Transcript Non-neoplastic globe pathology non-neoplastic globe

Non-neoplastic globe
pathology
Case 1
White mass in
vitreous
THIS MASS IN
THE VITREOUS
CAVITY IS
COMPOSED OF
WALL-TO-WALL
NEUTROPHILS
Gram + (dark blue) cocci.
Endogenous bacterial
endophthalmitis
Endophthalmitis
Inflammation of one or more coats of the
eye and adjacent intraocular spaces.
Infectious (exogenous or endogenous)
and non-infectious (lens induced, foreign
body)
Infective endophthalmitis
Causes after surgery: Gram + bacteria:Staphs,
streps, corynebacterium, propionibacterium
Gram- bacteria: pseudomonas, proteus,
haemophilus, klebsiella, E-coli, enterobacter.
Fungi: Aspergillus, candida, penicillium
Causes of endogenous endophthalmitis
Fungi: Candida and Aspergillus
Bacteria: Neisseria meningitidis, streptococcus,
staphs, bacillus cereus, nocardia
Case 2
History
Male adult
Leukaemia
On chemo.
Brain abscess
Dies
Total body biopsy (Autopsy).
Eyes examined by ophthalmic pathologist.
Retina in reasonable good shape
Full thickness necrosis of
neural retina, featuring
a homogeneous
eosinophilic appearance with loss
of cell details and
ghost outlines of cells.
Very little inflammation.
Cysts containing bradyzoites
(multiple black dots in pink cysts)
TOXOPLASMOSIS
Unicellular protozoal parasite.
Definitive host is CAT
Intermediate hosts: humans, rodents, fowl.
Toxoplasmosis
Parasite invades retinal cells directly
Focal retinitis with an overlying vitritis
In this case presented with ARN (well
recognised).
Toxoplasmosis
Years later-reactivation can occur in areas
of scars
Congenital and acquired forms
Congenital form-associated with
encephalomyelitis, hepatosplenomegaly
and retino-choroiditis
Histology of Toxoplasmosis
Protozoa in 3 forms



Free trophozoite-lives in intracellular vacuole.
Pseudocyst form-many protozoa enclosed by
retinal cell membrane.
Bradyzoite surrounded by self-made
membrane-becomes cyst and can be
extruded from retinal cells. Cyst forms when
environment hostile. Cyst can remain latent.
Case 3
Red eye
Patient just arrived from SouthEast Asia
Exudate in AC
Thickened iris
Granulomatous
inflammation
Pink, acid fast bacilli, stained
with Ziehl-Neelsen stain.
Other ways of detecting TB-Culture,
PCR.
TB UVEITIS
TB AND THE EYE
Direct innoculation, contiguous or bloodborne.
Lids, conj, orbit, cornea, episclera and
sclera, retina, optic nerve all involved.
Cornea-immune mediated reaction
(interstitial keratitis).
Choroid vulnerable-rich blood supply
NON-INFECTIVE
INFLAMMTION
1
Non-caseating naked
granulomas, in
retina
SARCOID AND EYE
Idiopathic
Afro-caribbeans
30 % ocular involvement
Uvea, retina, lacrimal gland
Anterior uveitis, pars planitis, retinal periphlebitis
Nodules on lids, conj, band keratopathy
Non-necrotising granulomatous inflammation + fibrosis
later on.
Naked granulomas.
Can undergo necrosis
Diagnosis of exclusion.
3
Iris expanded
Higher power shows diffuse
population of small lymphocytes
Mostly T cells (CD 3+).
UVEITIS
EXOGENOUS-POST TRAUMA
ENDOGENOUS-IDIOPATHIC and those with specific causes:
Anterior (iritis), intermediate (cyclitis), posterior (choroiditis)
Associations-juvenile RhA, ank spond (HLA B27)
Reiter’s, uc, enteritis (salmonella, shigella, yersinnia), psoriatic,
behcet’s
Fuch’s uveitis syndrome, VKH.
Causes-sarcoid, tb, leprosy, syphilis, parasites, fungi (candida,
coccidio, histo, blasto), HSV, VZV, EBV,
Complications of uveitis
Cornea-endothelial cell loss-BK, band
keratopathy
AC-scar formation-iris obliteration
Iris-atrophy, necrosis, loss of muscle, PAS,
rubeosis, ectropion uveae, immobile pupil,
iris bombe
Lens-posterior cataract secondary to lens
epithelial migration.
Complications of uveitis
Ciliary body-atrophy, cyclitic membrane
Vitreous-vascularisation, condensation,
PVD
Choroid-atrophy, scarring, chorioretinal
scar.
Retina-perivasculitis, cmo, exudative
detachment, rpe alterations.
Glaucoma-clogging due to cells, PAS,
pupil block, bombe, trabeculitis
4
Diffuse chronic
inflammation of
sclera-brawny type
Chronic inflammatory cells
Palisaded granulomatous
Inflammation of sclera with collagen degeneration (necrobiosis).
This is seen in nodular variant
scleritis
Often see this pattern
of inflammation in
connective tissue
disorder assoc. scleritis
Granulomatous inflammation again
SCLERITIS
Diffuse chronic inflammation in diffuse form,
Or : granulomatous inflammation with
collagen degeneration (necrobiosis) in
nodular form.
SCLERITIS
Anterior-diffuse, nodular and necrotising
with inflammation (brawny), necrotising
without inflammation (scleromalacia
perforans)
Posterior-30% associated with systemic
vasculitides, CTDs (rheumatoid, SLE,
PAN, Wegener’s, relapsing polychondritis
etc etc), lymphoma.
Complications of scleritis
Keratitis
Cataract
Uveitis
Glaucoma
Perforation of sclera
Retinal detachment
5
Choriocapillaris intact
Granulomatous (non-caseating)
inflammation of uvea
(choroid in this case), sparing the
choriocapillaries
Dalen-Fuch’s nodule-sub RPE granuloma
(arrow).
Reaction to uveal melanocytes….(current
thinking)
Histological differential: INFECTION,
SARCOID,VKH
DIFFERENTIAL
INFECTION, SARCOID,VKH
6
DIABETES AND THE
EYE
Should be very familiar with this
topic.
Pathogenesis
Irreversible non-enzymatic glycation of proteins occurs, for example:
of matrix proteins (platelet activator inhibitor -1); this affects cell migration/activation
of calcium channels in pericytes (responsiveness to endothelin-1-induced
contractility) and thereby affecting function
apoptosis has been linked to hyperglycemia and retinal pericyte death
hyperglycemic states deplete intracellular glutathione (defense against peroxidation)
hyperglycemic environments trigger upregulation of bax (apoptosis activator) and
downregulation of bcl-2 (apoptosis inhibitor) eventually causing capillary pericyte
and capillary endothelial cell death
-glycosylated hemoglobin levels correspond to increased risk of retinopathy
-growth factors that are considered to have a role in PDR include VEGF, Insulin likeGF I,
Fibroblast GF; chemical mediators include IL-8 and interferon induced protein
VEGF is associated with endothelial cell hypertrophy and capillary lumen obliteration
-evidence of an intra-ocular rennin-angiotensin system with vitreous pro-rennin in
diabetic
patients; intra-ocular angiotensin-II synthesis is elevated and may have a role in NVI
in DR
-abnormal platelets, abnormal red cell deformability (micro-displacement), altered
leucocyte
deformability and altered blood viscosity contribute to retinal vessel occlusion and
ischemia
-plasma lipids are associated with hard exudates
-growth hormone is thought to support development and progression of DR
Lacey vacuolation of
iris pigment
epithelium-due to
accumulation of
glycogen-present in
40% of enucleated
eyes from diabeticsDIABETIC IRIDOPATHY
Pink glycogen
deposits, with PAS
stain
Ectropion uveae, secondary to
rubeosis
New vessels on
anterior stromal
surface
Normal pars plicata
Grossly
thickened
basement
membrane of
pars plicata
Normal retinal arteriole
Arteriolosclerosis-note
thick wall-called hyalinisation.
Hyalinisation due to accumulation of
lipid and fibrin, from
leaky vessel, due to pericyte death
Exudative maculopathy-pink exudate
between RPE and fovea
Hard exudates-protein rich eosinophilic
material
settles in outer plexiform layer because
this is watershed zone between
retina’s 2 blood supplies. Therefore
cannot drain away easily.
Hard exudates composed of lipid
containing foamy
macrophages
Ovoid eosinophilic bodies of
varying size in optic fibre
layer
Pink bodies in
optic fibre layer-cotton wool spots
or cytoid bodies.
Indicate ischaemia and composed
of swollen axons from disturbed
axoplasmic flow-packed full
of organelles.
gliosis
Chronic ischaemia of retina.
Note loss of inner 2/3rd architecture
(RGCs, INL, IPL), and replaced by
gliosis-pink stuff.
ONL remains with outer photoreceptor
segments.
Proliferative diabetic retinopathy
Note new-vessels, surrounded
Fibrous tissue on retinal
surface.
PRP SCAR
Loss of choriocapillaris
Bruch’s
Loss of RPE
Gliotic retina
PRP SCAR-loss of RPE and choriocapillaris
Retinochoroidal atrophy
Retinal gliosis
Gliotic retina in direct apposition to Bruch’s
7
Occluded branch venule. Note
inflammation around vessel
-attempts at organisation
of thrombus
Perl’s stain picks up haemosiderin
Stains it intense blue.
This indicates previous intra-retinal
haemorrhage from BRVO
CRVO/BRVO
8
Hard druse. Pink, homogeneous nodular material
Lies between RPE basement membrane and
inner collagenous part of Bruch’s.
Note overlying RPE arophy
Drusen
Made up of:
Alpha 1 antitrypsin
Alzheiner amyloid beta protein
Amyloid p protein
Apolipoproteins B and E
Cholesterol esters
Clusterin
Complement factors
Complement receptor 1
Factor 10
Heparan sulfate proteoglycan
HLA DR
Immunoglubulins
MHC class 2 antigens
Peroxidized lipids
Phospholipids
TIMP-3
Transthyretin
Ubiquitin
vitronectin
Thickened Bruch’s
Fluffier, more diffuse, soft drusen
Thick Bruch’s, hard drusen and
complete loss of photoreceptors
Haemorrhage of CNVM.
CNVM lies between neural retina
And RPE
Eventual organisation of haemorrhage
Will lead to disciform scar.
RPE
choroid
RETINA
CNVM
RPE
Vessel of CNVM
CNVM
choroid
RPE
ARMD dry and wet
ARMD….
Commonest cause of legal blindness in
developed world.
Elderly Caucasian
Hallmarks=drusen, RPE atrophy, CNV
Pathogenesis ?
Defects in RPE-Bruch’s-choriocapillaris
complex
Collection of heterogeneous disorders
associated with multiple genetic and
environmental factors
ARMD pathogenesis ?
Bruch’s accumulates lipids, non-collagenous proteins,
extracellular matrix + collagen and elastin changes. This
occurs with aging.
Then…second phase…accumulation of basal linear
deposit (between RPE cell and its basement membrane)
and basal laminar deposit (between RPE basement
membrane and inner collagen layer of Bruch’s
membrane).
Lipofuscin accumulates in RPE.
Resultant increase in thickness of Bruch’s and impaired
molecular transport through Bruch’s and
RPE……photoreceptor cell death…..AMD.
Drusen=sign of sick RPE.
Thickening of Bruch’s thought to lead to
metabolic changes and hypoxia. This is a
stimulus for angiogenic factor release from RPE
cells. Basal laminar deposits associated with
neovascularisation. Choroidal
neovascularisation leads to-exudative AMDhaemorrhage-disciform scarring
Some AMD facts
Wet and dry forms
Risk factors: age (older), sex (women?), race
(white caucasian),light exposure (controversial),
cardiovascular (atheroma), diet (lipids, AREDS
study-zinc and anti-oxidants), smoking+
Complement factor H gene strongly associated
with AMD (up to 50% of cases). Single
nucleotide polymorphism (Tyr402-His). Thought
to lead to inappropriate inflammatory response
of which drusen is a product. Leads to death of
RPE and photoreceptors.