Global Burden of Eye and Vision Disease As Reflected in the Cochrane Database of Systematic Reviews

Research

Original Investigation Global Burden of Eye and Vision Disease as Reflected in the Cochrane Database of Systematic Reviews

Lindsay N. Boyers, BA; Chante Karimkhani, BA; John Hilton, MSc, MPhil; William Richheimer, MD; Robert P. Dellavalle, MD, PhD, MSPH

Supplemental content at IMPORTANCE Eye and vision disease burden should help guide ophthalmologic research jamaophthalmology.com prioritization. The Global Burden of Disease (GBD) Study 2010 compiled data from 1990 to 2010 on 291 diseases and injuries, 1160 disease and injury sequelae, and 67 risk factors in 187 countries. The Cochrane Database of Systematic Reviews (CDSR) is a resource for systematic reviews in health care, with peer-reviewed systematic reviews that are published by Cochrane Review Groups.

OBJECTIVE To determine whether systematic review and protocol topics in the CDSR reflect disease burden, measured by disability-adjusted life-years (DALYs), from the GBD 2010 project. This is one of a series of projects mapping GBD 2010 medical field disease burdens to corresponding systematic reviews in the CDSR.

DESIGN AND SETTING Two investigators independently assessed 8 ophthalmologic conditions in the CDSR for systematic review and protocol representation according to subject content. The 8 diseases were matched to their respective DALYs from the GBD 2010 project.

MAIN OUTCOMES AND MEASURES Cochrane Database of Systematic Reviews systematic review and protocol representation and percentage of total 2010 DALYs.

RESULTS All 8 ophthalmologic conditions were represented by at least 1 systematic review in the CDSR. A total of 91.4% of systematic reviews and protocols focused on these conditions were from the Cochrane Eyes and Vision Group. Comparing the number of reviews and protocols with disability, only cataract was well matched; glaucoma, macular degeneration, and other vision loss were overrepresented. In comparison, trachoma, onchocerciasis, vitamin A deficiency, and refraction and accommodation disorders were underrepresented.

CONCLUSIONS AND RELEVANCE These results prompt further investigation into why certain diseases are overrepresented or underrepresented in the CDSR relative to their DALY. With regard to ophthalmologic conditions, this study encourages that certain conditions get more focus to create a better representation of what is causing the most disability and mortality within this research database. These results provide high-quality and transparent data to inform future prioritization decisions.

Author Affiliations: Author affiliations are listed at the end of this article. Corresponding Author: Robert P. Dellavalle, MD, PhD, MSPH, Dermatology Service, Department of Veteran Affairs Medical Center, 1055 Clermont St, Box 165, Denver, CO JAMA Ophthalmol. 2015;133(1):25-31. doi:10.1001/jamaophthalmol.2014.3527 80220 (robert.dellavalle Published online September 18, 2014. @ucdenver.edu).

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he process of setting research agendas and priorities and systematic reviews. Unlike the Sight Loss and Vision Pri- is complex and multifactorial, with the aim to pro- ority Setting project, this work aimed to respond to clini- T vide the greatest public health benefit.1 While a uni- cians’ needs and was thus limited to the professionals’ form approach to establishing health research priorities is perspective.10 not appropriate for the unique situation and context in When it comes to research prioritization, burden of dis- which agendas are set, 9 common themes of good practice ease is one of many factors that may be considered. In par- have been identified including, but not limited to, determi- ticular, the Global Burden of Diseases (GBD), Injuries, and Risk nation of criteria that will guide prioritization decisions, Factors Study 2010 is the result of a worldwide collaboration determination of decision makers, and transparency.1 The of 500 researchers that scientifically and systematically quan- Cochrane Collaboration serves as an example of a large net- tified various health metrics of loss to diseases, injuries, and work of researchers that has established a diversity of risk factors by age and sex.11 The GBD 2010 included 291 dis- priority-setting methods by its various review groups.2 The eases and injuries, 67 risk factors, 1160 sequelae (nonfatal 10 guiding principles of Cochrane’s work are collaboration, health consequences) for 21 regions, 187 countries, and 20 age building on the enthusiasm of individuals, avoiding dupli- groups. The GBD 2010 uses improved methods for the estima- cation of effort, minimizing bias, keeping up to date, striv- tion of disability weights, which quantify the severity of health ing for relevance, promoting access, ensuring quality, conti- loss associated with a particular disease state. Disability- nuity, and enabling wide participation.3 adjusted life-years (DALYs) are a metric established by the GBD Within the Cochrane Library, the Cochrane Database of to analyze and compare years of healthy life lost. The DALY is Systematic Reviews (CDSR) contains reviews produced by 53 a combination of years lost owing to premature death and years Cochrane Review Groups. The CDSR serves as a source of peer- lived with disability. These data metrics enable comparison of reviewed systematic reviews in health care. It aims to pro- health data across boundaries of geography and time in a way vide evidence-based information to inform decision making that is more comprehensive, internally consistent, and com- for individuals, health care professionals, and policy makers parable than previous data sources.12-14 alike.4,5 Until now, Cochrane reviews have mainly focused on The aim of the current study was to assess representa- treatment effectiveness assessed in randomized clinical trials, tion of 8 ophthalmologic categories studied by the GBD although guidance on incorporating evidence from studies with 2010 within the CDSR and whether representation corre- other designs is being developed. sponds to GBD 2010 disability estimates for each category. One of the Cochrane Review Groups, the Eyes and Vision The current study is part of a larger series intending to map Group, registered with Cochrane in 1997 and has 200 mem- all 291 diseases studied by the GBD 2010 to representation in bers from 30 countries.6 This group seeks to create, sustain, major research databases.15,16 and encourage access to systematic reviews that synthesize information regarding all aspects of prevention and treatment 7 of eye disease and visual impairment. Its scope extends to aid Methods those affected by visual impairment or blindness in the ad- justment to their disability. Prioritization strategies for the The following 8 ophthalmologic categories were studied by the Cochrane Eyes and Vision Group specifically emphasize chief GBD 2010: refraction and accommodation disorders, cata- causes of blindness worldwide and regions with a large range racts, macular degeneration, glaucoma, trachoma, onchocer- of clinical practices and outcomes.7 The compiled systematic ciasis, vitamin A deficiency, and other vision loss. The other vi- reviews rely on data from randomized and quasirandomized sion loss category included a total of 57 eye conditions including clinical trials and create descriptive compilations where such choroidal degeneration, central retinal artery occlusion and dip- information is scarce. Primary outcome measurements are vi- lopia (see eTable 1 in the Supplement for a complete list of con- sual function such as visual acuity, assessment of visual field, ditions in the other vision loss category). Each ophthalmo- and assessment of vision-related quality of life.7 logic category was explored in the CDSR by searching the There are various efforts underway to help drive agendas condition name under title, abstract, keywords (see Table 1 and and priorities within the field of ophthalmology.8 For in- eTable 1 in the Supplement for International Statistical Clas- stance, the Sight Loss and Vision Priority Setting project, ini- sification of Diseases, 10th Revision [ICD-10] definitions and tiated in 2011, is supported and guided by the James Lind search terms for each ophthalmologic category).18 Both sys- Alliance.9 The priorities set by this group are within the con- tematic reviews and protocols were considered to assess oph- text of the UK National Health Service. This organization uses thalmologic disease representation in the database. the input of patients, caregivers, and health care profession- Certain GBD categories were ultimately excluded als to identify and prioritize unanswered questions or over- because ophthalmologic conditions were not the focus and looked issues regarding ophthalmology treatment, diagno- GBD metrics could not be attributed solely to the ophthal- sis, and prevention.9 The results are publicized to research mologic conditions. These categories included sense organ commissioning bodies to be considered for funding.9 Li et al10 diseases, other sense organ diseases, and other noncommu- conducted an eye and vision prioritization exercise on the topic nicable diseases. The category of vitamin A deficiency was of open-angle glaucoma. This study focused on creating and predominantly eye conditions (ICD codes of nonophthalmo- evaluating a framework to determine evidence gaps and pri- logic conditions were E50.8. E50.9, and E64.1); thus, it was oritize clinical questions by using clinical practice guidelines included.

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Table 1. GBD 2010 Ophthalmologic Conditions, the ICD-10 Codes That Define Them, and Terms Searched on the Cochrane Library

ICD-10 Codes Populating Ophthalmologic Ophthalmologic Category Condition in GBD 2010a Terms Entered Into Search Query Refraction and H49-H52 Refraction, accommodation disorders, paresis of accommodation, accommodation spasm of accommodation, paralytic strabismus, third nerve palsy, disorders oculomotor nerve palsy, fourth nerve palsy, trochlear nerve palsy, sixth nerve palsy, abducent nerve palsy, ophthalmoplegia, Kearns-Sayre syndrome, strabismus, esotropia, exotropia, hypertropia, hypotropia, heterotropia, cyclotropia, microtropia, monofixation syndrome, heterophoria, esophoria, exophoria, brown sheath syndrome, traumatic limitation of duction of eye muscle, Duane syndrome, binocular movement, palsy of conjugate gaze, convergence insufficiency, convergence excess, internuclear ophthalmoplegia, hypermetropia, myopia, astigmatism, anisometropia, aniseikonia, presbyopia, internal ophthalmoplegia Cataracts H25-H26 Cataracts, senile cataract, senile incipient cataract, subcapsular polar senile cataract, water clefts, senile nuclear cataract, cataracta brunescens, nuclear sclerosis cataract, Morgagnian type, senile hypermature cataract, infantile cataract, juvenile cataract, presenile cataract, traumatic cataract, complicated cataract, cataract in chronic iridocyclitis, glaucomatous flecks, drug-induced cataract, secondary cataract, Soemmerring ring Macular H35.3 Macular degeneration, angioid streaks of macula, cyst of macula, degeneration drusen of macula, degeneration of macula, hole of macula, puckering of macula, Kuhnt-Junius degeneration, senile macular degeneration, toxic maculopathy Glaucoma H40 Glaucoma, glaucoma suspect, ocular hypertension, primary open- angle glaucoma, primary angle-closure glaucoma, glaucoma secondary to eye trauma, glaucoma secondary to eye inflammation, glaucoma secondary to other eye disorders, glaucoma secondary to drugs Trachoma A71, A74.0, and B94.0 Trachoma, trachoma dubium, trachomatous, chlamydial conjunctivitis, paratrachoma Onchocerciasis B73 Onchocerciasis, Onchocerca volvulus infection, Onchocercosis, river blindness, Robles disease Abbreviations: GBD, Global Burden of Vitamin A E50.0-50.7 (E50.8, Vitamin A deficiency with conjunctival xerosis, vitamin A deficiency Disease; ICD-10, International deficiency E50.9, and E64.1 with Bitot spot, vitamin A deficiency with corneal xerosis, vitamin A Statistical Classification of Diseases, excluded because deficiency with corneal ulceration, vitamin A deficiency with not ophthalmologic keratomalacia, vitamin A deficiency with night blindness, vitamin A 10th Revision. conditions) deficiency with xerophthalmic scars of cornea, ocular manifestations a Specific ICD-10 codes used by GBD of vitamin A deficiency, cerophthalmia due to vitamin A deficiency, 2010 are published in a study by vitamin A eye, vitamin A blindness, vitamin A ocular Lozano et al.17

A systematic review or protocol was matched to 1 of the 8 though the GBD project studied 291 conditions, rankings only ophthalmologic categories according to its subject content, and include 176 conditions, excluding conditions for which the proj- the particular Cochrane Review Group that published each re- ect made no explicit estimates such as etiologies of diarrhea, view and date of publication were determined. For a review pneumonia, and more specific conditions under maternal or or protocol to be classified under a disease, the disease was re- congenital. Search parameters of global place, all conditions, quired to be a predominant focus of the abstract objectives and both sexes, DALY metric, and age standardized were used. The main results. If the systematic review or protocol included the DALY percentage change from 1990 to 2010 was also obtained search term in the title, it was automatically included. Re- from the GBD interactive arrow diagram for each ophthalmo- views or protocols with more than 1 category as a predomi- logic condition. Age standardization was used in the interac- nant focus were counted once within each respective cat- tive arrow diagram for DALY ranking and percentage change egory. For instance, if a review pertained to both cataracts and to eliminate effects of population growth and aging over the glaucoma, it was counted twice. 20-year span. Methods used by the GBD 2010 to generate DALY esti- Matching of the CDSR representation with GBD disability mates have been previously described.13,14 As previously men- estimates was accomplished by creating a data plot of repre- tioned, the DALY metric combines years of life lost owing to sentation vs disability to generate a linear line of best fit with premature mortality and years lived with a disability.19 Dis- a coefficient of determination (R2) and qualitatively determin- ability-adjusted life-year metrics for each of the 8 ophthalmo- ing whether conditions were well matched or not well matched. logic categories, expressed as the percentage of total DALYs of Because research prioritization of a major database, such as 291 conditions measured in the GBD 2010, were obtained from the CDSR, was not expected to solely correlate with a single the GBD Compare interactive time plot.20 Using this tool, search factor, qualitative rather than quantitative methods were used parameters of time plot, DALYs metric, global place, all ages, both to match funding with disability. sexes, and % units were selected for each ophthalmologic con- Two authors (L.N.B. and C.K.) collected data indepen- dition. The DALY rankings for the 8 ophthalmologic catego- dently, with consensus review during March 2014. Because the ries compared with 176 conditions measured in the GBD 2010 current study solely involved nonhuman subjects, institu- were obtained from the GBD interactive arrow diagram.21 Al- tional review board approval was not necessary.

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Table 2. Representation in the CDSR and DALY Metrics for 8 Ophthalmologic Conditions Studied by GBD 2010a

No. of DALY % Systematic %ofTotal Change of 2010 Reviews and Cochrane 2010 DALY DALY From DALY Rank Ophthalmologic Protocols in Group (Of 291 1990 to (Of 176 Condition the CDSR Contributions Conditions) 2010 Conditions) Other vision loss 26 (23 reviews, 19 Eyes and Vision, 0.25 +2 67 3 protocols) 5 Neonatal, and 2 Stroke Refraction and 15 (12 reviews, 15 Eyes and Vision 0.23 +1 68 accommodation 3 protocols) disorders Cataracts 19 (16 reviews, 16 Eyes and Vision 0.19 −30 74 3 protocols) and 3 Anesthesia Macular 20 (19 reviews, 20 Eyes and Vision 0.054 +56 132 degeneration 1 protocol) Glaucoma 30 (20 reviews, 30 Eyes and Vision 0.038 +31 147 10 protocols) Trachoma 4 (4 reviews, 4 Eyes and Vision 0.013 +48 165 Abbreviations: CDSR, Cochrane 0 protocols) Database of Systematic Reviews; Onchocerciasis 1 (1 review, 1 Eyes and Vision 0.02 −31 163 DALY, disability-adjusted life-year; 0 protocols) GBD, Global Burden of Disease; Vitamin A 1(1review, 1 Acute Respiratory 0.032 −9 153 a Arranged in order of decreasing deficiency 0 protocols) Infections percentage of total 2010 DALY.

only category that was well matched (Table 2). Glaucoma, Results macular degeneration, and other vision loss were overrepresented when matched with corresponding DALYs. Con- A total of 116 reviews and protocols represented the 8 oph- versely, trachoma, onchocerciasis, vitamin A deficiency, and thalmologic categories, with 106 (91.4%) of these being from refraction and accommodation disorders were underrepre- the Cochrane Eyes and Vision Group (Table 2). Glaucoma had sented in the CDSR relative to corresponding DALYs. the greatest representation in the CDSR, with 30 reviews and Twenty-six systematic reviews and protocols covered 57 protocols, followed closely by the other vision loss category, ophthalmologic conditions defined by the GBD 2010 other vi- with 26 reviews and protocols, and macular degeneration, with sion loss category (see eTable 1 in the Supplement for ICD codes 20 reviews and protocols. Those categories with lower repre- and conditions that comprise the other category; see eTable 3 sentation were trachoma, with 4 reviews, and onchocerciasis in the Supplement for included titles and eTable 5 for ex- and vitamin A deficiency, both with only 1 review. A list of all cluded titles). The Cochrane Eyes and Vision Group was re- included review and protocol titles for each condition is avail- sponsible for 73.1% of the systematic reviews in the CDSR for able in eTables 2 and 3 in the Supplement and a list of all ex- these 57 ophthalmologic conditions. cluded titles in eTables 4 and 5 in the Supplement. The range of review and protocol publication year was from 1999 to 2014, with 73.3% occurring from 2010 to 2014; the median and mode Discussion year was 2012. Looking at the global GBD 2010 DALY metrics, other vi- The 8 ophthalmologic categories assessed were represented sion loss had the greatest percentage of total DALY (0.25%), fol- by a total of 116 reviews and protocols in the CDSR, with most lowed by refraction and accommodation disorders (0.23%) (91.4%) published by the Eyes and Vision Group. While the (Table 2). Vitamin A deficiency had the lowest percentage of CDSR covers a broad diversity of ophthalmologic conditions, total DALY (0.032%) of the conditions assessed. The condi- prioritization is not solely guided by burden of disease data. tions that experienced an increase in DALY from 1990 to 2010 This was exemplified by the poor correlation between the CDSR listed from greatest to least were macular degeneration (per- representation and DALYs for the ophthalmologic categories, centage change in DALY from 1990 to 2010 was +56%), tra- which yielded an R2 of 0.23. Other factors and considerations choma (+48%), glaucoma (+31%), other vision loss (+2%), and play critical roles in the prioritization process by the CDSR. In refraction and accommodation disorders (+1%). The condi- addition, the fact that most reviews and protocols were pub- tions that experienced a decrease in DALY from 1990 to 2010 lished from 2010 to 2014 provided evidence of the current and listed from greatest to least were onchocerciasis (percentage frequently updated nature of the CDSR content. change in DALY from 1990 to 2010 was −31%), cataracts (−30%), and vitamin A deficiency (−9%). The 2010 DALY ranks for the Conditions for Which CDSR Representation Appeared 8 ophthalmic conditions assessed ranged from 67 for other vi- Well Matched With Disability Metrics sion loss to 153 for vitamin A deficiency. Cataract was the only category that was well matched with re- Comparing the CDSR representation with DALY metrics, spect to DALY and CDSR representation. Although cataracts had the overall R2 was 0.23, indicating an overall poor correlation the third highest DALY, the condition experienced the great- between these variables (Figure). Specifically, cataract was the est decrease in DALY from 1990 to 2010 of the conditions stud-

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Figure. Comparison of Ophthalmology Representation in Cochrane Database of Systematic Reviews to Percentage of Total 2010 Disability-Adjusted Life-Years

R2 = 0.23

30 Glaucoma

Other vision loss 25

20 Macular degeneration Cataracts

15 Refraction and accommodation disorders

10 Cochrane Systematic Reviews and Protocols, No. Reviews Systematic Cochrane

5 2 Trachoma The correlation coefficient (R ) equals 0.23 for the number of Cochrane Onchocerciasis systematic reviews and protocols Vitamin A deficiency 0 compared with the global percentage 0 0.05 0.1 0.15 0.2 0.25 0.3 of total 2010 disability-adjusted Total 2010 Disability-Adjusted Life-Years, % life-years for 8 ophthalmologic conditions.

ied. Age-related cataracts are the leading cause of blindness, proximately 120 million people worldwide, most of these cases, causing an estimated 51% of all blindness and affecting 19.7 mil- such as near sightedness, far sightedness, or astigmatism, could lion people worldwide.22 In addition, surgery for cataracts and be corrected with the assistance of eyeglasses, contact lenses, refractive errors are among the most cost-effective interven- or refractive surgery.23 Perhaps this existing knowledge of ef- tions in health care.22 fective interventions contributed to a relatively constant DALY from this category (+1%) from 1990 to 2010. Similarly, vita- Conditions for Which CDSR Representation Appeared min A deficiency and onchocerciasis demonstrated the low- Overmatched With Disability Metrics est 2010 DALYs of the 8 ophthalmologic conditions, in addi- Glaucoma, macular degeneration, and other vision loss were tion to large decreases in DALY from 1990 to 2010. Their low overrepresented when compared with their DALY metrics. CDSR representation may thus reflect the relative decreased Glaucoma not only had the greatest number of CDSR reviews burden of disease over time. In contrast, trachoma was un- and protocols, but also experienced a 31% increase in DALY derrepresented in the CDSR but experienced the second great- from 1990 to 2010. Similarly, macular degeneration experi- est 20-year increase in DALY (+48%) of all the conditions as- enced the greatest increase in DALY (+56%) of all the catego- sessed. While trachoma is the leading cause of infectious ries. The apparent overrepresentation of these 2 conditions in blindness in the world, the condition is irreversible and highly the CDSR is more accurately reflected by their 20-year disabil- contagious.23 Active efforts, such as those led by the World ity trends. Health Organization’s Alliance for the Global Elimination of Representing 57 eye conditions, the other vision loss cat- Trachoma, predominantly focus on prevention at the popu- egory was second in terms of CDSR representation, with 29 re- lation level.24 views and protocols and has the greatest DALY and highest DALY ranking of all the categories. This category experienced Limitations and Future Directions a DALY percentage change increase of 2%, the smallest of the Limitations of this study were related to synthesizing ophthal- 3 conditions that were overmatched. mologic presence in the CDSR and the use of GBD metrics. First, quantification of reviews and protocols in the CDSR was sub- Conditions for Which CDSR Representation Appeared ject to how the reviews and protocols were compiled. For in- Undermatched With Disability Metrics stance, multiple conditions may be covered in one review with Trachoma, onchocerciasis, vitamin A deficiency, and refrac- a broader focus, referred to as lumping. Alternatively, several tion and accommodation disorders were underrepresented in reviews may cover the same information, each with a more nar- the CDSR relative to their disability estimates. Of the condi- row focus, referred to as splitting.25 Hence, consideration of a tions studied, refraction and accommodation disorders had the systematic review as one unit of representation may not be ap- second greatest DALY.While uncorrected refractive errors are propriate for certain topics. In addition, the CDSR reviews syn- responsible for 43% of all visual impairment and affect ap- thesize studies and the best evidence in the literature. For this

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reason, meta-analyses for topics that lack studies in the lit- tion in the CDSR. There are likely a variety of factors con- erature are generally not possible in the CDSR. Variables be- tributing to the lack of correlation. Diseases with known yond Cochrane research prioritization determine database pres- cures, but with significant public health and economic bar- ence. Additionally, the assignment of a particular review or riers to treatment, such as vitamin A deficiency, were protocol by the study authors to a particular ophthalmologic underrepresented in the CDSR. Furthermore, economic category was not completely objective; the use of indepen- impact of diseases disproportionally affecting wealthy dent data collection by 2 authors with consensus review strove populations may contribute to overrepresentation in the to minimize this source of error. CDSR. This article highlighted ophthalmic diseases where Second, this study was also subject to limitations of the global burden fails to correlate with current research and GBD 2010 such as inconsistent or scarce data sources.26 The reviews. We suggest that considerations be taken of such ICD codes comprising disease categories were established by underrepresented and overrepresented ophthalmic condi- GBD collaborator consensus. These ICD codes were used to gen- tions in pursuit of future research, reviews, and funding. erate search terms and may not have generated all search re- Overall, global burden of disease comprises one of many sults pertaining to each topic. Several GBD categories were ex- factors guiding research prioritization of ophthalmic condi- cluded from the current study that did not focus exclusively tions by Cochrane Review Groups. The process of mapping sys- on ophthalmologic conditions because the DALYs could not be tematic reviews with disability metrics, such as DALY, pro- solely attributed to the ophthalmologic condition. In addi- vides reproducible, transparent, and valuable data for use in tion, the GBD 2010 does not provide disability estimates for future research prioritization discussions. Certainly, the allo- individual diseases in the other vision loss category. Further cation of research funds and topic prioritization is an intri- breakdown of this category would enable a more in-depth and cate process guided by many factors.1 Within Cochrane, pri- inclusive study of disease impact. As GBD data become avail- oritization processes are largely determined and maintained able on an annual basis, analysis of the relationship and trends by individual Cochrane Review Groups. between database representation and GBD disability over time This study is part of a series that aims to map all condi- can be explored further. Finally, this study did not explore the tions studied by the GBD to representation in various major contributions of disease inclusion in the CDSR other than global databases such as the CDSR.16 In the future, we hope that this disease burden such as the skewed financial burden of dis- initial manual mapping will become automated, using the ad- eases that disproportionately cause vision impairment in vanced and large-scale methods possible with computer pro- developed populations. grams and technological advances. Global burden of disease is a useful metric that may guide prioritization decisions. The GBD has created unprecedented public access of electronic in- Conclusions formation. As GBD metrics become increasingly used by health care professionals, policy makers, and individuals alike, the Overall, the global burden of ophthalmic conditions was global burden of disease may ultimately help to reduce re- poorly proportioned to the reviews and protocol representa- search gaps and profoundly impact the human population.

ARTICLE INFORMATION Acquisition, analysis, or interpretation of data: Disclaimer: The opinions expressed herein do not Submitted for Publication: May 13, 2014; final Boyers, Karimkhani, Richheimer. necessarily reflect those of the US Department of revision received June 24, 2014; accepted July 4, Drafting of the manuscript: Boyers, Richheimer. Veterans Affairs, the Centers for Disease Control 2014. Critical revision of the manuscript for important and Prevention, the National Institutes of Health, or intellectual content: All authors. The Cochrane Collaboration. Published Online: September 18, 2014. Administrative, technical, or material support: doi:10.1001/jamaophthalmol.2014.3527. Boyers, Karimkhani, Dellavalle. REFERENCES Author Affiliations: Georgetown University School Study supervision: Richheimer, Dellavalle. 1. Viergever RF, Olifson S, Ghaffar A, Terry RF. of Medicine, Washington, DC (Boyers); Columbia Conflict of Interest Disclosures: All authors have A checklist for health research priority setting: nine University College of Physicians and Surgeons, New completed and submitted the ICMJE Form for common themes of good practice. Health Res Policy York, New York (Karimkhani); Cochrane Editorial Disclosure of Potential Conflicts of Interest. Ms Syst. 2010;8:36. Unit, The Cochrane Collaboration, London, England Boyers and Dr Dellavalle are both employees of the (Hilton); Department of Ophthalmology, University 2. Nasser M, Welch V, Tugwell P, Ueffing E, Doyle J, US Department of Veterans Affairs. Dr Dellavalle is Waters E. Ensuring relevance for Cochrane reviews: of Colorado Anschutz Medical Campus, Denver also chair of the Colorado Skin Cancer Task Force. (Richheimer); Department of Dermatology, evaluating processes and methods for prioritizing Mr Hilton is an employee of The Cochrane topics for Cochrane reviews. J Clin Epidemiol.2013; University of Colorado Anschutz Medical Campus, Collaboration. No other disclosures were reported. Denver (Dellavalle); Department of Epidemiology, 66(5):474-482. Colorado School of Public Health, University of Funding/Support: Dr Dellavalle receives a salary 3. The Cochrane Collaboration. Our principles. http: Colorado Anschutz Medical Campus, Denver from the US Department of Veterans Affairs. Dr //www.cochrane.org/about-us/our-principles. (Dellavalle); Department of Dermatology, Denver Dellavalle is also supported by grants from the Accessed April 11, 2014. Veterans Administration Hospital, Denver, Colorado Centers for Disease Control and Prevention and National Institutes of Health. 4. The Cochrane Library. About the Cochrane (Dellavalle). Library. http://www.thecochranelibrary.com/view/0 Author Contributions: Ms Boyers and Dr Dellavalle Role of the Funder/Sponsor: The funders had no /AboutTheCochraneLibrary.html. Accessed April 11, had full access to all of the data in the study and role in the design and conduct of the study; 2014. collection, management, analysis, and take responsibility for the integrity of the data and 5. The Cochrane Library. About Cochrane systematic the accuracy of the data analysis. interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit reviews and protocols. http://www Study concept and design: Boyers, Karimkhani, .thecochranelibrary.com/view/0 Hilton, Dellavalle. the manuscript for publication.

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