The effect of oral MB500 on the ocular surface in dry eye patients: The preliminary results

1
The effect of oral MB500 on the ocular surface
in dry eye patients The preliminary results

• Mee Kum Kim, M.D.1,2, Youn Seok In, M.D.1,2, Joo
  Youn Oh, M.D.1,2,
• Jung Hwa Ko2, Hyun Joo Lee2, Myung-Gyu Park3,Won
  Ryang Wee, M.D.1,2,
• Jin Hak Lee, M.D.1,2
• Department of Ophthalmology, Seoul National
  University College of Medicine 1.
• Seoul National University Hospital Clinical
  Research Institute2,
• MD bioalpha3

Financial interest disclosure Youn Seok In
None, Joo Youn Oh None, Jung Hwa Ko None,
Hyun Joo Lee None, Won Ryang Wee None, Jin
Hak Lee None, Mee Kum Kim None Myung-Gyu Park
Yes The material in this presentation has not
been approved by the U.S. Food and Drug
Administration. The material in this presentation
has been approved by the Korea Food and Drug
Administration.
2
Introduction

• Hyaluronan (HA)
• - Polymer of D-glucuronic acid
  D-N-acetylglucosamine
• - Function lubricating, moisturing,
  anti-oxidant, anti-inflammatory
• and cell proliferative effects1, 2
• MB500 (Halutech, MD bioalpha, Daejeon, Korea)
• - Natural uridine derivatives
• - Transformed to UTP by uridine kinase
• ? Possibly increase biosynthesis of HA

3
Introduction

• Effect of MB500 on the cultured human corneal
  epithelial cells and keratocytes
  
  (Presented at ARVO, 2005)
• - MB500 shows no cellular toxicity at
  various concentrations.
• - MB500 increased biosynthesis of HA and
  glycosaminoglycan.
• - MB500 showed antioxidanat effects induced
  by H2O2.
• Effect of MB500 on corneal wound healing
• 
  
  (Presented at ARVO, 2005)
• - Corneal wound healing was rapid in the
  rabbits of study group with MB500,
• compared with control group.
• Effect of topical MB500 on the ocular surface in
  a rabbit dry eye model
• 
  
  (Presented at ASCRS, 2006)
• - Topical application of 2.5 and 5 MB 500
  increased the number of
• conjunctival goblet cells, when compared
  with Hyalein -treated group
• and control, in a rabbit dry eye model.

4
Purpose

• To investigate the effect of oral MB500 on the
  ocular surface in dry eye patients.

5
Patients Methods

• Performed in accordance with the tenets of the
  Declaration of Helsinki and with proper
• informed consent
• Patients
• - 17 patients who diagnosed as dry eye
• 1) with lower than 5 mm of wetting in the
  Schirmer strip
• 2) with the presence of corneal epithelial
  erosion
• - Oral MB500 (800mg/tab) or placebo was
  randomly administered
• 3 times a day for 3months.
• 1) MB 500 9 patients
• 2) Placebo 8 patients

Placebo
MB500
6
Patients Methods

• Measurement of Aqueous tear production
• - Tear production was measured in a
  double-blinded manner with the
• Schirmer test in the experimental and
  placebo groups at 0.5, 1, 2, and 3
• months after start of medication.
• Corneal fluorescein staining3
• - Fluorescein was applied into the inferior
  conjunctival sac and the cornea
• was examined with a slit lamp biomicroscope
  in cobalt blue light 3 minutes after
  instillation.
• - Puntate staining was recorded in a
  double-blinded fashion with a
• standardized grading system of 0 to 9 with
  summation of the numbers of
• stained division from each of the 9 areas in
  which
• the corneal surface was divided.

7
Patients Methods

• Ocular Surface Disease Index (OSDI)4
• - Patients answered the OSDI questionnaire
  (Table, below) at 0.5, 1, 2, and 3
• months after start of medication.
• - The 12 items of the OSDI questionnaire were
  graded on a scale of 0 to 4.
• (0 none of the time 1 some of the time
  2 half of the time 3 most of the
• time 4 all of the time)
• - OSDI was acquired. (sum of scores for all
  questions answered) x 100/(total
• number of questions answered) x 5

8
Patients Methods

• Measurement of conjunctival goblet cell density
• - Impression cytology5 was performed in the
  experimental and placebo groups
• at 0.5, 1, 2, and 3 months after start of
  medication.
• - Goblet cells were counted in 10 consecutive
  high power field (HPF).
• Statistical methods
• - Within each group, temporal changes in tear
  amount, corneal staining, OSDI,
• and goblet cell counts were compared using a
  paired t-test.
• - The difference between pre-treatment and
  posttreatment measurements in
• tear amount, corneal staining, OSDI, and goblet
  cell counts were obtained by
• subtracting pretreatment measurements from
  measurements at 3 months after
• treatment beginning in each group and the mean
  change was compared
• between the two groups using a Mann-Whitney
  test.

9
Results

• Aqueous tear production
• - The Schirmer wetting in MB500 group was
  significantly increased, compared with that in
  placebo group.

Pre- vs. Post-treatment p0.04 in MB500
p0.26 in placebo MB500 vs. placebo at 3 months
p0.016
10
Results

• Corneal fluorescein staining
• - The Schirmer wetting in MB500 group was
  significantly increased, compared with that in
  placebo group.

Pre- vs. Post-treatment p0.023 in MB500
p0.43 in placebo MB500 vs. placebo at 3 months
p0.002
11
Results

• Ocular Surface Disease Index
• - OSDI was decreased in both groups after 3
  months of medication, but it was
• not statistically significant.

Pre- vs. Post-treatment p0.24 in MB500
p0.32 in placebo MB500 vs. placebo at 3 months
p0.79
12
Results

• Conjunctival goblet cell density
• - The change in number of goblet cell from the
  baseline was not significant
• in MB500 and placebo groups at 3 months
  after medication.

Pre- vs. Post-treatment p0.87 in MB500
p0.42 in placebo MB500 vs. placebo at 3 months
p0.12
13
Results

• Conjunctival goblet cell density

After 3 months of MB500
Before MB500
14
Conclusion

• Oral administration of MB500 might be helpful in
  severe dry eye patients by increasing the amount
  of tear secretion and decreasing a corneal
  fluorescein staining.

15
References

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  hyaluronic acid on corneal epithelial cell
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• 2. W.Y John Chen, Giovanni Abatangelo. Functions
  of hyaluronan in wound repair, Wound Repair and
  regeneration 1999779-89.
• 3.Norn MS. Lissamine green vital staining of
  cornea and conjunctiva. Acta Ophthalmol (Copenh).
  197351483-491.
• 4.Walt JG, Rowe MM, Stern KL. Evaluating the
  functional impact of dry eye the Ocular Surface
  Disease Index. Drug Inf J. 1997311436.
• 5. Tseng SC. Staging of conjunctival squamous
  metaplasia by impression cytology. Ophthalmology
  198592728-33.