METABOLIC DISORDERS
WITH
OPTHALMOPATHIES
DR. A.KASIBABU M.D;D.N.B.
ASSOCIATE PROFESSOR
ANDHRA MEDICAL COLLEGE
VISAKHAPATNAM
ZINC
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Trace element for > 200 metalloenzymes
↑↑conc. In photoreceptors.
In deficiency state: rash around eye,
nose & mouth
Loss of cilia of eyebrow & lid margin.
Conjunctivitis
Thinning of corneal epithelium, with loss
of epithelial polarity in bowman’s layerleading to linear subepithelial scars.
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ZINC….
Rhodopsin &aqueous- production is
effected-↓(enzymes)alcohol
dehydrogenase&car.anhydrase
Ciliary body atrophy, optic atrophy&
cataract also seen.
In excess state: corneal
edema&white opacities on the
ant.lens capsule and ant.
Uveitis(↑I.O.pressure)
Copper
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Trace elements for oxidases .
X-linked recessive disorder- Menke’s
In deficiency states:
Atrophy of nerve fibre layer&
ganglion cells.
Lacy vacuolization of the iris pigment
epithelium
Fundus is blond or whitened but no
photophobia.
The above - Classified as albinoidism
Copper ….
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In excess states(called chalcosis):
Locally, intraocular foreign bodies of
copper are destructive- causing intense
inflammation & abscess formation
Electroretinogram is diminished.
Vitreous liquifies & disorganised
Deposits in lens, cornea &severe
ant.uveitis.
Sunflower cataract
Kaiser Fleischer’s ring in peripheral
descemet’s membrane- brownish
hue(Wilson’s disease)
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IRON
Iron deficiency: manifests as anemic
retinopathy (Hb% < 8gms%)
Retinal hemorrhages extending to
vitreous.
Vessels are tortuous (with yellowish
hue)
Cotton wool spots, white centered
hemorrhages
Appearance of central retinal vein
occlusion
IRON EXCESS
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Iron deposits in all ocular structures.
Hemosiderosis –Hb degradation products
Siderosis bulbi - iron only
Not seen in basement membrane(unlike Cu)
Pigmentary & inflammatory changes in the local
region
At cellular level - membrane damage to
mitochondria,microsomes due to increased lipid
peroxidation( in photoreceptors)
In the cornea: rust rings,develop with deposition
with in epethelial cells, keratocytes, bowman’s
layer,stromal lamelle
Systemic siderosis effects mainly choroid&sclera
Most patients don’t have visual symptoms.
Perilimbal pigmentation(due to ↑ melanin
production)&increased eyelid margin production.
VITAMIN DISORDERS
VITAMIN-A
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Deficiency states:
Night blindness (Nyctalopia) - dark
adaptation, electroretinographic findings,
visual field studies are abnormal but
reversible with treatment.-outer segment
degeneration of recep.
Conjuntival xerosis & bitots
spots.(interpalpebralconjunctiva with
keratinisation of the epithelium.)
↓ conjunctival mucous production leads to
thickening & opacification
Secondary infections may lead to scarring
of lacrimal ducts &further drying of eyes.
Cornea in vit A ↓
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Punctate keratopathy
Xerosis of cornea leads to
keratomalacia or a sharply
demarcated ulcer leading to
perforation
Fundus-xerophthalmic fundus with
retinal lesions & have a whitish
yellow appearance with irregular & ill
defined borders.
Vit-B1(Thiamine)
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Absorption effected by thiaminases in fish,
shrimp or absorptive disorders
↑requirement in- thyrotoxicosis, pregnancy
and lactation ,fever.
↓ utilisation in – thiamin responsive
megaloblastic anemia, branched chain
ketoaciduria & intermittent cerebellar
ataxia
↓TPPin neural tissue in subacute
necrotising encephalomyelopathy(Leigh’s
disease)
Main ocular side effects-optic atrophy. l
epithelial changes, rectus muscle palsies,
nystagmus in dry Beri beri.---whereas in
wet beriberi only systemic findings.
Vit-B12 deficiency
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Causes demyelination of peripheral nerves
&degeneration of axons affecting optic
nerve fibres
Epileptiform blinking of eyelids with
upward deviation of the eyes for
seconds.& pigmentary retinopathy in the
Post.pole
Optic atrophy with central & centrocaecal
scotomas
If severe, can lead to retinal hemorrhages
in the nerve fibre &outer plexiform
layers.—in megaloblastic anaemia.
Inborn errors of metabolism
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Homocystinuria:↓ of cystathionine βsynthase
↓methylcobalamin&B6
Autosomal recessive
Dislocation of lens (inferiorly, zonular
degen.)
Cataract
Glaucoma:
Also, pigmentary retinopathy.
Lacy vacuolization of iris pigment
epithelium&photoreceptor cell atrophy.
Partial loss of nerve fibre & ganglion cell
layer.
Optic atrophy. (in methy malonic aciduria
Endocrine Disorders
Hypercalcaemia
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Due tohyperparathyroidism/MEN1/MEN2
In MEN2 B – chr10 – enlarged corneal
nerves,facial neuroma affecting
eyelids. Band
keratopathy(cal.corn.epi.&bow.mem)
Scleral calcification as white flakes
Calcium deposits in pigmentary
epithelium of iris,ciliary body &
choroid –also perilimbal deposits—
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Hypocalcaemia
In hypoparathyroidism,
hypovitaminosis D.
Cataract.(small white or
polychromatic crystals in ant. Or
post. Cortex)
Kerato cojunctivitis
Papilloedema.(reversible)
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Tyrosinosis
↓ tyrosine amino transferase activity.
Type 1 - ↑risk of hepatocellular carcinoma.
Type 2- Richnar-Hanhart syndrome
-cornea- stellate/plaque like ulcersphotophobia&tearingsubepi.crysta.deposits.
-conjunctiva hyperaemic &
thickend.
-loss of Goblet cells,vacuolated
superficial
epithelial cells & sub
epithelial plasma cell infiltration.
Alkaptonuria
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Autosomal recessive, defect on chr.3.
↓of homogentisic oxidase.
Onchronosis: gray to blueish black
pigmentation of collagen.
Discolouration of sclera.-earliest one- more dense in interpalpebral zone,discrete droplets of brown pigment in
peripheral stroma.
Treatment: restriction of phenylalanin,
tyrosine.
Vit C reduce excretion of toxic metabolite
of homogentisic acid – benzoquinone acetic
Gout
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Disorder of purine metabolism with↑ s.uricacid
xanthine oxidase activity- urate reaches
saturation level(>420mg/dl),tissue deposition
&
crystalisation occur.
Lesch-nyhans syndrome (↓ hypo xanthine
PRPP transferase)- neurologic abnormality
Kelly-Seegmiller syndrome –only partial
deficiency-no neurological symptoms. Retinal
& gouty disease.
Urate crystals deposited in corneaintranuclear with non-bi refringent
crystals&,fine golden yellow epithelial
extending to limbus.
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ALBINISM (Hypo melanosis)
Occulo cutaneous form ↓pigmentation
Occular albinism-only eye is effected
& lacks visual pigment.
CYSTINOSIS: cystine crystals seen in
cornea by slit lamp microscopy.
HYPER ORNITHEMIA: ocular findings
are not much specific
Lysosomal enzyme storage
disorders
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Lysosomes produced by golgi
apparatus fuse with secondary
lysosomes (endo- sosomes) to digest
all types of material.
1.Muco polysaccharidosis
2.Mucolipidosis
3.Sphingolipidoses
4.Glycoprotein storage disorders
Mucopolysaccharoidosis-1
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α -iduronidase↓: ↑ dermatan sulphate &
heparin sulphate.
Severe form: Hurlers syndrome corneal clouding, retinal pigmentary
degeneration, optic atrophy,
papilloedema & glaucoma.
Inclusions are seen in epithelium of
cornea, lens, smooth muscle, iris
pigmentary epithelium, ciliary
epithelium &vascular endothelium.-also
in optic nerve pericytes.
Mucopolysaccharoidosis-1….
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Intermediate phenotype: HurlerScheie syn.
Corneal clouding, glaucoma,
papilloedema
Retinal degeneration & optic atrophy.
Mild form: scheie syndrome: corneal
clouding, pigmentary retinal changes,
papilledema, glaucoma & optic
atrophy.
Mucopolysaccharoidosis-2
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MPS -2: Iduronate sulfatase
deficiency (Hunter’ syndrome )
A : severe form –pigmentary
retinopathy in the setting of clear
cornea.
papilledema&optic
atrophy may occur.
B: mild form – retinal degenaration
at a slower rate and corneal opacities
are subtle. In both ,marked
thickening of sclera due to
membrane bound vesicles in unusual
Mucopolysaccharoidosis-3
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Type A(severe form) – Heparan Nsulfatase↓
Type B(milder)-N-Acetyl α
glucosaminidase↓
Type C(Mild) – Acyl coA : Glucosamine
N- Acetyl transferase↓.
Type D(Mildest)- N-Acetyl glucosamine
6 - sulfatase↓.
A clear cornea & no–
papilledema/glaucoma, retinal
Mucopolysaccharoidosis-4
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Marquio’s syndrome
Type A-N-Acetyl galactosamine-6sulphatase↓
Type B -β-galctosidase ↓
Corneal clouding, papilledema&lack of
pigmentary changes&no optic atrophy.
Mucopolysaccharoidosis-5(MPS-1
scheie)
Mucopolysaccharoidosis-6
(Maroteaux-lamy syndrome)-N-acetyl
hexosamine-4-sulphatase↓.
Mucopolysaccharides are deposited within
corneal epithelium, bowman’s layer &
keratocytes .
If severe-ganglion cell atrophy/ optic
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Mucopolysaccharoidosis-7(sly
syndrome)
β- glucuronidase↓-accumulation of
dermatan sulphate.
Mild corneal clouding (corneal deposits
may recur after grafting)
Pigmentary retinopathy
Papilledema & some times optic
atrophy.
sphingolipidosis
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Glycolipids with sphingosine base are not
degraded properly&accumulate in
cytoplasmic vesicles of lysosomes.
1.gangliosidosis:β-galactosidase↓.
- infantile&juvenile(no corneal
clouding,optic atrophy with material with
in optic neuronal cells.
- adult form(↑↑conc.in dendrites&
at nerve endings)
- in cases of β-galactosidase&
neuraminidase ↓- corneal
clouding,occasional cherry red spot.
Gangliosidosis :
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Taysach,s disease(GM2- accumulation)
First discovered by opthalmologistKLENK -1942
HEXOSEAMINIDASE A↓
Classic finding- cherry red spot(50% of
pts.)
Accumulation in dense ganglion cell layer
of macula- seen in infantile form.
Pigmentary retinal changes&optic
atrophy with occulomotor
abnormalities(juvenile form)
Retinitis pigmentosa is a secondary
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Abnormal macula with grey
discolouration&granular
pigmentation(with opacities) about
the fovea.
Type 1: acute(cherry red spot)
sub acute- macula
halo(1/2of macula) syndrome with
crystalloid opacities but no vision
deffect.
Type 2: accumulation in the
keratocytes of cornea,lens, ganglion
cells&optic nerve.
Sandhoff,s disease(hex.A&B ↓)-β
sub unit of enzyme -pleomorphic
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6.Fabrys: X-R; α galactosidase A↓( or
ceramide trihexosidase)
deposition of glycosphingolipids in
corneal epithelium as white to golden
brown material as a whorl like pattern.
lenticular changes in ant. Cortex or
capsule - a characteristic finding,is a
spoke like deposit in posterior lens
capsule
Treat – infusion of enzyme
Retinal vessels tortuous &a central
retinal art.occlusion.
Sausage like dilatation of venules
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2.Neimann picks diseasesphingomyelins acumulate in ocular
tissue.
3. Gauchers - β glucoserebrosidase ↓
↑serum ACP.
4. Krabbes - β galactosidase ↓
myelin absence in CNS,so optic
atrophy.
5.Metachromatic leukodystrophy↓aryl sulfatase A- reversal of
cerebroside:sulfatide ratio-optic
atrophy.
Retinitispigmentosa
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Related with abnormal lipid metabolism(ex:
Niemannpick’s disease)-A.D/A.R/X-R
Slowly progressive,with loss of
night&peripheral vision.
Associated with mutations in the protein
moiety of rhodopsin&peripherin/ROM-1.
Peripherin: a 344 A.A. residue protein located
in the rim region of disc membrane.
A mutation in exon 1 of the gene coding for
peripherin.
Specific change in peripherin is a C-to-T
transition in the first nucleotide of codon 46,that resulted in changing an arginine to stop
codon(a denovo mutation).