Update on General Medicine PDF 2015-2016 BCSC

 The American Academy of Ophthalmology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Academy of Ophthalmology designates this enduring material for a maximum of 10 AMA PRA Category 1 Credits™. Ph...

 The American Academy of Ophthalmology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Academy of Ophthalmology designates this enduring material for a maximum of 10 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. CME expiration date: June 1, 2018. AMA PRA Category 1 Credits™ may be claimed only once between June 1, 2015, and the expiration date. BCSC® volumes are designed to increase the physician’s ophthalmic knowledge through study and review. Users of this activity are encouraged to read the text and then answer the study questions provided at the back of the book. To claim AMA PRA Category 1 Credits™ upon completion of this activity, learners must demonstrate appropriate knowledge and participation in the activity by taking the posttest for Section 1 and achieving a score of 80% or higher. For further details, please see the instructions for requesting CME credit at the back of the book. The Academy provides this material for educational purposes only. It is not intended to represent the only or best method or procedure in every case, nor to replace a physician’s own judgment or give specific advice for case management. Including all indications, contraindications, side effects, and alternative agents for each drug or treatment is beyond the scope of this material. All information and recommendations should be verified, prior to use, with current information included in the manufacturers’ package inserts or other independent sources, and considered in light of the patient’s condition and history. Reference to certain drugs, instruments, and other products in this course is made for illustrative purposes only and is not intended to constitute an endorsement of such. Some material may include information on applications that are not considered community standard, that reflect indications not included in approved FDA labeling, or that are approved for use only in restricted research settings. The FDA has stated that it is the responsibility of the physician to determine the FDA status of each drug or device he or she wishes to use, and to use them with appropriate, informed patient consent in compliance with applicable law. The Academy specifically disclaims any and all liability for injury or other damages of any kind, from negligence or otherwise, for any and all claims that may arise from the use of any recommendations or other information contained herein. AAO, AAOE, American Academy of Ophthalmology, Basic and Clinical Science Course, BCSC, EyeCare America, EyeNet, EyeSmart, EyeWiki, Focal Points, IRIS, ISRS, OKAP, ONE, Ophthalmic Technology Assessments, Ophthalmology, Preferred Practice Pattern, ProVision, SmartSight, The Ophthalmic News & Education Network, and The Eye M.D. Association are, among other marks, the registered trademarks and trademarks of the American Academy of Ophthalmology. Cover image: From BCSC Section 12, Retina and Vitreous. Ultra-wide-field fundus photograph from a patient with von Hippel–Lindau disease. Courtesy of Colin A. McCannel, MD. Copyright © 2015 American Academy of Ophthalmology All rights reserved Basic and Clinical Science Course Louis B. Cantor, MD, Indianapolis, Indiana, Senior Secretary for Clinical Education Christopher J. Rapuano, MD, Philadelphia, Pennsylvania, Secretary for Ophthalmic Knowledge George A. Cioffi, MD, New York, New York, BCSC Course Chair Section 1 Faculty Herbert J. Ingraham, MD, Chair, Danville, Pennsylvania A. Luisa Di Lorenzo, MD, Troy, Michigan Maria Jancevski, MD, Birmingham, Michigan Jaclyn L. Kovach, MD, Naples, Florida Maria A. Woodward, MD, Ann Arbor, Michigan A. Jan Berlin, MD, Consultant, Portland, Maine Steven L. Mansberger, MD, MPH, Consultant, Portland, Oregon The Academy wishes to acknowledge the following committees for review of this edition: Vision Rehabilitation Committee: John D. Shepherd, MD, Omaha, Nebraska Practicing Ophthalmologists Advisory Committee for Education: Steven J. Grosser, MD, Primary Reviewer, Golden Valley, Minnesota; James M. Mitchell, MD, Primary Reviewer, Edina, Minnesota; Edward K. Isbey III, MD, Chair, Asheville, North Carolina; Alice Bashinsky, MD, Asheville, North Carolina; David J. Browning, MD, PhD, Charlotte, North Carolina; Robert G. Fante, MD, Denver, Colorado; Bradley Fouraker, MD, Tampa, Florida; Dasa Gangadhar, MD, Wichita, Kansas; James A. Savage, MD, Memphis, Tennessee European Board of Ophthalmology: Bahram Bodaghi, MD, PhD, EBO Chair, Paris, France; Christina N. Grupcheva, MD, PhD, FEBO, EBO Liaison, Varna, Bulgaria; Sébastien Abad, MD, PhD, Paris, France; Boris Bienvenu, MD, PhD, Caen, France; Sylvain Choquet, MD, Paris, France; Michel Drancourt, MD, PhD, Marseille, France; Thomas Hanslik, MD, PhD, Brest, France; Pierre Hausfater, MD, PhD, Paris, France; Gerard Helft, MD, PhD, Paris, France; Ina Kötter, MD, PhD, Hamburg, Germany; Frédérique Kuttenn, MD, Paris, France; Anne Leger, MD, Paris, France; David Saadoun, MD, PhD, Paris, France; Damien Sène, MD, PhD, Paris, France; Pascal Sève, MD, PhD, Lyon, France; Hélène Vallet, MD, Paris, France Financial Disclosures Academy staff members who contributed to the development of this product state that within the past 12 months, they have had no financial interest in or other relationship with any entity discussed in this course that produces, markets, resells, or distributes ophthalmic health care goods or services consumed by or used in patients, or with any competing commercial product or service. The authors and reviewers state that within the past 12 months, they have had the following financial relationships:* Dr Bienvenu: Crossject (C, L), CSL Behring (C), Genzyme (C), Octapharma (C), Sanofi (C) Dr Bodaghi: Abbott Medical Optics (C), Allergan (C, S), Bausch + Lomb Surgical (C), Novartis Pharmaceuticals (S), Santen (C), Xoma (C) Dr Browning: Aerpio (S), Alimera Sciences (C), Diabetic Retinopathy Clinical Research (S), Genentech (S), Novartis Pharmaceuticals (S), Pfizer (S), Regeneron Pharmaceuticals (S) Dr Choquet: Celgene (L), Janssen (L), Roche France (C) Dr Fante: Ophthalmic Mutual Insurance Company (C) Dr Fouraker: Addition Technology (C), Alcon Laboratories (C), Keravision (C), Ophthalmic Mutual Insurance Company (C) Dr Grosser: Ivantis (O) Dr Grupcheva: Johnson & Johnson (L), Laboratoires Théa (L) Dr Helft: Abbott (L), AstraZeneca (L), Bayer (L), Boehringer Ingelheim (C, L) Dr Isbey: Alcon Laboratories (S), Allscripts (C), Bausch + Lomb (S), Medflow (C) Dr Jancevski: Aldeyra Therapeutics (C) Dr Kötter: AbbVie (L), Actelion (L), Bristol-Myers Squibb (L), Chugai (L), Novartis (S), Pfizer (L), Roche (S), UCB (L) Dr Mansberger: Alcon Laboratories (C), Allergan (C, S), Envisia Therapeutics (C), Mobius (S), National Eye Institute (S), Santen (C) Dr Savage: Allergan (L) Dr Sève: Actelion (C), GSK (L), Pfizer (L), Sobi (L) Dr Woodward: National Eye Institute (S) *C = consultant fees, paid advisory boards, or fees for attending a meeting; L = lecture fees (honoraria), travel fees, or reimbursements when speaking at the invitation of a commercial sponsor; O = equity ownership/​stock options of publicly or privately traded firms (excluding mutual funds) with manufacturers of commercial ophthalmic products or commercial ophthalmic services; P = patents and/or royalties that might be viewed as creating a potential conflict of interest; S = grant support for the past year (all sources) and all sources used for a specific talk or manuscript with no time limitation The other authors and reviewers state that within the past 12 months, they have had no financial interest in or other relationship with any entity discussed in this course that produces, markets, resells, or distributes ophthalmic health care goods or services consumed by or used in patients, or with any competing commercial product or service. Recent Past Faculty James P. Bolling, MD Anne Louise Coleman, MD, PhD Eric P. Purdy, MD Gwen Sterns, MD Jonathan Walker, MD In addition, the Academy gratefully acknowledges the contributions of numerous past faculty and advisory committee members who have played an important role in the development of previous editions of the Basic and Clinical Science Course. American Academy of Ophthalmology Staff Dale E. Fajardo, EdD, MBA Beth Wilson, CHCP Vice President, Education Director, CME, Programs & Acquisitions Daniel Mummert Christine A. Arturo Director, Online Education & the Acquisitions Manager ONE Network Jasmine Chen Stephanie Tanaka Manager, E-Learning Publications Manager, BCSC Eric Gerdes D. Jean Ray Interactive Designer Production Manager Donna Scism Ann McGuire E-Editor/Proofreader Medical Editor, BCSC Crissa Williams Administrative Coordinator, BCSC 655 Beach Street Box 7424 San Francisco, CA 94120-7424 Contents Title Page Copyright Page Faculty and Disclosures General Introduction Visual Acuity Chart Objectives 1 Using Statistics in Clinical Practice Researching Answers to Clinical Questions Crucial Questions in Study Evaluation Understanding Study Design Case Reports Case Series Case-Control Studies Cross-sectional Studies Cohort Studies Clinical Trials Systematic Reviews and Meta-analyses of Clinical Trials Interpreting Diagnostic and Screening Tests The Straightforward Case Complicating Features Summary Discussing Benefits, Risks, Probabilities, and Expected Outcomes With Patients Applying Statistics to Measure and Improve Clinical Practice Issues in Designing a Measurement System Implementation of a Monitoring System Analysis of the Results Methods of Presenting Data to Facilitate Continuous Improvement Other Features of Continuous Quality Improvement Summary 2 Endocrine Disorders Recent Developments Diabetes Mellitus  Basics of Glucose Metabolism Definition, Diagnosis, and Screening Classification Clinical Presentation of Diabetes Mellitus Prevention of Diabetes Mellitus Management Complications of Diabetes Mellitus Ophthalmic considerations Thyroid Disease Physiology Testing for Thyroid Disease Hyperthyroidism Hypothyroidism Thyroiditis Thyroid Tumors Disorders of the Hypothalamic-Pituitary Axis Pituitary Adenomas Pituitary Apoplexy Multiple Endocrine Neoplasia Syndromes 3 Hypertension Recent Developments Introduction Classification of Blood Pressure and Diagnosis of Hypertension Etiology and Pathogenesis of Hypertension Evaluation of Patients With Hypertension Treatment of Hypertension Lifestyle Modifications Pharmacologic Treatment Antihypertensive Drugs Diuretics Angiotensin-Converting Enzyme Inhibitors Angiotensin II Receptor Blockers Calcium Channel Blockers β-Blockers α1-Blockers Combined α-Adrenergic and β-Adrenergic Antagonists Centrally Acting Adrenergic Drugs  Direct Vasodilators Combination Therapy Direct Renin Inhibitors Parenteral Antihypertensive Drugs Future Treatments and Targets for Hypertension Special Considerations Resistant Hypertension Ischemic Heart Disease Heart Failure Diabetes Mellitus and Hypertension Chronic Renal Disease Cerebrovascular Disease Obesity and the Metabolic Syndrome Obstructive Sleep Apnea Syndrome Left Ventricular Hypertrophy Peripheral Arterial Disease Ophthalmic considerations Orthostatic Hypotension Hypertension in Older Patients Women and Pregnancy Children and Adolescents Racial and Ethnic Variations in Hypertension in the United States Withdrawal Syndromes Hypertensive Crisis Ophthalmic considerations 4 Hypercholesterolemia and Cardiovascular Risk Recent Developments Introduction Lipoproteins, Cholesterol, and Cardiovascular Disease Risk Assessment Management The Role of Statins Metabolic Syndrome Ophthalmic considerations 5 Acquired Heart Disease Recent Developments  Ischemic Heart Disease Pathophysiology Risk Factors for Coronary Artery Disease Clinical Syndromes Noninvasive Cardiac Diagnostic Procedures Invasive Cardiac Diagnostic Procedures Management of Ischemic Heart Disease Congestive Heart Failure Symptoms Clinical Signs Diagnostic Evaluation Etiology Pathophysiology and Clinical Course Medical and Nonsurgical Management Invasive or Surgical Management Disorders of Cardiac Rhythm Bradyarrhythmias and Conduction Disturbances Premature Contractions Tachyarrhythmias Ophthalmic considerations 6 Cerebrovascular Disease Recent Developments Introduction Cerebral Ischemia Diagnosis and Management Carotid Occlusive Disease Intracranial Hemorrhage 7 Pulmonary Diseases Recent Developments Introduction Obstructive Lung Diseases Restrictive Lung Diseases Evaluation Treatment Nonpharmacologic Treatment Ophthalmic considerations  Pharmacologic Treatment Perioperative Considerations 8 Hematologic Disorders Recent Developments Blood Composition Erythropoiesis Anemia Iron Deficiency Anemia Inflammatory Anemia The Thalassemias Sideroblastic Anemia Vitamin B12 Deficiency Folic Acid Deficiency Hemolytic Anemias Disorders of Hemostasis Laboratory Evaluation of Hemostasis and Blood Coagulation Clinical Manifestations of Hemostatic Abnormalities Vascular Disorders Ophthalmic considerations Platelet Disorders Disorders of Blood Coagulation Primary Hypercoagulable States Ophthalmic considerations Secondary Hypercoagulable States 9 Rheumatic Disorders Recent Developments Introduction Rheumatoid Arthritis Spondyloarthropathies Ankylosing Spondylitis Reactive Arthritis Ophthalmic considerations Other Spondyloarthropathies Juvenile Idiopathic Arthritis Systemic Lupus Erythematosus Diagnosis  Ophthalmic considerations Antiphospholipid Antibody Syndrome Diagnosis Ophthalmic considerations Treatment Systemic Sclerosis Ophthalmic considerations Sjögren Syndrome Polymyositis and Dermatomyositis Relapsing Polychondritis Vasculitis Large-vessel Vasculitis Ophthalmic considerations Medium-sized–vessel Vasculitis Ophthalmic considerations Small-vessel Vasculitis Variable-vessel Vasculitis Ophthalmic considerations Medical Therapy for Rheumatic Disorders Corticosteroids Nonsteroidal Anti-inflammatory Drugs Methotrexate Leflunomide Hydroxychloroquine Sulfasalazine Gold Salts Anticytokine Therapy and Other Immunosuppressive Agents 10 Geriatrics Physiologic Aging and Pathologic Findings of the Aging Eye Outpatient Visits Elder Abuse Perioperative Considerations in the Management of Elderly Patients Psychology of Aging Normal Aging Changes Depression Alzheimer Disease and Dementia Osteoporosis  Falls 11 Behavioral and Neurologic Disorders Recent Developments Introduction Behavioral Disorders Mental Disorders Due to a General Medical Condition Schizophrenia Mood Disorders Somatoform Disorders Substance Abuse Disorders Ophthalmic considerations Pharmacologic Treatment of Psychiatric Disorders Antipsychotic Drugs Ophthalmic considerations Antianxiety and Hypnotic Drugs Ophthalmic considerations Ophthalmic considerations Neurologic Disorders Parkinson Disease Ophthalmic considerations Multiple Sclerosis Epilepsy Ophthalmic considerations Stroke Pain Syndromes Alzheimer Disease and Dementia Ophthalmic considerations 12 Preventive Medicine Recent Developments Screening Procedures Cardiovascular Diseases Cancer Infectious Diseases Immunization Hepatitis Influenza  Varicella-Zoster Measles Mumps Rubella Polio Tetanus and Diphtheria Pneumococcal Pneumonia Haemophilus influenzae Meningococcus Human Papillomavirus Travel Immunizations New and Future Vaccines 13 Cancer Recent Developments Introduction Etiology Radiation Therapy Ophthalmic considerations Chemotherapy Natural Products Angiogenesis Inhibitors Biologic Therapies Ophthalmic considerations 14 Infectious Diseases Recent Developments General Microbiology Staphylococcus Streptococcus Clostridium difficile Haemophilus influenzae Neisseria Pseudomonas aeruginosa Treponema pallidum Stages Diagnosis Management  Borrelia burgdorferi Stages Diagnosis Management Chlamydia trachomatis Mycoplasma pneumoniae Mycobacteria Tuberculosis Fungal Infections Toxoplasma Herpesvirus Herpes Simplex Varicella-Zoster Cytomegalovirus Ophthalmic considerations Epstein-Barr Virus Influenza Hepatitis Hepatitis A and B Hepatitis C and Other Forms of Hepatitis Human Papillomavirus Acquired Immunodeficiency Syndrome Etiology and Pathogenesis Clinical Syndromes Diagnosis Modes of Transmission Prognosis and Treatment Opportunistic Infections Ophthalmic considerations Update on Antibiotics Antibacterial Agents New Antibiotic Classes Antifungal Agents Antiviral Agents 15 Perioperative Management in Ocular Surgery Recent Developments Introduction  Preoperative Assessment Children and Adolescents Medication Use in the Preoperative Period Diabetes Mellitus Respiratory Diseases Preoperative Fasting Latex Allergy Universal Protocol Intraoperative Considerations Systemic Anesthetic Agents Local Anesthetic Agents Malignant Hyperthermia 16 Medical Emergencies and Ocular Adverse Effects of Systemic Medications Recent Developments Introduction Cardiopulmonary Arrest Syncope Shock Classification Assessment Treatment Anaphylaxis Seizures and Status Epilepticus Toxic Reactions to Local Anesthetic Agents and Other Drugs Ocular Adverse Effects of Systemic Medications Basic Texts Related Academy Materials Requesting Continuing Medical Education Credit Create a Self Test General Introduction The Basic and Clinical Science Course (BCSC) is designed to meet the needs of residents and practitioners for a comprehensive yet concise curriculum of the field of ophthalmology. The BCSC has developed from its original brief outline format, which relied heavily on outside readings, to a more convenient and educationally useful self-contained text. The Academy updates and revises the course annually, with the goals of integrating the basic science and clinical practice of ophthalmology and of keeping ophthalmologists current with new developments in the various subspecialties. The BCSC incorporates the effort and expertise of more than 80 ophthalmologists, organized into 13 Section faculties, working with Academy editorial staff. In addition, the course continues to benefit from many lasting contributions made by the faculties of previous editions. Members of the Academy’s Practicing Ophthalmologists Advisory Committee for Education, Committee on Aging, and Vision Rehabilitation Committee review every volume before major revisions. Members of the European Board of Ophthalmology, organized into Section faculties, also review each volume before major revisions, focusing primarily on differences between American and European ophthalmology practice. Organization of the Course The Basic and Clinical Science Course comprises 13 volumes, incorporating fundamental ophthalmic knowledge, subspecialty areas, and special topics: 1 Update on General Medicine 2 Fundamentals and Principles of Ophthalmology 3 Clinical Optics 4 Ophthalmic Pathology and Intraocular Tumors 5 Neuro-Ophthalmology 6 Pediatric Ophthalmology and Strabismus 7 Orbit, Eyelids, and Lacrimal System 8 External Disease and Cornea 9 Intraocular Inflammation and Uveitis 10 Glaucoma 11 Lens and Cataract 12 Retina and Vitreous 13 Refractive Surgery References Readers who wish to explore specific topics in greater detail may consult the references cited within each chapter and listed in the Basic Texts section at the back of the book. These references are intended to be selective rather than exhaustive, chosen by the BCSC faculty as being important, current, and readily available to residents and practitioners. Study Questions and CME Credit Each volume of the BCSC is designed as an independent study activity for ophthalmology residents and practitioners. The learning objectives for this volume are given following this General Introduction. The text, illustrations, and references provide the information necessary to achieve the objectives; the study questions allow readers to test their understanding of the material and their mastery of the objectives. Physicians who wish to claim CME credit for this educational activity may do so online by following the instructions at the end of the book. Conclusion The Basic and Clinical Science Course has expanded greatly over the years, with the addition of much new text and numerous illustrations. Recent editions have sought to place a greater emphasis on clinical applicability while maintaining a solid foundation in basic science. As with any educational program, it reflects the experience of its authors. As its faculties change and as medicine progresses, new viewpoints are always emerging on controversial subjects and techniques. Not all alternate approaches can be included in this series; as with any educational endeavor, the learner should seek additional sources, including such carefully balanced opinions as the Academy’s Preferred Practice Patterns. The BCSC faculty and staff are continually striving to improve the educational usefulness of the course; you, the reader, can contribute to this ongoing process. If you have any suggestions or questions about the series, please do not hesitate to contact the faculty or the editors. The authors, editors, and reviewers hope that your study of the BCSC will be of lasting value and that each Section will serve as a practical resource for quality patient care.  Objectives Upon completion of BCSC Section 1, Update on General Medicine, the reader should be able to describe the various factors to consider in critically reviewing clinical research explain the importance of the randomized, controlled clinical study in evaluating the effects of new treatments describe the classification, pathophysiology, and presentation of diabetes mellitus, as well as the diagnostic criteria for this disease describe the various therapeutic approaches for diabetes mellitus, including new insulins and oral agents classify the levels of hypertension by blood pressure measurements list the major classes of antihypertensive medications and some of their characteristics and adverse effects discuss the indications for dietary and pharmacologic treatment of hypercholesterolemia describe the various diagnostic procedures used in the evaluation of patients with coronary artery disease state the current treatment options for ischemic heart disease, heart failure, and cardiac arrhythmias list the common causes of stroke in patients encountered by ophthalmologists distinguish between obstructive and restrictive, reversible and irreversible, pulmonary diseases, and give examples of each type discuss the major behavioral disorders and possible therapeutic modalities for these conditions (including the ocular adverse effects of psychoactive medications) list some of the factors associated with a patient’s adherence or nonadherence to medical regimens explain the rationale for and value of screening programs for various systemic diseases discuss the major disease processes affecting most of the adult population, and briefly explain how preventive measures may reduce the morbidity and mortality that these diseases cause list the most prevalent types of cancer for men and for women together with the appropriate screening methods for detecting them describe current concepts about the etiologies of most malignancies describe traditional as well as more novel approaches to the treatment of various types of cancer describe the ophthalmic manifestations of the major systemic diseases covered in this volume list the most common human pathogens and their manifestations discuss the epidemiology, clinical features, and treatment of human immunodeficiency virus infection list the newer antiviral, antifungal, and antibacterial agents and their benefits and adverse effects describe the early manifestations and treatment of malignant hyperthermia describe the current American Heart Association guidelines for performing cardiopulmonary resuscitation CHAPTER 1 Using Statistics in Clinical Practice Ophthalmologists use clinical research to establish best practices for patient care. Clinical research can be complex, requiring an interdisciplinary group of clinicians, statisticians, and epidemiologists to design the study, analyze the data, and interpret the results. Researchers choose a study design based on the research questions, the population available, and the required resources and effort. This chapter will help the clinician understand how to critically review clinical research and apply the results in the clinical practice of ophthalmology. Researching Answers to Clinical Questions Formulating the clinical question is the first step in resolving a diagnostic or management issue. Examples of clinical questions in ophthalmology include: What is the prevalence of glaucoma in African Americans? Do racial and ethnic minority populations in the United States have a higher risk of proliferative vitreoretinopathy after pars plana vitrectomy? What is the expected survival of a corneal graft in a patient with Fuchs dystrophy? Clinicians can use several sources of information to research the answers to their questions. These include general textbooks on ophthalmology (eg, Duane’s Ophthalmology), journals with detailed reviews on specific subjects (eg, Survey of Ophthalmology [www.surveyophthalmol.com]), and educational material from the American Academy of Ophthalmology (www.aao.org/one) (eg, Preferred Practice Pattern guidelines, Focal Points modules). In addition, clinicians can use the Cochrane Library ( www.thecochranelibrary.com) to access high-quality meta-analyses regarding specific management issues (eg, surgery for nonarteritic ischemic optic neuropathy, intervention for involutional lower-eyelid ectropion). For more specific questions and data, clinicians can search online for primary sources of information using PubMed (www.ncbi.nlm.nih.gov/pubmed). PubMed provides detailed instructions on using appropriate keywords. PubMed usually identifies the type of study: from laboratory-based studies of basic science (eg, cell culture, molecular biology) to animal studies (eg, testing of new drugs or specific surgical techniques) to clinical studies (eg, case reports, case series, randomized controlled trials). The search can be narrowed based on the type of study desired. In evaluating a published study, and before committing time to critical reading, the clinician should review the abstract for the study purpose and methods to ascertain whether the study addresses the question of interest. For example, if the clinician is interested in determining whether use of a prostaglandin is beneficial in patients with open-angle glaucoma (OAG), examining data from the Early Manifest Glaucoma Trial (EMGT) would not be useful because prostaglandins were not used in the EMGT. Data from specific drug trials, on the other hand, would be pertinent. However, if the question is whether lowering intraocular pressure (IOP) is beneficial in patients with OAG, then both types of studies might be useful. Crucial Questions in Study Evaluation This section describes the steps to take to discern whether the study is valid and applicable to the clinician’s specific patients rather than applicable to only specific types of patients. Also, it is necessary to consider the recruitment strategy and characteristics of the study participants, sample size, intervention, outcomes of interest, and statistical methods used. Are the results generalizable to my patients? Is there a clear description of the process of selecting study participants (which patients were included or excluded)? This description lays the groundwork for understanding the setting of the study. Was it a clinic-based, multicenter, or community-based trial? For therapeutic trials, patient inclusion and exclusion criteria outline characteristics of those who were or were not treated with an intervention. Specific patient groups may have been excluded because they were considered a vulnerable population. For example, most trials of ocular hypotensive drugs exclude children and pregnant women; as a result, there are minimal data on the safety and efficacy of most ocular hypotensive agents in these 2 groups of patients. Thus, if the clinician must decide whether to use a specific ocular hypotensive agent in a pregnant woman or in a child, most of the evidence can be found only in individual case reports or retrospective case series. The clinician must next ascertain whether the results can be directly applied to particular patients. The first step in this process is exploring whether the study created selection bias by assigning the intervention to certain participants. Was the intervention randomly assigned? Was the treated group comparable to the control group? The purpose of randomly assigning an intervention to participants is to minimize bias on the part of the investigators and the patient. For example, an investigator may create selection bias by inadvertently enrolling less complex patients for a new surgery, potentially biasing their outcomes toward better results. Random allocation reduces the likelihood of selection bias. However, it does not always ensure that the participants assigned to each group are similar. To answer this question, the clinician must examine baseline participant characteristics that may affect the outcome. For example, when evaluating a study assessing the effect of lasers for treatment of diabetic retinopathy, the clinician should examine whether patients’ hemoglobin A1c levels, blood pressure, and other factors are similar between study groups, as these factors may alter the progression of retinopathy. Use of a control group is also important because it indicates whether the results of the intervention are above and beyond the effects of participants’ enrollment in a trial. The severity of disease is another factor to consider to establish whether the results can be applied to the clinician’s patients. Did the study include only a single disease severity group, or did it include different stages of disease, such as mild, moderate, and severe disease? Clinical trials may study a narrow subset of a disease, making the results applicable and generalizable only to similar patients. A common error is extrapolating such data to all patients and their varying degrees of disease severity. For example, if a particular treatment effect size is noted in patients with mild glaucomatous damage who underwent trabeculectomy but not in those with advanced glaucomatous damage, the study results should be applied only to similar patients—in this case, patients with mild glaucomatous damage. Was the sample large enough to detect a difference? Was the sample size (the number of participants in the study) established before the trial began and, if so, what criteria were used to determine the sample size? The sample size must have enough power to reject the null hypothesis. The null hypothesis is no difference (in the outcome of interest) exists in the group that received the intervention compared with the group that did not receive the intervention. A study must have enough power to reject the null hypothesis if a true difference exists between the groups. Power depends on the sample size, the expected difference in the outcome of interest (eg, improvement in visual acuity, resolution of macular edema) in the intervention group compared with the control group, and the variability (eg, standard deviation) of the outcome of interest. In general, an intervention with a larger treatment effect and smaller variability requires a smaller sample size. Is the intervention reproducible? The study should describe the intervention in enough detail to allow the experiment to be replicated. For example, a surgical study should explain all the steps of the procedure to allow different surgeons to perform it in the same manner in each case. Did all surgeons involved in the study perform it similarly, and were all of their results similar? Did the study include a training session before the start of the study, monitor specific aspects of the surgical procedure, and standardize postoperative care? In general, a study should avoid differences in study procedures except in regard to the intervention of interest. Is the outcome clearly defined and reliable? The outcomes of interest are usually specific to the disease being studied. At the outset of a study, the primary and secondary outcomes should be clearly stated. These outcomes are then used to determine whether the study was able to prove or disprove the null hypothesis. In most studies, the outcome of interest, as well as the expected change in this outcome, must be defined. For example, if the primary outcome is improvement in visual acuity, the study should indicate the logMAR value that represents improvement, the range, the distribution of results (eg, normal, skewed to the right or left), and the variability. Many outcomes (eg, visual acuity, IOP, macular thickness as measured with optical coherence tomography [OCT]) will have measurement error. This measurement error will increase the variability of the outcome of interest or create a difference in results when no true difference in outcomes exists. Therefore, a study should standardize measurement of the outcome of interest for all investigators. For example, the Ocular Hypertension Treatment Study created a standardized method to check IOP. The “recorder” placed the tonometry dial at 20 mm Hg while an “observer” measured the IOP and adjusted the dial to the intersection of the tonometry mires without viewing the dial. Finally, the recorder recorded the IOP measurement and changed the dial back to 20 mm Hg, then repeated the measurement sequence. The sequence was repeated a third time if the measurements differed by 2 mm Hg. By using a masked recorder and observer and repeating testing, the study created a standardized method intended to decrease measurement error and the variability of IOP measurement. Also, the study should try to mask the observer to the intervention to decrease the risk of investigator bias. Investigator bias may occur when the investigator expects a different result in the intervention group and adjusts his or her measurement of the outcome of interest to satisfy this expectation. Instead, a study should measure the outcome of interest as accurately and reliably as possible. If it does not, the study may underestimate or overestimate the effect of the intervention or encounter higher variability in the outcome of interest, affecting the conclusion of the study. Was the follow-up long enough? The validity of a study is anchored on (1) adequate duration of follow-up and (2) follow-up of all participants. Thus, in evaluating a study, the clinician should ask, How many of the participants completed follow-up? Did the study report outcomes for all participants? For example, in a study assessing the use of atropine eyedrops versus patching for treatment of amblyopia, a follow-up of 3– 6 months may be adequate; similar follow-up periods may be appropriate for tracking macular edema resolution after laser or drug therapy or visual acuity improvement after cataract extraction. Conversely, glaucoma progresses over long periods; therefore, trials assessing visual field loss in glaucoma would require longer follow-up, such as 5 years. Consequently, the typical rate of disease progression is an important guide in establishing the duration of follow-up required. The study should report the results for all participants. This may not be practical or feasible in all cases because of dropout from a study (eg, due to death during follow-up). The study should report the reasons for loss to follow-up and report any differences in reasons between the study groups. For example, participants in the intervention group of a drug trial may be more likely to drop out than those in the placebo group if they experience ocular adverse effects from the drug, such as burning or stinging. Are the treatments and outcomes clinically relevant? The clinician should ascertain whether the study’s results can be applied to his or her patients. Questions to consider include the following: Is the intervention available and applicable to the current practice environment? Are the outcomes clinically important? Are all clinically important outcomes evaluated? Is the treatment difference clinically significant? It is important to consider whether the intervention is useful in practice. It may be too expensive, too difficult to perform, or no longer in general use. If so, the study may pose little benefit to current clinical care. Is the analysis appropriate for the outcome? Statistical tests depend on the type of data used to determine the difference between 2 treatment groups. If the data are normally distributed (ie, they conform more or less to a bell-shaped curve) and are continuous (eg, macular thickness in a trial assessing the use of intravitreal corticosteroids for treatment of diabetic macular edema), then a Student t-test comparing the intervention and control groups can be performed. For continuous data that are not normally distributed, researchers can utilize nonparametric tests such as the Wilcoxon rank sum test. For categorical data (present or absent; small, medium, or large), the study may use a chi-square test. All of these tests provide a P value, which indicates the likelihood that a difference between the 2 groups is due to chance alone. Thus, a P value of