Recently Published Projects

Objectives: Purpose of the Review: The Centers for Medicare and Medicaid Services (CMS) nominated the topic to the Agency for Healthcare Research and Quality for a Technology Assessment. The scope of the report’s protocol was developed to inform CMS’s coverage decisions. The report will address contextual questions (CQs) and conduct a systematic review (SR). The CQs cover background material to help to understand the findings of the SR, including information on currently-used treatment modalities for OSA, the postulated rationales for use of CPAP, currently-used measures of AHI and related measures in contemporary research and clinical settings, validated sleep questionnaires. The CQs also cover discussion of the ideal study designs for establishing validity of surrogate or intermediate measures. The CQs will be addressed using a, best-evidence, but nonsystematic approach. The SR will (1) summarize evidence on the validity of measures of sleep and breathing as surrogates (or intermediate outcomes) for clinically significant outcomes in patients with OSA, effectively assessing the linkage between the former and the latter, and (2) synthesize evidence on the (comparative) efficacy, effectiveness and safety of CPAP to prevent clinically important outcomes. The SR will attempt to describe heterogeneity of treatment effects in terms of diversity of patient populations, devices and treatment protocols, outcome definitions and study design characteristics. For included randomized controlled trials (RCT), we will examine the concordance among AHI (and similar measures), validated sleep questionnaires, and clinical outcomes. The intended audience includes CMS and non-CMS stakeholders including guideline developers, clinicians and other providers of care for patients with OSA, healthcare policy makers, and patients.

Objectives: Purpose of the Review: The Centers for Medicare and Medicaid Services (CMS) nominated the topic to the Agency for Healthcare Research and Quality for a Technology Assessment. The scope of the report’s protocol was developed to inform CMS’s coverage decisions. The report will address contextual questions (CQs) and conduct a systematic review (SR). The CQs cover background material to help to understand the findings of the SR, including information on currently-used treatment modalities for OSA, the postulated rationales for use of CPAP, currently-used measures of AHI and related measures in contemporary research and clinical settings, validated sleep questionnaires. The CQs also cover discussion of the ideal study designs for establishing validity of surrogate or intermediate measures. The CQs will be addressed using a, best-evidence, but nonsystematic approach. The SR will (1) summarize evidence on the validity of measures of sleep and breathing as surrogates (or intermediate outcomes) for clinically significant outcomes in patients with OSA, effectively assessing the linkage between the former and the latter, and (2) synthesize evidence on the (comparative) efficacy, effectiveness and safety of CPAP to prevent clinically important outcomes. The SR will attempt to describe heterogeneity of treatment effects in terms of diversity of patient populations, devices and treatment protocols, outcome definitions and study design characteristics. For included randomized controlled trials (RCT), we will examine the concordance among AHI (and similar measures), validated sleep questionnaires, and clinical outcomes. The intended audience includes CMS and non-CMS stakeholders including guideline developers, clinicians and other providers of care for patients with OSA, healthcare policy makers, and patients.

Objectives: 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.

Objectives: 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.

Objectives: Background: In 2016, the United States Preventive Services Task Force (USPSTF) concluded that the current evidence was insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults (I Statement). Although the USPSTF found that screening can identify persons with impaired visual acuity and that effective treatments are available for common causes of impaired visual acuity, direct evidence found no differences between vision screening versus no screening on visual acuity or other clinical outcomes. Purpose: To systematically review the evidence on screening for impaired visual acuity in older adults 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 USPSTF report, and manually reviewed reference lists. Study Selection: Randomized controlled trials (RCTs) and controlled observational studies on benefits and harms of screening versus no screening; studies on diagnostic accuracy of screening tests and instruments (including questionnaires); and benefits and harms of vascular endothelial growth factor (VEGF) inhibitors for wet age-related macular degeneration (AMD) and antioxidant vitamins and minerals for dry AMD in adults age 65 years and older. 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 25 studies were included in this review (13 trials, 11 diagnostic accuracy studies, and one systematic review [of 19 trials]). Sixteen studies were carried forward from the 2016 review for the USPSTF, eight studies were new, and the systematic review utilized in the 2016 review for the USPSTF was updated to include six new trials. Four trials (N=4,819) of screening versus no screening, usual care, or delayed screening of older adults found no differences in visual acuity or other clinical outcomes. Visual acuity tests (3 studies; N=6,493) were associated with suboptimal diagnostic accuracy for identifying visual conditions compared with a complete examination by an ophthalmologist (sensitivity 0.27 to 0.75 and specificity 0.51 to 0.87); evidence on other screening tests was limited. Three studies (N=5,203) found that a screening question was not accurate for identifying older persons with impaired visual acuity compared with a visual acuity eye chart (sensitivity 0.17 to 0.81 and specificity 0.19 to 0.84). For wet AMD, four trials (N=2,086) found VEGF inhibitors associated with greater likelihood of ≥15 letters (3 lines) of visual acuity gain (risk ratio [RR] 2.92, 95% confidence interval [CI] 1.20 to 7.12, I2=76%; absolute risk difference [ARD] 10%), <15 letters (3 lines) of visual acuity loss (RR 1.46, 95% CI 1.22 to 1.75, I2=80%; ARD 27%) and having vision 20/200 or better (RR 1.47, 95% CI, 1.30 to 1.66, I2=42%; ARD 24%) at 1 year versus sham injection. VEGF inhibitors were associated with better vision-related function and quality of life measures versus sham injection at 1 and 2 years, the difference (~8 points on a 0 to 100 scale) was above the minimum clinically important difference threshold. For dry AMD, a systematic review of 19 trials found antioxidant multivitamins associated with decreased risk of progression to late AMD (3 trials, N=2,445 people, odds ratio [OR] 0.72, 95% CI 0.58 to 0.90) and >3 lines visual acuity loss (1 trial, N=1,791 people, OR 0.77, 95% CI 0.62 to 0.96) versus placebo. Results were primarily driven by the large (n=3,640) Age-Related Eye Disease Study (AREDS). Zinc was associated with decreased risk of progression to late AMD versus placebo (3 trials, N=3,790 people, OR 0.83, 95% CI 0.70 to 0.98) and decreased risk of >3 lines visual acuity loss that was of borderline statistical significance (2 trials, 3,791 people, RR 0.87, 95% CI 0.75 to 1.00). Evidence on the effects of other vitamins and mineral treatments was limited or showed no clear effects on AMD progression or visual acuity. The AREDS trial found zinc use associated with increased risk for hospitalization due to genitourinary causes versus nonuse (7.5% vs. 4.9%, RR, 1.47, 95% CI, 1.19 to 1.80); other serious harms were infrequent, with no differences between groups. The AREDS 2 trial found the AREDS formulation with beta carotene associated with increased risk of lung cancer versus the AREDS formulation without beta carotene when current smokers were excluded from the analysis (2.0% vs. 0.9%, p=0.04); almost all lung cancers occurred in former smokers. Limitations: Screening trials had methodological limitations that could have attenuated potential benefits; utilized an update to a previously included systematic review on antioxidant multivitamins and minerals for dry AMD; evidence on the effectiveness of treatment for dry AMD relied heavily on results of a single trial (AREDS); non-English–language studies excluded; too few randomized trials to perform formal assessments for publication bias with graphical or statistical methods for small sample effects; statistical heterogeneity in pooled estimates for VEGF inhibitors versus sham, though inconsistency was in magnitude (not direction) of effect. Conclusions: Impaired visual acuity is common in older adults and effective treatments are available for common causes of impaired visual acuity. Visual acuity testing is the reference standard for identifying impaired visual acuity, but has low diagnostic accuracy compared with an ophthalmological exam for identifying visual conditions not necessarily associated with impaired visual acuity; screening questions have low diagnostic accuracy compared with visual acuity testing. Direct evidence found no significant difference between vision screening in older adults in primary care settings versus no screening in visual acuity-related outcomes or other clinical outcomes.