Article

Glaucoma Screening in 2018

The when, why, how, and who of screening for glaucoma.

Glaucoma is a disease suited to screening. It can be detected at early stages of the disease and is treatable.1 The goal of screening is to detect glaucoma at the earliest possible stage in order to preserve visual function, and maintain quality of life for our patients. Prior research suggests that up to 40% of legal blindness noted in varied populations would be avoidable with appropriate screening and subsequent management.2-4 Glaucoma makes up a significant number of these needlessly blind patients (up to 15% in an urban black elderly population).2 Additionally, up to half of all patients with glaucoma are unaware of their diagnosis.5 Lowering intraocular pressure (IOP) is associated with reduced glaucoma onset and progression. This has been demonstrated in the Ocular Hypertension Treatment Study, The Advanced Glaucoma Intervention Study, The Collaborative Initial Glaucoma Treatment Study, and the Early Manifest Glaucoma trial.6-9 In addition to decreasing onset or progression of visual field defects, there are quantifiable morbidity and mortality benefits to treating glaucoma. Individuals with glaucoma who drive have been shown to have a higher risk of motor vehicle accidents when afflicted with more severe visual field defects.10 This has an impact not only on the well-being of our patients, but also on the safety of our communities.

A clinician can learn a great deal about whether they should screen for glaucoma by taking a thorough medical history. Some of the most pertinent prior diagnoses include a history of migraine, vasospasm, type 2 diabetes mellitus, hypertension, hypotension or shock. A family history of glaucoma should also be gathered. This should include which relatives were diagnosed with glaucoma, at what age, and with what severity; for example, whether treatment consisted of drops or surgery and whether the relative went blind from glaucoma.

Findings With an Ocular Exam

The ocular exam plays a large role in the initial and subsequent patient visits in screening for glaucoma. Important parts at the initial or first several visits should include best-corrected visual acuity, refraction, a pupil exam, IOP (prior to dilation or gonioscopy, by Goldmann applanation), motility, and alignment. The anterior-segment exam should include presence or absence of pigment, iris transillumination defects, exfoliative material, inflammatory precipitates, scarring, neovascularization of the iris, lens status and any other pertinent abnormalities. Gonioscopy with an indentation gonioprism should be performed for every patient with a glaucoma diagnosis or suspicion for developing glaucoma in the future.

A dilated fundus exam should be performed, with special attention paid to the appearance of the optic nerve head and retinal nerve fiber layer. Certain features may be suggestive of prior, ongoing, or future damage from glaucoma, including disc hemorrhage, thinning or notching of the neuroretinal rim (especially inferiorly or superiorly) and retinal nerve fiber layer, and excavation of the optic cup.11-13 A description or graphical representation (drawing) of the optic nerve head should be included.

Diagnostic Testing

Standard automated perimetry, stereo disc photographs, central corneal thickness, optical coherence tomography of the optic nerve head and retinal nerve fiber layer, and corneal hysteresis are all useful for investigating the risk of developing glaucoma or diagnosing manifest glaucoma in patients. Frequency doubling technology likely has an adjunctive role in glaucoma screening, as well.14

What Makes a Good Test?

Sensitivity (the ability of a test to correctly identify those with glaucoma) and specificity (the ability of a test to correctly identify those without glaucoma) are both important characteristics of a diagnostic test. However, neither sensitivity nor specificity take into account the population prevalence of a disease. This is of vital importance in glaucoma.

Positive and negative predictive values do take into account the prevalence of disease in the population. Positive predictive value (PPV) is the proportion of people testing positive for the disease who actually have it. Negative predictive value (NPV) is the proportion of people testing negative for the disease who actually do not have it. In higher prevalence populations, the positive predictive value of our screening tests is higher.

Receiver operating characteristic (ROC) curves are graphical displays that plot the sensitivity and false-positive rate help to separate those individuals with the condition from those individuals without the condition. Receiver operating characteristic curves give an idea about the usefulness of a test with a score of 0.5 being equivalent to random chance and 1.0 indicating an ideal test. They can be quite useful to determine thresholds for testing (for example, in novel glaucoma diagnostic technologies).

No individual test is sufficient to be used as a screening tool to detect incident glaucomatous disease. Automated visual field testing contains multiple caveats (including a learning curve for those taking the visual field). Structural tests, such as optical coherence tomography of the optic nerve head and retinal nerve fiber layer, likely have utility. However, they commonly result in false positives.15 In most circumstances, a combination of these tests is required.

In prior research, we identified a subset of screening tests geared to detect visually significant eye disease in American Indian/Alaska Natives of the Pacific Northwest, including glaucoma.16 The tests included visual acuity less than 20/40, abnormal FDT, abnormal nonmydriatic photographs, and abnormal confocal scanning laser ophthalmoscopy. This resulted in sensitivity of 94%, specificity of 32%, PPV of 57%, NPV of 84%, and a ROC curve of 83% of detecting visually significant eye disease, including glaucoma.

The Philadelphia Glaucoma Detection and Treatment Project17,18 performed a detection examination consisting of comprehensive history and ophthalmic exam with automated visual field testing and fundus color photography. By screening in a high-risk (aged 50 years or older, predominantly black and underserved) population in Philadelphia, 39% of their sample was found to have glaucoma related disease, including glaucoma (10%), or met the definition for glaucoma suspect (29%). This illustrates the importance of carefully selecting the population one is screening to maximize benefit to all involved.

Who Should Undergo Screening?

Clearly, there is a marked difference in glaucoma incidence or prevalence depending on the population. The biggest risk factor for glaucoma is older age. It is recommended to check IOP as part of the general comprehensive eye exam in asymptomatic adults.19 Other individual factors may greatly increase the relative risk of developing glaucoma.

Certain races/ethnicities have higher prevalence of glaucoma. The prevalence of open-angle glaucoma (OAG) in whites aged 40 years and older has been found to range between 1% and 2%. Open-angle glaucoma has been found to be up to 4 times more prevalent in black and Latino populations than white populations, with black persons at increased risk of blindness from glaucoma (up to 15 times higher than whites).20-22 This risk increases with increasing age. Primary angle-closure glaucoma (PACG) is much less common in white populations (estimated at 0.1% prevalence). However, Eskimo populations in the arctic have been found to have PACG prevalence up to 20-40 times higher than whites, with 17% of the population over 50 years old found to have occludable angles in one study.23 Northwest and Alaska Native Americans have been found to have prevalence of OAG up to 6%.24

A family history of glaucoma (particularly in first-degree relative(s)) increases the risk of glaucoma. Prevalence among siblings of patients with glaucoma has been found to range between 7% and 10%.25,26 Despite this, approximately half of individuals with an affected family member are unaware of their higher lifetime risk of glaucoma.27 Age of onset of family members and disease severity should factor in the decision about at what age to start screening for glaucoma during eye exams, and with what frequency the patient should be examined.

In the United States, Medicare Part B insurance takes some of these risk factors into consideration and covers screening eye exams for patients with specific risk factors, including a family history of glaucoma, patients aged 50 or older and African American, patients age 65 or older and Hispanic, and/or personal history of diabetes mellitus.28 Many individuals that meet the above criteria may not be aware, and it is our role as eye care providers to offer these services and implement the appropriate screening for the indicated populations.

How Can We Optimize Screening?

In addition to the risk factors in your population, we know that prevalence varies widely depending on location of testing. For example, the population in a medical clinic has a higher prevalence of glaucoma, but screening in the community outside of traditional health care settings can pick up earlier disease. One is more likely to find glaucoma at certain locations in the community, such as senior centers or nursing homes (even when controlling for age), or less commonly found, such as work sites.1,2,29 Public service announcements have been noted to be an effective tool in recruiting members of the population of interest for screening.30 Targeting higher risk individuals with such approaches is likely the most feasible and cost effective approach.31

How Frequently Should Screening Be Performed?

The frequency of screening depends on the individual or population risk factors, including age, race, family history, biometric data (such as central corneal thickness), gonioscopy, IOP, and risk of losing vision from glaucoma. Other patient characteristics such as burden of exams (financial or otherwise) and willingness to accept risk of vision loss play in to how frequently a patient should be screened. However, asymptomatic, low-risk individuals with reassuring testing can be followed with a general eye exam at regularly scheduled intervals. Higher risk individuals may need to be followed as frequently as every 2 months to 4 months, depending on the clinical and individual circumstances. Official recommendations on screening intervals vary widely.

The American Academy of Ophthalmology (AAO) recommends comprehensive eye exams at different intervals depending on age and risk factors.19,32 Individuals without any risk factors and younger than 40 years-old should be seen every 5 years to 10 years; those 40 years to 54 years old should be seen every 2 years to 4 years; and those 55 years to 64 years old should be seen every 1 year to 3 years. Individuals with risk factors (including nonwhite race) and younger than 40 years old should be seen every 1 year to 2 years; those 40 years to 54 years old every 1 year to 3 years; and those 55 years and older should receive comprehensive exams every 1 year to 2 years.

Despite the recommendations from the AAO, the United States Preventive Services Task Force (USPSTF) came out with a report in 2013 that evidence was insufficient (grade 1) to recommend routine glaucoma screening on an asymptomatic population.33 They included high-risk (family history, nonwhite race) individuals in their analysis and felt that the evidence was also insufficient for this group. The study authors’ defense for this recommendation is that there is no consensus on a gold standard for glaucoma diagnosis and that the existing (mostly cross-sectional studies) are at high risk of bias. They recommend performing randomized controlled trials in a population-based sample.

As glaucoma specialists, we are intuitively aware that the populations we interact with on a daily basis are higher risk. Therefore, implementing a screening program that is tailored to the population you care for is of paramount importance to the eye health and well-being of your patients. It should take into consideration population and individual level characteristics, as well as financial feasibility and sustainability, both of your practice and for the population at large. GP

REFERENCES

  1. Mansberger SL, Demirel S. Early detection of glaucomatous visual field loss: why, what, where, and how. Ophthalmol Clin North Am. 2005;18(3):365-373.
  2. Tielsch JM, Javitt JC, Coleman A, Katz J, Sommer A. The prevalence of blindness and visual impairment among nursing home residents in Baltimore. N Engl J Med. 1995;332(18):1205-1209.
  3. Tielsch JM, Sommer A, Witt K, Katz J, Royall RM. Blindness and visual impairment in an American urban population. The Baltimore Eye Survey. Arch Ophthalmol. 1990;108(2):286-290.
  4. Dana MR, Tielsch JM, Enger C, Joyce E, Santoli JM, Taylor HR. Visual impairment in a rural Appalachian community. Prevalence and causes. JAMA. 1990;264(18):2400-2405.
  5. Quigley HA, West SK, Rodriguez J, Munoz B, Klein R, Snyder R. The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. Arch Ophthalmol. 2001;119(12):1819-1826.
  6. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279.
  7. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713; discussion 829-730.
  8. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108(11):1943-1953.
  9. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration.The AGIS Investigators. Am J Ophthalmol. 2000;130(4):429-440.
  10. McGwin G Jr, Huisingh C, Jain SG, Girkin CA, Owsley C. Binocular visual field impairment in glaucoma and at-fault motor vehicle collisions. J Glaucoma. 2015;24(2):138-143.
  11. Jonas JB, Budde WM. Optic cup deepening spatially correlated with optic nerve damage in focal normal-pressure glaucoma. J Glaucoma. Aug 1999;8(4):227-231.
  12. Laemmer R, Nguyen TK, Horn FK, Mardin CY. Morphologic and functional glaucomatous change after occurrence of single or recurrent optic disc hemorrhages. Graefes Arch Clin Exp Ophthalmol. 2010;248(11):1683-1684; author reply 1685.
  13. Quigley HA, Sommer A. How to use nerve fiber layer examination in the management of glaucoma. Trans Am Ophthalmol Soc. 1987;85:254-272.
  14. Mansberger SL, Johnson CA, Cioffi GA, et al. Predictive value of frequency doubling technology perimetry for detecting glaucoma in a developing country. J Glaucoma. 2005;14(2):128-134.
  15. Chong GT, Lee RK. Glaucoma versus red disease: imaging and glaucoma diagnosis. Curr Opin Ophthalmol. 2012;23(2):79-88.
  16. Kopplin LJ, Mansberger SL. Predictive value of screening tests for visually significant eye disease. Am J Ophthalmol. 2015;160(3):538-546.
  17. Hark L, Waisbourd M, Myers JS, et al. Improving access to eye care among persons at high-risk of glaucoma in philadelphia--design and methodology: the Philadelphia Glaucoma Detection and Treatment Project. Ophthalmic Epidemiol. 2016;23(2):122-130.
  18. Waisbourd M, Pruzan NL, Johnson D, et al. The Philadelphia Glaucoma Detection and Treatment Project: detection rates and initial management. Ophthalmology. 2016;123(8):1667-1674.
  19. AAO PPP Committee, Hoskins Center for Quality Eye Care. Comprehensive Adult Medical Eye Evaluation. 2015. Available at: https://www.aao.org/preferred-practice-pattern/comprehensive-adult-medical-eye-evaluation-2015 . Accessed 9/1/2018.
  20. Friedman DS, Wolfs RC, O’Colmain BJ, et al; Eye Diseases Prevalence Research Group. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004;122(4):532-538.
  21. Javitt JC, McBean AM, Nicholson GA, Babish JD, Warren JL, Krakauer H. Undertreatment of glaucoma among black Americans. N Engl J Med. 1991;325(20):1418-1422.
  22. Varma R, Ying-Lai M, Francis BA, et al; Los Angeles Latino Eye Study Group. Prevalence of open-angle glaucoma and ocular hypertension in Latinos: the Los Angeles Latino Eye Study. Ophthalmology. 2004;111(8):1439-1448.
  23. Arkell SM, Lightman DA, Sommer A, Taylor HR, Korshin OM, Tielsch JM. The prevalence of glaucoma among Eskimos of northwest Alaska. Arch Ophthalmol. 1987;105(4):482-485.
  24. Mansberger SL, Romero FC, Smith NH, et al. Causes of visual impairment and common eye problems in Northwest American Indians and Alaska Natives. Am J Public Health. 2005;95(5):881-886.
  25. Kass MA, Becker B. Genetics of primary open-angle glaucoma. Sight Sav Rev. 1978;48(1):21-28.
  26. Sung VC, Koppens JM, Vernon SA, et al. Longitudinal glaucoma screening for siblings of patients with primary open angle glaucoma: the Nottingham Family Glaucoma Screening Study. Br J Ophthalmol. 2006;90(1):59-63.
  27. Eke T, Reddy MA, Karwatowski WS. Glaucoma awareness and screening uptake in relatives of people with glaucoma. Eye (Lond). 1999;13(Pt 5):647-649.
  28. U.S. Centers for Medicare & Medicaid Services. Your medicare coverage: glaucoma tests. 2018. Available at: https://www.medicare.gov/coverage/glaucoma-tests.html . Accessed 9/1/2018.
  29. Mansberger SL, Johnson CA, Cioffi GA. The results of screening frequency doubling technology perimetry in different locations of the community. J Glaucoma. 2007;16(1):73-80.
  30. Hoffelt Z, Fallon S, Wong BA, et al. Glaucoma public service announcements: factors associated with follow-up of participants with risk factors for glaucoma. Ophthalmology. 2011;118(7):1327-1333.
  31. Burr JM, Mowatt G, Hernandez R, et al. The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation. Health Technol Assess. 2007;11(41):iii-iv, ix-x, 1-190.
  32. AAO PPP Glaucoma Panel Hoskins Center for Quality Eye Care. Primary Open-Angle Glaucoma PPP. 2015. Available at: https://www.aao.org/preferred-practice-pattern/primary-open-angle-glaucoma-ppp-2015 . Accessed 9/1/2018.
  33. United States Preventive Services Task Force (USPSTF). Screening for glaucoma: comparative effectiveness report. 2013. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/glaucoma-screening . Accessed 9/1/2018.