Download Diabetic Macular Edema Treatment Options in Pregnancy

Diabetic Macular Edema
Treatment Options in Pregnancy
Dilraj S. Grewal, MD
Duke University Department of Ophthalmology
2351 Erwin Road, Box 3802, Durham, North Carolina, USA 27710
*Address for Correspondence
Dilraj Grewal, MD
Duke Eye Center,
2351 Erwin Rd, Box 3802
Durham, NC 27710 USA
Tel: +1 919 684-3316; fax: +1 919 681 6474
[email protected]
Word Count: 1155
Case Report
A 32-year-old female with an 18-year history of type 1 diabetes presented with
decreased vision in both eyes at the beginning of her third trimester (24 weeks
gestation) of her first pregnancy. Her BMI was 31.6 kg/m 2 and she had poor glycemic
control with the hemoglobin A1c two weeks prior being 8.0 but there was no history of
pre-ecclampsia. The pregnancy had been initiated without prior endocrinology
consultation.
Her vision was 20/80 in the right eye and 20/30 in the left. She was pseudophakic in
both eyes having undergone surgery for congenital cataracts several years ago. She
had moderate non-proliferative diabetic retinopathy (NPDR) right>left eye. Her last
dilated fundus examination was 3 years prior, which showed absence of diabetic
retinopathy. OCT revealed cystic intraretinal fluid (IRF) involving the fovea and subfoveal
subretinal fluid (SRF) (Figure 1A) in the right eye and IRF in the left eye. Her central
subfield thickness (CFT) was 561 microns in the right and 380 microns in the left.
Treatment options including anti-vascular endothelial growth factor (VEGF) agents,
intravitreal steroids and intravitreal dexamethasone slow-release implant (Ozurdex) were
discussed with the patient. After a detailed discussion of the risks and benefits, she
elected for observation.
At her next follow-up at 29-weeks gestation her insulin pump had been adjusted
following which her HbA1c improved to 7. There was improvement in her diabetic
macular edema (DME) with CFT improving to 390 microns and vision to 20/40 in the
right eye. OCT showed improvement in both SRF and IRF (Figure 1 B). At 36 weeks
gestation there was mild worsening of DME and reduction in vision to 20/50. Treatment
options were discussed again but she elected for continued observation as she was
expecting to deliver in 4 weeks.
Four weeks later she delivered a healthy girl weighing 3500g without complications.
Repeat examination 3 months following delivery showed an increase in DME (Figure 1C)
with worsening IRF and recurrent SRF in the right eye. Her vision had worsened to
20/70 and at this time she opted for an Ozurdex injection. Two months following the
dexamethasone intravitreal implant the IRF and SRF had resolved (Figure 1D). CFT
reduced to 281 microns and visual acuity improved to 20/20.
She presented 3 months later with a decrease in vision to 20/60. OCT revealed recurrent
foveal cystic IRF and a sliver of SRF (Figure 1 E), IOP was stable at 20mmHg. She was
breastfeeding her daughter and opted for a repeat Ozurdex. She responded well with
resolution of fluid and improvement in vision to 20/20. She developed a moderate steroid
response to 28mmHg following her second Ozurdex which was controlled with timolol
drops.
There has been no DME recurrence at 6 months follow-up since her last Ozurdex
injection. Her A1c four months post partum was 7.5. The DME in her left eye had
resolved spontaneously.
Discussion:
This case raises questions on the management of DME during pregnancy and lactation.
During pregnancy, diabetic retinopathy may progress to levels that would require
treatment, according to criteria commonly used in non-pregnant patients. 1,2 Concerns
about potential fetal side effects and paucity of documented experience make the
application of specific VEGF inhibition problematic in pregnant women and VEGF
inhibition is associated with theoretical risks for the fetus. Case reports of diabetic
retinopathy flaring up during pregnancy and waning after delivery suggests that
observation may be an option in some cases. 3
DME involving the center of the fovea (Early Treatment Diabetic Retinopathy Study
[ETDRS] grid center field thickness >350 μm) can occur during pregnancy. Clinical
management of DME presenting during pregnancy is generally guided by the experience
that it is often reversible. This led us to consider first conservative management and then
local pharmacotherapy with Ozurdex to reduce the immediate burden of visual loss and
improve the long-term visual prognosis. 4
The course of DME in pregnancy is poorly described. The question often debated is
whether DME during pregnancy can be left untreated because it has a tendency to
resolve after delivery. 5 A transient bout of DME usually does not cause permanent
reduction of visual acuity, but patients with a history of poor metabolic control are more
susceptible to problems persisting after delivery. The relationship between absolute
retinal thickness, cystoid edema, and visual acuity is not straightforward in DME.
Progression of diabetic retinopathy during pregnancy can be dramatic, but is
occasionally reversible.5 Onset or worsening of DME during pregnancy may be related to
rapidly tightening metabolic control especially in women who have been in poor
metabolic control prior to conception. 6 7
Although observation is certainly a reasonable option for pregnancy related DME, given
the worsening edema and declining visual acuity, the potential for improvement of vision
and protection against permanent damage to the fovea without the side effects of
photocoagulation arguably has better prognosis for long-term preservation of vision than
no treatment. Corticosteroids bind to cytoplasmic receptors that translocate to the
nucleus and cause transcriptional repression of a large number of genes whose
products participate in the inflammatory, vascular leakage, and angiogenesis cascades
involved in DME.
The dexamethasone implant been shown to reduce DME in clinical studies that excluded
pregnant patients and there are no independent controlled studies with Ozurdex in
pregnant women.8 Animal reproduction studies using topical ocular administration of
dexamethasone conducted in mice and rabbits have shown it to be relatively safe. 9
Although systemically administered corticosteroids are present in human milk and can
suppress growth and interfere with endogenous corticosteroid production, the systemic
concentration of dexamethasone following intravitreal treatment is very low. It is very
unlikely that Ozurdex could result in sufficient systemic absorption to produce detectable
quantities in human milk.9
Ozurdex can be used to treat patients who had symptomatic visual loss and foveal
thickening of a magnitude that would make patients eligible for intravitreal therapy in
routine clinical practice. Concillado et al demonstrated prompt and uniform reduction in
DME following intravitreal dexamethasone implant in 5 patients during pregnancy.4 SubTenon or intravitreal injection of triamcinolone acetonide was not considered in their
study because the efficacy of Ozurdex is arguably superior. 10 We assumed that the
duration and longevity of Ozurdex (3–6 months) was likely to cover the gestation period
from time of diagnosis of DME to delivery without any need for supplementary treatment.
Focal laser photocoagulation can be considered in such cases but carries its potentially
destructive effects.11 Subthreshold micropulse diode laser photocoagulation is another
potential option that can be considered in such cases. 12
The dexamethasone implant was chosen because systemic exposure is very small and
because glucocorticoid medication is accepted in pregnancy for a broad range of
imperative clinical indications. 13,14 The major risks to the mother are endophthalmitis,
cataract, and intraocular pressure rise, similar to non-pregnant patients.
While a controlled clinical trial of Ozurdex for the treatment of DME in pregnancy and
post partum is desirable to help guide clinical practice, such a trial is difficult to organize.
In conclusion Ozurdex is a viable option for management of DME in pregnancy and
while nursing.
Figure 1.
Serial Transfoveal optical coherence tomography enhanced depth of imaging scans
showing mild foveal cystic intraretinal fluid (IRF) at presentation (A) with a central
subfoveal thickness of 390 microns, and 20/80 vision. She was observed during the
pregnancy with mild improvement five weeks later (B). Four weeks following delivery she
presented with worsening IRF and new SRF and vision decreased to 20/70 (C). She
received her first Ozurdex injection, 8 weeks following which there was complete
resolution of IRF and SRF and improvement in vision to 20/20 (D). She developed
recurrent IRF and SRF 3 months later with reduction in vision to 20/60 (E) for which she
received a second Ozurdex injection with excellent response, complete resolution of fluid
and improvement in vision to 20/20 (F).
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