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Off-label use of intravitreal triamcinolone acetonide for diabetic macular edema in a pregnant patient

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We present a case of diabetic macular edema in a pregnant patient treated with a single intravitreal injection of triamcinolone acetonomide. Initial presentation and serial examinations after treatment included visual acuity, slit-lamp examination, indirect ophthalmoscopy, and optical coherence tomography. Resolution of visual acuity and macular edema were present six weeks after injection and persisted throughout the duration of the pregnancy without further intervention. No adverse outcomes for either mother or fetus were noted. To our knowledge, this is the first report of intravitreal triamcinolone administration in this patient population to be published in the medical literature.
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CASE REPORT
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DOI: 10.2147/OPTH.S14584
Off-label use of intravitreal triamcinolone
acetonide for diabetic macular edema
in a pregnant patient
Ahad Fazelat
Kameran Lashkari
Schepens Eye Research Institute,
Harvard Medical School,
Boston, MA, USA
Correspondence: Ahad Fazelat
243 Charles Street, Boston,
MA 02114-3096, USA
Tel +1 617 573 4199
Fax +1 617 864 6437
Email ahad_fazelat@meei.harvard.edu
Abstract: We present a case of diabetic macular edema in a pregnant patient treated with a
single intravitreal injection of triamcinolone acetonomide. Initial presentation and serial exami-
nations after treatment included visual acuity, slit-lamp examination, indirect ophthalmoscopy,
and optical coherence tomography. Resolution of visual acuity and macular edema were present
six weeks after injection and persisted throughout the duration of the pregnancy without further
intervention. No adverse outcomes for either mother or fetus were noted. To our knowledge,
this is the first report of intravitreal triamcinolone administration in this patient population to
be published in the medical literature.
Keywords: triamcinolone, macular edema, diabetes, pregnancy
Case report
A pregnant 23-year-old female with a six-year history of Type 1 diabetes presented with
a complaint of increased “blur” in both eyes for the previous two months. Her most
recent hemoglobin A
1c
was measured at 6.4%. She was six months’ pregnant at initial
presentation. On examination her best corrected visual acuity was 20/40 OU. Slit-lamp
examination was entirely unremarkable in both eyes. Dilated funduscopic examination
was significant for flame-shaped, dot, and blot hemorrhages in the posterior segment,
with associated macular edema and exudates bilaterally (Figures 1A and 1B). No retinal
neovascularization was noted. Optical coherence tomography (OCT) revealed a foveal
thickness of 578 ± 5 microns and 667 ± 8 microns in the right and left eye, respectively
(Figures 2A and 2B). All OCT scans were performed with the Stratus
®
optical coher-
ence tomograph (Zeiss-Humphrey Inc, Dublin, CA).
Examination findings were consistent with bilateral, nonproliferative diabetic retin-
opathy and clinically significant macular edema. After careful deliberation with the patient
and her obstetrician, a decision was made to treat the bilateral macular edema with intra-
vitreal triamcinolone acetonide injection. The patient received 0.05 mL of triamcinolone
acetonide 40 mg/mL in the left eye initially and in the right eye one week later.
The patient returned for re-examination six weeks after treatment. Best-corrected
visual acuity was 20/20 and 20/25 in the right and left eye, respectively. Funduscopic
examination revealed marked reduction in macular edema bilaterally. Repeat OCT
revealed a foveal thickness of 159 ± 5 microns and 202 ± 6 microns in the right and
left eye, respectively (Figures 3A and 3B).
Four months after treatment, the patient’s visual acuity remained stable bilaterally.
Slit-lamp examination and Goldman applanation tonometry did not reveal any
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Fazelat and Lashkari
intraocular hypertension or significant lenticular changes
at this visit or at any point after triamcinolone injection.
Funduscopic examination revealed only mild retinal thicken-
ing in the left eye. The patient delivered a full-term, healthy
baby boy weeks prior to this examination. The patient
reported no complications in pregnancy or parturition.
Discussion
Progression of diabetic retinopathy during pregnancy has
been described previously by several authors.
1,2
Visual
impairment in these cases can result from both proliferative
(eg, vitreous hemorrhage, retinal detachment) and nonpro-
liferative etiologies (eg, retinal hemorrhage, papillopathy,
macular edema).
1
Although macular edema may regress in
some cases after delivery, in other cases edema can persist
and can be associated with severe and persistent visual
dysfunction.
1
Data from large, randomized clinical trials have estab-
lished the benefits of argon laser photocoagulation for clini-
cally significant macular edema.
3
Focal laser photocoagulation
of actively leaking blood vessels or grid laser for areas of
Figure 1 A) Color fundus photograph of the right eye. B) Color fundus photograph
of the left eye.
Figure 2 A) Optical coherence tomograph of macula at initial presentation, right eye.
B) Optical coherence tomograph of macula at initial presentation, left eye.
Figure 3 A) Optical coherence tomograph of macula at six weeks following
injection, right eye. B) Optical coherence tomograph of macula at six weeks
following injection, left eye.
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Triamcinolone for diabetic macular edema in pregnancy
diffuse permeability can decrease clinically significant edema.
However, laser photocoagulation in close proximity to the
fovea increases the risk of inducing iatrogenic central scotoma
as a result of thermal injury to the tissues, or subsequent glial
proliferation.
There are many reports of off-label use of intravitreal
triamcinolone in cases of persistent and refractory diabetic
macular edema.
4
Improved visual acuity and decreased
foveal thickness have been documented by serial OCT after
a single injection. However, these effects do not appear to
persist beyond 3–4 months without repeated administration.
5
A Medline search using keywords “pregnancy”, “pregnant”,
“clinically significant macular edema”, “gestational diabetes”,
and “triamcinolone acetonide” revealed no case reports or
case series documenting the treatment of clinically significant
macular edema with intravitreal corticosteroids in a pregnant
patient.
Side effects of systemic corticosteroid administration
are well known. Major ophthalmic complications of intra-
vitreal corticosteroid injection include, but are not limited
to, cataract formation and increased intraocular pressure.
Although corticosteroid equivalents can be measured in the
aqueous three months after a single intravitreal injection, it
is not known how much corticosteroid is released into the
systemic circulation after a single intravitreal injection.
6
Thus, it is hard to estimate the systemic effects of intravitreal
corticosteroid therapy.
To date, there are no reports of teratogenic outcomes
with systemic corticosteroid use in pregnant human females.
However, teratogenic effects have been observed in many
species receiving equivalent systemic human doses.
7
Many
authors have noted maxillofacial deformity and, in particular,
cleft palate in mice which have received corticosteroids early
in gestation.
Our patient presented with bilateral clinically significant
diabetic macular edema and diminishing vision. The area of
greatest thickening was within the fovea of both the right and
left eyes, with little edema observed in the extrafoveal area.
Laser photocoagulation to this area carried a significant risk
of inducing a permanent central scotoma. We consulted the
patient’s obstetrician about the possibility of initiating intra-
vitreal corticosteroid therapy. Given the patient’s late stage
of pregnancy, we felt that intravitreal steroid posed little risk
to either mother or fetus. We were able to achieve resolution
of macular edema and improved visual acuity with a single
intravitreal dose to each eye.
In conclusion, we propose that intravitreal triamcinolone
injection may be a viable treatment modality for management
of clinically significant macular edema in pregnant patients.
The safety profile with administration of this medication is
enhanced if the steroid is administered after the first trimester.
We suggest a multidisciplinary approach and consultation
with an obstetrician whenever using corticosteroid therapy
in pregnant patients.
Disclosure
The authors report no conflicts of interest in this work.
References
1. Sinclair SH, Nessler C, Foxman B, Nicholas CW, Gabbe S. Macular
edema and pregnancy in insulin-dependent diabetes. Am J Ophthalmol.
1984;97:154–167.
2. Moloney JB, Drury MI. The effect of pregnancy on the natural course
of diabetic retinopathy. Am J Ophthalmol. 1982;93:745–756.
3. Early Treatment Diabetic Retinopathy Study Research Group. Treatment
techniques and clinical guidelines for photocoagulation of diabetic
macular edema. Early Treatment Diabetic Retinopathy Study Report
Number 2. Ophthalmology. 1987;94:761–774.
4. Chieh JJ, Roth D, Liu M, et al. Intravitreal triamcinolone acetonide for
diabetic macular edema. Retina. 2005;25:828–834.
5. Diabetic Retinopathy Clinical Research Network. A randomized trial
comparing intravitreal triamcinolone acetonide and focal/grid photo-
coagulation for diabetic macular edema. Ophthalmology. 2008;115:
1447–1459.
6. Furukawa S, Usada K, Abe M, Ogawa I. Histopathological findings of
cleft palate in rat embryos induced by triamcinolone acetonide. J Vet
Med Sci. 2004;66:397–402.
7. Kenalog-40 injection [Package insert]. Princeton, NJ: Bristol-Myers
Squibb Company; 2007.
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Triamcinolone acetonide (TAC), a synthetic glucocorticoid, induces cleft palate resulting from poor development of palatal shelves in mice. However, TAC has no effect on medial edge epithelial cells (MEE cells) in secondary palatal shelves. In the present study, we examined the relationship between the pathogenesis of cleft palate and the effects on MEE cells and palatal mesenchymal cells in rat embryos/fetuses exposed to TAC. Pregnant Wistar Hannover rats were given TAC intramuscularly at 0.5 mg/kg at gestation days (Day) 12, 13, and 14, then embryos/fetuses were harvested on Days 14.5, 15, 16 and 20. The effects of TAC were as follows; an inhibition of palatal mesenchymal cell proliferation on Day 14.5, a decrease in the density of palatal mesenchymal cells and MEE cells, and expression of epidermal growth factor (EGF) receptors in MEE cells on Day 15, and stratified squamous differentiation of MEE cells with expression of cytokeratin and EGF receptors on Day 16. These findings indicated that TAC inhibited the proliferation of mesenchymal cells and affected the differentiation of MEE cells into stratified squamous epithelia in the palatal shelves of rat embryos. However, these stratified squamous MEE cells partially fused with each other. Thus, we suspected that a major contributing factor to the formation of TAC-induced cleft palate might not be the altered differentiation of MEE cells, but the inhibition of mesenchymal cell proliferation.
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Intravitreal injection of triamcinolone acetonide has been advocated to treat exudative diabetic macular edema. The purpose of the study was to evaluate the clinical outcome of an intravitreal injection of triamcinolone acetonide as treatment for diffuse diabetic macular edema. This study was a retrospective, interventional, clinical case series examining 210 eyes of 174 patients who received an intravitreal injection of 1 or 4 mg of triamcinolone acetonide for treatment of diffuse diabetic macular edema. Inclusion criteria were clinically significant macular edema, visual acuity loss, and leakage shown by fluorescein angiography. Main outcome measures were visual acuity and intraocular pressure. Mean follow-up time +/- SD was 6.6 +/- 3.1 months. In the study group, visual acuity improved significantly (P < 0.001) from a median of 20/200 (mean logMAR, 0.92) at baseline to 20/80 (mean logMAR, 0.82) at 6 months. Mean intraocular pressure +/- SD increased from 15.4 +/- 3.4 mmHg (median, 16 mmHg; range, 6-26 mmHg) to a maximal value of 20.4 +/- 6.2 mmHg (median, 19 mmHg; range, 12-51 mmHg) during the follow-up period. Complications included culture-negative sterile endophthalmitis in six cases and cataract extraction in five eyes. Intravitreal injection of 1 to 4 mg of triamcinolone acetonide may benefit patients by improving visual acuity in eyes with clinically significant diabetic macular edema. This study did not provide significant evidence to justify its routine use in clinical practice for all patients with diabetic macular edema. A randomized clinical trial on this issue would provide more conclusive evidence and help identify those patients most likely to benefit from intravitreal triamcinolone acetonide.
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Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008;115: 1447-1459.