Retinal vascular occlusion in pregnancy: three case reports and a review of the literature

Retinal arterial occlusive diseases (RAO) in young patients are rare. Only 11.4% of all RAO occur in people under 50 years of age [1]. In pregnancy however, retinal vascular occlusive diseases may arise spontaneously or a preexisting constitution may deteriorate [2]. There are many physiologic adaptions during pregnancy that can induce vascular occlusive events [3]. These include complex cardiovascular [4‐7], hormonal [8, 9], hemostaseological [10, 11], and immunological changes [12, 13]. These adaptions not only increase the risk of a retinal vascular occlusive event but also of stroke during pregnancy. Furthermore and independent of pregnancy, patent foramen ovale (PFO)-related stroke is increasingly recognized as an important etiology of ischemic embolic stroke [14, 15]. Guidelines recommend exclusion of PFO and other sources of embolism in the case of RAO [16].

Normally, fluorescein angiography is a central part of diagnosing a retinal vascular occlusion. It has been established that fluorescein dye crosses the placenta into the fetal circulation [17], yet detrimental effects of fluorescein dye on a fetus have not been documented [18]. However, its use should be avoided during pregnancy. Optical coherence tomography angiography (OCTA) is a novel, noninvasive method for visualization of the functional retinal vessels measuring the movement of red blood cells [19] and therefore represents a good method for analyzing the perfusion of retinal vessels in pregnant patients. OCTA has made it for the first time possible to analyze microvascular changes such as in diabetes mellitus and hypertension during pregnancy.

Here we present a case series of three patients who visited our clinic owing to acute visual impairment. RAO were detected using OCT and OCTA, thus initiating the evaluation of systemic risk factors.

Case presentations

We present three cases with three distinctly different types of retinal vascular occlusion in pregnancy. Even though case 1 and 2 both depict CLRAO, there is a difference in the pathogenesis. Etiologically, CLRAO is of three distinct types: CLRAO associated with CRVO or hemi-CRVO (like in case 1), non-arteritic CLRAO alone (like in case 2), and arteritic CLRAO associated with giant cell arteritis [21].

The pathogenesis of CLRAO in CRVO is due to transient hemodynamic blockage of the cilioretinal artery caused by a sudden sharp rise in intraluminal pressure in the retinal capillary bed (due to CRVO) above the level of that in the cilioretinal artery. Unlike regular non-arteritic CLRAO, there is no thrombotic or embolic occlusion of the artery in this type [22]. Consistent with this, OCTA in our case showed reperfusion of the cilioretinal artery. (Fig. 1I). The resulting retinal atrophy (Fig. 1L, P) is likely to be caused by transient ischemia lasting longer than 1–2 hours [23, 24].

Non-arteritic CLRAO, as seen in patient 2, is caused by classical thromboembolic occlusion. In our case, the OCTA showed reperfusion 10 days after the onset of the scotoma (Fig. 2E), indicating transient occlusion of the cilioretinal artery. Over time, there was progressive atrophy of the retina, in particular of OPL and INL (Fig. 2H, M). Consistent with this, OCTA depicted no perfusion in the DCP (located in the INL and OPL) in the area of atrophy, while the ICP and SVP showed regular perfusion (Fig. 2I, N).

Paracentral acute middle maculopathy (like in case 3) was first described in 2013 by Sarraf et al. [25] and was identified as a variant of acute macular neuroretinopathy. However, it is currently regarded as a different entity from the latter and is a spectral-domain OCT finding characterized by a hyper-reflective band spanning the INL, which typically evolves to INL atrophy in later stages [26] as depicted in Fig. 3C. As previously described by Chu et al. [27], we were able to locate an irregular vascular network in ICP and nonperfusion in DCP on OCTA (Fig. 3D)—corresponding to the atrophy in INL. PAMM can be caused by potential infectious, inflammatory, vascular, toxic, and iatrogenic causes [26, 28, 29]. Recently, cases of PAMM during pregnancy were described [30‐32]. Like our patient, the three women were described as healthy and had an otherwise uncomplicated pregnancy. One was in her first and two were in their second trimester of pregnancy, like our patient.

OCTA was successfully performed in all three cases. Reperfusion was seen in cases 1 and 2, which could be considered a surrogate marker for better functional outcome in terms of a smaller scotoma due to a smaller atrophic area.

In pregnancy, preexisting conditions may deteriorate owing to hormonal, hematologic, metabolic, cardiovascular, and immunologic changes that induce retinal vascular occlusive events [2, 3]. Associated risk factors for events of retinal vascular occlusion are primary antiphospholipid antibody syndrome, high factor VIII, and low protein S [33]. Also, factor V Leiden mutation has been reported in a case of bilateral retinal vein occlusions [3]. Combined CRVO and CLRAO can occur with increased D-dimer level [34]. However, physiologic changes during pregnancy may play a role. Hormonal alterations increase angiopoietic factors, such as progesterone [35]. Cardiac output and heart rate are physiologically increased [5]. Physiologic hypercoagulability and thrombophilia [11] may also play a role in the pathogenesis of retinal vessel occlusion.

Our patients all had otherwise uncomplicated pregnancies, and laboratory blood tests did not reveal any defects or alterations. Two of the three women (case 2 and 3) possessed a PFO. This is a congenital heart defects with a short-circuit connection between the right and left atrium and is found in around 30% of all healthy adults [36]. Though the majority of patients with PFO are asymptomatic and do not possess an increased risk for developing a stroke, it is likely that other risk factors (such as hypercoagulability) need to be present for a stroke to occur [37]. It was found that PFO-related strokes occur mainly during the first two trimesters [14]. In cases 2 and 3, who both presented PFO, the occlusive event occurred during this time. Post-ischemic management of PFO consists of secondary prophylaxis (antiplatelet therapy) and closure in large-sized PFO shunts [38]. The treatment for retinal vascular occlusions is empirical, and should be performed in close cooperation with hemostaseologists, cardiologists, and obstetricians. We treated all cases with 100 mg acetylsalicylic acid orally, and patient 2 was recommended by cardiologists to undergo interventional PFO closure after pregnancy. Unlike the other two cases, the pathogenesis in case 1, that is, CRVO associated with CLRAO, is not thrombotic or embolic (22). This also reflects the fact that the internal examination was unremarkable. Nocturnal hypotension, being a risk factor, was ruled out. Antiplatelet therapy as secondary prophylaxis was initiated.

OCTA is a valuable option to noninvasively diagnose and analyze the retinal perfusion status in pregnancy when fundus fluorescein angiography should be avoided. Together with OCT imaging, OCTA allowed us to predict functional outcome in addition to the existing retinal occlusion-related atrophy.