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Oculus

Glaucoma Opinion IGR 21-1

Defining glaucomatous optic neuropathy using objective criteria from structural and functional testing. Iyer JV, Boland MV, Jefferys J, Quigley H. British Journal of Ophthalmology, July 2020; doi: 10.1136/bjophthalmol-2020-316237

By Donald C. Hood and C. Gustavo De Moraes


One could debate the premise of the Iyer et al. study, that glaucoma research would benefit from a single definition of glaucoma. For decades, researchers have employed definitions that were the most translational for their time. Iyer et al. have argued against that approach and proposed a new single definition based upon (objective) OCT and visual field (VF) results. However, let’s assume as they do, that a single definition is needed and that it should be based upon objective structural and functional tests.

In their study, alternative definitions were based upon 24-2 visual field (VF) tests and OCT cube disc scans. Their best performing criterion (definition) required an abnormal circumpapillary retinal nerve fiber layer thickness (cpRNFL) in the superior or inferior quadrant of the disc and an abnormal 24-2 GHT (glaucoma hemifield test) in the corresponding hemifield.

There are at least three main problems with their approach. First, summary statistics for the 24-2 test, including the GHT, and summary statistics for the OCT disc scan, including quadrant cpRNFL thickness, can miss glaucomatous damage.1-7 Thus, it is not surprising that their results were relatively disappointing.

It is not clear that we need a single definition of glaucoma

In particular, their data provide weak support for their best-performing definition. First, the sensitivity for eyes classified as “definite glaucoma” (DG) was only 77%. That is, about 25% of the eyes identified as DG were missed.

Second, it is likely that their definition will miss some eyes with damage to the most important retinal region, the macula,1,2 which is not only common but also plays a major role in vision related quality of life. To test the hypothesis that macular damage is missed, we applied their 24-2 GHT criteria to data we recently published.7 These data included 53 eyes classified as DG by the referring clinician, the same reference standard used by Iyer et al. The 24-2 (GHT) failed their test on two 24-2 VFs in 16 (30%) of these 53 DG eyes. Further, when the results from 10-2 VF and OCT cube scans were examined,7,8 their definition missed eyes with macular damage, including those with deep defects near fixation and/or diffuse damage, as expected.

Finally, their comparison of summary statistics is a suboptimal method for comparing VF and OCT data.1,2 For example, we have developed and validated an objective and automated method7,8 that topographically compares the abnormal regions on the 24-2 and/ or 10-2 VFs to those on OCT maps. This method missed only 6 (11%) of our 53 DG eyes, as compared to over 50% based upon their criteria. Of note, although their definition aims to bring state-of-the-art technology to define glaucoma, in its current form it is not making good use of the available OCT and VF data.

In sum, it is not clear that we need a single definition of glaucoma, even if “only” for research purposes (remember the importance of translational relevance for clinical use). However, it is clear that the one proposed by Iyer et al. is out-of-date and suboptimal.

References

  1. Hood DC, De Moraes CG. Challenges to the Common Clinical Paradigm for Diagnosis of Glaucomatous Damage With OCT and Visual Fields. Invest Ophthalmol Vis Sci. 2018;59(2):788-791.
  2. Hood DC, De Moraes CG. Four Questions for Every Clinician Diagnosing and Monitoring Glaucoma. J Glaucoma. 2018;27(8):657-664.
  3. De Moraes CG, Hood DC, Thenappan A, et al. 24-2 Visual Fields Miss Central Defects Shown on 10-2 Tests in Glaucoma Suspects, Ocular Hypertensives, and Early Glaucoma. Ophthalmology. 2017;124(10):1449-1456.
  4. Sullivan-Mee M, Karin Tran MT, Pensyl D, Tsan G, Katiyar S. Prevalence, Features, and Severity of Glaucomatous Visual Field Loss Measured With the 10-2 Achromatic Threshold Visual Field Test. Am J Ophthalmol. 2016;168:40-51.
  5. Wang DL, Raza AS, de Moraes CG, et al. Central Glaucomatous Damage of the Macula Can Be Overlooked by Conventional OCT Retinal Nerve Fiber Layer Thickness Analyses. Transl Vis Sci Technol. 2015;4(6).
  6. Kim KE, Jeoung JW, Park KH, Kim DM, Kim SH. Diagnostic classification of macular ganglion cell and retinal nerve fiber layer analysis: differentiation of false-positives from glaucoma. Ophthalmology. 2015;122(3):502-510.
  7. Hood DC, Tsamis E, Bommakanti N, Joiner DB, Al-Aswad LL, Blumberg DM, Cioffi GA, Liebmann JM, De Moraes CG. (2019) Structure-function agreement is better than commonly thought in eyes with early glaucoma. Invest Ophthalmol Vis Sci. 2019;60(13):4241-4248.
  8. Tsamis E, Bommakanti NK, Sun A, Thakoor KA, Moraes CGD, Hood DC. An Automated Method for Assessing Topographical Structure–Function Agreement

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