1. Updated: March 7, 2007

2. Understanding Corneal Staining and Responding to Andrasko
Material and data provided by Lynn Lasswell, OD, Stan Huth, MA,
Denise Tran, BS, Cheryl Skotnitsky, OD, PhD

3. What is staining?
Staining with a topical dye is a clinical procedure used to observe the integrity and vitality of the epithelial cells of the ocular surface
Fluorescein, Rose Bengal and lissamine green dyes are used in different staining procedures

4. Corneal staining with fluorescein dye
Orange fluorescein dye absorbs blue light and emits green light.
Stains corneal defects upon application by diffusing between cells and adjacent intercellular spaces and penetrating into the underlying stroma. Stains whenever there is disruption of cell-cell junctions. Intensity of the stain increases with cell degeneration or death due to membrane & junction damage.
Can stain healthy cells.
Staining is not blocked by tear components such as albumen and mucin.
Detects epithelial defects and assists in the diagnosis of erosions, corneal abrasion and keratitis.
Very useful in detecting permeability of the epithelium and endothelium.
Molecular structure, with 2 negative charges

5. Topical application of fluorescein: the orange dye is released from commercially available sterile paper strips by wetting the strips with sterile saline and then touching the conjunctiva
Assessment of the “Red Eye” September 20, 2006
Sept 20, 2006

6. Punctate (point-like) fluorescein staining of cornea epithelium arising from solution toxicity

7. What amount of staining is considered acceptable?
Corneal fluorescein staining occurs occasionally in virtually everyone, including contact lens and non-contact lens wearers.
Trace punctate or pinpoint fluorescein staining can occur in healthy, normal individuals as a result of a normal cornea expressing epithelial turnover of dying surface cells undergoing replacement with new cells arising from below.
Dundas M. Walker A. Woods RL. Clinical grading of corneal staining of non-contact lens wearers. Opthalmic Physiol Opt 2001; 21:30-5

8. Accepted Staining Methodologies
Efron
CCLRU (Sydney, Australia)
CCLR (University of Waterloo, Canada)

9. Efron Staining Scale

10. Efron Staining Scale
5 cornea sectors
5 point scale

11. Efron staining scale 5 Point Scale Grade 0: Not significant
Grade 2: Requires monitoring
Grade 3: Therapeutic Intervention
Grade 4: Treatment

12. Cornea and Contact Lens Research Unit (CCLRU)
School of Optometry and Vision Science, The University of New South Wales,
Sydney, Australia

13. CCLRU standard for corneal staining with fluorescein
TYPE
DEPTH
EXTENT

14. Punctate (point-like) fluorescein staining types are determined for each cornea zone
1: micropunctate
2: macropunctate
3: coalesced
macropunctate
4: patch (≥ 1mm)
0: none

15. Punctate (point-like) fluorescein staining of cornea epithelium: CCLRU types
Type 2: Macropunctate
30% of central zone
Type 4: Patch
30% of nasal zone

16. CCLRU Example Zone Type Depth Extent
Clinical Significance determined by zone with greatest staining:
Type is greater than Grade 2 (macropunctate)
and/or
Depth is greater than Grade 1 (superficial epithelial involvement)
Extent is greater than Grade 1 (1-15% surface involvement)
Zone Type Depth Extent
Zone 1
10%
Zone 2 1 2
20%
Zone 3 4
30%
Zone 4
Zone 5 3

17. Lyndon Jones, University of Waterloo
CCLR
Lyndon Jones,
University of Waterloo

18. CCLR (University of Waterloo)
CCLRU expanded by Dr. Jones, University of Waterloo
Changed 0-4 staining type to type
25=micropunctate
50=macropunctate
75=coalesced macropunctate
100= patches
Continues to use 5 zones
Multiplies staining type by percentage area of zone
Result ranges from 0-10,000 per zone, 0-50,000 global

19. CCLR Example 3 4 1 5 2 3 Global Score < 6000 or
T=25
%=10 1
T=50
%=20 5
%=30
T=0
%=0 2 3
Zone 1: 50 (macro) x 20= 1000
Zone 2: 0
Zone 3: 50 (macro) x 20= 1000
Zone 4: 25 (micro) x 10= 250
Zone 5: 50 (macro) x 30= 150
1000
250
3750 Global Score
3750/5= 750 Average Sector Score
Global Score < 6000 or
Average Sector score < 1200
is clinically insignificant

20. Andrasko corneal staining grid
Andrasko study
Staining method
Results
Andrasko et al., “Ocular Response Observed with Silicone Hydrogel Lenses and Multi-purpose
Solution Combinations” June 2006 Poster
< Sept. 21, 2006

21. “Nearly all corneal staining was micropunctate”- Andrasko Poster
Andrasko Study Design
A series of randomized, double-masked, crossover studies consisting of 9-14 subjects each were run.
Subjects with staining at baseline were excluded from the study.
Prior to wear, the contact lenses were soaked for 12 hrs in the solution tested.
Subject’s cornea was examined with fluorescein, cobalt filter and a yellow filter at baseline (after 15 minutes of lens wear), and after 2 hours and 4 hours of lens wear.
Len/solution comfort was evaluated with a 100 point scale at baseline and after 2 hours and 4 hours of lens wear.
“Nearly all corneal staining was micropunctate”- Andrasko Poster
Staining Grid chart depicts only average percent staining across all zones.

22. Lenses and Solutions Studied
Contact Lens
AcuVue 2
Proclear
Acuvue Advance
AcuVue Oasys
PureVision
O2 Optix
Focus Night and Day
BioFinity
Solution
Unisol
Clear Care
Opti-Free Express
Opti-Free Replenish
Renu MoistureLoc
Renu Multi-Plus
Walmart MPS (Renu MP)
Target MPS (Renu MP)
Complete MoisturePlus
AQuify

23. Andrasko Staining Method
Corneal staining was examined according to the following scale. The cornea was divided into five zones and staining was evaluated according to type (0-4) and area (0-100%) for each zone.

24. Average corneal staining results with each lens type at baseline, after 2 hrs, and after 4 hours of lens wear. For the most part, baseline to the 2 hr point showed the greatest increase in staining area Nearly all corneal staining was micropunctate, type 1.

25. Andrasko comfort vs. staining results
The only comfort data reported was for PureVision™
Found a moderate, inverse correlation between comfort and staining at 4 hours of lens wear across all combinations of MPS and contact lenses. (i.e, high staining, low comfort)
The plot below is of PureVision ™ lens only. It shows the average comfort rating at each visit, with the staining area % noted in parentheses.

26. Andrasko Staining Grid
Lens and Solution Combinations
Percentage of Average Corneal Staining Area at 2 Hours
Unisol1 4 Saline
Clear Care4
Opti-free Express1
Opti-free Replenish1
Renu Moistureloc3
Renu Multiplus3
Walmart MPS
Target MPS
Complete Moisture Plus2
Aquify4
Acuvue5 2 1% 2% 5%
25%
Acuvue Advance5
No Further Tesing
13%
16%
20%
Acuvue Oasys5
Testing Ongoing 3%
10% 9%
12%
Purevision3 6% 7%
73%
71%
48%
21%
O2 Optix4
24%
41%
18%
Focus Night & Day4 4%
36%
Updated: September 19, 2006
H2O2
POLYQUAD
Biguanides
Lens and Solution Combinations
Percentage of Average Corneal Staining Area at 2 Hours
under 10%
10% to 20%
over 20%
Note: the CCLRU acceptance standard for % area is up to 15% when only micropunctate type 1 staining is present

27. Andrasko Staining Grid
Lens and Solution Combinations
Percentage of Average Corneal Staining Area at 2 Hours
Unisol1 4 Saline
Clear Care4
Opti-free Express1
Opti-free Replenish1
Renu Moistureloc3
Renu Multiplus3
Walmart MPS
Target MPS
Complete Moisture Plus2
Aquify4
Acuvue5 2 1% 2% 5%
25%
Acuvue Advance5
No Further Tesing
13%
16%
20%
Acuvue Oasys5
Testing Ongoing 3%
10% 9%
12%
Purevision3 6% 7%
73%
71%
48%
21%
O2 Optix4
24%
41%
18%
Focus Night & Day4 4%
36%
Updated: September 19, 2006
H2O2
POLYQUAD
Biguanides
Lens and Solution Combinations
Percentage of Average Corneal Staining Area at 2 Hours
Same Products!
under 10%
10% to 20%
over 20%

28. Summary response to Andrasko
Only Type 1 micropunctate staining was found: this is common, even among non-lens wearers
Subjective estimates of % surface area are unreliable- staining results for the same solution varied by 17% in Andrasko (ReNu Multiplus = 24% and Walmart MPS = 41%; yet they are the same solution!)
The standard of acceptance for Type 1 micropunctate staining is ≤ 15% of the surface area for any sector, not 10% per Andrasko (Table II and ref. 15 in Snyder article)
Andrasko mixed studies to provide results (e.g., O2 Optix: OFX= 2%, CMP = 4.5% and Aquify = 7% in same study/ population. Andrasko reported 18% for CMP instead, taken from another study.
Our own SH compatibility studies, including staining, show CMP produces no significant staining with SH lenses, except PV

29. Studies

30. 0-4 staining scale used, summed scores for each of 5 corneal zones
An 8% incidence of moderate-to-severe staining among contact lens wearers is not uncommon and can arise from factors other than the care system
Nichols KK, Mitchell GL, Simon KM, Chivers DA, Edrington TB. Corneal staining in hydrogel lens wearers. Optom Vis Sci 2002;79:20-30.
PURPOSE: The purpose of this study was to determine the factors that contribute to corneal staining in hydrogel lens wearers by examining the following variables: type of lens worn, wearing time and lens replacement schedule, lens care system, and topical and systemic medication use.
METHODS: 500 full-time, successful hydrogel contact lens wearers were evaluated for corneal fluorescein staining.
0-4 staining scale used, summed scores for each of 5 corneal zones
Moderate (Grade 3) to severe (Grade 4) = cumulative score ≥ Grade 3 with at least one quadrant score ≥ 2.

31. Nichols staining study results
RESULTS: Corneal fluorescein staining was present in at least one eye in 55.7% of the hydrogel lens wearers examined in this study, and 8.0% had moderate-to-severe staining.
CONCLUSIONS: Staining occurs to some extent in many hydrogel contact lens patients, and is influenced by many factors. Moderate-to-severe staining, which may be more clinically significant, is associated with noncompliance with care systems, a conventional replacement schedule (not planned replacement or disposable lenses), and higher plus or minus lens powers (>3 diopters).

32. Comfort

33. Relationship of staining to comfort
For Your Understanding:
Corneal staining associated with hydrogel contact lens wear may or may not be associated with patient symptoms

34. Relationship of staining to comfort
Study Design:
At least 40 subjects in each cell
Subjects wore one of a range contact lenses for up to 3 months with disposal as per label
Silicone hydrogel lenses and multi-purpose solutions studied
ACUVUE ™ ADVANCE™
ACUVUE ™ OASYS™
PureVision™
O2 Optix™
Focus ™ Night & Day™
Examined solution toxicity, defined as diffuse punctate staining
Subjects rated comfort on a scale of 1-10 (1=poor, 10=excellent)
AOSEPT ClearCare ™
AQuify ™
ReNu with MoistureLoc ™
OPTIFREE EXPRESS ™
OPTI-FREE RepleniSH ™
Tilia et al., Institute for Eye Research, Australia
Papas et al. “Solution Toxicity in Soft Contact Lens Daily Wear is Asociated with Corneal Inflammation” Poster

35. Relationship of staining to comfort
Subjects were asked to rate their experience with their lenses on a scale of 1 to 10, where 1= poor and 10= excellent.
Controls
Toxic Staining Group
Subjects experiencing solution toxic staining report lower than average
comfort ratings than those who do not: upon insertion of the lens
(7.9±2.0 vs 8.4±1.6, p=0.02) and at the end of the day (6.7±2.1 vs 7.2±2.1, p=0.04 ).
Tilia et al., Institute for Eye Research, Australia
Papas et al. “Solution Toxicity in Soft Contact Lens Daily Wear is Asociated with Corneal Inflammation” Poster

36. Chart 1
Bausch & Lomb EyeMatters newsletter, Vol. 9-September 2006 Recognizing the Clinical Realities of Corneal Staining

37. Corneal Staining Summary
3 major staining methodologies
Regional preference
High degree of subjectivity
Great variability between practitioners
Need to drive wedge between Andrasko results and accepted staining methods
Call results into question
Nearly all staining was micropunctate
Multiple studies and patient populations were used
Identical products had vastly different results
No statistical significance identified
Transition to AMO data
Neutral Red Retention
5 studies in EVA on compatibility
Get back on message
Tear quality
Maintains corneal integrity
2 Demulcents
Eliminates microbial contamination from lens
Highly effective

38. Trademarks
The AMO logo, Blink-N-Clean, COMPLETE, the COMPLETE logo, COMPLETE MoisturePLUS and ULTRACARE are registered trademarks and Blink Contacts is a trademark of Advanced Medical Optics Inc.
OPTI-FREE, EXPRESS and REPLENISH are registered trademarks of Alcon, Inc.
RENU, MULTI-PLUS and MOISTURELOC are registered trademarks of Bausch & Lomb, Inc.
ACUVUE, ACUVUE 2, and ADVANCE are registered trademarks and ACUVUE Oasys is a trademark of Johnson & Johnson Corporation.
AQUIFY and NIGHT & DAY are registered trademarks and O2OPTIX is a trademark of Novartis AG Corporation.
CLEAR CARE is a registered trademark of CIBA Vision.
REFRESH and REFRESH Contacts are registered trademarks of Allergan, Inc.