasons to administer IV steroids (eg, patient is surgeon or airline pilot and must return to work as quickly as possible)

Pharmacologic testing for Horner syndrome: off-label use of apraclonidine recommended; confirms but cannot localize Horner syndrome; if Horner syndrome suspected, obtain MRI of entire oculosympathetic axis, not just brain; syndrome includes denervation hypersensitivity of α1 receptors in pupil dilator muscles; apraclonidine an α2 agonist with weak α1 affinity; if administration leads to reversal of anisocoria, patient likely has Horner syndrome; if MRI done on brain only, will miss lethal sequelae of syndrome (eg, Pancoast tumor of lung, extracranial carotid dissection); MRI should encompass area from hypothalamus to T2 vertebrae; request that radiologist design Horner protocol in preparation for eventual patient; information in radiology literature