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Department of Ophthalmology,
Osaka University Hospital

Conditions Treated
Corneal Regenerative Treatment for Chemical Burns or Corneal Burns due to Alkaline Corrosion, etc., Bullous Keratopathy, Stevens-Johnson Syndrome, Aniridia, Ocular Pemphigoid, and others
At present, corneal regenerative treatment is considered when normal corneal grafting is difficult.

Treatment Methods
(Corneal Regenerative Treatment Using Cultured (Tissue-Engineered)
Autologous Oral Mucosal Epithelial Cell Sheets)

The cornea is the transparent tissue, 0.5 mm in thickness, located in the foremost part of the eye. It consists of three layers of tissues, namely, the epithelium, parenchyma, and endothelium. Cornea transplants are performed through eye donations, for treating diseases in which the cornea becomes opaque or cloudy. However, the major problem with transplants is the critical shortage of cornea donors: over 10 million patients are waiting worldwide, while there are only 100,000 cornea donors. In addition, in regards to an ordinary cornea transplant that is performed for intractable corneal disease, both cure rates for corneal transparency in corneas (cases in which corneal transparency was retained) and visual recovery one year after surgery are approximately 20-40%. The incidence of rejection is approximately 20-30%, and the risk of contracting infectious diseases due to routine use of immunosuppressants is high.

For this reason, in the late 1990s, the autologous transplant of cultured corneal cells for a patient with unilateral eye disease was developed. Here, stem cells from the healthy eye of the patient are harvested and cultured in vitro in order to produce corneal-epithelial-like tissues, which are transplanted onto the diseased eye. This procedure solves the shortage of donor corneas and the rejection problem.

While this procedure is effective for patients with unilateral eye disease, it cannot be used for patients with bilateral eye disease, the overwhelming majority of patients. This problem motivated Dr. Kohji Nishida and his team to develop autologous transplants using cultured oral mucosal epithelial stem cells harvested from the lining of the mouth. In this method, the cells from the lining of a patient‘s mouth are cultured for 2 weeks to fabricate corneal-epithelial-tissue-like cell sheets, and then the cell sheet is placed on the cornea, from which the opaque surface (epithelium) has been excised.

We have performed this procedure on 15 patients, and performance results (follow-ups of 1 year) are as follows: the cure rate of corneal transparency is 93%, and the rate of visual recovery is 80%. In addition, no severe complications have occurred. Compared to cornea transplants using donated corneas, the performance results are vastly better. At present, this method is undergoing clinical research, and a multicentric study is scheduled to begin from 2011 in Japan.

However, this procedure can be applied only for patients with an impaired corneal epithelium. For eye diseases other than corneal disease, we perform cornea transplants using donated corneas.

Features of Our Department

In the ophthalmology department at our hospital, we have outpatient departments specializing in corneas, strabismic amblyopia/neuro-ophthalmological diseases, ocular inflammation, glaucoma, vitreoretinal diseases, and others. A number of prominent specialists, who rank at the top of their specialties in Japan, collaborate to provide highly advanced comprehensive therapies, from which even patients with co-existing multiple eye diseases can expect a recovery of vision. Particularly in the case of generative medicine of the eye, Japan has been taking the lead internationally. Here at our hospital, we pride ourselves in providing top-class medicine in this field, and offer cutting edge ocular surface reconstruction.

Treatment Results

Cornea Regenerative Treatment Using Cultured (Tissue-Engineered) Autologous Oral Mucosal Epithelial Cell Sheets
Number of Patients Operated On: 15
Male Patients: 8 Female Patients: 7 (Follow-up Period: 1 Year)
Cure Rate of Corneal Transparency 93% (14/15 eyes)
Rate of Visual Recovery 80% (12/15 eyes)
Severe Complications None

Furthermore, we are among the top in Japan in terms of performance results in treating intractable eye diseases, including using therapies with surgery and a laser. We performed a total of 2,232 surgeries in 2009. We provide a large number of cutting-edge surgical therapies such as corneal surgery, glaucoma surgery, vitreoretinal surgery, refractive surgery (Lasik, etc.), and other surgeries.

With regard to corneal regenerative treatment using cultured (tissue-engineered) autologous oral mucosal epithelial cell sheets, we are creating a system for admitting both domestic and international patients. For treating parenchymal or epithelial diseases, at present, there are no other procedures available except cornea transplants using donated corneas. Thus we are engaged in research to establish a treatment methodology using auto-transplantation within the next five years.

A Message to International Patients from Dr. Kohji Nishida at Our Department

There are many options when treating diseases with damaged corneal stem cells. Based on our comprehensive assessment, we are able to provide the best international top-class therapies, including generative medicine. When we succeeded in the world‘s first case of corneal regenerative treatment using cultured (tissue-engineered) autologous oral mucosal epithelial cell sheets, and published our research paper on this achievement in 2004, we received many inquiries from around the world, but were unfortunately unable to accept any patients. At last, we are now fully prepared to accept patients, and we hope to extend our services to international patients as well. As we are sure that we can provide highly advanced treatments, we would like you to consult us regarding ordinary cornea transplants and/or severe ocular surface diseases.

PROFILE

Dr. Kohji Nishida
Dr. Kohji Nishida

Dr. Kohji Nishida is Professor-in-Chief of the Department of Ophthalmology and Visual Science at the Osaka University Graduate School of Medicine. He earned his medical degree from the Osaka University Faculty of Medicine in 1988, and then joined the Salk Institute for Biological Studies in San Diego, California, as a research fellow in 1998. In 2006, he became a professor at Tohoku University. He has been a professor at Osaka University since 2010. His areas of research specialty are regenerative medicine and stem cell biology. He also currently serves as a councilor for the Japanese Ophthalmological Society, a member of the board of directors of the Japan Cornea Society, a member of the board of directors of the Keratoplasty Society of Japan, and a member of the Expert Committee on Research and Development for the Realization of Regenerative Medicine.

  • Nishida K, et al. Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med. 2004; 351: 1187-96.

Overview of the Treatment Schedule (Model Case)

You must have a cornea specialist after your return to your home country since follow-ups are crucial after a cell sheet transplant. Depending upon your case, our department may be able to refer you to a specialist in your home country.

After your admittance to the hospital is decided, you will need to wait 3–6 months before your visit to Japan.

A coordinator who can accommodate Chinese-speaking patients will be available in the near future.

Overview of Treatment Schedule

Photos

Cornea Regenerative Treatment Using Cultured (Tissue-Engineered) Autologous Oral Mucosal Epithelial Cell Sheets

Harvesting Oral Mucosa→ Culturing Cells for 2 Weeks in Cell Control Room→ Transporting Cell Sheets under Sterile Conditions to the Operating Room→
Harvesting Oral Mucosa Culturing Cells for 2 Weeks in Cell Control Room Transporting Cell Sheets under Sterile Conditions to the Operating Room
Recovering Cell Sheets→ Transplanting Cell Sheets  
Recovering Cell Sheets Transplanting Cell Sheets  
Established 1891
(Main hospital established in 1869)
Clinical Departments (Specialty Outpatient)
Cornea Outpatient, Medical Retina/Eye Inflammation, Cross-Eye (Strabismus)/Neuro-ophthalmology, Low Vision, Glaucoma, Severe Myopia (Nearsightedness), Surgical Retina
Payment Methods
Credit Card (VISA, JCB, MasterCard, American Express )

map

Address
2-15 Yamadaoka, Suita-shi, Osaka 565-0871
A short walk from the Osaka Monorail Handai-byoin-mae Station
35 minutes from the Shinkansen Shin-Osaka Station by car
30 minutes from Osaka International Airport (Itami Airport) by car
90 minutes from Kansai International Airport by car
URL
http://www.hosp.med.osaka-u.ac.jp/departments/ophthalmology.php