To Evaluate Choroidal and Retinal Thicknesses in Singleton versus Twin Pregnancies using Optical Coherence Tomography.

PURPOSE: The purpose of the study was to evaluate the choroidal and retinal thicknesses in singleton versus twin pregnancies.
MATERIALS AND METHODS: This study included 20 single and 20 twin pregnant women in their 3rd trimester with 20 age-matched healthy nonpregnant women as a control group. All participants underwent a detailed ocular examination. Cirrus enhanced depth imaging-optical coherence tomography was used for choroidal thickness (CT) with frame enhancement software. The study was divided into three groups: Group 1 - singleton pregnancy, Group 2 - twin pregnancy, and Group 3 - healthy nonpregnant controls. CT was measured from nasal, subfoveal, and temporal fields.
RESULTS: Regarding CT, the twin pregnancy group had the thickest choroid followed by the singleton pregnancy group and control group. There was a statistically significant difference between Group 2 and Group 3 in terms of nasal, subfoveal, and temporal CTs (P = 0.002, P = 0.001, and P = 0.003, respectively). There was a statistically significant difference between Group 1 and Group 3 regarding just subfoveal CT (P = 0.028). Regarding retinal thickness, there was a statistically significant difference between Group 1 and Group 3 regarding the mean macular volume and ganglion cell-inner plexiform layer thicknesses (P < 0.05). Furthermore, regarding mean retinal nerve fiber layer thickness, there was a statistically significant difference between Group 1 and Group 2 and between Group 2 and Group 3 (P = 0.004, P = 0.003, respectively).
CONCLUSION: Our study is the first one which evaluates choroidal and retinal thicknesses in twin pregnancies. We found that there was an increase in CT in the 3rd trimester of pregnancies and it was prominent in twin pregnancies. Copyright:

Introduction

It has been known that a pregnant woman undergoes significant anatomical and physiological changes during pregnancy. These changes occur after conception and every organ system in the body can be affected.[1] These changes are immunologic, metabolic, hormonal, renal, pulmonary, vascular, hematologic, and visual.[2] Ocular changes can be physiologic or pathologic and these changes can be more often transient but rarely permanent.[3] There has been an increase in twin pregnancies due to a greater proportion of older mothers and advances in reproductive medicine. It has shown that during twin pregnancies, there were much more physiological and pathological changes in the body compared to the singleton pregnancies.[4] There have been studies evaluating retinal and choroidal thickness (CT) in singleton pregnancies, but there is no study on retinal and CT in twin pregnancies.

From this point of view, we aimed to do the present study to evaluate CT and retinal thickness in twin pregnancies and to compare it with singleton pregnancies as well as with age-matched healthy nonpregnant women. We used enhanced depth imaging-optical coherence tomography (EDI-OCT) which is a noninvasive, objective, and reliable diagnostic tool for CT and retinal thickness measurements.

Materials and Methods

This comparative and prospective cross-sectional study was carried out at the Departments of Ophthalmology and Obstetrics and Gynecology at Gaziosmanpasa University Faculty of Medicine. The study followed the principles of the Declaration of Helsinki and was approved by the local institutional ethics committee. All participants were informed about the study and written consent form was signed by each participant regarding the present study.

This study included 60 participants who were divided into three groups. Group 1 contained 20 singleton pregnant women and Group 2 contained 20 twin pregnant women who were all in the 3rd trimester. Group 3 contained 20 age-matched healthy nonpregnant women.

All participants underwent a detailed ocular examination. Visual acuity, intraocular pressure, and anterior and posterior segment examinations were performed. Participants with best-corrected visual acuity logMAR 0.00, intraocular pressure <20 mmHg, and axial length 20–24 mm were included in this study. Contributors with retinal diseases, cataracts, uveitis, corneal diseases, history of ocular trauma, neurologic disorders such as optic neuritis, and cycloplegic refractive errors such as spherical and cylindrical > ± 1.00 diopter were excluded.

The OCT measurements were taken by one experienced examiner. Only one eye of each participant was assessed. A signal power >7 (Signal-to-noise ratio >7) was selected for the study. Measurements were assessed using spectral-domain OCT (Cirrus HD-OCT, Carl Zeiss Meditec, Model 5000, software version 6.5.0.772, Inc., Dublin, California, USA). For CT measurements, HD-5 line raster spaced 0.25 mm as a scan pattern was used. It was a 6 mm line consisting of 1024 A-scan/B-scans and averaging 4 B-scan/image which is detailed in a study by Manjunath et al.[5] CT measurements were determined manually from the outer border of the hyperreflective line coincident to the retinal pigment epithelium to the inner surface of the sclera. The CT measurements were obtained from the central subfoveal area [Figure 1] and at 1000 μm intervals nasally and temporally from the center of the fovea [Figure 2]. The CT measurements were done by one of the authors Sait Alim (SA) in a masked fashion without knowledge of subject information.

Figure 1

Subfoveal choroidal thickness

Figure 2

Temporal and nasal choroidal thicknesses

The retinal parameters measured were as follows: mean macular thickness (MMT), mean macular volume (MMV), peripapillary retinal nerve fiber layer (RNFL) thicknesses, and Ganglion cell-inner plexiform layer (GCIPL) thicknesses. To analyze macular and optic disc thicknesses, the scan protocol of macula (macular cube 512 × 128 × 1024 protocols) and optic disc (optic disc cube 200 × 200 protocols) was used. To analyze mean GCIPL thickness, the scan protocol of the macular cube (512 × 128 × 1024) was used.

The axial length of the patients and controls was measured with a biometer (Echoscan, US 4000, Nidek, Gamagori, Japan).

Statistical analysis

Data are expressed as mean and standard deviation. One-way analysis of variance was used to compare the continuous normal data among the groups. Tukey's HSD test was used for multiple comparisons after meaningful one-way analysis of variance. P < 0.05 was considered significant. Analyses were performed using SPSS 19 (IBM SPSS Statistics 19, SPSS Inc., an IBM Co., Somers, NY, USA).

Results

The study included 60 participants. The mean ages of the study groups are demonstrated in Table 1. There was no statistically significant difference regarding the age between the groups. The CT measurement results were as follows: the subfoveal CT was thicker in the twin pregnancy group followed by the singleton pregnancy group and control group. There was a statistically significant difference between Group 2 and Group 3 in terms of nasal, subfoveal, and temporal CTs (P = 0.002, P = 0.001, and P = 0.003, respectively). There was a statistically significant difference between Group 1 and Group 3 regarding just subfoveal CT (P = 0.028). The comparisons of nasal, subfoveal, and temporal CT measurements of the three groups are demonstrated in Table 1.

Table 1

Comparison of the age, nasal, subfoveal and temporal choroidal thickness measurements between the three groups

	Group 1	Group 2	Group 3	Pa	Pairwise comparisons (Pb)
					Group 1 and Group 2	Group 1 and Group 3	Group 2 and Group 3
Age	28,60±4,42	282,25±31,58	31,2±5,47	0,245	0,883	0,063	0,473
Nasal CT (µm)	267,10±29,85	290,5±35,98	246,25±37,87	0,003	0,118	0,263	0,002
Subfoveal CT(µm)	313,35±26,07	336,15±30,	286,6±38,52	<0,001	0,071	0,028	<0,001
Temporal CT(µm)	282,25±31,58	308,35±32,53	269,05±42,41	0,004	0,063	0,479	0,003

CT: Choroidal Thickness

The retinal thickness measurement results were as follows: there was no statistically significant difference between the three groups regarding central macular thickness and MMT which are demonstrated in Table 2. However, regarding MMV, there was a statistically significant difference between the singleton pregnancy group and healthy nonpregnant group (P = 0.041). MMV was lower in the singleton pregnancy group followed by the twin pregnancy group and followed by the healthy nonpregnant group. GCIPL was thinner in the singleton and twin pregnancy groups than in the healthy nonpregnant group. There was a statistically significant difference between the singleton and control groups and between twin pregnancy and control groups regarding GCIPL thickness (P = 0.002, P = 0.017, respectively). The mean RNFL thickness was higher in the twin pregnancy group than in the singleton and healthy nonpregnant groups. There was a statistically significant difference regarding mean RNFL thickness between Group 1 and Group 2 and between Group 2 and Group 3 (P = 0.004, P = 0.003, respectively). There was no statistically significant difference between the groups in terms of superior, nasal, inferior, and temporal RNFL thicknesses (P > 0.05). The RNFL thicknesses are showed in Table 3.

Table 2

Comparison of the central macular thickness, mean macular thickness, mean macular volume and ganglion cell- inner plexiform layer measurements between the three groups

	Group 1	Group 2	Group 3	Pa	Pairwise comparisons (Pb)
					Group 1 and Group 2	Group 1 and Group 3	Group 2 and Group 3
CMT (µm)	237,5±19,82	236,8±19,9	237,15±19	0,994	0,993	0,998	0,998
MMT (µm)	274,25±15,03	280,8±15,72	284,1±10,04	0,081	0,300	0,071	0,732
MMV (µm)	9,88±0,48	10,2±0,47	10,22±0,36	0,026	0,058	0,041	0,989
GCIPL (µm)	80,65±4,69	81,75±4,08	85,6±4,04	0,001	0,697	0,002	0,017

CMT: Central macular thickness, MMT: Mean macular thickness, MMV: Mean macular volume, GCIPL: Ganglion cell- inner plexiform layer

Table 3

Comparison of the total, superior, nasal, inferior and temporal RNFL thickness measurements between the three groups

	Group 1	Group 2	Group 3	Pa	Pairwise comparisons (Pb)
					Group 1 and Group 2	Group 1 and Group 3	Group 2 and Group 3
Total RNFL (µm)	92,65±9,59	102,5±10,62	92,55±7,19	0,001	0,004	0,999	0,003
Sup. RNFL (µm)	114,35±21,1	128,3±19,78	116,85±14,98	0,051	0,058	0,907	0,141
Nasal RNFL (µm)	70,6±7,05	77,8±10,54	71,9±13,37	0,083	0,091	0,921	0,194
Inf. RNFL (µm)	120,85±22,07	136,2±17,72	127,35±18,25	0,051	0,051	0,544	0,328
Temp. RNFL (µm)	64,05±9,98	66,35±7,96	70,35±8,21	0,080	0,686	0,068	0,326

RNFL: Retinal nerve fiber layer, Sup: superior, İnf: inferior, Temp: Temporal

Discussion

To the best of our knowledge, the present study is the first one to assess CT and retinal thickness in twin pregnancies. Our findings demonstrated that the CT increases parallel to the cardiac output during twin pregnancies in the 3rd trimester. It has been shown previously that during pregnancies, there was fluid retention in the body and there was much more fluid retention in the twin pregnancies.[6] According to our study during twin pregnancies, the CT increases much more than singleton pregnancies in the 3rd trimester. It is known that CT is an extremely good predictor for some chorioretinal disorders. In some chorioretinal diseases, the CT increases, e.g., central serous chorioretinopathy and polypoidal choroidal vasculopathy, whereas in some chorioretinal diseases, the CT decreases, e.g., degenerative myopia and diabetic retinopathy.[78910] We think that it is important to be aware of physiological changes in the chorioretinal system during pregnancies to distinguish it from pathological changes. From this point of view to our opinion, our present study will fill the gap regarding CT and retinal thickness alterations in twin pregnancies.

There was no study regarding retinal and CT measurements in twin pregnancies in the literature, but there were some studies regarding CT, macular thickness, macular volume, and RNFL thickness measurements in singleton pregnancies. In a study, Ataş et al.[11] found that CT and mean RNFL thickness were higher in healthy singleton pregnant women than in healthy nonpregnant women in their 3rd trimester. They also found that macular central subfield and foveal central thickness was thinner in pregnant women than in healthy nonpregnant women. A study by Sayin et al.[12] revealed that subfoveal CT was thicker in singleton pregnancy group than in the healthy nonpregnant and preeclampsia groups. A study carried out by Cankaya et al.[13] found that total macular volume and macular thickness were increased by the second and third trimester in singleton pregnancies. In another study, Demir et al.[14] analyzed foveal and parafoveal macular thickness in singleton pregnant women in their 3rd trimester. They found that the upper, temporal, and inferior paramacular areas were thicker in singleton pregnancy women than in healthy nonpregnant women. The authors in the previous studies emphasized that an increase in the CT, MMT, and MMV might be due to the fluid retention in the chorioretinal layer, especially in the 3rd trimester. Contrary to these studies regarding MMT and MMV, we found that MMV was thinner in the singleton and twin pregnancy groups than in the healthy nonpregnant group. Statistically, a significant difference was found between the singleton and healthy nonpregnant groups. We also found that MMT was thinner in the singleton and twin pregnancy groups than in the healthy nonpregnant group. However, the results revealed no statistically significant difference between the groups. According to our study, there was no fluid retention in the retinal layers. Our study demonstrated that mean RNFL thickness was higher in the twin pregnancy group than in the singleton and healthy nonpregnant groups. We found that the GCILP layer was thinner in the singleton and twin pregnancy women than in healthy nonpregnant women. We think that hormonal and immunological changes can be responsible for all these results.

Our present study has some limitations:first of all, the sample size was small. Second, the CT measurements were done manually because there was no automated software for EDI-OCT. Another limitation was that we could not measure the nonpregnant control participants in their follicular phase of the menstrual cycle. Larger prospective studies during and after conception and in the follicular phase of the control group (nonpregnant women) are needed to evaluate absolute retinal and CT alterations in pregnant women.

Conclusion

It is believed that hormonal changes are responsible for fluid retention and increased cardiac output during pregnancies. It is thought that fluid retention in the choroidal layer causes increased CT. Our study revealed that there was a prominent increase in the choroidal layer in twin pregnancies in the 3rd trimester which may be related to fluid retention in this layer. This study was presented as an oral presentation at 2, Live surgery symposium of the Turkish Ophthalmology Society 28 June-01july 2018, Pullman hotel Istanbul.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.