Dexamethasone Is Associated with Cataracts in Multiple Myeloma Even after Adjusting for Age: Results of a Large Cross-Sectional Survey
Authors: Banerjee Rahul , Hurtado Martinez Jorge Arturo , Barnes Mason S. , Flores Pérez Patricia Alejandra , Hydren Jay R. , Ahlstrom Jennifer M. , Cicero Kara I. , Kaur Gurbakhash , Taravati Parisa , Cowan Andrew J. 
Published: December 2024

Introduction: Many multiple myeloma (MM) therapies can increase the risk of ocular comorbidities such as bortezomib-related blepharitis or belantamab-related keratopathy. More recently, higher lifetime doses of dexamethasone (dex) have been associated with a higher risk of cataracts (Banerjee AJH 2024). Little is known about the interplay between plasma cell disorders, the aging process, and eye health in general.

Methods: A cross-sectional study surveyed patients with MM or precursor conditions through Healthtree Cure Hub, an online platform advocating for patient-focused research. Patients answered questions about their demographics, medical history, ocular comorbidities, frequency of eye health visits, and interference with instrumental activities of daily living (IADLs; i.e., driving) due to ocular disorders. Given the widespread use of dex in MM treatment regimens, patients with MM were also asked to report their typical weekly dex dose in milligrams (mg); this was categorized as high-dose (20-40 mg), low-dose (1-19 mg), or those that hadn't begun therapy (no-therapy). Age-adjusted logistic regression models (AALRMs) were employed to evaluate the associations between drug exposure and ocular conditions, using the formula: odds = e^(b0+ b1*Drug Exposure + b2 *age(yr)). Drug Exposure was coded as 1 for high-dose dexamethasone versus 0 for low-dose/non for the cataract model and 1 vs 0 for bortezomib exposure with regard to blepharitis. The output of the model was then converted to an odds ratio (OR) at the average age of the sample.

Results: Of n=582 respondents including 538 (92.4%) patients with MM, the mean age at survey completion was 65.9 ± 8.7 years; 36.3% (n=211) were aged 70+. Female patients comprised 61.5% of respondents; 5.5% were Black and 3.4% Hispanic or Latino/a. Dex exposures were high-dose in 49.8% (n=290), low-dose in 12.2% (n=71), and no-therapy in 30.4% (n=177, including MM precursors); the remaining patients were unsure. Cataracts were reported by 311 patients (53.4%), including 63.1% of the high-dose dex group, 53.5% of the low-dose dex group, and 50.8% of the no-therapy group; this difference in cataract prevalences between groups was significant (p&lt;0.05). Cataracts were asymptomatic in 46.3% (n=144), whereas 7.4% (n=23) of patients with cataracts reported resultant IADL limitations (e.g., driving); these proportions were comparable between the three dex groups. The AALRM for cataracts showed a significant positive association with high-dose dex (OR = 2.06, b1 = 0.7219, p &lt; 0.05), while a positive association with age (OR = 1.12 per year, b2 = 0.1136, p &lt; 0.001) was also observed. The intercept of the AALRM for dex was b0 = -7.507 (p &lt;0.001).

A majority of patients (57.9%, n=337) had received bortezomib at some point. Blepharitis or styes were reported by 23.0% (n=134), including 26.1% of bortezomib-exposed patients (n=88) versus 18.8% (n=46) of bortezomib-unexposed patients. The AALRM for blepharitis showed a positive association with bortezomib exposure (OR = 1.5, b1 = 0.4073, p &lt;0.05) and a negative association with age (OR = 0.97 per year, b2 = -0.0356, p &lt; 0.001). The intercept of the AALRM for bortezomib was b0 = 0.8926 (p = 0.09). Other common reported issues included dry eyes (38.8%, n=226) and glaucoma (7-11%, comparable between the three dex groups). With regard to eye health, 81.7% (n=476) reported seeing an optometrist or ophthalmologist at least once per year. Only 29.2% (n=170) recalled that their oncologist had recommended periodic eye exams.

Discussion: While limited by recall bias and sampling bias, our cross-sectional study of over 500 patients illustrates the wide spectrum of ocular comorbidities and toxicities in plasma cell disorders. Controlling for age using AALRMs is essential due to the confounding impact of advancing age on eye health conditions. Higher dex doses were associated with a twofold higher risk of cataracts in the AALRM that accounted for advancing age, an even stronger link than the association observed between bortezomib and blepharitis. Future research is in development to prospectively investigate whether dex reduction strategies can mitigate this longitudinal risk of cataracts. More broadly, our findings suggest that periodic eye exams - although inconsistently recommended by oncologists - are a key component of supportive care for patients living with MM.

Funding: HealthTree Foundation through patient donations.