Article

Identifying eyes with rapid glaucoma progression

Part one of a two-part series covers visual field testing.

Most forms of glaucoma are, fortunately, slowly progressive. This gives clinicians a lengthy period in which to detect worsening disease and adjust therapy with the goal of preserving the patient’s vision.

But, there also is great variability in how rapidly different patients progress. We can divide the glaucoma population into three groups: slow or normal progressors, fast progressors and catastrophic progressors.1 Clinicians agree that we should be more aggressive in treating fast and catastrophic progressors, but how do we identify them before severe progression and vision loss occurs?

RISK FACTORS

Fast progressors

The identification of fast progressors can begin even at the point of glaucoma diagnosis. A detailed family history is helpful — not only whether any family members have glaucoma, but also how many, which ones, severity and age of onset of disease. For example, a patient whose parents and siblings have glaucoma along with a history of glaucoma surgery and legal blindness in one parent has a different risk profile than a patient whose grandparent had glaucoma that was controlled with medical therapy.

Thin central corneal thickness is a risk factor for both conversion from ocular hypertension to glaucoma2 and for progression of existing glaucoma.3 Younger age of onset, especially with significant visual field and optic nerve damage, signals that the disease is aggressive and should be treated with special care. Certain ethnic groups are more likely to have glaucoma progress at a faster rate, such as those of African descent.4 Additionally, certain ocular signs, such as an optic disc hemorrhage5,6 or a large zone beta of peripapillary atrophy, confer a higher risk of progression.7

The factors most associated with glaucoma, such as higher IOP, larger cup-to-disc ratio and worse visual field, have a higher risk of progression.8-10 Finally, in certain high-risk individuals, genetic testing is warranted and can detect mutations that are associated with greater risk of progression.11

VISUAL FIELDS

Frequency of testing

Visual field testing is a key component of detecting glaucoma progression. However, because of the inherent variability in psychophysical testing, many and frequent visual fields are necessary to determine progression. After identifying a high-risk patient based on baseline characteristics, the frequency of testing should increase to three or more tests per year.

Chauhan and colleagues12 noted that the majority of a glaucoma population exhibit a change in visual field mean deviation (MD) over time between -0.5 and 0 dB/year. They estimated that approximately 5.8% will be fast progressors with MD change of greater than -1 dB/y, and that 1.5% will be catastrophic progressors with a rate of change of greater than -2.0 dB/y.

The researchers also estimated that three visual field exams per year would be necessary to detect progression in the catastrophic group within two years, two exams per year to detect it within three years and one exam per year to detect it within five years (see Table below).12

Table: Frequency of testing required to detect visual field progression in normal, fast and catastrophic progressors (VF=visual fields, dB=decibels, MD=mean deviation)12
Number of exams per year over x years
Progression rate of MD 2 years 3 years 5 years
Normal -0.5 dB/year 7 (VF per year) 5 3
Fast -1.0 dB/year 5 3 2
Catastrophic -2.0 dB/year 3 2 1

Alternative approach: Clustering tests

Crabb and Garway-Heath tested an alternative approach to visual field monitoring dubbed the “wait-and-see approach.”13 They used a mathematical visual field model with a progression rate of -2.0 dB/y to compare the estimated accuracy of progression detection. Tests were either “administered” evenly spaced every four months or every six months or they were clustered and measured two or three times at the beginning and end of the two-year period.

The researchers found that the model predicted better power of detection with the clustered approach, even with fewer total tests.

Pointwise linear regression

Caprioli et al hypothesize that current visual field analysis paradigms are not sufficient to identify fast progressors in a timely manner. This is due to the global nature of the visual field index (VFI) and mean deviation.14 Instead, they created a proprietary model that examines the rates of change for each testing point independent of the rest of the visual field. This allows one to identify areas that are progressing quickly as they stand out against the slowly progressing background points. This type of change would not be detected using global rates of change commonly employed in the current methods of progression analysis.

Timing and frequency recommendations

Since we do not have a beginning and end period of follow-up in clinical practice, I recommend clustering several visual field tests in the first six months of seeing a new patient to establish a clear baseline. Then, test every six months until a rate of change can be estimated. This should tell you whether the patient falls into the normal-, fast- or catastrophic-progressing categories and allow you to adjust therapy accordingly.

If progression is suspected, IOP control is borderline or treatment is changed meaningfully (i.e., surgery), cluster several more tests during another six-month period to detect progression or establish a new baseline.

WHERE TO TEST

The central visual field

Up to now, we have discussed the rates of progression of the visual field, but have not paid any attention to what areas of the visual field are changing. The patient relies on the central field for visual acuity and the paracentral areas for most useful vision. I highly recommend testing the foveal sensitivity, which correlates very well with visual acuity.

As for central 10-2 visual field testing (Figure 1, page 31)15, Liebman and colleagues have emphasized its importance, especially in patients with parafoveal scotomas.16 Asaoka also studied the predictive value of 10-2 testing and shown a representative patient in whom 10-2 testing showed a much more rapid rate of progression compared to 24-2 testing (Figure 2).

Figure 1: Mapping of 10-2 and 24-2 VF test points. Blue and green circles represent test points in the 24-2 VF and 10-2 VF, respectively. Red circles show points tested by both the 24-2 VF and 10-2 VF.15

Figure 2: The progression of MD in the 10-2 VF and 24-2 VF in a given patient. In this patient, the rate of progression of MD over the first six 10-2 VFs was -2.3 dB/year, whereas over the first nine 24-2 VFs the MD rate was -0.14 dB/year.15

The researchers have also proposed a technique called “lasso regression” that combines the data from a patient’s 24-2 tests to the 10-2 tests to further increase its accuracy to predict progression.

CONCLUSION

Visual fields are an invaluable tool for monitoring glaucoma patients for progression. Determine a patient’s risk factors to decide how frequently to monitor for progression. Cluster several tests at the initial presentation to establish a good baseline. Determine testing frequency based on the stability of these first tests as well as risk factors.

Follow with central visual field testing and foveal sensitivity in those with paracentral defects, or central island remaining, or with undefined visual symptoms or perception of worsening even with a stable peripheral visual field. Look for areas of fast progression that may be masked in global analyses.

With these tools, patients who are fast or catastrophic progressors can be identified and treated appropriately. OM

Part 2 will cover the use of OCT to monitor progression.

REFERENCES

  1. Chauhan BC, Malik R, Shuba LM, Rafuse PE, Nicolela MT, Artes PH. Rates of glaucomatous visual field change in a large clinical population. Invest Ophthalmol Vis Sci. 2014 Jun 10;55:4135-4143.
  2. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, 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 Jun;120:701-713.
  3. Zhang X, Dastiridou A, Francis BA, Tan O, Varma R, et al. Advanced Imaging for Glaucoma Study Group. Baseline Fourier-domain optical coherence tomography structural risk factors for visual field progression in the Advance Imaging for Glaucoma Study. Am J Ophthalmol. 2016 Dec;172:94-103.
  4. Khachatryan N, Medeiros FA, Sharpsten L, Bowd C, Sample PA, et al. The African Descent and Glaucoma Evaluation Study (ADAGES): predictors of visual field damage in glaucoma suspects. Am J Ophthalmol. 2015 Apr;159:777-787.
  5. Bengtsson B, Leske MC, Yang Z, Heijl A; EMGT Group. Disc hemorrhages and treatment in the early manifest glaucoma trial. Ophthalmology. 2008 Nov;115:2044-2048.
  6. DeMoraes CG, Prata TS, Liebmann CA, Tello C, Ritch R, Liebmann JM. Spatially consistent, localized visual field loss before and after disc hemorrhage. Invest Ophthalmol Vis Sci. October 2009. 50;10: 4727-4733.
  7. Jonas JB. Clinical implications of peripapillary atrophy in glaucoma. Curr Opin Ophthalmol. 2005 Apr;16:84-88.
  8. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000 Oct;130:429-440.
  9. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M; Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002 Oct;120:1268-1279.
  10. Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, et al; CIGTS Study Group. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001 Nov;108:1943-1953.
  11. Wiggs JL. Glaucoma genes and mechanisms. Prog Mol Biol Transi Sci. 2015;134:315-342.
  12. Chauhan BC, Garway-Heath DF, Goni FJ, Rossetti L, Bengtsson B, et al. Frequency of testing to detect visual field progression derived using a longitudinal cohort of glaucoma patients. BJO. 2008. 92;4:569-573. http://bjo.bmj.com/content/92/4/569.info . Accessed May 15, 2018.
  13. Crabb DP, Garway-Heath DF. Intervals between visual field tests when monitoring the glaucomatous patient: wait-and-see approach. Invest Ophthalmol Vis Sci. May 2012. 53;6: 2770-2776.
  14. Caprioli J, Mock D, Bitrian E, Afifi AA, Yu F, et al. A method to measure and predict rates of regional visual field decay in glaucoma. Invest Ophthalmol Vis Sci. June 2011;52:4765-4773.
  15. Asaoka R. Measuring Visual Field Progression in the Central 10 Degrees Using Additional Information from Central 24 Degrees Visual Fields and ‘Lasso Regression’. PLoS ONE 8(8): e72199. 2013. https://doi.org/10.1371/journal.pone.0072199 . Accessed April 26, 2018.
  16. Kung Y, Park SC, Simonson J, Su D, De Moraes CGV, et al. 10-2 Versus 24-2 Visual Field Progression Analysis in Glaucomatous Eyes with Initial Parafoveal Scotomata. Invest Ophthalmol Vis Sci. 2012;53:202.

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