1. QEMME Cornea Replacement
By: Qurat-ul-ain Ali, Edward Sam, Maksura Alam, Mieko Kanai and Estefany Condo

2. Keratoplasty v. Keratoprosthesis
Figure 1: (Left) Eye abnormalities due to mustard gas. (Right) Eye after simultaneous keratolimbal allograft and lamellar keratoplasty.
Source for Figure 1: Jafarinasab M R et al. Am J Ophthalmol; 152:925–

3. Keratoprosthesis Problem Solution Fig 4: OOKP (tooth in eye procedure)
Fig 1: Damage due to alkali burn
Fig 2: Damage due to corneal ulcer
Fig 5: Alphacor
Fig 6: Boston K-pro.
Fig. 3: Damage due to Herpes (Dendritic keratitis)
Sources:
Figure 1 LearnNursing. What to do in case of Burns ( Accessed 12/08/2012
Figure 2 Small tear in contact lens ( Accessed 12/08/2012
Figure 3 EyeAtlas. ( Accessed 12/08/2012
Figure 4 Gomaa A et al. Clinical and Experimental Ophthalmology; 38: 211–
Figure 5 Gomaa A et al. Clinical and Experimental Ophthalmology; 38: 211–
Figure 6 Aquavella JV MD, et al. Am J Ophthalmol. 140:1032–

4. Source: Tan DTH et al.Ophthalmology. 115:503–510. 2008
Figure a: 34 year old amn attacked with acid. Figure b: Men with left eye after Osteo-odonto keratoprosthesis(OOKP)
Source: Tan DTH et al.Ophthalmology. 115:503–

5. Cornea Anatomy and Physiology
1/6 of eyeball surface.
Dimensions: 11.7 mm horizontally by 10.6 mm vertically (anterior)
Other 5/6 of the eyeball’s surface Sclera.
Union between the cornea and the sclera is referred as the Sulcus Sclerae or Limbus
Figure 1, Layers of the Cornea, accessed October 29, 2012

6. Cornea Anatomy and Physiology
Superficial cells age and their desmosomes lose their attachment tone and end up lost in the tear film.
interwoven collagen fibrils
90% of the corneal thickness. Transparency due to uniform spacing of collagen fibrils
10 μm thick. Separates easily.
Contains numerous mitochondria, prominent endoplasmic reticulum, and a Golgi apparatus
Figure 2,Anatomy of the Eye, accessed October 29, 2012

7. Proposed Device Device Functions: Refraction (n=1.33) and focusing.
Source of Oxygen
Description:
Material: PHEMMA hydrogel and collagen
Dimensions: 10 nm diameter by 300μm thickness.
Purpose: Replace corneas damaged by alkali (NaOH) burns.

8. Keratoplasty Reconstructive surgery Donor tissue
Improves vision by replacing the tissue affected by disease or injury with donor tissue.
Incision is made with a trephine, each “corneal button” is different per patient.
Stitches are used to hold the graft in place and may not be taken out for several months.

9. Keratoprosthesis (K-Pro)
Keratoplasty is not a universal option
Ideal K-Pro would “restore corneal clarity, integrate with host tissues and withstand a hostile ocular surface environment” [Snell et al, Clin. Anat. Of the Eye, , 1998]
3 of the most used devices:
AlphaCor™
Boston K-Pro
Osteo-Odonto K-Pro

10. AlphaCor™
Composed of the hydrogel polymer poly(2-hydroxyethyl methacrylate) (PHEMA)
‘Core-and-Skirt’ design
PHEMA provides refractive power
Hydrogel acts similar to soft tissue (biointegration)

11. Boston K-Pro Biosynthetic
Composed of poly (methyl methacrylate) (PMMA) and donor cornea
Features a front plate, a donated corneal button, and a titanium-ring back plate
The donor button is sandwiched between the front plate and the back plate, the latter of which includes a locking mechanism and various holes to make the integration into the native ocular environment easier.
Snell et al, Clin. Anatomy of the Eye, , 1998

12. Osteo-Odonto K-Pro
Composed of PMMA and host tissue—tooth and oral mucosa
3-month duration
Cosmetic prosthesis is often attached
“uses the patient’s own tooth root and surround alveolar bone to support a centrally cemented optical cylinder.”
(Falcinelli et al, 123: , 2005)

13. Experimental Design
Obtain approval from institutional animal care and use committee
Population of rabbits will be determined by power analysis
Three groups: one control and two experimental
Rabbits’ corneas will be burned with alkali solution (NaOH)1
Hackett et al., Invest Ophthamol Vis Sci., 52: 651-7, 2011.

14. Experimental Design Control with no treatment
Group that receives collagen as a treatment
Group that receives hydrogel polymer poly(2-hydroxyethyl methacrylate) (PHEMA) as treatment1
Myung et al., Biotech. Progress, 24: , 2008.

15. Experimental Design
Polypropene molds will turn the collagen and PHEMA into suitable forms1
Endothelial cells will be taken from the Descemet’s membrane
Cells will be placed into culture media to create more
Culture media and growth factors.
Figure 1. Descemet’s membrane is between the stroma and endothelium.2
Proulx et al. Exp Eye Res. 95(1):68-75, 2012.
Figure 2. Anatomy of the Eye, accessed October 29, 2012.

16. Experimental Design
Slit-lamp biomicroscopy will be used to take photographs of the affected area1
Immunohistological staining will be used to ascertain other changes in morphology
895 Micro-Bionix Test System will be used to measure tensile strength of the implants
Hackett et al., Invest Ophthamol Vis Sci., 52: 651-7, 2011.

17. Experimental Design
Figure 2. Slit-lamp microscope used to take pictures of the affected area in the cornea.2
Crabb et al.; Tissue Engineering, 12: , 2006.
Eol surplus. Microscopes and Illuminators.
Figure 3. Diagram of the increasing stress a 895 Micro-Bionix Test System puts on the implants.1

18. Sample size determination

19. The data for the sample size determination was used from the article “Biomechanical and Microstructural characteristics of a Collagen Film-based Corneal Stroma Equivalent” written by Crabb RAB et al. (2006).
The purpose of this study is to characterize the microstructure and biomechanical properties of collagen film as function of time in culture for a single-film stromal equivalent.
(Crab et al., Tissue Engineering 2006, 12.6)

20. Collagen films are hydrated in culture media over weeks.
The average mean and standard deviation of Ultimate tensile strengths (UTS) were estimated from their graphs into Table.
Group
Control
Experimental
Mean & Standard deviation
0.43 ± 0.11
0.36 ± 0.11
(Crab et al., Tissue Engineering 2006, 12.6)

21. Two-sample t test calculator shown in Figure was used from a website
The sample size was determined to be 40 to obtain 80% of power (α=0.05).

22. Statistical Analysis Sample size of 40/group α= 0.05
Parameters to be tested
-amount of infection
-amount of transparency
- amount of strain on cornea

23. Amount of Infections in the Corneas
Clinical check every 3 months postoperative for the next 18 months for a total of 6 clinical checks in total.
Measure: The % total infections over the 18 months
Statistical Tests: A one way ANOVA (F-test, with P ≤ 0.05), followed by a multiple comparison test (Holm t-test)

24. Table 1: Number of Infections recorded per clinical check for each group over 18 months postoperative
Group
# of infection by 3rd month
# of infection by 6th month
# of infection by 9th month
# of infection by 12th month
# of infection by 15th month
# of infection by 18th month
% total infection
Collagen
corneal
PHEMA
Corneal
Control

25. Amount of Corneal Transparency
Transparency will be assessed once 1 month postoperative and then every 3 months along with the clinical checks for the next 18 months.
Transparency ranked on a scale of 0-3:
where 0 = most transparent, and 3= total obscuration of the pupil
Method taken from: Crabb RA, Chau EP, Evans MC, Barocas VH, Hubel A, (2006) Biomechanical and Microstructural Characteristics of a Collagen Film-based Corneal Stroma Equivalent. Tissue Engineering1. 12, pg( )

26. Amount of Corneal Transparency
Statistical Tests:
-A Repeated measure ANOVA (P ≤ 0.05) on each group.
one way ANOVA ( F test, P ≤ 0.05), after mean, standard deviation of the 18 months data have been obtained and tested for normal distribution.
A multiple comparison Test (Holm t-test) if difference is detected

27. Amount of Strain of Cornea
Create an Apparent stress (Mpa) vs. strain curve
Measure
- The Ultimate Tensile Strength (UTS): Peak of curve
- Modulus: Slope of the curve
Statistical Tests:
-A two way ANOVA (two factors: UTS and Modulus)
- A multiple comparison test
(Fisher PLSD test, P ≤ 0.05 )
Method taken from: Crabb RA, Chau EP, Evans MC, Barocas VH, Hubel A, (2006) Biomechanical and Microstructural Characteristics of a Collagen Film-based Corneal Stroma Equivalent. Tissue Engineering1. 12, pg( )