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Effect of dexamethasone
intravitreal implant in a corneal graft rejection
Nilufer Yesilirmak1, Evin Singar Ozdemir2,
Dilek D. Altinors3
1Department
of Cornea, Bascom Palmer Eye Institute, University of Miami Miller School of
Medicine, Miami, Florida 33136, USA
2Ankara
Training and Research Hospital, Ankara 06340, Turkey
3Baskent
University Hospital, Ankara 06490, Turkey
Correspondence
to:
Nilufer Yesilirmak.
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900
NW 17 St., Miami, Florida 33136, USA.
nxy28@med.miami.edu
Received:
2015-02-10
Accepted: 2015-06-16
DOI:10.18240/ijo.2016.03.28
Citation: Yesilirmak N, Ozdemir ES, Altinors DD. Effect of dexamethasone intravitreal implant in a
corneal graft rejection. Int J Ophthalmol
2016;9(3):475-477
Dear Sir,
I am Dr. Nilufer Yesilirmak, from the Department of
Cornea, Bascom Palmer Eye Institute, Miami, Florida, USA. We wrote to report a reduction of graft rejection
with dexamethasone intravitreal implant (Ozurdex®)
in a case with aphakia.
Ozurdex® (Allergan Inc., Irvine, CA, USA)
is an intravitreal implant containing a biodegradable material combined with
the active drug dexamethasone. It is a small rod-shaped, 0.46 mm in diameter
and 6 mm in length. Inside the eye, it provides sustained delivery of 0.7 mg of
preservative-free dexamethasone to the vitreous cavity and retina for up to
180d[1]. This implant is
proved to be effective in the treatment of macular edema following branch or
central retinal vein occlusions, posterior non-infectious uveitis, diabetic
macular edema, pseudophakic macular edema and neovascular age-related macular
degeneration [2].
Herein we report a different usage of Ozurdex®
implant for 51-year-old female diagnosed with corneal graft rejection in her
right eye. The patient had been followed at our clinic with chronic visual loss
in her right eye for 4y and undergone a penetrating keratoplasty 4y ago due to
a fungal keratitis scar. Simultaneously a cataract extraction had been
performed without implanting an intraocular lens. The outside surgeon probably
decided to implant it on another occasion after making sure that the cornea
survived. Because of the rejection, the patient had undergone her second
keratoplasty 2y ago. After the second keratoplasty her best-corrected visual acuity
(BCVA) was 0.5, however during the follow-up period, her vision decreased again
due to an epiretinal membrane and she underwent a pars plana vitrectomy.
On her last examination, the BCVA was 0.1 and
intraocular pressure (IOP) was 15 mm Hg, in the right eye. The anterior segment showed 1+
cells, 1+ flare and fine Khodadoust line which was considered as a rejection
(Figure 1A). The posterior segment was normal. Topical steroids were given 4
times a day and subtenon corticosteroid injections were applied twice a month
for 3mo. She responded well to each steroid injection, however,
because of frequent injections, her eyelids were bruised and became edematous
as well as her conjunctiva (Figure 1B). In order to reduce the number of
injections, an Ozurdex® implantation was performed through the superior
temporal quadrant of right eye, approximately 3- to 5-mm posterior to the
limbus (through the pars plana). After first week of implantation, the
Ozurdex® implant migrated into the anterior chamber (AC) and
wandered between the AC and vitreous cavity with head movements of the patient
without any corneal touch (Figure 2A). Therefore, patient was advised not to
lean forward too much and she learnt to keep the implant inside the eye by
adjusting her body movements. At 4wk post-implantation, the BCVA was 0.2, IOP
was 15 mm Hg and rejection regressed significantly (Figure 2B). At
8wk post-implantation, the BCVA was still 0.2, IOP was 18
mm Hg, cornea was clearer and the eye (conjunctiva and
eyelids as well) was quiescent with the implant in the vitreous cavity. On her last visit, at 11wk post-implantation, the BCVA was 0.1, IOP was 12 mm
Hg,
cornea was not clear and the implant was not seen in the vitreous cavity or AC.
At almost 3mo time, the implant was absorbed and the rejection seemed to be
started again.
Figure 1 Anterior
segment and external eye photography A:
The
appearance of
patient’s cornea upon arrival which showed 1+ cells, 1+ flare, pearl like
infiltrates (Arrow: Khodadoust line), corneal edema; B: Lid swelling and tissue damage related to multiple
steroid injections.
Figure 2 Anterior segment photography A: The appearance of the Ozurdex® implant in
the anterior chamber;
B: Regressed pearl like lesions, flare, cells and
diminished corneal edema can be seen.
Penetrating
keratoplasty is usually a successful surgical procedure but some factors may
cause graft rejection. According to literature immunologic rejection is one of
the most common causes for graft failure[3].
Guilbert et al[4]
observed
that lens status influenced the risk of rejection as well. Besides, severe
allograft rejection episodes results in endothelial cell density decrease that
leads to a lower reversibility rate[5].
Our case had both aphakia and rejection episodes that might have
increased the endothelial failure.
Corticosteroids
are usually strongest tools to reverse graft rejection usually. Even though our
case received intensive topical and subtenon corticosteroid therapy, rejection
progressed.
Due to the fact that the combination of subconjunctival and topical
corticosteroids was reported[6] as more effective in
reversing rejection than treatment with a single pulse of methylprednisolone
(500 mg) in combination with the topical corticosteroids, we decided to use Ozurdex® due to its long
lasting effect. Besides the patient could not tolerate immunomodulator
therapies. One week after the implantation, the implant dissolved and passed to
anterior chamber easily due to the aphakic and vitrectomized eye. At the following
examination, the rejection was significantly regressed. In contrast this,
according to literature there are some studies showing the Ozurdex®
implant migration to the anterior chamber in aphakic eyes, which resulted with
corneal decompensation due to the direct contact of the implant to the
endothelium[7-9].
Even, Marín-Lambíes et al[10] considered that the
implant of these devices in aphakic patients should be contraindicated.
Chang-Lin
et al[11] showed the concentration of dexamethasone in the vitreous
and retina raised to high levels within 60d of implantation, extending the
therapeutic period to 6mo and Myung et al[12] showed the duration of its effect was approximately 3-4mo. It has been mentioned that, in vitrectomized eyes
the half-life of drugs after intravitreal injection reduces and the drug
clearance increases from the vitreous[13].
Resembling to afore mentioned study, the Ozurdex® reached
its maximum effect within 2mo and instead of 6mo, it completely dissolved within 3mo, in our case.
In
long-term usage of corticosteroids, adverse effects such as glaucoma and
cataract may appear. It is reported that Ozurdex® can cause lower
incidence of IOP elevation requiring surgery and cataract extraction than the
other intravitreal corticosteroids[14].
In this study, we did not observe any long-term adverse effect associated with
the implantation. The patient did not complain of eyelid swelling as
seen in the photo before subtenon steroid injections. Therefore, this swollen
eyelid appearance was attributed to our repeated steroid injections. Due to Ozurdex® could provide higher and stable
corticosteroid levels without obvious adverse effects we might consider a
second implantation since the rejection started to be occurred again after the
implant dissolution.
In
conclusion, dexamethasone intravitreal implantation is
a minimally invasive treatment modality that might be an effective treatment
option in anterior segment inflammations, especially in aphakic and
vitrectomized eyes. Although there are no cases of dexamethasone intravitreal
implantation for corneal graft rejection in aphakic and vitrectomized eyes in the literature, this case
report provides an insight for future long-term studies. Future comparative
clinical studies with a large sample size and long-term follow-up will able to
provide better results and guidelines.
ACKNOWLEDGEMENTS
Conflicts
of Interest: Yesilirmak N, None; Ozdemir
ES, None; Altinors DD,
None.
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