OPTHALMIC MANIFESTATION

OF SYSTEMIC DISEASE AND

COMMON OPTHALMIC
DISORDER IN CHILDREN

Eric Yew Ho Qing (74718)

Nur Fatin Batrisyia binti Rumaizi (73711)
Laurencia Guyang Anak Juing (73530)
Sassy Decia anak Benjamin (73819)
Muhammad Shahrulnizam bin Hatity (73574)
Yvonne Siew Wei (77242)
Nabilah Natasya binti Abdul Karim (73647)
 01 02 03 04
Congenital
Leucoria and Nasolacrimal Thyroid Eye Diabetic
Retinoblastoma Duct Disease Retinopathy
Obstruction

CONTENTS
 LEUCORIA AND
RETINOBLASTOMA
 Leukocoria

The term leukocoria means "white pupil" (from the Greek "leukos"
meaning white and "kore" meaning pupil) and is the name given
to the clinical finding of a white pupillary reflex. It happens when
there is a disruption along the way where the light passes through
the transparent optical media (tear film, cornea, aqueous humour,
lens and vitreous body).
 Differential diagnosis of
leukocoria
1. Strabismus
Ocular misalignment causing asymmetric red reflex

2. Anisometropia
Difference in refractive errors causing asymmetric red reflex where one eye is dimmer
than the other. The healthy eye will have deep red reflex while the potentially amblyopic
eye has lighter and brighter reflex.

3. Retinoblastoma
A sinister cause of leukocoria.
 Differential diagnosis of
leukocoria
.4 Cataract
Aetiology: inherited, underlying disorders (TORCH), ocular
trauma, exposure to glucocorticoids and ionizing radiation
Clinical features: Presents as leukocoria, a dull red reflex,
halo in light, polyopia

5. Retinopathy of prematurity (ROP)

Presents with abnormal vascularization leading to fibrosis
and retinal detachment
Leukocoria is seen in advanced disease due to a large
tractional retinal detachment
 Differential diagnosis of
leukocoria
7. Coats disease
A vascular disease of the retina characterized by
retinal telangiectasis, subretinal exudate and retinal
detachment .
Clinical features: decreased visual acuity, strabismus,
leukocoria

8. Persistent fetal vasculature (Persistent hyperplastic primary vitreous)

Persistence of fetal tissue due to improper involution of the primary
vitreous body and hyaloid vasculature during gestation that blocks the
light passing to the back of the eye
Affected patient usually develop glaucoma
 Differential diagnosis of
leukocoria
9. Vitreous hemorrhage
Secondary to trauma, posterior uveitis or any vascular
abnormalities
Causes leukocoria when there is extensive organization of
the blood into a clot before degradation: over time, the
reddish of the blood is lost and the hemorrhage transforms
into whitish debris
 Retinoblastoma: Introduction

Commonest primary malignant intraocular tumor affecting children

Rare, occur in 1:20000 live births
Arises from retinal nuerons (neural retinal tumor)
 Genetics of Retinoblastoma

1.Heritable retinoblastoma (40%)

Bilateral and multifocal tumour
Predisposed to non-ocular cancers: pinealoblastoma
(trilateral retinoblastoma), osteosarcoma, melanoma

2. Non-heritable retinoblastoma (60%)

Unilateral and unifocal tumour
Not predisposed to second non-ocular cancers
 Pathogenesis of
Retinoblastoma
Endophytic: vertical growth of tumor toward and into viterous cavity- seeding
of tumor in viterous humor- enter the anterior chamber and layer behind the
cornea causing pseudo hypopyon
Exophytic: Vertical growth of tumor into subretinal space, leading to
exudative retinal detachment
Diffuse infiltration: tumor remain flat and grow intraretinally
Metastatic spread
Most common routes of metastatic spread are direct infiltration via optic
nerve to the central nervous system
Dispersion of tumor cells through cerebrospinal fluid to CNS
Hemogenous spreasd to lung, bone, liver
Classification: International Intraocular
Retinoblastoma Classification (IIRC)
Classification: International Intraocular
Retinoblastoma Classification (IIRC)
Classification: International Intraocular
Retinoblastoma Classification (IIRC)
Classification: International Intraocular
Retinoblastoma Classification (IIRC)
 Clinical presentation

Symptoms: Signs:
Leucocorea. (60%)
Early intra retinal lesion is placoid white lesion
Strabismus (20%)
Endophytic tumor grows towards viterous from
Cataract
rtina as a white mass that seed into the gel
Secondary glaucoma
Exophytic tumor grows outwards as a sibretinal
Pseudohypopyon
multilobulated white mass that detaching the
Orbital inflammation
retina
Proptosis
Clinical presentation
 Investigation
1.Red reflex testing- to screen for leukocoria using direct opthalmoscope

2. Opthalmologic examination under anesthesia- complete visualization of retina

and identification of tumor and subretinal or viterous seeding

3 . Ocular Ultrasound – assess tumor size, detect calcification

3. MRI – evaluate optic nerve, detect extraocular extension

4. Systemic assessment – detect metastasis include physical exam and MRI of orbit
& skull. If metastatic disease is present, bone scans, marrow aspiration &
lumbar puncture are performed
Treatment
 CONGENITAL
NASOLACRIMAL
DUCT OBSTRUCTION
(DACRYOSTENOSIS)
Dacryostenosis is commonly caused by obstruction at
the valve of Hasner or Rossenmuller.
Occurs in ~6% of newborns.
Most common cause of persistent tearing and ocular
discharge in baby.
Most often, it resolves spontaneously before the baby
reaches 1 year old.
No gender predilection.
Nasolacrimal duct obstruction can cause stasis of
tears in the lacrimal sac, which predisposes to
secondary bacterial infection of the lacrimal sac
(dacryocystitis); presented with swelling at medial
canthal tendon area.
 AETIOLOGY

Failure of complete development of the

nasolacrimal ducts by the 8th month of gestation.
 SIGNS & SYMPTOMS

Epiphora (excessive
tearing)
Crusting of the eyelid
Mucopurulent
discharge
Regurgitation on
pressure over the
lacrimal sac (ROPLAS)
 INVESTIGATIONS
1. Fluorescein dye disappearance test
A drop of sterile 2% fluorescein is instilled
into both conjunctival sac.

The child is observed with a cobalt blue

light 5 minutes later.

Persistence of the fluorescein dye in the

tear meniscus indicates nasolacrimal duct
obstruction.
2. Lacrimal system probing and irrigation
Hard stop (A):
Occurs when cannula enters the lacrimal sac, coming to a stop at the medial wall
of the sac, through which can be felt the rigid lacrimal bone.
This excludes complete obstruction of the canalicular system.
Gentle saline irrigation is then attempted.
If saline passes into the nose and throat, when it will be tasted by the patient, a
patent lacrimal system is present.

Soft stop (B):

Occurs when presses the soft tissue of the common canaliculus
This indicate there is a blockage in the canalicular system.
3. Jones test
Primary test (A)
Positive: fluorescein recovered from the nose
--> patency of the drainage system.
Negative: no dye recovered from the nose --
> partial obstruction or failure of the lacrimal
pump mechanism.

Secondary test (B)

Positive: fluorescein-stained saline recovered
from the nose --> partial obstruction of
nasolacrimal duct
Negative: unstained saline recovered from
the nose --> upper lacrimal dysfunction
 TREATMENT
1. Massage of lacrimal sac (Crigler technique)
The index finger is initially placed over the common canaliculus to
block reflux and then rolled over the sac, massaging downwards.
2. Nasolacrimal duct probing
Passage of a fine wire via the
canalicular system and
nasolacrimal duct to disrupt the
obstructive membrane.

May be preceded and followed by

irrigation to confirm the site of
obstruction and subsequent patency
respectively

Risks include the induction of

canalicular stenosis due to probe
trauma
3. Conventional dacryocystorhinostomy (DCR)
Lacrimal bypass surgery that creates a path from the lacrimal sac
through the lacrimal sac fossa directly into the middle meatus.
Indicated for obstruction beyond the medial opening of the common
canaliculus.
 TAKE HOME MESSAGE
Symptoms of nasolacrimal duct obstruction in children
can resolve spontaneously.

Probing with silicone tube placement often is the second

step in the treatment of CNLDO when primary probing
and irrigation fails.

Massage of the tear duct treatment was found to have a

higher rate of nonsurgical resolution of CNLDO than
observation alone.
THYROID EYE
DISEASE
What is thyroid eye disease?

Thyroid eye disease is an autoimmune disease of retroocular tissues,

in patient with Graves’ disease
It is caused by autoantibodies directed against thyroid-stimulating
hormone (TSH) receptor that is expressed in adipocytes and
fibroblast, together with the action of activated T cells, hence
initiating retro-orbital inflammatory environment.
This disorder is characterized by enlargement of extraocular muscle,
fatty tissue and connective tissue volume
TED is often associated with hyperthyroidism but it can also occur in
hypothyroidism (Hashimoto’s thyroiditis) and euthyroidism
TED is a self-limiting disease, may present in one of two stages :
Active stage : active inflammation leads to orbital muscle
enlargement, conjunctival injection, chemosis, ocular pain, swelling of
periocular tissue and eyelid
Quiescent stage follow spontaneous resolution of active phase

Primary thyrotoxicosis
(thyroid gland is enlarged, firm and diffuse)
predominantly eye >systemic manifestation
CAUSES
Grave’s disease
Thyroiditis
Thyroid adenoma
Toxic multinodular goiter/single hyper
functioning “hot” nodule
Types of TED
Type 1
symmetric
mild exophthalmos
lid retrsction

Type 2
extreme exophthalmos
compressive optic neuropathy
extraocular muscle involvement
 RISK FACTORS

1.Family history of Graves‘ disease or Hashimoto's disease

2.Smoking
3.Female
4.Radioiodine therapy
5.Poorly controlled thyroid function
6.Stress
7.Advancing age
PATHOPHYSIOLOGY
TSH receptor is expressed in adipocytes, fibroblasts of
extraocular muscle & orbital connective tissue
auto-antibodies target the fibroblasts in the eye muscles and
these fibroblasts differentiate into fat cells,the fat cells expand
and become inflamed
The orbital veins are compressed, and are unable to drain out
blood,resulting in orbital edema.
TSH receptor antibodies and cytokine activate fibroblast
This cause secretion of Glycosaminoglycans, GAG (hyaluronic
acid) and adipogenesis to occur
Accumulation of GAG lead to fluid accumulation, muscle
swelling and increased pressure within orbit
Displace eyeball forward (proptosis/exophthalmos)
Extraocular muscle dysfunction and in severe cases optic
nerve compression occurs
 EPIDEMIOLOGY
The prevalence of TED in Malaysia was 34.7% in three populations of Asian
patients with Graves’ disease
Within the Asian population, Lim et al.[10] found no significant difference in the
prevalence of TED in patients with Grave Disease between ethnically Indian,
Malay, and Chinese patients in Malaysia (Indians: 40%, Malays: 35.1%; Chinese:
34%, P = 0.928).
Female > Male
TED present usually in 40-50 years old
Men and older age are associated with more severe ophthalmopathy.
Untreated, TED tends to ‘burn itself out’ within 3-36 months
Recurrence is usually uncommon
 SIGN AND SYMPTOMS

Lid lag (von Graefe’s sign) found in 50% of Grave's disease

1. Dynamic form of eyelid lag associated with TED

2. Delayed descent of upper eyelid during downgaze
(contracture of the levator muscle d/t fibrosis)
3. Unilateral or bilateral, only upper eyelid affected

Exophthalmos
1. Unilateral or bilateral
2. Always axial (eye protrude directly forward)
3. Caused by increase in bulk of ocular muscles
and orbital fat
Restrictive extraocular myopathy

1. Limitation of elevation with

downward deviation (common)
2. Due to fibrosis (tethering) of inferior
rectus muscle
3. Often mild limitation of ocular
movements in all directions of gaze
4. Diplopia is most likely to occur due
to ocular misalignment
5. Others: adduction defect, depression
defect, abduction defect
Werner classification reflects the severity of the ophthalmopathy

• Grade 0- No signs or symptoms.

• Grade 1-Only signs.(lid retraction).
• Grade 2-Soft tissue involvement (Chemosis).
• Grade 3-Proptosis (minimum<23,moderate marked.28mm)
• Grade 4-Extraocular muscle involvement
• Grade 5- Corneal involvement.
• Grade 6-Loss of sight.
 EXAMINATION

Visual Acuity Pupillary light reflex Colour vision test

Extraocular
Visual Field Fundus examination
movement test

Exophthalmometer
 INVESTIGATIONS

Thyroid function test Thyroid auto antibodies Ultrasound B Scan

CT Scan of orbit MRI Scan of orbit

Ultrasound B Scan
CT Scan of orbit
MRI Scan of orbit
 MANAGEMENT

MILD MODERATE/SEVERE

Oral prednisolone
Smoking cessation
Orbital irradiation
Elevate bed
Cyclosporine, methotrexate
Selenium and vitamin D
Tarsorraphy
Lubricants
Surgical decompression
 COMPLICATIONS
Dysthyroid optic neuropathy Exposure keratopathy

Strabismus Glaucoma

TAKE HOME MESSAGES

Thyroid eye disease is an autoimmune disease of retroocular tissues, in patient
with Graves’ disease
Clinical features : lid retraction, restrictive myopathy, compression optic
neuropathy
 DIABETIC
RETINOPATHY
 EPIDEMIOLOGY

A total of 15,000 subjects were

examined with a response rate of
95.3%.
Untreated cataract (58.6%), diabetic
retinopathy (10.4%) and glaucoma
(6.6%) were the commonest causes
of blindness. (Chew et al., 2018)

MINISTRY OF HEALTH MALAYSIA, CLINICAL PRACTICE GUIDELINES SCREENING OF DIABETIC RETINOPATHY, JUNE 2011;
 EPIDEMIOLOGY
The prevalence of diabetic
retinopathy in Malaysia has been
reported to range from 44.1% to
48.6%. Other studies have shown
that the prevalence of diabetic
retinopathy in Malaysia is 12.3%
for Type 1 DM and 22.3% for Type
2 DM. (Ali et al., 2016)

From Diabetic Eye Registry

Malaysia, 50.7% (mild NPDR),
26.1% (moderate NPDR), 9.5%
)severe NPDR), 11.4% (PDR), and
12.8% etc

MINISTRY OF HEALTH MALAYSIA, CLINICAL PRACTICE GUIDELINES SCREENING OF DIABETIC RETINOPATHY, JUNE 2011;
 CLASSIFICATION

MINISTRY OF HEALTH MALAYSIA, CLINICAL PRACTICE GUIDELINES SCREENING OF DIABETIC RETINOPATHY, JUNE 2011
 PATHOPHYSIOLOGY
Hyperglycemia leads to the activation of
alternative pathways of glucose
metabolism[1] such as the polyol pathway,
advanced glycation endproducts (AGEs)
formation, protein kinase C (PKC)
activation, hexosamine pathway flux and
Poly(ADP-ribose) polymerase activation

The end result of these pathways is the

activation of cytokines and growth
factors, leading to vascular endothelial
dysfunction, increased vascular
permeability, and eventual microvascular
occlusion.
WANG W, LO ACY. DIABETIC RETINOPATHY: PATHOPHYSIOLOGY AND TREATMENTS. INT J MOL SCI. 2018 JUN 20;19(6):1816. DOI: 10.3390/IJMS19061816. PMID: 29925789; PMCID: PMC6032159.
MICROVASCULAR The earliest responses of the retinal blood vessels to
hyperglycemia are dilatation of blood vessels and blood
flow changes.
OCCLUSION These changes are considered to be a metabolic
autoregulation to increase retinal metabolism in diabetic
subjects.
Pericyte loss is another hallmark of the early events of
DR. Evidence of apoptosis of pericytes triggered by high
glucose has been shown in both in vitro and in vivo
studies.
In addition to pericyte loss, apoptosis of endothelial cells
and thickening of the basement membrane are also
detected during the pathogenesis of DR, which
collectively contribute to the impairment of the BRB [8].
Furthermore, pronounced loss of pericytes and
endothelial cells results in capillary occlusion and
ischemia.
Continued ischemia stimulates retinal cells to release
pro-angiogenic factors such as VEGF. Such factors
stimulate neovascularization to bypass damaged retinal
blood vessels. The formation of new blood vessels occurs
from existing capillaries as a result of angiogenesis
TARR JM, KAUL K, CHOPRA M, KOHNER EM, CHIBBER R. PATHOPHYSIOLOGY OF DIABETIC RETINOPATHY. ISRN OPHTHALMOL. 2013 JAN 15;2013:343560. DOI: 10.1155/2013/343560. PMID: 24563789; PMCID: PMC3914226.
 MICROVASCULAR LEAKAGE
BRB injury causes solute leakage and a rise in capillary
pressure, which increase the osmotic pressure of the
intercellular substance and lead to macular edema.
VEGF, a key factor involved in the progression of PDR
and DME, is believed to increase vascular permeability
by inducing phosphorylation of tight junction proteins
such as occludin and zonula occludens-1 (ZO-1)
A reduction in capillaries may increase the production
of VEGF and the rest of permeability factors, causing
the rupture of BRBs and the extravasation of plasmatic
protein into the interstitium#
Since pericytes are responsible for providing structural
support for capillaries, loss of them leads to localized
outpouching of capillary walls.
This process is associated with microaneurysm
formation, which is the earliest clinical sign of DR
Retinal arteriovenous dilation raises hydrostatic
pressure of capillaries, causing tissue edema via the
Starlin rule, resulting in capillary wall dilation
YANG J, LIU Z. MECHANISTIC PATHOGENESIS OF ENDOTHELIAL DYSFUNCTION IN
DIABETIC NEPHROPATHY AND RETINOPATHY. FRONT ENDOCRINOL (LAUSANNE). 2022
MAY 25;13:816400. DOI: 10.3389/FENDO.2022.816400. PMID: 35692405; PMCID:
(microaneurysms) and rupture (hematomas)
PMC9174994.
 SYMPTOMS SIGNS

Microaneurysm
Asymptomatic Retinal haemorrhage
Dark spots or strings Hard exudate
floating in vision Cotton wool spots
(floaters) Diabetic macular
Blurring of vision oedema
Blank or dark area in Venous change
visual field Intraretinal
Decrease visual acuity microvascular
Vision loss abnormalities
Proliferative retinopathy
1. Microaneurysm 2. Retinal haemorrhage

Earliest sign of diabetic retinopathy Occur due to rupture of aneurysms

Occur due to focal capillary dilatation Dot/blot haemorrhage: intraretinal
Develop in the inner nuclear layer, haemorrhages occur in middle layer
adjacent to areas of capillary non- Flame shaped haemorrhage: occur
perfusion in superficial layer
3. Hard exudate
Discrete, yellow deposition of
lipoprotein and lipid filled
macrophages
Occur due to leakage of capillaries
4. Cotton wool spots
Small fluffy white lesions with blurred
margin
Cotton wool spots are swollen axons
within nerve fibre layers that is
damaged
Large number of cotton wool spots
indicate significant iscahemia
5. Intraretinal microvascular 6. Venous changes
abnormalities

beading looping

segmentation

Arteriolar-venular shunts, bypassed

the capillary bed
Fine, irregular, red intra-retinal lines
that run from arterioles to venues
without crossing themajor vessels
Seen adjacent to area with marked
capillary hypo perfusion
Predictor of progression to
proliferative diabetic retinopathy
Severity is graded according to the
number of quadrants of affected
retina
7. Diabetic macular oedema
Cystoid appearance of oedema at the centre of macula
Impaired integrity of BRB leads to plasma solute leakage to interstitial space
causing oedema through increase osmotic pressure

Focal maculopathy Diffuse maculopathy

Well-circumscribed retinal thickening

Dot & blot haemorrhage with diffuse
with complete or incomplete rings of
retinal thickening
exudate
Fluorescein angiogram: extensive
Fluorescein angiogram: focal area of
hyperfluorescence
hyper fluorescence
8.Clinically significant macular 9. Proliferative retinopathy
oedema

Neovascularisation may remain within the retina

(IRMA) or project forwards into the vitreous
New vessels at the disc (NVD): neovascularisation on
or within one disc diameter of optic nerve
New vessels on the iris (NVI): rubeosis iridis,
progression to neovascular glaucoma
New vessels elsewhere (NVE): neovascularisation
further away from disc
INVESTIGATIONS
Opthalmoscopy: most commonly use to screen diabetic retinopathy
 Treatment

Patient’s education
1. General Diabetic control
Lifestyle modification

PRP: decrease the oxygen demand and the level of retinal hypoxia, with
subsequent downregulation of angiogenic factors and VEGF production by the
2. Pan-retinal
retinal tissue and subsequent increased oxygen perfusion to the remaining viable
photocoagulation
retina
Focal laser:occluding leaking micro aneurysms

Treat maculopathy: stabilise blood-retinal barrier, reduce VEGF production

Intravitreal injection: Triamcinolone
3. Intraocular steroid
Intravitreal implants: Ozurdex (Dexamethasone)-retreatment after 6 months of
previous treatment

Inhibit VEGF, prevent neovascularisation, reduce leakage and oedema

4. Anti-VEGF
e.g: Aflibercept, Ranizumab

5. Vitrectomy To clear vitreous haemorrhage, release fibrous traction and flatten retina
 Complication
Diabetic macular Take home message
oedema: swelling DR classification: NPDR &
macula ->visual loss PDR
Vitreous haemorrhage Diabetic macular oedema is
a common cause of visual
Retinal detachment
impairment
Secondary glaucoma
Mainstay treatment for PDR
Cataract
is pan retinal
photocoagulation