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Pranita Sahay
MBBS
EvolvingTrend of Drug
Delivery System in Uveitis
Pranita Sahay MBBS, Devesh Kumawat MBBS,
Koushik Tripathy MD, DNB, Vijay Kumar Sharma MS
Dr. Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences, New Delhi
Uveitis is an umbrella term that includes any
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tissue. It may be anterior, intermediate, posterior or
panuveitis. Intermediate, posterior uveitis, and panuveitis
are the most sight threatening types of uveitis. If no
infectious microbe is implicated in the disease process
then it is said to be idiopathic and treatment is aimed at
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of uveitis is corticosteroids which can be administered in
various forms- oral, intravenous, topical drops, periocular
injection, intravitreal injection or intraocular implants.
Immunosuppressive agents and immunomodulators are the
other class of drugs used in the management of idiopathic
uveitis. Long term use of systemic corticosteroids and
immunomodulators have high risk of systemic adverse
effects and topical medication have poor penetration to the
posterior segment of eye. This has lead to a new era of
invention of sustained drug delivery system1
.
Retisert®
Introduced by Bausch and Lomb (Rochester, NY, USA)
in 1951, it is a non biodegradable, sustained release
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been FDA-approved (Food and Drug Administration, USA)
for chronic macular edema due to chronic non infectious
posterior uveitis2
. Retisert is about the size of a grain of
rice and consists of a tablet encased in a silicone elastomer
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(PVA) membrane positioned between the tablet and the
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a PVA suture strut with silicone adhesive. It is implanted
into the vitreous cavity by par plana incision and then
suturing. The drug is delivered at initial rate of 0.6 μg/day,
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0.3 to 0.4 μg/day with no drug peaks and troughs, and it
lasts for approximately 1,000 days (30 months). During
clinical trials it has shown to decrease the recurrence of
episode from 54 % to 7% and 40% to 14% in two different
trials and also either stabilisation or an increase in visual
acuity in 80% patients was noted. The common ocular
adverse effects with Retisert are raised intraocular pressure
and cataract. MUST trial (Multicenter Uveitis Steroid
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glaucoma and 3.3 times increased cataract surgery rate3
.
Rare but the most dreaded one being endophthalmitis.
Another major disadvantage with Retisert is that it can’t be
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Iluvien®
Iluvien® (formerlyMedidurFA,AlimeraSciences,Alpharetta,
GA, USA) is a non biodegradable intravitreal implant of
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polyimide tube, 3.5mm in length and 0.37mm in diameter.
Unlike Retisert however, Iluvien® is injected into the eye
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with a 25-gauge needle, which allows a self sealing wound.
Figure 1: Retisert

2. 68 l DOS Times - Vol. 20, No. 3 September, 2014
Evolution: Evolving Trend of Drug Delivery System in Uveitis
The method of administration is similar to an intravitreal
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acetonide (FAc) inserts may cause fewer problems with
glaucoma than the surgically implanted device because
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(0.2 and 0.5μg/day for at 24-36 months and 18 months
respectively) and also because of a more posterior location
in the eye, which may decrease exposure to the trabecular
meshwork in the anterior chamber while still delivering
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(Figure 2). Three year results of FAME study (Fluocinolone
Acetonide Implant Compared to Sham Injection in Patients
With Diabetic Macular Edema) showed that by 36 months,
80-90% patients in FAc groups required cataract surgery
versus 27.3% of phakic controls. Approximately 20%
of patients in FAc groups experienced an intraocular
pressure (IOP) more than 30 mm Hg at any point in the
study compared to 4.3% of sham control patients; 5-8%
of patients in FAc groups required IOP-lowering surgery
compared to 0.5% for controls, respectively4
.
Surodex®
Surodex produced by Allergan(Allergan, Irvine, CA,
USA) is a rod-shaped biodegradable matrix implant of
dexamethasone and poly lactideco- glycolide acid (PLGA)
with hydroxypropyl methylcellulose (HPMC). It is 1.0×0.5
mm in size and has a drug release rate of 60 μg over 7–10
days. It is implanted into the anterior chamber following
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.
Ozurdex®
Ozurdex is produced by Allergan, Irvine, CA, USA is
also called Posurdex during trials. It is a biodegradable
intravitreal implant of dexamethasone 0.7 mg. The
Novadur™ drug delivery system containing poly (D, L-
lactide-co-glycolide) without preservative, degrades slowly
to lactic acid and glycolic acid. It has a preloaded single-
use specially designed applicator to facilitate the injection
of a rod-shaped implant directly into the vitreous cavity.
It is delivered via surgical sclerotomy or 22-gauge needle-
injector system. Its effect lasts for 6 months. Its adverse
effect being raised intraocular pressure which peaks at
around 60 days. Patients in whom the posterior capsule
of the lens is absent or has a tear are at risk of implant
migration into the anterior chamber. It is currently FDA
approved for central and branch retinal vein occlusion,
non infectious uveitis affecting the posterior segment and
diabetic macular oedema. HURON study is evaluating its
role in macular edema in posterior Uveitis (Figure 3).
Vitrasert
It is produced by Bausch and Lomb (Rochester, NY,
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device approved by the FDA in 1996 for treatment of
cytomegalovirus (CMV) retinitis. Human viruses sensitive
to ganciclovir include cytomegalovirus (CMV), herpes
Figure 2: Iluvein
Figure 3: 2]XUGH[

3. www. dosonline.org l 69
Uvea
simplex virus-1 and -2 (HSV- 1, HSV- 2), Epstein - Barr
virus (EBV) and varicella zoster virus (VZV). The device is
composed of drug and polymeric coats of polyvinyl alcohol
(PVA) and ethylenevinyl acetate (EVA). PVA is a permeable
polymer that regulates the rate of ganciclovir release and
EVA is an impermeable polymer that limits the surface
area of the device through which the active agent can be
released. Each implant contains around 4.5 mg to 6.4mg of
ganciclovir. It releases the drug at mean rate of 1.4μg/day
and a mean vitreous concentration of 4.1μg/ml is achieved.
The device has shown to have no initial burst effect.
The commercially available device is relatively large;
it requires a 4–5mm sclerotomy at the pars plana for
implantation. It releases the drug for 5 to 8 months. Since
it is nonbiodegradable the drug-depleted device needs to
be removed during a second procedure in order to implant
another device if required (Figure 4).
Iontophoresis
It uses electrical current to facilitate delivery of medication
or ions into the tissue for therapeutic purposes based on the
physical principle that like charges repel each other. Eye
gate (Optis Group, Paris, France) and OcuPhor (IOMED,
Salt Lake City) are two ophthalmic iontophoresis systems
under investigation. EGP-437 (dexamethasone phosphate
formulated for iontophoresis) is being evaluated for non-
infectious anterior uveitis (Figure 5).
Contact Lens
Contact lenses can absorb drugs and release over a period
of time. Silicon-hydrogel contact lens loaded with vitamin E
has been shown to increase dexamethasone release period
from 1 day to 7 - 9 days6
.
Nanoparticles
They have the ability to penetrate tissue better, resulting
in more controlled release of drug over longer duration.
Figure 4: Vitrasert
Tamoxifen-loaded nanoparticles injected intravitreally
have been shown to be effective in treating experimental
autoimmune uveitis (EAU) models whereas non-
encapsulated tamoxifen had no effect7
. Betamethasone-
encapsulated particles have successfully treated
experimental autoimmune uveoretinitis models8
.
However further reasearch is warranted to discover newer
avenues of treating uveitis.
References
1. Nahid Haghjou, Masoud Soheilian, Mohammad Jafar Abdekhodaie,
Sustained Release Intraocular Drug Delivery Devices for Treatment
of Uveitis. Journal of ophthalmic and vision research 2011;4: 317-
29.
2. Jaffe GJ, Martin D, Callanan D. Fluocinolone acetonide implant
(Retisert) for non-infectious posterior uveitis. Ophthalmology
2006;113:1020-27.
3. Kempen JH, Altaweel MM, Holbrook JT. Randomized comparison
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acetonide implant for intermediate, posterior, and panuveitis: the
multicenter uveitis steroid treatment trial [MUST]. Ophthalmology
2011;10:1916–26.
#PVQU[M #0 (#/' +PXGUVKICVQTU 'HſECE[ CPF 5CHGV[ QH +.78+'0
4
(Fluocinolone Acetonide [FAc] Intravitreal Insert) for the Treatment
of Diabetic Macular Edema. ARVO Meet Abstr 2011;52:6645.
.GG 5; %JGG 52 5WTQFGZ CHVGT RJCEQGOWNUKſECVKQP , %CVCTCEV
Refract Surg 2005;31:1479–80.
6. Kim, J, Peng CC, Chauhan A. Extended release of dexamethasone
from silicone-hydrogel contact lenses containing vitamin E. J Control
Rel. 2010; 148:110-16.
7. De Kozak Y, Andrieux K, Villarroya H. Intraocular injection of
tamoxifen-loaded nanoparticles:A new treatment of experimental
autoimmune uveoretinitis. Eur J Immunol. 2004; 34:3702-12
8. Sakai T, Kohno H, Ishihara T, et al. Treatment of experimental
autoimmune uveoretinitis with poly(lactic acid) nanoparticles
encapsulating betamethasone phosphate. Exp Eye Res. 2006;
82:657-63.
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over the sclera under the lower eyelid