Consider these evidence-based,1-14 sequential steps when scrutinizing the optic nerve with my mnemonic: N.E.R.V.E.S.*
N: “N” stands for the overall Nerve appearance, in terms of its size. The size provides context, making it the basis for the rest of the evaluation for glaucoma. For large nerves, large cupping is expected; for small nerves, small cupping is expected.1,15-19 However, moderate cupping in a small nerve is not expected and, in such scenarios, we should suspect glaucomatous optic neuropathy.
Also, when looking at the overall nerve appearance, make note of the insertion. For example, a highly myopic nerve may have more of a tilted insertion,20-22 therefore, making it difficult to evaluate. Further, it may even lead to false positives on future OCT testing.
E: If present, what is the Extent/amount of the neuroretinal rim loss and the location?16 Upon exam, and generally speaking, the inferior rim should be thicker than the superior rim, then the nasal rim, and finally the temporal rim in non-glaucomatous eyes. Applying this rule23 helps us identify (and differentiate) suspicious glaucomatous neuroretinal rim thinning. If the thinning is within 15° temporally of the superior and inferior rim, it’s glaucoma. In quantitative terms, we are trying to determine the minimum rim-to-disc ratio.24
While examining the neuroretinal rim, we should consider:
(1) Crescent-sign appearance. Among myopic patients, is there discontinuity between the inferior temporal rim and the superior temporal rim, thus forming a crescent-sign appearance within the optic nerve25? Such an appearance, and more commonly noted inferior temporally, can help distinguish between a patient who has myopia alone and a patient who has myopia and glaucoma.
(2) Neuroretinal rim pallor. While still “on the rim,” is there pallor? We must consider (and then test for) other causes of optic nerve cupping, visual field (VF) defects, and/or retinal nerve fiber layer (RNFL) defects when the pallor extends beyond cupping.26,27
R: Localized or diffuse RNFL defects28-31 increase glaucoma certainty, while also increasing the patient’s risk of VF defects.32
V: “V” is for all things Vascular. Look at the circumlinear optic nerve vessels33-34 for any vessel baring, the vessel diameter35,36 for any narrowing, the location of the central retinal vessel trunk1,37-39 for any notable eccentricity, the presence of emboli or collaterals suggestive of past artery40 or vein occlusions, respectively, and disc hemorrhages.1,41-45 If present, they correlate with the above neuroretinal rim loss and associated RNFL defects and are red flags for glaucoma that can’t be missed when examining the optic nerve.
E: Look at the Edges of the optic nerve for beta-zone parapapillary atrophy. This helps in differentiating glaucomatous eyes from normal eyes, as well as in identifying locations for future potential correlating VF progression.1,46-49
S: This stands for Suspicious. If anything looks suspicious for glaucoma,50,51 perform more patient-centric testing for glaucoma. If the evaluation and/or ancillary testing does not sync, consider non-glaucomatous optic atrophy,52-54 and proceed with additional blood work or imaging. (See bit.ly/OM 2403DistinguishingGlaucoma.)
* Restrictions apply: The provider must, every time, examine the optic nerve for qualitative features as described above (much more than cup-to-disc ratio) and put all sufficient, reliable, and appropriate testing in the context of the optic nerve.
References:
1. Jonas JB, Budde WM, Panda-Jonas S. Ophthalmoscopic evaluation of the optic nerve head. Surv Ophthalmol. 1999;43(4):293–320.2. DOI: 10.1016/s0039-6257(98)00049-6
2. 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;76(11):661–668.3. doi: 10.1016/j.optm.2005.08.029.
3. 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.
4. Gandhi M, Dubey S. Evaluation of the Optic Nerve Head in Glaucoma. J Curr Glaucoma Pract. 2013;7(3):106–114. doi: 10.5005/jp-journals-10008-1146.
5. Jonas JB, Bergua A, Schmitz-Valckenberg P, Papastathopoulos KI, Budde WM. Ranking of optic disc variables for detection of glaucomatous optic nerve damage. Invest Ophthalmol Vis Sci. 2000;41(7):1764–1773.
6. Susanna R Jr, Vessani RM. New findings in the evaluation of the optic disc in glaucoma diagnosis. Curr Opin Ophthalmol. 2007;18(2):122–128.7. doi: 10.1097/ICU.0b013e328040bfe0.
7. Skaat A, De Moraes CG, Bowd C, et al. African Descent and Glaucoma Evaluation Study (ADAGES): Racial Differences in Optic Disc Hemorrhage and Beta-Zone Parapapillary Atrophy. Ophthalmology. 2016;123(7):1476–1483. doi: 10.1016/j.ophtha.2016.03.025.
8. O’Neill EC, Gurria LU, Pandav SS, et al. Glaucomatous Optic Neuropathy Evaluation Project: Factors Associated With Underestimation of Glaucoma Likelihood. JAMA Ophthalmol. 2014;132(5):560–566. doi: 10.1001/jamaophthalmol.2014.96.
9. Greenfield, DS, Siatkowski RM, Glaser JS, Schatz NJ, Parrish 2nd RK. The cupped disc: Who needs neuroimaging? Ophthalmology. 1998 Oct;105(10):1866-74. doi: 10.1016/S0161-6420(98)91031-4.
10. 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;100:181–186.
11. Dias DT, Ushida M, Battistella R, Dorairaj S, Prata TS. Neurophthalmological conditions mimicking glaucomatous optic neuropathy: analysis of the most common causes of misdiagnosis. BMC Ophthalmol. 2017;17(1):2. doi: 10.1186/s12886-016-0395-x.
12. Zangalli C, Gupta SR, Spaeth GL. The disc as the basis of treatment for glaucoma. Saudi J Ophthalmol. 2011;25(4):381–387. doi: 10.1016/j.sjopt.2011.07.003.
13. Tan NYQ, Sng CCA, Jonas JB, Wong TY, Jansonius NM, Ang M. Glaucoma in myopia: diagnostic dilemmas. Br J Ophthalmol. 2019;103(10):1347‐1355. doi: 10.1136/bjophthalmol-2018-313530.
14. Shon K, Hye Jo Y, Won Shin J, Kwon J, Jeong D, Kook MS. Nasalization of Central Retinal Vessel Trunk Predicts Rapid Progression of Central Visual Field in Open-Angle Glaucoma. Sci Rep. 2020;10(1):3789. doi: 10.1038/s41598-020-60355-1.
15. Hoffman EM, Zangwill LM, Crowston JG, Weinreb RN. Optic Disk Size and Glaucoma. Surv Ophthalmol. 2007; 52(1):32-49. doi: 10.1016/j.survophthal.2006.10.002.
16. Jonas JB, Gusek GC, Naumann GO. Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes. Invest Ophthalmol Vis Sci. 1988; 29:1151–8.
17. Quigley HA, Coleman AL, Dorman-Pease ME. Larger optic nerve heads have more nerve fibers in normal monkey eyes. Arch Ophthalmol. 1991; 109:1441–3. doi: 10.1001/archopht.1991.01080100121056.
18. Jonas JB, Schmidt AM, Müller-Bergh JA, Schlötzer-Schrehardt UM Naumann GO. Human optic nerve fiber count and optic disc size. Invest Ophthalmol Vis Sci. 1992; 33:2012–8.
19. Jonas JB, Fernández MC, Naumann GO. Correlation of the optic disc size to glaucoma susceptibility. Ophthalmology. 1991;98:675–80. doi: 10.1016/s0161-6420(91)32234-6.
20. Jonas JB, Wang YX, Dong L, Panda-Jonas S. High Myopia and Glaucoma-Like Optic Neuropathy. Asia Pac J Ophthalmol (Phila). 2020;9(3):234-238. doi: 10.1097/APO.0000000000000288.
21. Chan PP, Zhang Y, Pang CP. Myopic tilted disc: Mechanism, clinical significance, and public health implication. Front Med (Lausanne). 2023;10:1094937. doi: 10.3389/fmed.2023.1094937.
22. Bak E, Lee KM, Kim M, Oh S, Kim SH. Angular Location of Retinal Nerve Fiber Layer Defect: Association With Myopia and Open-Angle Glaucoma. Invest Ophthalmol Vis Sci. 2020 Sep 1;61(11):13. doi: 10.1167/iovs.61.11.13.
23. Harizman N, Oliveira C, Chiang A, et al. The ISNT rule and differentiation of normal from glaucomatous eyes. Arch Ophthalmol. 2006;124(11):1579-83. doi: 10.1001/archopht.124.11.1579.
24. Kumar JRH, Seelamantula CS, Kamath YS, Jampala R. Rim-to-Disc Ratio Outperforms Cup-to-Disc Ratio for Glaucoma Prescreening. Sci Rep. 2019;9(1):7099. doi: 10.1038/s41598-019-43385-2.
25. Jonas JB, Budde WM, Panda-Jonas S. Ophthalmoscopic evaluation of the optic nerve head. Surv Ophthalmol. 1999; 43:293–320. doi: 10.1016/s0039-6257(98)00049-6.
26. Kim MJ, Kim SH, Hwang YH, Park KH, Kim TW, Kim DM. Novel screening method for glaucomatous eyes with myopic tilted discs: the crescent moon sign. JAMA Ophthalmol. 2014;132(12):1407-13. doi: 10.1001/jamaophthalmol.2014.2860.
27. 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):491-7. doi: 10.4103/0301-4738.86320.
28. Greenfield DS, Siatkowski RM, Glaser JS, Schatz NJ, Parrish RK. The cupped disc. Who needs neuroimaging? Ophthalmology. 1998;105(10):1866-74. doi: 10.1016/S0161-6420(98)91031-4.
29. Tatham AJ, Weinreb RN, Zangwill LM, Liebmann JL, Girkin CA, Medeiros FA. Estimated retinal ganglion cell counts in glaucomatous eyes with localized retinal nerve fiber layer defects. Am J Ophthalmol. 2013;156(3):578-587.e1. doi: 10.1016/j.ajo.2013.04.015.
30. Quigley HA. Examination of the retinal nerve fiber layer in the recognition of early glaucoma damage. Trans Am Ophthalmol Soc. 1986;84:920-966.
31. Sommer A, Katz J, Quigley HA, et al. Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol. 1991;109(1):77-83. doi: 10.1001/archopht.1991.01080010079037.
32. Kai-Ying Su C, Guo PY, Man Chan PP, Lam AKN, Shun Leung CK. Retinal Nerve Fiber Layer Optical Texture Analysis: Detecting Axonal Fiber Bundle Defects in Patients with Ocular Hypertension. Ophthalmology. 2023;130(10):1080-1089. doi: 10.1016/j.ophtha.2023.06.004.
33. Kasner O, Balazsi AG. Glaucomatous optic nerve atrophy: the circumlinear vessel revisited. Can J Ophthalmol. 1991;26(5):264-9.
34. Kortuem C, Dietter J, Bozkurt Y, et al. Vessel Evaluation in Patients with Primary Open-Angle Glaucoma, Normal Tension Glaucoma and Healthy Controls. Clin Ophthalmol. 2021;15:4269-4280. doi: 10.2147/OPTH.S320505.
35. Hall JK, Andrews AP, Walker R, Piltz-Seymour JR. Association of retinal vessel caliber and visual field defects in glaucoma. Am J Ophthalmol. 2001;132(6):855-9. doi: 10.1016/s0002-9394(01)01200-4.37.
36. Kawasaki R, Wang JJ, Rochtchina E, Lee AJ, Wong TY, Mitchell P. Retinal Vessel Caliber Is Associated with the 10-year Incidence of Glaucoma. The Blue Mountains Eye Study. Ophthalmology. 2013;120(1):84-90. doi: 10.1016/j.ophtha.2012.07.007.
37. Huang H, Jonas JB, Dai Y, et al. Position of the central retinal vessel trunk and pattern of remaining visual field in advanced glaucoma. Br J Ophthalmol. 2013; 97:96–100. doi: 10.1136/bjophthalmol-2012-302068.
38. Jonas JB, Fernandez MC. Shape of the neuroretinal rim and position of the central retinal vessels in glaucoma. Br J Ophthalmol. 1994; 78:99–102. doi: 10.1136/bjo.78.2.99.
39. Zhang H, Pia H, Sung MS , Park SW. Association Between Parapapillary Microvasculature Dropout and Central Retinal Vessel Trunk in Primary Open Angle Glaucoma. J Glaucoma. 2023;32(7):575-584. doi: 10.1097/IJG.0000000000002207.
40. 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.
41. Drance SM, Fairclough M, Butler DM, Kottler MS. The importance of disc hemorrhage in the prognosis of chronic open angle glaucoma. Arch Ophthalmol. 1977 Feb;95(2):226-8. doi: 10.1001/archopht.1977.04450020028004.
42. Suh MH, Park KH. Pathogenesis and Clinical Implication of Optic Disk Hemorrhage in Glaucoma. Surv Ophthalmol. 2014 Jan-Feb;59(1):19-29. doi: 10.1016/j.survophthal.2013.03.005.
43. Uhler TA, Piltz-Seymour J. Optic disc hemorrhages in glaucoma and ocular hypertension: implications and recommendations. Curr Opin Ophthalmol. 2008;19(2):89-94. doi: 10.1097/ICU.0b013e3282f3e6bc.
44. Healey PR, Mitchell P, Smith W, Wang JJ. Optic disc hemorrhages in a population with and without signs of glaucoma. Ophthalmology. 1998;105(2):216-23. doi: 10.1016/s0161-6420(98)92704-x.
45. Chung E, Demetriades AM, Christos PJ, Radcliffe NM. Structural glaucomatous progression before and after occurrence of an optic disc haemorrhage. Br J Ophthalmol. 2015;99(1):21-5. doi: 10.1136/bjophthalmol-2014-305349.
46. Healey P. Optic disc haemorrhage: the more we look the more we find. Clin Exp Ophthalmol. 2011;39(6):485-486. doi: 10.1111/j.1442-9071.2011.02648.x.
47. Uchida H, Ugurlu S, Caprioli J. Increasing peripapillary atrophy is associated with progressive glaucoma. Ophthalmology. 1998;105(8):1541-1545. doi: 10.1016/S0161-6420(98)98044-7.
48. Budde WM, Jonas JB. Enlargement of parapapillary atrophy in follow-up of chronic open-angle glaucoma. Am J Ophthalmol. 2004;137(4):646-54. doi: 10.1016/j.ajo.2003.11.021.
49. Teng CC, De Moraes CG, Prata TS, et al. The region of largest β-zone parapapillary atrophy area predicts the location of most rapid visual field progression. Ophthalmology. 2011;118(12):2409-13. doi: 10.1016/j.ophtha.2011.06.014.
50. Zhou D, Cao M, Duan X. Prevalence and diagnostic ability of β-zone parapapillary atrophy in open-angle glaucoma: a systematic review and meta-analysis. BMC Ophthalmol. 2022;22(1):72. doi: 10.1186/s12886-022-02282-5.
51. Chang RT, Singh K. Glaucoma Suspect: Diagnosis and Management. Asia Pac J Ophthalmol (Phila). 2016;5(1):32-7. doi: 10.1097/APO.0000000000000173.
52. Ahmad SS. Glaucoma suspects: A practical approach. Taiwan J Ophthalmol. 2018;8(2):74-81. doi: 10.4103/tjo.tjo_106_17.
53. Zhang YX, Huang HB, Wei SH. Clinical characteristics of nonglaucomatous optic disc cupping. Exp Ther Med. 2014;7(4):995-999. doi: 10.3892/etm.2014.1508.
54. Burgoyne C. The morphological difference between glaucoma and other optic neuropathies. J Neuroophthalmol. 2015;35 Suppl 1(0 1):S8-S21. doi: 10.1097/WNO.0000000000000289.
