Monitoring Progression in Advanced Glaucoma

An essential part of managing patients with glaucoma is monitoring progression of the disease, especially in patients with advanced-stage glaucoma whose vision is threatened. However, detection of progression is challenging in eyes with advanced glaucoma because of the reduced accuracy of structural thickness measurements1Mwanza J.C. Budenz D.L. Warren J.L. et al.Retinal nerve fibre layer thickness floor and corresponding functional loss in glaucoma.Br J Ophthalmol. 2015; 99: 732-737Crossref PubMed Scopus (61) Google Scholar and unreliable visual field test results.2Heijl A. Lindgren A. Lindgren G. Test-retest variability in glaucomatous visual fields.Am J Ophthalmol. 1989; 108: 130-135Abstract Full Text PDF PubMed Scopus (334) Google Scholar I have taken great interest in the results of the study by Hou et al (see page 1043),3Hou H. Moghimi S. Proudfoot J.A. et al.Ganglion cell complex thickness and macular vessel density loss in primary open-angle glaucoma.Ophthalmology. 2020; 127: 1043-1052Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar which proposed a usefulness of OCT angiography (OCTA) evaluation of macular vessel density to detect glaucoma progression in patients with advanced disease. The study determined the rates of structural thinning of the macular ganglion cell complex (GCC) and the reduction in vessel density in the superficial retinal capillary plexus in the macular area over 2 years in 80 eyes with primary open-angle glaucoma (POAG), 36 eyes with preperimetric glaucoma, and 23 eyes without glaucoma. Both macular GCC thickness and macular vessel density decreased significantly over time in all 3 groups, but the latter was more evident in the POAG group, with the rate increasing as glaucoma severity worsened. Because the rates of decrease in macular GCC thickness and macular vessel density were comparable in earlier-stage disease, with the rate of vascular decrease becoming more rapid in the later stage, the authors hypothesized that rates of structural thinning and vessel density decrease differ across different stages of the glaucoma continuum. Structural measurements using OCT are subject to a floor effect, restricting the usefulness of OCT for detecting disease progression beyond a minimum practical value.4Chan C.K. Miller N.R. Peripapillary nerve fiber layer thickness measured by optical coherence tomography in patients with no light perception from long-standing nonglaucomatous optic neuropathies.J Neuroophthalmol. 2007; 27: 176-179Crossref PubMed Scopus (53) Google Scholar Because OCTA does not have a detectable floor, it may be a promising tool for monitoring disease progression in patients with advanced-stage glaucoma.5Kim G.N. Lee E.J. Kim H. Kim T.W. Dynamic range of the peripapillary retinal vessel density for detecting glaucomatous visual field damage.Ophthalmol Glaucoma. 2019; 2: 103-110Abstract Full Text Full Text PDF Scopus (9) Google Scholar,6Moghimi S. Bowd C. Zangwill L.M. et al.Measurement floors and dynamic ranges of OCT and OCT angiography in glaucoma.Ophthalmology. 2019; 126: 980-988Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Of note, higher intraocular pressure during follow-up was significantly associated with more rapid macular GCC thinning, but not with the rate of change in macular vessel density. These findings suggested that OCTA measurements may be useful for evaluating glaucoma progression caused by factors other than high intraocular pressure. However, we have to keep in mind that it is crucial to differentiate statistical significance from clinical relevance. The findings of this study may become more clinically applicable once OCTA measurements of vessel density and evaluations of changes in vessel density become more established after the development of more reliable and reproducible algorithms. In addition, as mentioned by the authors,3Hou H. Moghimi S. Proudfoot J.A. et al.Ganglion cell complex thickness and macular vessel density loss in primary open-angle glaucoma.Ophthalmology. 2020; 127: 1043-1052Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar their study included only a limited number of eyes with advanced glaucoma (5 eyes), which may make debatable the clinical relevance of their results in advanced glaucoma. Moreover, at least 3 tests of each eye were required to assess progression. However, 3 tests are not usually sufficient to detect progression, let alone to evaluate the rate of progression, especially in eyes with advanced glaucoma. In the introduction to their study, the authors3Hou H. Moghimi S. Proudfoot J.A. et al.Ganglion cell complex thickness and macular vessel density loss in primary open-angle glaucoma.Ophthalmology. 2020; 127: 1043-1052Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar question whether vascular impairment is a primary or secondary consequence of glaucomatous damage, a question that their results could not answer. Detection of structural thinning becomes less sensitive as thinning progresses and reaches a minimum practical value,1Mwanza J.C. Budenz D.L. Warren J.L. et al.Retinal nerve fibre layer thickness floor and corresponding functional loss in glaucoma.Br J Ophthalmol. 2015; 99: 732-737Crossref PubMed Scopus (61) Google Scholar,4Chan C.K. Miller N.R. Peripapillary nerve fiber layer thickness measured by optical coherence tomography in patients with no light perception from long-standing nonglaucomatous optic neuropathies.J Neuroophthalmol. 2007; 27: 176-179Crossref PubMed Scopus (53) Google Scholar whereas evaluation of vessel density is less subject to these limitations.5Kim G.N. Lee E.J. Kim H. Kim T.W. Dynamic range of the peripapillary retinal vessel density for detecting glaucomatous visual field damage.Ophthalmol Glaucoma. 2019; 2: 103-110Abstract Full Text Full Text PDF Scopus (9) Google Scholar,6Moghimi S. Bowd C. Zangwill L.M. et al.Measurement floors and dynamic ranges of OCT and OCT angiography in glaucoma.Ophthalmology. 2019; 126: 980-988Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Therefore, it is difficult to determine whether the reduced vessel density in advanced glaucoma was due to primary vascular impairment or undetected structural thinning. Structural thickness measured using current OCT technology may not fully reflect the magnitude of loss of retinal ganglion cells. Thus, the authors’ hypothesis that the rates of structural and vascular impairments differ during different stages of glaucoma cannot be confirmed conclusively. Ganglion Cell Complex Thickness and Macular Vessel Density Loss in Primary Open-Angle GlaucomaOphthalmologyVol. 127Issue 8PreviewTo characterize the change rate of ganglion cell complex (GCC) thickness and macular vessel density in healthy, preperimetric glaucoma and primary open-angle glaucoma (POAG) eyes. Full-Text PDF