1. Copyright restrictions may apply JAMA Ophthalmology Journal Club Slides: Relationship Between Female Reproductive Factors and Choroidal Nevus in US Women Qiu M, Shields CL. Relationship between female reproductive factors and choroidal nevus in US women: analysis of data from the 2005-2008 National Health and Nutrition Examination Survey. JAMA Ophthalmol. Published online September 24, 2015. doi:10.1001/jamaophthalmol.2015.3178.

2. Copyright restrictions may apply Introduction Choroidal nevus is the most common clinically documented intraocular mass, with an estimated 1 in 8845 risk for transformation into malignant melanoma. Cutaneous nevi arise during puberty and change shape and color during pregnancy, suggesting that cutaneous melanocytes could be estrogen receptive. There are several reports of choroidal melanoma in pregnant women, but evidence regarding estrogen receptors in choroidal melanoma has been inconsistent. There have been several studies investigating female sex hormones and cutaneous nevi, cutaneous melanoma, and choroidal melanoma but no published reports about female reproductive factors and choroidal nevus.

3. Copyright restrictions may apply Introduction Objective –To characterize the relationship between female reproductive factors and choroidal nevus in a representative sample of US women.

4. Copyright restrictions may apply Study Design –Cross-sectional, population-based study using data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES). Participants –Women aged 40 years or older who completed the reproductive health questionnaire and underwent retinal imaging. Data Analysis –Predictor variables included age, sex, race, body mass index (BMI), age at menarche, oral contraceptive use, pregnancy, parity, age at first and last births, age at menopause, hysterectomy, oophorectomy, and hormone therapy use. –The main outcome measure was choroidal nevus on retinal imaging. Methods

5. Copyright restrictions may apply Limitations –The cross-sectional design did not identify direction of causation. –Associations could have arisen by chance and additional studies are needed to confirm the findings. –The NHANES does not contain data about iris nevus, conjunctival nevus, or cutaneous nevus, and it would have been useful to evaluate whether there was any association between female reproductive factors and these other melanocytic lesions. –The NHANES retinal imaging only included 2 postequatorial photographs. 45-Degree photograph centered on the macula. 45-Degree photograph centered on the disc. Methods

6. Copyright restrictions may apply Total sample size: 2505 women. Mean age: 56.5 years Racial distribution: 76.9% white, 10.1% African American, 8.4% Hispanic, and 4.8% other. Population-weighted prevalence of choroidal nevus in the 2 overlapping fundus photographs was 4.5%. Results

7. Copyright restrictions may apply Premenopausal women who first gave birth before age 20 years had 4 times higher odds of choroidal nevus than those who first gave birth after age 35 years (odds ratio [OR], 4.16; 95% CI, 1.29-13.45; P =.02). Premenopausal women who gave birth to their last child before age 25 years had 5 times higher odds of choroidal nevus than those who gave birth to their last child after age 35 years (OR, 4.89; 95% CI, 1.15-20.74; P =.03). These relationships were independent of total parity and years between the first and last births. The odds of choroidal nevus in postmenopausal women who were overweight and obese were 2 times higher than in postmenopausal women with normal BMI (OR, 2.11; 95% CI, 1.19-3.76, P =.01 for overweight and OR, 1.92; 95% CI, 1.13-3.25; P =.02 for obese). Results

8. Copyright restrictions may apply Results Multivariate Logistic Regressions Identifying Reproductive Factors Associated With Choroidal Nevus Each multivariate logistic regression is adjusted for age, race, BMI, and the factor of interest. Not all factors are shown in this slide; the full list of results is shown in the article. NA indicates not applicable. Characteristic Premenopausal Women (n = 551)Postmenopausal Women (n = 1800) OR (95% CI)P ValueOR (95% CI)P Value Age0.94 (0.84-1.05).241.01 (0.98-1.04)059 Race/ethnicity White1 [Reference]NA1 [Reference]NA African American0 (NA)NA0.05 (0.01-0.22)<.001 Hispanic0.26 (0.05-1.25).090.56 (0.26-1.24).15 Other2.19 (0.44-10.88).320.20 (0.02-1.67).13 BMI <18.53.32 (0.48-23.14).210 (NA)NA 18.5-24.91 [Reference]NA1 [Reference]NA 25.0-29.91.17 (0.31-4.45).822.11 (1.19-3.76).01 ≥30.01.38 (0.58-3.29).451.92 (1.13-3.25).02 Age at first period, y ≤110.92 (0.15-5.67).931.31 (0.44-3.86).62 120.60 (0.22-1.63).301.42 (0.56-3.59).45 131.03 (0.18-5.91).971.36 (0.60-3.10).45 141.37 (0.26-7.10).700.83 (0.34-2.04).67 ≥151 [Reference]NA1 [Reference]NA No. of live births 01 [Reference]NA1 [Reference]NA 11.48 (0.59-3.75).390.99 (0.29-3.41).99 20.79 (0.15-4.10).762.22 (0.77-6.37).13 30.67 (0.10-4.31).671.62 (0.55-4.78).37 ≥40.58 (0.09-3.97).241.20 (0.39-3.71).75 Age at first live birth, y ≤194.16 (1.29-13.45).021.17 (0.14-9.48).88 20-241.81 (0.55-5.94).322.02 (0.21-19.63).53 25-290.58 (0.12-2.78).481.28 (0.13-12.96).83 30-340.75 (0.16-3.65).720.64 (0.04-10.04).74 ≥351 [Reference]NA1 [Reference]NA Age at last live birth, y ≤244.89 (1.15-20.74).031.19 (0.56-2.51).65 25-290.71 (0.13-3.80).671.78 (0.98-3.22).06 30-341.06 (0.43-2.57).900.79 (0.30-2.05).61 ≥351 [Reference]NA1 [Reference]NA Age at last period, y ≤39NA 1.18 (0.52-2.67).69 40-44NA 1.27 (0.46-3.45).64 45-49NA 0.98 (0.42-2.26).96 50-54NA 0.98 (0.35-2.78).97 ≥55 NA 1 [Reference]NA

9. Copyright restrictions may apply The purpose of this cross-sectional, population-based study was to explore the relationship between female reproductive factors and choroidal nevus, a precursor to melanoma, in the US adult female population. –In premenopausal women, younger age at first and last births (before ages 20 and 25 years, respectively) was associated with more than 4 times higher odds of choroidal nevus compared with older age at first and last births (after age 35 years). –In postmenopausal women, higher BMI (>30) was associated with 2 times higher odds of choroidal nevus compared with normal BMI (18.5-24.9). This suggests that unopposed estrogen following early childbearing years or overproduction of estrogen through body adipocytes (higher BMI) could be related to development of choroidal nevus. Discussion

10. Copyright restrictions may apply Contact Information If you have questions, please contact the corresponding author: –Mary Qiu, MD, Wilmer Eye Institute, 600 N Wolfe St, Wilmer B-29, Baltimore, MD 21287 (mary.qiu@gmail.com). Funding/Support Support for this study was provided by the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (Dr Shields). Conflict of Interest Disclosures All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.