Health care stakeholder perceptions of vision loss

Health care stakeholder perceptions of vision loss

Accepted Manuscript Healthcare Stakeholder Perceptions of Vision Loss Gary C. Brown, MD, MBA, Melissa M. Brown, MD, MN, MBA PII: S0039-6257(18)30046-...

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Accepted Manuscript Healthcare Stakeholder Perceptions of Vision Loss Gary C. Brown, MD, MBA, Melissa M. Brown, MD, MN, MBA PII:

S0039-6257(18)30046-8

DOI:

https://doi.org/10.1016/j.survophthal.2018.11.001

Reference:

SOP 6828

To appear in:

Survey of Ophthalmology

Received Date: 21 February 2018 Revised Date:

6 November 2018

Accepted Date: 8 November 2018

Please cite this article as: Brown GC, Brown MM, Healthcare Stakeholder Perceptions of Vision Loss, Survey of Ophthalmology (2018), doi: https://doi.org/10.1016/j.survophthal.2018.11.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Healthcare Stakeholder Perceptions of Vision Loss

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Gary C. Brown, MD, MBA1-4

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Melissa M. Brown, MD, MN, MBA1-4

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From the Center for Value-Based Medicine®,1 Hilton Head, SC, Wills Eye Hospital,2 Jefferson Medical University, Philadelphia, PA, The Philadelphia Retinal Endowment Fund,3 Philadelphia, PA and the Department of Ophthalmology,4 Emory University School of Medicine, Atlanta, GA.

Disclosures: The authors have no conflicts of interests to declare relevant to the material presented herein. Drs. G. Brown and M. Brown are both shareholders in the Center for Value-Based Medicine®. No funding was received for this project.

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Corresponding Author: Gary C. Brown, MD, MBA Center for Value-Based Medicine®, Box 3417, Hilton Head, SC 29928. E-mail: [email protected]

11-06-18

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Abstract

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Perceptions of the quality-of-life (QOL) associated with vision loss vary widely. Herein, we

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consider the perceptions of patients with vision loss as the criterion for QOL quantification

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associated with vision loss. With the QOL instrument, time tradeoff utility analysis, the upper

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anchor of 1.00 is associated with permanent normal vision, while the lower anchor of 0.00 is

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associated with death. A time tradeoff utility of 0.26 is associated with no light perception

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bilaterally. Patients with legal blindness in the U.S. (< 20/200 vision bilaterally) have a mean time

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tradeoff utility of 0.47. The general public, however, associates legal blindness with a time

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tradeoff utility of 0.86. Thus, legally blind patients consider their QOL loss from blindness to be

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279% [(1.00-0.47/(1.00-0.86)] worse than does the American public. Public estimates of the QOL

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loss from blindness (utility=0.86) suggest it is less debilitating than patient QOL estimates for

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migraine headaches (utility=0.83). The mean medical student blindness utility estimate is 0.86,

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while that for non-ophthalmic physicians is 0.82. Ophthalmologists underestimated the QOL

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associated with vision loss in macular degeneration patients by 96%-750%. Underestimating the

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QOL loss from blindness likely diminishes the perceived benefit of blindness interventions.

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Minimization of interventional benefit by underestimating patient impairment from vision loss

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could lead to adverse consequences for patients with vision loss, vision research and those who

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treat vision loss.

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Abstract = 199 words

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ophthalmic patients

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public

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non-ophthalmic physicians

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medical students

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ophthalmologists

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perceptions of vision loss

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Introduction “Perception is reality” is an iconic phrase. One interpretation is that it means “the way a

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person sees the world is their truth, regardless of whether their conclusions are factually

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accurate or not.”1 Perceptions are gleaned from multiple factors. Often, perceptions about

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a group or other entity diverge dramatically, depending upon whom is evaluating it.16,32,64

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A major tool for assessing perceptions is polling. In a poll of 600 patients, the National

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Consumers League50 found that 30% of consumers, including those who wear glasses and

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contact lenses, believe optometrists have medical degrees. Fifty percent also believe

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optometrists are board certified, when licensure alone is typically required. The poll also

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noted that many prefer those with a medical degree for surgery, injections and prescribing

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medications.50 Thus, perceptions of the public about ophthalmologists vary, in part

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depending upon whether a person can differentiate an ophthalmologist from an

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optometrist.

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Perceptions can also be guided by inference. For example, if an ophthalmologist performs

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cataract surgery that dramatically improves a person’s vision and allows him or her to

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work and drive again, the person is likely to be pleased with the result. By inference, the

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same person is likely to have a high opinion of the surgeon who delivered the excellent

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result.32

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An instrument that numerically quantifies the quality-of-life (QOL) associated with a

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medical condition, in this instance vision loss, is utility analysis.2,5-19 It can also quantify

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the improvement in QOL conferred by a medical intervention, thus by inference likely

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influencing the patient perception of the person who administered the intervention.

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It is our intention herein to review data on the perceptions of different healthcare

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stakeholder cohorts on vision loss as it affects QOL. Sequelae of vision loss perceptions

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will also be addressed, especially in regard to interventions that reverse and prevent vision

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loss.

Quality-of-Life

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Utility analysis. Time tradeoff utility analysis, among others, has been used to quantify

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the vision-related, QOL improvement and cost-effectiveness (cost-utility) associated with

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multiple ophthalmic interventions.2,5-22-32,49.50,54,56,57,60,63,64 Utilities (time tradeoff, standard

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gamble, willingness-to-pay, multi-attribute, etc.) are often referred to as patient

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preferences, since a patient can theoretically prefer to give up something they value (time

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of life, lesser chance of death, money and so forth) to improve their health state or prefer

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to give up nothing and remain in the same health state.32 Utilities typically vary from

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anchors of 1.00 (normal bilateral vision permanently) to 0.00 (death).2,5-20,22-32,49.50,54,56,57,

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60,63,64

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bilaterally would cause vision utilities to not be comparable with those in other

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specialties, which routinely use the lower anchor of 0.00 to represent death.32 The closer a

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utility is to 1.00, the better the QOL associated with a condition, while the closer the

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utility is to 0.00, the poorer the QOL.28,32

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Using a lower utility anchor of 0.00 to represent no light perception vision

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Time tradeoff, vision utilities correlate most highly with vision in the better-seeing eye.5-

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20,22-32

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dramatically so at poorer visual acuity levels. Vision utilities are generally unaffected by

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the underlying cause of vision loss,29 gender,32 level of education,32 age,32 ethnicity,32 and

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the presence of systemic comorbidities.27,56 Highly reproducible at one month45 (intraclass

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correlation coefficient of 0.76) and one year14 (intraclass correlation coefficient of 0.52),

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time tradeoff vision utilities have been shown to have superior construct validity versus

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estimates from other QOL instruments, such as standard gamble utility analysis,

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willingness-to-pay utility analysis, and scaling methodology.32,60 Time tradeoff vision

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utilities are comparable across international borders.63 A list of time tradeoff vision

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utilities and time tradeoff utilities associated with non-ocular conditions is shown in Table

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As vision decreases in the better-seeing eye, the associated utility decreases,

Public Perception of Physicians

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A 2017 Gallup publication37 addressed Americans' ratings of honesty and ethical standards

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among professional in multiple job categories. The findings showed that 65% of medical

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doctors were viewed to have high or very high levels of honesty and ethical standards.

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Those with the highest honesty/ethical standards were nurses, with an 82% rating. They

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were followed by military officers (71%) and grade school teachers (66%). Among the

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lower performers were journalists (23%), HMO managers (12%) members of Congress

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(11%) and lobbyists (8%). A more complete list is shown in Table 2.

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Despite high public ethics and honesty perceptions, there are detractors for physicians.

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One Canadian study noted that 34% of the public were bothered by physician-

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pharmaceutical industry relationships, especially for: 1) fees paid by industry for

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recruiting patients for clinical studies and 2) using inside information about a new drug to

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make investment decisions.44 It has also been suggested that longer office waiting times65

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and/or communication differences between physicians and patients could contribute to

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conflict and/or distrust.36

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An Australian study showed that there was greater trust between patients and their primary

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care practitioner than between patients and specialists, not unexpected since most patients

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visit primary care physicians more often and thus have a closer relationship.43 The

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literature on comparisons of specific specialists with primary care doctors is scarce.

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Nonetheless, a dermatology study noted that, compared to dermatologists, primary care

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doctors were perceived to have a more critical profession by 63% of respondents, a more

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difficult job by 54% of respondents, and to work longer hours by 92% of those surveyed.3

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Dermatologists were also perceived to earn more than primary care physicians, but less

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than cardiologists or plastic surgeons.

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The perceptions of the QOL associated with vision loss from the perspectives of: 1)

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ophthalmic patients, 2) the general public, 3) non-ophthalmic physicians, 4) medical

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students and 5) ophthalmologists are discussed in the following sections. While there is

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certainly not a 100% correlation of perceptions of vision loss with perceptions of

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interventions to treat vision loss, the authors are of the opinion that non-ophthalmic

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stakeholders in healthcare will likely have a more positive opinion of these interventions if

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they perceive them to deliver considerable patient value (improvement in quality-of-life

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and/or length or life, though for ophthalmic interventions patient value is often defined by

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improvement in quality-of-life alone32), rather than patient value. If stakeholders perceive

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vision loss to be minimally disabling referent to other medical conditions, we believe they

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are less apt to consider interventions to correct and prevent vision loss as important and

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relevant. This could have adverse effects upon patients with vision loss, vision research,

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and those who deliver interventions to treat vision loss

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Ophthalmic Patient Perceptions of Vision Loss. The effect of patient vision loss upon

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QOL has been studied in detail with time tradeoff utility analysis.4-33 Time tradeoff

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utilities associated with various levels of vision loss in patients are shown in Table 1. The

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average patient undergoing cataract surgery in the better-seeing eye in 2013 was noted to

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have vision improvement from 20/83 (utility = 0.71) to 20/27 (utility = 0.858, including

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adverse events), a [(0.858 – 0.71)/0.71 =] 20.8% QOL gain associated with the surgery.12

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This is a considerable QOL gain compared to the 1-2% gain from interventions such as α-

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adrenergic blockers for prostatic hyperplasia and the 1.8% QOL gain from ibuprofen for

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the treatment of osteoarthritis (Table 3). A list of patient value gains associated with

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different healthcare interventions is shown in Table 3.

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In addition to the QOL gain delivered by ophthalmic interventions, the interventions can

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have a large financial return-on-investment (ROI) for the direct medical costs expended.

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For example, cataract surgery in 2013 had direct medical costs (physician, facility fees,

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drugs and so forth) of $2,653.12 If performed on a 20/83 better-seeing eye, it returned a net

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$121,198 to society over the direct medical costs. This was a 37.5% annual ROI on the

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direct medical costs expended and a 13-year ROI of 4,576%. The money returned to

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society, approximately 40% of which went to patients, came in the form of decreased

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wage loss, decreased trauma, decreased depression, less facility admissions, and decreased

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transportation, residence and activities of daily living costs made possible by better vision.

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Transportation, residence and activities of daily living costs can also be lumped into

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caregiver costs. The ROI numbers support the contention of William Nordhaus, the

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Nobel-winning economist who has written that medical advances accounted for 50% of

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the wealth created in the United States during the 20th century.53

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It is doubtful that most healthcare stakeholders appreciate the large costs associated with

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vision loss to 20/83, much less the $83,000 annual societal ophthalmic costs for a person

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with 20/800 or worse vision bilaterally.21 Patients with vision loss, however, do realize

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that increased costs are associated with poorer vision,21 possibly one factor that contributes

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to lower patient utilities associated with vision loss than the vision loss utility estimates

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from non-patient cohorts.64

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Ophthalmic Patient Perceptions of Vision Loss. The effect of patient vision loss upon

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QOL has been studied in detail with time tradeoff utility analysis.4-33 Time tradeoff

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utilities associated with various levels of vision loss in patients are shown in Table 1. The

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average patient undergoing cataract surgery in the better-seeing eye in 2013 was noted to

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have vision improvement from 20/83 (utility = 0.71) to 20/27 (utility = 0.858, including

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adverse events), a [(0.858 – 0.71)/0.71 =] 20.8% QOL gain associated with the surgery.12

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This is a considerable QOL gain compared to the 1-2% gain from interventions such as α-

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adrenergic blockers for prostatic hyperplasia and the 1.8% QOL gain from ibuprofen for

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the treatment of osteoarthritis (Table 3). A list of patient value gains associated with

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different healthcare interventions is shown in Table 3.

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In addition to the QOL gain delivered by ophthalmic interventions, the interventions can

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have a large financial return-on-investment (ROI) for the direct medical costs expended.

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For example, cataract surgery in 2013 had direct medical costs (physician, facility fees,

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drugs and so forth) of $2,653.12 If performed on a 20/83 better-seeing eye, it returned a net

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$121,198 to society over the direct medical costs. This was a 37.5% annual ROI on the

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direct medical costs expended and a 13-year ROI of 4,576%. The money returned to

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society, approximately 40% of which went to patients, came in the form of decreased

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wage loss, decreased trauma, decreased depression, less facility admissions, and decreased

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transportation, residence and activities of daily living costs made possible by better vision.

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Transportation, residence and activities of daily living costs can also be lumped into

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caregiver costs. The ROI numbers support the contention of William Nordhaus, the Yale

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economist who has written that medical advances accounted for 50% of the wealth created

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in the United States during the 20th century.52

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It is doubtful that most healthcare stakeholders appreciate the large costs associated with

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vision loss to 20/83, much less the $83,000 annual societal ophthalmic costs for a person

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with 20/800 or worse vision bilaterally.21 Patients with vision loss, however, do realize

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that increased costs are associated with poorer vision,21 possibly one factor that contributes

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to lower patient utilities associated with vision loss than the vision loss utility estimates

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from non-patient cohorts.64

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Non-Ophthalmic Physician Perceptions of Vision Loss. Stein et. al.64 also asked non-

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ophthalmic physicians to estimate the QOL loss associated with the same levels of AMD

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vision loss (mild, moderate and severe) presented to AMD patients and the public. The

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mean, non-ophthalmic physician, utility estimate for mild AMD vision loss (vision >

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20/30) was 0.93, while that for moderate AMD vision loss (vision 20/40-20/100) was

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0.88, and for severe AMD vision loss (vision < 20/200) was 0.82 (Table 4). There was a

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significant difference between AMD patient and non-ophthalmic physician mean utilities

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(p < 0.001) for the each of the mild, moderate and severe AMD vision loss levels, but no

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significant difference between the general public and non-ophthalmic physician cohorts

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for each of the three AMD vision loss severity levels.64

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These data suggest that non-ophthalmic physicians have a poor appreciation of the QOL

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associated with vision loss referent to patients. Non-ophthalmic physicians as a group

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believe loss of vision does not cause anywhere near the quality-of-life loss that patients

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with actual vision loss estimate. They therefore may be more likely to minimize the

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patient benefit conferred by ophthalmic interventions since they do not consider vision

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loss as particularly disabling, as is also the case for the general public.

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Medical Student Perceptions of Vision Loss. Chaudry et. al.34 studied the QOL

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perceptions of medical students about vision loss (Table 4). Medical student perceptions

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of the QOL diminution caused by vision loss were very similar to those of the general

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public and non-ophthalmic physicians, with no statistical difference between the three

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cohorts. Thus, they also dramatically underestimated the QOL diminution referent to

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actual AMD patients with different levels of vision loss (p < 0.0001). These data suggest

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that medical students are therefore also likely to minimize the patient benefit conferred by

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ophthalmic interventions.

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Ophthalmologist Perceptions of Vision Loss Referent to Those of Ophthalmic

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Patients16,32 Brown et al.16 measured the QOL estimates of ophthalmologists for different

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levels of AMD vision loss using time tradeoff utility analysis. These utilities were

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compared with those from AMD patients with different levels of vision loss. The results

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are shown in Table 5. Although the mean utilities are closer to those of AMD patients than

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the mean utilities of the general public, non-ophthalmologist physicians and medical

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students, they still differ significantly from those of the AMD patients (p < 0.001 for all

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levels of vision loss severity). For mild vision loss (20/20-20/40 in the better-seeing eye),

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the ophthalmologist mean utility estimate of 0.98 underestimated the AMD patient mean

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utility of 0.83 by 750%. Ophthalmologists underestimated the moderate vision loss

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(20/40-20/100) utility of AMD patients by 264%, the severe vision loss (< 20/200) utility

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by 96% and the very severe vision loss (< 20/800) utility by 103%.

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Zhu et. al.68 studied the time tradeoff utilities of diabetic patients with vision loss and

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those estimated by ophthalmologists and found that ophthalmologists also considerably

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underestimated the QOL diminution associated with diabetic retinopathic vision loss

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referent to patients. Despite the differences, the diabetic retinopathy vision utilities from

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Chinese patients were the same as the vision utilities from U.S. and Canadian diabetic

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patients,31,63 supporting the contention that that utilities are unique to human nature.32

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Differences between glaucoma patient utilities and ophthalmologist QOL estimates have

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also been noted.67

Data Interpretations

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Ophthalmic patient perceptions. Patient perceptions of the quality-of-life associated

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with vision loss suggest that many ophthalmic interventions confer considerable quality-of

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life gain. This is indeed the case for cataract surgery,12 vascular endothelial growth factor

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inhibitors for neovascular age-related macular degeneration,9 laser therapy for retinopathy

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of prematurity,15 topical glaucoma therapy,5 penetrating keratoplasty57 and other

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interventions.7,8

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It was demonstrated in 2014 by Christ and colleagues35 that poor vision is associated with

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increased mortality. Improving poor vision or maintaining vision with ophthalmic

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interventions can therefore improve length of life as well as quality-of-life.35 This

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phenomenon increases patient value gain (improvement in quality-of-life and/or length of

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life) from ophthalmic interventions.35 It has not been integrated into earlier cost-utility

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analyses.

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The authors herein believe that the considerable patient value delivered by ophthalmic

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interventions using patient vision utilities5.7-10,15,58 bodes well for these interventions in the

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future. Nonetheless, the assignment of less utility gain, as recommended by some4 for

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elderly and disabled patients, could derail the patient-derived value gains conferred by

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ophthalmic interventions. We very much opposed to this practice.

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General public perceptions. The First39 and Second4 Panels on Cost-Effectiveness in

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Health and Medicine recommended that utilities from the general community (public) be

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used in cost-utility analyses. The thinking of some economists in preferring public

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opinions for financial resource allocation is that patients might “game” the system and

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feign that their medical conditions are more debilitating than they believe they are,

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knowing that more resources would thus be directed toward their disease(s).32,39 Having

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personally collected over 30,000 patient utilities, the authors very much doubt this is the

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case. Select healthcare economists also believe that since the general public finances much

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of healthcare, the general public should have greater say in decisions that could affect the

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allocation of healthcare resources.32

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The consequences could be dramatic for interventions that reverse or prevent vision loss if

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future healthcare resource allocation decisions are based upon the preferences (utilities) of

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the general public, rather than upon the preferences of patients who have personally

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experienced vision loss.4,32,40 Utilizing a general community utility of 0.8664 for legal

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blindness (vision in the better eye of < 20/200) versus the 0.4716 utility from actual blind

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patients, would result in ophthalmic interventions for severe vision loss being undervalued

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by 279% referent to

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research dollars and/or to the physician Medicare Fee Schedule could have marked

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patient perceptions. Applying a 279% discount to ophthalmic

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adverse effects upon patients with vision loss, advancements from vision research, and

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those responsible for administering vision loss interventions.

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Non-ophthalmic physician perceptions. As seen from the data herein, our physician

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colleagues and soon to be physician colleagues, medical students, have a considerable

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underappreciation of the diminution in QOL associated with vision loss versus patients

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with actual vision loss.32,33,64 They therefore likely have an underappreciation of the

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considerable patient value (benefit) often conferred by ophthalmic interventions.2,5,7-12,15,24

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What could be the consequences? The RUC (Relative Value Scale Update Committee), a

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committee of 31 members across medicine, advises the Centers for Medicare and

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Medicaid Services (CMS) as to the resources needed for physicians to deliver services.

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This information is considered as Relative Value Units are developed which affect the cost

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of services. It is also very likely that non-ophthalmic physician colleagues will in other

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ways be involved in decisions to allocate medical resources. If it is believed that vision-

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improving or vision-sparing interventions deliver minimal patient benefit, it follows that

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less resources would likely be devoted to these interventions, very possibly hurting patient

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care.

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The number of medical schools requiring a formal ophthalmology rotation for students

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dropped from 68% in 2000 to 30% in 2004.55 By 2013, the number had dropped to 18%.59

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It is therefore not surprising that few non-ophthalmic physicians have familiarity with

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ophthalmology. We adhere to the dictum that if you are not at the table you are probably

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on the menu. Would reversing the decline in formal ophthalmic training lead to a greater

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appreciation of ophthalmic aspects germane to non-ophthalmic physicians?

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Poorer vision is associated with elements most relevant to general medicine and other

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specialties. These include: 1) the increased difficulties that patients with poor vision have

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with systemic disease management (quantifying medicine doses, taking medicines,

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maintaining hygiene and cleanliness, traveling to see physicians, difficulty affording

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medications, and so forth)32 2) the progressive increase in mortality associated with

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increasingly poor vision,35 3) systemic disease (diabetes mellitus, central retinal vein

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obstruction, central retinal artery obstruction, retinal emboli, atherosclerosis, systemic

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arterial hypertension, and so forth) signs that can be associated with vision loss, 4)

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increased trauma, depression and nursing home admissions and expenses associated with

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vision loss,21,47 and 5) an appreciation of the interventions available to reverse vision loss

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and maintain vision, thus improving length of life and quality-of-life. The authors believe

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that ophthalmic training in medical school would, if structured correctly, lead to an

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increased appreciation of these important systemic issues associated with vision loss.

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Conclusions

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Ophthalmic patients who live with, or have lived with, vision loss daily have a firsthand

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appreciation of the QOL associated with decreased vision. The authors believe that the

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perceptions of patients with vision loss should thus be the criterion, or gold standard, for

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assessing the QOL associated with vision loss. As per the perceptions of patients, the

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benefit conferred by interventions that improve or maintain vision compares well with

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interventions across other specialties. Few stakeholders in healthcare, however, realize

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this. The perceptions of the general public, non-ophthalmic physicians and medical

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students that vision loss nominally affects QOL is disturbing, since these groups will

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likely play a role in future research and healthcare resource allocation decisions.

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As per the recommendations of Ghosh38 when speaking with politicians (the ultimate

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allocators of healthcare resources since virtually all insurers follow Medicare as a

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benchmark),32 ophthalmologists should: 1) know all sides of the issue, 2) have credible

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data to support their side, 3) have a solution, 4) avoid speaking about money and income,

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5) tell the truth, and 6) be respectful. An example of credible data is knowing that patients

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perceive the marked loss of QOL associated with no light perception bilaterally as worse

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than that associated with a major stroke.32 This is an eye-opening reality. Advocating for

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patients with similar data demonstrating the marked decrease in QOL from vision loss, the

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increased mortality from vision loss, and the societal financial gains from reversing and

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preventing vision loss that increase the wealth of our nation, seems an approach that is

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honest, supported by credible scientific research, and in the best interests of the most

412

important people in medicine: our patients.

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Method of literature search. Our literature search included a systematic review of the literature utilizing PubMed, the National Library of Medicine, as well as the Bing and Google search engines. The key words used in the searches were: public perceptions of vision loss and public perceptions of ophthalmology, physician perceptions of vision loss and physician perceptions of ophthalmology, medical student perceptions of vision loss and medical student perceptions of ophthalmology, and patient perceptions of vision loss and ophthalmology, as well as quality-oflife perceptions of all the above. The references of articles uncovered in the search were then reviewed when believed to be relevant. It is of note that the terms public perceptions of ophthalmology, physician perceptions of ophthalmology and medical student perceptions of ophthalmology turned up no usable references in the peer-reviewed literature. 17

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Disclosures. The authors have no conflicts of interest with the work herein. Both Drs. Brown are shareholders in the Center for Value-Based Medicine®.

References

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1. Anonymous. What does perception is reality mean? From the Internet @ http://www.answers.com/Q/What_does_perception_is_reality_mean?#slide=2, accessed January 27, 2018 2. Beauchamp CL, Beauchamp GR, Felius J, Stager DR, Brown G, Brown M, Felius J. The costutility of strabismus surgery in adults J Am Soc Ped Ophthalmol 2007:10:394-9 3. Brezinski EA, Harskamp CT, Ledo L, Armstrong AW. Public perception of dermatologists and comparison with other medical specialties: Results from a national survey. J Am Acad Derm 2014;71:875-81. 4. Brock DW, Daniels N, Neumann PJ, Siegel JE. Ethical and distributive considerations, In Neumann PJ, Sanders GD, Russell LB et al. eds. Panel on Cost-Effectiveness in Health and Medicine. Second edition. New York, Oxford University Press, 2017, pp 319-27. 5. Brown GC, Stein JD, Brown MM, Spaeth GL, Wilson RS. Cost-utility analysis of timolol for the treatment for open-angle glaucoma. J J Ophthalmol. 2015, 1(2): 008 6. Brown GC, Brown MM, Brown HC, Kindermann S, Sharma S. A value-based medicine comparison of interventions for subfoveal neovascular macular degeneration Ophthalmology 2007;114:1170-1178 7. Brown GC, Brown MM, Kertes P. Value-based medicine, cost-utility analysis. The value of commonly used pharmaceuticals. Evid-Based Ophthalmol 2009;10:61-66 8. Brown GC, Brown MM, Kertes P. Value-Based Medicine® cost-utility analysis. Recent value measures and cost-utilities. Evid-Based Ophthalmol 2008;9:203-209. 9. Brown GC, Brown MM, Lieske HB, Brown KS, Colman S, Tran I. A Value-Based Medicine analysis of ranibizumab for neovascular macular degeneration. The return-on-investment and wealth of the nation. Int J Retina Vit (2017) 3:5 DOI 10.1186/s40942-016-0058-3 10. Brown GC, Brown MM, Lieske HB, Lieske PA, Brown KS. A Value-Based Medicine analysis of genetic testing for neovascular macular degeneration. Int J Ret Vitreous 2015:1:19. DOI: 10.1186/s40942-015-0016-5 11. Brown GC, Brown MM, Lieske HB, Lieske PA, Brown KS. Comparative effectiveness and cost-effectiveness analyses on the Implantable Miniature Telescope. Ophthalmology. 2011 Sep;118(9):1834-43. Epub 2011 Jul 2 12. Brown GC, Brown MM, Menezes A, Busbee BG, Lieske HB, Lieske PA. Cataract surgery cost-utility revisited in 2013. A new economic paradigm. Ophthalmology 120:2367-76. 13. Brown GC, Brown MM, Sharma S, Beauchamp G, Hollands H. The reproducibility of ophthalmic utility values. Trans Am Ophthalmol Soc 2001;99:199-203 14. Brown GC, Brown MM, Sharma S, Brown H. Patient perceptions of bilateral visual loss. A utility value analysis. International Ophthalmology 2000;22:307-312

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Acknowledgements. None

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15. Brown GC, Brown MM, Sharma S, Tasman W, Brown H. Cost-effectiveness of therapy for threshold retinopathy of prematurity. Pediatrics 1999;104(4):e47 16. Brown GC, Brown MM, Sharma S. Difference between ophthalmologist and patient perceptions of quality-of-life associated with age-related macular degeneration. Can J Ophthalmol 2000;35:27-32 17. Brown GC, Brown MM, Sharma S. The five senses: a patient preference-based comparative analysis. (Submitted for publication) 18. Brown GC, Brown MM, Stein JD, Smiddy WE. Vision-related quality-of-life associated with unilateral and bilateral ocular conditions. Ophthalmology 2018;125:965-971. 19. Brown GC, Brown MM, Turpcu A, Rajput Y. The cost-effectiveness of ranibizumab therapy for the treatment of diabetic retinopathy. Ophthalmology. 2015;122:1416-25. doi: 10.1016/j.ophtha.2015.03.032. Epub 2015 Apr 29 20. Brown GC, Sharma S, Brown MM, Kistler J. Utility values associated with age-related macular degeneration. Arch Ophthalmol 2000;118:47-51 21. Brown GC. Brown MM, Lieske HB, Tran I, Turpcu A, Colman S. The societal costs associated with neovascular, age-related macular degeneration in the United States. RETINA 2016;36:285-98 22. Brown GC. Vision and quality of life. Trans Am Ophthalmol Soc 1999;97:473-512 23. Brown MM, Brown GC, Brown HC, et al. Value-Based Medicine®, comparative effectiveness, and cost-effectiveness of topical cyclosporine for the treatment of dry eye syndrome. Arch Ophthalmol 2009;127:146-52 24. Brown MM, Brown GC, Brown HC, Irwin B, Roth Z. Comparative effectiveness and costeffectiveness analyses of VEGF-A inhibitor and 90Sr brachytherapy for neovascular macular degeneration. Evidence-Based Ophthalmology 2009;10:107-122 25. Brown MM, Brown GC, Sharma S, Brown H, Busbee B. Quality-of-life associated with unilateral and bilateral good vision. Ophthalmology 2001;108:643-647 26. Brown MM, Brown GC, Sharma S, Busbee B, Brown H. Quality of life associated with visual loss. A time tradeoff utility analysis comparison with medical health states Ophthalmology 2003;110:1076-1081 27. Brown MM, Brown GC, Sharma S, Hollands H. Quality-of-life and systemic comorbidities in patients with ophthalmic disease. Br J Ophthalmol 2002;86:8-11 28. Brown MM, Brown GC, Sharma S, Kistler J, Brown H. Utility values associated with blindness in an adult population. Br J Ophthalmol 2001;85:327-331 29. Brown MM, Brown GC, Sharma S, Landy J. Health care economic analyses and value-based medicine. Surv Ophthalmol 2003;48:204-223 30. Brown MM, Brown GC, Sharma S, Landy J. Quality of life with visual acuity loss from diabetic retinopathy and age-related macular degeneration. Arch Ophthalmol 2002;120:481484 31. Brown MM, Brown GC, Sharma S, Shah G. Utility values and diabetic retinopathy. Am J Ophthalmol 1999;128:324-330 32. Brown MM, Brown GC, Sharma S. Evidence-Based to Value-Based Medicine. Chicago, AMA Press, 2005, pp 1-324 33. Brown MM, Brown GC, Stein JD et. Age-related macular degeneration: economic burden and value-based medicine analysis. Can J Ophthalmol 2005;40:277-87. 34. Chaudry I, Brown GC, Brown MM. Medical student perceptions of quality-of-life associated with vision loss. Can J Ophthalmol 2015;50:217-24.

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35. Christ SL, Zheng DD, Swenor BK, et al. Longitudinal relationships among visual acuity daily functional status, and mortality. The Salisbury Eye Evaluation Study. JAMA Ophthalmol. 2014;132:1400-1406. 36. Collins RL, Haas A, Haviland AM, Elliott MN. What matters most to whom: racial, ethnic, and language differences in the health care experiences most important to patients. Med Care. 2017;55:940-947 37. Gallup News. Nurses keep health lead as most honest ethical profession. From the Internet @ http://news.gallup.com/poll/1654/honesty-ethics-professions.aspx, accessed January 26, 2018 38. Ghosh C. Ophthalmology and politics: Not-so-strange bedfellows. Rev Ophthalmol April 22, 2010, Available on the Internet @ https://www.reviewofophthalmology.com/article/ophthalmology-and-politics-not-so-strangebedfellows, accessed February 3, 2018 39. Gold MR, Patrick DL, Torrance GW, et al. Identifying and valuing outcomes. In: Gold MR, Siegel JE, Russell LB, Weinstein MC, eds. Cost-effectiveness in Health and Medicine. New York: Oxford University Press; 1996:82–134 40. Gothwal VK, Bagga DK, Rao HL, Bharani S, Sumalini R, Garudadri CS, Senthil S, Reddy SP, Pathak-Ray V, Mandal AK. Is utility-based quality of life in adults affected by glaucoma? Invest Ophthalmol Vis Sci. 2014;55:1361-9 41. Gupta O, Brown GC, Brown MM. A value-based medicine cost-utility analysis of idiopathic epiretinal membrane surgery. Am J Ophthalmol 2008;145:923-8. Epub 2008 Mar 10 42. Gupta V, Srinivasan G, Mei SS, Gazzard G, Sihota R, Kapoor KS. Utility values among glaucoma patients: an impact on the quality of life. Br J Ophthalmol. 2005;89:1241-4 43. Hardie EA, Critchley CR. Public perceptions of Australia's doctors, hospitals and health care systems. MJA 2008;189:210-4. 44. Holbrook A, Lexchin J, Pullenayegum E, Campbell C. What do Canadians think about physician-pharmaceutical industry interactions? Health Policy. 2013;112:255-63 45. Hollands H, Lam M, Pater J, Albiani D, Brown GC, Brown MM, Cruess AF, Sharma S. Reliability of the time trade-off technique of utility assessment in patients with retinal disease. Can J Ophthalmol 2001;36:202-209 46. HowDoEyeMatch.com. Understanding the 2015 Ophthalmology Match statistics. From the Internet @ http://www.howdoeyematch.com/understanding-the-2015-ophthalmology-matchstatistics/, accessed February 1, 2018 47. Hutton DW, Stein JD, Bressler NM for the Diabetic Retinopathy Clinical Research Network. Cost-effectiveness of intravitreous ranibizumab compared with panretinal photocoagulation for proliferative diabetic retinopathy: secondary analysis from a diabetic retinopathy clinical research network randomized clinical trial. JAMA Ophthalmol. 2017;135:576-584 48. Javitt JC, Zhou Z, Willke RJ. Association between vision loss and higher medical care costs in Medicare beneficiaries’ costs are greater for those with progressive vision loss. Ophthalmology. 2007;114:238-45 49. Luo BP, Brown GC, Luo SC, Brown MM. The quality-of-life associated with presbyopia. Am J Ophthalmol 2008;145:618-622 50. Membreno J, Brown MM, Brown GC, Sharma S, Beauchamp G. A cost-utility analysis of therapy for amblyopia. Ophthalmology 2002;109:2265-2271 51. National Consumers League. Who does what: consumers confused about eye care providers, training, M.D. status. From the Internet @ http://www.nclnet.org/who_does_what_consumers_confused_about

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_eye_care_providers_training_m_d_status, accessed January 27, 2018 52. National Residency Matching Program. Results and Data, 2017 Main Residency Match. Washington, DC, National Residency Matching Program 2017, p 36 53. Nordhaus WD. The health of nations: The contribution of improved health to living standards. Working paper 881. Cambridge, MA, National Bureau of Economic Research, 2002, pp 37-8 54. Olk RJ, Peralta E, Gierhart DL, Brown MM, Brown GC (2017) Combination therapy with dietary zeaxanthin for neovascular age-related macular degeneration. A randomized clinical trial. J Clin Exp Ophthalmol 8: 692. Doi: 10.4172/2155-9570 55. Quillen DA, Harper RA, Haik BG. Medical student education in ophthalmology: Crisis and opportunity. Ophthalmology 3005;112:2067-8 56. Real FJ, Brown GC, Brown HC, Brown MM. The effect of comorbidities upon ocular and systemic health-related quality of life. Br J Ophthalmol 2008;92:770-4 57. Roe RH, Lass JH, Brown GC, Brown MM. The cost-effectiveness of penetrating keratoplasty for keratoconus. Cornea 2008;27:1001-7 58. Scott AW, Bressler NM, Folkes S. Public attitudes about eye and vision health. JAMA Ophthalmol 2016;134:1111-18. 59. Shah M, Knock D, Waxman E. The state of ophthalmology medical student education in the United States and Canada, 2012 through 2013. Ophthalmology 2014;121:1160-3. 60. Sharma S, Brown GC, Brown MM, Hollands H, Robbins R, Shah G. Validity of the time trade-off and standard gamble methods of utility assessment in retinal patients. Br J Ophthalmol 2002;86:493-496 61. Sharma S, Brown GC, Brown MM, Hollands H, Shah GK. The cost-effectiveness of photodynamic therapy for fellow eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology 2001;108:2051-2059 62. Sharma S, Brown GC, Brown MM, Shah GK, Snow K, Brown H, Hollands H. Converting visual acuity to utilities. Can J Ophthalmol 2000;35:267-272 63. Sharma S, Oliver A, Bakal J, Hollands H, Brown GC, Brown MM. Utilities associated with diabetic retinopathy: results from a Canadian sample. Br J Ophthalmol 2003;87:259-61 64. Stein JD, Brown MM, Brown GC, Sharma S, Hollands H. Quality of life with macular degeneration. Perceptions of patients, clinicians and community members. Brit J Ophthalmol 2003;87:8-12 65. Teunis T, Thornton ER, Jayakumar P, Ring D. Time seeing a hand surgeon is not associated with patient satisfaction. Clin Orthop Relat Res. 2015;473:2362-8. 66. Yannuzzi NA, Chang JA, Brown GC, Smiddy WE. Cost-utility of evaluation for posterior vitreous detachment and prophylaxis of retinal detachment. Ophthalmology (in press) 67. Zhang S, Liang Y, Chen Y, Musch DC, Zhang C, Wang N. Utility analysis of vision-related quality of life in patients with glaucoma and different perceptions from ophthalmologists. J Glaucoma. 2015;24:508-14 68. Zhu X, Sun Q, Zou H, Zhang XX. PLOS (2015) Disparities between ophthalmologists and patients in estimating quality of life associated with diabetic retinopathy. PLoS ONE 10(12): e0143678. doi:10.1371/journal.pone.0143678

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Table 1. Time Tradeoff Vision Utilities and Time Tradeoff Utilities Associated with Systemic Conditions26,29,32 Ophthalmology Primary care Urology Ophthalmology Orthopedics Urology Endocrinology Ophthalmology Ophthalmology

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20/20 bilateral vision permanently Systemic arterial hypertension, treated Benign prostatic hyperplasia 20/20 vision one eye; fellow eye vision < 20/40 Total hip arthroplasty at one year Mild-moderate incontinence after TURP Diabetes mellitus 20/25 vision one eye; fellow eye vision < 20/40 20/40 vision, best eye ACR Class III hip osteoarthritis (performs selfcare, limited vocational/avocational activities) Home dialysis x 8 years 20/80 vision, best eye FEV < 60% of normal Loss of kidney transplant 20/200 vision, best eye Stroke, moderate to severe Severe angina ACR Class IV hip osteoarthritis (no self- care or vocational/avocational activities Counting fingers vision, best eye Coronary artery disease, AHA Class IV, no physical without discomfort, mostly bedbound Hand motions vision, best eye Myocardial infarction, severe Severe stroke No light perception bilaterally Stroke, Rankin 5, after 10 years

Time Tradeoff Utility 1.00 0.98 0.93 0.92 0.92 0.90 0.88 0.87 0.80

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Condition

Orthopedic surgery

0.79

Nephrology Ophthalmology Pulmonology Transplant surgery Ophthalmology Neurology Cardiology

0.72 0.70 0.66 0.62 0.62 0.61 0.53

Orthopedic surgery

0.52

Ophthalmology

0.52

Cardiology

0.45

Ophthalmology Cardiology Neurology Ophthalmology Neurology

0.35 0.30 0.30 0.26 0.20

(TURP = transurethral resection of the prostate, BPH = benign prostatic hyperplasia, FEV = forced expiratory volume)

Rankin 5 = Severe disability. Bedridden, incontinent, and requiring constant nursing care and assistance, ACR = American College of Rheumatology

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Table 2. Gallup Poll Data: Public Perceptions of Honesty and Ethical Standards of Professionals in Different Fields of Employment* Average 16% 24% 37% 31% 32% 32% 41% 41% 48% 39% 54% 53% 39% 47% 53%

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Nurses Military officers Grade school teachers Medical doctors Pharmacists Police officers Judges Clergy Nursing home operators Newspaper reporters Bankers Local officeholders TV reporters State officeholders Lawyers

High to Very High 82% 71% 66% 65% 62% 56% 43% 42% 26% 25% 25% 24% 23% 19% 18% 12%

48%

Members of Congress Car salespeople Lobbyists

11% 10% 8%

29% 48% 31%

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Low to Very Low 2% 3% 5% 4% 6% 12% 15% 13% 22% 35% 21% 20% 37% 33% 28% 31% (9% no opinion) 60% 39% 58%

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*Data from Gallup News. Nurses keep health lead as most honest ethical profession. From the Internet @ http://news.gallup.com/poll/1654/honestyethics-professions.aspx, accessed January 26, 2018.

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• • • • •

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α-adrenergic blockers for prostate hyperplasia Ibuprofen, 800 mg tid, for osteoarthritis Ibuprofen, 800 mg tid, for rheumatoid arthritis Loratadine for seasonal allergic rhinitis Statins (HMG-CoA reductase inhibitors) for hyperlipidemia Topical cyclosporine (Restasis) for dry eye syndrome β-adrenergic blockers for systemic arterial hypertension (6% - 9%) Olanzapine for schizophrenia Ranibizumab, intravitreal, subfoveal neovascular AMD, minimally classic & occult choroidal neovascularization Proton pump inhibitors for acute erosive esophagitis Antidepressants (SSRI, or Selective Serotonin Re-uptake Inhibitors) for major depression Cataract surgery in better-seeing eye; pre-operative vision = 20/83, post-operative vision = 20/27 Omeprazole for Zollinger-Ellison Syndrome

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Table 3. Quality-of-Life Gains Conferred by Various Healthcare Interventions Quality-of-Life Interventions Gain

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*= data from Center for Value-Based Medicine® internal files

1% - 2%50 1.6%* 7.8%* 3.7%* 3% - 5%50 7.1%50 6% - 9%49 9.5%* 17%49

13.3% - 26.2%49 20% -24%49 20.8%12 38.2%*

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General Public64

Non-ophthalmic Physicians64

Medical Students34 (years 1-2/3-4)

p-value (ANOVA)

0.8264

0.96

0.93

NA

< 0.0001

0.7364

0.92

0.96/0.95

< 0.0001

0.88/0.84

< 0.0001

0.4732

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Mild AMD: vision >20/30 in betterseeing eye Moderate AMD: vision 40/40–20/100 in better-seeing eye Severe AMD: vision < 20/200 in betterseeing eye

AMD Patients33,64

0.88

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Table 4. Mean Quality-of-Life Associated with AMD Using Time Tradeoff Utilities, as per the Perceptions of Healthcare Stakeholder Cohorts

0.86

0.82

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AMD = age-relate macular degeneration, NA = not available. Note that it has been demonstrated that the degree of vision loss, rather than the underlying cause, most closely correlates with the associated vision utility.21,29

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Table 5. Mean Time Tradeoff Utility Estimates from Ophthalmologists for Levels of Vision Loss Associated with AMD versus Utilities from AMD Patients with Actual Vision Loss16,64 Ophthalmologists

AMD Patients

p-value (t-test)

Mild: 20/20-20/40 Moderate: 20/50-20/100 Severe: < 20/200 Very severe: < 20/800

0.98 0.89 0.73 0.69

0.83 0.60 0.47 0.37

< 0.001 < 0.001 < 0.001 < 0.001

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Level of Vision Loss in Better-Seeing Eye

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AMD = age-related macular degeneration