This document discusses artificial tears and viscoelastic substances used to treat dry eye. It describes the components and functions of the normal precorneal tear film. Keratoconjunctivitis sicca or dry eye syndrome results from an inadequate tear film and its main causes are aqueous tear deficiency or evaporative dryness. Artificial tears are used to supplement the tear film and help relieve dry eye symptoms. The document outlines important characteristics of artificial tears like osmolarity, pH, preservatives, and viscoelastic substances. Common viscoelastic agents discussed include polyvinyl alcohol, povidone, hypromellose, carbomers, and sodium hyaluronate. The document provides details on the formulations and

1. Artificial
Tears and
Viscoelastic
Dr Gauri Sr
Shrestha
IOM, TU

2. The precorneal tear film
Lipid Layer (thickness 0.1 µm, origin: meibomian glands (major) and accessory
sebaceous glands
2

3. The precorneal tear film
Aqueous layer (thickness 71 µm, origin: lacrimal glands and the glands of Krause
and Wolfring)
Proteins,
salts, gel-
forming mucins
(MUC5AC)
Functions
• allow access of atmospheric oxygen to the
avascular corneal epithelium
• provide some antibacterial protection for
the eye (lysozyme, defensins, Lactoferrin,
sIgA)
• provide a regular surface to allow optimal
visual function
• flush away debris from the cornea and
conjunctival sac.
3

4. Known Tear
Components
with
Antimicrobial
Activity and
their Major
Source (ref)
AMPs = antimicrobial
peptides; sIgA =
secretory
Immunoglobulin A;
sPLA2 = secretory
phospholipase A2;
SLPI = secretory
leukocyte protease
inhibitor; SP-D =
surfactant protein D
4

5. The precorneal tear film
Mucin layer (thickness 0.02–0.05 µm, origin: conjunctival goblet cells, crypts of
Henle and the glands of Manz)
Functions
• allow the tear film to be attached to the the
corneal epithelial cells.
• act as a lubricant for eyelid movement over
the ocular surface (attach to glycocalex and
undergoes free movement across cornea)
• Prevent the attachment of bacteria to the
ocular surface
• Concentrate IgA at the mucosal surface.
• Entrap FB, debris and microorganism
entering the eye and expel it from the eye
Glycoproteins,
mucins (MUC1,
MUC4, MUC16
5

6. Keratoconjunctivitis sicca
(Dry eye syndrome)
• Keratoconjunctivitis sicca is
chronic, bilateral desiccation
of the conjunctiva and
cornea due to an inadequate
tear film.
• Symptoms: itching, burning,
irritation, and photophobia.
• Main two aetiologies:
1. Aqueous tear-deficient
2. Evaporative
Major etiological cause of dry eye in TFOS DEWS report in
6

7. The TFOS
DEWS II dry
eye
diagnostic
algorithm at a
glance
7

8. TFOT
(Tear
film-
orient
ed
therap
y)
8

9. Tear film-
oriented
therapy
based on
dry eye
disease
classificatio
n by ADES
(Asia Dry
Eye
Society)
9

10. Artificial tears (ATs) and the
precorneal tear film
10

11. Characteristics of artificial
tears
• Four requirements for artificial tears (Marquardt, 1986)
• not irritate the eye
• have a good lubricating effect
• have a long retention time
• not disturb the optics of the eye.
• Consider formula under following headings
• Osmolarity:
• pH
• Preservatives
• viscolizers.
11

12. Osmolarity
Osmolarit
y
(mOsm/L)
Condition Remark
305–310 Healthy tear
film
• 0.95% sodium chloride
• artificial tears from a 1.4%
sodium chloride or 2.5% boric
acid solution
≥329 Aqueous
deficient DED
• goblet cell density
• corneal glycogen level
• wetting of the ocular surface
210–239 Artificial tear • Dilute the hyperosmolar tear
film 12

13. pH
• A pH of 7.4, is normally selected for the pH of artificial tears
• Commercial preparations can range between pH 4–9
• Bicarbonate vastly improves the recovery of damaged corneas when
included in preservative-free artificial tears.
13

14. Preservatives
• Best option - preservative free preparation
• Single-use container (e.g. minims)
• Keep in the refrigerator to reduce bacterial growth
• Multidose formulation needs antibacterial
preservatives
• Benzalkonium chloride 0.01% - destabilise tear film,
shorten TBUT, damages corneal surface
• Cetrimide 0.01% (e.g., Viscotears) - irritation
• Sodium perborate (e.g., Genteel), sodium chlorite
(Refresh tears)
14

15. Viscolisers
• Viscosity of normal tear = 9mP
• Hyperviscous tear substitutes (10 – 44 mP)
• Remains longer in the lacrimal basin, blinking difficult
• E.g., Methylcellulose – highly viscous, blurred vision, sticking and
uncomfortable crusting of the eyelids
• Indication
• Mild dry eye: low viscous agent
• Moderate to severe dry eye: more viscous agent
15

16. Artificial tears (tear
substitutes)
• reduce symptoms if irritation, grittiness or a foreign body sensation
(e.g. adenoviral keratoconjunctivitis, concretions)
• reduce friction and enhance lubrication (e.g. floppy eyelid syndrome,
superior limbic keratoconjunctivitis)
• stabilize the tear film (e.g. persistent epithelial defect, rosacea
keratitis)
• protect from desiccation (e.g., ectropion, lagophthalmos).
16

17. Polyvinyl alcohol (PVA)
• is a non-ionic synthetic
surfactant and a contact lens
wetting solution.
• Has viscolizing properties
• A concentration of 1.4% has
low viscosity but remains in
the lacrimal basin for 30 min polyvinyl
alcohol 1.4%
17

18. Povidone (polyvinyl
pyrrolidine)
• is a mixture of essentially linear
synthetic polymers of 1-
vinylpyrolidin-2-one of different
chain lengths and molecular
weights
• Is a non-ionic surfactant
• Increases viscosity of a solution
at a concentration of 3–5%.
• Povidone iodine has been widely
used as a disinfectant including
the care of contact lenses.
PVA 1.4% +
povidone
0.6% +
PVA 1.4% +
povidone
0.6% +
chlorbutol
0.5%
PVA 1.4% +
povidone
0.6%
18

19. HPMB (Hypromellose,
hydroxpropyl methylcellulose)
• More viscous than PVA (polyvinyl alcohol)
0.3%
BAK
19

20. HPMB (Hypromellose,
hydroxpropyl methylcellulose)
Hydroxypropylmethylcellulose
(2% w/v)
Hydroxypropylmethylcellulos
e (0.3% w/w)
Gel
20

21. Hydroxyethyl cellulose
(Hyetellose)
• exhibit emollient and film-forming (cohesive) properties equal to
methylcellulose
• less viscous and cause less blurring of vision
Ingredients:Hydroxyethylcellulose
(HEC) 78.0 mg, Sodium Chondroitin
Sulfate, Boric Acid, Sodium Chloride,
Potassium Chloride, Disodium Edetate,
Polysorbate 80 21

22. Carboxymethyl cellulose
sodium (Carmellose sodium)
• is a formulation of methylcellulose with a high molecular weight
compound
• Can not penetrate the cornea.
• It is polyanionic (negatively charged) polymer with mucoadhesive
• has a retention time of 22 min on the healthy cornea.
Added
glyceri
ne 0.9% 22

23. Carbomers
• Carbomers are synthetic high
molecular weight polymers of acrylic
acid cross-linked with either allyl
ethers of sucrose or allyl ethers of
pentaerythritol.
• is the viscolizer used in Viscotears
0.2% and Gel Tears 0.2%.
• has good water-binding properties
• During blinking, liquefaction of the gel
occurs followed by a reformation of
the gel to reduce elimination from the
tear film
BAK
Cetrimide
Cetrimide
23

24. Ointments
• normally mixtures of various paraffins (relatively inert hydrocarbon
chemicals) with varying amounts of wool fat, lanolin.
• Liquid paraffin and paraffin yellow soft (simple eye ointment) melt at
ocular temperature
• Their greasy nature allows them to be retained for a longer period than
eyedrops.
• Because they blur vision, they are usually used, often as an adjunct, at
bedtime.
Product Soft
paraffin
Liquid
paraffin
Wool fat
(Lanolin)
Lacri- 57.3% 42.5% 0.2% 24

25. Sodium hyaluronate
• Sodium hyaluronate is a viscoelastic polymer normally present in the aqueous and
vitreous humour
• used to maintain a deep anterior chamber during anterior chamber surgery
• Topical sodium hyaluronate (0.18%) is non-cytotoxic
• used in the treatment of dry eyes when other artificial tear products have failed to
achieve satisfactory results.
• improve goblet cell density and reduce inflammation of the ocular surface
(Aragona et al 2002).
25

26. Mucomimetic agents
• A mucomimetic agent, hydroxypropylguarpolysaccharide (HP-guar) is employed
together with two demulcents – polyethylene glycol 400 (PEG) and propylene
glycol – and is preserved with polidronium chloride (polyquad).
• A preclinical study of this formulation demonstrated long-term desiccation
protection of the intact cornea and also epithelial cells in culture and has no
apparent deleterious effects on cells.
• It also provided conditions in which a damaged corneal epithelium can recover
normal barrier function (Ubels et al 2004).
• This agent has been shown to be more effective than carboxymethylcellulose in
reducing the signs and symptoms of dry eye (Christensen et al 2004).
26

27. Additional reading
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844110/
• https://www.researchgate.net/publication/335249492_A_Ne
w_Perspective_on_Dry_Eye_Classification_Proposal_by_the
_Asia_Dry_Eye_Society/figures?lo=1
• chrome-
extension://gphandlahdpffmccakmbngmbjnjiiahp/https://ww
w.researchgate.net/publication/335249492_A_New_Perspect
ive_on_Dry_Eye_Classification_Proposal_by_the_Asia_Dry_
Eye_Society/fulltext/5f52ad0792851c250b924dac/A-New-
Perspective-on-Dry-Eye-Classification-Proposal-by-the-
Asia-Dry-Eye-
Society.pdf?origin=figuresDialog_download&_rtd=e30%3D&_
tp=eyJjb250ZXh0Ijp7ImZpcnN0UGFnZSI6Il9kaXJlY3QiLCJwYWdl
IjoicHVibGljYXRpb24ifX0
• https://www.reviewofcontactlenses.com/article/understan
ding-the-tear-film
27

28. Thank
you
28