Simultaneous Bilateral Serous Retinal Detachments and Cortical Visual Loss in the PRES HELLP Syndrome

Preeclampsia/eclampsia, posterior reversible encephalopathy syndrome (PRES), and the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome are all complications of pregnancy which share some pathogenic features and risk factors. Both PRES and HELLP have been associated with visual loss. The underlying pathogenic mechanisms may be similar—breakdown of endothelial blood–brain in PRES or blood–retinal barrier in HELLP. The role of the coexistence of the 2 disorders (PRES/HELLP) in the same patient may manifest with both anterior and posterior visual pathway disease in the form of serous retinal detachments (SRD) and cortical visual loss. We describe the shared and distinct pathogenic mechanisms for both PRES and HELLP and their significance to ophthalmologists. To the best of our knowledge, this is the first such case to be described in the English language, neuro-ophthalmic literature. CASE REPORT A 26-year-old gravida one, parity one (G1P1) Hispanic female patient presented with acute, bilateral vision loss in the postpartum period, after a previously uncomplicated prenatal course. Past medical, surgical, family, and social histories were unremarkable. She was only taking prenatal vitamins. The patient was normotensive without seizure or proteinuria throughout her pregnancy. One-hour postpartum, the patient became acutely and markedly hypertensive with systolic blood pressure readings over 200 mm Hg. Serum laboratory testing showed marked thrombocytopenia, diffuse intravascular coagulopathy, and elevated liver function tests (Table 1). A diagnosis of HELLP syndrome was made. She developed progressively worsening headaches and altered mental status and was acutely encephalopathic. Cranial MRI showed T2-weighted hyperintensities in the posterior cortex (Fig. 1). Corresponding hyperintensities were seen on diffusion-weighted imaging (DWI) and on apparent diffusion coefficient (ADC) imaging. The MRI hyperintensities on T2, DWI, and ADC were believed to be consistent with "T2 shine through," and a diagnosis of vasogenic cerebral edema from PRES was made. Table 1. - Laboratory values for patient Laboratory Results AST (10–40 U/L) 2121 U/L Ferritin (12–150 ng/mL) 700 ng/mL Haptoglobin (30–200 mg/dL) <10 mg/dL Direct bilirubin (0–0.4 mg/dL) 10 mg/dL LDH (100–190 U/L) 1475 U/L D-dimer (0–0.4 μg/mL) 12.59 μg/mL PT (11.5–14.5 s) 18.1 s PTT (23–36 s) 38 s Total bilirubin (1.71–20.5 μmol/L) 15 μmol/L ALP (35–104 U/L) 326 U/L ALT (5–50 U/L) 678 U/L Reticulocyte count (normal 0.5%–2.1%) 2.9% Hemoglobin (12–15.5 g/dL) 8.3 g/dL Platelet count (normal 150–400 k/μl) 38 k/μL FIG. 1.: A. MRI of the brain with diffusion-weighted imaging (DWI) shows hyperintensities in posterior cortex as indicated by arrow. Hyperintensities are also seen in the same areas in the posterior cortex on T2-weighted imaging as indicated by arrow (B) and remains hyperintense on apparent diffusion coefficient (ADC) imaging as indicated by arrow (C), suggesting "T2 shine through" effect from vasogenic edema in PRES rather than cytotoxic edema (which would show hyperintensity on DWI and hypointensity on ADC) from ischemic stroke with true restricted diffusion. PRES, posterior reversible encephalopathy syndrome.The patient was admitted to the medical intensive care unit, and her blood pressure responded to intravenous titratable antihypertensive agents. On the second day of her admission, her encephalopathy symptoms subsided, but she had a new complaint of blurry vision in both eyes and ophthalmology was consulted. On examination, her best-corrected visual acuity was 20/50 in both eyes. Pupils measured 4 mm in dark and 2 mm in light in both eyes with no relative afferent pupillary defect. Intraocular pressure was 15 mm Hg in both eyes. Anterior segment examination was normal. Ophthalmoscopy showed a peripapillary cuff of subretinal fluid as well as a few smaller, multifocal areas of subretinal fluid, consistent with SRDs. Ocular coherence tomography (OCT) of optic disc showed no disc edema; however, some subretinal fluid was seen in the peripapillary area extending toward the macula. Subretinal fluid was also seen on OCT macula (Fig. 2). Visual field testing in both eyes showed some nonspecific field defects which may have been due to the serous detachments or choroidal ischemia, but no homonymous hemianopsia was seen (Fig. 3). Examination of the fundus showed peripapillary serous elevation of the retina extending to the macula in the right and left eyes (Fig. 4).FIG. 2.: A. Ocular coherence tomography (OCT) of optic disc shows no disc edema; however, some subretinal fluid, indicated by a white arrow, is seen in peripapillary area extending toward macula. Subretinal fluid, indicated by a white arrow, can also be seen on OCT macula (B). OD, right eye; OS, left eye; OU, both eyes.FIG. 3.: Visual field testing in both eyes shows some nonspecific field defects which may have been due to the serous detachments or choroidal ischemia, but no homonymous hemianopsia was seen.FIG. 4.: Fundus photograph of the right eye (A) shows peripapillary serous elevation (indicated by white star) of the retina. Fundus photograph of the left eye (B) shows similar serous elevation (indicated by white star). Although there is apparent torsion in the fundus photograph, this may be an artifact of testing as no other motility (e.g., skew deviation) symptoms or signs were present.DISCUSSION RD is a rare complication of pregnancy but occurs in up to 1%–2% of preeclamptic patients (1). Preeclampsia is diagnosed when a patient presents, after 20 weeks gestational age, with hypertension and evidence of end organ damage, most commonly proteinuria. The proposed pathophysiological cause of preeclampsia and its complications is abnormal placentation causing inadequate cytotrophoblastic invasion of the spiral arteries, subsequently resulting in placental ischemia (2). An analogous mechanism may be the cause of retinal detachments in preeclampsia. Under normal conditions, choroidal vessels supply the retinal pigmented epithelium (RPE), which functions to pump water out of the retina. Some studies have reported the cause of retinal detachment to be choroidal ischemia (3). An ischemic RPE cannot effectively pump water out of the retina, leading to the accumulation of subretinal fluid which ultimately causes SRDs (4). Choroidal ischemia and RPE damage have been found through imaging in preeclamptic patients (5). This suggests that choroidal ischemia and growth factor imbalances, such as increased vascular endothelial growth factor, may be the cause of RDs in patients with preeclampsia. HELLP is a different complication of pregnancy. The pathophysiology is not clearly defined but is theorized to be due to the placental factors endoglein and placental Fas-ligand triggering a thrombotic microangiopathy. This causes further platelet consumption and then hemolysis through shearing against these platelet deposits (6). In addition to this, placental Fas-ligand damages hepatocytes, causing elevated liver enzymes (6,7). Few cases of bilateral SRD in HELLP syndrome have been reported previously (8). In addition, a review of pregnancy complications found retinal detachments in only 0.9% of HELLP patients (9). It has been suggested that the retinal detachments in patients with disseminated intravascular coagulation can be attributed to choroidal damage secondary to ischemia or thrombosis (10). PRES is an uncommon clinicoradiological syndrome whose symptoms consist of headaches, seizures, altered consciousness, and visual disturbances. The exact mechanism is unknown, although it is theorized to be caused by both vasoconstrictive ischemic injury as well as endothelial dysfunction from circulating growth factors leading to the breakdown of the blood–brain barrier, both of which lead to vasogenic edema seen on imaging. Radiologically, PRES can be diagnosed through MRI. The MRI shows lesions in the posterior regions of the cerebral hemispheres, in the parietal and occipital lobes with extension into the basal ganglia, brainstem, and cerebellum. On T1-weighted MRI, the lesions are hypodense or dark. On T2-weighted MRI, they are hyperdense or bright. The DWI may be helpful in differentiating vasogenic edema from PRES from cytotoxic edema and ischemic stroke (11). Rarely, a PRES lesion can become ischemic and cytotoxic edema may be seen. SRDs have been noted in 2 cases of PRES. Vasoconstrictive and vasodilatory mechanisms may be the underlying pathophysiology. Vasodilation possibly contributes to PRES, as increased perfusion has been found in the edematous portions of the brain in patients with hypertensive encephalopathy. However, one of the cases of PRES associated with retinal detachments had residual Elschnig spots. Elschnig spots are indicative of areas of RPE ischemia, suggesting that the pathophysiology of the serous RDs related to PRES is more likely to be vasoconstrictive in nature (12). Another retrospective study showed that 87% of patients with PRES have diffuse vasoconstriction, focal vasculopathy, or vessel pruning of the posterior cerebral artery on imaging studies (13). It is plausible that this vasoconstriction extends to the choroidal vessels as well. Although vasodilation is possible, there is more evidence suggesting vasoconstriction has a significant role in PRES. Thus, 4 key underlying pathophysiologic causes are shared in these pregnancy-related disorders: endothelial dysfunction due to placental growth factors, vasoconstriction, vasodilation, and thrombosis. In our patient, there was no clear, single explanation for the mild subnormal visual acuity at the 20/50 level that did not recover after delivery. There was also no clinical or OCT evidence for subfoveal extension of the serous detachments. However, underlying choroidal ischemia and hypoperfusion cannot be completely excluded. In addition, although a strictly unilateral occipital lesion cannot produce degradation in central acuity (intact contralateral macular hemifield), an occult bilateral occipital subclinical ischemia or PRES could produce macular splitting and juxtaposed homonymous hemianopia that could degrade central vision. Humphrey visual fields were conducted after the patients vitals stabilized, about 5 days after the patient's initial presentation and visual acuity measurements. Although the underlying mechanisms for how PRES, HELP, and preeclampsia cause retinal detachment are still not completely understood, all 3 of these conditions have individually been reported to cause SRDs. In the present case, it is likely all 3 that are contributing to the patient's presentation. CONCLUSION Although PRES, HELLP, SRDs, and preeclampsia are well-known pregnancy-related syndromes, simultaneous SRDs in HELLP syndrome and cortical visual loss due to bilateral occipital lobe PRES in the setting of acute preeclampsia is uncommon. Ophthalmologists should be aware of the similarities and differences for these pregnancy-related conditions that may produce visual loss. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: T. Mitchell; b. Acquisition of data: S. Tabba; c. Analysis and interpretation of data: A. T. Kini. Category 2: a. Drafting the manuscript: A. T. Kini, S. Tabba, and T. Mitchell; b. Revising it for intellectual content: B. Al Othman and A. G. Lee. Category 3: a. Final approval of the completed manuscript: A. G. Lee.