Optical Coherence Tomography Observed Fundus Changes of Hypertensive Disorders Complicating Pregnancy

Background By optical coherence tomography(OCT) observed fundus changes of hypertensive disorders complicating pregnancy. Methods Inspected patients with hypertensive disorders complicating pregnancy accepted eye examination including corrected visual acuity, slit lamp examination, fundus examination, OCT Results 1.OCT examination results of abnormal 148, which neurosensory serous retinal detachment 84eyes (56.76%), pigment epithelium and the IS / OS layer change 38 eyes (25.68%), optic disc oedema and retinal haemorrhage and other changes of 26 eyes (17.56%). 2. Between different phenotypes OCT of Patients with oedema, proteinuria, blood pressure and course had differences (P <0.05), and had a correlation between the two.3. Between different phenotypes OCT of Patients with gestational age, age, whether it is the rst child was irrelevant (P> 0.05).4. Between different phenotypes OCT of Patients with visual acuity, fundus lesions and eye symptoms had differences (P <0.05), and had a correlation between the two (P <0.05). Conclusions OCT can understand the severity of fundus changes with hypertensive disorders complicating , and provide evidence about clinical diagnosis and

Our 98 inspected patients were the pregnant women, registered at our hospital from December 2016 to October 2019, who were all diagnosed, by Obstetric Department, with PIHS while being clear on previous history of Chronic Hypertension, cardiovascular disease, Diabetes, or kidney disease etc. All of these 98 patients, 63 of them are primipara, the rest of 35 ones are pluripara, who are aging from 23 to 45 with the average age of 29.10 ± 4.88, while in which, 12 patients are aging from 20 to 25, 51 patients are aging from 25 to 30, 18 patients are aging from 30 to 35, and 17 patients are aging over 35, are diagnosed with fundus change when they are under the eye examination. At their rst time visiting moment at our department for the eye examination, which is in their gestational age of 21 to 39 (only full weeks are counted), and the average gestational age of 34.03 ± 3.46, they have been diagnosed with PIHS averagely for 10.22 ± 8.60 days, and the average systolic and diastolic pressure are 178.28 ± 15.57 mmHg and 94.34 ± 6.16 mmHg respectively. While the data of the referenced group for the pregnant women who visited Obstetric Clinic in the corresponding period are 45 people (90 eyes), 35 of them are primipara, 15 ones are pluripara, whose corrected visual acuity are all over 1.0 with the age ranging from 24 to 42 with the average age of 27.12 ± 4.15, are all clear on PIHS, Diabetes, any organic eye disease or other systemic diseases effecting the eyes etc., and no history of Chronic Hypertension, cardiovascular disease, or kidney disease etc. At the visiting moment, which is in their average gestational age of 35 ± 3.12, the average systolic and diastolic pressure are 115.33 ± 5.61 mmHg and 74.21 ± 5.17 mmHg respectively. With the above comparisons, the statistical difference only exists in comparison on blood pressure, but not on age and gestational age.
1.2 According to Obstetrics (8th Edition) [2] , there are three criteria for diagnosing PIHS, and they are Hypertensive Disorders Complicating Pregnancy, Pre-eclampsia (mild and severe) and Eclampsia. Among 1.3 Each PIHS patient is assigned to a speci c doctor, whom will be in charge of the patient's fundus detection, OCT examination, blood pressure examination, proteinuria examination, oedema testing, and rating for the oedema and protein examination results.
1.4 With SPSS 20.0, the Chi-Square Tests will be run with the data of OCT phenotypes for the inspected patients and the referenced group, patients' oedema, proteinuria, blood pressure, disease progress, age, fundus lesion and eye symptom. When the theoretical frequency is less than 1, the Fisher Exact Test and Pearson conducted at the same time for analysis, the statistical signi cant is found (P < 0.05).

Results
2.1 OCT Phenotypes: Among the 98 inspected patients (196 eyes), the initial OCT examination reports that there are 148 eyes have eye symptoms, among which 84 eyes are with neurosensory serous retinal detachment (56.76%), including 50 eyes with detachment at central fovea of macula (Fig A), while 12 of the 50 are also complicating with epithelium oedema (Fig B), and 34 eyes with detachment at peripheral nerve around fovea centralis, which mainly happens to the peripheral area of the optic disc (Fig C), 38 eyes are with pigment epithelium and the IS / OS layer change (25.68%) (Fig D), and 26 eyes are with other changes, such as optic disc oedema and retinal haemorrhage etc. (17.56%) (Fig E & F) Among the 45 pregnant women (90 eyes) from the referenced group, there are 2 eyes have minor pigment epithelium and the IS / OS layer change, and no obvious eyes symptom is found from other women's OCT examination. The statistical difference could be found in these two groups OCT examination phenotypes (x 2 = 145.473, P = 0.000 < 0.05).
2.2 Categorise OCT Phenotypes into There Groups: Group One is for retinal nerve epithelium detachment. Group Two is for pigment epithelium (previously called as IS/OS layer) change. Group three is for optic disc oedema and retinal haemorrhage etc. The relationships between these three OCT phenotypes and the patients' general symptoms such as oedema, proteinuria, blood pressure and gestational age will be analysed respectively. ( Table 1) ( Table 3): According to the de ned grading method of blood pressure in Guide on Prevention and Control of Hypertension in China (Revised Edition in 2005), the blood pressure has been graded as Grade I, in which the hypertension systolic pressure ranges from 140 to 159 mmHg, or the diastolic pressure ranges from 90 to 99 mmHg; Grade II, in which the hypertension systolic pressure ranges from 160 to 179 mmHg, or the diastolic pressure ranges from 100 to 109 mmHg; and Grade III, in which the hypertension systolic pressure is equivalent to or higher than 180 mmHg, or the diastolic pressure is equivalent to or higher than 110 mmHg. Result

Discussion
Hypertensive Disorders Complicating Pregnancy has been used to be called as Pregnancy-Induced Hypertension Syndrome and shortened to PIHS. Generally speaking, it always happens after 20 weeks of the pregnancy with the pathophysiological changes of systemic small vessel spasm, endothelium injury and ischemia. With previous experience, the PIHS patients' fundus changes have close connection to the patients' general clinical manifestation. For example, the higher the blood pressure and proteinuria level are, which are the indicators for the severity of PIHS, the more obvious the fundus changes are [3] . Besides, since the retinal vessels in fundus is the only part for directly observing the vessel changes in living people, the fundus detection result is always a vital indicator for PIHS diagnosis. For patients with fundus change in early stage, if their blood pressure could be lowered accordingly, in which case they are clear on the fundus changes, after taking rest, being tranquillised, releasing spasm, taking hypotensor and diuretics etc., they could continue the pregnancy with the intensive monitor on the maternal-fetal status. Otherwise, if the patients are failed to respond to these medical treatments, especially when, after the treatments, they have the symptoms such as retinal oedema, exudation or haemorrhage, which means there is organic damage to the retina and general small artery, the pregnancy should be terminated accordingly to avoid any severe complication afterwards. Therefore, the diagnosis results on fundus change, especially on the severe retinopathy, should be a vital reference for the necessity of conducting pregnancy termination [4] . However, some of the severe retinal diseases, such as retinal oedema and limited retinal detachment etc., especially for the latter one, might be missed in the fundus detection by the eye ultrasound examination, for the contrast medium used in which are not suitable for the pregnant women. On the contrary, OCT, with its non-invasive and reproducible characteristic, high solution and cross section imaging technique, could be used for the ocular tissue micro-imaging, especially for the imaging of retina and its neighbouring tissues. There are some studies have found that the retinal disease is correlated to optic disc peripheral, the thickness of retinal nerve bre layer at the central fovea of macula, and the continuity change in the outer retinal structure [5,6,7] . Our study also nds that the OCT examination results for healthy pregnant women are normal, but the results are abnormal for the PIHS patients, which could be summarised into three phenotypes related to the patients' general system status, especially to the patients' blood pressure, oedema and proteinuria. The higher the blood pressure is, the severer the oedema and proteinuria will be. Also, the higher the blood pressure is, the more possible the patients will be diagnosed with retinal haemorrhage and optic disc oedema, which are seconded only to retinal epithelium oedema, in OCT. Besides, our study also nds that the OCT phenotypes will not be impacted by the patients' gestational age, age and the number of times for being pregnant, but by the patients' disease progress, in which case the patients with short disease progress will be more possible to be diagnosed with epithelium oedema, while the ones with long disease progress will be more possible to be in the middle of recovering from the fundus changes, for some of them have get the blood pressure under control.
With fundus angiography, some studies nd that it is quite common among the early stage PIHS patients that they have the symptom, in varied degrees, of slow choroid lling or without reperfusion, in other words, choroid ischemia, which are shown as faint or dark areas, indicating pigment epithelium change with damage and dysfunction caused by choroid ischemia, in the fundus angiography. [8,9,10] This change is often diagnosed in the patients' optic disc peripheral and the macular area, for which are areas most of the choroid artery watershed and vein vertical watershed are distributed around. With the comparatively poor blood circulation here, the optic disc peripheral and the macular area are also the areas with the greatest occurrence of dysfunctional choroid circulation and pigment epithelium damage, complicating with uid lled in the retina here, where OCT could detect properly, by ischemia and hypoxia. According to our study, the main OCT phenotypes for PIHS patients are neurosensory serous retinal detachment 84 eyes (56.76%), which is mainly diagnosed in the optic disc peripheral and the macular area, pigment epithelium and the IS / OS layer change 38 eyes (25.68%), optic disc oedema and retinal haemorrhage and other changes of 26 eyes (17.56%) respectively. Moreover, according to the patients' self-claim, the retinopathy in the macular and optic disc peripheral area has the predominant impact on their visual acuity. Our study also nds the OCT phenotypes are correlated to the patients' corrected visual acuity, the severity of the fundus changes and the patients' self-claimed symptoms, which not only proves the coherence between OCT and fundus detection, but also the advantage that OCT has for observing the retinal microstructure changes.
According to our study, for patients, who are diagnosed with neurosensory oedema retinal detachment by OCT, they are always in the middle of the disease progress with the severe fundus change and poor systemic health condition so that they are required to be taken care of by intensive monitoring on their eye and systemic health condition with positive medical treatment. The relevant medical solution of necessity, such as pregnancy termination, should be conducted in accordance with the monitoring. While, for patients, who are diagnosed with pigment epithelium and IS/OS layer change, they are always in the end of the disease progress, a recovering or stabilized period for the fundus changes, so that they should continue current treatment along with health condition observation. With OCT examination on their fundus recovering status when they visit our department, we nd that although some of the patients' health condition have been stabilised by getting blood pressure under control, the pigment epithelium and IS/OS layer change has not recovered yet.

Conclusions
Therefore, the pregnant women, with the gestational age longer than 20 weeks and the hypertension history or the potential to have unstable blood pressure, should take OCT and fundus detection while they are doing the prenatal examination so that their fundus changes status, which is a vital reference to clinical diagnosis, treatment and prognostic judgements, could be tracked accordingly.

Consent for publication
Written informed consent was obtained from the patient for publication of this study and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.