1. OPHTHALMIC
MANIFESATIONS
OF
HEMATOLOGICAL
MALIGNANCIES
Dr PAAVAN KALRA
DEPARTMENT OF OPHTHALMOLOGY,
S P MEDICAL COLLEGE,
BIKANER

2. BASICS
• Red blood corpuscles
• Platelets
• White blood corpuscles
Granulocytes
Neutrophils
Eosinophls
Basophils  Mast cells
Agranulocytes
Monocytes  Macrophages, Tissue Histiocytes
Lymphocytes
B cells  Plasma Cells- Immunoglobulins
T cells ( CD 4+ , CD 8+)
NK cells

3. HEMATOPOIESIS

4. • LYMPHOID ORGANS
Primary – Bone Marrow & Thymus
Secondary – Spleen, Lymph nodes, Mucosa
associated aggregates( e g payer‟s
patches, tonsils)
No Lymph nodes in Orbit
Mucosa associated lymphoid tissue present in sub
conjunctiva and in lacrimal gland

5. EVOLUTION OF TERMS & CONCEPTS in HEMATONCOLOGY
Virchow (1845, 1863) first coined the terms LEUKEMIA and
LYMPHOSARCOMA
„ LEUKEMIA „ was defined as disease affecting the blood
forming organs characterized by wide spread, rapid,
disorderly proliferations of „leukocytes’ and their precursors
and by the presence at some point during the course, of
immature leukocytes in BLOOD often in large numbers
1st description of Hodgkin‟s Disease – Carswell in 1828
Term “hodgkin‟s disease” by Wilks in 1865. later also came to be
known as Lymphadenoma
Term Lymphomas was initially used to describe benign
counterparts of of Lymphosarcoma. Later came to be used to
describe all forms of lymphoid neoplastic proliferations that
arise as discrete tissue masses. ( c/w Reactive Lymphoid
Hyperplasia)

6. • Gall & Mallory in 1942 – gave the first modern classification of
Lymphomas(Non Hodgkin‟s)
• Later classifications by Rappaport (1966), Lennert(1974),
Working Formulation(1982)
• REAL classification (1994) : clubbed Leukemias of Lymphoid
origin and Lymphomas(Hodgkin‟s & NHL) in one classification
• FAB classification of Myeloid Neoplasms( leukemias)-1970s
• WHO classification of hematopoeitic and lymphoid neoplasms
2001 & 2008
(based on disease presentation, morphology,
immunophenotype and genetics)

9. • Lymphoid neoplasms include a diverse group of tumors of B-
cell, T-cell, and NK-cell origin ( including Multiple Myeloma and
related disorders
• Myeloid neoplasms arise from early hematopoietic progenitors
a)acute myeloid leukemias, in which immature progenitor
cells accumulate in the bone marrow
b)myelodysplastic syndromes, which are associated with
ineffective hematopoiesis and resultant peripheral blood
cytopenias
c)chronic myeloproliferative disorders, in which increased
production of one or more terminally differentiated myeloid
elements usually leads to elevated peripheral blood counts.
• The histiocytoses are uncommon proliferative lesions of
macrophages and dendritic cells in the connective tissues

10. Leukemias : Hematological neoplasms with widespread
involvement of Bone Marrow and Blood
• According to clinical presentation
Acute leukemias – appearance of clinical features
early in the course with fatal outcome in couple of
years if left untreated
Chronic leukemias – insidous onset of symptoms
with relatively longer expected survival, terminating
in Blast Crisis

11. PATHOGENESIS
• Tumors of hematopoietic origin are often associated with
mutations that block progenitor cell maturation or
abrogate their growth factor dependence
• In some instances, these tumors originate from
transformed HSCs that retain the ability to differentiate
along multiple lineages, whereas in other instances the
origin is a more differentiated progenitor that has
acquired an abnormal capacity for self-renewal.
• The net effect of such derangements is an unregulated
clonal expansion of hematopoietic elements, which
replace normal marrow progenitors and often spread to
other hematopoietic tissues

12. PATHOGENESIS OF OPHTHALMIC
MANIFESTATIONS
• INFILTRATION OF BONE MARROW
ineffective hematopoieseis- anemia, thrombocytopenia,
thrombaesthenia, immunodeficiency, auto immunity
• INFILTRATION OF VESSEL WALLS – weakening &
endothelial damage
• INFILTRATION OF TISSUES
skin, occular adnexa, orbit, eye ball, optic nerve, visual
pathway, meninges
• MECHANICAL EFFECTS : tumor mass
• INCREASED INTRAVASCULAR CELL MASS
• HYPER VISCOSITY – paraproteinemia, increased cell
mass
• HYPERCOAGULABILITY

13. • ISCHEMIA & INFARCTION
• METABOLIC EFFECTS : Hypercalcemia, renal failure
• PARANEOPLASTIC SYNDROME : cerebellar
degeneration in lymphoma
• EFFECT OF THERAPY

14. CHANGES DUE TO HEMATOLOGIC
ABNORMALITIES

15. ANEMIA
• Conjunctival pallor
• Ophthalmoscopic signs ( Hb < 50%)
generalized pallor of fundus and optic disc
dilatation of retinal arteries and veins- equal calibre and color
retinal hemorrhage
extra retinal hemorrhage – choroidal, pre retinal/ sub hyaloid
retinal edema
retinal exudates –hard exudates
cotton wool spots

16. Multiple intraretinal and preretinal hemorrhages and Roth's
spots – case of severe anemia

17. • Ischemic optic neuropathy
• Pseudotumor cerebri

18. THROMBOCYTOPENIA AND THROMBOASTHENIA
• Lid ecchymosis
• Sub conjunctival hemorrhage – petechiae to ecchymosis
• Hematidrosis ( bloody tears)
• Hyphema
• Vitreous hemorrhage
• Retinal hemorrhages – variable colour
• Intracranial hemorrhage –
posterior visual pathway – homonymous hemianopia
cerebellum and brain stem – nystagmus & diplopia
• Bleeding tendency in leukemias contributed by the
perivascular infiltration

19. • Rarely massive intra orbital bleed causes sudden proptosis
compartment syndrome , compressive optic neuropathy

20. THROMBOTIC TENDENCY : Virchow‟s Triad
endothelial damage ( infiltration of the vessel wall)
altered blood flow – stasis or turbulence
hypercoagulable states – altered function of
platelets
HYPERVISCOSITY – Stasis of blood flow
paraproteinemia -Waldenstrom Macroglobulinemia > MM
(Rouleaux formation)
increased cell mass- polycythemia, thrombocythemia, and
leukocytosis
STASIS also contributed by mechanical compression of vessels
ISCHEMIA and INFARCTION

21. Polycythemia- increases RBCs
• Dilated tortuous arteries and veins
• disc edema
• Multiple Retinal hemorrhages,
• venous thrombosis
• Ischemic optic neuropathy
• Carotid and vertibro-basilar insufficiency.. Angio spasm,
thrombosis
• Cavernous Sinus Thrombosis
• conjunctival congestion

22. • NAION 
• CRVO 
• BRVO 
• STROKE

23. MECHANICAL EFFECTS

24. • Lids
Ptosis
Entropion
• Orbit
Occular deviation, restriction of movements
Proptosis – orbital and lacrimal gland involvement
Disc edema
• Vascular compression- arterial, venous
• Compressive Neuropathy
• Blockage of trabecular meshwork by neoplastic cells-
2ndary glaucoma

25. METABOLIC ABNORMALITIES

26. OCULAR HYPERCALCEMIA
• hematologic malignant neoplasms (multiple myeloma,
leukemia, or lymphoma) can elevate calcium levels
• the basement membranes and epithelial cells are more
likely to be affected. It is suggested that these sites are
relatively alkaline, favoring the deposition of calcium
salts. Calcification of corneal epithelium and Bowman‟s
layer

27. • In the conjunctival epithelium, white perilimbal deposits
occur.
• band keratopathy.
• Scleral calcification can be seen by computed
tomography and may appear clinically as white flecks.
• Pigmented layers of the iris, ciliary body, and choroid
may also demonstrate calcium deposits
DD
• dystrophic calcification, bony metastasis in solid tumors,
granulomatous diseases such as sarcoidosis,
hyperthyroidism, vitamin A intoxication, and renal failure

28. IMMUNODEFICIENCY
• the disease process
• Altered functions of neutrophils, macrophages and
lymphocytes – both innate and adaptive immune
system affected
• Effect of the therapy

29. • Opportunistic
infections
• CMV Retinitis 
• herpes virus
• toxoplasmosis
• fungal infections

30. Sub retinal abscess
• most cases of subretinal
abscess are due to
Nocardia, branching gram-
positive filamentous bacteria
• Other causes
Pseudomonas, Klebsiella,
and viridans streptococci
• chronic myeloid leukemia
and bone marrow transplant Sub retinal abscess with
exudative RD

31. • Rhino cerebral
mucormycosis

32. MANIFESTATIONS
vis a vis
TISSUES

33. RETINA
Retinal veins become distended and tortuous- first change
(most often because of anemia)
Retinal edema – maximal over optic disc
As disease progresses, retinal arteries become distended
and venous column becomes broken by AV crossings
into turgid sausage like segments

34. • Retinal infiltrates take the form of grayish white nodules
associated with local hemorrhage
• Sheathing of retinal vessels and intravascular
margination. Perivascular infiltrates, widest along
convexities of veins
( also seen in active chorioretinitis)
• Hard exudates and cotton wool spots may be seen; the
cotton wool spots may result from actual leukemic
infiltration of the retina or from nerve fiber layer infarction

35. • AML – extensive retinal
hemorrhages- sub hyaloid
extending to macula, flame shaped,
subhyaloid, Roth spots 
• Leukemic infiltration

36. • Roth Spots - leukemic
infiltrates surrounded by
hemorrhages
• DD
endocarditis
anemia
retinopathy in HIV
hypertensive or diabetic
retinopathy

37. • COTTON-WOOL SPOTS consist of accumulations of
cytoid bodies in the axons of the nerve fiber layer. The
accumulation of material is thought to be related to
disruption of axoplasmic transport by focal ischemia.
• These spots occur in
diabetes mellitus,
hypertension,
collagen vascular diseases,
anemia

38. • In chronic leukemias & paraproteinemia ( hyperviscosity)
Microaneurysms in the retinal periphery adjacent to
areas of ischemia and nonperffusion.
rarely progress to frank neovascularization in a sea-fan
pattern.
DD – Sickle cell anemia
Central and branch retinal vein occlusions

39. VITREOUS
Infiltration of the vitreous is rare but hematological malignancies
account for most no of cases of tumors involving vitreous
• Vitreous involvement may be the only ocular sign of an
intraocular malignancy
• The most common primary intraocular malignancy to involve
the vitreous is primary intraocular lymphoma
• Vitreous involvement may be purely inflammatory as these
malignancies can mimic posterior uveitis
• Clinically, the tumor cells in the vitreous
often adhere to create opacities that are larger than the
vitreous cells typically seen in
inflammatory vitritis.

40. UVEA
The acute leukemias are more
commonly associated with
choroidal involvement .
Leukemic nodular choroidal infiltrates
with overlying vitritis in a patient with
leukemia. 
Overlying retinal pigment epithelial
degeneration and clumping leads
to ‘leopard spot’ pattern which is
thought to be due to invasion or
compression of the choriocapillaris
by leukemia cells
DD - chronic subretinal fluid collection e g
Uveal effusion syndrome, CSR

41. • Choroidal masses with exudative RD
• cases with choroidal vessel infiltration – peculiar colour
of fundus yellow to light pink
• POSTERIOR CILIARY BODY CYSTS
Multiple myeloma &
Waldenstrom macroglobulinemia
(plasmacytoma)
• IRIS INFILTRATE
T Cell Lymphoma 

42. • ANTERIOR AND POSTERIOR UVEITIS
(MASQUERADE SYNDROMES)
PSEUDOHYPOPYON 
• SECONDARY GLAUCOMA

43. OPTIC NERVE
• prelaminar fluffy, white infiltrate
superficial to the lamina cribrosa on
the optic nerve head
• as a retrolaminar infiltrate visible
on neuroimaging in association
• An important distinction between
direct infiltration by leukemia cells
and disk edema from elevated
intracranial pressure due to
leukemic meningitis must be made.
As Orbital radiation can benefit in
infiltrative disease

45. ORBIT
Insiduous painless, proptosis, edema
mild restriction of occular movements, inability to close the lids
Bilateral orbital deposits in few cases
if pain + , pseudotumor is an important differential (30-40 yrs)
LYMPHOMA – ( old age)
GRANULOCYTIC SARCOMA myeloid infiltrates in child (<10y)

46. • LACRIMAL GLAND
painless, rubbery mass fixed to the
orbital rim
Downward and medial deviation
of the eyeball . Non axial Proptosis
CT scans usually show a homogeneous consistency with
indistinct borders characteristic of the infiltrative nature of
this lesion
• MICKULICZ syndrome 
• LACRIMAL SAC LYMPHOMA : 2nd most common
neoplastic cause of ephiphora

47. • Conjunctival leukemic infiltrate- Soft, hyperemic
SALMON PATCH

48. • LIDS
Mycosis Fungoides : ill defined spongy tumors of the lids.
This is a form of T-cell lymphoma.
elevated tumor with central
erosion

49. NEUROLOGY
Elevated Intracranial Pressure
Leukemic infiltration
Pseudotumor cerebri
Papilloedema
Cranial Nerve palsies – 3rd , 4th , 6th and 7th

50. • Strokes
involving visual pathway
cerebellum : nystagmus

51. OCCULAR ADVERSE EFFECTS OF
TREATMENT
• Pseudotumor cerebri therapy for acute promyelocytic
leukemia with all-trans retinoic acid (a vitamin A
derivative) and with arsenic Trioxide
• Steroid cataract
• Bone Marrow transplant : Graft versus Host Disease
cojunctival hyperemia, conjunctival chemosis,
pseudomembranous conjunctivitis, corneal sloughing
KCS, filamentary keratitis, immune mediated optic
neuritis

52. • Radiotherapy
Optic atrophy and
peripapillary RPE changes
Radiation retinopathy
Radiation cataract

53. THANK YOU