Serous Retinal Detachment in Pre-Eclampsia: A Systematic Review of Case Report Sebuah Tinjauan Sistematis Laporan Kasus: Ablasio Retina pada Pre-eklampsia

Serous Retinal Detachment is one of the preeclampsia complications which may be identified during the third trimester of pregnancy or postpartum period that may be related to pregnancy condition. We review case reports related to serous retinal detachment in preeclamptic patients from online databases such as MEDLINE/Pubmed and Science Direct from 2011 to 2021 in accordance with PRISMA guidelines. Authors independently screened abstracts of articles retrieved articles that were considered potentially relevant, and extracted the articles obtained. From 17 articles, serous retinal detachment is higher in severe preeclampsia and HELLP syndrome (88%). Most patients were indicated to do caesarean section (71%) as their mode of delivery due to managing severe preeclampsia. Although most patients (94%) reported retinal detachment involving the macular area, complete resolution was observed in all the patients (94%). Early detection of serous retinal detachment may increase awareness of early detection of severe preeclampsia and HELLP syndrome.


INTRODUCTION
Preeclampsia is the third leading cause of maternal morbidity and mortality (1).Globally, preeclampsia affects an estimated 2% to 8% of pregnancies (2,3).It is also responsible for 9% to 26% of maternal deaths in developing countries and 16% in developed countries (4).As a broad clinical spectrum disease, preeclampsia is categorised into preeclampsia, severe preeclampsia, eclampsia and Hemolysis-Elevated Liver enzymes-Low Platelets (HELPP) syndrome, which affects multiple organs (5).Dysfunction of the cardiovascular, hepatorenal, hematologic, neurologic, and visual systems are the offerings of the disease progression (3,5).
Studies demonstrated that the inception of preeclampsia starts with the failure of the trophoblastic invasion of maternal spiral arteries.These conditions lead to higher vascular resistance of uterine arteries, lower uteroplacental blood flow, and higher vascular permeability (6,7).Although the exact pathophysiology is unknown, in a hypertensive state, choroidal-retinal vessels showed the same abnormality resulting in subretinal fluid accumulation (8).The known mechanism might explain several visual symptoms in preeclamptic patients, such as blurred vision, diplopia, transient loss of vision, photopsia, and visual field deficit (9).
Serous retinal detachment (SRD) is one of the preeclampsia complications which may be identified unilaterally or bilaterally during pregnancy or the postpartum period.Prevalence of SRD is higher in a severe form of preeclampsia than in preeclampsia (10).Most of the patients with SRD had complete recovery without any surgical intervention within 2-12 weeks after the symptoms occurred (8).Sequelae rarely persist, but retinal detachment involving the macular area may hinder the complete visual resolution.Management of underlying disease is the primary choice in treating serous retinal detachment (8,11).Therefore, recognising serous retinal detachment in pregnant patients allows obstetricians and other healthcare workers to detect the more severe state of preeclampsia early.The aim of this study was to review case reports of serous retinal detachment in preeclampsia during the last decade.We evaluated parity, blood pressure, mode of delivery, macular involvement, recovery period and funduscopic examination.

Search Strategy
MEDLINE/Pubmed and Science Direct were used to identify studies related to retinal detachment in patients with preeclampsia, preeclampsia with severe features, eclampsia or HELLP syndrome.The terms used for systematic review were (retinal detachment) AND (preeclampsia OR eclampsia OR HELLP syndrome).All the th searches were performed up to October 11 , 2021, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline.

Eligible Criteria
Studies from online databases were screened based on inclusion and exclusion criteria.All studies written in English from 2011 to 2021 about retinal detachment in preeclampsia were included.We identified obstetric diagnosis of preeclampsia, preeclampsia with severe features, eclampsia, and HELLP syndrome based on the mentioned diagnosis in the study.We excluded cases with comorbid diseases such as retinal detachment due to diabetes mellitus, cortical visual pathology, and retinal detachment related to long-standing hypertension especially followed by hypertensive retinopathy or hypertensive chorioretinopathy.Patients with a history of retinal detachment were also excluded from the study.Non-case reports such as reviews, basic research, or commentaries were also excluded.
The recovery state of the patient consists of a complete and incomplete resolution.Complete resolution is defined as returning visual acuity to normal after a certain period of evaluation from the onset of retinal detachment or clearly mentioned by the authors.All funduscopy photos were re-interpreted by an ophthalmologist (MYA).Authors (HHPI, MAA, DGKJ) independently screened the titles and abstracts of articles found during the search and retrieved any that were considered potentially relevant.Disagreements and uncertainties among the authors were resolved through consulting with the expert (MYA, AD).

Data Extraction
We extracted 17 out of 142 studies related to retinal detachment in preeclampsia patients.Data items collected were age, parity, clinical manifestation, blood pressure (mmHg), obstetric diagnosis, mode of delivery, onset, funduscopy examination, recovery interval, recovery state and management for retinal detachment.Extraction of the data was performed independently by the authors (HHPI, MAA, DGKJ).Any disagreements and uncertainties were resolved by discussion with the experts (MYA).

RESULTS
The workflow of the search strategy is presented in Figure 1.An initial search from electronic databases found studies.After being excluded by abstract review,  2. The mean patient age was 30.17 years, aged between 20-41 years.Our parity analysis found that of 13 patients, 61% (7) were primipara, and 39% were multipara.Mean systolic and diastolic pressure was 186.35 mmHg (range 140-230) and 111.59 mmHg (mean 80-160), respectively.Most of the patients were diagnosed with severe preeclampsia feature (44%; 8 cases) and HELLP syndrome (44%, 8 cases).Around 55% (9) of the cases of retinal detachment in preeclampsia were identified during the postpartum period, and the rest, 45% (7), were identified during antepartum period.Detachment involving the macular area was identified in most cases (94%; 16 cases).Most of the cases (82%) were recovered completely without any additional sequelae, while 17% of the cases showed incomplete resolution.

DISCUSSION
Visual disturbance is one of the most frequent complications of preeclampsia.Choroidal-retinal vessel disruption due to hypertensive condition caused subretinal fluid accumulation (28).Serous retinal detachment is one of the preeclampsia complications which frequently occurs in primiparous women, bilaterally, and tends to be diagnosed during the last trimester or postpartum period (10).According to this study (Table 2) showed that primiparous women (61%) more frequent experience retinal detachment than multiparous women (39%).Like Prabhu in 2017, around 62,5% of retinal detachment occurred in primiparous women.Generalised endothelial dysfunction in preeclamptic conditions, which tends to increase in first pregnancies, is responsible for the progression of the disease (29,30).Many factors have been studied were associated with endothelial alteration in first pregnancy in preeclampsia, such Soluble fms-Like Tyrosine Kinase 1 (sFLT-1) and proangiogenic placental growth factor (PlGF) (30,31).
The incidence of retinal detachment is more prevalent in severe preeclampsia and HELLP syndrome than in preeclampsia.31 We found a higher number of cases of retinal detachment related preeclampsia with severe features (44%; 8 cases) and HELLP syndrome (44%; 8 cases) than in preeclampsia (12%, 2 cases).A study by Prabhu, 2017 showed that retinal detachment is seven times more common in preeclampsia or HELLP syndrome than in those without HELLP syndrome (28).This may be related to higher blood pressure even as a study conducted by Wei et al, 2021 showed that systolic blood pressure and diastolic blood pressure were higher in the retinal detachment group than in the non-retinal detachment group in preeclamptic patients (32).
The severity of ischemic placenta in hypertension-related gestational conditions may worsen vascular perfusion as it releases inflammatory cytokines, proangiogenic factors, and oxidative stress factors, which may induce endothelial dysfunction (33,34).Moreover, hypersensitivity to vasopressor, reduced response to vasodilator and decreased vasodilator factors occurred in the preeclamptic patient (29,33).Mimicking systemic vascular dysfunction, local necrosis of choriocapillaris followed by choroidal ischemia due to arteriolar vasoconstriction affect bloodretinal barrier integrity and increase vascular permeability (35).In addition, hemolysis of erythrocyte in HELLP syndrome may worsen the condition by occluding retinal arteries (36).Sequences of choroidal ischemia and necrosis lead to retinal pigment epithelium dysfunction in transporting ions and fluid as its main function.Therefore, subretinal accumulation and serous retinal detachment occurred in patients with preeclampsia (31).
Most of the patient with serous retinal detachment in preeclamptic patients were indicated with caesarean section (Table 2) due to termination in managing severe preeclampsia.A study by Vigil-De Gracia and Ortega-Paz L, 2011 showed that 76% of preeclamptic patients followed by serous retinal detachment have section cesarean as the mode of delivery (10).In this study, most preeclamptic patients followed by retinal detachment were resolved completely without any sequelae (Table 2).The detachment was resolved within 1 to 2 months after the onset (10).As in this study, most patients were completely resolved (82%) within a week to 6 months.Any surgical treatment is ineffective in managing retinal detachment in preeclampsia as retinal tears were absent.Managing preeclampsia as an underlying cause, such as blood pressure control, fluid management, and seizure prophylaxis, is the main choice in treating retinal detachment (5,11).
Blindness is a rare complication in preeclampsia.Around 94% of preeclamptic patients with retinal detachment resolved completely, although macular involvement was reported in almost all the patients (Table 2).A study by Prabhu, 2017 showed the incidence of blindness in preeclampsia was 0,17% (16 from 9199 cases of preeclampsia) (28).Reviewed cases from Chen and Chen in 2012 demonstrate incomplete visual resolution related to severe preeclampsia.24A different mechanism may be responsible in these cases.Delayed immunochemical reaction in response to severe preeclampsia may affect retinal pigment epithelium and cause serous subretinal accumulation (37).
There were several limitations in this study.Preeclamptic and eclamptic are life-threatening conditions that need abrupt systemic and etiologic management.Due to this condition, most preeclamptic ocular cases were underdiagnosed, with no particular development pattern.Secondly, inadequate follow-up may limit information on ocular resolution progression in preeclamptic patients.Hence, the resolution of visual acuity in the patients may be reported as incomplete.
The prevalence of serous retinal detachment is higher in severe pre-eclampsia and HELLP syndrome.A higher blood pressure that occurs in severe preeclampsia may play a role in the pathogenesis of retinal detachment.Most patients with serous retinal detachment are indicated for a caesarean section as their mode of delivery due to termination in managing severe preeclampsia.Therefore, obstetricians and general practitioners need to better understand serous retinal detachment in preeclampsia.It allows early detection of the severe form of preeclampsia.Managing underlying diseases is the main choice in treating serous retinal detachment-related preeclampsia.Complete resolution was reported in most of the patients, although macular involvement was reported in the patients.

Figure 1 .
Figure 1.Workflow of identifying related studies

Table 1 (
Serous Retinal Detachment in Pre-Eclampsia... Vol.32, No. 3, February potentially relevant studies were reviewed.A total of 17 articles were included in the study.Data items collected were age, parity, clinical manifestation, blood pressure (mmHg), obstetric diagnosis, mode of delivery, the onset of retinal detachment, funduscopy examination, recovery interval, recovery state and management for retinal detachment.Extraction of the data was performed independently by the authors.Any disagreements and uncertainties were resolved by discussion with the experts.Relevant data were extracted and entered a study database.Appendix).Patient characteristics, blood pressure, the onset of retinal detachment, location of detachment, visual acuity resolution and recovery period were summarised in Table