1.

Teori ttg sindrom mata kering (2) in end-stage Stevens-Johnson syndrome

patients may be totally keratinized, resulting in
Historically, dry eye disease (DED) was
absence of symptoms. However, such patients
considered to be due to either insufficient
may still suffer from visual disturbances, which
production or impaired stability of tears. There
are now considered to be among the
is now evidence that any abnormality of the
important symptoms of severe dry eyes. A new
ocular surface can trigger disequilibrium in all
definition and diagnostic criteria was proposed
the other components of tear dynamics. In
in 2006 as follows “Dry eye is a chronic disease
1995, the National Eye Institute/Industry
of tear fluid and keratoconjunctival epithelium
Workshop headed by Lemp concluded that
that results from various factors, and
“Dry eye is a disorder of the tear film due to
accompanies ophthalmic discomfort and
tear deficiency or excessive evaporation, which
abnormal visual function. The diagnostic
causes damage to the interpalpebral ocular
criteria are: 1) assessment of symptoms, 2)
surface and is associated with symptoms of
qualitative or quantitative disturbance of the
ocular discomfort.” This was a very solid
tear film (quantity: Schirmer I test less than 5
beginning for establishing a consensus among
mm/5 min; quality: BUT less than 5 sec), 3)
dry eye researchers. Tear deficiency was still
keratoconjunctival epithelial damage (staining
the central concept in dry eye. In 1995, the
score greater than 3 points). The presence of
Japanese Dry Eye Society proposed their first
all criteria renders a diagnosis of definite dry
definition and diagnostic criteria. At that time,
eye and the presence of two out of the three
the Japanese definition did not include the
criteria renders a diagnosis of probable dry
symptoms of DED because the ocular surface
eye”

Gambar 1. 2006 Diagnostik Jepang untuk Mata Kering.

Dry eye syndrome is a condition where the conjunctiva and cornea are not enclosed with a
healthy amount or quality of tear fluid. More than 50 million people are affected by dry eye syndrome
in the US alone. Dry eye symptoms include itching and burning of the eye, sensation of grittiness, light
sensitivity, blurred vision and inflammation, all of which significantly affect the quality of a patient’s
life. Patients with dry eyes apply rewetting solutions, lubricants, comfort agents, or artificial tears to
their eyes via eye drops to increase the viscosity of the tears in the eye, slowing tear drainage and to
increase the moisture on the ocular surface. But the eye drops are inconvenient because they have
low bioavailability, short ocular residence time and need frequent instillation, which lead to patient
non-compliance.

Dry eye is a common disorder of the pylori, computer users, and longterm contact
tear film that affects millions of people over lens wearers.
the age of 40 years worldwide, and there is
Table 1. Major Cause of Dry Eyes Disease
currently no cure for this disease. Artificial
Environmental Etiologies
tears provide lubrication but lack the
(Internal or External Conditions)
biologically active components found in
• Increased age
natural tears, which have a complex • Androgen deficiency
composition that includes water, salts, • Systemic medications (Table 2)
hydrocarbons, proteins, and lipids. • Ophthalmic medications (Table 3)
Additionally, the frequent application of • Benzalkonium chloride-containing ocular
artificial tear solutions containing chemical products
preservatives to prevent contamination has • Low intake of omega-3 fatty acids
been found to induce toxic and allergic • Low humidity environments
reactions, especially among those with • Environmental pollution; cigarette smoke
sensitive eyes • Extended visual tasks on electronic
devices, television Aqueous Tear-Deficient
The prevalence of dry eye syndrome Dry Eye Etiologies
increases with age. DES is a common disorder • Sjogren’s syndrome dry eye
of eyes affecting a significant percentage of the • Non-Sjogren’s syndrome dry eye: lacrimal
population, especially those older than 50 gland deficiency, lacrimal gland obstruction,
years of age. Middle-aged and older adults are reflex tears hyposecretion
the most commonly affected group because of Evaporative Dry Eye Etiologies
A. Intrinsic
the high prevalence of contact lens usage,
• Meibomian gland or lid aperture disorders
systemic drug effects, autoimmune diseases,
• Low blink rate
and refractive surgeries in these groups. The • Isotretinoin ocular effect
burden of DES will continue to increase, due to B. Extrinsic
increased life expectancy, as well as projected • Preservatives in ocular medications
population growth among the elderly. Surveys • Vitamin A deficiency
have estimated the prevalence of DES varying • Long-term contact lens use
between 5% and>30% in various age groups • Allergic conjunctivitis
across different countries and worldwide. The Table 2. Systemic Medications That May
estimated number of people affected by DES Aggravate or Cause Dry Eye
ranges from 25 to 30 million all over the world.  Alpha-agonists
Research also shows that DES can affect any  Antiandrogens
race and is more common in women than in  Antiarrythmic agents
men. In women at the age of 50–52 when  Anticholinergics or medications with
menopause usually sets in, an imbalance anticholinergic effects
occurs between the oestrogen and androgen  Antidepressants: selective serotonin
hormones. This excites inflammation in reuptake inhibitors and tricyclics
 Antihistamines
lacrimal gland and ocular surface, disrupting
 Antineoplastic agents
the normal homeostatic maintenance of the
 Antipsychotics
lacrimal gland and ocular surface. Up to 20% of
 Beta-blockers
persons with rheumatoid arthritis have KCS.
 Diuretics
Other individuals which are likely to be
affected include patients with Helicobacter
  Drugs secreted in tears: aspirin, DES and the duration of diabetes. This suggests
docetaxel, hydroxychloroquine, that examination for dry eye should be an
ibuprofen, isotretinoin integral part of the ocular examination in
 Isotretinoin patients with diabetes.
 Opioids
Table 3. Ophthalmic Medications Associated Ocular discomfort (including dry eye
with Aggravating or Causing Dry Eye feeling) is the second most reported symptom
 Adrenergic agonists–brimonidine, in artificially-created environments, where
apraclonidine people living in urban areas spend most of
 Antihistamines with mast cell stabilizing their time. These indoor environments tend to
effects -lopatadine, ketotifen, azelastine alter the tear film because of their low
 Antivirals – acyclovir, trifluridine humidity, and high air flow occurring inside
 Beta-blockers–betaxalol, carteolol, conventional buildings, airplanes, and vehicles
timolol, levobunolol, metipranolol also tends to produce dry eye. The use of visual
 Carbonic anhydrase inhibitors – display terminals has grown exponentially
brinzolamide, dorzolamide worldwide, which further impacts dry eye
 Cholinergic agents - pilocarpine prevalence negatively. The percentage of
 Decongestants–tetrahydrazoline, office workers using these devices and being
naphazoline diagnosed with dry eye has increased up to
 Mydriatics – cyclopentolate
10% and 21% in male and female Japanese
 NSAIDs – diclofenac, ketorolac
office workers, respectively. Adverse
 Preservative – benzalkonium chloride
environmental conditions could trigger the
 Prostaglandins–travoprost, latanoprost,
exacerbation of properly managed dry eye
bimatoprost
patients or borderline subjects. Therefore, our
 May not cause dry eye when used as the research group and others have studied the
sole ocular agent, but associated with clinical and tear changes occurring in dry eye
dry eye when patients are using more patients after exposing them to several
than one ocular agent. desiccating conditions to evaluate how
 Abbreviation: NSAIDs = Nonsteroidal thelacrimal functional unit responds to a
anti-inflammatory drugs. controlled adverse environment.
Diabetes mellitus (DM) has been
identified as one of the leading systemic risk
factors for DES. The reported prevalence of
DES in diabetics is 15–33% in those over 65
years of age and increases with age and is 50%
more common in women than in men. The
incidence of dry eye is correlated with the level
of glycated hemoglobin: the higher the level of
glycated hemoglobin, the higher the incidence
of dry eye. The Beaver Dam Eye Study reported
that approximately 20% of dry eyes occurred in
individuals with Type 2 diabetes aged between
43 and 86 years. Hom and De Land reported
that 53% of patients with either diabetes or
borderline diabetes had self-reported,
clinically relevant dry eyes. In a hospital-based
study, 54% of those with diabetes had DES and
there was a significant correlation between
 Risk Factor for Dry Eyes Disease
High level of evidence Moderate level of evidence Low level of evidence
 Age  Medications such as  Smoking
 Female sex tricyclic antidepressants,  Hispanic ethnicity
 Postmenopausal estrogen  selective serotonin  Anticholinergic drugs such
therapy reuptake inhibitors, as anxiolytics,
 Antihistamines  diuretics, beta-blockers antipsychotics
 Collagen vascular disease  Diabetes mellitus  Alcohol
 Corneal refractive surgery  HIV/HTLV1 infection  Menopause
 Irradiation  Systemic chemotherapy  Botulinum toxin injection
 Hematopoietic stem call  Cataract surgery with a  Acne
transplantation large incision  Gout
 Vitamin A deficiency  Keratoplasty  Oral contraceptives
 Hepatitis C  Isotretinoin  Pregnancy
 Androgen insufficiency  Low air humidity
 Sarcoidosis
 Ovarian dysfunction

2. Teori eye drop (2)
The most common technique of applying
drugs to the eyes is to directly apply the ocular
formulation on the surface of the eye. Eye
drops are the common form of formulation for
anterior segment disorders; however, they are
easily washed away by tears within 0.5–1 min
after application. Therefore, the duration of
the effect of a drug on the ocular surface is very
short. In addition, the eyes have protective
functions and structural features to maintain
their normal condition because they are
exposed to the external environment. This
makes it difficult to deliver the drug to the
desired site resulting in low drug
bioavailability. Thus, only less than 5% of the
administered dose of eye drops affects the
eyes.
compared with tears. The use of autologous
serum (AS) eye drops has been reported for
the treatment of severe dry eye and ocular
surface disorders, such as Sj¨ogren’s syndrome
(SS), superior limbic keratoconjunctivitis, graft-
versus-host disease, Stevens-Johnson
syndrome, ocular cicatricial pemphigoid,
recurrent corneal erosions, neurotrophic
keratopathy, Mooren’s ulcer, aniridic
keratopathy, and postkeratorefractive surgery.
AS eye drops are prepared as unpreserved
diluted blood solutions.
Appropriate therapy is selected based to
the disease severity and can range from
artificial tears, That provide palliative relief to
eye irritation in patients with tear deficiency,
to anti- inflammatory therapies for patients
with moderate to severe DES.

Eye drops that are produced by separating
the liquid and cellular components of a
patient’s blood have been demonstrated to
possess many of the same biological nutrients
that are found in natural tears. Serum and
tears show similar constituent concentrations,
with the exception of greater amounts of
vitamin A, lysozyme, transforming growth
factor-𝛽 (TGF-𝛽),and ffibronectin andreduced
amountsof immunoglobulin A (IgA), epithelial
growth factor (EGF), and vitamin C in serum
The major challenge of eye disease
treatment, including dry eye, is to enhance the
bioavailability of the ocular treatments. That
bioavailability is reduced because of the
complex structure of the ocular surface and its
high resistance to delivery of foreign
substances. Reflex tearing and blinking,
nonproductive absorption, nasolacrimal
drainage, metabolic degradation, and the
relative impermeability of the corneal
epithelial membrane are the responsible of
low time residence and low absorption of
drugs.
To overcome the low ocular bioavailability,
the application of frequent doses of the
therapeutic substances at high concentrations
is commonly used to achieve the desired
beneficial effects. This discontinuous dosing
not only results in extreme fluctuations in
ocular drug levels but also absorption of a
significant portion of the applied solution by
the conjunctiva or draining of the applied
solution by the nasolacrimal system into the
nasal cavity and then to the bloodstream. The
presence of certain drugs in the bloodstream
can induce undesirable systemic side effects.
The eye can be exposed to a series of
potentially toxic peak concentrations followed
by inadequate concentrations until the next
dose, which could lead to ocular and systemic
side effects and serious complications
depending on the therapeutic window and the
underlying pathophysiology.
The treatment of inflammatory eye
diseases such as severe allergic conjunctivitis
and uveitis is focused on the use of
corticosteroids as anti-inflammatory drugs.
These ophthalmic drugs used topically have
certain disadvantages ranging from the low
amount of drug penetrating through the
cornea to the limited residence time in the
precorneal area. This causes that the
suspensions need to be administered a greater
many times per day to obtain a significant
therapeutic effect. In other cases, in which the
posterior segment is affected, as in posterior
uveitis, intravitreal injections are used so that
the drug can reach the target. Moreover, the
main ocular side effect after topical
administration of corticosteroids include
cataracts and increased intraocular pressure,
which could induce visual disorders.
3. Teori bahan (4)
Among all the corticosteroids,
Fluorometholone (FMT) is characterized by a
highest pharmacological potency for
inflammations of the anterior segment of the
eye with a significantly lower risk of increasing
intraocular pressure.
Fluorometholone (FMT) [9α-fluoro-
11b,17α-dihydroxy-6α-methylpregna-1,4-
diene-3,20-dione] is a corticosteroid employed
for its glucocorticoid activity. It is thought to
act by the induction of phospholipase A2
inhibitory proteins, which control the
biosynthesis of potent mediators of
inflammation such as prostaglandins and
leukotrienes by inhibiting the release of their
common precursor, arachidonic acid.
Gambar 1. Struktur Kimia Fluorometholone
Fluorometholone (FML) is a
corticosteroid drug that is commonly used for
inflammatory diseases and dry eye syndrome.
The preparation of FML solution is difficult
owing to its low aqueous solubility . The
commercially available FML formulation is a
suspension (e.g., Flucon®Alcon Laboratories
Pty. Ltd., Fort Worth, TX, USA). FML in
suspension shows low bioavailability of around
1% and causes difficulty in delivering the
accurate dose, leading to inconvenience in
administering the suspension to the eye.
Therefore, excessive doses are often
administered to achieve the desired effect and
such dosing regimens may cause side effects,
such as elevated intraocular pressure.
In a previous study, fluorometholone was
not as potent as commonly used steroids in
reducing post-operative inflammation, but
other inconsistent results have been reported
Therefore, the efficacy of fluorometholone in
reducing inflammation after
phacoemulsification is unclear.
4. Teori pembuatan 5. Pengujian
6.