Differentiate glaucoma from non-glaucomatous optic neuropathy
Not all OCT retinal nerve fiber layer (RNFL) defects or visual field defects are glaucomatous. Just as we know the importance of placing the symptoms and the clinical findings of the patient in the context of their whole systemic condition, it is also important to put every structural test (RNFL, ganglion cell complex analysis [GCA]), and functional test (VF) in the context of the optic nerve appearance, and look for a correlation. After all, correlation increases certainty and decreases misdiagnosis.
In the last column, the question, “What does glaucoma look like?” was answered. As a corollary to that question, this month’s column will answer, “What else could it be?”
STRUCTURE-STRUCTURE CORRELATION
Glaucoma shows preferential neuroretinal rim loss, and in the early stages this is commonly observed in the inferior-temporal and superior-temporal sectors.1-11 As such, when performing additional structural testing, such as OCT RNFL scans, we should look in these specific sectors for correlation after systematically examining the optic nerve for structural damage.
In the early or moderate stages of glaucoma, any other areas of thinning outside these zones are either nonglaucomatous and/or false positives. With a false positive rate of at least 26.2% in 149 eyes of 77 healthy adults,12 and image-related artifacts in at least 15.2% to 36.1% of scans,13 “…misinterpretation of artifacts on OCT can lead to errors in clinical judgment, where both false reassurance and false concern can be created.”14
Such “errors in clinical judgment” are especially common in highly myopic patients who have a temporal RNFL pattern shift or in highly hyperopic patients who have a nasal RNFL pattern shift, resulting in false positives and potential over diagnosis and/or treatment.14*
To that point, true RNFL loss may be evident in patients who have optic nerve pallor — a common endpoint of over a dozen infiltrative, inflammatory, ischemic, and infectious etiologies. Such pallor, which often extends beyond the cupping level, may specifically be due to old nonarteritic ischemic events (particularly if the VF defect is inferior15), old branch retinal artery or vein occlusions (branch retinal artery occlusion) (especially if there is significant inter- and intra-eye macular thickness asymmetry16), or coexisting neurological conditions, such as a space-occupying lesion on the optic nerve.
Regarding this latter condition, we should suspect neurological etiologies if the patient is younger than age 50, has a BCVA worse than 20/40 (out of proportion to media clarity), VF defects that respect the vertical meridian, and any associated neurological symptoms.17-19 In such cases, additional bloodwork and/or imaging is indicated.
STRUCTURE-STRUCTURE-STRUCTURE CORRELATION
After systematically examining the optic nerve for structural damage and putting the OCT RNFL structural measurements in the context of this evaluation, we should add another structural analysis test, namely the GCA. However, we must remember that just as GCA can add supplemental certainty to our RNFL pattern defects, it can also show false positives in those who have age-related macular degeneration, epiretinal membranes, a history of vascular occlusions, high myopia, and epiretinal membranes, to name a few.14
STRUCTURE-STRUCTURE-STRUCTURE-FUNCTION CORRELATION
If glaucoma shows preferential structural neuro-retinal rim and macular ganglion cell loss, it will also correlate with associated VF pattern loss. Looking first for structural changes helps us predict and identify probable locations of functional loss.20 However, looking at the VF first, instead of the structural tests first, may cause us to miss early areas of glaucomatous defects and/or misdiagnose areas of glaucoma that are actually normal variations and artifacts. After correlating these structural and functional findings, we should look next for deepening and/or then enlargement of these areas to monitor for and better detect glaucomatous progression.21 If there is VF progression, we must always rule out other neuroretinal etiologies. In summary, the VF should look the same as, or better than, the optic nerve appearance.
S3FC = GLAUCOMA
Because “structural and/or functional testing should be conducted throughout the duration of the disease,”22 we should correlate these structural and functional tests appropriately and consistently. By applying these principles and this formula, we can accurately diagnose glaucoma earlier, and detect progression sooner. Let’s look for correlation, as correlation increases certainty and decreases misdiagnosis. OM
References:
1. Sihota R, Sidhu T, Dada T. The role of clinical examination of the optic nerve head in glaucoma today. Curr Opin Ophthalmol. 2021;32(2): 83-91. 10.1097/ICU.0000000000000734
2. Kirsch RE, Anderson DR. Clinical recognition of glaucomatous cupping. Am J Ophthalmol. 1973 Mar;75(3): 442-54. doi: 10.1016/0002-9394(73)91153-7.
3. Jonas JB, Budde WM, Panda-Jonas S. Ophthalmoscopic evaluation of the optic nerve head. Surv Ophthalmol. 1999;43(4): 293-320. doi: 10.1016/s0039-6257(98)00049-6.
4. Broadway DC, Nicolela MT, Drance SM. Optic disk appearances in primary open-angle glaucoma. Surv Ophthalmol. 1999;43 Suppl 1:S223-43. doi: 10.1016/s0039-6257(99)00007-7.
5. Spaeth GL, Henderer J, Liu C, et al. The disc damage likelihood scale: reproducibility of a new method of estimating the amount of optic nerve damage caused by glaucoma. Trans Am Ophthalmol Soc. 2002;100:181-5; discussion 185-6.
6. Fingeret M, Medeiros FA, Susanna R Jr, Weinreb RN. Five rules to evaluate the optic disc and retinal nerve fiber layer for glaucoma. Optometry. 2005 Nov;76(11): 661-8. doi: 10.1016/j.optm.2005.08.029.
7. Spaeth, GL, Lopes JF, Junk AK, et al. Systems for staging the amount of optic nerve damage in glaucoma: a critical review and new material. Surv Ophthalmol. 2006;51(4): 293-315. doi: 10.1016/j.survophthal.2006.04.008.
8. Primary Open Angle Glaucoma Preferred Practice Pattern – American Academy of Ophthalmology p 49.
9. American Optometric Association – Optometric Clinical Practice Guideline. Care of the Patient with Open Angle Glaucoma. https://www.aoa.org/AOA/Documents/Practice%20Management/Clinical%20Guidelines/Consensus-based%20guidelines/Care%20of%20the%20Patient%20with%20Open%20Angle%20Glaucoma.pdf. Accessed 1/3/22.
10. Budde WM, Jonas JB, Martus P, Gründler AE. Influence of optic disc size on neuroretinal rim shape in healthy eyes. J Glaucoma. 2000;9(5): 357-62. doi: 10.1097/00061198-200010000-00003.
11. Song BJ, Caprioli J. Measuring Glaucoma Progression in Clinical Practice in Glaucoma – Medical Diagnosis and Therapy. Elsevier Limited 2015. Chapter 23:268-276.
12. Kim NR, Lim H, Kim JH, Rho SS, Seong GJ, Kim CY. Factors associated with false positives in retinal nerve fiber layer color codes from spectral-domain optical coherence tomography. Ophthalmology. 2011;118(9): 1774-81. doi: 10.1016/j.ophtha.2011.01.058.
13. Asrani S, Essaid L, Alder BD, Santiago-Turla C. Artifacts in spectral-domain optical coherence tomography measurements in glaucoma. JAMA Ophthalmol. 2014;132(4): 396-402. doi: 10.1001/jamaophthalmol.2013.7974.
14. Chen JJ, Kardon RH. Avoiding Clinical Misinterpretation and Artifacts of Optical Coherence Tomography Analysis of the Optic Nerve, Retinal Nerve Fiber Layer, and Ganglion Cell Layer. J Neuroophthalmol. 2016;36(4): 417-438. doi: 10.1097/WNO.0000000000000422. * “Above average axial eye length, typically associated with high myopia, is associated with a thinner RNFL compared to the normal population. This is important because the normal population database used by the manufacturer specifically excludes subjects with a high refractive error (usually encompassing spherical equivalent between -5.00 and +5.00).”
15. Han S, Jung JJ, Kim US. Differences between Non-arteritic Anterior Ischemic Optic Neuropathy and Open Angle Glaucoma with Altitudinal Visual Field Defect. Korean J Ophthalmol. 2015;29(6): 418-23. doi: 10.3341/kjo.2015.29.6.418.
16. Sullivan-Mee M, Amin P, Pensyl D, Katiyar S. Differentiating Occult Branch Retinal Artery Occlusion from Primary Open-angle Glaucoma. Optom Vis Sci. 2018;95(2): 106-112. doi: 10.1097/OPX.0000000000001170.
17. Choudhari NS, Neog A, Fudnawala V, George R. Cupped disc with normal intraocular pressure: the long road to avoid misdiagnosis. Indian J Ophthalmol. 2011;59(6): 491-497. doi: 10.4103/0301-4738.86320.
18. Greenfield DS, Siatkowski RM, Glaser JS, Schatz NJ, Parrish RK. The cupped disc. Who needs neuroimaging?Ophthalmology. 1998;105(10): 1866-1874. doi: 10.1016/S0161-6420(98)91031-4.
19. Greenfield DS. Glaucomatous versus nonglaucomatous optic disc cupping: clinical differentiation. Semin Ophthalmol. 1999;14(2): 95-108. doi: 10.3109/08820539909056069.
20. Germano RAS, Germano CS, Susanna FN, Susanna R. Patterns of Visual Field Loss in Early, Moderate, and Severe Stages of Open Angle Glaucoma. J Glaucoma. 2022;31(7): 609-613. doi: 10.1097/IJG.0000000000001986. (Note: the results of this study showed that “as the severity of the glaucomatous VFDs increase, their patterns become more central, connected to the physiological blind spot and involving both hemifields. Interestingly, in the early stages of glaucomatous VFDs, 49% of the VFDs occurred in both hemifields which may have prognostic value and 28% of the defects are within the central 5 degrees of the fixation.”)
21. Boden C, Blumenthal EZ, Pascual J, McEwan G, Weinreb RN, Medeiros F, Sample PA. Patterns of glaucomatous visual field progression identified by three progression criteria. Am J Ophthalmol. 2004;138(6):1029-36. doi: 10.1016/j.ajo.2004.07.003.
22. R.N. Weinreb, D.F. Garway-Heath, C. Leung, J.G. Crowston. Progression of Glaucoma. Consensus Series – 8. Kugler Publications, Amsterdam, The Netherlands. 2011.
![]({"src":"/media/dzflsfbs/cover_om_0323.jpg","focalPoint":null,"crops":[{"alias":"thumbnail","width":1110,"height":700,"coordinates":null}]})