|Year : 2022 | Volume
| Issue : 3 | Page : 250-255
A comparative study on ocular manifestations in patients with polycystic ovary syndrome and healthy volunteers
Rakendu Puthiyedath1, Anthrayose C V. Kakkanatt1, Monsy Thomas Mathai1, Lola Ramachandran2, Amitha Sunny1, Sreelakshmi Arun1
1 Department of Ophthalmology, Jubilee Mission Medical College Hospital and Research Institute, Thrissur, Kerala, India
2 Department of Obstetrics and Gynaecology, Jubilee Mission Medical College Hospital and Research Institute, Thrissur, Kerala, India
|Date of Submission||12-May-2021|
|Date of Decision||14-May-2021|
|Date of Acceptance||15-May-2021|
|Date of Web Publication||22-Dec-2022|
Dr. Rakendu Puthiyedath
Department of Ophthalmology, Jubilee Mission Medical College Hospital and Research Institute, Thrissur - 680 005, Kerala
Source of Support: None, Conflict of Interest: None
Background: Polycystic ovary syndrome is a common endocrinological disorder of females in the reproductive age group.It can produce changes in the ocular tissues and thereby affect vision.In this study,we aim to compare intraocular pressure, central corneal thickness, central macular thickness, retinal nerve fiber layer thickness, Schirmers test and tear break up time between the eyes of women with and without PCOS. Methods and Material: This study included 60 eye of 30 women with PCOS(Group 1) and 60 eyes of 30 healthy women (Group 2). Intraocular pressures (IOP) were assessed using Goldman applanation tonometry, central corneal thickness (CCT) using pachymeter, retinal nerve fiber layer (RNFL) and central macular thickness (CMT) using optical coherence tomography (OCT), Schirmers test using standardized strips and tear break up time (TBUT) were assessed for all women. Results: The Mean Central Corneal Thickness, average RNFL, superior average RNFL and nasal average RNFL thicknesses were higher in patients with PCOS than in healthy women (all p<0.01) respectively. Schirmers test results and Tear Break Up Time values were significantly lower in the PCOS group (both p<0.01). The mean IOP and CMT were similar between the 2 groups. Duration of the disease was weakly positively correlated with CCT and superior RNFL and moderately positively correlated with average RNFL. Conclusions: Women with PCOS had significant increase in central corneal and retinal nerve fiber layer (average, superior, nasal quadrant) thickness and a significant decrease in Schirmer test and TBUT values. It is advisable that all women with PCOS undergo an eye examination for dry eye. Hormonal regulations prior to corneal and refractive surgeries may help improve outcomes.
Keywords: Central corneal thickness, polycystic ovarian syndrome, retinal nerve fiber layer thickness, Schirmer's test, tear breakup time
|How to cite this article:|
Puthiyedath R, Kakkanatt AC, Mathai MT, Ramachandran L, Sunny A, Arun S. A comparative study on ocular manifestations in patients with polycystic ovary syndrome and healthy volunteers. Kerala J Ophthalmol 2022;34:250-5
|How to cite this URL:|
Puthiyedath R, Kakkanatt AC, Mathai MT, Ramachandran L, Sunny A, Arun S. A comparative study on ocular manifestations in patients with polycystic ovary syndrome and healthy volunteers. Kerala J Ophthalmol [serial online] 2022 [cited 2023 Feb 8];34:250-5. Available from: http://www.kjophthal.com/text.asp?2022/34/3/250/364711
| Introduction|| |
Polycystic ovarian syndrome (PCOS) is a common endocrinological disorder that affects an estimated 4%–10% women of reproductive age. PCOS is associated with menstrual irregularities, ovulatory dysfunction, and symptoms associated with hyperandrogenism.,
In recent years, various studies have reported the presence of sex hormone receptors in various ocular tissues. PCOS can lead to changes in the ocular tissue and thereby affect the visual functions of these patients. We designed a cross-sectional study to determine the magnitude of retinal and other ocular changes in women with PCOS presenting to the ophthalmology department of a tertiary care teaching hospital in central Kerala.
| Subjects and Methods|| |
The study protocol was approved by the institutional ethics and research committee, and written informed consent was obtained from all participants before the enrolment in the study. Sixty women were enrolled in the study over a period of 18 months between January 2020 and June 2021. This included thirty patients with PCOS who were recruited from the Department of Obstetrics and Gynaecology at the study institute after confirming the diagnosis of PCOS.
PCOS was defined based on the 2003 Rotterdam criteria that included the following:
- Clinical and/or biochemical findings of hyperandrogenism
- Polycystic ovaries assessed on ultrasonography (existence of 12 or more follicles 2–9 mm in diameter in ovaries).
At least two out of the three criteria must be fulfilled for the diagnosis of PCOS. Thirty age-matched healthy females who presented to the ophthalmology department without any gynecological symptomatology, without PCOS, and with normal menstrual cycles were recruited as the comparator group.
This study excluded females with other endocrine disorders, impairment of hepatic and/or renal function, chronic use of drugs that can interfere with the metabolism of carbohydrates, lipids and with renal function (diuretics, antihypertensives, antilipidemics, and corticosteroids), use of Oral contraceptive pills (OCPs), smoking, alcohol, illicit drug use, any eye disorders including high myopes, history of intraocular surgeries.
A detailed medical history that included their age, personal, and family history was collected from each participant. The best-corrected visual acuity was estimated using Snellen chart. A detailed slit-lamp assessment of the anterior segment was done, and intraocular pressures (IOPs) were measured using a Goldmann applanation tonometer. Posterior segment assessments were done using indirect ophthalmoscopy with a 20D lens. The central corneal thickness (CCT) was measured using a pachymeter (full auto tonometer TX-20P Canon). The central macular thickness (CMT) and retinal nerve fiber layer (RNFL) assessments (all sectors) were done using optical coherence tomography (OCT) Cirrhus high definition OCT (Cirrhus HD OCT).
All patients underwent Schirmer's and tear breakup time (TBUT) test. An abnormal Schirmer's test was defined as soaking of Schirmer's strip <6 mm in 5 min. The tear film was examined at the slit lamp under cobalt blue filter in the TBUT test. An abnormal TBUT test was defined as an interval of <10 s between an eye blink and first appearance of a dry spot on the ocular surface.
The mean of continuous variables was compared using an independent sample t-test, and categorical variables were compared using a Chi-square test. A P < 0.05 was considered as statistical significance.
| Results|| |
The study included a total of 120 eyes from 30 patients in the PCOS group and 30 individuals in the control group. The mean age ± standard deviation of women with PCOS (25.73 ± 3.27 years) did not differ significantly (P = 0.582) from women without PCOS (26.20 ± 3.27 years) in the study population.
The mean IOP values in the PCOS group and control group were 15.51 ± 2.04 mmHg and 15.57 ± 2.89 mmHg, respectively (P = 0.896). The average CCT in PCOS group (555.13 ± 13.16 μm) was significantly higher (P < 0.01) than the control group (523.05 ± 13.93 μm). The mean value of the superior, nasal, and average RNFL thickness was significantly higher in the women with PCOS [Table 1]. No statistically significant difference (P = 0.815) was found between both the groups in terms of CMT.
The PCOS group had significantly lower mean Schirmer's test value and shorter TBUT compared to the control group [Table 1].
Duration of the disease showed a statistically significant weak positive correlation with CCT (r = 0.289) and superior RNFL (r = 0.319) and a moderate positive correlation with average RNFL (r = 0.379) [Figure 4], [Figure 5], [Figure 6].
|Figure 4: Correlation between duration of disease and central corneal thickness|
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|Figure 5: Correlation between duration of disease and superior retinal nerve fiber layer|
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|Figure 6: Correlation between duration of disease and average retinal nerve fiber layer|
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| Discussion|| |
PCOS is a common endocrinological disorder among women of reproductive age group. It is also known as hyperandrogenic ovulation or Stein-Leventhal syndrome. Several studies have shown the presence of Sex steroid hormones (SSH) (estrogen, progesterone, and androgen) receptors in various ocular tissues such as retina, lens, ciliary body, iris stroma, choroid, lacrimal gland, Meibomian gland More Details, palpebral, and bulbar conjunctiva. The elevated sex steroid levels in PCOS can affect the physiopathogenesis of the ocular tissue similar to the cardiovascular system and the endometrium.
We found that the CCT was significantly higher in the PCOS group than the control group. No significant difference was found between both the groups in terms of mean values of IOP and CMT. Furthermore, the average RNFL, average superior, and nasal RNFL thickness were significantly higher in women with PCOS than in healthy women. [Figure 1] shows optical coherence tomography of optic nerve head with normal retinal nerve fibre layer thickness in all quadrants. [Figure 2] and [Figure 3] shows increased retinal nerve fibre layer thickness in the superior and nasal quadrants in PCOS patients. The PCOS group also had a significantly lower mean Schirmer's test value and shorter TBUT than the control group.
|Figure 1: Optical coherence tomography optic disc showing normal retinal nerve fiber layer thickness|
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|Figure 2: Optical coherence tomography optic disc showing increased superior retinal nerve fiber layer thickness in polycystic ovarian syndrome patients|
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|Figure 3: Optical coherence tomography optic disc showing increased nasal retinal nerve fiber layer thickness in polycystic ovarian syndrome patients|
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Gonadal hormones play a major role in the homeostasis of the cornea through effects that are mediated by alpha and beta estrogen, progesterone, and androgen receptors in the nuclei of human corneal epithelial, stromal, and endothelial cells.,, Corneal thickness fluctuates with variations in the sex hormone levels, especially during ovulation and luteal phase of menstrual cycle where there is a significant increase in the estrogen levels., A study by Kiely et al. reported that a rise in the estrogen levels during the menstrual cycle was associated with an increase in the corneal thickness. Similar to our study, a significant increase in the CCT in PCOS patients was reported by Kebapcilar et al. The main reasons for these changes include: (1) insulin-like growth factor 1 induced inhibition of the corneal endothelial pump and increased endothelial permeability and (2) enhanced sodium reabsorption into the corneal tissues due to elevated androgen levels leading to water retention and corneal edema. However, a study by Demir et al. showed no significant difference in CCT between PCOS patients and normal women.
Different parts of the retina respond differently to the effects of androgenic hormones. [Table 2] shows the comparison of RNFL thickness with other studies. In the current study, the RNFL thickness was found to be significantly higher in the superior and nasal quadrants in the PCOS patients when compared to normal healthy women. In a similar study conducted by Demir et al., the RNFL thickness in the nasal and superotemporal quadrants of PCOS patients was found to be significantly higher in PCOS patients than the control group. A study performed by Açmaz et al. also showed similar results with a significantly higher nasal RNFL thickness in PCOS patients when compared to control group. This can be explained by the neurotrophic action of androgens, which are increased in the PCOS patients. Furthermore, hyperandrogenism in PCOS patients leads to elevated levels of nerve growth factor which is needed for ovarian follicular growth.
|Table 2: Comparison of retinal nerve fiber layer thickness with other studies|
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Sex hormonal variations can influence the tear function since these hormonal receptors are found in many components of the tear film: lacrimal gland, conjunctiva, goblet cells and their mucin products, the meibomian glands, and the cornea. Estrogen is an antagonist of meibomian gland function, and increased levels of estrogen in PCOS patients can lead to meibomian gland dysfunction and evaporative dry eye and visual impairment. Previous studies have reported lower Schirmer's test values, shorter TBUT, and increased incidence of dry eye in PCOS patients., Consistent with the previous studies, the current study also demonstrated a statistically significant lower Schirmer's test value and shorter TBUT in PCOS patients when compared to healthy women. [Table 3] shows the comparison of central corneal thickness, Schirmers test and Tear Break Up Time test values with other studies.
|Table 3: Comparison of central corneal thickness, Schirmer's test, tear breakup time values with other studies|
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The lack of pathological examinations is a limitation of the study. The study was done at a single center and may limit generalizability of these results. Further studies on population of women with PCOS from diverse settings can help to further validate these associations.
| Conclusion|| |
Women with PCOS had significant increase in central corneal and RNFL (average, superior, and nasal quadrant) thickness and a significant decrease in Schirmer's test and TBUT values. Our findings suggest that patients diagnosed with PCOS should undergo ophthalmic examination for the diagnosis and treatment of dry eye. Ophthalmologists must consider adequate precautionary measures, including hormonal regulations before corneal surgeries (LASIK, penetrating keratoplasty) in women with PCOS. More extensive research is recommended to obtain further details regarding the ocular manifestations of PCOS.
The authors would like to acknowledge the support from Jubilee Mission Medical College, Thrissur.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004;89:2745-9.
Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet 2007;370:685-97.
Acién P, Quereda F, Matallín P, Villarroya E, López-Fernández JA, Acién M, et al.
Insulin, androgens, and obesity in women with and without polycystic ovary syndrome: A heterogeneous group of disorders. Fertil Steril 1999;72:32-40.
Ogueta SB, Schwartz SD, Yamashita CK, Farber DB. Estrogen receptor in the human eye: Influence of gender and age on gene expression. Invest Ophthalmol Vis Sci 1999;40:1906-11.
Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7.
Gupta PD, Johar K Sr, Nagpal K, Vasavada AR. Sex hormone receptors in the human eye. Surv Ophthalmol 2005;50:274-84.
Wild RA, Carmina E, Diamanti-Kandarakis E, Dokras A, Escobar-Morreale HF, Futterweit W, et al.
Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: A consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010;95:2038-49.
Suzuki T, Kinoshita Y, Tachibana M, Matsushima Y, Kobayashi Y, Adachi W, et al.
Expression of sex steroid hormone receptors in human cornea. Curr Eye Res 2001;22:28-33.
Vécsei PV, Kircher K, Kaminski S, Nagel G, Breitenecker G, Kohlberger PD. Immunohistochemical detection of estrogen and progesterone receptor in human cornea. Maturitas 2000;36:169-72.
Wickham LA, Gao J, Toda I, Rocha EM, Ono M, Sullivan DA. Identification of androgen, estrogen and progesterone receptor mRNAs in the eye. Acta Ophthalmol Scand 2000;78:146-53.
Soni PS. Effects of oral contraceptive steroids on the thickness of human cornea. Am J Optom Physiol Opt 1980;57:825-34.
Leach NE, Wallis NE, Lothringer LL, Olson JA. Corneal hydration changes during the normal menstrual cycle–A preliminary study. J Reprod Med 1971;6:201-4.
Kiely PM, Carney LG, Smith G. Menstrual cycle variations of corneal topography and thickness. Am J Optom Physiol Opt 1983;60:822-9.
Kebapcilar AG, Tatar MG, Ipekci SH, Gonulalan G, Korkmaz H, Baldane S, et al.
Cornea in PCOS patients as a possible target of IGF-1 action and insulin resistance. Arch Gynecol Obstet 2014;290:1255-63.
Bowman WC, Rand MJ. Textbook of Pharmacology. Oxford u.Edinburg: Blackwell Scientific Publications; 1980.
Demir M, Guven D, Koc A, Ozdemir S, Can E. Retinal nerve fiber layer thickness in women with polycystic ovary syndrome. J Ophthalmol 2013;2013: 62-4.
Açmaz G, Ataş M, Gülhan A, Açmaz B, Ataş F, Aksoy H. Evaluation of the macula, retinal nerve fiber layer, and choroid thickness in women with polycystic ovary syndrome using spectral-domain optical coherence tomography. Reprod Sci 2014;21:1044-9.
Teberik K, Sağlam H, Başbuğ A, Karaaslan M, Kaya M, Sungur MA. Assessment of central corneal thickness, intraocular pressure and retinal nerve fiber layer thickness at women with polycystic ovary syndrome. Konuralp Tıp Dergisi 2017;9:142-5.
de Souza-Júnior JE, Garcia CA, Soares EM, Maranhão TM, Lemos TM, Azevedo GD. Polycystic ovary syndrome: Aggressive or protective factor for the retina? Evaluation of macular thickness and retinal nerve fiber layers using high-definition optical coherence tomography. J Ophthalmol 2015;2015:34-6.
Coksuer H, Ozcura F, Oghan F, Haliloglu B, Karatas S. Effects of hyperandrogenism on tear function and tear drainage in patients with polycystic ovary syndrome. J Reprod Med 2011;56:65-70.
Karaca Adıyeke S, Karaca I, Yıldırım S, Adıyeke M, Uyar İ, Türe G. Anterior Segment Findings in Women with Polycystic Ovary Syndrome. Turk J Ophthalmol 2017;47:24-7.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3]