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An atypical case of bilateral posterior scleritis in a patient with chronic lymphocytic leukemia

      Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, with 75% of affected individuals diagnosed between 55 and 84 years of age.
      • Washburn L.
      Chronic lymphocytic leukemia: the most common leukemia in adults.
      The prevalence rate of ocular involvement in CLL has been estimated to be approximately 12%, and presentations remain variable and inconsistent.
      • Buchan J.
      • McKibbin M.
      • Burton T.
      The prevalence of ocular disease in chronic lymphocytic leukemia.
      To our knowledge, bilateral posterior scleritis in a patient with CLL has not been reported in the literature.
      A 70-year-old male was admitted to Grand River Hospital in Kitchener, Ontario, for severe fatigue and malaise. He had a 9-year history of CLL, for which he was treated with 3 cycles of oral chlorambucil in the past. Approximately 11 days after conclusion of the second cycle of chemotherapy, he complained of 3 to 4 days of ocular irritation, pain with eye movements, and blurry vision bilaterally.
      At initial bedside examination, best corrected Snellen acuity (BCVA) was 20/70 bilaterally. Pupils were unremarkable. There was about –2 limitation with abduction but no proptosis in either eye. Intraocular pressure (IOP) measured with Tono-Pen (Reichert Technologies, Depew, N.Y.) was 20 and 24 mm Hg in right and left eyes, respectively. Significant hyperemic chemosis was present bilaterally for 360 degrees and was soft and nontender to palpation (Fig. 1). Multiple peripheral, small, dome-shaped choroidal effusions and diffuse creamy choroidal infiltrates were seen bilaterally on dilated fundus examination.
      Figure thumbnail gr1
      Fig. 1Three hundred sixty degrees of hyperemic chemosis bilaterally.
      To rule out local extension of metastatic malignancy, we performed neuroimaging with magnetic resonance imaging (MRI) of the head and orbits, and biopsy of bulbar conjunctiva (clinical history and examination findings were communicated to the pathologist, who reviewed the biopsy specimen). MRI revealed bilateral periorbital soft tissue swelling, marked preseptal edema, choroidal detachments bilaterally, marked hyperintensity of posterior sclera on the left more than the right, consistent with posterior scleritis, and no muscular, intraconal, or optic nerve infiltration (Fig. 2). Informed consent was obtained from the patient for excisional biopsy of the left eye’s bulbar conjunctiva, which showed mild acute inflammatory changes with stromal edema, mild neutrophilic and scattered eosinophilic infiltrates in the epithelium and stroma, but no sign of dysplasia or malignancy (Fig. 3). Complete blood count confirmed relapse of CLL (Table 1), and chemotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) was initiated by the patient’s oncologist. A 1-week course of Maxidex (dexamethasone) drops qid OU was prescribed.
      Figure thumbnail gr2
      Fig. 2Transverse section of orbital magnetic resonance imaging demonstrating diffuse extraconal and periorbital soft tissue swelling, marked preseptal edema, choroidal detachments bilaterally (red arrows), and hyperintensity of posterior sclera more noticeable on the left than the right.
      Figure thumbnail gr3
      Fig. 3Left bulbar conjunctival biopsy, under 10× magnification, yielding benign inflammatory changes but no malignancy.
      Table 1Complete blood count demonstrating elevated lymphocytes and decreased erythrocyte, hemoglobin, and hematocrit, which are consistent with relapse of chronic lymphocytic leukemia
      Blood Count ParameterLevelsReference RangeUnits
      LKC25.7 HH4.0–11.0×109/L
      ERC3.74 L4.40–5.90×1012/L
      HGB114 L130–180g/L
      HCT0.331 L0.370–0.500
      LYMPH#17.7 HH1.0–4.8×109/L
      LKC, leukocytes; ERC, erythrocytes; HGB, hemoglobin; HCT, hematocrit; LYMPH#, total lymphocyte count.
      Intravenous fluorescein angiography and fundus photographs unfortunately could not be performed until 1 month later when the patient was stable enough to be transferred to another hospital for the test, which yielded normal findings and no significant pathology (Fig. 4). Three weeks after initiation of chemotherapy, all choroidal effusions had resolved, but mild chemosis and subtle diffuse punctate creamy choroidal lesions remained. BCVA improved to 20/30 OD, 20/25 OS.
      Figure thumbnail gr4
      Fig. 4Fundus photographs (top) and late-phase intravenous fluorescein angiography (bottom) taken 2 months after initiation of chemotherapy demonstrating full resolution of choroidal lesions.
      Ten weeks after completion of chemotherapy, BCVA improved to 20/25 bilaterally. IOP also improved to 16 mm Hg, with complete resolution of chemosis and choroidal lesions in both eyes.
      CLL is the most common leukemia in Western countries; however, ocular manifestations are rare and variable, which makes it difficult for immediate recognition and for formulating a definitive treatment plan. CLL predominantly involves B cells and is characterized by proliferation of lymphocytes that accumulate within blood, bone marrow, lymph nodes, and extranodal tissue.
      • Hatton M.P.
      • Rubin P.D.
      Chronic lymphocytic leukemia of the orbit.
      Diagnosis of CLL is made via complete blood count and peripheral blood smears. Common complications of CLL include hemolytic anemia, lymphocytosis, autoimmune cytopenia unresponsive to corticosteroids, splenomegaly, fatigue, fevers, night sweats, weight loss, and nausea.
      • Washburn L.
      Chronic lymphocytic leukemia: the most common leukemia in adults.
      Ocular involvement may be either directly related to leukemic infiltration or indirectly because of compromised immune function, hyperviscosity, thrombocytopenia, anemia, or chemotherapy treatment, but any ocular involvement is rare.
      • Buchan J.
      • McKibbin M.
      • Burton T.
      The prevalence of ocular disease in chronic lymphocytic leukemia.
      Buchan et al.
      • Buchan J.
      • McKibbin M.
      • Burton T.
      The prevalence of ocular disease in chronic lymphocytic leukemia.
      reported a 12% prevalence rate of ocular disease in patients with CLL.
      The findings in this patient differ from previous literature of CLL with ocular involvement. First, previously reported ocular manifestations and secondary complications include conjunctival vascular anomalies,
      • Buchan J.
      • McKibbin M.
      • Burton T.
      The prevalence of ocular disease in chronic lymphocytic leukemia.
      unilateral acute retinal necrosis,
      • Buchan J.
      • McKibbin M.
      • Burton T.
      The prevalence of ocular disease in chronic lymphocytic leukemia.
      optic nerve infiltration,
      • Hatton M.P.
      • Rubin P.D.
      Chronic lymphocytic leukemia of the orbit.
      • Currie J.N.
      • Lessell S.
      • Lessell I.M.
      • Weiss J.S.
      • Albert D.M.
      • Benson E.M.
      Optic neuropathy in chronic lymphocytic leukemia.
      proptosis,
      • Skinnider L.F.
      • Romanchuk K.G.
      Orbital involvement in chronic lymphocytic leukemia.
      ophthalmoplegia,
      • Hatton M.P.
      • Rubin P.D.
      Chronic lymphocytic leukemia of the orbit.
      • Skinnider L.F.
      • Romanchuk K.G.
      Orbital involvement in chronic lymphocytic leukemia.
      ptosis,
      • Hatton M.P.
      • Rubin P.D.
      Chronic lymphocytic leukemia of the orbit.
      • Skinnider L.F.
      • Romanchuk K.G.
      Orbital involvement in chronic lymphocytic leukemia.
      orbital apex syndrome,
      • Garala K.
      • Jayaramachandran P.
      • Knopp M.
      • Critchley P.
      Orbital apex tumour caused by chronic lymphocytic leukaemia: an unlikely suspect.
      vitreous cells,
      • Hattenhauer M.G.
      • Pach J.M.
      Ocular lymphoma in a patient with chronic lymphocytic leukemia.
      bilateral lacrimal gland enlargement and chronic uveitis,
      • Kubicha-Trzaska A.
      • Gedliczka M.
      • Ramanowaska-Dixon B.
      Ocular masquerade syndrome in a patient with chronic lymphocytic leukemia.
      secondary endophthalmitis,
      • Kalina P.H.
      • Campbell R.
      Aspergillus terreus endophthalmitis in a patient with chronic lymphocytic leukemia.
      left lower lid and inferior orbital soft tissue masses with anterior uveitis and hypopyon,
      • Ong Y.L.
      • White S.
      Intra-vitreal methotrexate leads to resolution of intraocular chronic lymphocytic leukemia.
      bilateral retinal infiltrates,
      • Treppendahl M.B.
      • Andersen N.
      • Jurlander J.
      • Geisler C.
      A case of chronic lymphocytic leukemia with deletion 17p and bilateral retinal leukemic infiltrates.
      extraocular muscular infiltration,
      • Hatton M.P.
      • Rubin P.D.
      Chronic lymphocytic leukemia of the orbit.
      • Kiratli H.
      • Balci K.E.
      • Himmetoglu C.
      • Uner A.
      Isolated extraocular muscle involvement as the ophthalmic manifestation of leukaemia.
      among others. Unilateral scleral infiltration by CLL had been reported.
      • Burton B.J.L.
      • Cunningham E.T.
      • Cree I.A.
      • Pavesio C.E.
      Eye involvement mimicking scleritis in a patient with chronic lymphocytic leukaemia.
      However, bilateral posterior scleritis has yet to be reported in a patient with a history of CLL. Typically, posterior scleritis presents with marked periocular pain, decreased vision, pain with ocular movements, and can potentially involve the posterior segment through macular edema and exudative retinal or choroidal detachments.
      • Burton B.J.L.
      • Cunningham E.T.
      • Cree I.A.
      • Pavesio C.E.
      Eye involvement mimicking scleritis in a patient with chronic lymphocytic leukaemia.
      Orbital MRI assists in diagnosis as one would visualize hyperintensity around the globe, indicating an inflammatory process that is accentuated with gadolinium enhancement.
      • Maggioni F.
      • Ruffatti S.
      • Viaro F.
      • Mainardi F.
      • Lisotto C.
      • Zanchin G.
      A case of posterior scleritis: differential diagnosis of ocular pain.
      Our patient had findings consistent with posterior scleritis, although the severity of pain appeared to be less than expected. Nonetheless, scleritis with little or no pain had been reported; thus, imaging is crucial in helping with diagnosis of this condition.
      • Saikia P.
      • Nashed A.
      • Helbig H.
      • Hillenkamp J.
      Bilateral posterior scleritis: an idiopathic painless presentation.
      • Dodds E.M.
      • Irarrázaval L.A.
      • Scarfone A.
      • Gáspari E.
      Bilateral posterior scleritis.
      Second, the literature has yet to describe the complete resolution of bilateral ocular involvement after chemotherapy. The most common course of treatment for ocular involvement of CLL includes a combination of high-dose systemic steroids, external beam irradiation, laser photocoagulation, and (or) chemotherapy. For instance, Currie et al.
      • Currie J.N.
      • Lessell S.
      • Lessell I.M.
      • Weiss J.S.
      • Albert D.M.
      • Benson E.M.
      Optic neuropathy in chronic lymphocytic leukemia.
      reported 3 cases of CLL that required high-dose prednisone and external beam irradiation for complete resolution of ocular findings. Hatton and Rubin
      • Hatton M.P.
      • Rubin P.D.
      Chronic lymphocytic leukemia of the orbit.
      described a case of orbital CLL who required local radiation. The biopsy results for our case suggested that the ocular involvement was likely not from malignant infiltration but from reactive inflammatory cause at the time of CLL relapse. However, our patient was unable to undergo high-dose oral prednisone because of a history of severe intolerance. Instead, a short course of topical steroid was prescribed and the patient underwent 1 cycle of FCR chemotherapy with full resolution of the ocular findings.
      To our knowledge, this is the first reported case of bilateral posterior scleritis in a patient with CLL that resolved with topical steroid and systemic chemotherapy. Awareness and consideration of these atypical presenting signs will assist in future diagnosis of ocular involvement of CLL and may contribute to further understanding of the underlying pathophysiology.

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