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flammation, support of the reparative processes, and prevention of complications. These factors help to minimize scarring
and vision loss.1
The standard medical treatment used in acute ocular
chemical burns comprises topical steroids, topical antibiotics,
mydriatic cycloplegics, antiglaucoma therapy, citrate, and
ascorbate. Autologous serum drops and umbilical cord serum
drops have not been tried in the treatment of acute ocular
chemical injuries. However, autologous serum eye drops have
been shown to be effective in the treatment of various ocular
surface disorders including neurotrophic keratitis, severe dry
eye, persistent epithelial defects, and recurrent corneal erosions.29 Similarly umbilical cord serum has been shown to be
safe and effective in the treatment of neurotrophic keratitis,
dry eye syndrome, and persistent epithelial defects.8 12 Both
autologous serum and umbilical cord serum owe their efficacy
to the presence of various growth factors like epidermal
growth factor (EGF), acidic and basic fibroblast growth factor
(FGF), platelet-derived growth factor, hepatocyte growth factor,
vitamin A, transforming growth factor (TGF)-, substance P, insulin-like growth factor (IGF)-1, nerve growth factor (NGF), fibronectin, and serum antiproteases such as 2-macroglobulin.7,10,1214 The concentrations of EGF, TGF-, and NGF are
several times higher in umbilical cord serum than peripheral
blood serum.10,12 In the present study, we tested the hypothesis,
that umbilical cord serum with its higher concentration of these
growth factors may promote an early healing of the ocular surface
in cases of chemical burns.
MATERIALS
AND
METHODS
Patient Selection
Thirty-three eyes (of 32 patients) with acute ocular chemical burns
(grade III, IV, and V according to the Dua classification15) presenting
within 3 weeks of injury at our center were recruited in the study.
Patients with grade I, II, and VI injury and those with impending
perforation were excluded from the study. All patients were initially
subjected to first-aid therapy, which included irrigation with normal
saline to normalize the ocular surface pH and removal of any particulate matter or debris, as appropriate.
Randomization
A written informed consent was obtained, and the patients were
randomized into three groups. Group I received 20% umbilical cord
serum drops, group II received 20% autologous serum drops, and
group III received artificial tear drops prepared at our pharmacy (0.5%
hydroxypropylmethylcellulose and 0.3% glycerin). Randomization was
1087
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Sharma et al.
Clinical Features
0
1
2
3
4
in the serum each time before instilling the drops and to the discard
the drops if such contaminants were seen.
The autologous serum drops were prepared from the patients
blood in a manner similar to that described for umbilical cord serum.
Baseline Evaluation
A comprehensive history was taken with reference to nature of chemical to which the patient was exposed, duration of exposure, time
elapsed between exposure, and initial treatment and time elapsed
between exposure and presentation at our center.
Patients subjective assessment of pain was noted and scored as 1
(no discomfort), 2 (mild, minimal discomfort not interfering with daily
activities), 3 (moderate, interfering with daily activities), or 4 (severe,
unbearable).16
Best corrected visual acuity (BCVA) was recorded using the Snellen
chart. Detailed ophthalmic examination with a slit lamp and grading of
burns using the Dua classification15 was performed. Other parameters
noted at the initial visit included corneal clarity (Table 1), size and area
of epithelial defect, and extent of limbal ischemia. The size of the
epithelial defect was measured on the slit lamp, and the area was
obtained by the product of the dimensions of the largest diameter and
the diameter perpendicular to it.17
Patients were started on medical therapy comprising topical 0.3%
ofloxacin, every 6 hours, topical prednisolone acetate 1% every 2
hours, homatropine hydrobromide eye drops 2% three times a day,
topical ascorbate 10% every 2 hours, topical citrate 10% every 2 hours,
oral vitamin C 500 mg four times a day, preservative-free lubricants
every 2 hours and antiglaucoma medications (if required). Besides this,
group I received 20% umbilical cord serum drops 10 times a day, group
II received 20% autologous serum drops 10 times a day, and group III
received artificial tear drops (0.5% hydroxypropylmethylcellulose and
0.3% glycerin) 10 times a day.
Patients were followed up on days 1, 3, 7, 14, and 21 and at the end
of 1, 2, and 3 months. The primary end point was time to epithelialization, The other parameters assessed were pain score, limbal ischemia, size of epithelial defect, corneal clarity, and corneal vascularization, and symblepharon formation (if any). Clinical photographs were
obtained at each visit and documented by independent comparative
assessment by masked observers.
Statistical Analysis
Data were recorded on a predesigned pro forma and managed on a
spread sheet (Excel; Microsoft Corp., Redmond, WA). All entries were
checked for errors. Appropriate statistical tests were applied to analyze
the results. The Kruskal-Wallis test was used to compare epithelial
defect size and area, extent of limbal ischemia, and corneal vascularization between the three groups at each follow-up visit. The Wilcoxon
signed rank test was used to determine the significance of changes
within a group over a period (longitudinally). The 2 test was used to
compare the categorical variables.
Umbilical
Cord Serum
Autologous
Serum
30.1 11.2
26.9 7.8
31.0 8.2
6
4
2
6
4
1
3
6
1
3.7 4.4
7.9 5.6
6.5 5.3
Artificial
Tears
P
0.57
0.70
0.09
6
2
2
10
16
9
8
33
11
1
0
0
12
1
4
2
4
11
7
4
0
0
11
* P 0.125 at day 0.
P 0.011 at day 7.
1
0
4
5
10
3
7
0
0
10
0.00
0.06
0.44
M1
0.54 1.27
4.06 3.32
2.80 4.45
0.02
P*
0.00
0.25
1.0
Day 21
1.15 1.92
5.66 3.09
3.30 4.31
0.007
P*
0.02
0.11
1.0
Day 14
2.60 3.46
6.32 2.56
4.35 4.10
0.02
P*
0.19
0.57
1.0
Day 7
4.79 3.82
7.71 2.64
5.00 4.39
0.16
P*
0.73
1.0
1.0
Day 3
P*
6.43 3.60
8.55 2.58
5.7 4.25
0.30
Artificial Tears
EDD (mm)
Autologous
Serum
M2
Umbilical Cord
Serum
Day 1
Group
Day 0
P*
RESULTS
1
2
3
4
Total
0.08 0.29
1.65 2.10
1.20 2.57
0.05
P 0.13.
Data are expressed as the mean SD. CS, umbilical cord serum; AS, autologous serum; AT, artificial tears; EDD, epithelial defect diameter; EDA, epithelial defect area.
* Wilcoxon signed-rank test for the difference between baseline and sequential time points.
Kruskal-Wallis test for the difference between the three groups.
2
4
5
11
30.04 28.63 0.80 12.60 22.98 0.08 3.41 6.47 0.03 1.30 3.08 0.03 0.41 1.14 0.03 0.04 0.14 0.03
0.0 0.0 0.03
61.84 39.00 1.0 41.54 29.30 0.18 32.99 29.48 0.13 22.53 23.66 0.05 13.49 16.8 0.015 5.58 10.74 0.012 0.36 1.2 0.01
36.91 47.24 1.0 30.99 48.35 1.0 26.80 49.90 1.0 25.25 50.53 1.0 16.67 39.3 0.50 4.60 9.74 0.21 0.01 0.02 0.29
0.088
0.02
0.005
0.016
0.104
0.043
0.554
8
3
1
12
Grade III
Grade IV
Grade V
Total
EDA (mm2)
Total
0.00
0.01
0.04
Artificial
Tears
7.64 0.36
8.73 2.54
6.43 0.47
0.435
Group Autologous
Serum
CS
AS
AT
P
Umbilical
Cord Serum
P*
Grade
M3
P*
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Sharma et al.
FIGURE 1. Cord serum group: acute chemical burns at (1A) day 0, (1C) month 1, and (1E) month 3; fluorescein staining of acute chemical burns
at (1B) day 0, (1D) month 1, and (1F) month 3. Auto serum group: acute chemical burns at (2A) day 0, (2C) month 1, and (2E) month 3; fluorescein
staining of acute chemical burns at (2B) day 0, (2D) month 1, and (2F) month 3. Artificial tears group: acute chemical burns at (3A) day 0, (3C)
month 1, and (3E) month 3; fluorescein staining of acute chemical burns at (3B) day 0, (3D) month 1, and (3F) month 3.
FIGURE 2.
Autologous
Serum
1.04 8.36
1.29 4.31
0.0 (12.525.0)
0.0 (14.290.0)
9.72 12.22
1.29 4.31
0.0 (0.025.0)
0.0 (14.290.0)
22.17 14.03
3.03 11.9
25.0 (0.050.0)
0.0 (14.2933.3)
32.85 17.65
13.23 12.40
28.57 (0.066.7)
14.29 (0.033.3)
34.28 17.54
14.55 12.22
28.57 (0.066.7)
14.28 (0.033.0)
44.74 21.95
24.51 20.63
50.0 (0.083.3)
20.0 (0.057.14)
60.0 22.41
28.88 18.74
56.25 (20.0100.0)
25.0 (0.057.14)
73.43 25.51
35.64 25.60
75.0 (30.0100.0) 28.57 (0.080.0)
Artificial
Tears
0.0 0.0
0.70
0.0 (0.00.0)
1.67 5.27
0.017
0.0 (0.016.7)
11.0 15.56 0.01
0.0 (0.040.0)
16.6 17.8
0.02
15.48 (0.050.0)
20.76 21.09 0.041
17.42 (0.050.0)
28.09 21.71 0.092
26.67 (0.066.7)
33.19 21.92 0/007
40.0 (0.066.7)
43.71 28.71 0.008
53.57 (0.080.0)
Data are the mean percentage SD, with the median (range) of
the decrease in limbal ischemia.
1091
Symblepharon
Umbilical
Cord Serum
Autologous
Serum
Artificial
Tears
Total
Absent
Present
Total
9
3
12
3
8
11
5
5
10
17
16
33
P 0.073.
FIGURE 3.
DISCUSSION
The purpose of this study was to compare the efficacy of
autologous serum therapy and umbilical cord serum therapy in
achieving restoration of an intact ocular epithelium, control of
acute inflammatory reaction, support of the reparative processes, and prevention of complications in acute ocular chemical burns. The recently recognized role of growth factors and
the success of amniotic membrane transplantation in various
ocular surface disorders like persistent epithelial defects and
severe dry eye formed the basis of our study.16,18,19 EGF and
FGF both stimulate the proliferation of corneal epithelium.20,21
EGF in addition also increases the tensile strength of the
wounds.21 Topical application of neuronotropic substances
such as substance P, IGF-1, and nerve growth factor (NGF) has
been tried, to promote corneal wound healing.2226 Topical
fibronectin has also been used in the treatment of persistent
epithelial defects.27,28
Serum is beneficial for the ocular surface and owes its
efficacy to the presence of various growth factors. Autologous
Autologous Serum
Artificial Tears
Corneal Clarity
Day 0*
Month 3
Day 0*
Month 3
Day 0*
Month 3
1
2
3
4
Total
1
5
5
1
12
0
0
3
9
12
4
5
2
0
11
4
1
5
1
11
2
4
4
0
10
2
1
4
3
10
* P 0.535 at day 0.
P 0.048 at month 3.
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Sharma et al.
References
1. McCulley JP. Chemical injuries of the eye. In: Leibowitz HM,
Waring GO. Corneal Disorders: Clinical Diagnosis and Management. 2nd ed. Philadelphia: W.B. Saunders; 1998:770 790.
2. Fox RI, Chan R, Michelson JB, Belmont JB, Michelson PE. Beneficial effect of artificial tears made with autologous serum in patients
with keratoconjunctivitis sicca. Arthritis Rheum. 1984;27:459
461.
3. Tsubota K, Goto E, Fujita H, et al. Treatment of dry eye by
autologous serum application in Sjogrens syndrome. Br J Ophthalmol. 1999;83:390 395.
4. Rocha EM, Pelegrino FS, de Paiva CS, Vigorito AC, de Souza CA.
GVHD dry eyes treated with autologous serum tears. Bone Marrow Transplant. 2000;25:11011103.
5. del Castillo JM, del la Casa JM, Sardina RC. Treatment of recurrent
corneal erosions using autologous serum. Cornea. 2002;21:781
783.
6. Young AL, Cheng AC, Ng HK, et al. The use of autologous serum
tears in persistent epithelial defect. Eye. 2004;18:609 614.
7. Matsumoto Y, Dogru M, Goto E, et al. Autologous serum application in the treatment of neurotrophic keratopathy. Ophthalmology. 2004;111:11151120.
8. Vajpayee RB, Mukerji N, Tandon R, et al. Evaluation of umbilical
cord serum therapy for persistent corneal epithelial defects. Br J
Ophthalmol. 2003;87:13121316.
9. Yoon KC, Heo H, Im SK, You IC, Kim YH, Park YG. Comparison of
autologous serum and umbilical cord serum eye drops for dry eye
syndrome. Am J Ophthalmol. 2007;144:86 92.