In clinical practice, due to excellent visual function recovery, including visual acuity and visual fields, the prior ON is sometimes not confirmed. Also, subclinical optic neuropathy due to the diffuse demyelination that is present in MS
5 may result in a similar degree of average thinning of the pRNFL and GCIPL compared with MSON eyes. The intereye variability of pRNFL and GCIPL thicknesses were reported to have better discrimination power to identify possible prior ON (
Table 3).
3,11,12,14 However, the threshold criteria of the intereye differences only exhibited moderate discrimination powers, except for the study of Xu et al.
12 Using 6 μm derived from 99th percentile of a normal population (233 subjects), Xu et al.
12 reported 96% sensitivity to determine prior ON in mixed patients including MS (51%), idiopathic (41%), and neuromyelitis optica spectrum disorder (8%). Because of the mixed etiology of ON, the cutoff and its associated sensitivity may not be recommended as a routine tool for diagnosing ON in patients with MS.
3 However, a recent international study reported an optimal intereye difference threshold of the GCIPL for identifying prior unilateral ON,
13 and the sensitivity of a 4-μm cutoff of GCIPL yielded similar results in previous studies.
11,14 Coric et al.
11 studied intereye GCIPL percentage difference normalized to the absolute thickness level of retinal layers and found that a 6% intereye difference in the GCIPL had 62% sensitivity. Nolan et al.
13 reported a 4-μm intereye GCIPL difference to identify prior ON based on a large sample size (477 patients with unilateral ON and 253 HC subjects). The intereye difference (4 μm) of the U Zone thickness provided a 73% sensitivity in the present study, and the cutoff of 3 μm of the U Zone thickness provided 77% sensitivity, which are slightly better than previous studies,
11,13,14 except for the study of Xu et al.
12 Notably, the moderate sensitivity of the GCIPL in determining prior ON may be due to the ubiquitous occurrence of subclinical ON, which is often asymptomatic.
3 Approximately one-third of patients with MS with intereye differences greater than 4 μm reported no history of ON. These patients may have subclinical ON. If subclinical ON occurred in the fellow eyes, the intereye differences may be diminished, which may explain our finding that approximately 6-fold of fellow eyes had GCIPL thickness in the U Zone below the cutoff value (i.e., 82.3 μm or reduction 4.5 μm compared with HC). Therefore, combining the cutoff of the GCIPL of individual eyes and the cutoff of intereye thickness difference is recommended for identifying optic nerve lesions, including subclinical optic nerve pathology.