Retina 2

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Baghdad medical college
2015 - 2016
The retina
Anatomy:
The retina is divided into two major components:
1- Outer, pigmented monolayer known as Retinal Pigmented Epithelium (RPE).
2- Inner, multilayered (nine) lamina called the Neural Retinal (Sensory
Retina)(SR).

Retinal pigmented epithelium (RPE):

- Single layer of hexagonal cells, containing melanin pigments (melanosomes).
- The adhesion between the RPE & (SR) is weaker than that between the RPE and
choroid, which underlies the RPE. There is a potential space lies between RPE &
SR called subretinal space(SRS).

Functions of RPE:

1- The tight junctional complexes intervening between the cells of RPE forming
the "Outer Blood-Retinal Barrier" which prevents extracellular fluid from
choroid to enter the subretinal space.
2- Actively pumps ions and water out of the SRS.
3- Mechanical support to the photoreceptors (rods & cones).
4- Play a critical role in the retinal metabolism & photochemistry, hence, the
RPE is essential for normal vision.
* Photochemistry: chemical reactions in photoreceptors due to photo-stimulation,
converting light stimulus into electrical impulses transmitted through the
fibers of the optic nerve.
Sensory retina (nine layers):
From outermost (near RPE) layer towards innermost (near vitreous):
1- Photoreceptors layer (Rods and cones) adjacent to RPE.
2- Outer limiting membrane (Acellular layer).
3- Outer nuclear layer (Horizontal cells).
4- Outer plexiform.
5- Inner nuclear layer (Bipolar cells).
6- Inner plexiform layer.
7- Ganglion cells layer.
8- Nerve fibers layer (long axons of ganglion cells).
9- Inner limiting membrane (Acellular layer in contact with the vitreous).
The axons of ganglion cells from all over the retina converge to form the optic
disc (the blind spot) which represent the distal end of the optic nerve where
the proximal end relay at lateral geniculate body and midbrain.
- There are probably 120 million rods, which are mainly concerned with vision at
low light levels (night vision) and are predominant in the periphery of the
retina and 10 million cones, which are responsible for color vision and high
acuity visual tasks (day vision and reading). Cones are most concentrated in a
specialized central region of the retina "Foveola centralis".

Blood supply:

- The outer one third (1/3) of retina (including RPE, photoreceptors and half of
the outer nuclear layer) is supplied from choroidal blood vessels which are
formed by arborization of 10-20 short ciliary arteries arising from ophthalmic
artery and entering the eyeball through separated foramina.
Venous drainage of this part of retina is also by choroidal circulation to the
four vortex veins (2 superior and 2 inferior) which are leaving the eye nearly
at the equator and draining their blood to the superior and inferior ophthalmic
veins respectively and then to the cavernous sinus.
- The inner 2/3rd of retina is supplied by 2-3 levels of capillary network
inside retinal layers arising from central retinal artery, which is a branch of
ophthalmic artery.
The venous drainage of retina is through central retinal vein which also passing
its blood to the superior ophthalmic vein and then to the cavernous sinus.
Both central retinal vein and artery are entering the eyeball with the optic
nerve through the scleral canal.

Blood supply of the retina

Blood-Retinal Barrier (BRB):
It is composed of two components:
1- Outer BRB: is formed by the tight junctions between RPE cells.
2-Inner BRB: is formed by the tight junctions between the endothelial cells of
retinal blood vessels.
Even small molecules doesn't pass freely through this barrier.
* In comparison to the retinal blood vessels, choroidal blood vessels are
fenestrated and haven't such tight junctions and large molecules can pass
through them freely to the extracellular tissue.

Applied anatomy:

1- The macula: it is a round area at the posterior pole measuring 5.5 mm in
diameter, found temporal and inferior to the optic disc. It contains
xanthophylls (yellow) pigment (so it is called macula lutea) and more than one
layer of ganglion cells.
2- The fovea: it is a depression in the inner retinal surface at the center of
the macula with a diameter of 1.5 mm (equal to optic disc diameter). By
ophthalmoscope, it gives rise to oval light reflex because of abrupt increased
thickness of the retina at its border.

3- The foveola: it forms the central floor of the fovea and has a diameter of

0.35 mm. It is the thinnest part of retina. In this area there is no ganglion
cell layer and consists only of photoreceptors (cones only). It is concerned
with color and day vision. The retina in foveola is composed of RPE, outer
limiting membrane, photoreceptors (cones only) and nerve fiber layer.


A fundus photograph shows the foveola (a), fovea (b), parafovea (c), and
perifovea (d).

Retinal Detachment (RD)

It is separation of the sensory retina from the RPE by subretinal fluid (SRF)
accumulated in SRS.
Types of retinal detachment:
1- Rhegmatogenous RD: (Rhegma = break)
Is occurs secondary to a full thickness defect (either a hole or tear) in the
SR, which permits SRF derived from abnormally liquefied vitreous gel to gain
access to the SRS leading to separation of them.
The main factor for rhegmatogenous RD is abnormal liquefaction of vitreous humor
gel which causes separation of fluid from solid compartment of the vitreous. The
solid compartment is shrinking in front of retina causing traction on the retina
which occasionally ends with retinal tear. This traction is perceived by the
patient as flashes of light (photopsia). The fluid compartment then passes
through these tears into SRS separating RPE from SR.
Causes:
a- Idiopathic.
b- High myopia associated with predisposing peripheral retinal degeneration.
c- Trauma.
d- Intraocular surgery, e.g. cataract surgery.
e- Hereditary diseases of vitreous and retina, e.g. Stickler's syndrome.
f- In association with tractional RD.


Symptoms:
a- Photopsia (flashes of light): caused by traction on the retina due to acute
Posterior Vitreous Detachment "PVD: separation of posterior vitreous face from
internal limiting membrane of retina".
b- Floaters: are moving vitreous opacities perceived when they cast a shadow
upon the retina. These opacities are either opacities within the abnormally
degenerated vitreous or RBC duo to involvement of blood vessels by retina tear
or glial cells (astrocytes) which are normally present between the vitreous
posterior surface and the optic disc. This glial tissue around the optic disc
when separated from it with the posterior vitreous face in a form of ring called
Weiss ring which is pathognomonic for PVD.
* (a) & (b) reported in 60% of patients with spontaneous rhegmatogenous RD, then
after a variable period the patient notice:
c- Peripheral visual field defect which progress to:
d- Decreased central visual acuity (drop vision): when macula is involved.
* so any patient presented with photopsia or floaters needs to examine the
retina meticulously by three-mirror contact lens with slit lamp or indirect
ophthalmoscope, and any retinal tear or hole must manage it without any delay as
prophylactic measure to avoid RD.

Treatment of rhegmatogenous RD:

For those 60% of spontaneous RD who are presented with photopsia and floaters,
if their retinae are flat (no RD) and just there is retinal break (hole or
tear). The treatment is prophylactic laser photocoagulation around those breaks
to create adhesions between sensory retina and RPE to prevent movement of fluid
from vitreous to SRS.
However, if RD is ensured and there is accumulation of fluid in SRS, there is NO
role for laser (as the RPE and SR are far away from each other) and treatment is
surgery (traditional retinal reattachment surgery).


2- Non-rhegmatogenous RD:
a- Tractional RD:
In which, the sensory retina is pulled away from the RPE by contracting
vitreoretinal membranes. The source of SRF is unknown.
Causes:
i- Advanced diabetic eye disease.
ii- Retinopathy of prematurity "ROP" (retrolental fibropathy or fibroplasia):
due to high O2 concentration given to premature infants with low birth weight.
iii- Sickle cell retinopathy.
iv- Penetrating trauma.

Symptoms of tractional RD:

Photopsia and floaters are usually absent because vitreoretinal traction
develops insidiously and it is not associated with acute PVD.
i- Visual field defect: it is the main complaint, which progress slowly and may
become stationary for months or years.
ii- Decreased central visual acuity: if tractional detachment progress to
involve the macula.
Treatment: surgery, Vitrectomy (which include excision of abnormal vitreous
[fibro vascular membranes] to relieve traction, then it is replaced by synthetic
oily fluid e.g. Silicon oil.


b- Exudative (serous) RD:
In which, SRF is derived from the choroid gains access to the SRS through
damaged RPE. There is a defect in RPE which is due to either:
Ocular causes:
i- Uveitis (posterior uveitis).
ii- Posterior scleritis.
iii-Retinoblastoma.
iv- Choroidal tumours.
Or Systemic causes:
i- Malignant hypertension.
ii- Eclampsia.
iii- Uremic patient.

Symptoms:

- Photopsiae is absent (no vitreoretinal traction).
- Floaters may be present if it is associated with uveitis (vitritis).
- Visual field defect develops suddenly & progress rapidly.
- Bilateral eye involvement is possible.
Treatment: towards the cause. Most commonly medical treatment to control the
above listed ocular and systemic causes.


Diabetic Retinopathy
Pathogenesis:
Diabetic retinopathy (DR) is a microangiopathy primarily affecting the
arterioles, capillaries and post-capillary venules, although large vessels may
also be involved.
The main pathology in DR is: either microvascular occlusion.
Or microvascular leakage.

Microvascular occlusion occurs due to:

1- Thickening of the blood vessels basement membrane.
2- Damage and proliferation of the endothelial cells.
3- Increased RBC formation.
4- Increased platelet stickiness and aggregation.

The consequences of microvascular occlusion:

The occlusion of blood vessels leads to retinal ischemia and hypoxia. Hypoxic
retinal tissue elaborate vasoformative substances "Growth factors" in an attempt
to revascularize hypoxic retinal tissue by new blood vessels formation
"Neovascularization", formed at optic disc "NVD (=NeoVascularization of the
Disc)", or elsewhere in the retina "NVE (=NeoVascularization Elsewhere in
retina)", and occasionally on the iris "Rubeosis Iridis".


Microvascular leakage occurs due to:
1- Breakdown of the inner BRB leads to leakage of plasma constituents into the
retina.
2- Physical weakening of the capillary walls results in localized saccular
outpouchings of the vessel wall termed "Microaneurysms" which may leak.
The consequences of leakage and increased vascular permeability include the
development of intraretinal haemorrahges and oedema.
Clinically DR may be:
1- Background DR.
2- Pre-proliferative DR.

3- Proliferative DR.

4- Advanced diabetic eye disease(ADED).
5- Maculopathy, which associates (1), (2),(3) and even (4).
1- Background DR:
Fundoscopy shows: a- Microaneurysms (saccular dilatations).
b- Exudation (leakage of lipoprotein).
c- Retinal oedema (due to leakage of fluid).
d- Intaretinal Haemorrhages: Dot-blot haemorrhage or flame-shaped haemorrhage at
level of nerve fiber layer. Sometimes it is difficult to differentiate
intraretinal haemorrhages from microaneurysm, however, can be differentiated by
fluorescein angiography, as aneurysms will leak dye.
Management:
It requires NO treatment, but should be reviewed every 6 months. In addition,
patients need to control of diabetes and associating factors as hypertension,
anemia and renal failure.
2- Pre-proliferative DR:
Fundoscopy shows, in addition to all features of background DR, the following:
a- Cotton wool spots which represent focal infarction of retinal nerve fiber
layer due to occlusion of pre-capillary arterioles. Interruptions of axoplasmic
transport with subsequent build-up of transported material within the axis
(axoplasmic stasis) are responsible for the white appearance of the lesions.
b- Intra Retinal Microvascular Abnormalities (IRMA), which represent shunts that
run from retinal arterioles to venules, bypassing the capillary bed.
Management:
Should be watched closely every 3 months because of the risk of PDR
(Proliferative Diabetic Retinopathy) is high. Laser photocoagulation is usually
not needed unless:
a- Regular follow-up is not possible.
b- Vision in the fellow eye has been already lost due to PDR.
Also, patient need to control the blood sugar and associating factors.


3- Proliferative DR (PDR):
Affects 5-10% of the diabetic population, type 1 diabetics are at particular
risk. By fundoscopy, neovascularization is the hallmark of PDR, either at disc
(NVD) or elsewhere (NVE). Pre-retinal haemorrhage or intravitreal haemorrhage
due to sudden rupture (either spontaneous or associating valsalva manoeuvre) of
the walls of these abnormally fragile blood vessels (NVD or NVE) and the patient
complains of sudden drop of vision. Finally, there will be organization of blood
into fibrous tissue causing tractional RD that may end with ADED.

Management:

Pan-Retinal Photocoagulation (PRP), it is a destructive procedure, where normal
retinal tissue around the temporal arcades (temporal blood vessels) is
photocoagulated and destructed in order to decrease retinal ischaemia by
decreasing O2 demand. Then the neovascularization resolves spontaneously (no
hypoxia → no growth factors). Now a day, new drugs are used in addition with
PRP e.g. Ranibizumab (Lucentis) which are acting as anti vascular endothelial
growth factor (anti VEGF) to regress these neovasculariztion. These drugs
injected directly inside the vitreous under local anesthesia through the area of
pars plana.
If pre-retinal or intravitreal hemorrhage occur, it is impossible to do PRP and
only anti VEGF can be given until this blood resolve spontaneously or remove by
vitrectomy.


Side effects of PRP:
a- Constriction of visual field (loss of peripheral visual field).
b- Nyctalopia (night vision).

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4- Maculopathy (macular DR):
Is might be associated with: a- Background DR.
b- Pre-proliferative DR.
c- Proliferative DR.
It is the involvement of the fovea by oedema and exudates (leakage) or ischaemia
(occlusion). Diabetic maculopathy is the most common cause of visual impairment
in diabetic patients particularly those with type 2 diabetes.
Management:
Fluorescein angiography by injection of IV fluorescein with fundal photograph
and OCT should be done to differentiate between leakage type (edematous or
exudative maculopathy) and ischaemic type (ischaemic maculopathy) and to find
the site of leakage in first type.
For exudative and edematous maculopathy, the treatment is direct (focal laser
photocoagulation) to occlude the site of leakage. Also, intravitreal
triamcinolone and anti VEGF having a role in treatment of maculopathy specially
if it is sever and diffuse, with or without focal laser treatment.
For ischaemic maculopathy, no treatment available. If laser photocoagulation is
done for such cases, it induce more ischaemia and more deterioration of visual
acuity (laser is contraindicated in ischaemic maculopathy).
5- Advanced diabetic eye disease (ADED):
Serious vision-threatening complication of diabetic retinopathy occurs in
patients who have not had laser therapy or in whom laser photocoagulation has
been unsuccessful or inadequate.
Fundoscopy shows:
a- Hemorrhage. (pre-retinal or intravitreal).
b- Tractional RD: due to fibrovascular membranes formation or fibrous tissue
formation due to organization of pre-retinal or intravitreal hemorrhage.
Management:
Vitrectomy +Anti VEGF+ Endolaser (PRP).
* Endolaser: done in the theatre by applying the laser through a fiberoptic
probe in the eye, instead of using slit-lamp biomicroscope.


Age-Related Macular Degeneration (AMD)
Definition: A common, chronic, usually bilateral, progressive degenerative
disorder of the macula lead to some degree of visual loss in association with
drusen and geographical atrophy of the RPE or changes associated with subretinal
neovascularization in individuals over 50 Years old.
AMD is the leading cause of irreversible severe visual loss in the Western
World in individuals over 60 years old. The prevalence of severe visual loss
increases with age. In the USA, at least 10% of individuals between the ages of
65 and 75 years have lost some central vision as a result of AMD. Among those
older than 75, 30% are affected to some degree. The two main types of AMD are
non-exudative (dry) and exudative (wet) Although only 10% of AMD patients have
the exudative form, 88% of legal blindness attributable to AMD is the result of
this type.
The earliest clinically detectable feature of AMD is the appearance of
asymptomatic yellow excrescences beneath the RPE, called drusen, which are
distributed symmetrically at both posterior poles of retinae. Drusen may vary in
number, size, shape, degree of elevation and extent of associated changes in the
RPE. Drusen are rarely clinically visible before the age of 45 years; they are
not uncommon between the ages of 45 and 60 Years and almost universal
thereafter. With advancing age they increase in size and number.
Histopathologically, Loss of central vision in AMD is the result of changes that
occur in response to deposition of abnormal material between the basement
membrane of RPE and choroid.. This abnormal material is derived from the RPE,
and its accumulation is thought to result from failure to clear the debris
discharged into this region.
Loss of visual acuity typically results from progressive degeneration of the
choriodal capillaries, retinal pigment epithelium (RPE), and photoreceptors. The
advanced form of the disease is characterized by submacular neovascularization,
geographic atrophy (atrophy of the RPE, choriocapillaris, and photoreceptors),
or both.
The disease virtually always begins as the non-neovascular or dry form of AMD
and may progress to geographic atrophy or the neovascular (wet) form of the
disease in one or both eyes. When neovascularization occurs, there is
commensurate accumulation of fluid, hemorrhage, and lipid exudation within the
macula that can culminate in fibrosis referred to as a disciform scar at the
macula. A patient can have advanced dry AMD in both eyes, advanced wet AMD in
both eyes, or dry AMD in one eye and wet AMD in the fellow eye. It is
controversial whether the wet and dry forms of AMD represent two distinct
disease entities or end-stage manifestations of the same disease. Once advanced
AMD develops in one eye, there is an increased likelihood of having geographic
atrophy or neovascularization in the fellow eye.
OCULAR MANIFESTATIONS
Affected individuals with AMD typically are asymptomatic in the early stages of
the disease. The onset is subacute for dry AMD, but as the disease progresses
they report blurred vision or metamorphopsia in one or both eyes. Decreased
reading ability, especially in dim light, and difficult and slow dark and light
adaptation. AMD may go undetected until abrupt visual loss is noted from the
conversion of dry AMD to wet AMD. Wet AMD typically shows a more rapid
progression of visual acuity loss relative to its non-neovascular counterpart
(dry type)
DIAGNOSIS AND ANCILLARY TESTING.
clinical findings :
Visual acuity loss from AMD occurs when an individual older than 50 years has
geographic atrophy in the macula, a PED, and/or neovascularization. Other
clinical findings, such as drusen, hyperpigmentation, and hypopigmentation help
confirm the diagnosis, but their presence alone may not be associated with
visual loss. Clinical examination is usually sufficient to establish a diagnosis
of AMD. Subtle macular abnormalities, especially subretinal fluid, are best
detected by stereoscopic slit-lamp biomicroscopic examination using a contact
lens, optical coherence tomography (OCT), and/or stereoscopic viewing of fundus
photographs with fluorescein angiography (FA).