From the Department of Ophthalmology (MS), Hanyang University College of Medicine, Guri Hospital, Gyeonggi-do; the Department of Ophthalmology (MS, MJK, HT), University of Ulsan College of Medicine, Asan Medical Center, Seoul; and the Department of Pediatric Oncology (JJS), University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Presented as a poster at the 9th International Ocular Inflammation Society Congress, Paris, France, September 17–20, 2007.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Myoung Joon Kim, MD, Department of Ophthalmology, University of Ulsan, College of Medicine, Asan Medical Center, 388-1 Pungnap-2-dong, Songpa-gu, Seoul, Korea 138-736.
Although ocular symptoms may be the first manifestation of leukemia, the anterior segment is not a common site for extramedullary relapse. We report a case of chronic myeloid leukemia in which the only sign of relapse was anterior uveitis with hypopyon that was refractory to topical corticosteroid therapy.
A 7-year-old boy presented with redness in his left eye that had started 1 week earlier. On examination, his visual acuity was 20/25 in the right eye and 20/125 in the left eye. Intraocular pressure was 16 mm Hg in the right eye and 33 mm Hg in the left eye. Slit-lamp examination findings were normal for the right eye but revealed conjunctival injection, hypopyon, and a cream-colored membrane over the iris in the left eye (Fig. 1). Fundus examination findings were normal for both eyes.
Figure 1. Anterior Segment Photography of the Left Eye Showed Conjunctival Injection, Hypopyon, and a Cream-Colored Membrane Covering the Iris.
A detailed medical history was obtained, which revealed that the patient had suffered chronic myeloid leukemia 15 months previously, for which he had been treated with chemotherapy and had undergone allogenic bone marrow transplantation 11 months previously. After remaining well for 4 months, central nervous system relapse was found in a cerebrospinal fluid study. The patient subsequently underwent radiotherapy of the brain for approximately 2 weeks. After this time, the results of systemic examination and peripheral blood, bone marrow, and cerebrospinal fluid tests were all normal and he received imatinib mesylate maintenance therapy. Four months after finishing radiotherapy, the above-mentioned eye symptoms developed.
The patient was diagnosed as having anterior uveitis with secondary glaucoma at initial presentation and was administered topical prednisolone acetate 1% six times a day and dorzolamide/timolol twice a day. The patient did not respond to treatment, so anterior chamber aspiration was performed on the sixth day after the initial examination.
A cytologic smear test showed an abundance of leukemic blasts; hence pseudouveitis secondary to leukemic infiltration was suspected (Fig. 2). Systemic work-up revealed no evidence of leukemic relapse.
Figure 2. Cytologic Examination of Anterior Chamber Paracentesis Showed an Abundance of Leukemic Blasts.
Donor leukocyte infusion was performed twice. Despite donor leukocyte infusion, there were 4+ cells in the anterior chamber and elevation of the iris. The patient’s visual acuity was 20/30 and intraocular pressure was 19 mm Hg in the left eye. Ultrasound biomicroscopy images showed thickening of the iris stroma (Fig. 3).
Figure 3. (Left) Anterior Segment Photography of the Left Eye Showed Iris Elevation. (Right) Ultrasound Biomicroscopy Images of the Iris Showed Thickening of the Iris Stroma.
One week later, the patient’s visual acuity had decreased to 20/300 and intraocular pressure had increased to 28 mm Hg. The size of the iris nodules increased and hypopyon was observed. The patient received central nervous system irradiation for 2 weeks. After 10 days of treatment, the patient’s visual acuity had improved to 20/40, the anterior chamber reaction had completely disappeared, and the iris elevation was flattened. Although the left eye returned to its normal appearance, the patient died of pneumonia 6 months after radiotherapy without experiencing relapse of leukemia.
The uveitis masquerade syndromes are a group of disorders that present as intraocular inflammatory processes but are in fact non-inflammatory diseases.1–3 In affected patients, intraocular inflammation is secondary to an initial disorder of the intraocular cells and opacities are of non-inflammatory origin.2
It is important to distinguish ocular inflammation from uveitis masquerade syndromes to manage the disease and preserve visual acuity and, in some cases, even the life of a patient. However, diagnosis is difficult owing to unusual clinical presentations and the absence of uniform clinical features.
The eye is less often affected, either directly or indirectly, in chronic leukemia than in acute leukemia.4 Although systemic manifestations usually precede ocular manifestation, ocular manifestation may be the only symptom of chronic myeloid leukemia recurrence, as was seen in our patient.5,6 Definite diagnosis of uveitis masquerade syndromes is often based on the results of anterior chamber paracentesis. In the current case, the presence of large anterior chamber cells, flare, and creamy membranes on the iris suggested the possibility of uveitis masquerade syndromes. The patient’s history of chronic myeloid leukemia was particularly important for achieving the correct diagnosis, but the definite diagnosis was based on cytologic smear results that showed an abundance of leukemic blasts.
The mechanism by which leukemic blasts migrate to the anterior chamber is uncertain. Dadeya et al. suggested that leukemic cells, sequestrated in the central nervous system, probably enter the long posterior ciliary vessels in the subarachnoid space surrounding the optic nerve and pass into the anterior chamber through the iris vessels.7
Leukemic infiltration of the iris, either nodular or diffuse, has rarely been reported.4,8,9 Martin described a case of a 59-year-old man who was suffering from chronic lymphatic leukemia and had bilateral uveitis with leukemic infiltration of the iris.4 Allen and Straatsma reported only 2 cases of iris involvement among 38 eyes studied.9 In our case, iris infiltration was observed.
When a patient presents with hypopyon, an accurate diagnosis requires differentiation of many diseases. These include uveitis, unsuspected trauma, juvenile xanthogranuloma, retinoblastoma, retinoschisis, persistent hyperplastic vitreous, leukemia, and lymphoma.7,10,11 Leukemic hypopyon, as seen in the current patient, is a rare manifestation of chronic myeloid leukemia so an accurate diagnosis can be difficult.
For accurate diagnosis, we suggest aspiration of the intraocular cellular infiltrate for cytopathologic examination, and all cases of refractory hypopyon uveitis with or without systemic manifestation should be treated without delay. Early recognition and therapeutic intervention may preserve the sight, and even the life, of the patient.12
Imatinib mesylate is a tyrosine kinase that induces apoptosis of Philadelphia chromosome-positive (Ph+) cells.13 Anterior chamber relapse in patients with Ph+ leukemia treated with imatinib mesylate has been reported in only one adult patient.13 We report the first case of isolated anterior chamber relapse of chronic myeloid leukemia in a child treated with imatinib mesylate.
- Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis: Fundamentals and Clinical Practice, 2nd ed. St. Louis: Mosby; 1996:385–395.
- Rothova A, Ooijman F, Kerkhoff F, Van Der Lelij A, Lokhorst HM. Uveitis masquerade syndrome. Ophthalmology. 2001;108:386–399. doi:10.1016/S0161-6420(00)00499-1 [CrossRef]
- Birnbaum AD, Tessler HH, Goldstein DA. A case of hypopyon uveitis nonresponsive to steroid therapy and a review of anterior segment masquerade syndromes in childhood. J Pediatr Ophthalmol Strabismus. 2005;42:372–377.
- Martin B. Infiltration of the iris in chronic lymphatic leukemia. Br J Ophthalmol. 1968;52:781–785. doi:10.1136/bjo.52.10.781 [CrossRef]
- Lipton JH, McGowan HD, Payne DG. Ocular masquerade syndrome in lymphoid blast crisis of chronic myeloid leukemia. Leuk Lymphoma. 1995;20:161–163. doi:10.3109/10428199509054769 [CrossRef]
- Blodi FC. The difficult diagnosis of choroidal melanoma. Arch Ophthalmol. 1961;69:147.
- Dadeya S, Malik KP, Guliani BP, Dewan S, Mehta R, Gupta VS. Acute lymphocytic leukemia presenting as masquerade syndrome. Ophthalmic Surg Lasers. 2002;33:163–165.
- Fonken HA, Ellis PP. Leukemic infiltrates in the iris. Arch Ophthalmol. 1966;76:32–36.
- Allen RA, Straatsma BL. Ocular involvement in leukemia and allied disorders. Arch Ophthalmol. 1961;66:490–508.
- Ayliffe W, Foster CS, Marcoux P, et al. Relapsing acute myeloid leukemia manifesting as hypopyon uveitis. Am J Ophthalmol. 1995;119:361–364.
- Tsai T, O’Brien JM. Masquerade syndromes: malignancies mimicking inflammation in the eye. Int Ophthalmol Clin. 2002;42:115–1131.
- Yi DH, Rashid S, Cibas ES, Arrigg PG, Dana MR. Acute unilateral leukemic hypopyon in an adult with relapsing acute lymphoblastic leukemia. Am J Ophthalmol. 2005;139:719–721. doi:10.1016/j.ajo.2004.09.074 [CrossRef]
- Hurtado-Sarrio M, Dutch-Samper A, Taboada-Esteve J, Martinez-Dominguez JA, Senent-Peris ML, Menezo-Rozalen JL. Anterior chamber infiltration in a patient with Ph+ acute lymphoblastic leukemia in remission with imatinib. Am J Ophthalmol. 2005;139:723–724. doi:10.1016/j.ajo.2004.09.075 [CrossRef]