February 2011
Volume 52, Issue 2
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Clinical Trials  |   February 2011
Evaluation of Umbilical Cord Serum Therapy in Acute Ocular Chemical Burns
Author Affiliations & Notes
  • Namrata Sharma
    From the Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India;
  • Manik Goel
    From the Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India;
  • Thirumurthy Velpandian
    From the Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India;
  • Jeewan S. Titiyal
    From the Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India;
  • Radhika Tandon
    From the Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India;
  • Rasik B. Vajpayee
    From the Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India;
    the Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia; and
    the Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
  • 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, 1087-1092. doi:10.1167/iovs.09-4170
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      Namrata Sharma, Manik Goel, Thirumurthy Velpandian, Jeewan S. Titiyal, Radhika Tandon, Rasik B. Vajpayee; Evaluation of Umbilical Cord Serum Therapy in Acute Ocular Chemical Burns. Invest. Ophthalmol. Vis. Sci. 2011;52(2):1087-1092. doi: 10.1167/iovs.09-4170.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

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% HPMC+0.3% 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.)

Ocular 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 inflammation, 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. 2 9 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)-β, substance P, insulin-like growth factor (IGF)-1, nerve growth factor (NGF), fibronectin, and serum antiproteases such as α2-macroglobulin. 7,10,12 14 The concentrations of EGF, TGF-β, 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 classification 15 ) 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 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 −20.0°C and after opening, they were stored at 4.0°C. 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 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. 
Patient's 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 classification 15 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  
Table 1.
 
Corneal Clarity Grading
Table 1.
 
Corneal Clarity Grading
Scale Clinical Features
0 No anterior segment structure visible
1 Severe corneal haze, pupil not visible
2 Corneal haze, iris details not seen, pupil visible
3 Slight corneal haze, iris details seen
4 Clear cornea
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 χ2 test was used to compare the categorical variables. 
Results
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). 
Table 2.
 
Pretreatment Variables in the Three Groups
Table 2.
 
Pretreatment Variables in the Three Groups
Umbilical Cord Serum Autologous Serum Artificial Tears P
Age in years, mean ± SD 30.1 ± 11.2 26.9 ± 7.8 31.0 ± 8.2 0.57
Nature of chemical 0.70
    Acid 6 6 3
    Alkali 4 4 6
    Others 2 1 1
Time in days between exposure and presentation at RPC, mean ± SD 3.7 ± 4.4 7.9 ± 5.6 6.5 ± 5.3 0.09
According to Dua's 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. 
Table 3.
 
Grade of Injury (Dua's classification)
Table 3.
 
Grade of Injury (Dua's classification)
Grade Umbilical Cord Serum Group Autologous Serum Artificial Tears Total
Grade III 8 2 6 16
Grade IV 3 4 2 9
Grade V 1 5 2 8
Total 12 11 10 33
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). 
Table 4.
 
Pain Score at Presentation and at Day 7
Table 4.
 
Pain Score at Presentation and at Day 7
Pain Score Group
Umbilical Cord Serum Autologous Serum Artificial Tears
Day 0* Day 7† Day 0* Day 7† Day 0* Day 7†
1 1 11 1 7 1 3
2 0 1 4 4 0 7
3 3 0 2 0 4 0
4 8 0 4 0 5 0
Total 12 12 11 11 10 10
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 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). 
Table 5.
 
Healing of Epithelial Defect in the Three Groups
Table 5.
 
Healing of Epithelial Defect in the Three Groups
Day 0 Day 1 P * Day 3 P * Day 7 P * Day 14 P * Day 21 P * M1 P * M2 P * M3 P *
EDD (mm)
CS 7.64 ± 0.36 6.43 ± 3.60 0.73 4.79 ± 3.82 0.19 2.60 ± 3.46 0.02 1.15 ± 1.92 0.00 0.54 ± 1.27 0.00 0.30 ± 0.78 0.00 0.08 ± 0.29 0.00 0.0 ± 0.0 0.01
AS 8.73 ± 2.54 8.55 ± 2.58 1.0 7.71 ± 2.64 0.57 6.32 ± 2.56 0.11 5.66 ± 3.09 0.25 4.06 ± 3.32 0.06 2.8 ± 2.87 0.02 1.65 ± 2.10 0.01 0.18 ± 0.60 0.00
AT 6.43 ± 0.47 5.7 ± 4.25 1.0 5.00 ± 4.39 1.0 4.35 ± 4.10 1.0 3.30 ± 4.31 1.0 2.80 ± 4.45 0.44 1.85 ± 3.89 0.18 1.20 ± 2.57 0.04 0.05 ± 0.15 0.04
P 0.435 0.30 0.16 0.02 0.007 0.02 0.10 0.05 0.55
EDA (mm2)
CS 61.50 ± 47.97 42.35 ± 30.95 1.0 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
AS 79.10 ± 44.03 76.51 ± 43.17 1.0 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
AT 51.80 ± 48.45 41.45 ± 47.38 1.0 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
P 0.375 0.098 0.088 0.02 0.005 0.016 0.104 0.043 0.554
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 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.
 
Progression of mean epithelial defect diameter.
Figure 2.
 
Progression of mean epithelial defect diameter.
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). 
Table 6.
 
Percentage Decrease in Limbal Ischemia
Table 6.
 
Percentage Decrease in Limbal Ischemia
Umbilical Cord Serum Autologous Serum Artificial Tears P
Day 1 1.04 ± 8.36 −1.29 ± 4.31 0.0 ± 0.0 0.70
0.0 (−12.5–25.0) 0.0 (−14.29–0.0) 0.0 (0.0–0.0)
Day 3 9.72 ± 12.22 −1.29 ± 4.31 1.67 ± 5.27 0.017
0.0 (0.0–25.0) 0.0 (−14.29–0.0) 0.0 (0.0–16.7)
Day 7 22.17 ± 14.03 3.03 ± 11.9 11.0 ± 15.56 0.01
25.0 (0.0–50.0) 0.0 (−14.29–33.3) 0.0 (0.0–40.0)
Day 14 32.85 ± 17.65 13.23 ± 12.40 16.6 ± 17.8 0.02
28.57 (0.0–66.7) 14.29 (0.0–33.3) 15.48 (0.0–50.0)
Day 21 34.28 ± 17.54 14.55 ± 12.22 20.76 ± 21.09 0.041
28.57 (0.0–66.7) 14.28 (0.0–33.0) 17.42 (0.0–50.0)
Month 1 44.74 ± 21.95 24.51 ± 20.63 28.09 ± 21.71 0.092
50.0 (0.0–83.3) 20.0 (0.0–57.14) 26.67 (0.0–66.7)
Month 2 60.0 ± 22.41 28.88 ± 18.74 33.19 ± 21.92 0/007
56.25 (20.0–100.0) 25.0 (0.0–57.14) 40.0 (0.0–66.7)
Month 3 73.43 ± 25.51 35.64 ± 25.60 43.71 ± 28.71 0.008
75.0 (30.0–100.0) 28.57 (0.0–80.0) 53.57 (0.0–80.0)
Figure 3.
 
Progression of limbal ischemia.
Figure 3.
 
Progression of limbal ischemia.
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 months, significantly fewer patients in the cord serum group had vascularization, when compared with the other two groups (P = 0.03). 
Table 7.
 
Corneal Clarity Grade at Presentation and at Month 3
Table 7.
 
Corneal Clarity Grade at Presentation and at Month 3
Corneal Clarity Group
Umbilical Cord Serum Autologous Serum Artificial Tears
Day 0* Month 3† Day 0* Month 3† Day 0* Month 3†
1 1 0 4 4 2 2
2 5 0 5 1 4 1
3 5 3 2 5 4 4
4 1 9 0 1 0 3
Total 12 12 11 11 10 10
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). 
Table 8.
 
Presence of Symblepharon at 3 Months
Table 8.
 
Presence of Symblepharon at 3 Months
Symblepharon Group Total
Umbilical Cord Serum Autologous Serum Artificial Tears
Absent 9 3 5 17
Present 3 8 5 16
Total 12 11 10 33
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. 22 26 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-β, substance P, IGF-1, NGF, fibronectin, and serum antiproteases such as α2-macroglobulin, which facilitates the proliferation, migration, and differentiation of ocular surface epithelium. 7,13,14 The concentration of vitamin A, TGF-β1, 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- β, substance P, IGF-1, and NGF. 9 EGF, TGF-β, 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  
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. 
Footnotes
 Presented at the annual meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, May 2009.
Footnotes
 Disclosure: N. Sharma, None; M. Goel, None; T. Velpandian, None; J.S. Titiyal, None; R. Tandon, None; R.B. Vajpayee, None
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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 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.
 
Progression of mean epithelial defect diameter.
Figure 2.
 
Progression of mean epithelial defect diameter.
Figure 3.
 
Progression of limbal ischemia.
Figure 3.
 
Progression of limbal ischemia.
Table 1.
 
Corneal Clarity Grading
Table 1.
 
Corneal Clarity Grading
Scale Clinical Features
0 No anterior segment structure visible
1 Severe corneal haze, pupil not visible
2 Corneal haze, iris details not seen, pupil visible
3 Slight corneal haze, iris details seen
4 Clear cornea
Table 2.
 
Pretreatment Variables in the Three Groups
Table 2.
 
Pretreatment Variables in the Three Groups
Umbilical Cord Serum Autologous Serum Artificial Tears P
Age in years, mean ± SD 30.1 ± 11.2 26.9 ± 7.8 31.0 ± 8.2 0.57
Nature of chemical 0.70
    Acid 6 6 3
    Alkali 4 4 6
    Others 2 1 1
Time in days between exposure and presentation at RPC, mean ± SD 3.7 ± 4.4 7.9 ± 5.6 6.5 ± 5.3 0.09
Table 3.
 
Grade of Injury (Dua's classification)
Table 3.
 
Grade of Injury (Dua's classification)
Grade Umbilical Cord Serum Group Autologous Serum Artificial Tears Total
Grade III 8 2 6 16
Grade IV 3 4 2 9
Grade V 1 5 2 8
Total 12 11 10 33
Table 4.
 
Pain Score at Presentation and at Day 7
Table 4.
 
Pain Score at Presentation and at Day 7
Pain Score Group
Umbilical Cord Serum Autologous Serum Artificial Tears
Day 0* Day 7† Day 0* Day 7† Day 0* Day 7†
1 1 11 1 7 1 3
2 0 1 4 4 0 7
3 3 0 2 0 4 0
4 8 0 4 0 5 0
Total 12 12 11 11 10 10
Table 5.
 
Healing of Epithelial Defect in the Three Groups
Table 5.
 
Healing of Epithelial Defect in the Three Groups
Day 0 Day 1 P * Day 3 P * Day 7 P * Day 14 P * Day 21 P * M1 P * M2 P * M3 P *
EDD (mm)
CS 7.64 ± 0.36 6.43 ± 3.60 0.73 4.79 ± 3.82 0.19 2.60 ± 3.46 0.02 1.15 ± 1.92 0.00 0.54 ± 1.27 0.00 0.30 ± 0.78 0.00 0.08 ± 0.29 0.00 0.0 ± 0.0 0.01
AS 8.73 ± 2.54 8.55 ± 2.58 1.0 7.71 ± 2.64 0.57 6.32 ± 2.56 0.11 5.66 ± 3.09 0.25 4.06 ± 3.32 0.06 2.8 ± 2.87 0.02 1.65 ± 2.10 0.01 0.18 ± 0.60 0.00
AT 6.43 ± 0.47 5.7 ± 4.25 1.0 5.00 ± 4.39 1.0 4.35 ± 4.10 1.0 3.30 ± 4.31 1.0 2.80 ± 4.45 0.44 1.85 ± 3.89 0.18 1.20 ± 2.57 0.04 0.05 ± 0.15 0.04
P 0.435 0.30 0.16 0.02 0.007 0.02 0.10 0.05 0.55
EDA (mm2)
CS 61.50 ± 47.97 42.35 ± 30.95 1.0 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
AS 79.10 ± 44.03 76.51 ± 43.17 1.0 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
AT 51.80 ± 48.45 41.45 ± 47.38 1.0 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
P 0.375 0.098 0.088 0.02 0.005 0.016 0.104 0.043 0.554
Table 6.
 
Percentage Decrease in Limbal Ischemia
Table 6.
 
Percentage Decrease in Limbal Ischemia
Umbilical Cord Serum Autologous Serum Artificial Tears P
Day 1 1.04 ± 8.36 −1.29 ± 4.31 0.0 ± 0.0 0.70
0.0 (−12.5–25.0) 0.0 (−14.29–0.0) 0.0 (0.0–0.0)
Day 3 9.72 ± 12.22 −1.29 ± 4.31 1.67 ± 5.27 0.017
0.0 (0.0–25.0) 0.0 (−14.29–0.0) 0.0 (0.0–16.7)
Day 7 22.17 ± 14.03 3.03 ± 11.9 11.0 ± 15.56 0.01
25.0 (0.0–50.0) 0.0 (−14.29–33.3) 0.0 (0.0–40.0)
Day 14 32.85 ± 17.65 13.23 ± 12.40 16.6 ± 17.8 0.02
28.57 (0.0–66.7) 14.29 (0.0–33.3) 15.48 (0.0–50.0)
Day 21 34.28 ± 17.54 14.55 ± 12.22 20.76 ± 21.09 0.041
28.57 (0.0–66.7) 14.28 (0.0–33.0) 17.42 (0.0–50.0)
Month 1 44.74 ± 21.95 24.51 ± 20.63 28.09 ± 21.71 0.092
50.0 (0.0–83.3) 20.0 (0.0–57.14) 26.67 (0.0–66.7)
Month 2 60.0 ± 22.41 28.88 ± 18.74 33.19 ± 21.92 0/007
56.25 (20.0–100.0) 25.0 (0.0–57.14) 40.0 (0.0–66.7)
Month 3 73.43 ± 25.51 35.64 ± 25.60 43.71 ± 28.71 0.008
75.0 (30.0–100.0) 28.57 (0.0–80.0) 53.57 (0.0–80.0)
Table 7.
 
Corneal Clarity Grade at Presentation and at Month 3
Table 7.
 
Corneal Clarity Grade at Presentation and at Month 3
Corneal Clarity Group
Umbilical Cord Serum Autologous Serum Artificial Tears
Day 0* Month 3† Day 0* Month 3† Day 0* Month 3†
1 1 0 4 4 2 2
2 5 0 5 1 4 1
3 5 3 2 5 4 4
4 1 9 0 1 0 3
Total 12 12 11 11 10 10
Table 8.
 
Presence of Symblepharon at 3 Months
Table 8.
 
Presence of Symblepharon at 3 Months
Symblepharon Group Total
Umbilical Cord Serum Autologous Serum Artificial Tears
Absent 9 3 5 17
Present 3 8 5 16
Total 12 11 10 33
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