Screening for Glaucoma in Adults - 2 of 2 (Diagnostic Accuracy Studies)

Project Summary Title and Description

Screening for Glaucoma in Adults - 2 of 2 (Diagnostic Accuracy Studies)
Structured Abstract Background: In 2013, the United States Preventive Services Task Force (USPSTF) concluded that the evidence was insufficient to assess the balance of benefits and harms of screening for primary open angle glaucoma in adults (I Statement). Although the USPSTF found that treatment of increased intraocular pressure (IOP) and early glaucoma reduces progression of visual field defects, it found inadequate evidence on the effects of treatment on the development of impaired vision or quality of life. There was no direct evidence on benefits and harms of glaucoma screening versus no screening. Purpose: To systematically review the evidence on screening and treatment of glaucoma for populations and settings relevant to primary care in the United States. Data Sources: We searched the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and MEDLINE (through February 9, 2021), reviewed the studies in the prior reports, and manually reviewed reference lists. Study Selection: Randomized controlled trials (RCTs) of screening and referral; studies on diagnostic accuracy of currently utilized screening tests (optical coherence tomography [OCT], optic disc photography, ophthalmoscopy and biomicroscopy, pachymetry, tonometry, and visual fields); and RCTs of medical therapy versus placebo or no treatment, recently approved medical therapies versus older therapies, and selective laser trabeculoplasty versus medical therapy. Data Extraction: One investigator abstracted data and a second checked accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): A total of 83 studies (N=76,807) were included in this review (30 trials, and 53 diagnostic accuracy studies). Sixteen studies were carried forward from the prior review and 67 studies were new. One RCT (n=616) found vision screening (including components for glaucoma) by an optometrist was associated with no difference in visual acuity or vision-related quality of life compared with no screening, but greater risk of falls (likelihood of at least 1 fall 65% vs. 50%, relative risk [RR] 1.31, 95% confidence interval [CI] 1.13 to 1.50). No study evaluated effects of referral to an eye health provider versus no referral on vision or other health outcomes. Evidence on accuracy of screening tests for identifying persons with glaucoma was most robust for spectral domain-OCT retinal nerve fiber layer thickness (15 studies, N=4,242, sensitivity 0.79, 95% CI 0.74 to 0.84 and specificity 0.91, 95% CI 0.85 to 0.95), area under the receiver operating characteristic curve (16 studies, N=4,060) 0.90, 95% CI 0.86 to 0.93 and spectral domain-OCT ganglion cell analysis (nine studies, N=1,522, sensitivity 0.72, 95% CI 0.64 to 0.78 and specificity 0.91, 95% CI 0.79 to 0.96), tonometry (13 studies, N=32,892, sensitivity 0.46, 95% CI 0.29 to 0.65 and specificity 0.94, 95% CI 0.89 to 0.97), and the Humphrey Visual Field Analyzer (seven studies, N=11,426, sensitivity 0.87, 95% CI 0.73 to 0.94 and specificity 0.78, 95% CI 0.57 to 0.91). Evidence on other screening tests (swept source-OCT, optic disc photography, ophthalmoscopy and biomicroscopy, and pachymetry) was limited. A pilot study and followup found telemedicine screening in primary care associated with variable sensitivity for identifying persons with glaucoma but high specificity. Evidence on the accuracy of instruments for identifying patients at higher risk of glaucoma was limited to one study that was of limited applicability to screening because prior diagnosis of glaucoma was one of the key risk factors. Medical therapy for ocular hypertension and untreated glaucoma was associated with greater reduction in IOP (16 trials, N=3,706, mean difference -3.14 millimeters mercury [mm Hg], 95% CI -4.19 to -2.08) decreased likelihood of glaucoma progression (7 trials, N=3,771, RR 0.68, 95% CI 0.49 to 0.96; absolute risk difference -4.2%) and increased risk of ocular adverse events (2 trials, RR 1.21, 95% CI 1.10 to 1.33 and RR 3.52, 95% CI 2.46 to 5.02) versus placebo or no treatment. One trial (n=461) found no differences between medical therapy versus placebo or no treatment in visual acuity, quality of life, or function. Recently approved medical therapies for glaucoma (netarsudil and latanoprostene bunod) were associated with similar or slightly greater reduction in IOP versus older therapies (6 trials, N=3,128), but increased risk of adverse events. Selective laser trabeculoplasty and medical therapy were associated with similar effects on IOP, visual acuity, visual fields, quality of life, and adverse events (4 trials, N=957). Limitations: Excluded non-English language studies; statistical heterogeneity in pooled analyses on effects of medical therapy versus placebo or no treatment on IOP, though inconsistency was in the magnitude (not direction) of benefit; evidence on effects of treatment on visual impairment, quality of life, and function remains very limited; excluded case-control studies of diagnostic accuracy; evaluation of publication bias limited by small numbers of studies and statistical heterogeneity; most head-to-head comparisons excluded. Conclusions: Direct evidence on glaucoma screening versus no screening is limited and showed no benefits on vision-related quality of life or function, and increased risk of falls. Screening tests (OCT, visual field assessment) can identify persons with OAG with reasonable accuracy. Treatment for ocular hypertension or untreated OAG is associated with reduction in IOP and reduced risk of glaucoma progression based on visual fields or optic nerve changes, but limited evidence on the association with visual outcome, quality of life, and function indicates no clear effects.
Authors of Report
Shelley Selph, MD, MPH Ian Blazina, MPH Christina Bougatsos, MPH Rebecca Jungbauer, DrPH Rongwei Fu, PhD Sara Grusing, MPH Daniel Jonas, MD, MPH Shandiz Tehrani, MD, PhD
Methodology description
Systematic Review
The final research plan, which serves as a protocol, was published on the USPSTF website here:
Funding Source
AHRQ Contract No. HHSA-290-2015-00011-I, Task Order No. 75Q80119F32015

Key Questions

1. Key Question 4. What is the accuracy of screening for diagnosis of OAG?
2. Key Question 5. What is the accuracy of instruments for identifying patients at higher risk of OAG?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

Title Authors Year
Diagnostic Accuracy of Spectralis SD OCT Automated Macular Layers Segmentation to Discriminate Normal from Early Glaucomatous Eyes. Pazos M; Dyrda AA; Biarnes M; Gomez A; Martin C; Mora C; Fatti G; Anton A 2017 Aug
A comparative evaluation of segmental analysis of macular layers in patients with early glaucoma, ocular hypertension, and healthy eyes. Aksoy FE; Altan C; Yilmaz BS; Yilmaz I; Tunc U; Kesim C; Kocamaz M; Pasaoglu I 2020 Nov
Structure-function relationships using spectral-domain optical coherence tomography: comparison with scanning laser polarimetry. Aptel F; Sayous R; Fortoul V; Beccat S; Denis P 2010 Dec
Diagnostic ability of spectral-domain optical coherence tomography peripapillary retinal nerve fiber layer thickness to discriminate glaucoma patients from controls in an elderly population (The MONTRACHET study). Arnould L; De Lazzer A; Seydou A; Binquet C; Bron AM; Creuzot-Garcher C 2020 Dec
Automated imaging technologies for the diagnosis of glaucoma: a comparative diagnostic study for the evaluation of the diagnostic accuracy, performance as triage tests and cost-effectiveness (GATE study). Azuara-Blanco A; Banister K; Boachie C; McMeekin P; Gray J; Burr J; Bourne R; Garway-Heath D; Batterbury M; Hernandez R; McPherson G; Ramsay C; Cook J 2016 Jan
Detection of psychophysical and structural injury in eyes with glaucomatous optic neuropathy and normal standard automated perimetry. Bagga H; Feuer WJ; Greenfield DS 2006 Feb
Technology and the Glaucoma Suspect. Blumberg DM; De Moraes CG; Liebmann JM; Garg R; Chen C; Theventhiran A; Hood DC 2016 Jul 1
The relationship between intraocular pressure and glaucoma in a defined population. Data from the Egna-Neumarkt Glaucoma Study. Bonomi L; Marchini G; Marraffa M; Morbio R 2001 Jan-Feb
Topographic correlation and asymmetry analysis of ganglion cell layer thinning and the retinal nerve fiber layer with localized visual field defects. Casado A; Cervero A; Lopez-de-Eguileta A; Fernandez R; Fonseca S; Gonzalez JC; Pacheco G; Gandara E; Gordo-Vega MA 2019
Glaucoma and intraocular pressure in EPIC-Norfolk Eye Study: cross sectional study. Chan MPY; Broadway DC; Khawaja AP; Yip JLY; Garway-Heath DF; Burr JM; Luben R; Hayat S; Dalzell N; Khaw KT; Foster PJ 2017 Sep 13
Glaucoma screening using relative afferent pupillary defect. Charalel RA; Lin HS; Singh K 2014 Mar
Can intraocular pressure asymmetry indicate undiagnosed primary glaucoma? The Chennai Glaucoma Study. Choudhari NS; George R; Baskaran M; Ve RS; Raju P; Vijaya L 2013 Jan
Analysis of inner and outer retinal layers using spectral domain optical coherence tomography automated segmentation software in ocular hypertensive and glaucoma patients. Cifuentes-Canorea P; Ruiz-Medrano J; Gutierrez-Bonet R; Pena-Garcia P; Saenz-Frances F; Garcia-Feijoo J; Martinez-de-la-Casa JM 2018
Diagnostic Accuracy of Technologies for Glaucoma Case-Finding in a Community Setting. Dabasia PL; Fidalgo BR; Edgar DF; Garway-Heath DF; Lawrenson JG 2015 Dec
Comparison of disc damage likelihood scale, cup to disc ratio, and Heidelberg retina tomograph in the diagnosis of glaucoma. Danesh-Meyer HV; Gaskin BJ; Jayusundera T; Donaldson M; Gamble GD 2006 Apr
Linear discriminant score for differentiating early primary open angle glaucoma from glaucoma suspects. Deshpande GA; Bawankule PK; Raje DV; Chakraborty M 2019 Jan
Goldmann applanation tonometry compared with corneal-compensated intraocular pressure in the evaluation of primary open-angle Glaucoma. Ehrlich JR; Radcliffe NM; Shimmyo M 2012 Sep 25
Facilitating Glaucoma Diagnosis With Intereye Retinal Nerve Fiber Layer Asymmetry Using Spectral-Domain Optical Coherence Tomography. Field MG; Alasil T; Baniasadi N; Que C; Simavli H; Sobeih D; Sola-Del Valle D; Best MJ; Chen TC 2016 Feb
Population and high-risk group screening for glaucoma: the Los Angeles Latino Eye Study. Francis BA; Varma R; Vigen C; Lai MY; Winarko J; Nguyen B; Azen S 2011 Aug 5
Diagnostic accuracy of nerve fibre layer, macular thickness and optic disc measurements made with the RTVue-100 optical coherence tomograph to detect glaucoma. Garas A; Vargha P; Hollo G 2011 Jan
Screening for glaucoma: a comparison of ophthalmoscopy and tonometry. Hammond EA; Begley PK 1979 Nov-Dec
Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: confirmation between eye screening and comprehensive eye examination diagnoses. Hark LA (Companion to Hark LA 2019, PMID 30946709) ; Myers JS; Ines A; Jiang A; Rahmatnejad K; Zhan T; Leiby BE; Hegarty S; Fudemberg SJ; Mantravadi AV; Waisbourd M; Henderer JD; Burns C; Divers M; Molineaux J; Pizzi LT; Murchison AP; Saaddine J; Pasquale LR; Haller JA; Katz LJ 2019 Dec
Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: Intraocular Pressure Measurements Found in a Population at High Risk for Glaucoma. Hark LA; Myers JS; Pasquale LR; Razeghinejad MR; Maity A; Zhan T; Hegarty SE; Leiby BE; Waisbourd M; Burns C; Divers M; Molineaux J; Henderer JD; Haller JA; Katz LJ 2019 Apr
Early glaucoma detection using the Humphrey Matrix Perimeter, GDx VCC, Stratus OCT, and retinal nerve fiber layer photography. Hong S; Ahn H; Ha SJ; Yeom HY; Seong GJ; Hong YJ 2007 Feb
Sensitivity and specificity of tests to detect eye disease in an older population. Ivers RQ; Optom B; Macaskill P; Cumming RG; Mitchell P 2001 May
Automated suprathreshold screening for glaucoma: the Baltimore Eye Survey. Katz J; Tielsch JM; Quigley HA; Javitt J; Witt K; Sommer A 1993 Nov
Evaluation of macular ganglion cell analysis compared to retinal nerve fiber layer thickness for preperimetric glaucoma diagnosis. Kaushik S; Kataria P; Jain V; Joshi G; Raj S; Pandav SS 2018 Apr
Retinal nerve fiber layer measurement and diagnostic capability of spectral-domain versus time-domain optical coherence tomography. Kaushik S; Singh Pandav S; Ichhpujani P; Gupta A; Gupta P 2011 Sep-Oct
Performance of optical coherence tomography for distinguishing between normal eyes, glaucoma suspect and glaucomatous eyes. Kiddee W; Tantisarasart T; Wangsupadilok B 2013 Jun
The effects of peripapillary atrophy on the diagnostic ability of Stratus and Cirrus OCT in the analysis of optic nerve head parameters and disc size. Kim SY; Park HY; Park CK 2012 Jul 3
Diagnostic accuracy of macular ganglion cell-inner plexiform layer thickness for glaucoma detection in a population-based study: Comparison with optic nerve head imaging parameters. Koh V; Tham YC; Cheung CY; Mani B; Wong TY; Aung T; Cheng CY 2018
Crete, Greece glaucoma study. Kozobolis VP; Detorakis ET; Tsilimbaris M; Siganos DS; Vlachonikolis IG; Pallikaris IG 2000 Apr
Comparison of the Abilities of SD-OCT and SS-OCT in Evaluating the Thickness of the Macular Inner Retinal Layer for Glaucoma Diagnosis. Lee KM; Lee EJ; Kim TW; Kim H 2016
Diagnostic Ability of Wide-field Retinal Nerve Fiber Layer Maps Using Swept-Source Optical Coherence Tomography for Detection of Preperimetric and Early Perimetric Glaucoma. Lee WJ; Na KI; Kim YK; Jeoung JW; Park KH 2017 Jun
Comparison of glaucoma-diagnostic ability between wide-field swept-source OCT retinal nerve fiber layer maps and spectral-domain OCT. Lee WJ; Oh S; Kim YK; Jeoung JW; Park KH 2018 Sep
The Framingham Eye Study monograph: An ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973-1975. Leibowitz HM; Krueger DE; Maunder LR; Milton RC; Kini MM; Kahn HA; Nickerson RJ; Pool J; Colton TL; Ganley JP; Loewenstein JI; Dawber TR 1980 May-Jun
Comparison of standard automated perimetry, frequency-doubling technology perimetry, and short-wavelength automated perimetry for detection of glaucoma. Liu S; Lam S; Weinreb RN; Ye C; Cheung CY; Lai G; Lam DS; Leung CK 2011 Sep 21
A novel tele-eye protocol for ocular disease detection and access to eye care services. Maa AY; Evans C; DeLaune WR; Patel PS; Lynch MG 2014 Apr
Diagnostic Accuracy of Technology-based Eye Care Services: The Technology-based Eye Care Services Compare Trial Part I. Maa AY; Medert CM; Lu X; Janjua R; Howell AV; Hunt KJ; McCord S; Giangiacomo A; Lynch MG 2020 Jan
Comparison of different screening methods for the detection of visual field defects in early glaucoma. Marraffa M; Marchini G; Albertini R; Bonomi L 1989 Jan
Development of a new algorithm based on FDT Matrix perimetry and SD-OCT to improve early glaucoma detection in primary care. Morejon A; Mayo-Iscar A; Martin R; Ussa F 2019
Automated perimetry, tonometry, and questionnaire in glaucoma screening. Mundorf TK; Zimmerman TJ; Nardin GF; Kendall KS 1989 Nov 15
Structure-function relationship and diagnostic value of RNFL Area Index compared with circumpapillary RNFL thickness by spectral-domain OCT. Park HY; Park CK 2013 Feb
Comparing spectral-domain optical coherence tomography and standard automated perimetry to diagnose glaucomatous optic neuropathy. Rao HL; Yadav RK; Addepalli UK; Begum VU; Senthil S; Choudhari NS; Garudadri CS 2015 Jun-Jul
The Diagnostic Ability of Ganglion Cell Complex Thickness-to-Total Retinal Thickness Ratio in Glaucoma in a Caucasian Population Sarigul Sezenoz A; Gur Gungor S; Akman A; Ozturk C; Cezairlioglu S; Aksoy M; Colak M 2020 Mar 5
Diagnostic Performance of Peripapillary Retinal Nerve Fiber Layer Thickness for Detection of Glaucoma in an Elderly Population: The ALIENOR Study. Schweitzer C; Korobelnik JF; Le Goff M; Rahimian O; Malet F; Rougier MB; Delyfer MN; Dartigues JF; Delcourt C 2016 Nov 1
Asian-specific vertical cup-to-disc ratio cut-off for glaucoma screening: An evidence-based recommendation from a multi-ethnic Asian population. Soh ZD; Chee ML; Thakur S; Tham YC; Tao Y; Lim ZW; Mani B; Wong TT; Aung T; Cheng CY 2020 Dec
Comparison of retinal nerve fiber layer thickness measured by Cirrus HD and Stratus optical coherence tomography. Sung KR; Kim DY; Park SB; Kook MS 2009 Jul
A population-based evaluation of glaucoma screening: the Baltimore Eye Survey. Tielsch JM (Companian to Katz J 1993); Katz J; Singh K; Quigley HA; Gottsch JD; Javitt J; Sommer A 1991 Nov 15
Screening for glaucoma in the community by non-ophthalmologically trained staff using semi automated equipment. Vernon SA; Henry DJ; Cater L; Jones SJ 1990
Analysis of Ganglion Cell Complex and Retinal Nerve Fiber Layer Thickness in Glaucoma Diagnosis. Vidas S; Popovic-Suic S; Novak Laus K; Jandrokovic S; Tomic M; Jukic T; Kalauz M 2017 Sep
The Evonik-Mainz Eye Care-Study (EMECS): Development of an Expert System for Glaucoma Risk Detection in a Working Population. Wahl J; Barleon L; Morfeld P; Lichtmess A; Haas-Brahler S; Pfeiffer N 2016
Diagnostic ability of macular ganglion cell-inner plexiform layer thickness in glaucoma suspects. Xu X; Xiao H; Guo X; Chen X; Hao L; Luo J; Liu X 2017 Dec

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