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Intravitreal Implant
Options for Patients
With Diabetic Eye
Disease
The following articles discuss the use of the two intravitreal corticosteroids approved for
treatment of diabetic macular edema, as well as other indications.
Dexamethasone Intravitreal
Implant: Pharmacology and
Clinical Update
By Scott W. Cousins, MD
WATER SOLUBILITY
Triamcinolone is minimally water-soluble and becomes
a depot of crystals that release steroid, resulting in a long
half-life.5 Conversely, dexamethasone has two additional
hydroxyl groups in the acetonide functional group, making it significantly more hydrophilic compared with triamcinolone and fluocinolone.6 Water solubility has two
benefits: a shorter half-life, which makes it amenable as a
sustained-release medication by allowing controlled and
steady release6; and less aggregation onto ocular structures
such as the trabecular meshwork,7 which appears to result
in lower rates of intraocular pressure (IOP) elevation.
IOP CONSIDERATIONS
When using intravitreal corticosteroids in our practice, we
ensure that patients have a clear understanding of the risk
for cataract progression and possible ocular hypertension.
We find that patients are less concerned about cataract,
viewing cataract surgery as a matter of when rather than if.
Most patients are accepting of drops for ocular hypertension, but glaucoma surgery is always an undesirable course.
Among the various intravitreal steroid options, the dexamethasone intravitreal implant has a favorable IOP profile.
In the MEAD trial, incisional glaucoma surgery was
required in 0.6% of patients with DME treated with the
700-g dose of the dexamethasone intravitreal implant.1
By comparison, 33.8% of patients treated with the 0.59-mg
fluocinolone acetonide implant (Retisert, Bausch + Lomb),8
4.8% of patients treated with the 0.19-mg fluocinolone acetonide implant (Iluvien, Alimera Sciences),9 and 1.2% treated
with 4.0mg of intravitreal triamcinolone10,11 required incisional glaucoma surgery in the respective large clinical trials
evaluating these therapies in patients with DME.
As reflected in the MEAD study results, we find that
IOP elevation with the dexamethasone intravitreal
implant is mild and predictable. These elevations peak
at 6 to 8 weeks after injection and then return to close
to baseline by 3 or 4 months.1 In our practice, we have
not experienced the so-called staircase progressive IOP
elevation with repeated injections as is sometimes seen
with triamcinolone. IOP elevation with triamcinolone
Figure. The efficacy of the dexamethasone intravitreal implant for DME with poor response to anti-VEGF agents is
illustrated. The patients eye had previously undergone vitrectomy for nonclearing vitreous hemorrhage (A). DME was
treated with ranibizumab 0.3 mg (Lucentis, Genentech; A). There was a subtle response seen 5 weeks after injection (B).
The patient returned after 11 weeks with worsening intraretinal fluid (C). Aflibercept (Eylea, Regeneron) was administered.
There was minimal response seen after 6 weeks, and another aflibercept injection was used (D). There was worsening of
edema 8 weeks subsequently, and the patient was switched to the dexamethasone intravitreal implant (E). The edema
acutely resolved for the first time, seen 7 weeks after injection of the dexamethasone intravitreal implant (F). There was
mild intraretinal fluid on follow-up examination 8 weeks later, and aflibercept was administered (G). The edema worsened
8 weeks later, and it was decided to resume treatment with the dexamethasone intravitreal implant (H). The edema
resolved 8 weeks subsequently (I). The patient remains on the dexamethasone intravitreal implant every 3 to 4 months
on an as-needed basis, demonstrating excellent control of edema for more than a year.
ADVANTAGE OF A DRAWBACK
The dexamethasone intravitreal implant and the two
fluocinolone acetonide implants are all sustained-release
devices, but they differ in their durations of action. The
fluocinolone implants were designed to last for 3 years.
Significantly fewer injections are required, but, once the
implant is placed, the eye is committed to potentially
3 years of steroid exposure and accompanying IOP
complications. On the other hand, the dexamethasone
intravitreal implant, while initially designed to last for
6 months, usually provides clinically meaningful effects
for 3 to 4 months based on our experience with refractory edema. The drawback of requiring more injections
becomes an advantage when managing IOP issues,
because the steroid effects subside sooner.
CONCLUSION
The dexamethasone intravitreal implant is an efficacious steroid delivery system that provides sustained
release of a safe and potent steroid in a controlled and
56RETINA TODAYSEPTEMBER 2015
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8. Pearson PA, Comstock TL, Ip M, et al. Fluocinolone acetonide intravitreal implant for diabetic macular edema: a
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9. Campochiaro PA, Brown DM, Pearson A, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide
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month 24, 28% of patients treated with 0.19 mg fluocinolone acetonide achieved a 15-letter or greater improvement
in BCVA compared with 16% in the control group (P = .002).4
Center point retinal thickness measured on optical coherence tomography showed that patients in the fluocinolone
acetonide 0.19 mg group had a mean reduction of 167.7 m
at 1 week, and that this thickness reduction was sustained
through month 24.4
Safety
Safety was studied over 36 months in the FAME trials.
Adverse events (AEs) were consistent with other ocular
corticosteroids and were manageable in nature.4 The most
common AE was cataract, with 82% of patients in the
fluocinolone acetonide treatment group reporting cataract
compared with 50% in the control group. Cataract extraction was performed in 80% of these patients, compared with
27% of the control group. Increased IOP was reported in
20% of the fluocinolone acetonide patients compared with
4% in the control group; however, only 5% of patients experiencing increased IOP required incisional surgery. The study