Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Ophthalmic Manifestations of Hematological Malignancies


Published on

Published in: Health & Medicine, Technology

Ophthalmic Manifestations of Hematological Malignancies

  2. 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
  4. 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. 5. EVOLUTION OF TERMS & CONCEPTS in HEMATONCOLOGYVirchow (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 numbers1st description of Hodgkin‟s Disease – Carswell in 1828Term “hodgkin‟s disease” by Wilks in 1865. later also came to be known as LymphadenomaTerm 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. 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)
  7. 7. • 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
  8. 8. 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
  9. 9. 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
  10. 10. 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
  11. 11. • ISCHEMIA & INFARCTION• METABOLIC EFFECTS : Hypercalcemia, renal failure• PARANEOPLASTIC SYNDROME : cerebellar degeneration in lymphoma• EFFECT OF THERAPY
  13. 13. 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
  14. 14. Multiple intraretinal and preretinal hemorrhages and Roths spots – case of severe anemia
  15. 15. • Ischemic optic neuropathy• Pseudotumor cerebri
  16. 16. 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
  17. 17. • Rarely massive intra orbital bleed causes sudden proptosis compartment syndrome , compressive optic neuropathy
  18. 18. THROMBOTIC TENDENCY : Virchow‟s Triad endothelial damage ( infiltration of the vessel wall) altered blood flow – stasis or turbulence hypercoagulable states – altered function of plateletsHYPERVISCOSITY – Stasis of blood flow paraproteinemia -Waldenstrom Macroglobulinemia > MM (Rouleaux formation) increased cell mass- polycythemia, thrombocythemia, and leukocytosisSTASIS also contributed by mechanical compression of vesselsISCHEMIA and INFARCTION
  19. 19. 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
  20. 20. • NAION • CRVO • BRVO • STROKE
  22. 22. • 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
  24. 24. 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
  25. 25. • 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
  26. 26. IMMUNODEFICIENCY• the disease process • Altered functions of neutrophils, macrophages and lymphocytes – both innate and adaptive immune system affected• Effect of the therapy
  27. 27. • Opportunistic infections• CMV Retinitis • herpes virus• toxoplasmosis• fungal infections
  28. 28. 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
  29. 29. • Rhino cerebral mucormycosis
  30. 30. MANIFESTATIONS vis a vis TISSUES
  31. 31. RETINARetinal veins become distended and tortuous- first change (most often because of anemia)Retinal edema – maximal over optic discAs disease progresses, retinal arteries become distended and venous column becomes broken by AV crossings into turgid sausage like segments
  32. 32. • 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
  33. 33. • AML – extensive retinal hemorrhages- sub hyaloid extending to macula, flame shaped, subhyaloid, Roth spots • Leukemic infiltration
  34. 34. • Roth Spots - leukemic infiltrates surrounded by hemorrhages• DD endocarditis anemia retinopathy in HIV hypertensive or diabetic retinopathy
  35. 35. • 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
  36. 36. • 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
  37. 37. 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.
  38. 38. UVEAThe acute leukemias are morecommonly associated withchoroidal involvement . Leukemic nodular choroidal infiltrates with overlying vitritis in a patient with leukemia. Overlying retinal pigment epithelialdegeneration and clumping leadsto ‘leopard spot’ pattern which isthought to be due to invasion orcompression of the choriocapillarisby leukemia cellsDD - chronic subretinal fluid collection e gUveal effusion syndrome, CSR
  39. 39. • 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 
  41. 41. 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
  42. 42. ORBITInsiduous painless, proptosis, edemamild restriction of occular movements, inability to close the lidsBilateral orbital deposits in few casesif pain + , pseudotumor is an important differential (30-40 yrs)LYMPHOMA – ( old age)GRANULOCYTIC SARCOMA myeloid infiltrates in child (<10y)
  43. 43. • 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
  44. 44. • Conjunctival leukemic infiltrate- Soft, hyperemic SALMON PATCH
  45. 45. • LIDS Mycosis Fungoides : ill defined spongy tumors of the lids. This is a form of T-cell lymphoma. elevated tumor with central erosion
  46. 46. NEUROLOGYElevated Intracranial Pressure Leukemic infiltration Pseudotumor cerebri Papilloedema Cranial Nerve palsies – 3rd , 4th , 6th and 7th
  47. 47. • Strokes involving visual pathway cerebellum : nystagmus
  48. 48. 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
  49. 49. • Radiotherapy Optic atrophy and peripapillary RPE changes Radiation retinopathy Radiation cataract
  50. 50. THANK YOU