1.

Dasar-dasar penurunan visus mata tenang

Loss of visual acuity may be due to abnormalities anywhere along the
optical and neurologic visual pathway. One must therefore consider
refractive (focusing) error, lid ptosis, clouding or interference from
the ocular media (eg, corneal edema, cataract, or hemorrhage in the
vitreous or aqueous space), and malfunction of the retina (macula),
optic nerve, or intracranial visual pathway.

A distinction should be made between decreased central acuity and

peripheral vision. The latter may be focal, such as a scotoma, or more
expansive, as with hemianopia. Abnormalities of the intracranial visual
pathway usually disturb the visual field more than central visual acuity.

Transient loss of central or peripheral vision is frequently due to

circulatory changes anywhere along the neurologic visual pathway
from the retina to the occipital cortex, for example amaurosis fugax and
migrainous scotoma.

The degree of visual impairment may vary under different circumstances. For
example, uncorrected nearsighted refractive error may seem worse in dark
environments. This is because pupillary dilation allows more misfocused rays
to reach the retina, increasing the blur. A central focal cataract may seem
worse in sunlight. In this case, pupillary constriction prevents more rays from
entering and passing around the lens opacity. Blurred vision from corneal
edema may improve as the day progresses owing to corneal
dehydration from surface evaporation.

Riordan-Eva, P., & Whitcher, J. P. (2008). Vaughan & Asbury General

Ophthalmology, 17th Edition. McGraw-Hill Companies Inc.

MATA TENANG VISUS TURUN

MENDADAK
Uveitis Katarak
PERLAHAN
posterior Glaukoma sudut
Perdarahan terbuka
vitreus Retinopati
Ablasio penyakit sistemik
retina Retinitis
Oklusi arteri pigmentosa
Neuritis Kelainan refraksi
optik
2. Anatomi dan fisiologi dari Lensa, Corpus Vitreum, dan Retina
Perhaps the most dramatic morphologic change occurs when the epithelial
cells elongate to form lens fiber cells. This change is associated with a
tremendous increase in the mass of cellular proteins in the
membranes of each fiber cell. At the same time, the cells lose organelles,
including cell nuclei, mitochondria, and ribosomes. The loss of these
organelles is optically advantageous because light passing through
the lens is no longer absorbed or scattered by these structures.
However, because these new lens fiber cells lack the metabolic functions
previously carried out by the organelles, they are now dependent on
glycolysis for energy production.

No cells are lost from the lens; as new fibers are laid down, they crowd and
compact the previously formed fibers, with the oldest layers being the most
central. The oldest of these, the embryonic and fetal lens nuclei, were
produced in embryonic life and persist in the center of the lens. The
outermost fibers are the most recently formed and make up the cortex of the
lens.

Basic Clinical Science Course Lens and Cataract Section 11 . (2008-

2009). Singapore: American Academy of Ophthalmology.

- Nucleus. It is the central part containing the oldest fibres. It consists

of different zones, which are laid down successively as the
development proceeds. In the beam of slit-lamp these are seen as
zones of discontinuity. Depending upon the period of development, the
different zones of the lens nucleus include:
 o Embryonic nucleus. It is the innermost part of nucleus which
corresponds to the lens up to the first 3 months of gestation.
It consists of the primary lens fibres which are formed by
elongation of the cells of posterior wall of lens vesicle.
o Fetal nucleus. It lies around the embryonic nucleus and
corresponds to the lens from 3 months of gestation till birth.
Its fibres meet around sutures which are anteriorly Y-
shaped and posteriorly inverted Y-shaped. Infantile nucleus
corresponds to the lens from birth to puberty, and
o Adult nucleus corresponds to the lens fibres formed after puberty
to rest of the life.
- Cortex. It is the peripheral part which comprises the youngest lens
fibres.

Khurana, K. A. (2007). Comprehensive Ophthalmology 4th Edition. New

Delhi: New Age International (P) Ltd.
The crystalline lens is a transparent structure playing main role in the
focussing mechanism for vision. Its physiological aspects include :
- Lens transparency,
- Metabolic activities of the lens, and
- Accommodation
Lens transparency
Factors that play significant role in maintaining outstanding clarity and
transparency of lens are:
- Avascularity,
- Tightly-packed nature of lens cells,
- The arrangement of lens proteins,
- Semipermeable character of lens capsule,
 - Pump mechanism of lens fibre membranes that regulate the
electrolyte and water balance in the lens, maintaining relative
dehydration and
- Auto-oxidation and high concentration of reduced glutathione in the
lens maintains the lens proteins in a reduced state and ensures the
integrity of the cell membrane pump

The normal human lens contains approximately 66% water and 33%
protein, and this amount changes very little with aging. The lens cortex is
more hydrated than the lens nucleus. About 5% of the lens volume is
the water found between the lens fibers in the extracellular spaces.
Within the lens, sodium and potassium concentrations are maintained at 20
millimolars (mM) and 120 mM, respectively. Aqueous and vitreous levels are
markedly different, with the sodium concentration maintained at 150 mM
and potassium at 5 mM.
Calcium homeostasis is also critical to the lens. The normal
intracellular level of calcium in the lens epithelial cells is approximately 100
nanomolars, whereas the exterior calcium level is close to 1 mM. This large
transmembrane calcium gradient is maintained primarily by the calcium
pump (Ca2+-ATPase). The lens cell membranes are also relatively
impermeable to calcium. Free calcium levels in lens fiber cells are much
higher, averaging 10 micromolars. Loss of calcium homeostasis can be
highly disruptive oflens metabolism. Increased levels of calcium can
result in many deleterious changes, including depressed glucose
metabolism, formation of high-molecular-weight protein
aggregates, and activation of destructive proteases.
Membrane transport and permeability are also important
considerations in lens nutrition. Active amino acid transport takes place
at the lens epithelium by a mechanism dependent on the sodium gradient,
which is brought about by the sodium pump. Glucose enters the lens by a
process of facilitated diffusion not directly linked to an active transport
system. The waste products of lens metabolism leave the lens by simple di
ffusion. A variety of substances, including ascorbic acid, myo-inositol, and
choline, have specialized transport mechanisms in the lens.
Metabolism
Lens requires a continuous supply of energy (ATP) for active transport
of ions and aminoacids, maintenance of lens dehydration, and for a
continuous protein and GSH synthesis. Most of the energy produced is
utilized in the epithelium which is the major site of all active transport
processes. Only about 10-20% of the ATP generated is used for protein
synthesis.
Source of nutrient supply. The crystalline lens, being an avascular
structure is dependent for its metabolism on chemical exchanges with
the aqueous humour. The chemical composition of the lens vis a vis
aqueous humour and the chemical exchange between the two is depicted in
Fig. 8.3.
Pathways of glucose metabolism. Glucose is very essential for the
normal working of the lens. Metabolic activity of the lens is largely limited to
epithelium, and cortex, while the nucleus is relatively inert. In the lens, 80%
glucose is metabolised anaerobically by the glycolytic pathway, 15
percent by pentose hexose monophosphate (HMP) shunt and a small
proportion via oxidative Kreb's citric acid cycle. Sorbitol pathway is
relatively inconsequential in the normal lens; however, it is extremely
important in the production of cataract in diabetic and galactosemic patients.

Over time, lens proteins aggregate to form very large particles that
become water insoluble and that scatter light, thus increasing the opacity of
the lens. However, it should be noted that the water-insoluble protein
fraction increases with age, even if the lens remains relatively transparent.
Conversion of the water-soluble proteins into water-insoluble proteins
appears to be a natural process in lens fiber maturation, but it may occur to
excess in cataractous lenses.
In cataracts with significant browning of the lens nucleus (brunescent
cataracts), the increase in the amount of water-insoluble protein correlates
well with the degree of opacification.
In markedly brunescent cataracts, as much as 90% of the nuclear
proteins may be in the insoluble fraction. Associated oxidative changes
occur, including protein-ta-protein and protein-to-glutathione disulfide bond
formation. These changes produce decreased levels of the reduced form of
glutathione and increased levels of glutathione disulfide (oxidized
glutathione) in the cytoplasm of the nuclear fiber cells. It is the general view
that glutathione is essential to maintain a reducing environment in the lens
cytoplasm. Depletion of the reduced form of glutathione accelerates protein
cross-linking, protein aggregation, and light scattering.
With age and, more notably, with brunescent nuclear cataract
formation, the nuclear proteins become increasingly insoluble in urea. In
addition to the increased formation of disulfide bonds, these nuclear proteins
are highly cross-linked by nondisulfide bonds.
This insoluble protein fraction contains yellow-to-brown pigments that
are found in higher concentration in nuclear cataracts. Increased
fluorescence is generated by the nondisulfide cross-links that form in
brunescent nuclear cataracts.
Hejtmancik jF, Piatigorsky j. Lens proteins and their molecular
biology. In: Albert DM. jakobiec FA, eds. Principles and Practice of
Ophthalmology. 2nd ed. Philadelphia: Saunders; 2000: 1409-1428.
 Rate limiting

Feedback (-)

Glutation reductase and aldose reductase act

Low affinity to Glucose

rmeability of the lens to sorbitol

Low affinity to Sorbitol Stimulated

Sorbitol accumulation

Rate limiting

NADP accumulation

Feedback (-)

creased osmotic gradient

25% ATP
3%
Drawing in water

swelling of the fibers

on of the normal cytoskeletal architecture
opacification of the lens
Oxidative Damage and Protective Mechanisms
Free radicals are generated in the course of normal cellular metabolic
activities and may also be produced by external agents such as radiant
energy. These highly reactive free radicals can lead to the damage of lens
fibers. Peroxidation of lens fiber plasma or lens fiber plasma membrane lipids
has been suggested as a factor contributing to lens opacification.
In the process of lipid peroxidation, the oxidizing agent removes a
hydrogen atom from the polyunsaturated fatty acid, forming a fatty acid
radical, which, in turn, attacks molecular oxygen, forming a lipid peroxy
radical. This reaction may propagate the chain, leading to the formation of
lipid peroxide (LOOH), which eventually can react further to yield
malondialdehyde (MDA), a potent cross-linking agent. It has been
hypothesized that MDA cross-reacts with membrane lipids and proteins,
rendering them incapable of performing their normal functions.
Because oxygen tension in and around the lens is normally low, free
radical reactions may not involve molecular oxygen; instead, the free
radicals may react directly with molecules. DNA is easily damaged by free
radicals. Some of the damage to the lens is reparable, but some may be
permanent. Free radicals can also attack the proteins or membrane lipids in
the cortex. No repair mechanisms are known to ameliorate such damage,
which increases with time. In lens fibers, where protein synthesis no longer
takes place, free radical damage may lead to polymerization and cross-
linking of lipids and proteins, resulting in anincrease in the water-insoluble
protein content.
The lens is equipped with several enzymes that protect against free
radical or oxygen damage. These include glutathione peroxidase, catalase,
and superoxide dismutase. Superoxide dismutase catalyzes the destruction
of the superoxide anion, O2-, and produces hydrogen peroxide: 2 O2- 2H+ -
2H2O2+ O2. Catalase may break down the peroxide by the reaction: 2H 2O2
2H2O + O2. Glutathione peroxidase catalyzes the reaction: 2GSH +LOOH
GSSG + LOH + H2O. The glutathione disulfide (GSSG) is then reconverted
toglutathione (GSH) by glutathione reductase, using the pyridine nucleotide
NADPH provided by the HMP shunt as the reducing agent: GSSG + NADPH +
H+ 2GSH + NADP+. Thus, glutathione acts indirectly as a major free
radical scavenger in the lens. In addition, both vitamin E and ascorbic acid
are present in the lens. Each of these substances can act as a free radical
scavenger and thus protect against oxidative damage.
Exposure of the lens to an increased level of oxygen during long-term
hyperbaric oxygen therapy leads to a myopic shift, increased opacification of
the lens nucleus and, in many cases, the formation of nuclear cataracts. The
lens is also exposed to increased levels of oxygen during retinal surgery and
for months following vitrectomy. Because vitrectomy is associated with very
high rates of nuclear cataract formation, it has been suggested that the low
oxygen level existing around the lens protects it from oxidative damage and
that loss of the gel structure of the vitreous body increases exposure of the
lens to oxygen and the risk of nuclear cataracts.
Andley UP, Liang JJN, Lou ME Biochemical mechanisms of age-
related cataract. In: Albert DM, Jakobiec FA, eds. Principles and
Practice of Ophthalmology. 2nd ed. Philadelphia: Saunders; 2000:
1428-1449.
Beebe DC. Lens. In: Kaufman pL, Aim A, eds. Adler's Physiology
of the Eye: Clinical Applimtion. 10th ed. St Louis: Mosby; 2003: 117-
158.
Bloemendal H, de Jong W, Jaenicke R, Lubsen NH, Slingsby C,
Tardieu A. Aging and vision: structure, stability and function of lens
crystallins. Prog Biophys Mol Bioi. 2004;86(3):407 -485.
Jaffe NS, Horwitz J. Evolution and molecular biology oflens
proteins. In: Podos SM, Yanoff M, eds. Textbook of Ophthalmology,
vol 3, Lens and Cataract. New York: Gower Medical Publishing; 1992.

3. Katarak
Definition

The crystalline lens is a transparent structure. Its transparency may be

disturbed due to degenerative process leading to opacification of lens fibres.
Development of an opacity in the lens is known as cataract.

Classification

A. Etiological classification
a. Congenital and developmental cataract
b. Acquired cataract
1. Senile cataract
2. Traumatic cataract (see page 405)
3. Complicated cataract
4. Metabolic cataract
5. Electric cataract
6. Radiational cataract
7. Toxic cataract e.g.,
a. Corticosteroid-induced cataract
b. Miotics-induced cataract
c. Copper (in chalcosis) and iron (in siderosis) induced
cataract.
 8. Cataract associated with skin diseases (Dermatogenic
cataract).
9. Cataract associated with osseous diseases.
10. Cataract with miscellaneous syndromes e.g.,
a. Dystrophica myotonica
b. Down's syndrome.
c. Lowe's syndrome
d. Treacher - Collin's syndrome
B. Morphological classification (Fig. 8.4)
a. Capsular cataract. It involves the capsule and may be:
i. Anterior capsular cataract
ii. Posterior capsular cataract
b. Subcapsular cataract. It involves the superficial part of the
cortex (just below the capsule) and includes:
i. Anterior subcapsular cataract
ii. Posterior subcapsular cataract
c. Cortical cataract. It involves the major part of the cortex.
d. Supranuclear cataract. It involves only the deeper parts of
cortex (just outside the nucleus).
e. Nuclear cataract. It involves the nucleus of the crystalline lens.

KATARAK

DEVELOPMENTAL DEGENERATIF

A.Hialoidea
persisten PRIMER SEKUNDER
Polaris anterior
Polaris posterior Insipien
Aksialis Imatur
Zonularis Matur
Stelata Hipermatu
Totalis
Khurana,
r
K. A. (2007). Comprehensive Ophthalmology 4th Edition. New
Kongenital
Delhi: New Age International (P) Ltd.
membranasea
Clinical presentations

Common

Change in visionreduced acuity, contrast sensitivity, or color

appreciation, glare, monocular diplopia, or ghosting.
Change in refractiontypically a myopic shift due to nuclear sclerosis.
Change in fundus viewclinicians may have difficulty looking in long
before the patients feel they have difficulties looking out. This may be
a problem when trying to monitor or treat posterior segment disease
such as diabetic retinopathy or macular degeneration.

Uncommon

Phacomorphic glaucoma

The large cataractous lens may cause anterior bowing of the iris with
secondary angle closure. Presentation may occur as acute angle
closure with high IOP, shallow AC, and fixed semi dilated pupil.
Phacomorphic glaucoma can be distinguished from primary angle closure
glaucoma by the presence of an ipsi lateral swollen cataractous lens
and contralateral open angle with deep AC.

Phacolytic glaucoma
The hypermature cataract loses soluble lens proteins through the
anterior capsule, causing trabecular obstruction and subsequent
secondary open angle glaucoma. Note raised IOP, lens protein in a deep
AC (may form a pseudohypopyon), open angles, and hypermature cataract.

Phacoanaphylactic uveitis (i.e., phacoantigenic, lens-induced granulomatous

uveitis)

Phacoanaphylactic uveitis is a misnomer, as the inflammatory response is

not a type I phacoanyphylactic response but a granulomatous
inflammatory response to lens proteins. This condition usually follows
traumatic capsular rupture or postoperative retention of lens material (it
must be distinguished from endophthalmitis). The IOP may be high, normal,
or low.

4. Indikasi operasi katarak

Role of Quality of Life

Cataract/IOL surgery improves quality of life better than any other medical
procedure known to mankind. Cataract surgery is indicated when the
patient's quality of life is being affected by visual impairment, when
there is a diminution in vision if the patient is exposed to light or at
night, and when the preoperative evaluation indicates that the
potential for restoration of sight is good. How much a patient's quality
of life is impaired from a cataract is relative, varying with the patient's
occupation and age. The key factor is not to wait until a nuclear
cataract becomes hard. With time, the lens fiber density becomes a hard
nuclear brunescent cataract. With most modern phacoemulsification
techniques it may become increasingly difficult to perform surgery if
the lens becomes extremely dense or brunescent.

Waiting too long may require that the surgeon operate on dense nuclear
cataracts, which increases the risk of posterior capsule tears, whether we
perform planned extracapsular or a phacoemulsification. This complication
may lead to other rather serious problems such as dislocated nucleus,
retinal detachment, macular edema, bullous keratopathy and
inflammation.

The Role of Visual Acuity

There are very few strict criteria for recommending cataract surgery. In the
United States, however, many professional review organizations have
indicated that the reduction of Snellen distance acuity to 20/40 or
worse as a result of cataract is sufficient indication in and of itself
for cataract surgery. This is generally the minimum standard for
driving. In some of the advanced, developed countries, being unable to
obtain a driver's license may seriously affect a person's life because he/she
may be disqualified to drive to the market or shop to purchase food and
other materials essential to daily existence. However, in many cases surgery
may be indicated without reduction of visual acuity to the level of 20/40 if
the patient has difficulty performing activities of daily living.
Because patients have varying occupational and recreational needs, some
patients may need cataract surgery prior to having their vision reduced to
20/40 by standard tests. In addition, near vision in some cases may be
compromised more than distance acuity particularly in the case of central
posterior subcapsular cataracts. The trend toward early removal of cataract
offers the advantage of operating on a younger age group, many of whom
are still productive members of society. Their need for early return to
their usual lifestyle is extremely important.

The older population, often living alone, also benefits from early
visual recovery. These high expectations and needs require that the
ophthalmic surgeon perform superior surgery to obtain excellent
postoperative visual acuity and early visual rehabilitation.

As emphasized by Gimbel, symptoms of cataracts include complaints of a

yellowing of vision, glare, halos, decreased night vision, and generally
blurred vision in adults. Nuclear sclerosis which is a typical form of age-
related cataracts may also induce a myopic shift and patients may give a
history of having changed their glasses several times within a short
period of time. In children cataracts may present as leukocoria and
may result in strabismus and/or amblyopia if not treated promptly.

Contrast Sensitivity and Glare Disability

In evaluating a patient with cataract and in the process of deciding when

that person requires cataract/IOL surgery, it is fundamental to keep always in
mind that standard Snellen acuity measurements do not give any
information with regard to symptoms of disabling glare. As a matter of fact,
very good visual acuity with the Snellen chart in the physician's examining
room may lead the ophthalmologist to making the wrong decision and
recommendations unless he or she takes other factors into consideration. In
later years, we have become increasingly aware that diminished contrast
sensitivity which interferes with sharp vision under different color
backgrounds or target luminance, is an essential element of sight and a
highly limiting factor in the presence of cataract. This is perceived by the
patient for example when he or she is unable to read a computer screen at
the airport if the background is light blue and the print is light yellow even
though visual acuity in the physician's refracting lane was 20/30 or 20/25.
The same for disabling glare.

These are two additional very important issues in determining when the
cataract should be removed. For many years this judgment has been based
on Snellen visual acuity. But a patient can score quite well on Snellen acuity
while suffering in real life. Posterior subcapsular cataracts are notorious for
interfering with reading, even when distance vision is good, and may induce
a great deal of glare. Snellen acuity may be 20/20 or 20/25, but against
oncoming headlights while driving at night, for instance, the glare may
diminish the functional vision to 20/100 or even 20/200. People with nuclear
sclerosis, the most common form of cataract, tend to be bothered by
decreased contrast sensitivity rather than glare. Although glare disability and
contrast sensitivity are distinctly different, the terms often are erroneously
interchanged. The testing characteristics of each, however, may overlap, and
a reduction in one function often leads to a diminution in the other, further
adding to the confusion of their differences. As clarified by Samuel Masket,
M.D., glare disability is a light-induced visual symptom. Contrast sensitivity
testing is a means of vision analysis, analogous to a markedly expanded
form of Snellen acuity evaluation at varied amounts of target luminance.
Contrast Sensitivity Characteristics

Like audiometry, which measures the sensitivity of the hearing apparatus to

stimuli at different audio frequencies, contrast sensitivity analysis
determines the ability of the visual system to perceive objects of differing
contrasts as well as sizes.

A patient who has a reduction in contrast sensitivity might perceive the

small, highly contrasted targets on a Snellen test line but be incapable of
identifying larger objects at reduced contrast. There are alterations in the
visual system that can cause visual loss that are not detected by the
determination of Snellen visual acuity but may be evaluated by testing of
contrast sensitivity function. This is unlike disabling glare, which determines
the effect of extraneous light on visual performance. Contrast sensitivity
evaluation is a measurement of the resolving power of the eye at varied
contrasts between image and background.

A number of useful contrast and glare sensitivity testing methods have been
devised. They are accessible and inexpensive. Unfortunately, standardization
of these techniques has not yet been achieved. It is essential that the
clinician be fully aware of these two factors that may impinge on the
patient's real vision or quality of vision, in addition to the Snellen acuity test.

Relation of Glare to Type of Cataract

Neumann et al. have determined that nuclear cataract is more likely to be

associated with nighttime glare disability, while cortical cataract formation is
associated with daylight glare, and posterior subcapsular cataracts may
induce glare disability associated with bright, direct sunlight or bright central
light sources. Cortical cataracts seem more likely to cause glare symptoms
than nuclear cataracts. Masket points out that frequently, patients with
dense central posterior subcapsular cataracts frequently retain excellent
distance Snellen acuity as measured in the refracting lane, yet they perform
poorly on any of the available glare testing devices. Such patients may have
severely lower visual function during daylight driving although they do well
with the Snellen acuity chart. In essence, the Snellen chart evaluates
quantity of vision. Contrast sensitivity tests evaluate quantity and quality of
vision. The equipment to perform the test is accessible and inexpensive. It is
basically a chart about 0.3 meters in size and it costs about US$200.00

5. Anatomi dan fisiologi dari Lensa, Corpus Vitreum, dan Retina

Vitreous humour is an inert, transparent, jelly-like structure that fills the
posterior four-fifth of the cavity of eyeball and is about 4 ml in volume. It is a
hydrophilic gel that mainly serves the optical functions. In addition, it
mechanically stabilizes the volume of the globe and is a pathway for
nutrients to reach the lens and retina.

Structure. The normal youthful vitreous gel is composed of a network of

randomly-oriented collagen fibrils interspersed with numerous
spheroidal macromolecules of hyaluronic acid. The collapse of this
structure with age or otherwise leads to conversion of the gel into sol. The
vitreous body can be divided into two parts: the cortex and the nucleus (the
main vitreous body).
1. Cortical vitreous. It lies adjacent to the retina posteriorly and lens,
ciliary body and zonules anteriorly. The density of collagen fibrils is greater in
this peripheral part. The condensation of these fibrils form a false
anatomic membrane which is called as anterior hyaloid membrane
anterior to ora serrate and posterior hyaloid membrane posterior to
ora. The attachment of the anterior hyaloid membrane to the posterior lens
surface is firm in the young and weak in the elderly whereas posterior
hyaloid membrane remains loosely attached to the internal limiting
membrane of the retina throughout life. These membranes cannot be
discerned in a normal eye unless the lens has been extracted and posterior
vitreous detachment has occurred.

2. The main vitreous body (nucleus). It has a less dense fibrillar

structure and is a true biological gel. It is here where liquefactions
of the vitreous gel start first. Microscopically the vitreous body is
homogenous, but exhibits wavy lines as of watered silk in the slit-lamp
beams. Running down the centre of the vitreous body from the optic disc to
the posterior pole of the lens is the hyaloid canal (Cloquets canal) of
doubtful existence in adults. Down this canal ran the hyaloid artery of the
foetus.

Attachments. The part of the vitreous about 4 mm across the ora

serrata is called as vitreous base, where the attachment of the
vitreous is strongest. The other firm attachments are around the
margins of the optic disc, foveal region and back of the crystalline
lens by hyloidocapsular ligament of Wieger.
 6. Vascular disease of retina
DIABETIC RETINOPATHY

The exact cause of diabetic microvascular disease is unknown. It is believed

that exposure to hyperglycemia over an extended period results in a
number of biochemical and physiologic changes that ultimately
cause endothelial damage. Specific retinal capillary changes include
selective loss of pericytes and basement membrane thickening,
which favor capillary occlusion and retinal non perfusion, as well as
decompensation of the endothelial barrier function, which allows
serum leakage and retinal edema to occur. A large number of
hematologic and biochemical abnormalities have been correlated with the
prevalence and severity of retinopathy:

increased platelet adhesiveness

increased erythrocyte aggregation
 abnormal serum lipids
defective fibrinolysis
abnormal levels of growth hormone
up regulation of vascular endothelial growth factor (VEGF)
abnormalities in serum and whole blood viscosity

However, the precise role of these abnormalities-individually or in

combination-in the pathogenesis of retinopathy is not well defined.

Retinopati Diabetika:

Terdapat 4 proses biokimiawi yang terjadi pada hiperglikemia kronis yang

diduga berhubungan dengan timbulnya retinopati diabetik, antara lain:

- Akumulasi Sorbitol
Hiperglikemi kronis peningkatan aktv enzim aldose reduktase (pada
jarringan saraf, retina, lensa, glomerolus dan dinding pembuluh
darahakumulasi dari sorbitol. Sorbitol merupakan suatu senyawa gula
dan alkohol yang tidak dapat melewati membrana basalis sehingga
akan tertimbun dalam jumlah yang banyak dalam sel. Kerusakan sel
terjadi akibat akumulasi sorbitol yang bersifat hidrofilik sehingga sel
menjadi bengkak akibat proses osmotik.
- Pembentukan protein kinase C (PKC)
o Hiperglikemiapeningkatan sintesis de novo dari diasilgliserol
aktivitas PKC di retina dan sel endotel vaskular meningkat,
 o PKC diketahui memiliki pengaruh terhadap agregasi trombosit,
permeabilitas vaskular, sintesis growth factor dan vasokonstriksi.
Peningkatan PKC secara relevan meningkatkan komplikasi
diabetika, dengan mengganggu permeabilitas dan aliran darah
vaskular retina.
o Peningkatan permeabilitas vaskularterjadinya ekstravasasi
plasma viskositas darah intravaskular meningkat disertai
dengan peningkatan agregasi trombosit yang saling berinteraksi
menyebabkan terjadinya trombosis.
o Selain itu, sintesis growth factorpeningkatan proliferasi sel otot
polos vaskular dan matriks ekstraseluler termasuk jaringan
fibrosa,penebalan dinding vaskular, ditambah dengan aktivasi
endotelin-1 yang merupakan vasokonstriktorlumen vaskular
makin menyempit. Seluruh proses tersebut terjadi secara
bersamaan, hingga akhirnya menyebabkan terjadinya oklusi
vaskular retina.
- Pembentukan Advanced Glycation End Product (AGE)
o Glukosa mengikat gugus amino membentuk ikatan kovalen
secara non enzimatik. Proses tersebut pada akhirnya akan
menghasilkan suatu senyawa AGE. Efek dari AGE ini saling
sinergis dengan efek PKC dalam menyebabkan peningkatan
permeabilitas vaskular, sintesis growth factor, aktivasi endotelin
1 sekaligus menghambat aktivasi nitrit oxide oleh sel
endotelakan meningkatkan risiko terjadinya oklusi vaskular
retina.
o AGE terdapat di dalam dan di luar sel, berkorelasi dengan kadar
glukosa. Akumulasi AGE mendahului terjadinya kerusakan sel.
Pada pasien DM, sedikit saja kenaikan glukosa maka
meningkatkan akumulasi AGE yang cukup banyak, dan akumulasi
ini lebih cepat pada intrasel daripada ekstrasel.
- Pembentukan Reactive Oxygen Speciesi (ROS)
o ROS dibentuk dari oksigen dengan katalisator ion metal atau
enzim yang menghasilkan hidrogen peroksida (H2O2),
-
superokside (O2 ).
o Pembentukan ROS meningkat melalui autooksidasi glukosa pada
jalur poliol dan degradasi AGE. Akumulasi ROS di jaringan akan
menyebabkan terjadinya stres oksidatif yang menambah
kerusakan sel.
 Pandelaki K. 2007. Retinopati Diabetik dalam Buku
Ajar Ilmu Penyakit Dalam. Edisi IV Jilid III. Editor: Aru W.
Sudoyo dkk. Departemen ilmu penyakit dalam Fakultas
Kedokteran Universitas Indonesia: Jakarta
Classification

Diabetic retinopathy has been variously classified. Presently followed

classification is as follows:

1. Non-proliferative diabetic retinopathy (NPDR)

a. Mild NPDR
b. Moderate NPDR
c. Severe NPDR
d. Very severe NPDR
2. Proliferative diabetic retinopathy (PDR)
3. Diabetic maculopathy
4. Advanced diabetic eye disease (ADED)

Non-proliferative diabetic retinopathy (NPDR)

Ophthalmoscopic features of NPDR include:

Microaneurysms in the macular area (the earliest detectable lesion).

Retinal haemorrhages both deep (dot and blot haemorrhages) and
superficial haemorrhages (flame-shaped).
Hard exudates-yellowish-white waxy-looking patches are arranged in
clumps or in circinate pattern. These are commonly seen in the
macular area.
Retinal oedema characterized by retinal thickening.
Cotton-wool spots (if > 8, there is high risk of developing PDR).
Venous abnormalities, beading, looping and dilatation.
Intraretinal microvascular abnormalities (IRMA).
Dark-blot haemorrhages representing haemorrhagic retinal infarcts.

On the basis of severity of the above findings the NPDR has been
further classified as under:

1. Mild NPDR (Fig. 11.14A).

At least one microaneurysm or intraretinal hemorrhage.

Hard/soft exudates may or may not be present.

2. Moderate NPDR (Fig. 11.14B)

Moderate microaneurysms/intraretinal hemorrhage.

Early mild IRMA.

Hard/soft exudates may or may not present.

3. Severe NPDR. Any one of the following (4-2-1 Rule) (Fig. 11.14C):

Four quadrants of severe microaneurysms/ intraretinal hemorrhages.

Two quadrants of venous beading.

One quadrant of IRMA changes.

4. Very severe NPDR. Any two of the following (4-2-1 Rule) (Fig. 11.14D):

Four quadrants of severe microaneurysms/ intraretinal hemorrhages.

Two quadrants of venous beading.

One quadrant of IRMA changes.

Proliferative diabetic retinopathy (PDR)

Proliferative diabetic retinopathy (Figs. 11.14 E&F) develops in more than 50

percent of cases after about 25 years of the onset of disease. Therefore, it is
more common in patients with juvenile onset diabetes. The hallmark of
PDR is the occurrence of neovascularisation over the changes of very
severe non-proliferative diabetic retinopathy. It is characterised by
proliferation of new vessels from the capillaries, in the form of
neovascularisation at the optic disc (NVD) and/or elsewhere (NVE) in
the fundus, usually along the course of the major temporal retinal
vessels. These new vessels may proliferate in the plane of retina or spread
into the vitreous as vascular fronds. Later on condensation of connective
tissue around the new vessels results in formation of fibrovascular epiretinal
membrane. Vitreous detachment and vitreous haemorrhage may
occur in this stage.

Types. On the basis of high risk characteristics (HRCs) described by diabetic

retinopathy study (DRS) group, the PDR can be further classified as below:

1. PDR without HRCs (Early PDR) (Fig. 11.14E), and

2. PDR with HRCs (Advanced PDR). High risk characteristics (HRC) of PDR are
as follows (Fig. 11.14F):

NVD 1/4 to 1/3 of disc area with or without vitreous haemorrhage (VH)
or pre-retinal haemorrhage (PRH)
NVD < 1/4 disc area with VH or PRH
NVE > 1/2 disc area with VH or PRH