This document discusses components of artificial tears and lubricating eye drops. It describes the natural components of tears not found in artificial tears, such as growth factors and antibodies. It also outlines the typical components of artificial tears, including water, polymers, electrolytes, and preservatives. Several polymers used in artificial tears are described in detail, including hydroxypropyl methylcellulose and carboxymethylcellulose. The uses, properties, and side effects of these polymers are summarized.
2. Tear film structure and components
History
Artificial tear
Ophthalmic demulcents
Lubricating eye drops ( CMC , HPMC,HPC,PVA)
Sodium chloride and zinc sulphate
Carbomers and ointments
Dyes (Sodium fluorescein, lissamine , ICG, Rose Bengal stain)
Other dyes
References
3.
4.
5.
6. Natural tears are made up of components not found in artificial tear products
EGF epidermal growth factor, fibronectin which supports proliferation ,
maturation , migration, differentiation of corneal and conjunctival epithelia.
Also contains Ig G , lysozymes and complement which has bacteriostatic
properties.
7. Eye baths ( they called collyrium )were used in ENGLAND in 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 eyes wide open,
ensured lavage by blinking several times and then removed the cup with the
head once more bowed forward.
8. Lubricants preparation formulated as artificial tears usually contains;
Inorganic electrolyte
Preservative
Water soluble polymeric system
9. Indication of use
Symptomatic relief of dry eye
Symptomatic relief of irritants and
Symptomatic relief of exposure
Refreshment of contact lenses and prosthesis
As a basis for topical medication( e.g. fort antibiotic drop)
10.
11. Solvent water
Active ingredient Water soluble polymer
Viscosity Polymers concentration
Preservatives Prevention of contamination
Electrolytes Balanced tonicity
Buffers ph
Antioxidants Vit A sometimes
Lipids Phospholipids sometimes
19. Demulscent property
Increases solubility
0.1 to 2%
Lubricating and soothing
Lipid that integrates with existing oil layer, thickening it and reducing
evaporation
Povidone iodine has been widely used as a disinfectant including the care of
contact lenses.
20. Binds multiples of its weight in water, lowers tear osmolarity
Adheres to ocular surface
Stabilizes and evens out the tear film
Highly viscous until blink thins it out
Topical sodium hyaluronate (0.18%) is non-cytotoxic and has been used in the
treatment of dry eyes when other artificial tear products have failed to achieve
satisfactory results.
It has been found to improve goblet cell density and to reduce inflammation of
the ocular surface (Aragona et al 2002)
22. Carboxymethyl cellulose is a cellulose derivative that consists of the cellulose
backbone made up of glucopyranose monomers and their hydroxyl groups
bound to carboxymethyl groups.
Added in food products as a viscosity modifier or thickener and emulsifier
One of the most common viscous polymers used in artificial tears, and has
shown to be effective in the treatment of aqueous tear-deficient dry eye
symptoms and ocular surface staining .
The viscous and mucoadhesive properties as well as its anionic charge allow
prolonged retention time in the ocular surface
Sodium carboxymethylcellulose is the most commonly used salt.
Methyl cellulose is a hydrophilic white powder in pure form and dissolves in
cold (but not in hot) water, forming a clear viscous solution or gel.
Used to be marketed under trade name tylose.
23. In a randomized clinical study of patients with mild or moderate forms of eye
dryness, ophthalmic treatment with sodium carboxymethylcellulose resulted in
a diminished frequency of symptoms compared to the placebo group .
Carboxymethylcellulose interacts with human corneal epithelial cells to
facilitate corneal epithelial wound healing and attenuate eye irritation in a
dose-dependent manner .
It exhibits protective actions on the ocular surface in various applications; it
mediates cytoprotective effects on the ocular surface when applied prior to
contact lenses and reduces the incidence of epithelial defects during LASIK .
24. Carboxymethyl cellulose binds to the surface of corneal epithelial cells via its
glucopyranose subunits binding to glucose receptors GLUT-1 .
The residence time of carboxymethylcellulose bound to corneal cells is
approximately 2 hours as indicated by a short-term binding assay.
Binding of carboxymethylcellulose to the matrix proteins stimulated corneal
epithelial cell attachment, migration, and re-epithelialization of corneal wounds
26. It is synthesized by the alkali-catalyzed reaction of cellulose with
chloroacetic acid.
The polar (organic acid) carboxyl groups render the cellulose soluble and
chemically reactive.
The resultant mixture produces about 60% CMC plus 40% salts (sodium
chloride and sodium glycolate). This product is the so-called technical CMC
which is used in detergents. A further purification process to remove these
salts produces the pure CMC used for food, pharmaceutical, and dentifrice
(toothpaste) applications.
Functional properties of CMC depend on the degree of substitution of the
cellulose structure (i.e., how many of the hydroxyl groups have taken part in
the substitution reaction), as well as the chain length of the cellulose
backbone structure and the degree of clustering of the carboxymethyl
substituents.
28. Ocular uses
-Carboxymethylcellulose is an artificial substitute for tears.
- It is used as a lubricant for dry eyes. It is also used for the temporary relief of
burning, irritation and/or discomfort due to dryness of eyes.
-Moreover, it is used to lubricate and re-wet soft and rigid gas permeable contact
lenses.
Systemic uses
- It is also used as laxatives, diverticulosis, hemorrhoids and irritable bowel
syndrome.
Culinary uses
-Chewing gums, peanut butters , biscuits as an emulsifier
29. Enzymology
-CMC is a highly specific substrate for endo-acting celluloses, as its structure
has been engineered to decrystallize cellulose and create amorphous sites that
are ideal for endoglucanase action.
Used in the manufacture of capsules in nutritional supplements. Its edible and
nontoxic properties provide a vegetarian alternative to the use of gelatin.
30. Virtually unabsorbed and little or no degradation of absorbable products occurs
in the human digestive tract.
In humans, virtually 100 percent of orally ingested methyl cellulose can be
recovered in the feces within four days, indicating that absorption does not
occur.
31. Visual disturbances and eye discharge while using this medicine.
Some other side effects of this medicine include redness of the eye, eye
irritation, burning and discomfort, eyelid swelling and itching of the eye.
32. The risk or severity of adverse effects can be increased when CMC is used with;
- acetazolamide
-alloin
-amiloride
The therapeautic efficacy of CMC is decreased when used with;
-aclidinium
-amantadine
-amlodipine
-
33. Hypromellose , short for hydroxypropyl methylcellulose (HPMC), is a
semisynthetic, inert, viscoelastic polymer that forms colloid solution when
dissolved in water.
It is a solid, and is a slightly off-white to beige powder in appearance and may
be formed into granules.
The compound forms colloids when dissolved in water. This non-toxic
ingredient is combustible and can react vigorously with oxidizing agents.
Acts as a thickening agent, coating polymer, bio adhesive, solubility enhancer
in solid dispersions, and binder in the process of granulation and in modified
release formulations
Commonly used as a controlled delivery component in oral medicaments that
provides the release of a drug in a controlled fashion, effectively increasing the
duration of release of a drug to prolong its therapeutic effect.
34. Used as an ophthalmic protectant and lubricant, in artificial tears, and as a
diagnostic aid (contact lens procedures; gonioscopy).
Hydroxypropyl methylcellulose 0.3% as a contact lens solution is clear, viscous,
and easy to apply; does not require irrigation after use; and has levels of
convenience, safety, and visual recovery superior to the standard 2.5% solution
characteristics. The 0.3% gel could be used as an effective and convenient
gonioscopic and ophthalmoscopic contact medium.
35. Hypromellose is considered an inert substance – a methyl and hydroxypropyl
mixed ether of cellulose as it has no direct pharmacological activity.
The viscosity promoting properties of hypromellose prolong the retention time
and improve adhesion of synthetic tears to the cornea and conjunctiva. As a
result, the tear film breakdown time is prolonged and/or the tear film stability
is enhanced. A stable tear film protects the cornea from dryness .
36. Promotes corneal wetting by the stabilization and thickening the precorneal
tear film and prolonging the tear film breakdown time, which is usually
shortened in dry eye conditions. Hypromellose also acts to lubricate and
protect the eye .
In the typical dry eye, and particularly in case of mucin deficiency; surface
activity and its adsorptive capacity make hypromellose optimal for this use.
Hypromellose has a physical-chemical action and leads to, in an aqueous
solution, a reduced surface tension as well as an increased level of viscosity.
Hypromellose adheres well to the cornea and conjunctiva and provides ample
moisture.
37. Hypromellose is considered low toxicity to non-toxic .
Adverse events may include blurred vision and contact dermatitis .
Hypersensitivity and intolerance reactions may occur (for example, eye
burning, pain, increased lacrimation, a sensation of foreign body, conjunctival
hyperemia, eyelid swelling, pruritus).
The stickiness sensation of the eyelids, the decreased sense of smell,
photosensitivity .
38. Ophthalmic applications
-as a semisynthetic substitute for tear-film
-Its molecular structure is predicated upon a base celluloid compound that is
highly water-soluble. Post-application, celluloid attributes of good water
solubility reportedly aid in visual clarity.
-When applied, a hypromellose solution acts to swell and absorb water, thereby
expanding the thickness of the tear-film. Hypromellose augmentation therefore
results in extended lubricant time presence on the cornea, which theoretically
results in decreased eye irritation, especially in dry climates, home, or work
environments
- On a molecular level, this polymer contains beta-linked D-glucose units that
remain metabolically intact for days to weeks.
-Hypromellose 2% solution has been documented to be used during surgery to
aid in corneal protection and during orbital surgery.
39. Excipient/tableting ingredient
-hypromellose has been used as an excipient in oral tablet and capsule
formulations, where, depending on the grade, it functions as controlled release
agent to delay the release of a medicinal compound into the digestive tract.
-used as a binder and as a component of tablet coatings
Use in construction materials
HPMC is used primarily in construction materials like tile adhesives and renders
where it is used as a rheology modifier and water retention agent.
40. 1) Hypromellose is joined in hot water, be mixed with hypromellose mixture;
2) add remaining cold water, be placed in ice-water bath, be stirred to the
viscous solution that forms clarification.
In step 1), the temperature of hot water is between 70~100 ° of C, and
preferably temperature is 80~90 ° of C.
2.5% for gonioscopy traditionally
Opcare 0.3%, 0.5%, 0.7%
Moisol 0.5% ( 5ml, 10 ml)
41. Hydroxypropyl cellulose is an ether of cellulose where some of the hydroxyl
groups of the cellulose have been hydroxypropylated .
HPC has a combination of hydrophobic and hydrophilic groups, so it has a
lower critical solution temperature (LCST) at 45 °C. At temperatures below the
LCST, HPC is readily soluble in water; above the LCST, HPC is not soluble.
HPC forms liquid crystals and many mesophases according to its concentration
in water. Such mesophases include isotropic, anisotropic, nematic and
cholesteric. The last one gives many colors such as violet, green and red.
42. Hydroxypropyl cellulose (cellulose, 2-hydroxypropyl ether) is a derivative of
cellulose with both water solubility and organic solubility.
It acts to stabilize and thicken the precorneal tear film and prolong the tear film
breakup time which is usually accelerated in patients with dry eye states.
Hydroxypropyl cellulose also acts to lubricate and protect the eye.
It usually reduces the signs and symptoms resulting from moderate to severe
dry eye syndromes, such as conjunctival hyperemia, corneal and conjunctival
staining , exudation, itching, burning, foreign body sensation, smarting,
photophobia, dryness and blurred or cloudy vision. Progressive visual
deterioration which occurs in some patients may be retarded, halted, or
sometimes reversed.
43. Hydroxypropyl cellulose is a derivative of cellulose that is soluble in both
water and organic solvents.
It is particularly good at trapping water and producing a film that serves as a
barrier to water loss.
Hydroxypropyl cellulose possesses good surface activity but does not gel as it
forms open helical coils.
In general Hydroxypropyl cellulose is a water-soluble thickener, emulsifier
and film-former often used in tablet coating.
44. Studies conducted in rats fed 14 C-labeled hydroxypropyl cellulose
demonstrated that when orally administered, hydroxypropyl cellulose is not
absorbed from the gastrointestinal tract and is quantitatively excreted in the
feces.
45. Lacrisert, is a formulation of HPC used for artificial tears. It is used to treat
medical conditions characterized by insufficient tear production such as
keratoconjunctivitis sicca), recurrent corneal erosions, decreased corneal
sensitivity, exposure and neuroparalytic keratitis.
HPC is also used as a lubricant for artificial eyes.
HPC is used as a thickener, a low level binder and as an emulsion stabiliser .
In pharmaceuticals it is used as a binder in tablets.
HPC is used as a sieving matrix for DNA separations by capillary and
microchip electrophoresis.
HPC is the main ingredient in Cellugel, which is used in book conservation.
Cellugel is described as "A safe, penetrating consolidant for leather book
covers affected by red rot" and is produced by Preservation Solutions.
46. It is manufactured by reacting alkali cellulose with propylene oxide at elevated
pressure and temperature to yield a highly substituted cellulose ether, with 3.4–
4.1 mol of hydroxypropyl substituent per mole of anhydroglucose backbone
units .
Lacisert – 5 mg insert
47. Polyvinyl alcohol is a water-soluble synthetic polymer obtained by
polymerization of vinyl alcohol.
It is white and odorless.
48. As a synthetic resin with hydrophilic properties, it increases the persistence of
tear film and therefore lubricates and soothes dry/irritated eyes .
49. Polyvinyl alcohol is poorly absorbed from gastrointestinal tract, and readily
eliminated from the body .
50. When injected intravenously, polyvinyl alcohol has a half-life of 90 min.
Intraocularly, in eye drop form, the half-life is 7.2 minutes .
51. PVA is used in a variety of medical applications because of its
biocompatibility, low tendency for protein adhesion, and low toxicity.
Polyvinyl alcohol is found in ophthalmic solutions as a lubricant to prevent
irritation or to relieve dryness of the eyes .
Specific uses include cartilage replacements, contact lenses. Polyvinyl alcohol
is used as an aid in suspension polymerizations. Another application is
photographic film.
Nowadays PVA-based polymers are being used widely in additive
manufacturing. For example, 3D printed oral dosage forms demonstrate great
potential in the pharmaceutical industry. It is possible to create drug-loaded
tablets with modified drug-release characteristics where PVA is used as a
binder substance.
Medically, it may also used as the embolic agent in a Uterine Fibroid
Embolectomy (UFE)
52. Adverse effects include eye pain and changes of vision, and redness or
irritation of the eye .
Mild stinging or irritation of the eye, crusting of eyelid, eye pain, ocular
hyperemia, eye pruritus, foreign body sensation, eye discharge, and increased
lacrimation may also occur .
53. PVA is prepared by hydrolysis of polyvinyl acetate or sometimes other vinyl
ester-derived polymers with formate or chloroacetate groups instead of acetate.
The conversion of the polyvinyl esters is usually conducted by base-catalysed
transesterification with ethanol:
[CH2CH(OAc)]n + C2H5OH → [CH2CH(OH)]n + C2H5OAc
The properties of the polymer are affected by the degree of transesterification.
54. Sodium chloride, also known as salt, common salt, table salt or halite, is an
ionic compound with the chemical formula NaCl, representing a 1:1 ratio of
sodium and chloride ions.
Sodium chloride is the primary salt in seawater and in the extracellular fluid of
many multicellular organisms. It is listed on the World Health Organization
Model List of Essential Medicines.
This product is used to reduce swelling of the surface of the eye (cornea) in
certain eye conditions. Decreasing swelling of the cornea may lessen eye
discomfort or irritation caused by the swelling. This product works by drawing
fluid out of the cornea to reduce swelling.
55. This intravenous solution is indicated for use in adults and pediatric patients as
a source of electrolytes and water for hydration. Also, designed for use as a
diluent and delivery system for intermittent intravenous administration of
compatible drug additives.
Corneal edema
Increased intraocular pressure
56. Sodium, the major cation of the extracellular fluid, functions primarily in the
control of water distribution, fluid balance, and osmotic pressure of body
fluids. Sodium is also associated with chloride and bicarbonate in the
regulation of the acid-base equilibrium of body fluid. Chloride, the major
extracellular anion, closely follows the metabolism of sodium, and changes in
the acid-base balance of the body are reflected by changes in the chloride
concentration.
57. Absorption of sodium in the small intestine plays an important role in the
absorption of chloride, amino acids, glucose, and water. Chloride, in the form
of hydrochloric acid (HCl), is also an important component of gastric juice,
which aids the digestion and absorption of many nutrient.
58. Sodium and chloride — major electrolytes of the fluid compartment outside of
cells (i.e., extracellular) — work together to control extracellular volume and
blood pressure. Disturbances in sodium concentrations in the extracellular fluid
are associated with disorders of water balance.
59. The salt that is taken in to gastro intestinal tract remains for the most part
unabsorbed as the liquid contents pass through the stomach and small bowel.
On reaching the colon this salt, together with the water is taken in to the blood.
As excesses are absorbed the kidney is constantly excreting sodium chloride,
so that the chloride level in the blood and tissues remains fairly constant.
Further more, if the chloride intake ceases, the kidney ceases to excrete
chlorides.
60. The rare inadvertent intravascular administration or rapid intravascular
absorption of hypertonic sodium chloride can cause a shift of tissue fluids into
the vascular bed, resulting in hypervolemia, electrolyte disturbances,
circulatory failure, or augmented hypertension.
Eye discomfort, burning, redness, or temporary blurred vision may occur.
63. Lithium carbonate
Lithium citrate
Lithium hydroxide
-Sodium chloride may increase the excretion rate of drugs above which could
result in a lower serum level and potentially a reduction in efficacy.
Tolvaptan
-The risk or severity of adverse effects can be increased when Sodium chloride
is combined with Tolvaptan.
64. Optical usage
Defect-free NaCl crystals have an optical transmittance of about 90% for
infrared light, specifically between 200 nm and 20 µm. They were therefore
used in optical components (windows and prisms) operating in the spectral
range.
Firefighting
Sodium chloride is the principal extinguishing agent in fire extinguishers (Met-
L-X, Super D) used on combustible metal fires such as magnesium, potassium,
sodium, and NaK alloys (Class D).
Thermoplastic powder is added to the mixture, along with waterproofing (metal
stearates) and anti-caking materials (tricalcium phosphate) to form the
extinguishing agent.
When it is applied to the fire, the salt acts like a heat sink, dissipating heat from
the fire.
65. Food industry and agriculture
-Many microorganisms cannot live in a salty environment: water is drawn out of
their cells by osmosis. For this reason salt is used to preserve some foods, such
as bacon, fish, or cabbage.
Medicine
-Sodium chloride is used together with water as one of the primary solutions for
intravenous therapy. Nasal spray often contains a saline solution.
Water softening
66. Sodium chloride will be synthesized by reacting sodium bicarbonate with
hydrochloric acid.
Ph – 7
0.9% Nacl
2 to 4% used in corneal oedema
67. For swelling of the cornea: 2 to 4%
For ophthalmic dosage form (eye drops):
-Adults—Use 1 or 2 drops every 3 or 4 hours, or as directed by your doctor.
-Children—Use and dose must be determined by your doctor.
For ophthalmic dosage form (eye ointment):
-Adults—Apply small amount (1/4 inch) to the inside of the eyelids every 3 or 4
hours, or as directed by your doctor.
-Children—Use and dose must be determined by your doctor.
68. Zinc sulfate is the inorganic compound with the formula ZnSO4 and
historically known as "white vitriol“( white powder)is odorless. It is on the
World Health Organization's List of Essential Medicines, a list of the most
important medication needed in a basic health system.
Zinc sulfate, an astringent helps to reduce redness and irritation.
A locally acting pharmacologic agent which, by precipitating protein, helps to
clear mucous from the surface of the eye
69. Zinc has been identified as a cofactor for over 70 different enzymes, including
alkaline phosphatase, lactic dehydrogenase and both RNA and DNA
polymerase. Zinc facilitates wound healing, helps maintain normal growth
rates, normal skin hydration and the senses of taste and smell.
70. Zinc improves the absorption of water and electrolytes, improves regeneration
of the intestinal epithelium, increases the levels of brush border enzymes, and
enhances the immune response, allowing for a better clearance of the
pathogens.
71. Approximately 20 to 30% of dietary zinc is absorbed, primarily from the
duodenum and ileum. The amount absorbed is dependent on the bioavailability
from food.
Zinc is the most bioavailable from red meat and oysters.
After absorption, zinc is bound in the intestine to the protein metallothionein.
Endogenous zinc can be reabsorbed in the ileum and colon, creating an
enteropancreatic circulation of zinc.
72. After absorption zinc is bound to protein metallothionein in the intestines. Zinc
is widely distributed throughout the body. It is primarily stored in RBCs,
WBCs, muscles, bones, Skin, Kidneys, Liver, Pancreas, retina, and prostate.
73. Primarily fecal (approximately 90%); to a lesser extent in the urine and in
perspiration.
75. Medicine
In medicine it is used together with oral rehydration therapy (ORT) and an
astringent
Manufacturing
It is also used as an electrolyte for zinc electroplating, as a mordant in dyeing,
and as a preservative for skins and leather.
76. Zinc sulfate powder is an eye irritant.
Ingestion of trace amounts is considered safe, and zinc sulfate is added to
animal feed as a source of essential zinc, at rates of up to several hundred
milligrams per kilogram of feed. Excess ingestion results in acute stomach
distress, with nausea and vomiting appearing at 2–8 mg/Kg of body weight.
77. Zinc sulfate can cause a decrease in the absorption of
- Ciprofloxacin
- Carbamazepine
- Gatifloxacin
- Tetracycline
resulting in a reduced serum concentration and potentially a decrease in efficacy.
78. Avoid milk and dairy products. Separate the use of zinc from these products by
at least 2 hours before administration. Separate for 2 hours after administration
if these products also contain phosphorus.
Do not take with bran and high fiber foods. For optimal absorption, take zinc at
least 2 hours before or after eating high-fiber foods.
Take on an empty stomach. Take at least 1 hour before and 2 hours after eating
for optimal absorption. Zinc can be taken with food to reduce gastrointestinal
upset.
79. Zinc sulfate is produced by treating virtually any zinc-containing material
(metal, minerals, oxides) with sulfuric acid.
Specific reactions include the reaction of the metal with aqueous sulfuric acid:
Zn + H2SO4 + 7 H2O → ZnSO4•7H2O + H2
Pharmaceutical-grade zinc sulfate is produced by treating high-purity zinc
oxide with sulfuric acid:
ZnO + H2SO4 + 6 H2O → ZnSO4•7H2O
0.25% w/v
80. Carbomer 980 (polyacrylic acid) is the viscolizer used in Viscotears and Gel
Tears.
The gel has good water-binding properties, which help to form a stable tear
film.
It shows thixotropic properties (i.e. the gel is reversible). During blinking,
liquefaction of the gel occurs followed by a reformation of the gel to reduce
elimination from the tear film.
Marquardt (1986)found that liquid gels had a retention time seven times
greater than PVA .
They can provide protection during sleep when few natural tears are produced.
Liquivisc , viscotears 0.2%
81. These are normally mixtures of various paraffins (relatively inert hydrocarbon
chemicals) .
Liquid paraffin and paraffin yellow soft(simple eye ointment) melt at ocular
temperature and their greasy nature allows them to be retained for a longer
period than eye drops.
Because they blur vision, they are usually used, often as an adjunct, at bedtime
82.
83. Fluorescein is an organic compound and dye. It is available as a dark
orange/red powder slightly soluble in water ( yellow)and alcohol.
Dibasic dye of xanthine series
(C20H12O5Na), has a low molecular weight (376.27 Da)
Biologically inert
Dye concentration and pH can affect the intensity of fluorescence. Maximum
fluorescence occurs at a pH of 7.4 ,approximately 80% of the dye molecules
bind to plasma proteins.
84. 1871 ; First fluorescein dye was made by Bayer
M Straub ( 1888 ) used dye for vital staining if eye
Burk (1910 ) used to detect retinal disease
85. Fluorescein sodium is used extensively as a diagnostic tool in the field of
ophthalmology.
Fluorescein is a fluorescent compound or fluorophore having a maximum
absorbance of 485 to 500 nm and an emission maximum of 520 -530 nm.
The yellowish-green fluorescence of the compound can be used to demarcate
the vascular area under observation, distinguishing it from adjacent areas.
It is applied topically in the form of a drop or it can be injected intravenously
to produce a fluorescein angiogram.
Topical fluorescein is a useful tool in the diagnosis of corneal abrasions,
corneal ulcers, herpetic corneal infections, and dry eye. Fluorescein
angiography is used to diagnose and categorize macular edema, diabetic
retinopathy, inflammatory intraocular conditions, and intraocular tumors.
86. Fluorescein and its metabolites are mainly eliminated via renal excretion
within 24 to 36 hours of administration.
Dark yellow or orange urine
87.
88. In ophthalmology
-Tear film drainage studies- Jones test
-Contact lens fitting assessment
-Fluorescein angiography
-Test for dry eye-TBUT
-Applanation tonometry
-Staining techniques;siedels test, staining for epithelial defects
89. Plant science
Fluorescein has often been used to track water movement in groundwater to
study water flow and observe areas of contamination or obstruction in these
systems.
Oilfield application
Fluorescein dye solutions, typically 15% active, are commonly used as an aid to
leak detection during hydrostatic testing of subsea oil and gas pipelines and
other subsea infrastructure. Leaks can be detected by divers carrying an
ultraviolet light.
91. The excretion of Fluorescein can be decreased when combined with
Acetazolamide
Acyclovir
Amoxicillin
92. Liable to become infected with bacteria and, at the same time, are frequently
used on damaged tissue that is prone to infection, very great care must be taken
in their use.
Ps. aeruginosa is an especially dangerous pathological microorganism with
which fluorescein eye drops are inclined to become invaded. Phenyl mercuric
acetate or nitrate in 0.002% strength is the best bactericide for preserving these
particular eye drops.
However, the safest method of their employment is
sterile single-dose units or sterile fluorescein-impregnated paper strips,
both of which are readily available and to be highly recommended.
93. Fluorescein is an organic compound that has wide use as a synthetic coloring
agent. It is prepared by heating phthalic anhydride and resorcinol over a zinc
catalyst, and it crystallizes as a deep red powder.
Also called resorcinolpthalein
Available as fluorescein strip 2%
Solutions containing 500 mg fluorescein are available in vials of 10 mL of 5%
fluorescein or 5 mL of 10% fluorescein. Also available are 3 mL of 25%
fluorescein solution .
94. Belonging to class of organic compound xanthene- brownish red in colour.
Its disodium salt in ophthalmic solutions has been used as a diagnostic agent in
suspected damage to conjunctival and corneal cells.
The stain is also used in the preparation of Foraminifera for microscopic
analysis, allowing the distinction between forms that were alive or dead at the
time of collection.
Rose Bengal is a pink stain derived as an analogue of fluorescein.
A form of rose Bengal is also being studied as a treatment for certain cancers
and skin conditions. The cancer formulation of the drug, known as PV-10, is
currently undergoing clinical trials for melanoma, breast cancer. and
neuroendocrine tumors. The company also has formulated a drug based on rose
Bengal for the treatment of eczema and psoriasis; this drug, PV-10, is currently
in clinical trials as well.
95. Indicated as a diagnostic agent in routine ocular examinations or when
superficial conjunctiva or corneal tissue change is suspected, and as an aid in
the diagnosis of keratoconjunctivitis sicca, keratitis, abrasions or corrosions as
well as the detection of foreign bodies.
96. Rose Bengal is a staining agent that visualized ocular surfaces of both diseased
and dead cells in vivo .
Various studies demonstrate the cytotoxic effects of rose bengal in different
cell cultures, including smooth-muscle cells from human intestine, endothelial
cells from bovine pulmonary artery, rabbit Tenon fibro-blasts, and rabbit and
human corneal epithelial cells .
97. Rose Bengal stains both the nuclei and cell walls of dead or degenerated
epithelial cells of the cornea and conjunctiva, and stain the mucus of the
precorneal tear film.
It is proposed that the staining ability of rose Bengal is dependent on the status
of tear film protection rather than cell viability, as tear components such as
albumin and mucin can block the rose Bengal uptake .
It induces intrinsic cytotoxic effects by causing cellular morphologic changes,
subsequent loss of cellular motility, cell detachment, and cell death . It
mediates inhibitory actions on bovine corneal endothelial cells and attenuates
cell proliferation.
98. Tear component comprising of different proteins, such as albumin (although
not very common as tear component), lactoferrin, and transferrin, can bind to
rose Bengal dye and act as diffusion barrier to prevent dye uptake by cells and
subsequent cell staining.
Lysozymes in tear film can also bind to rose Bengal to form precipitates to
attenuate cell uptake .
100. Derivatives and salts
Rose Bengal can be used to form many derivatives that have important medical
functions. One such derivative was created so to be sono sensitive but photo
insensitive, so that with a high intensity focused ultrasound, it could be used in
the treatment of cancer.
Dendritic keratitis:
Rose Bengal will stain the areas of the dendritic ulcer. It is restricted to the
processes of the ulcer and does not diffuse to surrounding areas.
Keratoconjunctivitis sicca:
The parts that are stained are the exposed triangular areas in the interpalpebral
conjunctiva. Such staining constitutes a better diagnostic indication of dry eye
than the Schirmer tear test.
101. • Exophthalmos:
this is great enough to deny the eye of the normal
protection of the lids, drying will occur, which will lead to changes in
the exposed area.
• Pressure areas due to contact lens wear:
Practitioners can use rose Bengal during their initial assessment of patients for
contact lens tolerance. It is equally useful in follow-up visits, when stains might
be found on the cornea or bulbar or palpebral conjunctiva and,although not
serious, provide an indication that modification of the lens.
102. Rose Bengal is used to suppress bacterial growth in several microbiological
media, including Cooke's rose Bengal agar.
Rose Bengal dye is mixed with the homogenate of Brucella and pH of the
solution is maintained at 3.8, and this dye is used to diagnose Brucellosis by
agglutinating the suspected serum. Rose Bengal is slightly irritating and toxic
to the eye.
It has also been used as an insecticide.
104. ICG is a tricarbocyanine, anionic dye. Its structural formula is 2,2’-indo-
6,7,6’,7’-dibenzocarbocyanine sodium salt with a molecular weight of
774.96 Da.
ICG sodium salt is normally available in powder form and can be
dissolved in various solvents; 5% (< 5% depending on batch) sodium
iodide is usually added to ensure better solubility.
ICG was developed in the Second World War as a dye in photography
and tested in 1957 at the Mayo Clinic for use in human medicine by I.J.
Fox.
The absorption and fluorescence spectrum of ICG is in the near infrared
region.
105. ICG absorbs mainly between 600 nm and 900 nm and emits fluorescence
between 750 nm and 950 nm.
The fluorescence spectrum is very wide. Its maximum values are approx. 810
nm in water and approx. 830 nm in blood.
About 98% of ICG is bound to plasma protein, in particular to globulins.
107. Indocyanine Green for Injection USP undergoes no significant extrahepatic or
enterohepatic circulation; simultaneous arterial and venous blood estimations
have shown negligible renal, peripheral, lung or cerebro-spinal uptake of the
dye.
Indocyanine Green for Injection USP is taken up from the plasma almost
exclusively by the hepatic parenchymal cells and is secreted entirely into the
bile. Indocyanine Green Injection USP a helpful index of hepatic function.
108. The dye is excreted in bile in unconjugated form by liver.
Clearance of dyes which are removed from the circulation principally by the
liver constitutes one of the best methods for evaluating hepatic function.
109. In ophthalmology
Indocyanine green angiography
(ICGA) is a diagnostic procedure used to examine choroidal blood flow and
associated pathology. Standard dosage is 25 mg of ICG dissolved in 3 ml saline,
and 1 mL of the solution is injected.
The near infrared light used in ICGA penetrates ocular pigments such as
melanin and xanthophyll, as well as exudates and thin layers of sub-retinal
vessels.
Indocyanine green angiography is widely used to study choroidal
neovascularization in patients with exudative age-related macular degeneration.
In non exudative AMD, ICGA is used in classification of drusen and associated
sub retinal deposits.
110. ICG has the ability to bind 98% to plasma proteins – 80% to globulins and
20% to alpha-lipoprotein and albumin – and thus, in comparison with
fluorescein as a marker, has a lower leakage (slower emergence of dye from
the vessels, extravasally).Because of the plasma protein binding, ICG stays for
up to 20 to 30 minutes in the vessels (intravasally). When the eye is examined,
it thus stays for a long time in tissues with a higher blood flow, such as the
choroid and the blood vessels of the retina.
Capsulorhexis
Capsulorhexis is a technique used to remove the lens capsule during cataract
surgery. Various dyes are used to stain lens capsule during cataract surgery. In
1998, Horiguchi et al. first described the use of indocyanine green dye (0.5%)
for capsular staining to assist cataract surgery.ICG-enhanced anterior and
posterior capsulorhexis is useful in childhood cataract surgery. Although ICG is
approved by US FDA, still there is no approval for intraocular use of the dye.
111. Selectively over-heating cells (especially cancer)
-ICG absorbs near infra-red, especially light with a wavelength of about 805
nanometers. A laser of that wavelength can penetrate tissue. That means, dying
tissue with injected ICG allows an 800 nm to 810 nm laser to heat or overheat
the dyed tissue without harming the surrounding tissue.
-That works particularly well on cancer tumors, because tumors naturally absorb
more ICG than other tissue. When ICG is injected near tumors, tumors react to
the laser 2.5 times as much as the surrounding tissue does.
-ICG and laser therapy has been shown to kill human pancreatic cancer cells.
-ICG and an infrared laser have also been used the same way to treat acne
vulgaris.
112. ICG is metabolized microsomally in the liver and only excreted via the liver
and bile ducts; since it is not absorbed by the intestinal mucous membrane, the
toxicity can be classified as low.
It has been known since September 2007 that ICG decomposes into toxic
waste materials under the influence of UV light, creating a number of still
unknown substances.
A study published in February 2008, however, shows that ICG (the substance
without UV effect) is basically, as such, of only minor toxicity.
Occasionally – in one out of 42,000 cases – slight side-effects occur in humans
such as sore throats and hot flushes.
113. ICG as a pregnancy category C drug, meaning that adequate studies of safety
have not been conducted.
Effects such as anaphylactic shock, hypotension, tachycardia, dyspnea and
urticaria only occurred in individual cases; the risk of severe side-effects rises
in patients with chronic kidney impairment. Caution should also be observed in
patients affected by liver diseases.
114. Atropine
Atenolol
Cyclosporine
Dexamethasone
Erythromycin
may decrease the excretion rate of Indocyanine green acid form which could
result in a higher serum level.
115. Each vial of Indocyanine Green for Injection USP contains 25 mg of
Indocyanine Green as a sterile lyophilized powder with no more than 5%
sodium iodide.
Indocyanine Green for Injection USP has a pH of approximately 6.5 when
reconstituted.
116. This vital stain was introduced in 1973 by Norn as an alternative to rose
Bengal for assessing the ocular surface.
It is an organic dye that is synthetically produced and its molecular
weight is 576.6 Daltons.
Lissamine green is a diphenyl-naphthyl methane derivative of the
phenylmethane dye, whereas fluorescein and rose Bengal fall into the
category of xanthine dyes.
The DEWS II Report recommends that lissamine green (along with
Fluorescein assessment) should be used when evaluating ocular surface
damage. Using both stains is the most appropriate diagnostic technique
for evaluating ocular surface damage and that the benefits of using
lissamine green outweighed any risks.
117. Norm’s original research concluded lissamine green ‘shows a high level of
affinity in staining degenerated cells, dead cells and mucous fibrils, with this
staining being well defined and easily visualized with a slit lamp.
There is general agreement that lissamine green is useful when assessing
conjunctival integrity but has limited use in corneal integrity assessment due to
poor visibility against dark iris backgrounds.
However, lissamine green appears to be underutilized in routine optometric
practice and there are a number of potential reasons for this:
Lack of understanding
Belief that use of Fluorescein is sufficient
Making decisions based on other clinical findings or reported symptom
118. However, the staining properties of lissamine green makes it the best choice for
evaluating the integrity of the bulbar conjunctival epithelium and the marginal
zone of the conjunctiva (Marx’s line) when looking for lid margin changes
such as lid wiper epitheliopathy (LWE)
119. Lissamine green has a peak absorption at 624-635nm, the red end of the visible
spectrum. When illuminated with white light our eyes will see the reflected or
non-absorbed coloured light which is bluish green for lissamine green.
Using a red filter (figure 3), for example Hoya 25A or Kodak Wratten 92,
enhances visualisation of the dye by transmitting the wavelengths that
lissamine green absorbs giving a black appearance, any staining therefore
indicates where the dye is present.
120. Lissamine green is dose dependent, instilling too little will result in a limited
amount of staining. In clinics, impregnated paper strips are popular, these are
moistened with about 10-20ul of saline10 applied to the lower fornice.One
percent is the optimal concentration, as mild ocular irritation has been reported
with 2% and 3% solutions, whereas 1% is generally well tolerated.
Kim and Foulks12 concluded that the optimal time for evaluating conjunctival
staining is between one and four minutes after instillation. Instant viewing of
the staining pattern could result in misinterpretation due to any pooled dye
which has not dissipated
In contact lens patients, circumlimbal staining observed with lissamine green
may be an indicator of contact lens induced conjunctival staining (CLICS)—
indicating that the lens is too tight or has a sharp edge design.
121. For clinical use, lissamine green is available as 1.5mg impregnated strips.
122.
123. Alcain blue
-A complex copper-containing compound used in 1% solution and specific for staining
mucus. Alcian blue is used to counterstain rose Bengal, which, in addition to staining
dead cells, also stains mucus (Norn 1972).
Trypan blue
This stains mucus and dead cells which have undergone structural changes
Bromothymol blue
This is a narrow range pH indicator that changes color around pH 7
and stains degenerate and dead cells and mucus. It is used to assess the
damage caused by chemical agents such as lime.
124. Tetrazolium and iodotetrazolium
-Both these compounds have been used for the vital staining of tumors and
assessing corneal grafts (Norn 1972).
-They are by nature pro-stains because the compounds are reduced inside cells
to a red dye formazan. The color takes about 4 min to develop. Tetrazolium
stains degenerate – not dead or living – cells. Living healthy cells are not stained
because of the impermeability of the cell membrane and dead cells are not
stained because the enzymes needed to reduce the dye to formazan are not
present.
125. Ophthalmic drugs diagnostic and therapeutic effects –Graham Hopkins and
Richard pearson
Drugs in ophthalmology , Donald s fong s
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