Predictors of the development of retinal vascular diseases in women after preeclampsia
* Impact factor according to the SCIENCE INDEX 2017
O.V. Kolenko1,2, E.L. Sorokin1,3, N.S. Khodzhaev4, N.V. Pomytkina1, G.V. Chizhova2, A.A. Fil1, Ya.E. Pashentsev1
1Khabarovsk branch of S.N. Fedorov NMRC “MNTK “Eye Microsurgery”, Khabarovsk, Russian Federation
2Postgraduate Institute for Public Health Professionals, Khabarovsk, Russian Federation
3Far Eastern State Medical University, Khabarovsk, Russian Federation
4S.N. Fedorov NMRC “MNTK “Eye Microsurgery”, Moscow, Russian Federation
Background: in recent years, retinal vascular diseases occur more frequently, in particular, in younger individuals.
Aim: to assess choroidal blood flow in pregnant women with preeclampsia and after birth.
Materials and Methods: 42 pregnant women with preeclampsia aged 21–40 years were included in the study group. 30 women with normal pregnancy aged 19–38 years were included in comparison group 1. 27 women without pregnancy aged 35–57 years with vascular diseases of posterior eye segment were included in comparison group 2. Controls were 25 healthy age-matched (19–43 years) women without pregnancy. Linear blood flow velocity in short posterior ciliary arteries and prothrombin index were measured in all women.
Results: reduced linear blood flow velocity in short posterior ciliary arteries in the third trimester of pregnancy was revealed in pregnant women with preeclampsia. However, in 6 to 8 months after birth these parameters have returned to normal values. In 12 women, these parameters were still low while prothrombin index was high. Retinal vein occlusions occurred in all these women after 6.5 to 8.5 years.
Conclusion: our findings demonstrate that measurin g linear blood flow velocity in short posterior ciliary arteries and prothrombin index in pregnancy complicated with preeclampsia as well as within a year after birth may help to identify risk groups for vascular retinal diseases.
Keywords: choroidal blood flow, short posterior ciliary arteries, pregnancy, preeclampsia, prothrombin index, vascular retinal diseases, retinal vein occlusion.
For citation: Kolenko O.V., Sorokin E.L., Khodzhaev N.S. et al. Predictors of the development of retinal vascular diseases in women after preeclampsia. Russian Journal of Clinical Ophthalmology. 2019;19(4):189–194.
Retinal vein occlusions account for a large proportion of all retinal vascular disorders. Therefore, many authors try to predict the risk of their development and study their late negative consequences from the viewpoint of vitreoretinal and laser surgeon [1, 2].
Pregnancy complicated by preeclampsia is associated with higher risks of systemic vascular disorders. Numerous published data demonstrate that endothelial dysfunction is the major pathogenic mechanism of these vascular abnormalities [3–12].
Previously, we have demonstrated that preeclampsia increases the risk of retinal vein occlusions which occur within various terms after childbirth. We have established their association with endothelial dysfunction which develops in preeclampsia [5, 6].
Published data demonstrate that up to 95% of the arterial blood enters the eye through the short posterior ciliary arteries thus generating choroidal blood flow . Considering this, we have evaluated hemodynamic parameters in short posterior ciliary arteries in preeclampsia since it could help to reveal any hallmarks to make easier the understanding of pathogenic mechanisms of the development of hemodynamic abnormalities in the posterior eye segment in the late postnatal period.
Color Doppler imaging is one of the objective methods to study regional ocular hemodynamics. This technique measures a number of objective parameters of linear blood flow velocity [14, 15]. Published data do not address regional hemodynamics of short posterior ciliary arteries in preeclampsia. Meanwhile, this aspect is of both scientific and practical importance in terms of predicting the risk of retinal vascular disorders in later life.
To assess choroidal blood flow during the pregnancy complicated by preeclampsia and after the delivery.
Patients and methods
The study was performed in compliance with the Declaration of Helsinki (1964) and the 2000 Edinburgh revision as well as the Federal Law of the Russian Federation “On the fundamentals of health protection of citizen in the Russian Federation” and the Law of the Russian Federation “On Personal Data”. All women have provided informed consent before the study.
Inclusion criteria for the study group were pregnancy complicated by preeclampsia and neither systemic nor ocular comorbidities.
42 pregnant women with preeclampsia aged 21-40 years were included in the study group. In all women, preeclampsia was verified by obstetricians and gynecologists based on the set of clinical and laboratory tests. Moderate preeclampsia was diagnosed in 32 women and severe preeclampsia was diagnosed in 10 women. 28 women were pregnant for the first time and 14 women had repeat pregnancy.
All women underwent inpatient treatment for preeclampsia. Antihypertensive agents were prescribed in addition to the prevention of seizures, thrombosis, and hemorrhages .
Comparison group 1 included 30 women aged 19-38 years with normal pregnancy matched for pregnancy rate.
Comparison group 2 included 27 non-pregnant women aged 35-57 years (27 eyes) with retinal vein occlusions and their consequences. 19 women were diagnosed with branch retinal vein occlusions and 8 women were diagnosed with post-thrombotic proliferative retinopathy.
Control group included 25 healthy age-matched 19-43 years non-pregnant women.
Linear blood flow velocity in short posterior ciliary arteries using LOGIQTM ultrasound system (GE Healthcare, USA) with 4-12 mHz multi-frequency linear transducer was measured in all women. The spectrum of Doppler frequency shift was recorded. Major quantitative parameters of the blood flow in short posterior ciliary arteries, i.e., peak systolic velocity (Vmax), end-diastolic velocity (Vmin), mean blood flow velocity (Vmed), resistance index (RI), and pulsatility index (PI) were measured. Published data suggest that Vmax, Vmin, and Vmed characterize vascular patency, i.e., the presence or the absence of occlusions [13, 17]. RI and PI indirectly characterize vascular wall elasticity; therefore, their elevation indicates vasoconstriction or stenosis while their reduction indicates vasodilatation [14, 18].
In addition, prothrombin index (PTI) regarded as an objective parameter of blood coagulation was measured in all women. PTI is calculated as the percentage ratio of the clotting time of control plasma sample to the clotting time of tested plasma sample (normal range: 70-120%). Reduced PTI indicates hypocoagulation and increased PTI indicates hypercoagulation [19, 20].
In the study group and comparison group 1, the measurements were performed twice, i.e., in the third trimester of pregnancy (35-36 weeks) and 6 to 8 months after childbirth. In the control group and comparison group 2, the measurements were performed once.
Dynamic changes in the parameters were analyzed. Parameters were also compared between the groups.
Statistical analysis was performed using IBM SPSS Statistics 20 software. Data are represented as M ± σ, M is mean value and σ is standard deviation. A posteriori pairwise Kruskal–Wallis test using Mann–Whitney test for independent samples was applied. Wilcoxon test was applied to compare related samples. Critical significance level was 0.05.
Table 1 illustrates our findings. By the third trimester of pregnancy, Vmax, Vmin, and Vmed were lower both in the study group and comparison group 2 (p < 0.05) and similar in comparison group 1 (р > 0.05) as compared with the control group. Therefore, hemodynamic parameters of posterior eye segment are almost similar by the third trimester of normal pregnancy as compared with non-pregnant women.
PI and RI were significantly higher as compared with the control group and comparison group 1 (p < 0.05). However, the highest PI and RI were revealed in comparison group 2 as compared with the control group and comparison group 1 (p < 0.05). PI and RI were similar in comparison group 2 as compared with the study group (p > 0.05).
PTI was the highest in comparison group 2 and demonstrated significant differences as compared with the control group and comparison group 1 in the third trimester of pregnancy (p < 0.05). No significant differences were revealed as compared with the control group either in the third trimester of pregnancy or in 6 to 8 months after childbirth (p > 0.05).
In the study group, average Vmax and Vmed have increased 6 to 8 months after childbirth as compared with the third trimester of pregnancy (р < 0.05).
Dynamic observation of study group women has demonstrated that non-ischemic branch retinal vein occlusions occurred in 12 women (29%) 6.5 to 8.5 years after childbirth. Superior and inferior temporal branch retinal vein occlusion was diagnosed in 8 and 4 eyes, respectively (see Fig. 1).
Best-corrected visual acuity has reduced to, on average, 0.5 ± 0.2 in all these women. Fundus examination has discovered flame-shaped intraretinal hemorrhages along the affected branches of central retinal vein, hard exudates, and focal or diffuse macular edema (see Fig. 2). Macular volume measured by optical coherence tomography was, on average, 10.9 ± 0.8 mm3.
To determine the effect of baseline linear blood flow parameters in short posterior ciliary arteries on the development of retinal vascular complications, we have subdivided study group into two subgroups. Subgroup 1 has included 12 women with branch retinal vein occlusions. Subgroup 2 has included 30 women who did not develop vascular retinal disorders within this period. Retrospective comparative analysis of baseline linear blood flow parameters in short posterior ciliary arteries in both subgroups was performed.
It was demonstrated that in the third trimester of pregnancy Vmax, Vmin, and Vmed were significantly lower in subgroup 1 as compared with subgroup 2 of the study group (p < 0.05). The degree of their reduction was 15% to 50%.
Table 2 illustrates these findings. 6 to 8 months after childbirth, no increase in these parameters was detected in subgroup 1 of the study group. Moreover, these parameters tended to reduce further as compared with the first trimester of pregnancy although insignificantly (7.98 ± 1.08 cm/sec and 8.54 ± 1.14 cm/sec, 2.21 ± 0.31 cm/sec and 2.46 ± 0.37 cm/sec, 4.42 ± 0.56 cm/sec and 4.77 ± 0.55 cm/sec, respectively; p > 0.05). In addition, PI and RI tend to increase insignificantly in subgroup 1 of the study group 6 to 8 months after childbirth as compared with the third trimester of pregnancy (1.32 ± 0.20 and 0.97 ± 0.16 as compared with 1.20 ± 0.17 and 0.92 ± 0.14, respectively; р > 0.05).
Vmax, Vmin, and Vmed have significantly increased in subgroup 2 of the study group 6 to 8 months after childbirth (р < 0.05).
Comparative retrospective analysis of PTI levels in the third trimester of pregnancy has demonstrated that this parameter was higher at baseline in subgroup 1 as compared with subgroup 2 of the study group, however, the difference was insignificant (р > 0.05). 6 to 8 months after childbirth, insignificant moderate increase in PTI levels was revealed in subgroup 1 of the study group (р > 0.05). Meanwhile, in subgroup 2 of the study group, average PTI levels were similar 6 to 8 months after childbirth as compared with the first trimester of pregnancy (р > 0.05). Moreover, PTI levels in subgroup 2 of the study group were similar as compared with the control group (р > 0.05).
Our previous studies have demonstrated that preeclampsia is characterized by increased endothelin-1 tear levels and increased von Willebrand factor plasma levels. These changes are observed after childbirth as well. The result is oxidative stress events in ocular regional system manifested by the release of excessive free radical oxidation products [5, 6]. These factors have negative impact on choroidal hemodynamics as demonstrated by reduced Vmax, Vmin, and Vmed and increased PI and RI in short posterior ciliary arteries in the third trimester of pregnancy. These parameters were back to normal 6 to 8 months after childbirth in 71% of women. However, 12 women with branch retinal vein occlusions occurred later in life were characterized by significantly lower Vmax, Vmin, and Vmed in the third trimester of pregnancy as compared with pregnant women with preeclampsia without retinal vascular disorders later in life (p < 0.05). In subgroup 1 of the study group, this phenomenon was associated with increased PTI in the third trimester of pregnancy (p > 0.05). 6 to 8 months after childbirth, PTI levels were higher in women with previous preeclampsia and retinal vascular diseases later in life as compared with the control group (p < 0.05).
We hypothesize that reduced linear blood flow parameters in short posterior ciliary arteries in preeclampsia in the third trimester of pregnancy which are not back to normal within the first year after childbirth and increased PTI levels after childbirth are the predictors of the development of retinal vascular diseases in the late postnatal period.
Our findings demonstrate that pregnancy complicated by preeclampsia is characterized by 1.3-1.4-fold reduction of Vmax, Vmin, and Vmed in short posterior ciliary arteries in the third trimester of pregnancy as compared with normal pregnancy and healthy non-pregnant women (p < 0.05).
In 71% of women with previous preeclampsia, Vmax, Vmin, and Vmed in short posterior ciliary arteries were back to values similar to that of the control group 6 to 8 months after childbirth.
Retrospective analysis has demonstrated that 12 women with branch retinal vein occlusions occurred in the late postnatal period were characterized by significantly reduced Vmax, Vmin, and Vmed in short posterior ciliary arteries and moderately increased PTI in the third trimester of pregnancy as well as 6 to 8 months after childbirth.
Comparative assessment of choroidal hemodynamics and PTI measurements in the third trimester of pregnancy and 6 to 8 months after childbirth in women with preeclampsia will help to identify risk groups for retinal vascular diseases.
Our findings demonstrate that reduced Vmax, Vmin, and Vmed and increased PI and RI in the third trimester of pregnancy complicated by preeclampsia as well as no positive changes in these parameters 6 to 8 months after childbirth can be considered as the predictors of retinal vascular disorders.
About the authors:
1,2Oleg V. Kolenko — MD, PhD, Associate Professor of the Department of Ophthalmology, Director, ORCID iD 0000-0001-7501-5571;
1,3Evgeniy L. Sorokin — MD, PhD, Professor, Professor of the Department of General and Clinical Surgery, Deputy Scientific Director, ORCID iD 0000-0002-2028-1140;
4Nazrulla S. Khodzhaev — MD, PhD, Professor, Deputy Director for Organizational Work and Innovative Development, ORCID iD 0000-0002-7614-628X;
1Natal’ya V. Pomytkina — MD, PhD, ophthalmologist of the Department of Laser Surgery, ORCID iD 0000-0003-3757-8351;
2Galina V. Chizhova — MD, PhD, Professor, Chancellor, ORCID iD 0000-0003-1408-7496;
1Anastasiya A. Fil — MD, Scientific Associate, ORCID iD 0000-0002-3846-3647;
1Yaroslav E. Pashentsev — MD, Junior Scientific Associate, ORCID iD 0000-0001-5446-0633.
1Khabarovsk branch of S.N. Fedorov NMRC “MNTK “Eye Microsurgery”. 211, Tikhookeanskaya str., Khabarovsk, 680033, Russian Federation.
2Postgraduate Institute for Public Health Professionals. 9, Krasnodarskaya str., Khabarovsk, 680009, Russian Federation.
3Far Eastern State Medical University. 35, Murav’yeva-Amurskogo str., Khabarovsk, 680000, Russian Federation.
4S.N. Fedorov NMRC “MNTK “Eye Microsurgery”. 59A, Beskudnikovskiy blvd, Moscow, 127486, Russian Federation.
Contact information: Oleg V. Kolenko, e-mail: firstname.lastname@example.org. Financial Disclosure: no author has a financial or property interest in any material or method mentioned. There is no conflict of interests. Received 03.09.2019.
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