Retinal Manifestations of Leukemia - Leukemic Retinopathy

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Introduction:

Leukemic Retinopathy is the most common ocular manifesation of Leukemia.


Disease Entity:

• Leukemia is a myeloproliferative disorder caused by an abnormal proliferation of immature leucocytes. Intraocular involvement in leukemia can be upto 90%.

• Both acute and chronic leukemia can cause ocular manifestations.

• Retina is the most common ocular tissue to be involved in leukemia.

• Leukemic retinopathy was first described by Liebriech in 1861 [1]

Figure 1: Fundus of the right eye of a patient with acute myeloid leukemia showing retinal hemorrhages suggestive of leukemic retinopathy Image Courtesy: Rajan Eye Care Hospital, Chennai, India

• Retinal manifestations are usually due to indirect complications of leukemia especially due to hematological abnormalities (Figure 1)


Pathophysiology:

Ocular complications of leukemia can either be [2]:

1. Primary or Direct due to infiltration by leukemic tumour cells

2. Indirect/ Secondary

- Hematological abnormalities: Anemia, Thrombocytopenia

- CNS involvement

- Opportunistic infections

- Chemotherapy related


Pathogenesis: [3]

Prolonged leukocytosis increased number of circulating platelets --> Increased whole blood viscosity --> Reduced blood flow and vascular stagnation --> Peripheral capillary dropout and microaneurysm formation --> Proliferative retinopathy


Systemic History:

• History of leukemia or any other malignancies- acute/chronic

• History of any other systemic illnesses

• History of treatment such as chemotherapy


Ocular History:

• Visual loss - Onset, Duration

• Unilateral/bilateral

• Seeing a red shower of dots/ black shadow

• Visual field defects



Signs: [2]

1. Dilated and tortuous veins – early manifestations due to hematological disturbances [4]

2. Retinal hemorrhages at all levels – especially in the posterior pole, and extension to the vitreous

• Preretinal hemorrhages

• Superficial hemorrhages

• Dot and blot hemorrhages

Figure 2: Fundus photo of the left eye showing white centered hemorrhages or Roth Spots Image Courtesy: Rajan Eye Care Hospital, Chennai, India

• White centered hemorrhages/ Roth Spots (Figure 2)

• Sub-ILM hemorrhages

Figure 3: Fundus photo of the left eye showing a subhyaloid hemorrhage Image Courtesy: Rajan Eye Care Hospital, Chennai, India

• Subhyaloid hemorrhage (Figure 3)

• Vitreous hemorrhage


ROTH SPOTS [5] (Figure 2)

White centered hemorrhages known as ‘Roth spots’ result from retinal capillary rupture and extrusion of whole blood. This is followed by platelet adhesion to the damaged endothelium initiating a coagulation cascade and formation of a white lesion in the centre of the hemorrhage which is a platelet-fibrin thrombus. In leukemia, the white centre could correspond to an accumulation of leukemic cells.

Figure 4: Fundus photo of right eye showing cotton wool spots around the disc Image Courtesy: Rajan Eye Care Hospital, Chennai, India

3. Cotton wool spots (Figure 4)

Secondary to clusters of cells occluding retinal arterioles, not usually associated with hematological parameters

4. Leukemic Infiltrates:

• It is generally associated with high blood counts, fulminant disease and early mortality.

• Usually, but not always seen with surrounding hemorrhage [6]

• Grey-white streaks along vessels caused by local perivascular infiltrates.

• Large grey, white nodules of varying sizes in the retina.

• Subretinal infiltrates- referred to as subretinal hypopyon

• Optic nerve infiltration

• Choroidal infiltrates – Serous retinal detachments, RPE detachments, discrete choroidal masses

• Vitreous infiltrates: Internal limiting membrane acts as an effective barrier for leukemic cells infiltration. But they can rarely invade the vitreous from the optic disc. Can be associated with vitreous hemorrhage. [6]

Figure 5: Fundus photo of the right eye showing a central retinal vein occlusion Image Courtesy: Rajan Eye Care Hospital, Chennai, India

5. Vascular occlusions- Bilateral CRVO due to hyperviscocity (Figure 5)

6. Peripheral Microaneurysms- due to viscosity of elevated WBC count, does not correlate with hemoglobin or platelet level

7. Peripheral neovascularization similar to sickle cell anemia seen in CML- associated with chronic elevated WBC count

8. Retinal detachments

9. Vitreous infiltrates

10. Choroidal infiltrates

11. Opportunistic infections – CMV retinitis, Ocular toxoplasmosis, Viral retinitis

12. Optic nerve involvement

Diagnosis:

  • History of leukemia
  • Detailed fundus evaluation
  • Laboratory tests
  • Complete blood count – to look for anemia, thrombocytopenia, pancytopenia
  • Peripheral blood smear- for blast cells
  • Bone marrow biopsy – infiltration by blast cells
  • Flow cytometry and immunophenotyping


Management:

Treatment of underlying leukemia by chemotherapy, immunotherapy or radiotherapy.

Prognosis:

The 5-year survival rate was found to be significantly lower in those with leukemic retinopathy on presentation than in those without ophthalmic involvement (21.4% vs. 45.7%).

Patients with clinical leukemic retinopathy may have more aggressive systemic disease that might lead to a worse prognosis. [7]

References:

  1. Liebreich: Atlas, 1863, as quoted inW.S. Duke-Elder Text-book of Ophthalmology vol. III, Mosby, St Louis (1941), Article 2740
  2. 2.0 2.1 Sharma T, Grewal J, Gupta S, Murray PI. Ophthalmic manifestations of acute leukaemias: the ophthalmologist's role. Eye. 2004 Jul;18(7):663-72.
  3. Rosenthal AR. Ocular manifestations of leukemia: a review. Ophthalmology. 1983 Aug 1;90(8):899-905.
  4. Ballantyne AJ, Michaelson IC. Textbook of the Fundus of the Eye. Williams and Wilkins: Baltimore, 1970; 290–292.
  5. Allen RA, Straatsma BR. Ocular involvement in leukaemia and allied disorders. Arch Ophthalmol 1961; 66: 490–508.
  6. 6.0 6.1 Kuwabara T, Aiello L. Leukaemic military nodule in retina. Arch Ophthalmol 1964; 72: 494–497.
  7. Retina E-Book: 3 Volume Set By Charles P. Wilkinson, David R. Hinton, SriniVas R. Sadda, Peter Wiedemann, Stephen J. Ryan