Table 2 Studies investigating corneal confocal microscopy (CCM) in central nervous system disorders

MS

Bitirgen et al. (2017)

To assess corneal sub-basal nerve plexus morphologic features, corneal DC density in patients with MS.

cross-sectional (87 subjects: 57 MS, 30 controls)

CNFD、CNBD、CNFL were reduced but DC density was increased in patients with MS compared with healthy controls.

[68]

Mikolajczak et al. (2017)

To investigate the effect of MS on corneal nerve fibers and DC in the sub-basal nerve plexus using in CCM.

cross-sectional (52 subjects: 26 MS, 26 controls)

significant reduction in total corneal nerve fiber density in MS patients compared to controls. DC density was similar in both groups.

[69]

Petropoulos et al. (2017)

To evaluate whether CCM detects axonal degeneration and whether this is associated with retinal nerve fiber degeneration and clinical disability in patients with MS.

cross-sectional (50 subjects: 25 MS, 25 controls)

CNFD、CNBD、CNFL were reduced patients with MS compared with healthy controls. The EDSS and MSSS correlated significantly with CNBD.

[70]

Dementia

Ponirakis et al. (2019)

To determine whether there is any association of corneal nerve fiber measures with cognitive function and functional independence in patients with MCI and dementia.

cross-sectional (76 subjects: 30 MCI, 26 dementias, 20 controls)

CNFD、CNBD、CNFL were reduced in patients with MCI and dementia compared to controls. CNFD、CNBD、CNFL were significantly associated with cognitive function and functional independence in MCI and dementia.

[25]

ALS

Ferrari et al. (2014)

To examine a group of sporadic ALS patients with CCM.

cross-sectional (15 subjects: 8 ALS, 7 controls)

CNFD、CNFL were reduced but CNT was increased in ALS patients compared with healthy controls. ALS-SS-bulbar score was significantly related to CNFL and CNFD.

[71]

FRDA

Pagovich et al. (2018)

To evaluated the severity of neurological manifestations in FRDA with CCM.

cross-sectional (37 subjects, 23 FRDA, 14 controls)

CNFD、CNFL were reduced in FRDA compared to healthy controls.

[75]

WD

Sturniolo et al. (2015)

to investigate central corneal changes and in particular to assess the parameters of corneal SBNP in patients affected by WD.

cross-sectional (48 subjects: 24 WD, 24 controls)

NFLD, NF, NBe and NFr were lower, whereas FT was significantly higher in WD subjects compared to controls.

[72]

IS

Khan et al. (2017)

To investigate the use of CCM in patients presenting with acute IS.

cross-sectional (158 subjects: 130 acute IS, 28 controls)

CNFD、CNBD、CNFL were reduced in patients with acute IS compared with healthy controls.

[73]

Gad et al. (2019)

To determine if CCM can identify corneal nerve and endothelial cell abnormalities with TIA or minor IS.

cross-sectional (54subjects: 14 TIA, 22 minor IS, 18 controls)

CCM identifies corneal nerve fiber loss and endothelial cell abnormalities in patients with TIA and minor IS.

[74]