ocular DRUG DELIVERY SYSTEMS: MECHANISMS AND PROGRESSIONS
pptfreepaperMaurice Heunen NCC 2014 Extended Wear Tear Fim Secrets AAO VERSION
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3. • Conference proceedings Dutch Contact Lens
Conference 2014.
• Subject: Extended wear tear film secrets page 87.
• Several small studies show a diurnal change in tear film
composition. There appears to be a substantial increase
in secretory immunoglobulin A concentration after a
night’s sleep. Additionally, activated complement has
been reported. These findings have led to the hypothesis
of a physiological nocturnal inflammatory state of the
tear film. Contact lens extended or closed eye wear
gained popularity due to the introduction of silicone
hydrogel materials and orthokeratology. Unfortunately,
we still don’t understand the pathways that lead to
deposition and the role of deposition in inflammatory
processes. Therefore I strongly recommend further
research in this area.
4. Extended Wear
Tear Film Secrets
Maurice M.T.H. Heunen, MSc
Director Optometrisch Centrum Oud Geleen
7. Protein Extraction Effectiveness
Method Protein extracted from
Lotrafilcon B (µg/lens)
TFA/ACN 8.04 ± 3.75
Urea 3.29 ± 2.32
Acetone 2.06 ± 1.15
TCA 0.31 ± 0.23
Powell et al., Lipophilic versus hydrodynamic modes of uptake and
release by contact lenses of active entities used in multipurpose
solutions, CLAE, 2009
8. Extraction efficiency of TFA/ACN
Extraction efficiency in %
for TFA/ACN for Albumin
Lens Material
73.5 ± 5.6 Lotrafilcon B
91.5 ± 3.4 Galyfilcon A
81.5 ± 5.8 Balafilcon A
Subbaraman et al., Efficacy of an Extraction Solvent used to Quantify
Albumin deposition on Hydrogel Contact Lens Materials, Eye & Contact
Lens, 2009
10. Dr Barr’s Hypothesis (1989)
• Not the amount of protein, but
the state of the protein elicits
inflammatory responses.
Barr et al., Protein and Elemental Analysis of
Contact Lenses of Patients with SLK or
GPC, Optometry and Vision Science, 1989
11. Lysozyme activity
Active protein Reference
Etafilcon >94% Subbaraman et al., Protein
Deposition and Symptoms
with Daily Wear Etafilcon
Lenses, OVS, 2012
Balafilcon A approximate
50%
Luensmann & Jones, Protein
deposition on contact lenses
CLAE, 2012
Lotrafilcon A+B ≤25% Luensmann & Jones, Protein
deposition on contact lenses
CLAE, 2012
12. Lipids on Silicone Hydrogels
Problem:
Wide variety of extraction
chemicals and methodology.
Pucker et al., In Vitro Lipid Deposition on Hydrogel
and Silicone Hydrogel Contact Lenses, IOVS, 2010
Hatou et al., Biochemical analyses of lipids deposited
on silicone hydrogel lenses, Journal of Optometry,
2010
13. Lipids on Silicone Hydrogels
Key Points:
•Majority cholesterol deposits
•Little bit polar phospholipids
•Care systems might play a role
•Deposit formation pathways
remain unknown
Hatou et al., Biochemical analyses of lipids deposited
on silicone hydrogel lenses, Journal of Optometry,
2010
Heynen et al., Quantification of Non-Polar Lipid
Deposits in Senofilcon A Contact Lenses, OVS, 2011
14. Gipson, The Ocular Surface: The Challenge to Enable and Protect
Vision, IOVS, 2007
15. Closed eye sub inflammatory?
Increase in IgA concentration
(closed eye)
BUT
N=6
No p-value
Sack et al., IOVS, 1992
18. Immunoglubulin or Antibody
• Soluble proteins secreted by
activated B cells or by plasma
cells in response to an
antigen.
• Recognises antigen &
initiates complement fixation
and opsonisation.
19. Closed eye sub inflammatory?
Higher presence of complement
C3 and Factor B (closed eye)
BUT
N=8
No p-value
Willcox et al., IOVS, 1997
20. Closed eye sub inflammatory?
Increase in IgA concentration
upon waking by 9-fold ANOVA
p=0.005
Increase in albumin concentration
upon waking by 9-fold ANOVA
p=0.006
BUT
N=9
Pooled R+L eye samples
21. Conclusions
• SiHy’s might have relatively more
deposited denatured proteins than
traditional hydrogels.
• Deposits might elicit inflammation,
but its pathways remain unclear.
• The closed eye tear film may have a
sub inflammatory state.