Risk factors for dry eye disease in adult granulosa cell tumors: Implications for quality of life

Aslı Geçgel; Zeynep Gökdere; Oğuzcan Özkan; Gürdeniz Serin; Melis Palamar; Şaziye Burçak Karaca; Erdem Göker; Ulus Ali Şanlı

doi:10.19161/etd.1802914

TR EN

Erişkin granüloza hücreli tümörlerde kuru göz hastalığının risk faktörleri: Yaşam kalitesi açısından bulgular

Abstract

Amaç: Erişkin granüloza hücreli tümörler (EGHT), genellikle uzun klinik seyir ve geç nükslerle karakterize, nadir görülen östrojen üreten over neoplazmlarıdır. Bu hasta grubunda kuru göz hastalığının (KGH) araştırılması önemlidir; çünkü EGHT’ye bağlı hormonal değişiklikler ve uygulanan tedaviler oküler sağlığı etkileyebilir. Bu çalışmanın amacı, EGHT hastalarında KGH sıklığını belirlemek ve KGH ile yaş, menopoz durumu, klinikopatolojik özellikler, komorbiditeler ve onkolojik tedaviler arasındaki ilişkileri değerlendirmektir. Gereç ve Yöntem: Bu retrospektif, tek merkezli çalışmada, 2012–2024 yılları arasında tanı almış, histopatolojik olarak doğrulanmış 55 EGHT hastası değerlendirildi. KGH; oftalmoloji konsültasyon kayıtları, belgelenmiş oküler semptomlar ve Schirmer testi sonuçları (≤5 mm/5 dk) dâhil olmak üzere objektif değerlendirmeler temel alınarak tanımlandı. Klinikopatolojik parametreler, menopoz durumu, adjuvan tedaviler, komorbiditeler ve KGH arasındaki ilişkiler, IBM SPSS Statistics for Windows, Sürüm 22.0 (IBM Corp., Armonk, NY, ABD) kullanılarak gerçekleştirilen tek değişkenli ve çok değişkenli lojistik regresyon analizleri ile değerlendirildi. Bulgular: KGH, hastaların %23,6’sında (n=13) saptandı. KGH olan hastalar, düzeltilmemiş karşılaştırmalarda tanı anında daha yaşlıydı (ortalama 55,2’ye karşı 48,6 yıl); ancak lojistik regresyon analizlerinde yaşın KGH ile bağımsız bir ilişkisi gösterilemedi. Tek değişkenli analizlerde KGH ile menopoz durumu, ER veya inhibin ekspresyonu, FIGO evresi, endometrial patoloji, nüks veya adjuvan tedavi türü arasında istatistiksel olarak anlamlı bir ilişki gözlenmedi. Çok değişkenli lojistik regresyon modelinde komorbidite (OR 1,696; %95 GA 0,809–3,554; p=0,162) ve tümör çapı >10 cm (OR 2,375; %95 GA 0,648–8,708; p=0,192) KGH olasılığında artış yönünde, ancak istatistiksel olarak anlamlı olmayan eğilimler gösterdi. Tanımlayıcı karşılaştırmalarda paklitaksel bazlı tedavi alan EGHT hastalarında KGH prevalansı sayısal olarak daha yüksekti, ancak bu fark istatistiksel olarak anlamlı değildi. Sonuç: KGH, EGHT tanılı hastalarda özellikle ileri yaştaki bireylerde, komorbiditesi olanlarda ve taksan temelli tedavi alan hastalarda göz önünde bulundurulmalıdır. Standart onkolojik takip sürecine kısa bir oküler yüzey taramasının entegre edilmesi, gözden kaçabilen semptomların saptanmasını kolaylaştırabilir ve hasta konforu ile yaşam kalitesini artırabilir.

Keywords

Risk factors for dry eye disease in adult granulosa cell tumors: Implications for quality of life

Abstract

Aim: Adult granulosa cell tumors (AGCTs) are rare estrogen-producing ovarian neoplasms that typically exhibit a prolonged clinical course and late recurrences. Investigating dry eye disease (DED) in this patient population is essential, as AGCT-related hormonal alterations and therapeutic interventions may affect ocular health. This study aimed to determine the prevalence of DED among patients with AGCT and to assess its associations with age, menopausal status, clinicopathological features, comorbidities, and oncologic treatments. Materials and Methods: This retrospective, single-center study evaluated 55 patients with histopathologically confirmed AGCT diagnosed between 2012 and 2024. DED was identified based on ophthalmology consultation records, documented ocular symptoms, and objective testing, including Schirmer test results (≤5 mm/5 min). Associations among clinicopathological parameters, menopausal status, adjuvant treatments, comorbidities, and DED were assessed using univariate and multivariate logistic regression analyses, conducted with SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA). Results: DED was detected in 23.6% (n=13) of patients. Patients with DED were older at diagnosis in unadjusted comparisons (mean 55.2 vs. 48.6 years); however, age was not independently associated with DED in logistic regression analyses. In univariate analyses, no statistically significant associations were observed between DED and menopausal status, ER or inhibin expression, FIGO stage, endometrial pathology, recurrence, or type of adjuvant therapy. In the multivariable logistic regression model, comorbidity (OR 1.696; 95% CI, 0.809–3.554; p=0.162) and tumor size >10 cm (OR 2.375; 95% CI, 0.648–8.708; p=0.192) showed non-significant trends toward higher odds of DED. In descriptive comparisons, patients who received paclitaxel-based therapy had a numerically higher prevalence of DED, although this difference was not statistically significant. Conclusions: Dry eye disease should be actively considered in patients with adult granulosa cell tumors, especially among older adults, individuals with comorbidities, and those receiving taxane-based therapy. Integrating brief ocular surface screening into standard oncologic follow-up could facilitate the identification of underrecognized symptoms and enhance patient comfort and quality of life.

Keywords

Supporting Institution

This research received no external funding.

Ethical Statement

The study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Ege University Medical Research Ethics Committee (approval number: 25-9T/79, dated September 4, 2025).

References

Pilsworth, J.A., et al., Adult‐type granulosa cell tumor of the ovary: a FOXL2‐centric disease. The Journal of Pathology: Clinical Research, 2021. 7(3): p. 243-252.
Temtanakitpaisan, A., P. Kleebkaow, and A. Aue-aungkul, Adult-type Granulosa Cell Ovarian Tumor: Clinicopathological Features, Outcomes, and Prognostic Factors. Asian Pacific Journal of Cancer Care, 2019. 4(2): p. 33-37.
Salkeni, M.A., et al., Advanced granulosa cell tumors of the ovary: a review with a focus on current and novel therapeutic approaches. Journal of Immunotherapy and Precision Oncology, 2024. 7(4): p. 263-271.
4Alnsour, S., B. Hsieh, and L. Bielory, Bridging diagnostic gaps in anterior ocular inflammatory surface diseases. Current Opinion in Allergy and Clinical Immunology, 2025. 25(5): p. 374-381.
Bartlett, J.D., et al., Associations between signs and symptoms of dry eye disease: a systematic review. Clinical ophthalmology, 2015: p. 1719-1730.
Findlay, Q. and K. Reid, Dry eye disease: when to treat and when to refer. Australian prescriber, 2018. 41(5): p. 160.
Huang, A., et al., Placebo or vehicle effects on dry eye signs and symptoms in randomized controlled trials: A systematic review and meta-analysis. Survey of Ophthalmology, 2025.
Song, J.-Y., et al., Association between menstrual irregularity and dry eye disease: a population-based study. Cornea, 2016. 35(2): p. 193-198.

Lee, C.-Y., et al., The association between ovarian cancer and the incidence of newly developed dry eye disease: a nationwide population-based study. Life, 2024. 14(4): p. 530.
Long, X., et al., The shared mechanism and potential diagnostic markers for premature ovarian failure and dry eye disease. Scientific Reports, 2024. 14(1): p. 16178.
Prat, J., Staging Classification for Cancer of the Ovary, Fallopian Tube, and Peritoneum: Abridged Republication of Guidelines From the International Federation of Gynecology and Obstetrics (FIGO). Obstet Gynecol, 2015. 126(1): p. 171-4.
Fujimoto, T., et al., Histopathological prognostic factors of adult granulosa cell tumors of the ovary. Acta Obstet Gynecol Scand, 2001. 80(11): p. 1069-74.
Babarović, E., et al., Adult Granulosa Cell Tumors of the Ovary: A Retrospective Study of 36 FIGO Stage I Cases with Emphasis on Prognostic Pathohistological Features. Anal Cell Pathol (Amst), 2018. 2018: p. 9148124.
Shim, S.-H., et al., A long-term follow-up study of 91 cases with ovarian granulosa cell tumors. Anticancer research, 2014. 34(2): p. 1001-1010.
Şahin, M., et al., The experıance of tertıary center for adult granulosa cell tumor: whıch factors predıct survival? J Ovarian Res, 2024. 17(1): p. 127.
Musa, M., et al., Diagnostic methods for managing dry eyes. World journal of methodology, 2025. 15(4): p. 101033.
Craig, J.P., et al., TFOS DEWS II definition and classification report. The ocular surface, 2017. 15(3): p. 276-283.
Willcox, M.D., et al., TFOS DEWS II tear film report. The ocular surface, 2017. 15(3): p. 366-403.
Deo, N. and P. Nagrale, Dry eye disease: an overview of its risk factors, diagnosis, and prevalence by age, sex, and race. Cureus, 2024. 16(2).
Sethi, P., et al., Dry eye in postmenopausal women: A hospital based analysis Type of article–Original Research. European Journal of Cardiovascular Medicine, 2024. 14: p. 743-747.
Qian, L. and W. Wei, Identified risk factors for dry eye syndrome: A systematic review and meta-analysis. PloS one, 2022. 17(8): p. e0271267.
Machairoudia, G., et al., Prevalence and risk factors of dry eye disease in patients treated with aromatase inhibitors for breast cancer. Clinical and Experimental Optometry, 2024. 107(4): p. 415-419.
Soni, M., S. Walia, and P. Jain, Dry eye disease in head and neck cancer patients undergoing radiotherapy. Indian Journal of Ophthalmology, 2023. 71(4): p. 1556-1560.
Chen, X., et al., Alterations in meibomian glands in patients treated with intensity-modulated radiotherapy for head and neck cancer. Scientific Reports, 2021. 11(1): p. 22419.
Chen, C.-T., et al., Nasopharyngeal Carcinoma and Its Effect on Dry Eye Disease: A Nationwide Cohort Study. International Journal of Environmental Research and Public Health, 2022. 20(1): p. 387.
Yaacoub, S., L. Hajj, and A. Khairallah, A clinicopathological study about the epidemiology of granulosa cell tumors in Lebanon. BMC cancer, 2024. 24(1): p. 309.
Tsai, Y.-R., et al., Hyperandrogenism in polycystic ovary syndrome augments Estrogen synthesis through AR-FOXL2–mediated activation of the aromatase gene in granulosa cells. Journal of Ovarian Research, 2025. 18(1): p. 200.
Seen, S. and L. Tong, Dry eye disease and oxidative stress. Acta Ophthalmologica, 2018. 96(4): p. e412-e420.
Kuo, Y.-K., et al., Tear function in patients with diabetes mellitus: A systematic review and meta-analysis. Frontiers in Endocrinology, 2022. 13: p. 1036002.
Shujaat, S., et al., Determination of risk factors and treatment of dry eye disease in Type 1 diabetes before corneal complications at Sindh Institute of Ophthalmology and Visual Sciences. The open ophthalmology journal, 2017. 11: p. 355.
Kam, K.W., et al., A review on drug-induced dry eye disease. Indian Journal of Ophthalmology, 2023. 71(4): p. 1263-1269.
Fraunfelder, F.T., J.J. Sciubba, and W.D. Mathers, The role of medications in causing dry eye. Journal of ophthalmology, 2012. 2012(1): p. 285851.
Leonardi, A., et al., Dry eye and systemic diseases. Saudi J Ophthalmol, 2025. 39(1): p. 5-13.
Chiang, J.C.B., et al., A cross-sectional study of ocular surface discomfort and corneal nerve dysfunction after paclitaxel treatment for cancer. Scientific Reports, 2021. 11(1): p. 1786.
Masalkhi, M., et al., Impact of immune checkpoint inhibitors on vision and eye health. Eye, 2024. 38(15): p. 2854-2856.
Lum, F., Comment on Ophthalmic Immune-Related Adverse Events and Association With Survival: Results From a Real-World Database. American Journal of Ophthalmology, 2025. 270: p. 277.
Martens, A., et al., Ocular adverse events associated with immune checkpoint inhibitors, a scoping review. J Ophthalmic Inflamm Infect, 2023. 13(1): p. 5.

Details

Primary Language

English

Subjects

Clinical Oncology

Journal Section

Research Article

Authors

Aslı Geçgel ^*
0000-0001-6942-9858
Türkiye

Zeynep Gökdere
0000-0002-8868-988X
Türkiye

Oğuzcan Özkan
0000-0002-4075-7775
Türkiye

Gürdeniz Serin
0000-0003-4204-0601
Türkiye

Melis Palamar
0000-0002-2494-0131
Türkiye

Şaziye Burçak Karaca
0000-0003-2638-1625
Türkiye

Erdem Göker
0000-0001-6180-713X
Türkiye

Ulus Ali Şanlı
0000-0002-0062-6105
Türkiye

Publication Date

June 10, 2026

Submission Date

October 15, 2025

Acceptance Date

January 9, 2026

Published in Issue

Year 2026 Volume: 65 Number: 2

DOI

https://doi.org/10.19161/etd.1802914

IZ

https://izlik.org/JA79UL97AT

Cite

RIS / Bibtex

APA

Geçgel, A., Gökdere, Z., Özkan, O., Serin, G., Palamar, M., Karaca, Ş. B., Göker, E., & Şanlı, U. A. (2026). Risk factors for dry eye disease in adult granulosa cell tumors: Implications for quality of life. Ege Tıp Dergisi, 65(2), 237-246. https://doi.org/10.19161/etd.1802914

AMA

1.Geçgel A, Gökdere Z, Özkan O, et al. Risk factors for dry eye disease in adult granulosa cell tumors: Implications for quality of life. EJM. 2026;65(2):237-246. doi:10.19161/etd.1802914

Chicago

Geçgel, Aslı, Zeynep Gökdere, Oğuzcan Özkan, et al. 2026. “Risk Factors for Dry Eye Disease in Adult Granulosa Cell Tumors: Implications for Quality of Life”. Ege Tıp Dergisi 65 (2): 237-46. https://doi.org/10.19161/etd.1802914.

EndNote

Geçgel A, Gökdere Z, Özkan O, Serin G, Palamar M, Karaca ŞB, Göker E, Şanlı UA (June 1, 2026) Risk factors for dry eye disease in adult granulosa cell tumors: Implications for quality of life. Ege Tıp Dergisi 65 2 237–246.

IEEE

[1]A. Geçgel et al., “Risk factors for dry eye disease in adult granulosa cell tumors: Implications for quality of life”, EJM, vol. 65, no. 2, pp. 237–246, June 2026, doi: 10.19161/etd.1802914.

ISNAD

Geçgel, Aslı - Gökdere, Zeynep - Özkan, Oğuzcan - Serin, Gürdeniz - Palamar, Melis - Karaca, Şaziye Burçak - Göker, Erdem - Şanlı, Ulus Ali. “Risk Factors for Dry Eye Disease in Adult Granulosa Cell Tumors: Implications for Quality of Life”. Ege Tıp Dergisi 65/2 (June 1, 2026): 237-246. https://doi.org/10.19161/etd.1802914.

JAMA

1.Geçgel A, Gökdere Z, Özkan O, Serin G, Palamar M, Karaca ŞB, Göker E, Şanlı UA. Risk factors for dry eye disease in adult granulosa cell tumors: Implications for quality of life. EJM. 2026;65:237–246.

MLA

Geçgel, Aslı, et al. “Risk Factors for Dry Eye Disease in Adult Granulosa Cell Tumors: Implications for Quality of Life”. Ege Tıp Dergisi, vol. 65, no. 2, June 2026, pp. 237-46, doi:10.19161/etd.1802914.

Vancouver

1.Aslı Geçgel, Zeynep Gökdere, Oğuzcan Özkan, Gürdeniz Serin, Melis Palamar, Şaziye Burçak Karaca, Erdem Göker, Ulus Ali Şanlı. Risk factors for dry eye disease in adult granulosa cell tumors: Implications for quality of life. EJM. 2026 Jun. 1;65(2):237-46. doi:10.19161/etd.1802914