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. Surveillance was conducted through January 21, 2022.

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=75,887) 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 0.75 to 0.83 and specificity 0.92, 95% CI 0.87 to 0.96), 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 (9 studies, N=1,522, sensitivity 0.74, 95% CI 0.68 to 0.80 and specificity 0.91, 95% CI 0.80 to 0.96), tonometry (13 studies, N=32,892, sensitivity 0.48, 95% CI 0.31 to 0.66 and specificity 0.94, 95% CI 0.90 to 0.96), and the Humphrey Visual Field Analyzer (6 studies, N=11,244, sensitivity 0.87, 95% CI 0.69 to 0.95 and specificity 0.82, 95% CI 0.66 to 0.92). 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:

The screening trial had methodological limitations and few patients were referred for glaucoma evaluation; 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.