A Case Report of Dexamethasone Associated Vision Loss in A Young Multiple Myeloma Patient

Abstract

Dexamethasone is a highly potent glucocorticoid commonly used in the treatment regimens of Multiple Myeloma (MM). This case report describes an acute vision loss developed in a female patient, after starting Bortezomib-Cyclophosphamide-Dexamethasone regimen (VCd) for newly diagnosed MM. Opthalomology evaluation revealed the diagnosis of central serous chorioretinopathy, which was completely resolved after stopping dexamethasone. This case emphasizes the need for close monitoring and optimization of steroid dose in patients with MM and other plasma cell dyscrasias.

Keywords

Introduction

Multiple Myeloma (MM) is a malignancy of plasma cells, poses significant challenges in clinical management due to its complex pathophysiology and varied presentation. The disease’s propensity to cause anemia, hypercalcemia, bone lesions and renal impairment necessitates aggressive treatment strategies to mitigate symptoms, prevent disease progression and improve patient outcomes. The VCd regimen, consisting of bortezomib, cyclophosphamide and dexamethasone is a triplet treatment regimen for MM, particularly in the upfront setting. This combination therapy leverages the synergistic effect of these agents to induce antitumor responses and achieve improved survival rates in MM.1 Dexamethasone, a potent corticosteroid, plays a critical role in the VCd regimen, providing anti-inflammatory, immunosuppressive and anti-tumor effects that complement the mechanisms of action of bortezomib and cyclophosphamide. However, the prolonged use of dexamethasone is associated with a range of adverse effects, including metabolic disturbances, neuropsychiatric changes and ocular complications.2 This report documents a rare instance of dexamethasone induced vision loss in a patient undergoing treatment for multiple myeloma with the VCd regimen. The occurrence of this adverse event highlights the importance of vigilant monitoring and timely intervention in patients receiving dexamethasone as part of their treatment protocol. Furthermore, it underscores the need for clinicians to be aware of the potential risks associated with dexamethasone therapy and to implement strategies to mitigate these risks and optimize patient outcomes.

Case Presentation: A 42 year old female lady with history of anemia of 1 year and recent acute kidney injury (AKI) presented with bone pains, anorexia and fatigue of 3 weeks. She had no known comorbidities and was not taking any regular medications. Evaluation showed Hb of 8.5 g/dL, creatinine 3.8 mg/dL, serum calcium level 11.5 mg/dL. Bone marrow aspiration and biopsy reports revealed 80% kappa light chain restricted plasma cells and renal biopsy showed kappa light chain deposition. Urine free light chain assay also revealed high kappa light chain and elevated kappa/lambda ratio. After evaluation by a Haematologist, she was diagnosed to have kappa light chain MM with kappa light chain deposition disease.  She was started with bortezomib based induction regimen (intravenous bortezomib 1.5mg/m2 and intravenous dexamethasone 40 mg OD x 4 days) along with antiviral prophylaxis with aciclovir and empiric allopurinol in view of anticipated hyperuricemia of tumor lysis. We planned to add cyclophosphamide in the subsequent weeks, along with a weekly VCd regimen (weekly once bortezomib, cyclophosphamide and dexamethasone). She came back on day 4 of initial week of bortezomib - dexamethasone course with tumor lysis syndrome (hyperkalemia, hyperphosphatemia, hyperuricemia and worsening of creatinine from baseline of 3.8 to 4.6 mg/dL). She was improved with aggressive hydration and intravenous rasburicase. She complained of biateral blurring of vision during the second week consultation (day 8 of cycle 1 bortezomib induction) in Haematology department. Hence, on day 8 of cycle 1, bortezomib 2 mg was given subcutaneously and dexamethasone 8 mg (dose reduced) was administered orally. On the basis of sub-retinal fluid in both eyes, an Opthalmologist’s consultation was sought and the patient was evaluated with Fundus Fluorescein Angiography (FFA). After FFA, Opthalmologist advised to apply an eye drop of tropicamide and phenylephrine combination in both eyes. On day 15 of cycle 1, she was given bortezomib 2.4 mg and dexamethasone 20 mg orally. She developed fluid retention after third week bortezomib and dexamethasone, which was managed with furosemide. Her vision loss remained unchanged still at the fourth week of bortezomib therapy. In view of disease related maculopathy, cyclophosphamide 250 mg (low dose) once weekly oral dose added from the day 22 of cycle 1 Bortezomib based regimen and increased oral dexamethasone dose to 40 mg once weekly. At the time of starting second cycle of bortezomib (fifth week), she claimed an improvement in the blurring of vision and continued the same VCd dose of fourth week. In the subsequent weeks, VCd continued at the same dose and she reported persistent blurring of vision even after the ninth week of MM treatment with steroid. From tenth week, dexamethasone was omitted from VCd regimen to look for the improvement in her vision and same dose of cyclophosphamide and bortezomib continued. Urine free light chain assay after 2 cycles (8 weeks) of bortezomib based regimen was suggestive of a good response (near to very good partial response (VGPR)) to the MM induction treatment. She reported a complete reversal of vision loss after stopping dexamethasone. Subsequently, she continued bortezomib with low dose steroids, which were tolerated well and remains a good response to MM.

DISCUSSION: In the past decade, VCd is one of the common and effective triplet induction regimen for newly diagnosed transplant eligible MM.1 According to previous studies, MM or other monoclonal gammopathy patients may present with visual impairment due to paraproteinemia.3,4,5 Blurring or loss of vision associated with steroid treatment and chemotherapy have been published in clinical reports.2,6,7 Various routes of exogenous cortecosteroids such as enteral and parenteral routes have been shown to be linked with central serous chorioretinopathy.8,9 Several mechanisms contribute to the pathophysiology of decreased visual acuity induced by steroids. Inhibition of collagen synthesis, increased permeability of the choriocapillaries and dysfunction in ion pumping with a reversal of ionic current direction are the proposed mechanisms for central serous chorioretinopathy.9,10,11 Glucocorticoids reduce the production of prostaglandins, which regulate the aqueous outflow. Corticosteroids may increase intra ocular pressure (IOP), which can be reversed, if detected early. If left untreated, it can lead to glaucomatous optic neuropathy, which is irreversible.12 In our case, there is subretinal fluids in both eyes during steroid therapy, which was also reported by  Balakrishnan S et al. after intraarticular steroid injection to the knee joint.6 F. Bandello et al. also reported a case of bilateral central serous chorioretinopathy developed in a patient treated with systemic corticosteroids for Non-Hodgkin lymphoma.13  A systematic review of 49 patients with steroid induced vision loss revealed that triamsinolone was the most common steroid injection associated with decreased visual acuity, may be due to the low solubility,  large particle size and extensive particle aggregation. The above study in patients who received facial and periorbital steroid injections also showed that, dexamethasone has not been associated with vision loss due to the vascular occlusion.14 

CONCLUSION: Clinical Haematologists, Oncologists and other health care providers dealing with chemotherapy and steroids want to be aware of this complication of steroid therapy, and cessation of steroids or dose modification to the patients who developed blurring of vision or loss of visual acuity. In the patients with previous history of central serous chorioretinopathy, periodical ophthalmology evaluation with opthalmoscopic examination is essential to look for asymptomatic or early steroid related retinopathy and to prevent ophthalmology complications.

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