You are on page 1of 6

Clinical Trials

Evaluation of Umbilical Cord Serum Therapy in Acute


Ocular Chemical Burns
Namrata Sharma,1 Manik Goel,1 Thirumurthy Velpandian,1 Jeewan S. Titiyal,1
Radhika Tandon,1 and Rasik B. Vajpayee1,2,3
PURPOSE. To evaluate the role of umbilical cord serum therapy
in cases of acute ocular chemical burns.
METHODS. In a double-blind prospective randomized controlled
clinical study, 33 eyes of 32 patients with acute ocular chemical burns of grade III, IV, and V severity were randomized into
three groups: umbilical cord serum (n 12), autologous serum (n 11), and artificial tears (0.5% HPMC0.3% glycerin;
n 10). In addition, all eyes received standard medical therapy. The parameters evaluated were pain score, size, and area
of epithelial defect, extent of limbal ischemia, corneal clarity,
and symblepharon formation. The patients were followed up at
day1, 3, 7, 14, and 21 and at the end of months 1, 2, and 3.
RESULTS. Mean time to complete epithelialization was
21.16 26.81, 56.6 35.5, and 40.13 35.79 days in cord
serum, autologous serum, and artificial tears groups respectively (P 0.02). By day 21, the mean percentage decrease in
epithelial defect diameter was 94.63 11.99 with cord serum
compared with 53.17 34.81 and 64.22 42.43 with autologous serum and artificial tears, respectively (P 0.01). By
month 3, the extent of limbal ischemia with cord serum
showed a mean percentage decrease of 73.43 25.51 compared with 35.64 25.60 and 43.71 28.71 with autologous
serum and artificial tears, respectively (P 0.008). More patients had clear corneas with cord serum compared with autologous serum and artificial tears (P 0.048). No significant
difference was seen between the groups with regard to symblepharon formation (P 0.07).
CONCLUSIONS. Umbilical cord serum therapy is more effective than
autologous serum eye drops or artificial tears in ocular surface
restoration after acute chemical injuries. (www.controlled-trials.
com number, ISRCTN08131903.) (Invest Ophthalmol Vis Sci.
2011;52:10871092) DOI:10.1167/iovs.09-4170

cular chemical burns are a serious ocular emergency that


require prompt treatment and meticulous follow-up. The
primary objectives of therapy in a case of acute ocular chemical burns are promotion of epithelialization, reduction of in-

From the Rajendra Prasad Centre for Ophthalmic Sciences, All


India Institute of Medical Sciences, New Delhi, India; the 2Centre for
Eye Research Australia, University of Melbourne, Melbourne, Victoria,
Australia; and the 3Royal Victorian Eye and Ear Hospital, Melbourne,
Victoria, Australia.
Presented at the annual meeting of the Association for Research in
Vision and Ophthalmology, Fort Lauderdale, Florida, May 2009.
Submitted for publication June 17, 2009; revised December 21,
2009, and February 24, 2010; accepted March 19, 2010.
Disclosure: N. Sharma, None; M. Goel, None; T. Velpandian,
None; J.S. Titiyal, None; R. Tandon, None; R.B. Vajpayee, None
Corresponding author: Rasik B. Vajpayee, Centre for Eye Research
Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, Victoria 3002, Australia;
rvajpayee@gmail.com.
Investigative Ophthalmology & Visual Science, February 2011, Vol. 52, No. 2
Copyright 2011 The Association for Research in Vision and Ophthalmology, Inc.

Downloaded From: http://iovs.arvojournals.org/ on 10/12/2015

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

A double-blind prospective randomized controlled clinical trial was


planned that was approved independently by the institutional review
board of the Rajendra Prasad Centre for Ophthalmic Sciences and the
Ethics Committee of the All India Institute of Medical Sciences. The
study complied with the tenets of the Declaration of Helsinki.

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

1088

Sharma et al.

IOVS, February 2011, Vol. 52, No. 2

TABLE 1. Corneal Clarity Grading


Scale

Clinical Features

0
1
2
3
4

No anterior segment structure visible


Severe corneal haze, pupil not visible
Corneal haze, iris details not seen, pupil visible
Slight corneal haze, iris details seen
Clear cornea

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.

performed with a random numbers table, which was used to assign


each eye labeled from 1 to 33 to each group. In bilateral cases, each eye
was randomized separately.
All patients had their blood drawn for preparation of autologous
serum drops. These were prepared using the standard protocol followed at our Ocular Pharmacology services. The drops were returned
labeled SERUM, which was autologous serum, umbilical cord serum, or
artificial tears. The drops were instilled in the affected eye 10 times a
day. The allocation of the three groups was divulged only after the
study was completed, thereby masking both the patients and the
investigator to the knowledge of the groups to which they were
assigned.

Umbilical Cord Serum and Autologous Serum:


Collection, Preparation, and Storage
The umbilical cord blood was collected from mothers with uncomplicated caesarean deliveries after obtaining informed consent and
screening for parenterally transmitted diseases such as hepatitis B,
hepatitis C, HIV, and syphilis. These investigations were performed at
the time of antenatal care registration and were subsequently repeated
at the time of cord blood collection and after the preparation of serum
sample.
The blood was collected by directly cannulating the umbilical vein
with the component transfer bag (Terumo Penpol, Ltd., Thiruvananthapuram, India) plastic cannula, taking all sterile precautions after the
infant was removed from the field and the umbilical cord was clamped.
The blood was allowed to drain by gravity from the placenta. When the
blood flow stopped, the needle was removed from the umbilical cord,
and the blood in the tubing was milked into the bag to maximize
collection. No anticoagulants were used during the procedure. The
blood was allowed to clot, and the serum was obtained by centrifuging
it at 1800g for 10 minutes. It was then diluted with sterile balanced salt
solution and dispensed into glass containers as a 20% solution. The
sample was also subjected to spectrophotometric analysis to look for
any lysed red blood corpuscles. Unopened serum bottles were stored
at 20.0C and after opening, they were stored at 4.0C. A culture for
bacterial and fungal contaminants was sent on each occasion when a
fresh serum batch was prepared.
The patient using the serum was asked to store it in a cool place,
preferably in a refrigerator. The patient was instructed to use an open
vial within 7 days and to return for a fresh vial after that. The patient
was also told to look for the presence of any threadlike floating objects

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.

TABLE 2. Pretreatment Variables in the Three Groups

Age in years, mean SD


Nature of chemical
Acid
Alkali
Others
Time in days between exposure and
presentation at RPC, mean SD

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

RPC, Rajendra Prasad Centre for Ophthalmic Sciences.

Downloaded From: http://iovs.arvojournals.org/ on 10/12/2015

Artificial
Tears

P
0.57
0.70

0.09

6
2
2
10

16
9
8
33

Pain Score Day 0* Day 7 Day 0* Day 7 Day 0* Day 7


1
0
3
8
12

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.

Downloaded From: http://iovs.arvojournals.org/ on 10/12/2015

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

0.30 0.78 0.00


2.8 2.87 0.02
1.85 3.89 0.18
0.10

M2
Umbilical Cord
Serum

Day 1

Group

Day 0

TABLE 4. Pain Score at Presentation and at Day 7

TABLE 5. Healing of Epithelial Defect in the Three Groups

A total of 33 eyes with acute ocular chemical burns were


studied and followed up for a minimum of 3 months. Twelve
eyes received umbilical cord serum therapy, 11 received autologous serum therapy, and 10 received artificial tears. The mean
ages at presentation were 30.1 11.2, 26.9 7.8, and
31.0 8.2 years in the umbilical cord serum group, autologous
serum group, and artificial tears group respectively, and were
comparable (P 0.57; Table 2). The mean time interval between exposure of the chemical and presentation to us was
5.93 5.26 days, which was comparable between the three
groups (P 0.09). There were 15 eyes exposed to acid, 14 to
alkali, 2 to cement, and 1 each to Cidex (a disinfectant) and
coloring agent. The groups were comparable with regard to
the nature of the chemical (P 0.71).
According to Duas classification, 16 of 33 eyes had a grade
III injury, 9 had a grade IV injury, and 8 had grade V injury
(Table 3). The groups were comparable in the distribution of
patients according to the grade of injury. No case of symblepharon was present in any of the three groups at the time of
presentation.
Seventeen of the 33 patients had a pain score of 4 at
presentation, and 3 of 33 had no pain (pain score 1) at presentation (Table 4). By day 7, 21 of the 33 patients had a pain score
of 1, and none of the patients had a pain score of 4. The three
groups were comparable with regard to pain at the time of
presentation (P 0.13). However, by day 7 the patients in
the cord serum group showed better pain relief (P 0.01;
Table 4).
The mean epithelial defect diameter (EDD) at presentation
was 7.64 0.36, 8.73 2.54, and 6.43 0.47 mm in the cord
serum group, autologous serum group, and artificial tears group,
respectively, and were comparable (P 0.435; Table 5). By day 7,
the mean EDD was 2.60 3.46, 6.32 2.56, and 4.35 4.10
mm in the cord serum group, autologous serum group, and
artificial tear group, respectively (Fig. 1). A statistically significant decrease was seen in the cord serum group (P 0.02),
but the decrease in the other two groups was not statistically

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

CS 61.50 47.97 42.35 30.95 1.0


AS 79.10 44.03 76.51 43.17 1.0
AT 51.80 48.45 41.45 47.38 1.0
P
0.375
0.098

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*

TABLE 3. Grade of Injury (Duas classification)

0.0 0.0 0.01


0.18 0.60 0.00
0.05 0.15 0.04
0.55

Cord Serum in Acute Ocular Burns

IOVS, February 2011, Vol. 52, No. 2

1089

1090

Sharma et al.

IOVS, February 2011, Vol. 52, No. 2

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.

significant (P 0 0.11 and P 1.0 in the autologous serum


group and artificial tears group, respectively). The autologous
serum group achieved a statistically significant decrease in
EDD by the end of month 1, whereas the artificial tear group
could achieve a statistically significant decrease in EDD only by
the end of month 2 (Table 5; Fig. 2). The mean epithelial defect
area (EDA) at presentation were 61.50 47.97, 79.10 44.03,
and 51.80 48.45 mm2 in the cord serum group, autologous
serum group, and artificial tear group, respectively, and were
comparable (P 0.38; Table 5). By day 7, the mean EDAs were
12.60 22.98, 41.54 29.30, and 30.99 48.35 mm2 in the
cord serum group, autologous serum group, and artificial tear
group, respectively (P 0.02; Table 5). A statistically significant decrease was seen in the cord serum group (P 0.08),
but the decrease in the other two groups was not statistically
significant (P 0 0.18, P 0.99) in the autologous serum
group and artificial tears group, respectively (Table 5).
Complete epithelialization was achieved in all 12 eyes in
cord serum group, 10 of 11 eyes in the autologous serum group
and 9 of 10 eyes in the artificial tears group. The mean time to
complete epithelialization was 21.16 26.81, 56.6 35.5,
and 40.13 35.79 days in the cord serum group, autologous
serum group, and artificial tear group, respectively (P 0.02).

Patients in the cord serum group showed a statistically


significant decrease in limbal ischemia compared with the
other two groups. The mean percentage decrease in limbal
ischemia from baseline at day 3 was 9.72 12.22,
1.29 4.31, and 1.67 5.27 in the cord serum group, autologous serum group, and artificial tear group, respectively
(P 0.017; Table 6). The decrease in limbal ischemia continued to be significantly greater in the cord serum group, and by
the end of 3 months, the mean percentage decrease in
limbal ischemia was 73.43 25.51, 35.64 25.60, and
43.71 28.17 in the cord serum group, autologous serum
group, and artificial tear group, respectively (P 0.01;
Table 6 and Fig. 3).
The three groups were comparable with regard to corneal
clarity at presentation (P 0.54; Table 7). However, at the end
of 3 months, patients in the cord serum group showed significantly clearer corneas compared with the other two groups.
Nine of 12 patients had grade IV corneal clarity in the cord
serum group compared with 1 of 11 in autologous serum
group and 3 of 10 in the artificial tears group. Corneal clarity
had shown a significant improvement in the cord serum group
(P 0.04; Table 7). None of the patients in either group had
corneal vascularization at presentation. By the end of 3
TABLE 6. Percentage Decrease in Limbal Ischemia
Umbilical
Cord Serum
Day 1
Day 3
Day 7
Day 14
Day 21
Month 1
Month 2
Month 3

FIGURE 2.

Progression of mean epithelial defect diameter.

Downloaded From: http://iovs.arvojournals.org/ on 10/12/2015

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.

Cord Serum in Acute Ocular Burns

IOVS, February 2011, Vol. 52, No. 2

1091

TABLE 8. Presence of Symblepharon at 3 Months


Group

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.

Progression of limbal ischemia.

months, significantly fewer patients in the cord serum group


had vascularization, when compared with the other two
groups (P 0.03).
Sixteen of 33 patients had symblepharon by the end of 3
months. There was no statistically significant difference between the three groups (P 0.07; Table 8).
No significant complications associated with umbilical cord
serum or autologous serum use was observed during the study.

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

serum contains various growth factors, such as EGF, acidic and


basic FGF, platelet-derived growth factor, hepatocyte growth
factor, vitamin A, TGF-, substance P, IGF-1, NGF, fibronectin,
and serum antiproteases such as 2-macroglobulin, which facilitates the proliferation, migration, and differentiation of ocular surface epithelium.7,13,14 The concentration of vitamin A,
TGF-1, IGF-1, NGF, fibronectin, and lysozyme is higher in
serum than in tears, whereas EGF and vitamin C are found in
higher concentrations in tears.7,29 Thus, serum is a complex
mixture that cannot be duplicated by any artificial tear substitute. Umbilical cord serum has been shown to contain many
growth factors such as EGF, vitamin A, TGF- , substance P,
IGF-1, and NGF.9 EGF, TGF-, and NGF concentrations are
several times higher in umbilical cord serum than peripheral
blood serum.10,12 Substance P is also found in higher concentrations in cord serum than in autologous serum (though the
difference is statistically nonsignificant). Vitamin A and IGF-1
concentrations are higher in autologous serum than in cord
serum.10,12
Umbilical cord serum has been used in the treatment of
various ocular surface disorders and has been found to be very
effective. Vajpayee et al.8 compared the efficacy of autologous
serum drops and umbilical cord serum drops in the treatment
of persistent epithelial defects and found that umbilical cord
serum leads to faster healing of persistent epithelial defects
than does autologous serum drops. They also found that the slit
lamp can be used for the accurate measurement of the epithelial defect size in such cases.17 Yoon et al.10 12 used umbilical
cord serum therapy for the treatment of dry eye syndrome,
neurotrophic keratitis, and dry eye associated with graft versus
host disease (GVHD) and in all the settings found it to be very
effective. Yoon et al. conducted a study to compare the therapeutic efficacy of autologous serum eye drops and umbilical
cord serum eye drops in the treatment of severe dry eye
syndrome and found that umbilical cord serum eye drops were
more effective in decreasing symptoms and keratoepitheliopathy and increasing goblet cell density in such patients compared with autologous serum eye drops.9

TABLE 7. Corneal Clarity Grade at Presentation and at Month 3


Group
Umbilical Cord
Serum

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.

Downloaded From: http://iovs.arvojournals.org/ on 10/12/2015

1092

Sharma et al.

To the best of our knowledge, this is the first study to


compare the efficacy of autologous serum therapy and umbilical cord serum therapy in cases of acute ocular chemical
burns. Our findings corroborate the fact that cord serum is
more efficacious than autologous serum, as we found significantly better results (in terms of faster epithelial defect healing
rate, better corneal clarity, lesser vascularization, and greater
decrease in limbal ischemia) with umbilical cord serum therapy than autologous serum therapy. The mechanism of action
of cord serum is likely to be the same as that of autologous
serum, the difference being a higher concentration of growth
factors which may in fact stimulate the growth of stem cells
and thus lead to faster healing.
Umbilical cord serum therapy has certain other advantages
over autologous serum therapy.9,10,30 A large amount of sample can be drawn from the umbilical vein at the time of
delivery, so that the requirement for several patients can be
met at the same time. In addition, umbilical cord serum therapy can be used in patients with poor general health or blood
dyscrasias such as GVHD.9,10 Our study also corroborated the
fact that cord serum or autologous serum as a 20% solution is
a safe and nontoxic preparation that can be prepared easily and
used.
Umbilical cord serum therapy, however, has certain disadvantages when compared with autologous serum therapy. The
risk of allergies and possibility of transmitting parenterally
transmitted organisms must be kept in mind. Moreover, legal
and ethical issues may be of concern when using cord serum
therapy. The importance of testing the mothers for parenterally transmitted organisms such as HIV, HBV, and HCV at least
twice (once at antenatal clinic registration and then at the time
of delivery) to account for the window period of infection
cannot be overemphasized.

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.

Downloaded From: http://iovs.arvojournals.org/ on 10/12/2015

IOVS, February 2011, Vol. 52, No. 2


10. Yoon KC, You IC, Im SK, Jeong TS, Park YG, Choi J. Application
of umbilical cord serum eyedrops for the treatment of neurotrophic keratitis. Ophthalmology. 2007;114:16371642.
11. Yoon KC, Jeong IY, Im SK, Park YG, Kim HJ, Choi J. Therapeutic
effect of umbilical cord serum eyedrops for the treatment of dry
eye associated with graft-versus-host disease. Bone Marrow Transplant. 2007;39:231235.
12. Yoon KC, Im SK, Park YG, Jung YD, Yang SY, Choi J. Application
of umbilical cord serum eyedrops for the treatment of dry eye
syndrome. Cornea. 2006;25:268 272.
13. Poon AC, Geerling G, Dart JK, Fraenkel GE, Daniels JT. Autologous
serum eyedrops for dry eyes and epithelial defects: clinical and in
vitro toxicity studies. Br J Ophthalmol. 2001;85:1188 1197.
14. Liu L, Hartwig D, Harloff S, Herminghaus P, Wedel T, Geerling G.
An optimized protocol for the production of autologous serum eye
drops. Graefes Arch Clin Exp Ophthalmol. 2005;243:706 714.
15. Dua HS, King AJ, Joseph A. A new classification of ocular surface
burns. Br J Ophthalmol. 2001;85:1379 1383.
16. Tamhane A, Vajpayee RB, Biswas NR, et al. Evaluation of amniotic
membrane transplant as an adjunct to medical therapy as compared with medical therapy alone in acute ocular burns. Ophthalmology. 2005;112:19631969.
17. Mukerji N, Vajpayee RB, Sharma N. Technique of area measurement of epithelial defects. Cornea. 2003;22:549 551.
18. Blanco AA, Pillai CT, Dua HS. Amniotic membrane transplantation
for ocular surface reconstruction. Br J Ophthalmol. 1999;83:399
402.
19. Tseng SCG, Prabhasawat P, Barton K, et al. Amniotic membrane
transplantations with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency.
Arch Ophthalmol. 1998;116:431 441.
20. Tripathi BJ, Kwait PS, Tripathi RC. Corneal growth factors: a new
generation of ophthalmic pharmaceuticals. Cornea. 1990;9:299.
21. Singh G, Foster CS. Epidermal growth factor in alkali burned
corneal epithelial wound healing. Am J Ophthalmol. 1987 15;103:
802 807.
22. Brown SM, Lamberts DW, Reid TW, et al. Neurotrophic and anhidrotic keratopathy treated with substance P and insulin like
growth factor1 (letter). Arch Ophthalmol. 1997;115:926 927.
23. Chikama T, Fukuda K, Morishige N, Nishida T. Treatment of
neurotrophic keratopathy with substance-P-derived-peptide
(FGLM) and insulin like growth factor1 (letter). Lancet. 1998;
351:17831784.
24. Tan MH, Bryars J, Moore J. Use of nerve growth to treat congenital
neurotrophic corneal ulceration. Cornea. 2006;25:352355.
25. Lambiase A, Rama P, Bonini S, et al. Topical treatment with nerve
growth factor for corneal neurotrophic ulcers. N Engl J Med.
1998;338:1174 1180.
26. Bonini S, Lambiase A, Rama P, et al. Topical treatment with nerve
growth factor for neurotrophic keratitis. Ophthalmology. 2000;
107:13471351.
27. Gordon JF, Johnson P, Musch DC, and the Chiron Vision Fibronectin Study Group. Topical fibronectin ophthalmic solution in the
treatment of persistent defects of corneal epithelium. Am J Ophthalmol 1995;119:281287.
28. Phan TM, Foster CS, Boruchoff SA, et al. Topical fibronectin in the
treatment of persistent corneal epithelial defects and trophic ulcers. Am J Ophthalmol. 1987;104:494 501.
29. Tsubota K, Higuchi A. Serum application for the treatment of
ocular surface disorders. Int Ophthalmol Clin. 2000;40:113122.
30. Yoon KC, Heo H, Jeong IY, Park YG. Therapeutic effect of umbilical cord serum eyedrops for persistent epithelial defect. Korean J
Ophthalmol. 2005;19:174 178.

You might also like