This document discusses various tear substitutes and artificial tears. It begins by covering the history of eye baths and artificial tears dating back to the 16th century. It then discusses different types of artificial tears including autologous serum, various polymers like cellulose derivatives, polyols, dextran 70, and hyaluronic acid. It also discusses newer technologies like punctal plugs, collagen implants, soft contact lenses, and electrical stimulation to increase tear production. The document concludes by discussing various preservatives used in artificial tears and newer disappearing preservatives.

1. Tear substitutes
Moderator:Dr.Poornima Raj B
Presenter:Dr.Prathibha S

4. History:
• Eye baths(they called Collyrium) were used in
England in the 16th century.
• To use the eye cups (cobalt blue glass bottle),
the patient applied it to the eye with the head
bowed forward, threw the head back with the
eye open, ensured lavage of the eye by
blinking several times and then removed the
cup with the head once more bowed forward.

6. • these artificial tears spread poorly across the
ocular surface and their short retention time
led to transient relief and very high frequency
of instillations.

7. Autologous serum:
• Our natural tears are made up of key
components not found in artificial tear products,
such as epidermal growth factor (EGF),
fibronectin and vitamin A, which support the
proliferation, maturation, migration and
differentiation of corneal and conjunctival
epithelia.
• We also know that serum contains IgG,
lysozymes and complement, which have
bacteriostatic properties.

8. • Using an 18-gauge needle, approximately
40ml of blood is collected into six 8.5cc blood
tubes.

9. • The collected blood is set aside to clot for two
hours at room temperature.
• Then the blood is centrifuged at 5,600 rpm for 10
minutes.
• The serum is filtered through a 25mm
polyethersulfone disc filter before mixing with
saline.
• Filtration is performed to remove fibrin strands,
which are believed to lessen the effect of ASEDs.
• Each 8.5cc tube of blood yields approximately
4cc of serum (24cc total)

10. Peripheral corneal infiltrate and ulcer
• Eyelid eczema
• Microbial keratitis in patients with an epi-
defect
• Increased discomfort or epitheliopathy
• Temporary bacterial conjunctivitis
• Scleral vasculitis and melting in RA patients
• Immune complex deposition with 100%
serum

11. Transplantation of salivary glands
• One of these involves restoration of lacrimal
function by transplanting ( in the case of the
parotid gland, rerouting) minor salivary glands
to inferior fornix, but these procedures
yielded a hypo-osmotic tear composition and
subsequent epithelial edema.

12. • The three procedures reported include
• (1) transposition of the excretory duct (Stensen’s
duct) of the parotid gland to the inferior fornix.
• (2) free transplantation of the sublingual gland
to the upper conjunctival fornix without
microvascular anastomosis.
• (3) free transplantation of the SMG with
microvascular anastomosis and implantation of
its excretory duct into the upper temporal fornix.

14. Second generation artifical eye drops:

15. Eye drops:
• Lubricants preparations formulated as
artificial tear solutions usually contain
inorganic electrolytes
preservatives
water soluble polymeric system.

17. • Sodium chloride,potassium
chloride,magnesium chloride and other
variuos ions help to maintain tonicity and PH
of the formulation.
• benzalkonium
chloride,chlorobutanol,thimerosal,EDTA,meth
ylparaben and ethylparaben are used to
prevent bacterial contamination

18. lubricants:Replacement of tear
Indications of use :
A) symptomatic relief of dry eye.
B) symptomatic relief of irritants.
C) symptomatic relief of exposure .
D) refreshment of contact lenses & prosthesis.
E) as basis for preparing topical medications . (
e.g. ; fort antibiotic drop)

20. Anatomy of an artificial tear

21. Artificial Tear Eye drops
 Solvent water
 Active ingredient water soluble polymers
 Viscosity polymers concentration
 Preservatives prevention of contamination
 balanced tonicity Inorganic electrolytes
NaCl&KCL equivalent to 0.9% NaCl
 P.H buffers
 Anti-oxidants Sometimes Vit. A
 Lipids phospholipids

22. IdealTear Substitute
Works like
normal tears
Should not alter the
clarity
Lower surface tension of
the tear film
Forms a hydrophilic
layer
Enhances the tear
volume
Should not react with
the tear proteins
Should not alter the
lipid layer

23. Ideal tear substitute
pH: 6.5 to 7.5
Refractive Index: 1.336
Surface Tension: 40.1
+/- 1.5 dyne/cm
Osmolarity: 302
+/- 6.3 mosm / L
Viscosity: 6-12 cps

24. FDA - 6 groups of Ophthalmic
Demulcents
• Cellulose derivatives
• Liquid polyols
• Dextran 70
• Gelatin
• Povidone
• Hyaluronic acid

25. Cellulose Derivatives
• CMC: 0.25 - 2%
• HPMC: 0.2% -0.3%
• Oil in water emulsion
• Also helps Mucin and lipid deficiency
• Can be blended with Glycerine, Carnitine,
Erythritol
• Blurring of vision present.

26. Cellulose derivatives
Viscosity
Retention time
on eye surface
Celluvisc 350
+ + + + + +
Liquigel 70 +
+ +
Systane 10 +
+ +
Refresh Tears
1 +

27. • Reliable viscosity agent
• Seldom used
Gelatin

28. polyols
Sugar hydrogenated
carbohydrates-polyhydric alcohols
Propylene glycol (PG)0.3%
Polyethylene glycol 400 0.4%(PEG
400)
Does not increases the viscosity
Combined with HP guar
Together forms a cross linked
Mucomimetic layer
Increase Retention time
Protects corneal surface &
promotes repair
Better lubricity > HPMC > CMC

29. Dextran 70
High mole.wt.polysacharide
Enhances the demulcent nature of HMC
Tears Naturale: 0.3% HPMC +0.1% dextran 70
More viscous & Soothing drop
Increases the retention time
Evaporative dry eyes

30. glycerine
Polyols
Glycerine 0.2%
Absorbs water
Polysorbate 80 used oil incorporated emulsions
Refresh endura, Soothe etc.
Inactive ingredient in restasis along with cyclosporine A

31. Polyvinyl alcohol
One of early
lubricants .
Hydrophilic
polymer
All purpose
lubricant
Almost doubles
TUBT
0.1% to 4%
Tears plus
Can be combined
with PEG 400 or
povidone (0.6%)

32. povidone
Iodine -antiseptic
Demulcent property
Increses solubility
Pataday -Olopatadine 2%
Increases the retention time

33. Hyaluronic
Normally found in joints,
vitreous gel & tears
High water retaining
property
Increases bio adhesion
Example: Blink tears,
Hyla, Hyvisc, etc.
More useful in Aqueous
deficiency

34. Carbomer 980
Cross
linked Poly
Acrylate
Polymer
High
clarity &
viscosity
Short flow
properties
High
retention
time on
eye

35. Osmoprotectants
L Carnitine
Erythritol
Taurine
Trehalose,
etc.

36. Bi-carbonate
Normal component of natural tears
It helps in maintaining Mucin layer
everywhere
It helps in repairing and maintaining
epithelial layer

37. Potassium
It helps in maintaining Corneal Thickness

38. Mild- 0.5 % CMC,
0.3% HPMC or
Carbomer
Moderate - polyols
+/- gelling agents
Severe - 1% CMC ,
hyaluronic acid, with
osmo protectants
Combination of 2 different
tear substitutes
Totally preservative free
Ointments, gels
WhichTear
Substitute?

39. 2.OINTMENTS.
• Second most common method .
• Petroleum,lanolin and other oil topical
ointments.
• When instilled in eye,they dissolve at the
temperature of ocular surface and disperse
with tear fluids.
• Ointment is retained in the cul-de-sac longer
than artifical tear substitutes.

41. • Applied directly on inferior conjunctival sac a
0.25 to 0.50 inch ribbon.
• Dosage: bed time, severe(day time)
ointments block the access of
solutions should be instilled prior to
ointments.

42. Indications:
• Exposure keratitis
• Decreased corneal sensitivity
• Recurrent corneal erosions
• Keratitis sicca(usually bedtime)
• After removal of foreign body
• During and following surgery.

43. Contraindications:
• Hypersensitivity to any component use of
contact lens

44. Newer lubricant eye gel:
• Carbopal 980(polyacrylic acid) a gelling agent
with high water binding power that
transforms from gel to liquid upon contact
with the ocular tissue.
• Available in 10ml tube.
• Minimises blurring and streaking common
with thick tears and ointments.

45. 3.Ocular inserts:
• Use of preservative free water soluble polymeric
insert(lacriset ie;preservative free).
• Cylindrical rod which contains 5mg hydroxy
propylmethylcellulose is placed in lower cul-de-
sac.
• later it imbibes fluid and swells.
• Strats dissolving within 6-8hrs releasing polymers
to the ocular surface for 12-24hours.

48. • Disadvantage:
cost, manual dexeterity, blurred vision as rod dissolves
causing the tear film to thicken( this can be minimised with
isotonic saline)
Adverse reaction:
1.transient blurring of vision.
2. ocular irritation and discomfort
3. matting/stickness of eyelashes
4.photophobhia, hypersensitivity,edema of eyelids
and hyperemia.

49. 4.Soft contact lens therapy

50. • Hydrophilic bandage lenses.
• provide a tear reservoir but it should be used
in conjunction with replacement tears
• Caution should be taken because such
patients are prone to contact lens intolerance
and super infections .
• Forniceal scarring may dislodge the lenses.

51. 5.Punctal plugs:
• mechanical occlusion of lacrimal puncta to
block the tear drainage and thereby
prolonging action of natural tears along with
artifical tears.

53. • Type: 1) silicone based plug
2) temporary absorable collagen implant
following placement the implant swells
impeding tear flow upto 2weeks before the
total implant is absorbed.

54. 6.Collagen implant:
• Absorable intracanalicular collagen implant in
2,3, and 4mm size.
• Patient should be informed that relief may
not occur immediately after insertion and no
removal is necessary if implant dissolves
within 5-7days.
• Permanent treatment(non dissolvable silicone
plugs).

57. Electrical stimulators:
Date of download: 6/17/2017 The Association for Research in Vision and Ophthalmology Copyright © 2017. All rights reserved.
From: Enhanced Tearing by Electrical Stimulation of the Anterior Ethmoid Nerve
Invest. Ophthalmol. Vis. Sci.. 2017;58(4):2341-2348. doi:10.1167/iovs.16-21362
Figure Legend:
Neural control of the tear film. Neural pathways from the sphenopalatine ganglion (SPG) and superior cervical ganglion
(SCG) control meibomian glands, lacrimal gland, and goblet cells.2–12 Electrical stimulation of the anterior ethmoid
increases aqueous tears22,23 and could also affect production and secretion of lipid and mucin.

58. 7.Electrical stimulation:
• Electrical stimulation of the lacrimal nerve,lacrimal
gland, anterior ethmoid nerve,and cornea increase tear
volume.
• A recent clinical trial demonstrated reduction in dry eye
symptoms using intranasal electrical stimulation of the
anterior ethmoid nerve at least four times a day.
• Direct stimulation of the lacrimal gland efferent nerves
increases tear volume and secretion of the gland proteins
and electrolytes, which drain through the nasolacrimal
ducts within minutes.

59. • However, stimulation of the afferent pathways (i.e.,
anterior ethmoid) could recruit other ocular glands
and cells to provide lipid and mucin, thereby
enabling a longer lasting relief

61. Neural control of the tear film.
• Neural pathways from the sphenopalatine
ganglion (SPG) and superior cervical ganglion
(SCG) control meibomian glands, lacrimal
gland, and goblet cells.
• Electrical stimulation of the anterior ethmoid
increases aqueous tearsand could also affect
production and secretion of lipid and mucin.

63. • (a) was powered wirelessly
using an external controller
(b) The device delivered
cathodic-first, biphasic,
charge-balanced pulses of
2.3 to 2.8 mA
• (c). Pulse duration and
frequency, as well as the on-
off duty cycle
• (d), were adjusted using the
external controller.

64. • . Dorsal-ventral (a) and
lateral (b) radiographs
showing the
neurostimulator (white
arrows) implanted between
the nasal septum and
mucosa, with the active
electrode approximately 3-
cm deep, facing the mucosa.

65. PRESERVATIVES IN ARTIFICIAL
TEAR SUBSTITUTES:

67. • Quaternary ammonium compounds
(benzalkonium chloride,polyquad),
• alcohols (chlorobutanol)
• other compounds (chlorhexidine, sorbic acid,
potassium sorbate, boric acid).
• Mercurial agent thimerosal, much used in the
past, has been abandoned because of its high
potential to provoke not only toxic but also
allergic reactions.

68. Benzalkonium Chloride
• BAK is the most prevalent and its cytotoxicity is
well-documented.
• Reports have shown that BAK can accumulate in
ocular tissue and can cause different types of cell
death with frequent dosing.
• It’s thought that patients at greatest risk for BAK-
induced adverse effects are those suffering from dry
eyes.

69. • Because of the lack of natural tears in these
patients, the BAK in each eye drop is not as
diluted as it would be in a patient with normal
tear formation.
• This may damage the corneal epithelium (top
layer of the eye) contributing to ocular surface
disease.
• Using more than 4 – 6 drops per day increases the
likelihood of BAK-induced adverse effects.

71. DISAPPEARING PRESERVATIVES
• These are the preservatives which on contact
with eye the preservative is converted to
dilute hydrogen peroxide which then changes
into water and oxygen within minute of
contacting the eye.

72. • Purite
• SOC (stabilised oxycholor complex)
• sodium perborate.

73. • Stabilized oxychloro complex (SOC) has been
found to have no in vivo or in vitro evidence
of cytotoxicity.
• It is effective at unusually low concentrations
(0.005%)
• which can be degraded into components
normally found in tears, such as sodium ions,
chloride ions, oxygen, and water.

74. Reference:
• Ashok Garg “Textbook of ocular
therapeutics”.
• A.K Khurana “Anatomy and Physiology of eye”.
• Zimmerrman “Textbook of ocular
pharmacology”.
• ARVO journal.

75. Thank you