Exudative Retinal Detachment

Exudative Retinal Detachment
Dr R S Walpitagamage
Registrar in Ophthalmology
TH Kandy

Introduction
• Exudative retinal detachment develops when fluid collects in the subretinal space.
• The subretinal space between the photoreceptors and the retinal pigment epithelium is
the remnant of the embryonic optic vesicle.
• In the developed eye the subretinal space is of minimal size, but it can reopen under
pathological conditions that disrupt the integrity of blood-retinal barrier.
• Inflammatory, infectious, infiltrative, neoplastic, vascular, and degenerative conditions
may be associated with blood-retinal barrier breakdown and the sequential
development of exudative retinal detachment.
• This elaborate on the pathogenesis and the differential diagnosis of exudative retinal
detachment and specifically discuss the spectrum of diseases associated with exudative
retinal detachment in uveitis clinics.

Epidemiology
• No data are available to suggest the incidence or prevalence of ERD.
• Every pathological condition (inflammatory, infectious, vascular, neoplastic, and
degenerative) is potentially capable of violating the integrity of the BRB and results
in the development of ERD.
• The spectrum of associated diseases is wide, ranging from isolated ocular conditions
to multisystemic diseases.

Pathogenesis
• ERD develops when fluid collects in the subretinal space as a result of disruption of
the integrity of the BRB.
• The BRB plays an important role in the homeostatic regulation of the retinal
microenvironment by controlling fluid and molecular movement between the ocular
vascular beds and the retinal tissues and prevents leakage into the retina of
macromolecules and other potentially harmful agents.
• The BRB consists of inner and outer components.
• The inner BRB (iBRB) is formed by the tight junctions (TJs) between neighboring
capillary endothelial cells that rest on a basal lamina covered by the foot processes
of astrocytes and Muller cells.
• Pericytes, separated from the endothelial cells by the basal lamina, are the third cell
type of relevance to the iBRB.
• Astrocytes, Müller cells, and pericytes are thought to contribute to the proper
functioning of the iBRB.

• The outer BRB (OBRB) is formed by TJ between cells
of RPE.
• The RPE resting upon the underlying Bruch
membrane separates the neural retina from the
fenestrated choriocapillaris and plays an important
role in transporting nutrients from the blood to the
outer retina.
• The apical surface of the RPE shows long projecting
processes (villi) that partially envelop the outer
segments of the photoreceptors.
• These villi are involved in the phagocytosis of outer
segment disks.
• The metabolic interaction between these apical villi
and the photoreceptors, for example, exchange of
metabolites such as vitamin A and amino acids, is
considered to be critical for the maintenance of
visual function.

• There are no structural attachments between
the RPE and the outer retina, but neural cell
adhesion molecules expressed on the apical
surface of the RPE cells create adhesion
between the retina and RPE although
functional factors may be more important.
• Although inter-RPE cell TJs are important in
the control of paracellular movement of fluids
and molecules between the choroid and
retina, the polarized distribution of membrane
proteins in the RPE is also important.
• As the integrity of the BRB is dependent on
the normal functioning of the cells that
determine its structure, hypoxia-ischemia
secondary to inflammatory, infectious,
infiltrative, neoplastic, vascular, and
degenerative conditions may be associated
with BRB breakdown.
RPE
SRF
PED

Diagnosis
• Symptoms
• Depending on
cause
• Usually no
photopsia- no
traction
• Floaters – if
vitritis
• VF defect may
develop
suddenly and
progress
rapidly
• Detailed
systemic
history to find
the etiology
Examination
• Physical findings
depending on the
cause
• Fundus – RD
convex
configuration,
surface smooth
not corrugated
• Detached retina is
very mobile and
exhibits the
phenomenon
“shifting fluid”
• Other findings
depending on
cause
History Investigations
OCT
B scan
UBM
FFA
ICGA
Ophthalmic imaging Hematological
and serological
tests
Imaging
XR
CT
MRI
Microbiologi
cal tests and
pathological
tests

Diagnosis
• It is imperative to keep in mind that ERD may develop in association with a protean number of pathological
conditions, ranging from isolated ocular to generalized systemic conditions.
• Diagnosis thus necessitates a road-map pathway through which information is collected by means of ocular and
medical history, physical and ocular examination, and ancillary tests.
• On one hand, thorough medical and ocular history may help to reveal a possible link to an underlying systemic
disease or on the other hand, ERD may be the presenting manifestation leading to the unfolding of the
underlying etiology (e.g, choroidal metastasis).
• Physical examination is essential to assess the extent and severity of systemic involvement (neurologic, cardio-
respiratory, intestinal, genitourinary, articular, and cutaneous).
• A complete ophthalmic examination is the key step that allows the ophthalmologist to precisely document the
ocular findings.
• Tailored work-up is then performed to confirm or rule-out possible diagnoses (e.g., serpiginous choroiditis,
choroidal hemangioma, and so on).
• Ancillary ophthalmic imaging tests such as FA, Indocyaninegreen angiography, OCT, and echography may be
selectively performed to better illustrate the involved structure and the extent of involvement and to monitor
disease course.
• Systemic investigations (blood tests, X-rays, CT scan, and magnetic resonance imaging) are selectively
performed.
• Ultimately, the collective information (by revealing specific as-sociations) leads to ascertaining the definitive
diagnosis

Etiology of ERD
Uveitic entities associated with ERD Non Uveitic entities associated with ERD
Inflammatory conditions Infectious conditions Choroidal pathologies Retinal pathologies Miscellaneous
1. Vogt-Koyangi-Harada
2. Sympathetic
ophthalmia
3. Posterior scleritis
4. Serpiginous
choroiditis
5. Behcet’s disease
6. Relapsing
polychondritis
7. Intermediate uveitis
1. Tuberculosis
2. Syphilis
3. Dengue
4. Lyme disease
5. CMV retinitis
6. Nematode infestation
7. Fungal infection
1. Choroidal melanoma
2. Choroidal osteoma
3. Choroidal
hemangioma
4. Choroidal lymphoma
5. Choroidal metastases
6. Hematological
malignancies
1. Coat’s disease
2. Vasoproliferative
tumours
3. Retinal astrocytic
hamartoma
4. Vitreoretinal
lymphoma
5. Familial exudative
vitreoretinopathy
6. Retinal vein occlusion
7. Diabetic macular
oedema
8. Preeclampsia/eclampsi
a/HELLP
9. HUS and TTP
10. Idiopathic macular
telengectasia
11. Wet ARMD
1. CSCR
2. Uveal effusion
syndrome
3. Cavitatary optic disc
anomalies
4. Bilateral diffuse
uveal melanocytic
proliferation
5. Acute paraneoplastic
polymorpous
vitelliform
maculopathy

Etiology of ERD
Infectious conditions Choroidal pathologies Retinal pathologies Miscellaneous
1. Tuberculosis
2. Syphilis
3. Dengue
4. Lyme disease
5. CMV retinitis
7. Fungal infection
3. Choroidal
hemangioma
6. Hematological
malignancies
1. Coat’s disease
tumours
hamartoma
4. Vitreoretinal
lymphoma
vitreoretinopathy
7. Diabetic macular
oedema
a/HELLP
9. HUS and TTP
telengectasia
11. Wet ARMD
1. CSCR
2. Uveal effusion
syndrome
anomalies
uveal melanocytic
proliferation
polymorpous
vitelliform
maculopathy
Inflammatory conditions
2. Sympathetic
ophthalmia
4. Serpiginous
choroiditis
6. Relapsing
polychondritis

Vogt-Koyangi-Harada (VKH)
• Idiopathic multisystem autoimmune disease
• Predominantly affects females in their second to
fifth decades of life and ethnic groups with more
heavily pigmented skin.
• Severe bilateral granulomatous posterior or pan
uveitis associated with ERD, disk edema, and
vitritis , with eventual development of a sunset
glow fundus.
• Multiple ERDs with diffuse choroiditis typically
presenting as early manifestations.
• Marked choroidal thickening and delayed
choriocapillaris filling with subsequent break
down of RPE barrier integrity, leading to
accumulation of serous material and finally to

Sympathetic ophthalmia
• Previously reported predominantly in
males with biphasic peaks in children and
the elderly because of the greater
incidence of accidental trauma and ocular
surgery, respectively. Nowadays, the
incidence is increasing after surgery in
females and in elderly patients.
• Bilateral granulomatous panuveitis
consequent to ocular surgery or
penetrating injuries.
• Multilobular ERD associated with yellow-
white midperipheral sub-RPE nodules
(Dalen-Fuchs nodules)

Bahcet’s disease
• Behcet's disease is a chronic, relapsing, multisystem,
idiopathic inflammatory disorder characterized by a triad of
oral ulcers, genital ulcers, and ocular lesions.
• However, the spectrum of disease is even wider with the
involvement of articular, intestinal, vascular, urogenital, and
neurologic systems, besides the mucocutaneous and ocular
finding.
• Primarily affects young males , in the third or fourth decade
of life. Strongly associated with HLA B 51
• Diffuse vitritis , retinal infiltrates , sheathing of
predominantly retinal veins, and occlusive vasculitis.
• ERD is a rare manifestation, reported in association with
severe and hemorrhagic retinal vasculitis.

Serpiginous choroiditis
• Predominantly young to middle-aged
males. HLA B7
• ERD is rarely reported.
• Usually bilateral.
• Gray-yellow choroidal lesions in
peripapillary/macular area with
centrifugal extension.
• Progressive choroiditis leading to loss of
choriocapillaris and atrophy of the
overlying RPE with scarring.

Relapsing polychondritis
• Predominantly seen in middle-aged Caucasians,
with no gender predilection.
• ERD is seen in association with posterior
scleritis.
• Proptosis, eyelid edema, extraocular muscle
palsy, episcleritis/scleritis, conjunctivitis, corneal
infiltrates , peripheral ulcerative keratitis,
corneal thinning and perforation, iridocyclitis,
sclero uveitis, retinopathy, optic neuritis, and
ERD.
• Chronic posterior scleritis causing multiple RPE
defects and oBRB compromise.

Posterior scleritis
• Predominantly young to middle aged females
• Choroidal folds, optic disk edema, macular edema, annular ciliochoroidal
detachment.
• ERD is frequent manifestation.
• Choroidal thickening, choroidal perfusion delay with resultant leakage points
through the RPE.

Tuberculosis
• Primarily an airborne infection that spreads
from one person to another when a person
with pulmonary or laryngeal tuberculosis
coughs or sneezes, expelling droplets that
contain Mycobacterium tuberculosis.
• Chalazion-like nodules, orbital granulomas,
anterior, intermediate, posterior uveitis, and
endophthalmitis.
• ERD-Usually in association with choroidal
tubercles, tuberculomas, retinal vasculitis, or
as part of paradoxical TB-associated immune
reconstitution inflammatory syndrome.
• Treatment-Systemic steroids combined with
anti tuberculous therapy.

Syphilis
• May be transmitted trans placentally
to the fetus or acquired postnatally by
sexual contact.
• Anterior, intermediate, posterior, or
panuveitis, neuroretinitis,
episcleritis/scleritis, keratitis.
• Described in association with punctate
inner retinitis, chorioretinitis,
panuveitis.
• Treatment-Parenteral penicillin is the
drug of choice for ocular syphilis. Oral
corticosteroids can be used to treat
inflammatory complications.

Etiology of ERD
Inflammatory conditions Infectious conditions Retinal pathologies Miscellaneous
2. Sympathetic
ophthalmia
4. Serpiginous
choroiditis
6. Relapsing
polychondritis
1. Tuberculosis
2. Syphilis
3. Dengue
4. Lyme disease
5. CMV retinitis
7. Fungal infection
1. Coat’s disease
tumours
hamartoma
4. Vitreoretinal
lymphoma
vitreoretinopathy
7. Diabetic macular
oedema
a/HELLP
9. HUS and TTP
telengectasia
11. Wet ARMD
1. CSCR
2. Uveal effusion
syndrome
anomalies
uveal melanocytic
proliferation
polymorpous
vitelliform
maculopathy
3. Choroidal
hemangioma
6. Hematological
malignancies
Choroidal pathologies

Choroidal melanoma
• Usually seen in Caucasians, in the sixth decade.
• Pigmented dome-shaped mass with median basal
dimension of 11mm and thickness of 4.5mm
• Clinically detected in 75% of the iBRB and oBRB
eyes, however, all eyes have microscopic SRF.
• ERD is a risk factor for tumor growth, metastasis,
and tumor related death.
• ERD is due to increase permeability of both iBRB
and oBRB.
• Proton beam radiotherapy, plaque brachytherapy,
and stereotactic radiation therapy among others.
Surgical drainage of SRF at time of irradiation was
applied, also intravitreal TA and IVB.

Choroidal osteoma
• More in young female patients in their early
twenties.
• Juxtapapillary, yellow-white to orange-red
lesions.
• ERD due to multiple pinpoint leakage sites
over the osteoma with gradual atrophy of
the overlying RPE and Bruch's membrane,
resulting in degenerated oBRB.
• ERD carries poor visual prognosis, more as a
result of CNV.
• Treatment-IVB, FLT, spontaneous resolution
of SRF also reported.

Choroidal hemangioma
• Circumscribed hemangioma presents at a mean age of 47 years.
• Diffuse hemangioma (part of Sturge-Weber syndrome) presents
at a mean age of 8 years.
• Circumscribed tumors are discrete, round, orange-red, posterior
to the equator near or temporal to optic disk with a pigmented
rim.
• Diffuse tumors appear as diffuse red ("tomato-catsup) fundus
appearance with choroidal thickening and increased tortuosity of
retinal vessels.
• SRF was reported to occur in 81% of patients with circumscribed
tumors.
• RPE alterations develop indicating degenerative changes with a
resultant imbalance between accumulation and removal of SRF.
• PDT, laser, anti-VEGF therapy may be used for primary
management of localized tumor.
• For patients with extensive ERD, they can be treated using
radiotherapeutic modalities .
• For the diffuse tumor, EBR, proton beam therapy, brachytherapy,
PDT, and anti-VEGF therapy.

Coat’s disease
• Coats' disease is retinal telangiectasia within the
macula and periphery vessels and secondary resulting
in subretinal accumulations of exudates, forming
yellow white mounds with superficial crystalline
deposits if long standing, commonly occurs in
temporal macula and mid periphery.
• Male predominance with a mean age at diagnosis of 5
years
• ERD is due to chronic low level of leakage from the
telangiectatic retinal vessels.
• ERD extent increases as the vascular and exudative
components of the disorder proceed, until a total ERD
overlying a yellow-green subretinal mass results.
• Treatment – Observation, Laser, cryotherapy, Surgery if
RD.

Vasoproliferative tumors
• Primary VPTs more in females, with a mean age of 44 years at presentation.
Secondary VPTs have a younger mean age at presentation.
• Yellow-red, often ill-defined retinal-based mass, far-peripheral, inferotemporal
location with exudates and ERD.
• Primary VPTs tend to be solitary, small, and between the globe equator and
oraserrata. Secondary VPTs are more often multifocal and bilateral.
• ERD- similar to coat’s disease.

Retinal astrocytic hamartoma
• Classically seen in association with tuberoussclerosis
complex (50% of cases)
• Small, sessile noncalcified lesion in the nerve fiber
layer, or a multinodular yellow white calcified
lesion, or as a combination of 2.
• Initially iBRB is involved however with progressive
growth and retinal destruction also oBRB may be
damaged.
• ERD consists of yellow, lipoproteinaceous exudation
in the sensory retina and subretinal space, with
spontaneous resolution of SRF usually within 4
weeks.
• If ERD persists more than 6 weeks , treatment
should be considered.
• Laser, PDT, IVB

Diabetic macular oedema
• Risk factors for developing DME glycemic blood
pressure control, duration of DM, lipid metabolism,
presence of nephropathy, obesity, genetic factors,
nutrition, and pregnancy.
• Thickening and cystoid oedema of the macula often
with hard exudates.
• ERD has been described in15%-30% of patients with
DME.
• ERD occurs due to transient migration of fluid from
the cystoid spaces in the retina to the subretinal
space, another theory is that it occurs subsequent to
failure of the RPE pump mechanism.
• Treatment- FLT, Anti VEGF

Retinal vein occlusion
• Associated with increasing age, high blood
pressure, diabetes, glaucoma and various
disorders of the blood.
• Engorgement and dilatation of the retinal veins,
commonly associated with intraretinal
hemorrhage ,retinal oedema, CWS, exudates
and ME.
• ERD was described in association with all types
of RVO and was found to correlate with the
extent of retinal non perfusion.
• Extensive leakage from capillaries affected by
RVO may migrate to the subretinal space,
resulting in ERD.
• IV steroid and anti VEGF, Laser.

ARMD
• It is the leading cause of irreversible
blindness in adults over 50 years of age.
• The hallmark of neovascular AMD is the
development of CNV characterized by fluid
exudation, RPE detachment, hemorrhage
and scarring.
• ERD has been reported in70%-85% of
patients, described in association with all
lesion types.
• ERD due to RPE damage and oBRB
dysfunction, with subsequent disruption of
the ELM-photoreceptor complex by invasion
and proliferation of the CNV.
• Treatment- IV anti VEGF

• Vitreoretinal lymphoma
• Familial exudative vitreoretinopathy
• Preeclampsia/eclampsia/HELLP
• HUS and TTP

Central serous chorioretinopathy
• CSCR primary affects men in their 3rd and 4th
decades
• ERD and or RPE detachment , changes most
often confined to the macula.
• Hyperpermeable choroidal vessels are thought
to produce increased tissue hydrostatic
pressure , which promotes the formation of RPE
detachment (PEDs), overwhelms the barrier
function of the RPE and leads to areas of fluid
accumulation between the retina and RPE.
• FLT and low fluence PDT
• Epilerenone- a mineralocorticoid receptor
antagonist is being investigated

Treatment
Medical treatments Interventional therapy
1. Corticosteroids and immunomodulatory
therapy
2. Biologic therapy
3. IV Anti VEGF
4. Other
1. FLT
2. Cryotherapy
3. Low dose plaque radiotherapy
4. PDT

Corticosteroids and immune modulatory therapy
• The most commonly used approach for the treatment of ERD in noninfectious uveitis such
as in VKH syndrome is high-dose systemic corticosteroids (IV 1 g/day or prednisone 1
mg/kg/day) followed by oral steroids in tapered doses.
• Slow steroid taper is important because treatment of less than 6-month duration is
associated with recurrences of ERD.
• ERD may rarely recur despite prolonged therapy or may be unresponsive to treatment in
some cases.
• Different immunosuppressive and biological agents have been used in these refractory
cases and also as steroid-sparing due to long-term steroid use
• These agents included cyclosporine A, azathioprine, methotrexate, mycophenolate, nofetil,
and infliximab.
• Andrade and colleagues successfully used intravitreal triamcinolone acetonide in the
treatment of the acute phase of VKH with marked decrease in the extent of ERD in the first
week after the injection and subsequent return to normal retinal thickness in all eyes.

Biologic therapy
The main groups of biologic agents include
• TNF alpha inhibitors(etanercept, infliximab, and adalimumab),
• interferon alpha-2,interferon-beta,
• specific cell inhibitors (rituximab and daclizu-mab),
• receptors antagonists (anakinra and efalizumab).Infliximab, a chimeric
(immunoglobulin G1-1gG1) mono-clonal antibody containing human and
murine portions targeting TNF-a, has been shown to be an effective
immunosuppressant for the treatment of refractory non infectious uveitis
in adults and children
• There is a growing body of evidence indicating that infliximab may be a
successful alternative especially for cases of refractory VKH unresponsive
to conventional therapy.

Intravitreal anti vascular endothelial growth factor
• Anti-VEGF therapy, owing to its anti angiogenic and anti
permeability properties, has been used in the management of
conditions characterized by associated SRF exudation.
• For example, IVB, a recombinant humanized monoclonal anti-VEGF
antibody, has been reported to be effective in CSC patients with
duration over 3 months.
• In acute CSC of 3 months of symptom duration, IVB may not be of
therapeutic benefits compared with observation because of the
spontaneous resolution.
• In DME, ARMD, CRVO the benefit of anti VEGF to reduce SRF is
proven with many studies.

Eplerenone
• Eplerenone - a mineralocorticoid receptor antagonist, has been explared as a
treatment option for chronic CSC given the increasing evidence of
overstimulation of the mineralocorticoid- receptor in choroidal endothelial cells,
inducing vasodilatation, hyperpermeability, and accumulation of SRF.
• Bousquet and colleagues and Singh and colleagues reported that-following
therapy, there was a significant reduction in SRF and improved VA thus suggest in
have a role in selected cases with unresolved CSC.
• Cakir and colleagues reported in the largest treated with eplerenone that 29 % of
patients with chronic CSC demonstrated complete resolution of SRF with oral
administration of eplerenone.
• Improvement in VA was more likely among patients with subtle RPE changes and
an intact ellipsoid zone than those with chronic atrophic CSC and widespread
RPE atrophy at baseline.

Focal laser photocoagulation(FLT)
• Focal laser photocoagulation(FLT) for example, delivered to the leakage site
is one of the treatment options in CSC.
• This treatment attempts to produce a "sealing" of the RPE defect as
identified through FA.
• An additional effect is promoting the pump function of the RPE through
stimulation of adjacent RPE cells.
• Although patients receiving laser treatment showed a faster flattening of
the ERD, laser treatment appeared less effective in achieving improvement
in VA or reducing new episodes of active CSC.
• Laser application in a subthreshold setting (micro pulse diode laser
photocoagulation [810 nm]) was also explored in acute and chronic CSC.

Cryotherapy and low-dose plaque radiotherapy
• Cryotherapy and low-dose plaque radiotherapy were used in
the treatment of peripheral retinal elevations in parsplanitis
associated with telangiectatic vessel leakage.
• Regression of the former peripheral pathologies and
absorption of the hard exudates with resolution of the retinal
elevation was reported in 4 of 5 eyes by Pollack and colleague.

PDT
• PDT with verteporfin in the treatment of CSC is believed to act
on the pathogenic mechanism leading to choroidal vascular
hyperpermeability.
• PDT is suggested to have a possible direct action on the
choriocapillaris endothelium leading to choriocapillaris
occlusion, achieving both blood flow stasis and reduction of
vascular permeability.
• Promising results were reported in several publications.

Prognosis
• As ERD is associated with a wide spectrum of underlying
pathologies, its prognosis is determined by the prognosis of
that specific condition.
• Illnesses that are generally self-limited such as ERD in
preeclampsia and pregnancy-associated CSC have excellent
visual prognosis, whereas conditions leading to irreversible loss
of tissue, such as CMV retinitis or Behcet uveitis, may have
dismal visual outcomes.

Conclusions
• ERD may develop as a consequence to any pathological condition that violates the integrity-of the
inner or the outer BRB.
• It is therefore encountered in the setting of conditions that affect the retinal vasculature and
conditions which primarily affect the choriocapillaris, RPE, outer retinal complex.
• Insight into the pathogenesis of each of those pathological conditions may allow better
understanding of the cellular and molecular mechanisms involved and may thus enable
ophthalmologists to implement local and systemic therapies that modulate the course of those sight-
threatening diseases.
• Prompt diagnosis and institution of appropriate therapy is indispensable for reducing the risk of
ophthalmic complications.
• Future research in regenerative medicine may attempt to change the course and outcome of chronic
diseases through the possibilities of engineering damaged tissues via stimulating the body's own
repair mechanisms or by growing tissues in the laboratory and safely implanting them when the body
cannot heal itself.
• This may hold promise for limiting potential visual morbidity in pathological conditions associated
with ocular blood barrier functional and structural deficits.

Exudative Retinal Detachment

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Exudative Retinal Detachment

Similar to Exudative Retinal Detachment (20)

More from Rasika Walpitagamage

More from Rasika Walpitagamage (6)

Recently uploaded

Recently uploaded (20)

Exudative Retinal Detachment

Editor's Notes