Ocular Surface Pathology in Patients Suffering from Mercury Intoxication
Abstract
:1. Introduction
2. Methods
2.1. Patients
2.2. Clinical Evaluation and Tear Sample Collection
- (1)
- Ocular surface-related symptom questionnaire. The Ocular Surface Disease Index (OSDI), consisted of 12 questions that evaluated symptoms experienced in the preceding week. The questionnaire was self-administered and scored on a range of 0 to 100. Based on their OSDI score, each patient was categorized as having no symptoms (score 0–12) or as having mild (score 13–22), moderate (score 23–32 points), or severe (score 33–100) ocular surface-related symptoms [9].After completing the OSDI questionnaire, we asked each patient which eye he considered the most symptomatic. That eye was used for tear sampling, osmolarity measurement, esthesiometry, microscopy, and in statistical analyses of the clinical tests. If both eyes were equally symptomatic, the eye was selected by computer-generated randomization.
- (2)
- Tear sample collection for molecular analysis. We followed our previous protocol in which unstimulated basal tear samples were collected non-traumatically from the external canthus, avoiding reflex tearing as much as possible [10]. One microliter of tear sample was collected with a glass capillary micropipette (Drummond, Broomall, PA, USA). Each sample was then diluted 1:10 in a sterile collection tube containing ice-cold Cytokine Assay Buffer (Milliplex, Millipore Merck Life Science SLU, Madrid, Spain). Tubes with tear samples were kept cold (4 °C) during collection and then stored at −80 °C until assayed.
- (3)
- Tear osmolarity. The osmolarity of each tear sample was assessed by the TearLab osmometer (TearLab Corporation, San Diego, CA, USA) analysis of a 50-nL tear sample collected from the external canthus. Although the cutoff value for abnormal tear osmolarity can vary according to different authors, following the manufacturer’s indications, values above 308 mOsm/L were considered higher than normal [11].
- (4)
- Conjunctival bulbar hyperemia. The nasal and temporal conjunctivas were assessed independently with a slit-lamp biomicroscope (SL-8Z; Topcon Corp, Tokyo, Japan) based on the Efron scale (0–4 score). The final score was the average of the nasal and temporal values [11].
- (5)
- Tear break-up time (T-BUT). Tear stability was assessed by T-BUT. After instillation of 5 μL of 2% sodium fluorescein into the inferior fornix, the time between the last of three blinks and the appearance of the first dry spot was measured three times, and the mean value was recorded. Values of less than 7 s are currently considered abnormal [11].
- (6)
- Ocular surface integrity. Corneal and conjunctival integrity were evaluated with fluorescein and lissamine green staining, respectively. The Oxford scheme (0–5 score) for grading the staining of both areas was used [11]. Corneal fluorescein staining was evaluated 2 min after instillation of 5 μL of 2% sodium fluorescein. The cobalt blue filter of the slit lamp was used with a yellow Wratten no. 12 filter (Eastman Kodak, Rochester, NY, USA) over the light source. Nasal and temporal bulbar conjunctival staining was evaluated using lissamine green strips (GreenGlo; HUB Pharmaceuticals, LLC, Rancho Cucamonga, CA, USA) wetted with 25 μL sodium chloride and then gently applied into the inferior fornix.
- (7)
- Tear production. Tear production was assessed with two different tests: tear lysozyme level assay and Schirmer’s test without topical anesthesia. The tear lysozyme concentration test is routinely performed in our institution as a marker of aqueous-deficient dry eye (DE), as previously detailed [12]. Briefly, tears were sampled by applying a 5-mm diameter filter paper disc in the inferior fornix, and the eye was held closed for 1 min. The assay was carried out with the Micrococcus lysodeikticus (ATCC 4698, M3770; Sigma-Aldrich, St. Louis, MO, USA) agar diffusion assay in Mueller Hinton agar plates (Bio Merieux, Marcy l’Etoile, France). Lysozyme concentration was calculated from a standard curve of the inhibition hallux generated with several concentrations of commercial lysozyme (ATCC 4698, L6876; Sigma-Aldrich). Values of less than 1000 μg/mL were considered abnormal and thus indicative of low tear production [12].Immediately after the lysozyme tear production assay, the Schirmer test was performed by placing a sterile strip (I-DEW tear strips, Entod Research Cell UK, Ltd., London, UK) in the lateral canthus of the inferior lid margin. Subjects were asked to maintain eye closure during the test, and the length of wetting was measured after 5 min. Results below 5-mm length were considered abnormal [11].
- (8)
- Corneal sensitivity. Corneal sensitivity was measured with a prototype Belmonte’s non-contact gas esthesiometer as previously reported by our group [13]. The corneal threshold for mechanical and thermal (cold and heat) sensitivities was determined in the central cornea using the method of levels. Three-second air pulses of adjustable flow rate and temperature were applied to the center of the cornea for determining corneal sensitivity thresholds. The mechanical threshold was always determined first. The probe of the esthesiometer was mounted on a base adapted to a slit lamp. Subjects were instructed to look at a fixation target at 3 m, and the tip was placed perpendicular to the corneal apex, 5 mm from the surface, measured with a transparent ruler. Mechanical stimulation consisted of a series of variable flows of medicinal air (0–200 mL/min). Air was heated at the tip of the probe at 50 °C so that it reached the ocular surface at 34 °C to prevent a change in corneal temperature caused by the airflow. Thermal thresholds were determined by heating or cooling the air to produce changes in basal corneal temperature of ± 0.1 °C, with a 10 mL/min flow below the mechanical threshold. A noise (a click produced by opening the gas valve) indicated the start of the pulse. Immediately after each stimulation pulse, the subject was asked to report the presence or absence of sensation. The order of heat and cold threshold measurement was randomized. Results were compared with a control group of 22 healthy males whose characteristics have been described above.
- (9)
- In vivo confocal microscopy (IVCM). Laser scanning IVCM of the cornea was performed using the Rostock cornea module of the Heidelberg Retina Tomograph 3 (Heidelberg Engineering GmbH, Heidelberg, Germany). Before examination, a drop of anesthetic was instilled, and an eye speculum was used to keep the lids wide open. A drop of Viscotears Gel (Carbomer 980, 0.2%; Novartis Farmacéutica S.A., Barcelona, Spain) was deposited on the objective lens, thus avoiding direct contact of the TomoCap with the cornea. At least three good quality, non-overlapping images from the sub-basal nerve plexus of the central cornea were obtained using sequence and/or volume scans, and were used for the analysis. Each image was comprised of 384 × 384 pixels covering an area of 400 × 400 μM (0.16 mm2) with a transverse optical resolution of 2 μM, an axial optical resolution of 4 μM, and an acquisition time of 0.024 s.For IVCM image analysis, two masked observers analyzed the following in the three images: (1) nerve morphology parameters of density, length, branching density, and grade of tortuosity; (2) density of dendritic cells; (3) presence of neuromas; and (4) reflectivity from the confocal images, as an index of optic densitometry or transparency of cornea [14]. The mean value between the two observers for each parameter was computed for statistical analysis.Nerve density (n/mm2) and length (mm/mm2) were measured using the plugin NeuronJ (http://www.imagescience.org/meijering/software/neuronj/ accessed on 25 May 2021) from the ImageJ and provides quantification. The number of nerve branch points and dendritic cells (identified in the sub-basal nerve plexus by their distinctive features, i.e., bright cell bodies with dendritic form structures), were manually determined using the multipoint tool of the ImageJ software, and the densities calculated (n/mm2) as described in a previous study [15]. The grade of nerve tortuosity was evaluated according to the scale (0–4) reported by Oliveira-Soto and Efron [16] for main nerves. The histogram of each image based on the ImageJ plugin was used to obtain the mean reflectivity or optic densitometry [14]. These parameters were compared with well-established values for normal corneas and performed with the same type of confocal microscope. Specifically, we used data from Giannacare et al. [17] for nerve length, and from our group for nerve density, density of nerve branches, density of dendritic cells, [15] and nerve tortuosity and reflectivity [14].
- (10)
- Analysis of tear cytokine concentrations. A commercial customized immunobead-based array was used to analyze the concentration of 23 cytokines and chemokines in tear samples with a Luminex IS-100 (Luminex Corporation, Austin, TX, USA). The concentrations of interleukin (IL)-1β IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-5, IL-6, chemokine (C-XC motif) ligand 8 (CXCL8)/IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-17A, chemokine (C-X-C motif) ligand 10 (CXCL10)/interferon gamma-induced protein 10 (IP-10), chemokine (C-C motif) ligand 2 (CCL2)/MCP-1, chemokine (C-C motif) ligand 3 (CCL3)/MIP1-αchemokine (C-C motif) ligand 5 (CCL5)/regulated on activation, normal T-cell expressed and secreted (RANTES), chemokine (C-C motif) ligand 11 (CCL11/eotaxin-1), chemokine (C-X3-C motif) ligand 1 (CX3CL1)/fractalkine, interferon gamma (IFN)-γ, matrix metalloproteinase-9 (MMP-9), tumor necrosis factor (TNF)-α, epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) were measured simultaneously with a customized 23-plex SPR assay (SPR591 HCYTO- 60K, 23X-Milliplex). The samples were analyzed following the manufacturer’s low volume sample protocol that only uses 10 μL of sample/standards per assay, as previously described [10]. Data were stored and analyzed with the “Bead View Software” (Upstate-Millipore Corporation, Watford, UK). Standard curves were used to convert fluorescence units to molecule concentrations (pg/mL). The minimum detectable concentration, based on manufacturer specifications, was 1.2 pg/mL. Molecules that were detected in less than 30% of the samples were not statistically analyzed any further. Results were compared with a control group of 22 healthy males from our files, whose characteristics have been described above.
2.3. Statistical Analysis
3. Results
3.1. Clinical Tests
3.2. Corneal Sensitivity
3.3. IVCM Findings
3.4. Analysis of Tear Cytokine Concentration
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient N°/Age | Onset of Symptoms (Weeks after Exposure) | Osdi (Range 0–100; Normal <12) | Tear Osmolarity (Normal <308 Mosms/L) | Conjunctival Redness (0–4) | T-But (Normal ≥7 s) | Corneal/Conjunctival Staining (Range 0–5) | Schirmer Test (Normal >5 Mm)/Tear Lysozyme Level (Normal ≥1000 μM/mL) | Corneal Sensitivity Thresholds * Mechanical/Heat/Cold |
---|---|---|---|---|---|---|---|---|
1/45 | 10 | 35.00 | 330 | 0 | 2 | 0/1 | 5/881 | 165/+2.16/−1.12 |
2/29 | 12 | 20.80 | 329 | 0 | 10 | 0/0 | 25/4934 | 100/+0.80/−0.80 |
3/49 | 1 | 52.00 | 323 | 0 | 2 | 1/1 | 22/1369 | 200/+0.80/−2.72 |
4/47 | 1 | 84.00 | 353 | 0 | 12 | 0/0 | 10/511 | 160/+2.16/−3.20 |
5/39 | 2 | 14.50 | 377 | 0 | 9 | 0/0 | 18/209 | 90/+1.60/−0.80 |
6/28 | 0 | 14.50 | 298 | 0 | 6 | 0/0 | 3/548 | 50/+1.60/−1.20 |
7/30 | 1 | 50.00 | 318 | 0 | 16 | 0/0 | 6/1000 | 85/+4.00/−4.00 |
8/37 | 1 | 58.30 | 330 | 0 | 9 | 1/1 | 4/593 | 190/+1.60/−2.40 |
9/50 | 2 | 50.00 | 330 | 1 | 7 | 0/0 | 11/654 | 172/+2.80/−3.52 |
10/44 | 2 | 22.90 | 316 | 0 | 16 | 0/0 | 25/1415 | 190/+2.16/−1.44 |
11/42 | 2 | 29.10 | 338 | 0 | 12 | 0/0 | 6/629 | Not performed |
12/52 | 0 | 27.00 | 400 | 0 | 14 | 0/0 | 15/1186 | 200/+3.20/−3.52 |
13/51 | 3 | 65.90 | 323 | 2 | 3 | 1/1 | 1/391 | 200/+0.32/−3.20 |
14/36 | 4 | 70.40 | 332 | 0 | 11 | 0/0 | 13/153 | 120/+3.20/−1.20 |
15/45 | 1 | 50.00 | 356 | 0 | 10 | 0/0 | 8/316 | 200/+4.00/−4.00 |
16/36 | 2 | 35.00 | 330 | 0 | 2 | 0/1 | 5/881 | 100/+2.80/−2.20 |
17/47 | 1 | 75.00 | 338 | 0 | 8 | 2/1 | 13/1000 | 142/+2.80/−4.00 |
18/38 | 4 | 12.00 | 297 | 0 | 9 | 0/0 | 7/588 | 200/+3.60/−3.20 |
19/40 | 3 | 27.00 | 400 | 0 | 14 | 0/0 | 15/1186 | 175/+1.20/−2.80 |
20/42 | 1 | 45.00 | 349 | 0 | 12 | 0/0 | 6/1849 | 200/+2.64/−4.00 |
21/56 | 2 | 75.00 | 342 | 0 | 12 | 1/1 | 5/760 | 130/+1.92/−0.56 |
22/41 | 1 | 64.50 | 288 | 2 | 14 | 1/1 | 10/316 | 35/+4.00/−4.00 |
Mean (SD) | 2.54 (2.95) | 44.5 (22.04) | 336.23 (28.71) | 9.55 (4.39) | 10.59 (6.97)/970.90 (984.02) | 147.81 (53.36)/ +2.35 (+1.10)/ −2.57 (−1.24) | ||
Median [IQR] | 0 [0] | 0 [0.75]/0 [1] |
Study Group (n = 21) | Control Group (n = 22) | ||||||
---|---|---|---|---|---|---|---|
Sensitivity Threshold | Mean (SD) | 95% CI | Mean (SD) | 95% CI | p Value | ||
Inferior | Superior | Inferior | Superior | ||||
Mechanical (mL/min) | 147.81(53.36) | 123.52 | 172.10 | 69.64 (43.07) | 49.49 | 89.80 | 0.0001 |
Thermal hot (°C) | +2.35 (+1.10) | +1.85 | +2.85 | +1.3 (+0.89) | +0.89 | +1.72 | 0.0018 |
Thermal cold (°C) | −2.57 (−1.24) | −3.13 | −2.00 | −1.83 (−1.32) | −2.45 | −1.22 | 0.0470 |
Nerve Parameters | ||||||
---|---|---|---|---|---|---|
Patient No./Age * (years) | Density (n/mm2) | Length (mm/mm2) | Tortuosity (0–4) | Density of Branching (n/mm2) | Dendritic Cell Density (n/mm2) | Reflectivity (Gray Units) |
1/45 | 9.0 | 10.90 | 3.0 | 6.5 | 3.5 | 99.70 |
2/29 | 8.0 | 13.77 | 3.0 | 3.0 | 0.5 | 76.29 |
3/49 | 4.0 | 19.91 | 3.0 | 0.5 | 0.0 | 92.00 |
4/47 | 7.0 | 16.05 | 2.0 | 0.0 | 14.0 | 83.97 |
5/39 | 4.0 | 11.39 | 1.5 | 0.0 | 3.0 | 98.97 |
6/28 | 8.0 | 11.99 | 2.0 | 0.5 | 2.0 | 88.22 |
9/50 | 4.5 | 9.06 | 2.0 | 0.0 | 12.0 | 79.30 |
10/44 | 3.5 | 20.51 | 2.0 | 1.0 | 28.5 | 99.50 |
11/42 | 6.0 | 11.79 | 1.0 | 0.0 | 0.0 | 93.66 |
12/52 | 5.0 | 19.45 | 3.0 | 1.0 | 4.5 | 83.42 |
14/36 | 2.0 | 26.15 | 3.0 | 0.0 | 5.0 | 101.23 |
17/47 | 4.0 | 17.78 | 2.0 | 1.0 | 15.5 | 118.75 |
18/38 | 13.0 | 16.04 | 3.0 | 5.5 | 23.0 | 104.56 |
19/40 | 8.5 | 16.81 | 2.0 | 6.5 | 16.5 | 79.02 |
21/56 | 9.5 | 16.89 | 2.0 | 4.5 | 8.50 | 97.72 |
Mean (SD) | 6.4 (2.9) | 15.90 (4.54) | 2 (2.5) | 9.1 (8.9) | 93.09 (11.56) | |
Median [IQR] | 2.0 [1.0] |
Study Group Mean (SD) or Median [IQR] | Control Group Mean (SD) or Median [IQR] | p Value | |
---|---|---|---|
Nerve density (n/mm2) | 6.4 (2.9) | 10.5 (3.3) [15] | 0.0006 |
Nerve length (mm/mm2) | 15.90 (4.54) | 14.50 (2.90) [17] | 0.2151 |
Density of nerve branching (n/mm2) | 2.0 (2.5) | 52.4 (26.2) [15] | <0.0001 |
Grade of nerve tortuosity (0–4) | 2.0 [1.0] | 1.9 (0.8) [14] | 0.1201 |
Density of dendritic cells (n/mm2) | 9.1 (8.8) | 57.5 (70.2) [15] | 0.0063 |
Reflectivity (Gray units) | 93.09 (11.56) | 87.16 (13.10) [14] | 0.1731 |
Tear Cytokine | Study Group | Control Group | p Value * | ||||
---|---|---|---|---|---|---|---|
Detection | Concentration pg/mL | Detection | Concentration pg/mL | ||||
n | % [95%CI] | mean [95%CI] | n | % [95%CI] | mean [95%CI] | ||
IL-1β | 11 | 50.0 [30.72; 69.28] | 18.36 [9.32; 36.16] | 10 | 45.5 [25.07; 67.33] | 14.52 [7.07; 29.82] | 0.6247 |
IL-1RA | 19 | 86.4 [64.04; 96.41] | 1559.04 [612.89; 3965.78] | 12 | 57.1 [34.44; 77.41] | 1031.97[457.15; 2329.54] | 0.4923 |
IL-2 | 14 | 63.6 [40.83; 81.97] | 38.83 [20.81; 72.44] | 6 | 40 [17.46; 67.11] | 17.45 [10.53; 28.93] | 0.0761 |
IL-4 | 13 | 59.1 [36.68; 78.52] | nc | 6 | 28.6 [12.19; 52.31] | nc | - |
IL-5 | 10 | 45.5 [25.07; 67.33] | 16.75 [7.10; 39.49] | 9 | 40.9 [21.48; 63.32] | 6.36 [2.94; 13.62] | 0.0878 |
IL-6 | 19 | 86.4 [64.04; 96.41] | 93.53 [56.92; 153.68] | 22 | 100 [81.50; 100] | 23.82 [9.4; 60.34] | 0.011 |
IL-8/CXCL8 | 18 | 81.8 [58.99; 94.01] | 62.53 [29.73; 131.53] | 11 | 50 [30.72; 69.28] | 23.64 [9.99; 55.88] | 0.0856 |
IL-9 | 15 | 68.2 [45.12; 85.27] | 32.81 [17.58; 61.24] | 9 | 60 [32.89; 82.54] | 49.00 [27.12; 88.54] | 0.4011 |
IL-10 | 7 | 31.8 [14.73; 54.88] | nc | 2 | 22.2 [3.95; 59.81] | nc | - |
IL-12p70 | 10 | 45.5 [25.07; 54.88] | 329.58 [204.46; 531.28] | 15 | 68.2 [45.12; 85.27] | 63.31 [23.70; 169.13] | 0.0045 |
IL-13 | 19 | 86.4 [64.04; 96.41] | 131.22 [74.39; 231.45] | 21 | 95.5 [75.12; 99.76] | 152.63 [80.37; 289.86] | 0.7154 |
IL-17A | 10 | 45.5 [25.07; 67.33] | 56.04 [31. 9; 98.48] | 4 | 80 [29.88; 98.95] | 35.86 [19.36; 66.43] | 0.4916 |
IP-10/CXCL10 | 21 | 95.5 [75.12; 99.76] | 6806.46 [3124.56; 14,826.99] | 21 | 100 [80.76; 100] | 22,900.94 [16,099.67; 32,575.40] | 0.0063 |
MCP-1/CCL2 | 18 | 81.8 [58.99; 94.01] | 427.52[219.29; 833.51] | 10 | 90.9 [57.12; 99.52] | 329.39 [201.37; 538.80] | 0.6151 |
MIP-1αCCL3 | 4 | 18.2 [5.99; 41.01] | nc | 0 | 0 [0.00; 34.45] | nc | - |
RANTES CCL5 | 13 | 59.1 [36.68; 78.52] | 354.00 [192.08; 652.42] | 17 | 81 [57.42; 93.71] | 61.14 [30.51; 122.50] | 0.0003 |
Eotaxin/CCL11 | 7 | 31.8 [14.73; 54.88] | n/c | 2 | 18.2 [3.21; 52.25] | nc | - |
Fractalkine/ CX3CL1 | 14 | 63.6 [40.83; 81.97 | 1621.12 [838.99; 3132.34] | 14 | 87.5 [60.41; 97.80] | 1094.22 [593.23; 2018.30] | 0.4125 |
IFN-γ | 13 | 59.1 [36.68; 78.52] | 50.69 [19.26; 133.37] | 11 | 52.4 [30.34; 73.61] | 15.25 [7.13; 32.62] | 0.0521 |
MMP-9 | 18 | 81.8 [58.99; 94.01] | 524.80 [205.12; 1342.73] | 12 | 92.3 [62.09; 99.60] | 313.56 [92.99; 1057.38] | 0.5378 |
TNF-α | 14 | 63.6 [40.83; 81.97] | 24.97 [12.55; 49.68] | 11 | 50.0 [30.72; 69.28] | 11.61[5.80; 23.23] | 0.1103 |
EGF | 17 | 77.3 [54.18; 91.31] | 445.69 [177.01; 1122.21]) | 22 | 100 [81.50; 100] | 1333.78 [852.56; 2086.60] | 0.0339 |
VEGF | 19 | 86.4 [64.04; 96.41] | 4733.30 [3406.12; 6577.61] | 10 | 66.7 [38.69; 87.01] | 983.05 [573.75; 1684.33] | <0.0001 |
Tear Molecule | Concentration (pg/mL) Mean (Standard Deviation)/Median [Interquartile Range] | Fold Change (Log2) | Adjusted p Value | |
---|---|---|---|---|
Cluster 1 | Cluster 2 | |||
IL-1β | 12.47 (9.89)/9.94 [11.80] | 108.82 (73)/109.45 [73.58] | 3.02 | 0.0009 |
IL-1RA | 17918.94 (42897.86)/1120.00 [5331.25] | 3075.62 (2899.16)/1455.00 [3310.00] | 0.70 | 0.6152 |
IL-2 | 22.39 (18.04)/17.99 [22.57] | 197.18 (92.58)/182.00 [43.25] | 3.48 | <0.0001 |
IL-4 | 217.01 (191.75)/149.35 [204.63] | 1129 (774.36)/1138.50 [1009.25] | 2.57 | 0.0003 |
IL-5 | 8.95 (8.66)/6.14 [10.52] | 175.86 (125.80)/169.00 [141.93] | 4.67 | <0.0001 |
IL-6 | 69.05 (51.35)/61.4 [85.19] | 305.62 (156.63)/314.50 [124.50] | 2.44 | 0.0001 |
IL-8/CXCL8 | 289.27 (883.19)/33.35 [72.04] | 192.36 (113.63)/158.00 [162.90] | 2.21 | 0.0144 |
IL-9 | 19.9 (15.13)/16.71 [23.90] | 169.93 (107.48)/156.00 [33.68] | 3.34 | <0.0001 |
IL-10 | 61.22 (44.61)/53.41 [67.89] | 509.64 (415.36)/535.00 [423.75] | 2.62 | 0.0078 |
IL-12p70 | 195.14 (101.51)/188.51 [172.44] | 1163.38 (456.5)/1065.00 [491.75] | 2.72 | <0.0001 |
IL-13 | 91.64 (65.76)/88.70 [91.02] | 511.62 (256.37)/466.50 [177.75] | 2.84 | 0.0001 |
IL-17A | 32.19 (20.14)/29.02 [31.45] | 250.71 (118.73)/260.50 [93.50] | 3.13 | <0.0001 |
IP-10/CXCL10 | 21,081.29 (33,089.71)/10,660.00 [19,848.25] | 13,318.75 (5612.46)/12,800.00 [6342.50] | 1.33 | 0.1529 |
MCP-1/CCL2 | 578.88 (1088.12)/237.50 [397.44] | 1931.38 (1509.72)/2065.00 [2257.75] | 2.50 | 0.0083 |
RANTES/CCL5 | 224.68 (214.75)/145.24 [118.81] | 1652.62 (613.31)/1625.00 [382.50] | 3.37 | <0.0001 |
Eotaxin/CCL11 | 35.72 (54.9)/19.54 [27.23] | 218.59 (263.31)/142.70 [212.31] | 2.38 | 0.0284 |
Fractalkine/CX3CL1 | 1596.81 (3124.23)/643.47 [555.99] | 7427.5 (1900.32)/7595.00 [1407.50] | 3.38 | 0.0001 |
IFN-γ | 27.2 (34.91)/15.86 [17.22] | 650.12 (352.83)/662.50 [316.25] | 5.44 | <0.0001 |
MMP-9 | 11,773.76 (40,665.8)/289.00 [1937.85] | 1233.25 (902.46)/837.50 [1375.75] | 1.42 | 0.2081 |
TNF-α | 14.18 (11.59)/10.67 [15.54] | 154.51 (97.55)/138.50 [48.38] | 3.79 | <0.0001 |
EGF | 2982.49 (8168.04)/145.50 [2205.38] | 1728.88 (1192.08)/1895.00 [2116.25] | 2.29 | 0.0981 |
VEGF | 3644.16 (1891.64)/3585.00 [2770.00] | 10,180 (3691.33)/10,200.00 [3345.00] | 1.60 | 0.0002 |
Test | Cluster 1 | Cluster 2 | p Value |
---|---|---|---|
OSDI questionnaire (0–100) mean (SD) | 38.09 (20.19) | 55.58 (21.89) | 0.0723 |
Tear osmolarity (mOsms/L) mean (SD) | 338.64 (31.03) | 332 (25.56) | 0.6137 |
Conjunctival redness (0–4) median [IQR] | 0 [0] | 0 [0.5] | 0.2295 |
T-BUT (seconds) mean (SD) | 10.57 (3.98) | 7.75 (4.77) | 0.1517 |
Ocular surface integrity (0–5) median Corneal staining Conjunctival staining | 0 [0] 0 [0] | 0.5 [1.0] 1.0 [1.0] | 0.1246 0.0656 |
Tear production mean (SD) Schirmer test (mm/5 min) Lysozyme tear level (μg/mL) | 10.71 (7.14) 1209.79 (1143.54) | 10.38 (7.15) 552.88 (403.12) | 0.8372 0.0189 |
Corneal sensitivity thresholds mean (SD) Mechanical (mL/min) Thermal hot (°C) Thermal cold (°C) | 149.54 (51.94) +2.58 (+1.01) −2.71 (−1.31) | 145 (59.10) +1.98 (+1.20) −2.33 (−1.17) | 0.8555 0.2342 0.4008 |
Corneal imaging in vivo confocal microscopy Nerve density (n/mm2) mean (SD) Nerve length (mm/mm2) mean (SD) Nerve branching density (n/mm2) mean (SD) Nerve tortuosity (0–4) median [IQR)]Dendritic cell density (n/mm2) mean (SD) Reflectivity (Gray units) mean (SD) | 7.0 (2.9) 15.41 (3.65) 2.3 (2.4) 2.2 [0.6] 11.10 (9.79) 92.05 (13.46) | 5.2 (2.8) 16.88 (6.35) 0.1 (0.3) 2.5 [0.7] 2.88 (2.1) 95.17 (7.20) | 0.2786 0.5728 0.0417 0.5034 0.0291 0.6391 |
Maximum mercury levels * mean (SD) Blood (μg/L) Urine (μg/g creatinine) | 398.57 (273.61) 121.64 (121.65) | 359.75 (314.61) 384.75 (396.88) | 0.7647 0.0373 |
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Cañadas, P.; Lantigua, Y.; Enríquez-de-Salamanca, A.; Fernandez, I.; Pastor-Idoate, S.; Sobas, E.M.; Dueñas-Laita, A.; Pérez-Castrillón, J.L.; Pastor Jimeno, J.C.; Calonge, M. Ocular Surface Pathology in Patients Suffering from Mercury Intoxication. Diagnostics 2021, 11, 1326. https://doi.org/10.3390/diagnostics11081326
Cañadas P, Lantigua Y, Enríquez-de-Salamanca A, Fernandez I, Pastor-Idoate S, Sobas EM, Dueñas-Laita A, Pérez-Castrillón JL, Pastor Jimeno JC, Calonge M. Ocular Surface Pathology in Patients Suffering from Mercury Intoxication. Diagnostics. 2021; 11(8):1326. https://doi.org/10.3390/diagnostics11081326
Chicago/Turabian StyleCañadas, Pilar, Yrbani Lantigua, Amalia Enríquez-de-Salamanca, Itziar Fernandez, Salvador Pastor-Idoate, Eva M. Sobas, Antonio Dueñas-Laita, José Luis Pérez-Castrillón, Jose C. Pastor Jimeno, and Margarita Calonge. 2021. "Ocular Surface Pathology in Patients Suffering from Mercury Intoxication" Diagnostics 11, no. 8: 1326. https://doi.org/10.3390/diagnostics11081326