The prevalence of type 2 diabetes mellitus (T2DM) has increased worldwide, and the number of pregnant women with T2DM has increased similarly.1 Pregnancy is a well-known risk factor for progression of diabetic retinopathy (DR), so it is important to follow DR carefully during the perinatal period,2 especially in patients who present with DR following conception.3 However, the methodology to identify microvascular changes is limited because fluorescein angiography (FA) generally is contraindicated during pregnancy. A newly developed technology, optical coherence tomography angiography (OCTA), visualizes noninvasively the pathologic microvascular changes in chorioretinal diseases.4,5 We recently demonstrated the usefulness of OCTA during the perinatal period for observing reperfusion of the choriocapillaris in hypertensive choroidopathy.6 In the current report, we used OCTA to follow marked DR progression related to pregnancy and hypertension.
A 27-year-old pregnant woman with an 11-year history of T2DM and no kidney dysfunction presented to our eye institute at 5 weeks of gestation. Her HbA1c level was 8.0% and the body mass index was 33.2. The bilateral visual acuity was 20/20, and the intraocular pressure was normal. Mild bilateral nonproliferative DR (NPDR) was observed during a fundus examination, and some microvascular abnormalities (ie, microaneurysms and small capillary nonperfusion) were observed using OCTA (DRI OCT Triton; Topcon, Tokyo, Japan). Fundus observation and OCTA showed no significant DR progression until delivery (Figure 1; Figure A). However, her blood pressure (BP) increased to a maximum of 180/110 mm Hg at 39 weeks of gestation without previous warnings. A cesarean section was performed based on the diagnosis of pregnancy-induced hypertension (PIH). The HbA1c ranged from 6.3% to 7.1% during pregnancy.
Clinical course of the right eye before and after delivery. Fundus photographs and macular 3 × 3-mm optical coherence tomography angiography (OCTA) images were obtained at 10 weeks of gestation (a–c), 37 weeks of gestation (d–f), and 6 weeks after delivery (g–i). The images in the second row (b, e, h) show the superfical vascular plexus, and those in the third row (c, f, i) show the deep capillary plexus centered on the fovea. Before delivery, microaneurysms (yellow circles) and small capillary nonperfusion (yellow arrows) are seen. There are no apparent differences between 10 weeks (b, c) and 37 weeks of gestation (e, f), except for slight enlargement of the foveal avascular zone (e, green arrow). After delivery, multiple flame-shaped retinal hemorrhages are seen (g), and OCTA shows new areas of decreased flow (blue arrows) in both plexuses (h, i).
Clinical course of the left eye before and after delivery. Fundus photographs and macular 3 × 3-mm optical coherence tomography angiography (OCTA) images obtained at 20 weeks of gestation (a–c), at 37 weeks of gestation (d–f), and 6 weeks after delivery (g–i). The images in the second row (b, e, h) show the superficial vascular plexus, and the images in the third row (c, f, i) show the deep capillary plexus centered on the fovea. As in the right eye, microaneurysms (yellow circles) and small capillary non-perfusion (yellow arrows) are observed before delivery; there are no apparent differences between 20 weeks (b, c) and 37 weeks of gestation (e, f). However, after delivery, multiple flame-shaped retinal hemorrhages and soft exudates are observed (g), and OCTA shows new areas of flow (blue arrows) in both plexuses (h, i).
Six weeks after delivery, the HbA1c level was stable (6.8%) but BP remained high at 160/97 mm Hg. Bilateral fundus observation revealed that flame-shaped retinal hemorrhages increased dramatically, and OCTA visualized that capillary nonperfusion also increased (Figure 1; Figure A). Eight weeks after delivery (BP 160/110 mm Hg), a gray, band-like opacity was seen in the right perifovea around the third branch of the retinal arterioles. OCTA showed a decreased flow signal from the arterial branch and flow voids around it in the superficial and deep slabs (Figure 2). FA also showed delayed filling of the arterial branch. However, 2 hours later, repeated OCTA showed perfusion of the arteriolar branch and nearby capillaries (Figure 2). Fifteen weeks after delivery (BP 150/100 mm Hg), increased retinal hemorrhages, dilated radial peripapillary capillaries (RPCs), and macular edema (ME) with some subretinal fluid were observed (Figure 3). Two weeks after starting antihypertensive medication (nifedipine 20 mg/day), BP returned to almost the normal level at 128/81 mm Hg, and the hemorrhages and dilatation of the RPCs decreased. The ME also decreased, and the subretinal fluid resolved without any ocular treatment (Figure 3).
Fundus images 8 weeks after delivery. (a) A fundus photograph shows a gray band-like retinal opacity (circle). (b–e) Fluorescein angiography images were obtained at 19 seconds (b, d) and 47 seconds (c, e) after injection. The rectangles in b and c are enlarged on d and e, respectively. The third branch of the arterioles (arrows) has delayed filling but is not occluded. (f–h) Optical coherence tomography angiography (OCTA) images in the superfical (f) and deep (g) plexuses show flow voids corresponding to the arterial branch (circles). A flow-overlaid B-scan (h) at the blue lines on en-face OCTA images (f, g) shows a hyperrefective band in the middle retina and decreased flow signal in the arterial branch (yellow arrows). (i–k) Repeated OCTA images 2 hours after the first scan show reperfusion of the arterial branch and nearby capillaries in both plexuses (i, j, yellow circles). A flow-overlaid B-scan (k) also shows increased flow signal in the arterial branch (yellow arrow).
The fundus images before (a–c) and after (d–e) starting antihypertensive therapy. (a) Before therapy (blood pressure [BP] 15 weeks after delivery, 150/100 mm Hg), marked flame-shaped hemorrhages and some hard exudates are seen. (b) A 9 × 9-mm optical coherence tomography angiography (OCTA) image of the full-thickness retina shows irregulary dilated radial peripapillary capillaries (RPCs). (c) A macular OCT map (upper row) shows macular edema, especially nasally; horizonal (middle row) and vertical (lower row) images show cystic changes in the outer nuclear layer and subretinal fuild under the fovea. (d). After hypertensive therapy (BP 17 weeks after delivery, 128/81 mm Hg), the hemorrhages are decreased. (e) OCTA also shows that some areas of dilation of the RPCs are decreased (yellow circles). (f) OCT images show that the cystic edema is decreased and the subretinal fluid has resolved.
Previous studies have reported that pregnancy itself, the duration of diabetes, the baseline level of retinopathy, the level of glycemic control, and hypertension are risk factors for worsening of DR during pregnancy.3,7–9 Other studies have shown that hypertensive disorders are more common in pregnant patients with diabetes than in pregnant patients without diabetes,10,11 and one of four women had hypertensive disorders during pregnancy.12 Another study reported that hypertension during pregnancy may have a greater effect on long-term DR levels than glycemic control because women who developed pre-eclampsia or PIH had a greater risk of developing DR that required laser photocoagulation after long-term follow-up.13
The current case had the previously mentioned cumulative risk factors (ie, long duration of T2DM and DR at conception). Moreover, noninvasive OCTA enabled visualization of capillary-level changes even before delivery (Figure 1) and showed that the patient already had some capillary dropout, despite the diagnosis of mild NPDR during a fundus examination. Consequently, the DR was markedly progressed, in particular, after delivery. Furthermore, during the perinatal period, the OCTA findings were helpful for determining the possible reason why the hypertensive state could accelerate exacerbation of the DR.
First, OCTA showed decreased flow signals from the arterial third branch and flow voids around it in the superficial and deep slabs in the parafoveal region and a hyperreflective band in the mid-retina on B-scan images (Figure 2). We estimated that these findings were a kind of paracentral acute middle maculopathy (PAMM), which presents with hyperreflective band-like lesions within the mid-retina on structural OCT; the causes of PAMM have been reported to be extrinsic, idiopathic, and various retinal vasculopathies including DR, hypertensive retinopathy, and retinal artery and vein occlusion.14,15 PAMM was observed previously during pregnancy,16 but in the current case, OCTA captured the onset of PAMM and the recovery phase (Figure 2). The PIH in the current patient was treatment-naïve at that point; thus, this short-term change might have been a spasm of the mid-sized arterial branch, similar to that in hypertensive retinopathy, and not temporal thrombotic occlusion, because the FA images showed that the artery was not occluded but had reduced perfusion (Figure 2).
Second, 2 weeks after the start of antihypertensive therapy without any ocular procedures, the flame-shaped retinal hemorrhages and dilation of the RPCs tended to decrease, and the ME also decreased as the BP mostly normalized (Figure 3). Because the autoregulation of the retinal blood flow is impaired in DR,17 elevated BP may augment the retinal blood flow resulting in capillary dilation and increased hydrostatic pressure resulting in tissue edema. These two representative events (ie, PAMM and ME) support the speculation that the persistent PIH after delivery could have exacerbated the DR during the perinatal period.
Because this is one case report, the retinal perfusion status should be analyzed prospectively before and after delivery in more pregnant patients, and physicians should be aware of systemic conditions such as PIH. Future OCTA studies will clarify the association between PIH and DR prognosis during pregnancy. In conclusion, OCTA is useful to closely follow DR during the perinatal period. PIH could be a risk factor for worsening of DR, especially in eyes with pre-existing DR before delivery.
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