Estrogen and progesterone receptors have been observed in different ocular tissues, such as the cornea, the conjunctiva, the Meibomian glands, the lens, the choroid, and the retina. The expression of estrogen and progesterone receptors in the eye is responsible for their ocular effects and various studies published in the literature about these receptors and their role in changing eye structures[2]. Oral Contraceptive Pills are widely used for contraception, but they are also indicated in menorrhagia, endometriosis, acne and hirsutism, fibroid uterus and premenstrual syndrome[8].
Reviewing the impact of combined oral contraceptives on ocular tissues showed that the OCP has multiple adverse effects on ocular tissues[1], which include dry eye symptoms related to decreased lipid production[9], asymptomatic corneal edema, contact lenses discomfort and intolerance[10]. Significant increase in the central corneal thickness values was also reported in patients using OCP[11] There are also retinal neuro-ophthalmologic complications involving the 6th cranial nerve paralysis, parietal syndrome, hemianopsia, papillary edema, and retrobulbar neuritis[12]. The vascular complications of OCP include central retinal artery or vein occlusion, intraocular hemorrhages, aneurysms, macular or disc edema, and acute ischemic optic neuropathy[13]. Also, they have been associated with high rates of cardiovascular events, venous thromboembolic disease, ischemic strokes, and breast cancer[14,15].
There are also some studies concerning the effect of sex hormone fluctuations during the menstrual cycle on the eye. Some researchers have shown that these hormone fluctuations exhibited correlations with changes in ocular tissue. Tear production, stability, dryness, and inflammation were significantly related to hormonal fluctuations in the menstrual cycle. Impairment of these functions appeared to be related to the estrogen peak during the follicular phase, especially in patients with a dry eye[16]. During the menstrual cycle, the corneal thickness is thinner at the beginning of the cycle and thicker at the end[17]. Evaluation of the effects of the menstrual cycle on the choroidal thickness of healthy women of reproductive age showed a significant decrease in thickness in the mid-luteal phase of the menstrual cycle[18]. Also, the choroidal thickness measured by SD-OCT was reported to be significantly thinner in postmenopausal women than healthy reproductive-age women, which speculated to be secondary to menopausal estrogen deficiency[19].
In this study, we were evaluating the thickness of the macula, the RNFL, GCL, and CT in women who received OCP (0.03 mg ethinylestradiol and 0.15 mg levonorgestrel) regularly for at least one year. We observed that the thickness of all the macular parameters, the cube macular volume, the RNFL, the GCL, and the CT decreased significantly in the OCP group compared to the control group. These thinning effect of the OCP are similar to age-related hormonal changes in which thinning of the macula is due to macular atrophy or RNFL atrophy[20]. In this study, these findings were not considered related to age since the average age of the women was 30.48 ± 3.4 years.
Apart from the study done by Madendag et al[7] in 2017, concerning the effect of OCP on the thickness of the macula, the RNFL and the choroid using OCT, there are no other available data. Madendag et al used OCP containing 0.03 mg ethinylestradiol and 3 mg drospirenone. They found that all OCT measurements of macular parameters were considerably decreased in the OCP group compared to the control group except the foveal center thickness which remained unchanged. They speculated that the absence of blood vessels in the fovea could be the cause of unaffected fovea. They also found that only the average of the RNFL, the nasal-inferior, and the temporal-inferior parts of the RNFL was considerably slimmer in the OCP group but the other parts of the RNFL remained unchanged. They also reported unchanged CT. They speculated that using a combined oral contraceptive could be the cause of unaffected CT since the estrogen is opposed by the progesterone.
In accordance with our study is that all macular variable values were considerably lower in the OCP group compared to the control. The same was applied to the cube macular volume which decreased in both studies. Controversial with our results is reporting thinning of only parts of the peripapillary RNFL and not all the parts. They also reported unaffected choroid. We reported significant thinning of all parts of RNFL, all parts, of GCL and the choroid.
We also compared our data of the control group regarding the MT, CT, and NFL thickness (Table 2,3) with the normative data of other studies using SD-OCT. Liu et al[21] , using Cirrus HD-OCT reported CST of 262.4±22.8 μm, macular thickness (MT) of 281.3±14.5 μm, and macular volume (MV) of 10.1±0.6 mm3, respectively. Manjunath et al[22] , reported mean subfoveal (CT) of 272±81μm, showing a thin choroid nasally, thickest choroid sub-foveally, and thinner choroid temporally. Using Spectralis SD-OCT, Bindu et al[23] , provided the normative data of MT and RNFL thickness in Indians. They reported normal central foveal thickness of 260.1±18.19 um. The nasal inner quadrant showed maximum retinal thickness (338.88 ± 18.17 um). The mean RNFL thickness was 101.43±8.63 um with maximum thickness in the inferior quadrant. El-Hifnawy et al[24,25] collected normative MT and RNFL thickness data in the Egyptian population, the mean CST was 262.70±19.64 μm and the mean NFLT was 101.74±10.05 μm. The mean MT values were significantly greater in men than in women and were found to be less than those seen in the studies published previously on Caucasians using Spectralis SD-OCT
Although the values in our study are in the normative range of other studies, SD-OCT measurements cannot be compared between different machines because each technology’s normative database is derived from a different population of different racial or ethnic groups. Sex and age also have an influential effect.