Cord Blood Serum Drops for Dry Eye Disease, Dry Eye Symptoms, and Corneal Neuropathy... and maybe even helps Glaucoma

Umbilical Cord Blood (UCB), also used as Cord Blood Serum (CBS), has been used to heal corneal ulcer, erosions, neuropathy, severe dry eye, persistent epithelial defects, neurotrophic keratopathy, recurrent corneal erosions, ocular chemical burn, and corneal refractive surgery (Ref 2-8 below). Studies have shown that Umbilical Cord Blood (UCB) contains a higher level of growth factors, nerve growth factor, and other neurotrophic factors than compared to Autologous Serum. 

We are now offering this to patients. We have an IRB approval to study the effects of cord blood in comparison to using Autologous, Adipose Derived, Stem Cells (AADSC) inserted into the meibomian glands. Our hope is to have patients use cord blood drops in one eye and have AADSC insertion into the meibomian glands of the other eye and compare the results over 1, 3, 6mo, 1yr, 3yr. 
For now, we are providing Cord Blood drops to patients who have not found relief with all other options. 

The next question is: since Cord Blood cells can become Nerve Growth Factor, will using Cord Blood drops work better or as well as NGF, especially in patients who have corneal neuropathy?

Studies below have shown Cord Blood is safe and effective. Still it is experimental and not FDA approved.

There is a recent paper noted below ** that indicated Cord Blood Serum may help patients with Glaucoma. The theory is that CBS contains a combination of growth factors, pluripotent stem cells, and cytokines, which potentially exert a neuroprotective action to help prevent optic nerve damage and blindness. CBS, the authors note, is a natural source to potentially protect against neurodegenerative ocular disorders. They report that 2 patients showed improvement of their Mean Deviation and Pattern Standard Deviation on visual fields. They note that this incidentally observed amelioration in these two patients deserves further investigation in this respect.

They report only 2 cases, and the study has many confounding factors: for instance, maybe the CBS improved the patients' tear film so they did better on the repeat Visual Field test because of improvements in the tear film alone and not because of an actual improvement in optic nerve function. But the report is interesting none the less. 

No side effects have been published with using UCB in the eye, but the same is true for Autologous Serum: UCB must be kept frozen and refrigerated as follows:
1.  Unopened bottles MUST be stored in a freezer at -20℃. Can last for 3 to 6 months. 
2.  Opened bottles MUST be kept in a refrigerator at 4℃ for 7 days, and then Thrown OUT.
3.  Drops cannot be left out.
4.  UCS eye drops are usually instilled 4 to 6 times per day as required in addition to non-preserved artificial tears, Xiidra or Restasis if using, and an antibiotic drop (ie, Moxifloxacin 2x/day). 

Here is the protocol we will be following:
Consent Form From donors: laboratory examination should be performed at 8 and 38 gestational weeks to test for human immunodeficiency and hepatitis B and C viruses. 
After fetal delivery: about 60 to 80 ml of umbilical cord blood is sampled from the umbilical cord vein. The blood is kept for 2 hours at room temperature. After 15 minutes of centrifugation at 3,000 ×g, the serum is carefully isolated under sterile conditions. The serum is then diluted to a 20% concentration with balanced salt solution. The aliquots of diluted serum are placed into sterile 5-ml bottles with ultraviolet light protection. 
Opened bottles are kept in a refrigerator at 4℃ for 7 days, and unopened bottles are stored in a freezer at -20℃ for 3 to 6 months. UCS eye drops are usually instilled 4 to 6 times per day as required in addition to artificial tears and antibiotics.

Here are some key References:

1. Cornea. 2017 Aug;36(8):915-921. doi: 10.1097/ICO.0000000000001257.

Efficacy of 2-Month Treatment With Cord Blood Serum Eye Drops in Ocular Surface Disease: An In Vivo Confocal Microscopy Study.

Giannaccare G1, Buzzi M, Fresina M, Velati C, Versura P.

Author information

Abstract

PURPOSE:

To investigate the morphological changes of corneal epithelium and subbasal nerves by in vivo confocal microscopy in patients with ocular surface disease (OSD) treated with cord blood serum (CBS) eye drops.

METHODS:

Twenty patients with OSD (mean age 61.1 ± 12.6 years) were included in this prospective 1-arm study and treated with CBS eyedrops for 2 months. Corneal sensitivity, Schirmer test score, breakup time, subjective symptoms [Ocular Surface Disease Index (OSDI) and Visual Analogue Scale (VAS)], and corneal staining were evaluated before (T0) and after (T1) treatment. In vivo confocal microscopy analyzed giant epithelial cells, subbasal nerve number and tortuosity, neuromas, beading, and dendritic cells (DCs) in the central cornea.

RESULTS:

OSDI, Visual Analogue Scale, and Oxford grading values significantly decreased at T1 versus T0 (respectively, 44.1 ± 18.9 vs. 74.2 ± 13.9; 3.7 ± 1.5 vs. 8.9 ± 0.9; and 2.4 ± 1.1 vs. 3.3 ± 1.3; P < 0.0001), whereas corneal sensitivity, Schirmer test score, and breakup time significantly increased (respectively, 49.5 ± 2.6 vs. 47.9 ± 2.9; 3.2 ± 2.0 vs. 2.4 ± 2.2; 4.6 ± 3.1 vs. 3.8 ± 2.1; P < 0.0001). Corneal nerve morphology improved at T1 versus T0 with a higher total nerve number (3.4 ± 1.6 vs. 2.5 ± 1.6 per frame) and lower tortuosity (3.0 ± 0.7 vs. 3.5 ± 0.6) (P < 0.01). The number of patients presenting with giant epithelial cells, beading, and neuromas decreased at T1. DC density did not change after treatment. The detection of neuromas and higher DC density at T0 were associated with greater OSDI reduction at T1 (P < 0.001).

CONCLUSIONS:

CBS eye drops significantly improved corneal nerve morphology and subjective symptoms in patients with severe OSD. The presence of neuromas and higher dendritic cell density at baseline were associated with greater reduction of discomfort symptoms after treatment.

2. Blood derived eye drops for the treatment of cornea and ocular surface diseases.

Giannaccare G, Versura P, Buzzi M, Primavera L, Pellegrini M, Campos EC.

Transfus Apher Sci. 2017 Aug;56(4):595-604. doi: 10.1016/j.transci.2017.07.023. Epub 2017 Aug 8. Review.

Table 4  Clinical studies for umbilical cord serum eye drops therapy in ocular surface diseases.

Study	Design	Condition	Patients (n)	Control arm	Frequency	Duration of treatment	Concomitant therapy	Results
Yoon et al. [52]	Prospective interventional	RCE	35	Tear substitutes	4–6×/day	1 year	Tear substitutes	Less recurrences in UCBS group
Yoon et al. [53]	Prospective interventional	NK	28	None	6–10×/day	Until healing	Tear substitutes, levofloxacin	100% healing within 4.4 weeks as a mean
Vajpayee et al. [47]	Prospective randomized double-blind	PED	59	Autologous serum	6×/day	21 days	None	Higher percentage of re-epithelization in UCBS group
Sharma et al. [51]	Prospective randomized double-blind	Chemical injury	32	Autologous serum/tear substitutes	10×/day	3 months	Ofloxacin, prednisolone acetate, homatropine hydrobromide, sodium citrate, ascorbate, tear substitutes	Higher percentage of corneal transparency in UCBS group
Erdem et al. [48]	Prospective interventional	PED	14	None	10×/day then 5×/day	21 days	Tear substitutes, lomefloxacin	75% healing within 12 days
Versura et al. [43]	Prospective interventional	PED	30	None	8×/day	1 month	None	Significant reduction of epithelial damage

NK, neurotrophic keratitis; PED, persistent epithelial defect; RCE, recurrent corneal erosion; UCBS, umbilical cord blood serum.

Table 1. Controlled clinical trials for autologous serum eye drops therapy in dry eye syndrome.

Study	Patients (n)	Control arm	Dilution	Frequency	Duration of treatment	Concomitant therapy	Results
Tananuvat [23]	12	Saline solution	20%	6×/day	2 months	None	36% improvement of symptoms; 33% improvement of RBS, 39% improvement of FS
Noble [24]	16	Conventional treatment	50%	NA	3 months	None	Significant improvement of symptoms and IC
Kojima [25]	20	Preservative-free tear substitutes	20%	6×/day	2 weeks	None	Significant improvement of symptoms, TFBUT, RBS and FS
Urzua [26]	12	Tear substitutes	20%	4×/day	2 weeks	None	Significant improvement of OSDI. No change in TFBUT and FS
Celebi [27]	20	Preservative-free tear substitutes	20%	4×/day	1 month	None	Significant improvement of OSDI, and TFBUT. No change of corneal damage and Schirmer test

FS, fluorescein staining; IC, impression cytology; OSDI, ocular surface disease index; RBS, rose bengal staining; TFBUT, tear film break-up time.

3. Br J Ophthalmol. 2015 Jan;99(1):108-12. doi: 10.1136/bjophthalmol-2013-304801. Epub 2014 Aug 19.

Comparative role of 20% cord blood serum and 20% autologous serum in dry eye associated with Hansen's disease: a tear proteomic study.

Mukhopadhyay S1, Sen S2, Datta H2.

Author information

Abstract

BACKGROUND:

To compare the role of topically applied serum therapy with preservative-free artificial tear (AT) drops in patients with moderate to severe dry eye in Hansen's disease along with change in tear protein profile.

METHODS:

144 consecutive patients were randomly divided into three groups. After a baseline examination of clinical parameters, each of the patients received designated modality of topical therapy six times a day for 6 weeks. Post-treatment documentation of clinical parameters was done at 6 weeks, and then at 12 weeks after discontinuation of topical therapy. Analysis of three tear proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis) was done at baseline, at the first and second post-treatment visits.

RESULTS:

In the cord blood serum (CBS) group, except for McMonnies score and staining score, all other clinical parameters showed continued improvement in the first and second post-treatment analyses. In the autologous serum (ALS) group, all the clinical parameters except Schirmer's I showed significant improvement in the first post-treatment analysis .This was sustained at a significant level in the second analysis except for tear film break-up time (TBUT) and conjunctival impression cytology grading. In the AT group, all the parameters improved at a non-significant level except for TBUT in the first analysis. In the next analysis, apart from McMonnies score and TBUT, other clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme, lactoferrin levels improved in both post-treatment measurements (statistically insignificant).Total tear protein continued to increase at statistically significant levels in the first and second post-treatment analyses in the CBS group and at a statistically insignificant level in the ALS group. In the AT group, the three tear proteins continued to decrease in both the analyses.

CONCLUSIONS:

In moderate to severe dry eye in Hansen's disease, serum therapy in comparison with AT drops, improves clinical parameters and causes betterment in tear protein profile.

4.

Blood-derived topical therapy for ocular surface diseases.

Soni NG, Jeng BH.

Br J Ophthalmol. 2016 Jan;100(1):22-7. doi: 10.1136/bjophthalmol-2015-306842. Epub 2015 Jul 15. Review.

PMID:

 

26178904

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Select item 255688425.

Use of umbilical cord serum in ophthalmology.

Yoon KC.

Chonnam Med J. 2014 Dec;50(3):82-5. doi: 10.4068/cmj.2014.50.3.82. Epub 2014 Dec 17. Review.

6.  Vajpayee, R.B. et al., Evaluation of umbilical cord serum therapy for persistent corneal epithelial defects. British journal of ophthalmology, 2003; 87(11):1312-1316. 

Of note, parents can bank their baby's cord blood: 

To learn more about cord blood banking, visit Parent's Guide to Cord Blood Foundation at https://parentsguidecordblood.org/en/news/umbilical-cord-blood-serum-eye-drops

Good review also here:

https://parentsguidecordblood.org/en/news/umbilical-cord-blood-serum-eye-drops

Umbilical Cord Blood Serum Eye Drops May 2015 Yvonne Holt, MD Yvonne Holt, MD, Medical Director at Netcells Biosciences, South Africa The ocular (eye) surface includes two major territories: the cornea and the conjunctiva, bordered by the upper and lower eyelids. It is imperative that this ocular surface remains healthy to ensure clear vision, maintain comfort and guard against infections. Role of tears in healthy eyes The ability to form tears plays an essential role in the maintenance of a healthy cornea and conjunctiva. The tear film over the eye's surface consists of mucus, aqueous, and lipid layers and contains many growth factors and vitamin A, which are essential for regulating the proliferation, differentiation, and maturation of the ocular surface epithelium. Ocular surface disorders, including dry eye disease, are characterized by a decrease in quality and quantity of the tear film and changes in cell characteristics of the conjunctival epithelium. These disorders can severely affect eyesight and quality of life. Patients with ocular surface diseases suffer from loss of vision, discomfort and pain, infection, erosion, ulceration, and destruction with scarring of the eye surface. Conventional treatments for ocular surface disorders include the application of artificial tears, topical anti-inflammatory agents, therapeutic contact lenses, and surgery to block the lacrimal puncta so that tears do not drain away. Similarity between blood and tears It is known that human blood serum contains many growth factors and other components that are similar to tears. Patients suffering from ocular surface diseases have often relied on serum made from their own blood to treat dry eye symptoms and to help heal erosions of the eye surface.   Here is a list of components in blood that resemble tears: (1) growth factors such as: epidermal growth factor (EGF), acidic and basic fibroblast growth factors, platelet-derived growth factor, hepatocyte growth factors, and transforming growth factors (TGF-α). Also fibronectin, serum antiprotease (α2-macroglobulin), vitamin A, neurotropic factors [substance P, insulin-like growth factor (IGF)-1, and nerve growth factor (NGF)], (2) prealbumin, (3) oil and (4) antioxidants. Subsequently, it was discovered that umbilical cord blood serum contained similar growth factors and Vitamin A. 

Cord blood has 2-3 times higher concentrations of these factors than adult blood serum and tears themselves. 

Umbilical cord blood serum is effective in stimulating and regulating the proliferation, differentiation, and maturation of the ocular surface epithelium. In addition cord blood serum has been shown to have anti-inflammatory effects. Finally, cord blood serum has bacteriostatic effects due to antibacterial agents such as IgG, lysozymes and complement. The efficacy of Umbilical Cord Blood Serum has been demonstrated in the following conditions: Severe Dry eye with or without primary Sjögren's syndrome Ocular Graft-Versus-Host-Disease (GVHD) Persistent Epithelial Defects Corneal and conjunctival ulcers from any cause Recurrent corneal erosions Chemical burns Neurotrophic keratitis Refractory surgery Post Corneal Transplant Therefore, it is recommended that umbilical cord blood serum drops can be used in any condition that may cause delayed epithelial healing of the eye or dysfunctional tear film. The drops have been successfully used in both adults and children. Source of cord blood serum Umbilical Cord Blood Serum eye drops are prepared from the umbilical cord blood donated by consenting mothers during the birthing process. All donors sign an informed consent and are screened for the following transmissible diseases: HIV, Hepatitis B & C, HTLV, Syphilis and CMV. The serum is discarded if any of these are positive. The umbilical cord blood is collected from the umbilical vein of the placenta after delivery of the baby. The blood is left to clot at room temperature and centrifuged to separate the serum fraction from the cellular fraction. All samples are tested for bacterial and fungal contamination to ensure sterility of the product. The serum fraction is diluted to a 20% dilution and decanted into 5 ml eye dropper bottles using aseptic techniques in a clean room environment. The bottled serum is then frozen at -80°C for long term storage. A cord blood collection volume can range from 60ml-120ml. The serum fraction is usually about 40% of the volume. After testing and 20% dilution, about 20-40 bottles of serum can be produced from a single cord blood collection. As there are no preservatives in the eye drops, they must be stored frozen. The eye drops can be stored at a temperature less than -25°C for up to 2 years and at -18°C for 1 year. On prescription by a doctor, the eye drops are dispensed to a patient frozen, shipped from the laboratory on dry ice. At home, the patient must store the drops in their home freezer. To use the drops, the bottle of frozen drops must be thawed at room temperature and thereafter stored in the refrigerator at 2-8°C for a maximum of 7-10 days. Regimen of patient therapy Ophthalmologists suggest that patients use the cord blood serum eye drops in the affected eye or eyes in doses of 1-2 drops, up to 4-5 times per day, for up to 4-6 weeks. The drops can be used daily on a long term basis in patients who consistently have severe dry eyes. Treatment can be alternated between artificial tears and cord blood serum as the doctor sees fit. Topical administration of umbilical cord blood serum does not cause adverse effects on the eye, because the serum has reduced immunogenicity. The titres of IgM and IgG antibodies are low and anti-A and anti-B antibodies are absent or only weakly detectable in the serum. The eye is also an immune privileged site with low immunogenicity on the surface. Umbilical cord blood serum does not contain any preservatives and does not cause any toxic or allergic reactions in the eye. Umbilical cord blood serum has been shown to have great healing properties in ocular surface disorders. It is easy to collect and is immediately available to the patient in convenient bottles. It is also very useful in patients who have poor general health and who are unable to give blood to obtain their own serum. References Yoon, K.C; Use of Umbilical cord serum in ophthalmology; Chonnam Med J. 2014; 50:82-85 Vajpayee, R.B. et al., Evaluation of umbilical cord serum therapy for persistent corneal epithelial defects. British journal of ophthalmology, 2003; 87(11):1312-1316. Dr. Yvonne Holt is the Medical Director at Netcells Biosciences, a South African private stem cell and human tissue bank. Dr. Holt graduated from Wits University as a medical doctor and has a diploma in Paediatrics and Transfusion Medicine. Netcells specialises in the long term storage of baby stem cells (umbilical cord blood and tissue stem cells), adult stem cells (peripheral blood and adipose tissue stem cells), semen, human heart valves, amniotic tissue membrane used in ophthalmic surgery, and the production of umbilical cord blood serum eye drops. Dr. Holt is available to answer questions at Yvonne.Holt@netcells.co.za To learn more about cord blood banking, visit Parent's Guide to Cord Blood Foundation at https://parentsguidecordblood.org/en/news/umbilical-cord-blood-serum-eye-drops

Chonnam Med J. 2014 Dec; 50(3): 82–85.

Published online 2014 Dec 17. doi:  10.4068/cmj.2014.50.3.82

PMCID: PMC4276795

PMID: 25568842

Use of Umbilical Cord Serum in Ophthalmology

Kyung Chul Yoon

Author information ► Article notes ► Copyright and License information ▼ Disclaimer

Copyright © Chonnam Medical Journal, 2014

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

This article has been cited by other articles in PMC.

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INTRODUCTION

Blood preparations including autologous serum (AS), plasma rich in growth factors, platelets, and umbilical cord serum (UCS) have been introduced to treat many ocular diseases because they contain a high concentration of biologically active components and growth factors. The tear film consists of mucin, aqueous, and lipid layers and contains many growth factors and vitamin A, which are essential for regulating the proliferation, differentiation, and maturation of the ocular surface epithelium. Ocular surface disorders including dry eye disease or keratoconjunctivitis sicca are characterized by a decrease in quality and quantity of the tear film and squamous metaplasia of the conjunctival epithelium. Conventional treatments for ocular surface disorders include the application of artificial tears, topical anti-inflammatory agents, secretagogues, therapeutic contact lenses, and punctal occlusion.1 Because peripheral blood serum (PBS) harbors essential tear components and growth factors, AS eye drops have been used for the treatment of severe ocular surface diseases. We found that UCS contains a higher level of essential tear components, growth factors, and neurotrophic factors than AS, and UCS eye drops can be applied in various ocular conditions such as severe dry eye disease, persistent epithelial defects, neurotrophic keratopathy, recurrent corneal erosions, ocular chemical burn, and corneal refractive surgery.2,3,4,5,6,7,8

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CONVENTIONAL SERUM TREATMENT IN OPHTHALMOLOGY

Serum contains many growth factors [epidermal growth factor (EGF), acidic and basic fibroblast growth factors, platelet-derived growth factor, hepatocyte growth factors, and transforming growth factors (TGF-β)], fibronectin, serum antiprotease (α2-macroglobulin), vitamin A, neurotrophic factors [substance P, insulin-like growth factor (IGF)-1, and nerve growth factor (NGF)], prealbumin, oil, and antioxidants. Therefore, it can provide the corneal and conjunctival epithelium with basic elements for epithelial regeneration that are lacking in artificial tears.9

PBS is known to have higher vitamin A, TGF-β1, IGF-1, NGF, fibronectin, and lysozyme concentrations and lower immunoglobulin A, EGF, and vitamin C concentrations than tears.10 In an animal model of corneal epithelial defects after refractive surgery, 20% serum eye drops led to faster epithelial healing than artificial tears by decreasing apoptosis of keratocytes, migration of fibroblasts and myofibroblasts, and migration of inflammatory cells.11 According to controlled studies, AS treatment was shown to provide better improvement in symptoms and signs of ocular surface diseases than artificial tears did.12,13Clinically, AS eye drops have been effectively used to treat dry eye associated with Sjögren's syndrome2 or graft-versus-host disease (GVHD),3 persistent epithelial defects,4,5 neurotrophic keratopathy,6 superior limbic keratoconjunctivitis,7 and recurrent corneal erosions.8 AS has also been applied during or after ocular surgeries including macular hole surgery, vitrectomy in patients with diabetes, and trabeculectomy.14,15,16

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COMPARISON OF PERIPHERAL BLOOD SERUM AND UMBILICAL CORD SERUM

We have verified that UCS also harbors a high concentration of growth factors, neurotropic factors, and essential tear components.17,18 Compared with the levels in PBS, concentrations of EGF and TGF-β are 3 and 2 times higher, respectively, in UCS. Although the vitamin A concentration in UCS is lower than that in PBS, it is higher than the concentration in normal tears. UCS has higher NGF and substance P and lower IGF-1 concentrations compared with PBS. UCS-supplemented culture medium supports the proliferation and differentiation of epithelial cells in the conjunctiva and limbus, and UCS contains a higher concentration of growth factors and cytokines than fetal bovine serum and adult serum.19

Previous studies have also shown that UCS is superior to AS in the treatment of various ocular surface diseases.20,21,22,23 An initial study showed that UCS could provide faster healing of the corneal epithelium than AS.20 We reported that compared with AS, UCS was more effective in decreasing symptoms and epithelial staining in severe dry eye and increasing goblet cell density in Sjögren's syndrome.21 Additionally, UCS eye drops were shown to be more effective in improving corneal wound healing and reducing corneal haze compared with AS eye drops in ocular chemical burn.22,23

From a clinical aspect, UCS therapy has several advantages over AS therapy. A larger amount of serum can be collected from the umbilical vein at one time, and many patients obtain benefit from this sampling without waiting for additional preparations. In addition, UCS therapy is feasible in patients who have a poor general condition or blood dyscrasia, especially hematologic malignancy.

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PREPARATION OF UMBILICAL CORD SERUM EYE DROPS

Umbilical cord blood can be obtained from mothers during delivery. From donors, laboratory examination should be performed at 8 and 38 gestational weeks to test for human immunodeficiency and hepatitis B and C viruses. After fetal delivery, about 60 to 80 ml of umbilical cord blood is sampled from the umbilical cord vein. The blood is kept for 2 hours at room temperature. After 15 minutes of centrifugation at 3,000 ×g, the serum is carefully isolated under sterile conditions. The serum is then diluted to a 20% concentration with balanced salt solution. The aliquots of diluted serum are placed into sterile 5-ml bottles with ultraviolet light protection. Opened bottles are kept in a refrigerator at 4℃ for 7 days, and unopened bottles are stored in a freezer at -20℃ for 3 to 6 months. UCS eye drops are usually instilled 4 to 6 times per day as required in addition to artificial tears and antibiotics.

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SAFETY AND STABILITY OF UMBILICAL CORD SERUM

Among the components of serum, EGF, vitamin A, and TGF-β are well preserved for up to 1 month in a refrigerator at 4℃ and up to 3 months in a freezer at -20℃.4 A strict protocol for preparation and storage is essential for the safety of serum use.

Topical administration of UCS does not cause adverse effects on the eye, because the components of serum include growth factors and tear components, rather than umbilical cord tissue-derived cells, which may result in reduced immunogenicity.24 The titres of IgM and IgG2 antibodies are low in umbilical cord blood, and anti-A and anti-B antibodies are absent or only weakly detectable in UCS.25 Serum has a bacteriostatic effect because it contains antibacterial agents such as IgG, lysozyme, and complement. In addition, because serum contains no preservatives, serum therapy can avoid the risk of toxic reaction in the ocular surface.

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CLINICAL APPLICATION OF UMBILICAL CORD SERUM IN OPHTHALMOLOGY

We have safely and effectively applied UCS eye drops for the treatment of intractable ocular conditions including dry eye disease with or without Sjögren's syndrome, GVHD, persistent epithelial defects, neurotrophic keratopathy, recurrent corneal erosions, ocular chemical burn, and keratorefactive surgery.17,18,21,22,26,27,28,29

The efficacy of 20% UCS eye drops was evaluated in patients with severe dry eye disease with or without Sjögren's syndrome after 2 months of treatment.17 Tear film breakup time, corneal epithelial staining score, grade of conjunctival squamous metaplasia, goblet cell density, and symptom score significantly improved after UCS use. Our study comparing the therapeutic effect between AS and UCS in the treatment of severe dry eye disease revealed that, although both serum treatments led to improvement of symptoms and signs, symptom and corneal staining scores were lower in the UCS group after 1 and 2 months of treatment.21 In Sjögren's syndrome patients, goblet cell density was higher in the UCS group than in the AS group after 2 months of treatment.21 Recently, it was reported that the use of standardized and quality-controlled UCS eye drops was a promising therapy for the healing of severely injured corneal epithelium as well as the relief of subjective symptoms in severe cases of dry eye.30

GVHD, which is one of the major complications after allogeneic hematopoietic stem cell transplantation, can result in many ocular diseases. Among the GVHD-related ocular diseases, dry eye is the most frequent manifestation, leading to serious complications such as punctuate keratitis, persistent epithelial defects, and keratinization, ulceration, or perforation of the cornea. The use of UCS can be an effective treatment option for severe ocular surface manifestations associated with GVHD. In patients with GVHD-related dry eye, symptom score, corneal sensitivity, tear film breakup time, and corneal staining score significantly improved after 2 months of UCS treatment, and the improvement was maintained by 6 months after treatment.27

Persistent epithelial defects of the cornea are caused by medications, chemical or thermal injury, secondary infection following herpetic keratitis, and autoimmune diseases such as rheumatoid arthritis, ocular cicatrical pemphigoid, and erythema multiforme. The use of UCS could effectively decrease the defect size and shorten the healing time in patients with persistent corneal epithelial defects.20,26

Neurotrophic keratitis is characterized by impaired healing of the corneal epithelium due to damage to trigeminal innervations and depletion of trophic mediators. Causative factors include herpes simplex and zoster keratitis; chemical, physical, and surgical injuries; neurosurgical procedures for acoustic neuroma and meningioma; and systemic diseases such as diabetes, multiple sclerosis, and leprosy. We applied UCS eye drops in patients with neurotrophic keratitis who did not respond to conventional treatment. The epithelial defect healed at around 4 weeks, and visual acuity as well as corneal sensitivity also improved after treatment.18

Recurrent corneal erosion syndrome is defined as repeated episodes of corneal de-epithelization that result from trauma or dystrophy of the cornea, resulting in pain, tearing, and potential visual loss. We found that the use of 20% UCS eye drops significantly reduced the number of recurrences compared with artificial tears.28

In ocular chemical burn, early epithelial wound healing is essential to prevent serious long-term complications, which include ulceration, neovascularization, and opacification. UCS treatment showed better epithelial wound healing and lower corneal haze scores compared with PBS or conventional treatment.22,31 In addition, stromal inflammation and the interleukin-1β level in the cornea were decreased in the UCS-treated group.22

Finally, UCS treatment can be tried for ocular complications associated with Stevens-Johnson syndrome and ocular cicatrical pemphigoid, ocular surface keratinization, Mooren's ulceration, and epithelial maintenance after ocular surface reconstruction or corneal refractive surgery. Application of 20% UCS eye drops in addition to conventional treatment after laser epithelial keratomileusis could reduce early postoperative corneal haze and improve tear film and ocular surface parameters.29

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COMPLICATIONS AND CONSIDERATIONS OF UMBILICAL CORD SERUM

Although no significant complications have been documented, potential adverse effects should always be considered when using UCS. Despite two laboratory examinations in pregnant donors, the possibility of transmission of blood-borne infectious or blood-borne diseases cannot be absolutely excluded. In addition, bacterial contamination and allergy are other possible problems. Legal and regulatory issues as well as additional costs for serum preparation should also be considered before obtaining the serum.

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SUMMARY AND FUTURE APPLICATIONS

Owing to the high concentrations of essential tear components, growth factors, and neurotrophic factors in UCS, UCS eye drops can be safely and effectively applied in intractable ocular conditions such as severe dry eye disease with or without Sjögren's syndrome, ocular GVHD, persistent epithelial defects, neurotrophic keratopathy, recurrent corneal erosions, ocular chemical burn, and surface problems after corneal refractive surgery.

Mesenchymal stromal cells can be obtained from umbilical cord blood, amniotic fluid, and adipose tissue as well as bone marrow. Umbilical cord blood contains not only hematopoietic progenitor cells but also mesenchymal progenitor cells.32 Corneal stromal cells have mesenchymal stromal cell-like characteristics.33 Therefore, it is expected that umbilical cord blood could be used in corneal tissue engineering and regeneration. Furthermore, human umbilical cord blood cells can differentiate into retinal nerve cells.34 In the future, human cord blood cells may be used for the regeneration of retinal nerve cells in retinal degeneration or dystrophy.

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Footnotes

None declared.

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References

1. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007) Ocul Surf. 2007;5:75–92. [PubMed]

2. Tsubota K, Goto E, Fujita H, Ono M, Inoue H, Saito I, et al. Treatment of dry eye by autologous serum application in Sjögrens syndrome. Br J Ophthalmol. 1999;83:390–395. [PMC free article] [PubMed]

3. Ogawa Y, Okamoto S, Mori T, Yamada M, Mashima Y, Watanabe R, et al. Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Bone Marrow Transplant. 2003;31:579–583. [PubMed]

4. Tsubota K, Goto E, Shimmura S, Shimazaki J. Treatment of persistent corneal epithelial defect by autologous serum application. Ophthalmology. 1999;106:1984–1989. [PubMed]

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Invest Ophthalmol Vis Sci. 2011 Feb 25;52(2):1087-92. doi: 10.1167/iovs.09-4170.

Evaluation of umbilical cord serum therapy in acute ocular chemical burns.

Sharma N1, Goel M, Velpandian T, Titiyal JS, Tandon R, Vajpayee RB.

Author information

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 day 1, 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.).

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. 

**

Case Rep Ophthalmol Med. 2018 Jul 25;2018:2381296. doi: 10.1155/2018/2381296. eCollection 2018.

Topical Treatment with Cord Blood Serum in Glaucoma Patients: A Preliminary Report.

Campos E1, Versura P1, Giannaccare G1, Terzi A2, Bisti S3, Di Marco S3, Buzzi M2.

Author information

Abstract

PURPOSE:

To report data which happened to be observed in two glaucoma patients treated with Cord Blood Serum (CBS) eye drops.

DESIGN:

A case report and retrospective data analysis.

METHODS:

CBS topical eye drops, characterized in advance for growth factors (GFs) content, were administered for two months with the aim to relieve their subjective symptoms, in two patients who had referred ocular surface discomfort, although in absence of any sign of keratopathy. As patients were also affected by advanced glaucoma at risk of vision loss and under treatment with hypotensive drugs, they had been also monitored over the same period with IOP controls and visual field tests in our unit.

RESULTS:

During subsequent visits, data from Mean Deviation and Pattern Standard Deviation in the visual fields were retrospectively collected and compared with before and after treatment with CBS, and an amelioration was observed.

CONCLUSIONS:

CBS contains a combination of GFs, which potentially exert a neuroprotective action and elect CBS as an interesting natural source to be delivered in neurodegenerative ocular disorders. The incidentally observed amelioration in these two patients deserves further investigation in this respect.