Eun Young Choi; Tae Im Kim; Kyoung Yul Seo; Eung Kweon Kim; Hyung Keun Lee

doi:10.7469/JKOS.2015.56.05.680

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Choi, Kim, Seo, Kim, and Lee: Corneal Microstructural Changes in Non-Sjögren Dry Eye Using Confocal Microscopy: Clinical Correlation

Original Article

J Korean Ophthalmol Soc 2015;56(5):680-686.

Published online: 7 September 2015

DOI: https://doi.org/10.7469/JKOS.2015.56.05.680

Corneal Microstructural Changes in Non-Sjögren Dry Eye Using Confocal Microscopy: Clinical Correlation

Eun Young Choi, MD¹, Tae Im Kim, MD, PhD^1,², Kyoung Yul Seo, MD, PhD^1,², Eung Kweon Kim, MD, PhD^1,², Hyung Keun Lee, MD^1,²

¹Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea,

²Institute of Corneal Dystrophy Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea

￭ Address reprint requests to Hyung Keun Lee, MD Department of Ophthalmology, Yonsei University Gangnam Severance Hospital, #211 Eonju-ro, Gangnam-gu, Seoul 135-720, Korea Tel: 82-2-2019-3440, Fax: 82-2-3463-1049 E-mail: shadik@yuhs.ac

Received 23 August 201424 November 2014 Accepted 20 April 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

초록

Purpose:

To investigate the relationship between changes of corneal epithelium and subbasal nerves in non-Sjögren dry eye using in vivo confocal microscope (IVCM) and self-reported clinical symptoms.

Methods:

The present study included 40 patients with dry eye and 18 healthy control subjects. The dry eye group underwent an evaluation of dry eye symptoms using visual analogue scale (VAS) score and was subdivided into 2 groups; score 0-5 as the low VAS score (LVS) group and score 6 - 10 as the high VAS score (HVS) group. The tear film break-up time, fluorescein staining, Schirmer test and microstructural imaging of epithelium, and subbasal nerve at cornea center with IVCM were performed on both eyes of each patient. Twenty-three normal eyes and 54 eyes of dry eye patients were included in the study. Cell densities and morphological characteristics were analyzed using ImageJ and NeuronJ softwares.

Results:

Both LVS and HVS groups had decreased cell density of superficial, intermediate, and basal epithelium ( p < 0.001). Intermediate epithelial cells were more decreased in the dry eye group with more severe symptoms ( p < 0.0001). Subbasal nerve density ( p < 0.005) was more decreased and nerve beadings, tortuosity, and reflectivity increased in the HVS group than both LVS and control groups ( p < 0.05).

Conclusions:

The alterations of corneal cellular level in dry eye patients visualized using IVCM are correlated with pathology and clinical symptoms and may be useful objective criteria in diagnosis and monitoring treatment efficacy.

Keywords: Confocal microscopy, Dry eye, In vivo confocal microscopy (IVCM), Non-Sjögren dry eye

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Figure 1.

In vivo confocal images of cornea. Superficial epithelium. Compared with (A), (B), and (C) had more decreased cell density. (A) Showing regularly arranged cells with dark nuclei. (B) and (C) showing squamous metaplasia, hyperreflectivity as compared to control. Intermediate epithelium. Compared with (D) and (E), (F) had more decreased cell density. Basal epithelium. Compared with (G), (H) and (I) had more decreased cell density. Bar, 100 μ m. LVS = low visual analogue scale score; HVS = high visual analogue scale score.

Figure 2.

In vivo confocal images of cornea. Subbasal nerve. Compared with (A) and (B), (C) had more decreased subbasal nerve density and had more increased subbasal nerve beadings, tortuosity, and reflectivity. Bar, 100 μ m. LVS = low visual analogue scale score; HVS = high visual analogue scale score.

Table 1.

Demographic data and clinical test results

	Control	LVS	HVS	p-value
Eyes (n)	23	26	28	N/A
Age (years)	47.87 ± 15.93	54.39 ± 11.28	50.38 ± 15.62	0.37
Sex (M/F)	7/11	4/16	9/11	0.53
BCVA (log MAR)	0.02 ± 0.07	0.03 ± 0.08	0.02 ± 0.05	0.21
Duration of dry eye (months)		41.78 ± 52.76	27.11 ± 26.44	0.32
Time of treatment (months)		18.40 ± 23.06	15.28 ± 19.37	0.67
Schirmer test (mm/5 min)	12.8 ± 2.50	6.00 ± 1.41	5.13 ± 0.89	<0.001^{^*,†}; 0.44^‡
FTBUT (s)	7.5 ± 2.64	3.00 ± 0.69	1.94 ± 1.00	<0.001^{^*,†}, <0.05^‡
Oxford scheme grade	0.13 ± 0.34	1.61 ± 1.24	1.94 ± 0.92	0.06^{^*}, <0.05^†, 0.14^‡
VAS score	0.17 ± 0.49	2.56 ± 1.42	7.25 ± 1.00	<0.001^{^*,†,‡}

Values are presented as mean ± SD unless otherwise indicated; Data in parentheses are 95% confidence interval; p-value is by ANOVA.

LVS = low VAS score; HVS = high VAS score; N/A = not applicable; BCVA = best corrected visual acuity; FTBUT = fluorescein tear breakup time; VAS = visual analogue scale; ANOVA = analysis of variance.

^* Control vs. LVS;

^† Control vs. HVS;

^‡ LVS vs. HVS.

Table 2.

Cell densities of corneal superficial, intermediate, and basal epithelium by IVCM analysis

	Epithelium
	superficial (cells/mm²)	Intermediate (cells/mm²)	Basal (cells/mm²)
Control	1,234 ± 149	6,931 ± 126	11,478 ± 586
LVS	864 ± 51	5,832 ± 232	9,023 ± 222
HVS	789 ± 31	5,316 ± 265	8,688 ± 209
p-value	<0.001^*,†; 0.17^‡	<0.0001^*,†,‡	<0.001^*,†; 0.06^‡

Values are presented as mean ± SD; Data in parentheses are 95% confidence interval; p-value is by ANOVA.

IVCM = in vivo confocal microscope; LVS = low visual analogue scale score; HVS = high visual analogue scale score; ANOVA = analysis of variance.

^* Control vs. LVS;

^† Control vs. HVS;

^‡ LVS vs. HVS.

Table 3.

Density and morphological characteristics of corneal subbasal nerve by IVCM analysis

	Subbasal nerve
	Density (μ m/mm²)	Beading (No./mm)	Tourtuosity (grade, 0-4)	Reflectivity (grade, 0-4)
Control	12,030.05 ± 2,203.55	178.70 ± 27.39	1.6 ± 0.6	2.3 ± 0.6
LVS	10,434.00 ± 2,347.73	302.72 ± 18.04	3.0 ± 0.6	2.8 ± 0.5
HVS	9,884.56 ± 2,548.56	329.38 ± 24.13	3.7 ± 0.5	3.0 ± 0.4
p-value	<0.005^*,†,‡	<0.001^*,†; <0.01^‡	<0.001^*,†; <0.05^‡	<0.05^*,†; 0.72^‡

Values are presented as mean ± SD; Data in parentheses are 95% confidence interval; p-value is by ANOVA.

IVCM = in vivo confocal microscope; LVS = low visual analogue scale score; HVS = high visual analogue scale score.

^* Control vs. LVS;

^† Control vs. HVS;

^‡ LVS vs. HVS.

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