Eye: the door to undiagnosed chronic myeloid leukaemia

Abstract

Chronic myeloid leukaemia (CML) is a myeloproliferative neoplasm that can present in varied ways from incidental finding on haemogram to symptomatic presentation such as splenomegaly. We report an interesting case of a 22-year-old man who presented with loss of vision in right eye for 1 month. There were no pre-existing ocular or systemic diseases. On detailed ocular examination, a diagnosis of right eye rubeosis iridis, hyphaema, cataract and vitreous haemorrhage with left eye suspected leukaemic retinopathy was made. Routine haemogram revealed high leucocytosis. Systemic evaluation with investigations confirmed the diagnosis of CML and the patient was started on appropriate therapy.

Background

Chronic myeloid leukaemia (CML) is described as a triphasic disease: chronic, accelerated and blast phase. There have been numerous efforts to optimise management strategies but still there are many questions, which remain unanswered. One among the uncertain issues is ophthalmological manifestations and the guidelines of therapy. Ophthalmological manifestations are among the uncommon presentations of CML and can vary from incidental finding during the ocular examination to blurred vision and partial or complete loss of vision. Ophthalmic manifestation can sometime be the first presentation and failure to recognise this can lead to delay in the diagnosis of this disorder and can be fatal.

Case presentation

A 22-year-old previously healthy Indian man presented with diminution of vision in right eye associated with pain, redness and watering for 1 month. He had a local ophthalmic consultation and was suspected to have neovascular glaucoma (NVG) of the right eye and was referred to glaucoma clinic of tertiary eye care centre.

He presented with no perception of light in the right eye and the best-corrected visual acuity in left eye was 20/20. Anterior segment evaluation of right eye showed presence of conjunctival congestion, diffuse corneal oedema with central epithelial defect, corneal endothelial staining, shallow anterior chamber with hyphaema, rubeosis iridis and cataract (figure 1A). Intraocular pressure (IOP) measurement was deferred in view of corneal epithelial defect. The view to fundus was obscured by presence of hyphaema and cataract. Ultrasound B Scan of right eye was performed. Anterior segment evaluation of left eye was essentially within normal limit with IOP of 12 mm Hg by applanation tonometer. Fundus examination of left eye showed a medium-sized disc with 0.3 cup:disc ratio, with peripapillary infiltration. The vessels were dilated and tortuous containing salmon pink colour blood column with intraretinal haemorrhages in all four quadrants along with perivascular and subretinal infiltrate in macular region and peripheral retina (figure 2A). Suspecting a systemic pathology, we performed general examination which revealed presence of petechial haemorrhages on dorsum of palm and mild splenomegaly. Revisiting the history, it was found that he had been experiencing weight loss for past 2 months.

Figure 1.

(A) Slit lamp photo of RE-corneal oedema with endothelium staining, presence of hyphaema. (B) RE B scan-low to medium echoes, high reflective clumps, medium reflective band with disc attachment, suggestive of vitreous haemorrhage along with retinal detachment. RE, Right eye.

Figure 2.

(A) LE fundus photo—before initiation of treatment for chronic myeloid leukaemia (CML) showing dilated and tortuous vessels containing salmon pink colour blood column with intraretinal haemorrhages in all four quadrants along with peripapillary, perivascular and subretinal infiltrates in macular region and peripheral retina. (B) LE fundus photo—1 month after initiation of CML therapy—showing resolving retinal haemorrhages, vessel tortuosity and infiltrates. (C) LE fundus photo—6 months after initiation of CML therapy—showing complete resolution of haemorrhages, infiltrates. LE, Left eye.

The patient was diagnosed with hyphaema, rubeosis iridis and cataract of the right eye and suspected leukaemic retinopathy of the left eye.

Haematology showed an abnormally high white cell count (WCC). Peripheral smear, bone marrow was suggestive of CML and BCR-ABL by reverse transcriptase Polymerase chain reaction (RT-PCR)was positive which confirmed the diagnosis of CML. He was started on imatinib (300 mg, oral, two times per day) after cytoreduction with hydroxyurea. Ophthalmological treatment in the form of topical steroids and cycloplegics were started as conservative management for right eye.

At 1 month after initiation of treatment for CML, although vision in the right eye did not improve, he was symptomatically better. The IOP of RE was 14 mm Hg. Left eye fundus evaluation showed resolving tortuosity of blood vessels, haemorrhages and infiltrates.

At last visit, there was complete resolution of haemorrhages and infiltrates in the left eye. The patient was advised for regular ophthalmic and oncology follow ups.

Investigations

Ultrasound B scan of the right eye showed low to medium reflectivity dot and clump echoes, along with membranous high reflectivity band with disc attachment. Features were suggestive of vitreous haemorrhage and retinal detachment (figure 1B).

Optical coherence tomography of the left eye through the retinal infiltrate shows hyper reflective inner retinal layers with indistinct details (figure 3A).

Figure 3.

(A) LE OCT macula through the retinal infiltrate shows hyper-reflective inner retinal layers with indistinct details before chronic myeloid leukaemia (CML) therapy. (B) LE OCT macula 1 month after start of treatment for CML showing resolved infiltrates. LE, Left eye. OCT, Optical coherence tomography.

Haemogram showed high WCC count of more than 250 cells ×10⁹/L. Haemoglobin 98 g/L, red cell count 3.2 10¹²/L. Peripheral smear showed numerous immature granulocytes. BCR-ABL by PCR was positive.

Differential diagnosis

The differential diagnoses considered in the case were based on the common causes of neovascularisation of iris (NVI) and hyphaema.

Traumatic hyphaema

Negative history of trauma ruled out this condition.

Ocular inflammation

Viral keratouveitis or chronic uveitis

There was an absence of raised IOP, keratic precipitates and patchy iris atrophy. The anterior chamber of left eye was quiet with an absence retinal periphlebitis. Also, retinal infiltrates did not show overlying vitreous haze hence a possibility of uveitis was ruled out.

Drug induced hyphaema

Absence of history of drug intake like aspirin, warfarin ruled out this cause.

Malignancies

Various malignancies like retinoblastoma, malignant melanoma, ciliary body medulloepithelioma, metastatic cancer can cause NVG with hyphaema. However, absence of mass lesion on B-scan in right eye ruled out these conditions.

Retinal ischaemia

1. Proliferative diabetic retinopathy is a common cause of NVI.

Absence of history of diabetes with no diabetic retinopathy changes in left eye ruled out this condition.

1. Central retinal vein or artery occlusion and carotid artery occlusion are also known causes of NVI and hyphaema.

In view of dilated veins with haemorrhages, a morphological interpretation of venous stasis retinopathy was made. But the salmon-coloured blood in veins and dull altered reddish retinal hue led us to believe that the venous stasis was due to increased haematocrit, a differential of polycythaemia or leukaemia was considered. Also, the patient had no typical known risk factors such as diabetes, hypertension or cardiac diseases.

Retinal vascular occlusion or carotid occlusive disease typically do not cause retinal detachment or traction noted on B scan in this case, so these conditions were less likely considered.

1. Sickle cell retinopathy

Negative patient’s case history and family history of any form of sickle cell disease ruled out this condition.

Chronic retinal detachment

It is a common cause of NVI and often found on B scan as in this case but the posterior segment view was obscured in view of advanced cataract. The findings of the fellow eye were suspicious pointed towards a systemic aetiology.

Iris juvenile xanthogranuloma

Usually present with recurrent hyphaema with raised IOP in first decade of life.

Absence of iris lesion along with normal IOP in 22 years old ruled out this condition.

Treatment

Based on the clinical findings and investigation reports, he was diagnosed to be a confirmed case of CML with leukaemic retinopathy of left eye and an absolute right eye. He was referred to a haematooncologist and was treated for CML with chemotherapy. Right eye was managed conservatively for symptomatic relief.

Outcome and follow-up

There was reduction in tortuosity of blood vessels along with resolution of retinal haemorrhages and infiltrates in the left eye and the vision was maintained. The symptoms in the right eye were relieved (figure 2A).

We have kept the patient on regular follow-up so as to diagnose at earliest if any ocular complications develop due to CML or imatinib.

Discussion

Myeloproliferative neoplasms (MPNs) are relatively rare haematological malignancies. CML is the most common MPN and represent clonal neoplastic proliferation of the myeloid or, possibly, pluripotent stem cells. The dominance of the granulocytic series is manifested as CML. It is characterised by the t (9:22) chromosomal translocation that leads to expression of BCR-ABL fusion protein leading to increasing proliferation and inhibiting apoptosis in haematopoietic progenitors.¹ CML is the most common adult leukaemia in India. The median age at diagnosis is 38–40 years.² Ocular manifestations as first presentation can be seen only in 5%–10% CML patients.³

Ophthalmic involvement in leukaemias is uncommon and literature is scarce. The two major categories in which they can be classified: (1) primary or direct leukaemicinfiltration and (2) secondary or indirect involvement.⁴ The ophthalmic manifestations are varied and include intraretinal and preretinal haemorrhages, cotton wool spots, perivascular sheathing and neovascularisation. Roth spot haemorrhages may represent areas of retinal leukaemic infiltration. Other manifestations include nerve fibre layer infarcts, subhyaloid and vitreous haemorrhages and papilloedema secondary to raised intracranial pressure.⁵ Leukaemic retinopathy is commonly found in acute leukaemia and signifies poor prognosis.

Leukaemic infiltration quite often affects the choroid and may present with an exudative detachment.

There are no precise guidelines of treatment in these patients. Most of them are treated with medication which includes tyrosine kinase inhibitors, hydroxyurea or immunotherapy.

This case is unique being diagnosed as CML following evaluation for cause of vision loss in a young male. Early diagnosis can lead to initiation of prompt treatment which is beneficial not only to save vision but also stabilise systemic condition.

Patient’s perspective.

After losing one eye, I was shocked to know that I am suffering from leukaemia. However, I am happy that I got the treatment at correct time and my left eye vision could be saved. The doctors informed me that I need to continue the therapy and should be on regular follow ups.

Learning points.

• Young patient presenting as unexplained hyphaema or neovascular glaucoma—remember haematological malignancies as one of the differential diagnosis.

• Chronic myeloid leukaemia patients presenting with ophthalmic manifestations carry poor prognosis, so prompt diagnosis is important.

• Leukaemic proliferative retinopathy is more common in chronic leukaemia than acute, due to long-standing retinal non perfusion.