Consensus 10

10^th Consensus Meeting: Diagnosis of Primary Open Angle Glaucoma

Seattle, USA, April 30, 2016

Edited by: R.N. Weinreb, D.F. Garway-Heath, C. Leung, F.A. Medeiros, J. Liebmann
2016. Many photos and figures. Hardbound.
ISBN-10: 90 6299 262 5.
ISBN-13: 978 90 6299 262 1
Published by: Kugler Publications.
Click here for more information on all publications in the Consensus series.

See meeting photos

Summary Consensus Points

• Structure
• Vision function
• Structure and function
• Risk factors (ocular)
• Risk assessment
• Screening

Section 1 – Structure

1. Clinical evaluation and documentation of the optic nerve head is essential for the diagnosis and the monitoring of glaucoma.
2. Clinical diagnosis of glaucoma is predicated on the detection of a thinned retinal nerve fiber layer (RNFL) and narrowed neuroretinal rim.
   Comments: These features often are accompanied by deformation of the optic nerve head (ONH) (cupping). These features often appear first in the supero- or inferotemporal
   quadrants. Although these features are characteristic of POAG, it is important to exclude non-glaucomatous optic neuropathies.
3. Detecting progressive glaucomatous RNFL thinning and neuroretinal rim narrowing are the best currently available gold standards for glaucoma diagnosis.
   Comment: Disease-related damage should be differentiated from age-related change.
4. The diagnosis of glaucoma does not always require the detection of visual field defects with perimetry.
   Comments: Perimetric defects that correspond to structural findings increase the likelihood of glaucoma. Perimetry is indispensable for documentation and monitoring of functional decline in glaucoma.
5. Assessment of the color and the configuration (size and shape) of the neuroretinal rim is important to differentiate glaucomatous from non-glaucomatous optic neuropathies.
   Comment: A pale rim suggests non-glaucomatous optic neuropathy.
6. Photography is effective to document glaucomatous optic disc appearance and nerve fiber layer damage.
   Comments: Photography is particularly useful for detecting and documenting optic disc hemorrhage and rim color. Stereophotography is particularly useful for documenting optic disc topography.
7. Imaging technologies including optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy (CSLO) and scanning laser polarimetry (SLP) provide an objective and quantitative approach to detect and monitor glaucoma.
8. OCT may be the best currently available digital imaging instrument for detecting and tracking optic nerve structural damage in glaucoma.
9. RNFL thickness is the most clinically helpful parameter of the ones currently available with OCT.
   Comments: Macular RGC loss in glaucoma also can be detected by OCT. RNFL thickness and macular RGC loss are complementary. Pitfalls of OCT such as artifacts and false segmentation should be considered when using OCT. GCIPL thickness (macula): The macula has the highest density of RGCs.
10. It is difficult in myopic eyes to differentiate those with and without glaucoma.
    Comments: In myopic eyes, documented progressive optic neuropathy can be used to make the differential diagnosis of glaucoma. Reference databases do not currently include highly myopic eyes and, therefore, are not appropriate for diagnosing RNFL damage in them.

Section 2 – Vision function

1. Functional testing is essential for the evaluation, staging and monitoring of glaucoma
   Comment: Standard automated perimetry (SAP) is the reference standard for all functional testing.
2. Clinical decisions should be made based on reliable visual field tests.
   Comments: Visual field defects should be reproducible and/or should be consistent with the location of the optic nerve defects. The most important reliability criterion is the false positive rate.
3. In the presence of glaucomatous optic neuropathy, a Glaucoma Hemifield Test (GHT) ‘outside normal limits’ in a reliable visual field indicates that glaucomatous visual field loss is present.
   Comment: For instruments not calculating a GHT, an abnormal (P < 5%) pattern standard deviation (PSD) or square-root-loss variance (sLV) likely have similar diagnostic value.
4. When glaucomatous optic neuropathy (GON) is suspected, a GHT criterion of ‘outside normal limits’ or ‘borderline’ in a reliable visual field increases the probability that an eye has glaucoma.
   Comment: The level of probability for glaucoma depends on the presence and magnitude of other risk factors for glaucoma (such as raised intraocular pressure) and the quality of evidence that there is no GON.
5. Before a visual field defect can be confirmed as glaucomatous, retinal and non-glaucomatous optic disc conditions should be excluded by a careful examination of the retina and optic disc.
   Comment: If the pattern of visual field loss suggests a neurological origin, or if there is incongruity between the pattern of visual field loss and optic disc and retinal nerve fiber layer appearance, then further investigation is warranted (e.g., color vision testing, neuroimaging).
6. Standard white-on-white automated perimetry (SAP), with a fixed testing matrix covering at least the central 24 degrees, is preferred for the diagnosis of glaucomatous visual field loss.
   Comments: Goldmann size III stimuli are conventionally used in most automated perimeters in clinical practice for glaucoma diagnosis. For more severe cases size V, increases the dynamic range and reduces variability of test results. Using the 10-2 strategy, in addition to the conventional 24-2 Humphrey grid, can improve the detection of central functional loss
7. Threshold algorithms are preferred over supra-threshold algorithms for glaucoma diagnosis.
   Comment: Supra-threshold algorithms can be helpful in cases of unreliable results from threshold testing algorithms.
8. Neither short-wavelength automated perimetry (SWAP) nor frequency doubling technology (FDT) perimetry have superior diagnostic precision to SAP.
   Comments: Patients should be followed consistently with same visual function test and ideally one with statistical support for recognizing change. The more diagnostic tests that are performed, the more likely it is that one will be ‘outside normal limits’, therefore increasing the number of false positive results.
9. Patients who are at risk for glaucoma and have normal standard automated perimetry (SAP) should have their visual function monitored to detect deterioration and hence establish a glaucoma diagnosis.
   Comment: The earliest evidence for glaucoma may be functional or structural. Therefore, both should be measured to ensure that the onset of glaucoma damage is not overlooked.
10. Deterioration may be first detected by the glaucoma hemifield test (GHT) (or summary parameters) or by trend analysis of measurements over time. Which analysis is most sensitive varies between patients and so both should be done.
    Comments: Progressive functional loss identified by SAP may be a generalized reduction in visual field sensitivity alone, or focal loss alone, or a combination of both. If trend analysis indicates a change in VFI, MD or mean defect, then one needs to exclude media opacity (e.g., cataract).
11. There only is weak evidence for the use of functional measurements other than SAP to detect the earliest signs of deterioration.
12. There is a limited role for ERG testing in the routine diagnosis and management of glaucoma.
    Comment: PERG and PhNR testing are not substitutes for standard automated perimetry (SAP), nor are they substitutes for optical coherence tomography (OCT) imaging.
13. The classification of glaucomatous functional damage in stages of increasing severity is a useful tool in the management of patients affected with chronic glaucoma.
    Comment: Staging provides a summary metric of disease severity which may guide treatment decisions.
14. While staging systems may be clinically useful, no current staging system shows all the information present in a visual field printout.
    Comment: For instance, staging systems do not identify the location of damage.
15. POAG-related functional impairment affects patients’ ability to perform daily activities and also their well-being (vision-related quality of life). Worse vision-related quality of life is associated with greater severity of the disease.
    Comment: Vision-related quality of life may be assessed with questionnaires, by performance tasks (e.g., reading), event monitoring (e.g., falls) and measures of behavior (e.g., GPS trackers).
16. Understanding how glaucoma and glaucoma treatment affects patients’ quality of life, and how this varies across the severity continuum, can have practical value in the clinic. It can inform treatment choices and communication to patients of the implications of disease worsening.
17. The impact of glaucomatous visual field loss on vision-related function and quality of life depends on the location of the defect in the field of vision and the task involved.
    Comment: risk of falling, eye-hand coordination and mobility may be most affected by loss in the inferior hemifield, whereas reading may be more affected by superior hemifield loss.
18. Aspects of glaucoma other than visual field loss, such as reduced central contrast sensitivity and acuity (in more advanced disease), may affect vision-related function and quality of life.
    Comment: Contrast sensitivity is more strongly associated with specific aspects of reading performance than visual field measures.

Section 3 – Structure and function

1. In glaucoma, there is a continuous relationship between standard structural and functional (dB for visual field) measurements, which appears nonlinear with current methods of testing and conventional scaling of metrics.
   Comment: When both are transformed into linear scales, then a linear relationship between structure and function can be observed.
2. Current structural and functional measurement methods show considerable variability.
3. Visual field test locations are spatially related to regions on the optic nerve head, peripapillary retina and macular area.
   Comment: Understanding these spatial relationships can be useful for the diagnosis of glaucoma.
4. With current technology, detection of structural defects generally precedes detectable functional defects in glaucoma patients while functional defects can precede structural defects in some patients.
   Comment: Structural tests based on the comparison to the normative data tend to show a statistically significant glaucomatous change earlier compared to the functional tests because
   of a greater variability in functional tests.
5. The likelihood of the diagnosis of glaucoma is increased through corroboration of abnormal structural and functional tests.
   Comment: The likelihood of the diagnosis of glaucoma is increased further if there is progressive change or if additional risk factors are present, such as raised intraocular pressure.
6. When available, OCT (or an alternative imaging modality) and disc photographs with acceptable quality at baseline should be performed, against which accurate detection of change can be made.
   Comments: Disc photography is a useful adjunct for detecting hemorrhages and pallor, and also for assessing change compared with future clinical examinations. Disc hemorrhages can only
   be seen on clinical examinations and disc photographs.
7. As yet there is no widely-accepted method of combining the results of structural and functional tests.
   Comment: Several proposed methods for combining structural and/or functional measurements offer advantages over traditional parameters and continue to be investigated.
8. Physicians should be aware of false-positive tests and over-diagnosing glaucoma, which are more likely when using a large number of diagnostic tests.
   Comment: Although using multiple parameters may increase overall diagnostic sensitivity, the chance will also increase of falsely labeling a change significant.

Section 4 – Risk factors (ocular)

1. Although POAG may develop at any IOP, there is strong evidence supporting higher mean intraocular pressure during follow-up as a risk factor for development and progression of glaucomatous damage.
   Comments: There is insufficient evidence and further studies are needed to elucidate which IOP parameter(s) (mean, peak and/or fluctuation, area under IOP curve, etc.) is most important in determining risk of glaucoma development or progression. There is insufficient evidence implicating IOP fluctuations as an independent risk factor for glaucoma development or progression.
2. Low ocular perfusion pressure (OPP) (the difference between systemic blood pressure and intraocular pressure) is associated with increased prevalence of open-angle glaucoma in cross-sectional studies.
   Comments: The value of OPP monitoring in daily clinical practice is not established. Due to the intrinsic relationship between OPP and IOP, it is difficult to establish an independent contribution of OPP as a risk factor for the development of glaucoma.
3. There is insufficient evidence supporting the role of provocative tests, such as the water-drinking test, as providing independent contribution to assess risk of glaucoma development and progression.
   Comment: Prospective longitudinal studies are necessary to clarify whether the water-drinking provocative test can provide additional information over office-based IOP measurements in establishing risk of glaucoma development or progression.
4. There is strong evidence supporting the role of central corneal thickness (CCT) as an important predictive factor for glaucoma development in ocular hypertensives and glaucoma suspects. Baseline CCT measurements should be obtained in patients suspected of having glaucoma.
   Comments: Algorithms to correct IOP based on CCT measurements are not recommended for routine use in clinical practice. There is insufficient evidence to conclude whether or not CCT is a true independent risk factor for glaucoma development or progression, or whether its effect is related to a tonometric artifact. There is no evidence that serial CCT measurements have value in clinical evaluation glaucoma.
5. There is strong evidence implicating lower corneal hysteresis as a risk factor for glaucoma development and progression.
   Comments: There is insufficient evidence about the mechanisms by which corneal hysteresis is associated with risk of glaucoma progression.
6. Existing evidence suggests that individuals with myopia have an increased risk of developing open angle glaucoma, with the risk being greater for people with high myopia.
   Comments: Diagnosis of glaucoma among myopic eyes can be challenging. Confirmed evidence of glaucomatous progression from a well-defined baseline is important for a correct diagnosis in many myopic individuals.
7. Disc hemorrhage is associated with increased risk of developing glaucoma and it is a marker for glaucomatous progression.
   Comment: Consideration of treatment escalation or closer follow-up should be given for patients presenting with optic disc hemorrhages.
8. Predictive models (risk calculators) may provide objective assessment of individual risk and their use should be considered in patients suspected of having glaucoma.
   Comment: Current validated risk calculators apply only to OHT patients. Moreover, they do not include all known risk factors.

Section 5 – Risk assessment

1. Primary open-angle glaucoma (POAG) occurs at all ages, and the incidence and prevalence accelerates with age.
2. Populations with the highest incidence and prevalence of POAG have African ancestry.
   Comment: Due to the earlier age of disease onset, the average duration of POAG may be greatest in individuals of African ancestry.
3. Hispanics may have higher incidence and prevalence of POAG than individuals of European ancestry (non-Hispanic whites).
4. Older age is a risk factor for glaucoma onset and progression.
5. Although an increased prevalence of POAG in men has been reported, there is not enough evidence to support an association of POAG risk with male gender.
6. Lower socioeconomic status may be associated with later presentation of POAG.
7. First-degree relatives of POAG patients are at higher risk for glaucoma.
8. Although genetic association studies have revealed multiple associated loci for POAG, there is little value for routine genetic testing to diagnose or predict the development of glaucoma at the current time.
9. There is consistent, but weak, positive association between diastolic blood pressure and IOP and between systolic blood pressure and IOP in population- based studies.
10. Lower blood pressure (BP) and ocular perfusion pressure are associated with higher glaucoma prevalence and incidence across all racial groups.
    Comment: It is not known whether ocular perfusion pressure (OPP ) is an independent risk factor for glaucoma due to the fact that IOP is intrinsically used in the calculation as performed with current methods.
11. The relationships between diastolic blood pressure, systolic blood pressure, systemic hypotension or systemic hypertension, and POAG are inconsistent.
12. The relationship between treatment of systemic hypertension and the development of POAG remains unclear.
    Comment: There are data suggesting that some patients being treated for systemic hypertension may be at greater risk for development of POAG.
13. The role of nocturnal systemic hypotension in the development of glaucoma is not known.
14. The evidence that obstructive sleep apnea is a risk factor for open-angle glaucoma (OAG) is weak and warrants further study.
15. Diabetes mellitus likely increases the risk for glaucoma onset.
16. There is insufficient evidence to determine if thyroid disease is associated with glaucoma.
17. Although there is some evidence that reduction of estrogen production in post-menopausal women increases glaucoma risk, there is insufficient evidence for hormonal replacement.

Section 6 – Screening

1. Glaucoma is the leading cause of irreversible blindness worldwide.
   Comment: In some countries, as many as 90% of glaucoma patients remain undiagnosed.
2. Screening everyone for glaucoma is an ideal proposition, but it is not logistically feasible. It would also result in an unacceptably high number of individuals with a false-positive diagnosis of glaucoma.
   Comment: To be effective, screening programs should select participants at substantial risk for glaucoma.
3. The cost-effectiveness of screening for POAG alone has not been demonstrated.
   Comment: Cost-effectiveness for glaucoma may be enhanced when done with other ocular conditions that cause visual impairment, including uncorrected refractive error, cataract, diabetic retinopathy, and age-related macular degeneration.
4. First-degree relatives of individuals with POAG and those with significant risk factors should be examined.