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HIGHER STATE EDUCATIONAL INSTITUTION OF UKRAINE
"UKRAINIAN MEDICAL STOMATOLOGICAL ACADEMY"
“APPROVED”
at the meeting of otorhinolaryngology
with ophthalmology department
“___”__________20___
Head of the Department
____ S.B. Bezshapochny
METHODICAL INSTRUCTIONS FOR
PRACTICAL CLASSES
OF OPHTHALMOLOGY
FOR MEDICAL FACULTY STUDENTS
Subject
Ophthalmology
Topic № 12-13
Content module №
Theme:
Glaucoma
Course
IV
Faculty
Medical
1. ACTUALITY OF THE TOPIC:
There are a number of diseases, which are not lead to death, but deprive person of
joy to perceive the wonderful world of sun and colors. "Dark Water," "yellow
water", "green cataract", "ophthalmic migraine", "glaucoma" - a name that people
gave to one of the most insidious diseases of the eye. Significant spread of primary
glaucoma, difficulty of early diagnosis and prognosis is serious reason for constant
attention to this disease by the medical workers of different professions (dentists,
physicians, surgeons, etc.).
Today in Ukraine more than 40.2% of patients with glaucoma in the adult
population and about 105 million glaucoma patients in the world.
There are 5 factors that determine the socio-economic importance of glaucoma:
- A significant number of patients
- A large percentage of incurable blindness in patients with glaucoma
- A chronic course of illness
- Irreversible loss of visual function
- Significant public spending on health, social and personal rehabilitation of
patients with glaucoma.
2. AIMS
- To understand current state of the problem
To learn:
- Research methods of measurement IOP
- Classification of glaucoma
- Symptoms of an acute attack of glaucoma and first aid
- Treatment of congenital glaucoma
- Clinic of primary glaucoma
- Treatment of primary glaucoma
- Diseases that can lead to secondary glaucoma
- Clinic and treatment of secondary glaucoma.
3. TASKS FOR SELF-TRAINING FOR PRACTICAL CLASSES
3.1 List of key terms, parameters, characteristics to learn for the topic
Term
1. Glaucoma
2. Tonometry
3. Normal IOP
4. Types of the angle of anterior
chamber of the eye
5. Gonioscopy
Definition
Glaucoma is a chronic, progressive
disease that affects the optic nerve to
the development of a specific optic
neuropathy, characteristic changes in
the visual field and decreased visual
function, in some cases accompanied by
a periodic or persistent increase in
intraocular pressure
Measurement of intraocular preasure
Tonometric - 16-25 mm Hg, true - 9-22
mm Hg.
Open - the angle in which all the
drainage structures and channels for the
outflowing of intraocular fluid are
available and closed - the angle blocked
by the root of the iris.
Method of studying structure of the
angle of anterior chamber of the eye
with help of lenses.
3.2. Questions:
1. Anatomical and physiological features of structure of the anterior chamber angle
of the eye.
2. Mechanism of regulation of IOP.
3. Methods IOP study.
4. Gonioscopy, types of the anterior chamber angle.
5. The classification of glaucoma.
6. Pathogenesis, clinic and treatment of patients with congenital glaucoma.
7. The etiology of primary glaucoma.
8. Classification of primary glaucoma, its detailed characteristics.
9. The volume of the necessary studies in patients with glaucoma.
10. The principles of conservative therapy of glaucoma.
11. Clinic of acute attack of angle-closure glaucoma.
12. The methods of surgical treatment of glaucoma.
13. Preventing the emergence and development of glaucoma. The principles of
clinical examination.
3.3 Practical skills:
1. Measurement of IOP by palpation
2. Evaluating measurement of IOP for Maklakov..
3. Emergency care during an acute attack of glaucoma.
4. CONTENT OF THE TOPIC:
The term glaucoma refers to a group of diseases that have in common a characteristic
optic neuropathy with associated visual function loss. Although elevated intraocular pressure
(IOP) one of the primary risk factors, its presence or absence does not have a role in the
definition of the disease. Three factors determine the IOP:
- the rate of aqueous humor production by the ciliary body;
- resistance to aqueous outflow across the trabecular meshwork - Schlemm's canal system; the
specific site of resistance is generally thought to be in the juxtacanalicular meshwork;
- the level of episcleral venous pressure.
In most individuals, the optic nerve and visual field changes seen in glaucoma are
determined by both the level of the IOP and the resistance of the optic nerve axons to pressure
damage.
Regardless of the IOP the presence of glaucoma is defined by a characteristic optic
neuropathy consistent with excavation and undermining of the neural and connective tissue
elements of the optic disc and by the eventual development of characteristic visual field defects.
Preperimetric glaucoma is a term that is sometimes used to denote glaucomatous changes in the
optic disc in patients with normal visual fields, as determined by white-on-white perimetry.
Since the correct application of this term depends on the sensitivity of the visual function test
used, the development of new, more sensitive tests may allow earlier confirmation of this type of
glaucoma, while the patient is within this preperimetric phase.
Classification of glaucoma
Type
Open-angle glaucoma
Primary open-angle glaucoma
Normal-tension glaucoma
Characteristics
Not associated with known ocular or systemic
disorders that cause increased resistance to
aqueous outflow or damage to optic nerve;
usually associated with elevated IOP
Considered in continuum of POAG;
terminology often used when IOP is not
elevated
Juvenile open-angle glaucoma
Terminology often used when open-angle
glaucoma diagnosed at young age (typically
10- 30 years of age)
Glaucoma suspect
Normal optic disc and visual field associated
with elevated IOP
Suspicious optic disc and/or visual field with
normal lOP
Secondary open-angle glaucoma
Increased resistance to trabecular meshwork
outflow associated with other conditions
(pigmentary glaucoma, phacolytic glaucoma,
steroid-induced glaucoma, exfoliation, anglerecession glaucoma)
Increased posttrabecular resistance to outflow
secondary to elevated episcleral venous
pressure (carotid cavernous sinus fistula)
Angle-closure glaucoma
Primary angle-closure glaucoma with relative
pupillary block
Acute angle closure
Subacute angle closure
(intermittent angle closure)
Chronic angle closure
Secondary angleclosure glaucoma with
pupillary block
Movement of aqueous humor from posterior
chamber to anterior chamber restricted;
peripheral iris in contact with trabecular
meshwork
Occurs when IOP rises rapidly as a result of
relatively sudden blockage of the trabecular
meshwork
Repeated, brief episodes of angle closure with
mild symptoms and elevated IOP, often a
prelude to acute angle closure
IOP elevation caused by variable portions of
anterior chamber angle being permanently
closed by peripheral anterior synechiae
(For example, swollen lens, secluded pupil)
Secondary angleclosure glaucoma without
pupillary block
Posterior pushing mechanism: lens-iris
diaphragm pushed forward (posterior segment
tumor uveal effusion)
Anterior pulling mechanism: anterior segment
process pulling iris forward to form peripheral
anterior synechiae (iridocorneal endothelial
syndrome, neovascular glaucoma,
inflammation)
Plateau iris syndrome
An anatomic variation in the iris root in which
narrowing of the angle occurs independent of
pupillary block
Childhood glaucoma
Primary congenital glaucoma
Glaucoma associated with congenital
anomalies
Secondary glaucoma in infants and children
Primary glaucoma present from birth to first
few years of life
Associated with ocular disorders (anterior
segment dysgenesis, aniridia)
Associated with systemic disorders (rubella,
Lowe syndrome)
(For example, glaucoma secondary to
retinoblastoma or trauma)
Intraocular Pressure and Aqueous Humor Dynamics
Aqueous humor formation is a biological process that is subject to circadian rhythms.
Aqueous humor is formed by the ciliary processes, each of which is composed of a double layer
of epithelium over a core of stroma and a rich supply of fenestrated capillaries. Each of the 80 or
so processes contains a large number of capillaries, which are supplied mainly by branches of the
major arterial circle of the iris. The apical surfaces of both the outer pigmented and the inner
nonpigmented layers of epithelium face each other and are joined by tight junctions, which are
an important component of the bloodaqueous barrier. The inner nonpigmented epithelial cells,
which protrude into the posterior chamber, contain numerous mitochondria and microvilli; these
cells are thought to be the actual site of aqueous production. The ciliary processes provide a large
surface area for secretion.
Aqueous humor formation and secretion into the posterior chamber result from:
-
active secretion, which takes place in the double-layered ciliary epithelium,
-
ultrafiltration,
-
simple diffusion.
Active secretion, or transport. consumes energy to move substances against an electrochemical
gradient and is independent of pressure. The identity of the precise ion or ions transported is not
known, but sodium, chloride, and bicarbonate are involved. Active secretion accounts for the
majority of aqueous production and involves, at least in part, activity of the enzyme carbonic
anhydrase II. Ultrafiltration refers to a pressure-dependent movement along a pressure gradient.
In the ciliary processes, the hydrostatic pressure difference between capillary pressure and IOP
favors fluid movement into the eye, whereas the oncotic gradient between the two resists fluid
movement. Diffusion is the passive movement of ions across a membrane related to charge and
concentration.
In humans, aqueous humor has an excess of hydrogen and chloride ions, an excess of ascorbate,
and a deficit of bicarbonate relative to plasma. Aqueous humor is essentially protein free, which
allows for optical clarity and reflects the integrity of the blood-aqueous barrier of the normal eye.
Albumin accounts for about half of the total protein. Other components include growth factors;
several enzymes, such as carbonic anhydrase, lysozyme, diamine oxidase, plasminogen activator,
dopamine-hydroxylase, and phospholipase A2; and prostaglandins, cyclic adenosine
monophosphate (cAMP), catecholamines, steroid hormones, and hyaluronic acid. Aqueous
humor is produced at an average rate of2.0-2.5 ~μL|min, and its composition is altered as it
flows from the posterior chamber, through the pupil, and into the anterior chamber. This
alteration occurs across the hyaloid face of the vitreous, the surface of the lens, the blood vessels
of the iris, and the corneal endothelium and is secondary to other dilutional exchanges and active
processes.
Aqueous formation varies diurnally and drops during sleep. It also decreases with age, as does
outflow facility. The rate of aqueous formation is affected by a variety of factors, including
-
integrity of the blood-aqueous barrier
-
blood flow to the ciliary body
-
neurohumoral regulation of vascular tissue and the ciliary epithelium
Aqueous Humor Outflow
Aqueous humor outflow occurs by 2 major mechanisms: pressure-dependent outflow
and pressure-independent outflow. The facility of outflow varies widely in normal eyes. The
mean value reported ranges from 0.22 to 0.30 μL/min/mm Hg. Outflow facility decreases with
age and is affected by surgery, trauma, medications, and endocrine factors. Patients with
glaucoma and elevated IOP have decreased outflow facility.
Trabecular Outflow
Traditional thought contended that most of the aqueous humor exits the eye by way of the
trabecular meshwork- Schlemm's canal - venous system. However, recent evidence questions the
exact ratio of trabecular to uveoscleral outflow. As with outflow facility, this ratio is affected by
age and by ocular health . The meshwork is classically divided into 3 parts (Fig 1). The uveal
part is adjacent to the anterior chamber and is arranged in bands that extend from the iris root
and the ciliary body to the peripheral cornea. The corneoscleral meshwork consists of sheets of
trabeculum that extend from the scleral spur to the lateral wall of the scleral sulcus. The
juxtacanalicular meshwork, which is thought to be the major site of outflow resistance, is
adjacent to, and actually forms the inner wall of, Schlemm's canal. Aqueous moves both across
and between the endothelial cells lining the inner wall of Schlemm's canal
The trabecular meshwork is composed of multiple layers, each of which consists of a
collagenous connective tissue core covered by a continuous endothelial layer covering. It is the
site of pressure-dependent outflow. The trabecular meshwork functions as a 1-way valve that
permits aqueous to leave the eye by bulk flow but limits flow in the other direction, independent
of energy.
In most older eyes, trabecular cells contain a large number of pigment granules with in their
cytoplasm that give the entire meshwork a brown or muddy appearance. In addition, the number
of trabecular cells decreases with age, and the basement membrane beneath them thickens. There
are relatively few trabecular cells- approximately 200,000- 300,000 cells per eye.
Schlemm's canal is completely lined with an endothelial layer that does not rest on a continuous
basement membrane. The canal is a single channel, with an average diameter of approximately
370 μm, and is transversed by tubules. The inner wall of Schlemm's canal contains giant
vacuoles that have direct communication with the intertrabecular spaces.
The outer wall is actually a single layer of endothelial cells that do not contain pores. A complex
system of vessels connects Schlemrn's canal to the episcleral veins, which subsequently drain
into the anterior ciliary and superior ophthalmic veins. These, in turn, ultimately drain into the
cavernous sinus.
When IOP is low, the trabecular meshwork may collapse, or blood may reflux into Schlemm's
canal and be visible on gonioscopy.
Uveoscleral Outflow
In the normal eye, any nontrabecular outflow is termed uveoscleral outflow. Uveoscleral outflow
is also termed pressure-independent outflow. A variety of mechanisms are likely involved,
predominantly aqueous passage from the anterior chamber into the ciliary muscle and then into
the supraciliary and suprachoroidal spaces. The fluid then exits the eye through the intact sclera
or along the nerves and the vessels that penetrate it. As noted, uveoscleral outflow is largely
pressure-independent and is believed to be influenced by age. Uveoscleral outflow has been
estimated to account for 5%-15% of total aqueous outflow, but recent studies indicate it may be a
higher percentage of total outflow, especially in normal eyes of young people. It is increased by
cycloplegia, adrenergic agents, prostaglandin analogs, and certain complications of surgery (eg,
cyclodialysis) and is decreased by miotics.
Intraocular Pressure
Normal level of intraocular pressure
Factors influencing intraocular pressure
IOP varies with a number of factors, including the following:
-
time of day,
-
heartbeat,
-
respiration,
-
exercise,
-
fluid intake,
-
systemic medications,
-
topical medications.
`
Methods of examination
Ophthalmoscopy
Ophthalmoscopy should be done routinely in all cases. Accurate ophthalmoscopy through an
undilated pupil is however difficult to perform. Although direct ophthalmoscopy is most
commonly done, indirect ophthalmoscopy and slit-lamp biomicroscopy will be helpful in the
evaluation.
Indirect ophtalmoscopy
Indirect ophthalmoscopy is possible to perform with the patient sitting upright in the examination
chair. The examination room should be dimly lit, and the ophthalmologist should be darkadapted.
Principles
Indirect ophthalmoscopy provides a stereoscopic view of the fundus. The light emitted from the
instrument is transmitted to the fundus through a condensing lens held at the focal point of the
eye which provides an inverted and laterally reversed image of the fundus. This image is viewed
through a special viewing system in the ophthalmoscope. As the power of the condensing lens
decreases the working distance and the magnil1cation are increased but the field of view is
reduced and vice versa.
Gonioscopy
Goldmann gonioscopy
The patient should be advised that the lens will touch the eye but cause not more than slight
discomfort. The patient should also be requested to keep both eyes open at all times and not to
move the head backwards when the lens is being inserted.
a. The preliminary steps are the same as already described for fundus examination.
b. The angle is visualized with the small dome-shaped gonioscopic mirror (if a three-mirror lens
is being used).
c. Initially the mirror is placed at the 12 o'clock position to visualize the interior angle and then
rotated clockwise. The slit beam should be 2mm wide and when viewing different positions it is
usually best to rotate the beam so that its axis is at right angles to the mirror.
d. When the view or the angle is obscured by a convex iris it is possible to 'see over the hill' by
asking the patient to look in the direction of the mirror.
e. When the plane or the iris is flat the patient should be asked to look away from the mirror in
order to obtain a view parallel to the iris with optimal image quality.
Normal angle structures are shown on fig 2
Tonometry
Maklacov tonometry
Other tonometers
Tono-Pen is a hand-held self-contained battery powered portable contact tonometer (Fig. 3). The
probe tip contains a transducer that measures the applied force. A microprocessor analyses the
force/time curve generated by the transducer during corneal indentation to calculate IOP. The
instrument correlates well with Goldmann tonometry although it slightly overestimates a low
IOP and underestimates a high IOP. Its main advantage involves the ability to measure IOP in
eyes with distorted or oedematous corneas as well as through a bandage contact lens.
Non-contact tonometers are based on the principle of applanation but instead of using a prism
the central part of the cornea is flattened by a jet of air. The time required to sufficiently flatten
the cornea relates directly to the level of IOP. The instrument is easy to use and does not require
topical anaesthesia. It is therefore particularly useful for screening by non-ophthalmologists. Its
main disadvantage is that it is accurate only within the low-to-middle range.
The jet of air can startle the patient both with its apparent force and noise. A non-contact
tonometer may be nonportable (fig 4) or portable.
Perimetry
The visual field may be described as an island of vision surrounded by a sea of darkness. It is not
a flat plane but a three-dimensional structure akin to a hill of vision. The outer aspect of the
visual field extends approximately 60° superiorly 60° nasally 80° inferiorly and 90° temporally.
Visual acuity is sharpest at the very top of the hill (i.e. the fovea) and then declines progressively
towards the periphery the nasal slope being steeper than the temporal. The blind spot is located
temporally between 10° and 20°
Confocal scanning laser tomography
Physics. The Heidelberg Retinal Tomograph (HRT) is a scanning laser ophthalmoscope that can
interpret difrerences in the prolile or the optic nerve head and peripapillary retinal nerve fibre
layer (NFL) a to produce a computerized three-dimensional topographical image.
This profile is then compared to a regression analysis derived profile.
- images or the disc and peripapillary retina are shown at the top of the display (Fig. 5). In the
topographic image (top left) the cup is represented in red the neuroretinal rim in green and
the slope in blue.
- the reflectivity image (top right) is divided into six sectors. 1\ green tick within a sector
indicates within normal limits a yellow exclamation mark borderline and a red cross abnormal.
The two cross-section images (top centre and middle) show the amount of cupping in the vertical
and horizontal planes.
Pathology o f Glaucoma.
The pathologic alteration is governed by the severity and duration of raised ocular tension. The
structural alterations in different tissues are as follows:
Cornea. There are edema in all the layers, separation of the basal cells, presence of filaments,
bullae and pannus. Degenerations may occur. Epithelial oedema occurs when the IOP exceeds
45 mm Hg.
Limbus. Distension of the vessels and formations of new anastomoses are common.
Trabecular-Schlemm’s canal system. The changes include: (a) fragmentation of the collagens;
(b) proliferation and foamy degeneration of the endothelial cells; (c) narrowing of the
intertrabecular spaces; (d) abundance of acid mucupolyaccharides in the trabecular meshwork;
(e) decrease or absence of the giant vacuoles in the inner wall endothelium of Schlemm’s canal;
and (f) collapse of Schlemm’s canal.
Electron microscopy in advanced cases of primary open-angle glaucoma has shown extracellular
plaques present in the trabecular meshwork and Schlemm’s canal.
Uveal tract. This shows oedema followed by fibrosis.
Retina. Atrophy and cyst formation of the ganglion cells, degeneration of the plexiform layers,
disintegration of the nuclear layer, matting and flattening of the rods and cones, and replacement
of the nerve fibre layer by gliosis and haemorrhage from the sclerotic vessels are present.
Optic disc. Atrophy and cupping are characteristically present.
Sclera. Ectasia and staphyloma are seen
Clinical features. Chronic simple glaucoma is a bilateral affection with a very slow progress and
is insidious in onset. The early symptoms include aches about the eyes and mild headaches. Any
subject above the age of 40 years requiring especially frequent change in presbyopic glasses
should be examined for any evidence of this affection. It must be noted that in some cases,
signs of central retinal vein thrombosis may be the first evidence of the underlying glaucoma.
Diagnosis. Diagnosis essentially depends on the following investigations.
Ophthalmoscopic examination. It is rather difficult to distinguish early optic disc changes from
a physiologic excavation of the disc especially when the latter is deep. Two marked changes in
glaucoma of some duration are pallor and cupping. The possible variants are: (a) pathological
cupping with atrophy; (b) pathological cupping without atrophy; (c) atrophy with minimal
pathological cupping; and (d) atrophy with no pathological cupping.
Cupping possibly results from mechanical pressure and ischaemia. The pressure causes forcing
the lamina cribrosa backwards leading to squeezing of the nerve fibres and then to disturbed
axoplasmic flow.
Glaucomatous optic disc (Fig.5) should be assessed under the following headings:
- Cup diameter and extent
- Cup asymmetry
- Colour
- Depth of cupping
- Displacement of the vessels
- Pulsation of the retinal arteries
- Peripapillary halo
- Fluorescein angiography
- Retinal nerve fibre layer
- Disc haemorrhages
- Digital imaging.
Cup diameter and extent. The edges of the glaucomatous cup may reach the disc margin. In
its initial stage a glaucomatous cup preferentially affects the inferolateral quadrant of the optic
disc. Cups with a vertical diameter greater than the horizontal are probably glaucomatous. The
cup/disc diameter (C/D) ratio is a genetically determined characteristic. In about 80 per cent of
glaucomatous eyes this ratio is greater than 0.3. About 17 percent of the general population have
also a similar ratio of above 0.3.5
Cup asymmetry. It is a valuable sign, especially if it is marked.
Colour. The degree of pallor indicates the extent of atrophy. Glial atrophy is caused by
ischaemia.
Depth o f cupping. It may be quite deep, and it is usually measured by focusing a blood vessel
at the edge of the cup and then on the floor.
Displacement o f the blood vessels. They may be dragged on to the nasal side. In a deep
excavation, they are seen at the edge of the cup and disappear below the overhanging edge till
they are suitably focused on the floor of the excavation.
Pulsation o f the retinal arteries. When the IOP has approached or exceeded diastolic pressure in
the central retinal artery, an arterial pulsation is observed easily. It is not diagnostic of glaucoma,
since it is present in other conditions like aortic regurgitation and aneurysm.
Retinal nerve fibre layer (RNFL). Normally RNFL appears as fine parallel lines crossing the
larger retinal vessels and reaching the optic disc. These are best seen in darkly pigmented ocular
fundus and visualized by red-free monochromatic light. In glaucoma these appear as slit-like
grooves usually one disc diameter above and below the disc.1
Disc haemorrhages. Splinter haemorrhages are sometimes seen over the optic disc.
Tonometry. Tonometry is the most commonly performed test for simple glaucoma. However, an
applanation tonometer is more reliable than a Schiotz tonometer. A constant difference of 4 mm
Hg ocular tension between the two eyes of an individual or a diumal variation of more than
5 mm Hg Schiotz is suspicious. In simple glaucoma there are four types of diumal variation: (a)
rise of tension in the morning, 10 per cent; (b) rise of tension in the afternoon, 25 per cent; (c)
biphasic variation, 55 per cent; and (d) the flat type, rarely seen. In glaucoma, the ocular tension
remains normal between its diumal variations in the early stage, but as the disease progresses the
variations increase and the tension rises further. A single tonometry reading is of no value.
Tonography. Though tonography was considered to be one of the most important tests in
diagnosing early cases of simple glaucoma, but today many experts on glaucoma do not place so
much importance to this test. The more the resistance to aqueous outflow the lesser the exit of
aqueous from the eye, and subsequently there will be higher IOP. Normal coefficient of aqueous
outflow is 0.20. If this is less than 0.16 it is suggestive of glaucoma, but if it is less than 0.13
it is indicative of glaucoma.
Visual field study (Fig 6 ).8,10 Visual field study is a very valuable method of investigation
essential for diagnosis, prognosis and assessment of efficiency of treatment. The field changes
are the result of either individual nerve fibre bundle damage or of ischaemia.
Fig 1. Three layers of trabecular meshwork (shown in cutaway views): uveal, corneoscleral,
and juxtacanalicular
Fig 2. Normal angle structures
Fig 3. a) Tono-pen,
b) Tono-pen in use
Fig 4. Non-contact tonometer
Fig 5. Heidelberg retinal tomograph of a normal eye
Fig 6. Visual field changes in chronic simple
glaucoma; 1. baring of the blind spot; 2. Seidel’s
scotoma; 3. Bjerrum’s scotoma; 4. Bjerrum’s scotoma
and Rocnnc’s scotoma; 5. Rocnne’s nasal step connected
with Bjerrum’s scotoma; 6. final stage in visual field
change showing remnant of the central field.
Literature
1.Albert DM, Jakobiec. Principles and Practice of Ophthalmology. Philadelphia
: Saunders/Elsevier, 2008.
2.Gass JDM. A Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment.
- 1997 (505-11).
3.Harry J, Misson G. Clinical Ophthalmic Pathology. Butterworth/Heinemann. 2001
4.Kanski JJ. Clinical Ophthalmology. Butterworth/Heinemann. - 2007
5.Yanoff M, FineBS. Ocular pathology. A color atlas. 2nd edition.- Yanoff, Fine. 1992
6. http://secure-ecsd.elsevier.com/uk/files/Bowling_FM_combined.pdf
7.http://blogsdelagente.com/evellincherf/atlas-of-clinical-ophthalmology-thirdedition-pdf-free-download/