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Ophthalmic Manifestations of Acute Leukaemias T Sharma Et Al 664

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Ophthalmic Manifestations of Acute Leukaemias T Sharma Et Al 664 Eye (2004) 18, 663–672 & 2004 Nature Publishing Group All rights reserved 0950-222X/04 $30.00 www.nature.com/eye 1 1 2 1 Ophthalmic T Sharma , J Grewal , S Gupta and PI Murray REVIEW manifestations of acute leukaemias: the ophthalmologist’s role Abstract neoplastic cells. Ophthalmic involvement can be classified into two major categories: (1) primary With evolving diagnostic and therapeutic or direct leukaemic infiltration, (2) secondary or advances, the survival of patients with acute indirect involvement. The direct leukaemic leukaemia has considerably improved. This infiltration can show three patterns: anterior has led to an increase in the variability of segment uveal infiltration, orbital infiltration, ocular presentations in the form of side effects and neuro-ophthalmic signs of central nervous of the treatment and the ways leukaemic system leukaemia that include optic nerve relapses are being first identified as an ocular infiltration, cranial nerve palsies, and presentation. Leukaemia may involve many papilloedema. The secondary changes are the ocular tissues either by direct infiltration, result of haematological abnormalities of haemorrhage, ischaemia, or toxicity due to leukaemia such as anaemia, thrombocytopenia, various chemotherapeutic agents. Ocular hyperviscosity, and immunosuppression. These involvement may also be seen in graft-versus- can manifest as retinal or vitreous haemorrhage, host reaction in patients undergoing infections, and as vascular occlusions. In some allogeneic bone marrow transplantation, or cases the ocular involvement may be simply as increased susceptibility to infections asymptomatic. In one prospective study, there as a result of immunosuppression that these was a high prevalence of asymptomatic ocular 1 patients undergo. This can range from simple Birmingham and Midland lesions in childhood acute leukaemia.1 In the era bacterial conjunctivitis to an endophthalmitis. Eye Centre, Birmingham, UK before effective antileukaemic therapy, Leukaemia can present as pathology in the retinopathy was believed to be of no prognostic 2Tata Memorial Hospital, adnexae, conjunctiva, sclera, cornea, anterior significance in acute leukaemia.2,3 However, Mumbai, India chamber, iris, lens, vitreous, retina, choroid, recent reports have demonstrated that the and optic nerve. Recognition of the varied Correspondence: PI Murray presence of ocular involvement is associated ocular presentations is also important in Academic Unit of with poor prognosis in acute childhood assessing the course and prognosis of Ophthalmology Division of leukaemias.3 Therefore, it is important to leukaemia. We have presented a systematic Immunity and Infection consider an ophthalmic evaluation at the time of Birmingham and Midland approach taking each part of the eye in turn diagnosis of acute leukaemia in adults and Eye Centre Sandwell and and outlining how leukaemia has been shown West Birmingham Hospitals children. to affect it. NHS Trust City Hospital In the review that follows, we present a Eye (2004) 18, 663–672. doi:10.1038/sj.eye.6701308 Dudley Road Birmingham current classification of leukaemia with a brief Published online 27 February 2004 B18 7QU, UK outline of cytochemical features and Tel: 0121 507 6851 immunophenotype of acute leukaemia, and Fax: 0121 507 6853 Keywords: leukaemia review; eye E-mail: P.I.Murray@ describe varied leukaemic involvement of the manifestations; complications; side effects of bham.ac.uk ocular tissues. therapy Published online: 27 February 2004 Classification of the leukaemia (Table 1) Introduction Various classifications of leukaemia exist in the None of the authors has a The leukaemias are malignant neoplasms of the literature based on cell type involved, state of financial and proprietary haematopoietic stem cells, characterized by maturity, morphological and cytochemical interest in a product or lack diffuse replacement of the bone marrow by characteristics, and immunophenotype of the thereof. Ophthalmic manifestations of acute leukaemias T Sharma et al 664 Table 1 The Classification of the Leukemias It is widely accepted that CML, polycythemia vera, essential thrombocytosis, and myeloid metaplasia Leukaemias represent clonal neoplastic proliferation of the myeloid Acute or, possibly, pluripotent stem cells. If the erythrocyte Lymphocytic precursors dominate, the resulting clinical disorder is MorphologicFL1/L2/L3 classified as polycythemia vera; on the other hand, Immunophenotype- B-lineage-80% dominance of the granulocytic series is manifested as K Early B precursor- CML. Analogous to CML, it is possible to segregate K Pre-B cell- chronic lymphoproliferative disorders. This group K Mature B – includes CLL and hairy cell leukaemia, both of K T-lineage- 15% which are neoplastic proliferations of lymphoid cells, Mixed lineage-o5% Undifferentiated-o2% most often of B-cell lineage. As proliferative disorders of Myelocytic lymphoid cells, these are related to Non Hodgkin’s M0FMinimally differentiated AML lymphomas. M1FAML without differentiation M2FAML with differentiation M3FAcute Promyelocytic leukaemia Morphologic, cytochemical features, and F M4 Acute Myelomonocytic leukaemia immunophenotype in acute leukaemia5 M5FAcute monocytic leukaemia M6FAcute erythroleukaemia Under normal conditions, blast forms constitute fewer F M7 Acute megakaryocytic leukaemia than 5% of the nucleated cells of the bone marrow and are seen in the peripheral blood except during periods of Chronic Chronic myeloid leukaemia: clonal origin from pluripotent profound overproduction of blood cells. Blast cells are cell-related to myeloproliferative disorder primitive precursors, lacking many of the features of Philadelphia Chromosome-Translocation-C22 p-C-9p) differentiation. Lymphoid blasts are differentiated from Chronic lymphocytic leukaemia myeloid blast on the basis of standard morphologic and B-cell lineageF95% cytochemical differences, based on these, acute T-cell lineageF5% leukaemias are subdivided. Within the French-American- Miscellaneous related disorders British (FAB) classification, ALL has been subdivided Hairy cell leukaemia into three types: L1, L2, and L3, while subdivisions of Chronic B-cell leukaemia AML are called M0–M7. Some early clinical trials have Leukaemic cells with hair-like cytoplasmic projection suggested that L2 morphology conveys a worse Myeloproliferative disorder Polycythemia vera prognosis than L1 morphology, but in most recent trials Myeloid metaplasia with myelofirbrosis of ALL, FAB classification was not found to be an independent prognostic variable. This led to correlation of cytochemical reactions with both morphology and leukaemic cells. 4,5 The most widely used and clinically immunologic cell surface markers.5 Identification of useful classification divides leukaemia into acute and immunophenotypic subtypes of ALL allowed a chronic forms. The acute leukaemias are characterized by classification that was more precise and biologically replacement of the bone marrow with very immature oriented than the morphologic approach, although in cells called blasts. Chronic leukaemias are associated, at AML expression of immunologic markers is least initially, with well-differentiated (mature) heterogeneous. Immunophenotyping has prognostic leucocytes. Two major variants of acute and chronic implications in B-cell ALL, while in AML it has leukaemia are recognized: lymphocytic and myelocytic diagnostic value in differentiation from ALL, especially (myelogenous). This simple classification has four in M0. Classification of leukaemia by immunophenotype patterns of leukaemia: acute lymphocytic is based on the expression of a pattern of lineage- (lymphoblastic) leukaemia (ALL), chronic lymphocytic associated antigens; no single antigen is truly lineage leukaemia (CLL), acute myelocytic (myeloblastic) specific.5 Most ALLs are of B-cell origin, mainly of the leukaemia (AML), and chronic myelocytic leukaemia early B-precursor type. ALLs of B-cell lineage express (CML). Approximately 5% of acute leukaemias are CD19 and CD22, the latter antigen is first expressed in difficult to characterize as either ALL or AML, and some the cytoplasm and later in the membrane. T-cell lineage may be classified as acute undifferentiated leukaemia ALL is defined by the cytoplasmic or membrane (AUL). This simple classification separates leukaemia expression of CD3. Detailed description of various from closely related neoplastic disorders of immunophenotypes is beyond the scope and objective of haematopoietic stem cells. this article. Eye Ophthalmic manifestations of acute leukaemias T Sharma et al 665 Table 2 Ophthalmic Manifestations of Leukaemia Lids Ectropion, oedema, mechanical ptosis Conjunctiva Chemosis, conjunctival mass, corkscrew vessels, conjunctivitis Cornea Keratitis-limbal infiltration or secondary to immunosuppression or graft-versus-host disease, sterile ring ulcers, pannus, melt syndrome, dry eyes, epithelial changes secondary to chemotherapy Orbit Exophthalmos, orbital/preseptal cellulitis, endophthalmitis, dacryocystitis Iris, angle, anterior chamber and lens Glaucoma, uveitis, hyphaema, pseudohypopyon (yellow/grey), heterochromia, cataract secondary to treatment Retina Haemorrhages at all levels, perivascular infiltrates, retinitis, vitreous haemorrhage, microaneurysms, cotton wool spots, peripheral neovascularisation, retinal detachments, drusen, vascular occlusion, retinitis secondary to opportunistic infections Choroid Thickened with associated serous retinal detachment Optic nerve and CNS Nausea, vomiting, lethargy,
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