0795 Dexamethasone Ophthalmic Implants (Ozurdex and Dextenza) · 9/17/2019 · B. Non-infectious...
Transcript of 0795 Dexamethasone Ophthalmic Implants (Ozurdex and Dextenza) · 9/17/2019 · B. Non-infectious...
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Dexamethasone Ophthalmic Implants (Ozurdex and Dextenza)
Clinical Policy Bulletins Medical Clinical Policy Bulletins
Policy History Last
Review
09/17/2019
Effective: 02/05/201
Next Review:
08/27/2020
Review History
Definitions
Additional Information
Number: 0795
Policy *Please see amendment for Pennsylvania Medicaid at the end of this CPB.
I. Aetna considers Ozurdex (dexamethasone intravitreal implant) medically
necessary for the treatment of the following indications:
A. Macular edema secondary to branch or central retinal vein occlusion
B. Non-infectious uveitis affecting the posterior segment of the eye (e.g.,
pars planitis)
C. Diabetic macular edema (DME).
II. Aetna considers Ozurdex (dexamethasone intravitreal implant) therapy not
medically necessary for members with the following contraindications:
A. Ocular or periocular infections (viral, bacterial, or fungal)
B. Advanced glaucoma
C. Aphakic eyes with rupture of the posterior lens capsule
D. ACIOL (anterior chamber intraocular lens) and rupture of the posterior
lens capsule.
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III. Aetna considers Ozurdex experimental and investigational for the
treatment of the following indications (not an all-inclusive list) because of
insufficient evidence of its effectiveness for these indications:
A. Acute zonal occult outer retinopathy (AZOOR)
B. Coats' disease
C. Cystoid macular edema (CME) associated with retinitis pigmentosa,
sympathetic ophthalmia or syphilis-related uveitis
D. Macular edema secondary to acute retinal necrosis, idiopathic retinal
vasculitis, aneurysms, neuroretinitis (IRVAN) syndrome, or tuberculosis
uveitis
E. Non-arteritic anterior ischemic optic neuropathy
F. Proliferative vitreoretinopathy
G. Pseudophakic macular edema (Irvine-Gass syndrome) except for
pseudophakic persons with DME
H. Radiation maculopathy
I. Reducing the risk of conjunctivitis from cytarabine
J. Vasoproliferative tumor
IV. Aetna considers combined cataract surgery and Ozurdex experimental and
investigational for the treatment of cataract and macular edema because of
insufficient evidence of the effectiveness of this approach.
V. Aetna considers combined intravitreal anti-vascular endothelial growth
factor (VEGF) and Ozurdex experimental and investigational for the
treatment of diabetic macular edema, and punctate inner choroidopathy
because of insufficient evidence of the effectiveness of this approach.
VI. Ozurdex is contraindicated and considered unproven in individuals with
advanced glaucoma and ocular or periocular infections.
VII. Aetna considers Dextenza (dexamethasone ophthalmic insert) medically
necessary for the treatment of ocular pain following ophthalmic surgery
(i.e., cataract surgery).
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VIII. Aetna considers Dextenza experimental and investigational for all other
indications (e.g., allergic conjunctivitis) (not an all-inclusive list) because of
insufficient evidence of the effectiveness of this approach.
See also
CPB 0719 - Fluocinolone Acetonide Intra-Vitreal Implant (Retisert and Iluvien)
(0719.html)
Background
Ozurdex (dexamethasone intravitreal implant) is an intravitreal implant containing
0.7 mg (700 μg) dexamethasone in the Novadur solid polymer drug delivery
system. Ozurdex is preloaded into a single‐use, specially designed DDS applicator
to facilitate injection of the rod‐shaped implant directly into the vitreous of the eye.
Dexamethasone, a potent corticosteroid, has been shown to suppress inflammation
by inhibiting multiple inflammatory cytokines resulting in decreased edema, fibrin
deposition, capillary leakage and migration of inflammatory cells.
Ozurdex contains a corticosteroid (dexamethasone), and has been approved by the
U.S. Food and Drug Administration (FDA) for the treatment of macular edema
following branch retinal vein occlusion (BRVO) or central retinal vein occlusion
(CRVO). Ozurdex (dexamethasone) is also indicated for non‐infectious uveitis
affecting the posterior segment of the eye and for the treatment of diabetic macular
edema.
Retinal Vein Occlusion
Retinal vein occlusion is a blockage of a portion of the venous circulation that
drains the retina and is second only to diabetic retinopathy as the most common
retinal vascular cause of visual loss. It generally does not occur until later in life
and may have several causes, including: hypertension, atherosclerosis, diabetes,
and glaucoma. When a blockage occurs, pressure builds up in the capillaries
causing hemorrhages and leakage of fluid and blood. This can lead to macular
edema (ME) and ischemia of the macula. There are 2 basic types of retinal vein
occlusion: central retinal vein occlusion (CRVO) and branch retinal vein occlusion
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(BRVO). Central retinal vein occlusion is obstruction of the retinal vein at the optic
nerve and BRVO is obstruction of a portion of the venous circulation that drains the
retina.
Central retinal vein occlusion (CRVO) is a common retinal vascular disorder. The
exact etiology is unknown, however may be caused by arteriosclerotic changes in
the central retinal artery or from a thrombotic occlusion of the central retinal vein.
Occlusion of the central retinal vein leads to backup of the blood in the retinal
venous system and increases resistance to the venous blood flow. This increased
resistance causes stagnation of the blood and ischemia to the retina. Ischemic
damage to the retina stimulates increase production of vascular endothelial growth
factor (VEGF), and increased levels of VEGF stimulate neovascularization of the
posterior and anterior segment of the eye.
Central vein occlusion can also be further categorized as either ischemic or non-
ischemic. Ischemic CRVO is the more severe form and presents with severe visual
loss, extensive retinal hemorrhages, and cotton‐wool spots. Poor perfusion of the
retinal and patients may end up with neovascular glaucoma and painful blind eye.
Nonischemic CRVO is the milder form of the disease and presents with good
vision, few retinal hemorrhages and cotton‐wool spots, and good perfusion to the
retina. This type may resolve fully with good visual outcome or may progress to the
ischemic type. Most individuals with ischemic CRVO develop the complications of
ME that ultimately lead to blindness. The non-ischemic type maintains better blood
flow to the retina through collateral circulation, thus, preventing the dreaded
complications of the ischemic type.
In branched retinal vein occlusion (BRVO) the blockage occurs in a smaller branch
of the vessels that connect to the central retinal vein. Branch retinal vein occlusion
occurs 3 times more often than CRVO and may include both systemic factors (e.g.,
hypertension) as well as local anatomic factors (e.g., arterio-venous
crossings). Both types of retinal vein occlusion can lead to macular edema or
growth of fragile new blood vessels.
While there are similarities in the pathogenesis and clinical nature of both forms of
retinal vein occlusion, each has unique etiologies, differential diagnosis,
management and prognosis. Central retinal vein occlusion is difficult to treat. No
known effective treatment is available for either the prevention or treatment of
CRVO. Pan-retinal photocoagulation (PRP) has been used in the treatment of
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neovascular complications of CRVO, however, no definite guidelines exist
regarding the exact indication and timing of PRP. Other treatments with varying
degrees of success include: aspirin, anti-inflammatory agents, isovolemic
hemodilution, plasmapheresis, systemic anti-coagulation, fibrinolytic agents,
systemic corticosteroids, local anti-coagulation with intravitreal injection of
alteplase, intravitreal injection of triamcinolone, and intravitreal injection of
bevacizumab.
Mohamed et al (2007) assessed the evidence for the effectiveness of interventions
to improve visual acuity (VA) and prevent or treat neovascularization secondary to
CRVO. Randomized controlled trials (RCTs) of more than 3 months' follow-up
comparing intervention with a control group were included for review. The authors
reviewed 17 RCTs that met their inclusion criteria. They evaluated 4 RCTs on laser
photocoagulation and reported that grid macular laser photocoagulation did not
improve VA in CRVO with ME. Prophylactic PRP did not prevent angle and iris
neovascularization in ischemic CRVO, but resulted in regression of angle and iris
neovascularization and reduced progression to neovascular glaucoma. Four RCTs
reported improvement in VA with in-patient hemodilution, 2 RCTs demonstrated no
significant improvement, and 1 RCT showed deterioration in VA after out-patient
hemodilution. Randomized clinical trials evaluating ticlodipine, troxerutin, and
streptokinase showed limited or no benefit. The authors concluded that (i) there is
limited le vel I evidence for any intervention to improve VA in patients with
CRVO, (ii) PRP resulted in regression of neovascularization, and ( iii)
hemodilution may improve vision in some patients, but data a re conflicting.
The authors stated in their conclusion that more robust RCTs evaluating current
treatments for CRVO are needed.
A Cochrane systematic review on the use of intravitreal steroids versus observation
for CRVO-ME (Gewaily and Greenberg, 2009) found no relevant RCTs and
concluded that "[t]here is inadequate evidence for the use of intravitreal steroids for
CRVO-ME due to a paucity of RCTs and well-designed observational studies on
the topic; therefore, it is still an experimental procedure."
The Standard Care versus Corticosteroid for Retinal Vein Occlusion (SCORE)
study, a phase III clinical trial conducted at 84 clinical sites and supported by the
National Eye Institute (NEI) at the National Institutes of Health (NIH), included
participants with CRVO (n = 271) and BRVO (n = 411) in 2 separate trials. The
SCORE study reported that intravitreal injections of a corticosteroid medication
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could reduce vision loss due to CRVO-ME and that treated patients were also 5
times more likely to regain vision after 1 year than patients who were under
observation. The study compared intravitreal triamcinolone (1 mg and 4 mg doses)
versus observation for eyes with vision loss associated with CRVO-ME. Of those
participants in the observation, 1 mg, and 4 mg groups, 7 %, 27 %, and 26 %
achieved the primary outcome measure of a gain in VA letter score of 15 or more
from baseline to month 12, respectively. The odds of achieving the primary
outcome were 5.0 times greater in the 1 mg group than the observation group
(odds ratio [OR], 5.0; 95 % confidence interval [CI]: 1.8 to 14.1; p = 0.001) and 5.0
times greater in the 4 mg group than the observation group (OR, 5.0; 95 % CI: 1.8
to 14.4; p = 0.001); there was no difference identified between the 1 mg and 4 mg
groups (OR, 1.0; 95 % CI: 0.5 to 2.1; p = 0.97). The rates of elevated intra-ocular
pressure and cataract were similar for the observation and 1 mg groups, but higher
in the 4 mg group. The authors concluded that intra-vitreal triamcinolone is
superior to observation for treating vision loss associated with CRVO-ME in
patients who have characteristics similar to those in the SCORE-CRVO trial. The
1-mg dose has a safety profile superior to that of the 4-mg dose. The authors
concluded that intra-vitreal triamcinolone in a 1-mg dose, following the re-treatment
criteria applied in the SCORE study should be considered for up to 1 year, and
possibly 2 years, for patients with characteristics similar to those in the SCORE-
CRVO trial (Ip et al, 2009).
In general, BRVO has a good prognosis. Between 50 to 60 % of patients report a
final VA of 20/40 or better without treatment. Thus, comparative studies are
necessary to determine whether improvements in VA are a result of the procedure
or simply the natural course of the condition. Laser photocoagulation, as
demonstrated by the Branch Vein Occlusion Study (BVOS; Scott et al, 2009), is the
gold standard for the treatment of ME and ocular neovascularization following
BRVO. However, the limited functional outcomes achievable by means of laser
treatment have prompted researchers to try alternative options.
McIntosh et al (2007) assessed the evidence for the effectiveness of interventions
to improve VA and to treat neovascularization secondary to BRVO and/or BRVO-
ME. Randomized clinical trials with more than 3 months' follow-up were included
for review. The authors reviewed 12 RCTs that met their inclusion criteria. The
authors evaluated 5 RCTs on laser photocoagulation and reported that grid macular
laser photocoagulation was effective in improving VA in 1 large multi-center RCT
(the BVOS study, Scott et al, 2009), but 2 smaller RCTs found no significant
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difference. The BVOS study found that scatter retinal laser photocoagulation was
effective in preventing neovascularization and vitreous hemorrhage in patients with
neovascularization, but a subsequent RCT found no significant effect. Randomized
clinical trials evaluating intravitreal steroids (n = 2), hemodilution (n = 3), ticlopidine
(n = 1), and troxerutin (n = 1) showed limited or no benefit. The authors concluded
that (i) there is limited le vel I evidence for any interventions for BRVO, (ii) the
BVOS study showed t hat macular grid l aser photocoagulation is an effective
treatment for ME a nd imp roved v ision in eyes with VA of 20/40 to 20/200, and
(iii) scatter laser photocoagulation can effectively treat neovascularization. The
authors concluded that the effectiveness of many new treatments is not supported
by current evidence.
The SCORE-BRVO trial evaluated the use of 2 different dosages of intravitreal
triamcinolone for treating vision loss from BRVO-ME and reported that laser
treatment is safer than corticosteroid injections and is equally effective. The study
compared intravitreal triamcinolone (1-mg and 4-mg doses) with standard of care
(i.e., grid photocoagulation in eyes without dense macular hemorrhage and deferral
of photocoagulation until hemorrhage clears in eyes with dense macular
hemorrhage) for eyes with vision loss associated with BRVO-ME (n = 411). Of
those participants in the standard care, 1-mg, and 4-mg groups, 29 %, 26 %, and
27 % achieved the primary outcome measure of a gain in VA letter score of 15 or
more from baseline to month 12, respectively. None of the pair-wise comparisons
between the 3 groups was statistically significant at month 12. The rates of
elevated intraocular pressure and cataract were similar for the standard care and 1
mg groups, but higher in the 4 mg group. The authors found no difference in VA at
12 months for the standard care group compared with the triamcinolone groups;
however, rates of adverse events (particularly elevated intra-ocular pressure and
cataract) were highest in the 4 mg group. The authors concluded that
photocoagulation as applied in the SCORE study remains the standard of care for
patients with vision loss associated with BRVO-ME who have characteristics similar
to participants in the SCORE-BRVO trial and that grid photocoagulation should
remain the benchmark against which other treatments are compared in clinical trials
for eyes with vision loss associated with BRVO-ME (Scott et al, 2009).
Several processes have been implicated in the breakdown of the blood-retinal
barrier that leads to ME, including the production of inflammatory mediators (e.g.,
prostaglandins and interleukin-6), increased amounts of vascular permeability
factors (e.g., vascular endothelial growth factor) and the loss of endothelial tight
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junction proteins. Corticosteroids are thought to have beneficial effects on these
processes, but delivering therapeutic concentrations of any medication to the retina
while limiting systemic exposure presents a challenge. Intra-vitreal injections of the
corticosteroid triamcinolone have shown promise in the treatment of ME.
Dexamethasone, a more potent corticosteroid than triamcinolone, has been shown
to produce high intra-vitreal levels of the drug, however, a short intra-ocular half-life
after intra-vitreal injection (approximately 3 hours) has led to the investigation of
other delivery methods.
Ozurdex (dexamethasone intra-vitreal implant) (Allergan, Irvine, CA) was approved
by the U.S. Food and Drug Administration (FDA) in June 2009 for the treatment of
ME associated with CRVO or BRVO. The rod-shaped biodegradable intra-vitreal
implant contains 0.7 mg of dexamethasone and is injected directly into the eye
(vitreous) through a small pars plana incision or puncture. A solid polymer drug
delivery system called Novadur (Allergan, Irvine, CA) gradually releases
dexamathasone for up to 6 months. Biodegradable polymers release the drug as
they themselves degrade and are finally absorbed within the body.
The FDA's approval of Ozurdex was based on results from 2 randomized, double-
masked, multi-center clinical studies (n = 853). The studies demonstrated a
statistically significant improvement in 3 or more lines of VA in approximately
20 to 30 % of treated patients within 60 days post-implantation compared to sham.
The duration of improvement continued for approximately 30 to 90 days and was
effective in both CRVO and BRVO. The most significant adverse effect was an
increase in intra-ocular pressure that occurred in 106 patients (25 %), which
peaked at 60 days and returned to baseline levels by day 180. Three patients (0.7
%) required laser or surgical procedures as a result. Conjunctival hemorrhage
occurred in 85 patients (20 %). Ozurdex is the first FDA-approved therapy for ME
related to retinal vein occlusion. The proposed benefit of a sustained-release intra-
vitreal corticosteroid insert such as Ozurdex is the potential for fewer injections.
Intra-vitreal injections have been associated with endophthalmitis, eye
inflammation, increased intra-ocular pressure, and retinal detachments.
According to the prescribing information, Ozurdex is for ophthalmic intravitreal
injection. The intravitreal injection procedure should be carried out under controlled
aseptic conditions. Following the intravitreal injection, patients should be monitored
for elevation in intraocular pressure and for endophthalmitis.
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According to the prescribing information, Ozurdex is contraindicated in patients with
active or suspected ocular or peri-ocular infections including most viral diseases of
the cornea and conjunctiva, including active epithelial herpes simplex keratitis
(dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal
diseases. Furthermore, Ozurdex is also contraindicated in individuals with
advanced glaucoma.
Intravitreal corticosteroid injection‐related effects have been associated with
endophthalmitis, eye inflammation, increased intraocular pressure, and retinal
detachments. Patients should be monitored regularly following the injection.
Ozurdex (dexamethasone intravitreal implant) should not be utilized in patients with
a hypersensitivity to dexamethasone or any components of the product. The safety
and effectiveness of Ozurdex in pediatric patients has not been established.
Diabetic Macular Edema
Treatment options currently available for the treatment of diabetic macular edema
include photocoagulation (laser therapy), intravitreal corticosteroids and intravitreal
anti‐vascular endothelial growth factor agents (VEGF).
In June 2014, Ozurdex sustained-release, biodegradable dexamethasone
intravitreal implant 0.7 mg was approved by the FDA for adult patients with diabetic
macular edema who have artificial lens implants or are scheduled for cataract
surgery (Allergan, 2014). The approval was based on the Macular Edema:
Assessment of Implantable Dexamethasone in Diabetes (MEAD) trial, which
included 2 multi-center, 3-year, sham-controlled, masked, randomized clinical
studies of patients with 15 or more letters improvement in best corrected visual
acuity (BCVA) from baseline. The sustained-release biodegradable steroid
implant uses a solid polymer to suppress the inflammation that causes diabetic
macular edema (DME) by releasing the steroid over an extended period, without
the need for monthly steroid injections. In September 2014, the FDA approved
expanded indications for Ozurdex for the treatment of the general population of
patients with DME, based on ongoing review of clinical data demonstrating efficacy
and safety.
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The Ozurdex implant uses a biodegradable polymer implant that releases
dexamethasone over an extended period of time to suppress inflammation, which
plays a key role in the development of DME (Allergan, 2014). The most common
adverse events in the studies of Ozurdex for DME included cataracts and elevated
intraocular pressure. An increase in mean intra-ocular pressure (IOP) was seen
with each treatment cycle; mean pressure generally returned to baseline between
treatment cycles. The labeling states that Ozurdex should not be used in persons
with glaucoma.
Injections into the vitreous in the eye, including those with Ozurdex, are associated
with endophthalmitis, eye inflammation, increased IOP, and retinal detachments
(Allergan, 2014). Use of corticosteroids may produce posterior subcapsular
cataracts, increased IOP, glaucoma, and may increase the establishment of
secondary eye infections due to bacteria, fungi, or viruses. The labeling for
Ozurdex states that it should not be used in patients that have any infections or
diseases in the eye, or surrounding eye area, including most viral diseases of the
cornea and conjunctiva, including active herpes viral infection of the eye, vaccinia,
varicella, mycobacterial infections, and fungal diseases
Other adverse effects among patients with DME included conjunctival blood spot,
reduced vision, conjunctival swelling and/or inflammation, floaters, dry eye, vitreous
detachment, vitreous opacities, retinal aneurysm, foreign body sensation, corneal
erosion, inflammation of the cornea, anterior chamber inflammation, retinal tear,
drooping eyelid, and high blood pressure (Allergan, 2014).
Boyer et al (2013) reported on the results of 2 RCTs to evaluate the safety and
efficacy of Ozurdex dexamethasone intravitreal implant (DEX) 0.7 and 0.35 mg in
the treatment of patients with DME. Two randomized, multi-center, masked, sham-
controlled, phase III clinical trials with identical protocols were conducted. Data
were pooled for analysis. Study subjects were 1,048 patients with DME, BCVA of
20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of greater
than or equal to 300 μm by optical coherence tomography (OCT). Patients were
randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX
implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for
patients treated at month 36) at less than or equal to 40 scheduled visits. Patients
who met re-treatment eligibility criteria could be re-treated no more often than every
6 months. The pre-defined primary efficacy end-point was achievement of greater
than or equal to 15-letter improvement in BCVA from baseline at study end. Safety
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measures included adverse events and IOP. Mean number of treatments received
over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg,
and sham, respectively. The percentage of patients with greater than or equal
to 15-letter improvement in BCVA from baseline at study end was greater with DEX
implant 0.7 mg (22.2 %) and DEX implant 0.35 mg (18.4 %) than sham (12.0 %; p ≤
0.018). Mean average reduction in CRT from baseline was greater with DEX
implant 0.7 mg (-111.6 μm) and DEX implant 0.35 mg (-107.9 μm) than sham (-41.9
μm; p < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9
%, 64.1 %, and 20.4 % in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham
groups, respectively. Increases in IOP were usually controlled with medication or
no therapy; 2 patients (0.6 %) in the DEX implant 0.7 mg group and 1 (0.3 %) in the
DEX implant 0.35 mg group required trabeculectomy. The investigators concluded
that the DEX implant 0.7 mg and 0.35 mg met the primary efficacy end-point for
improvement in BCVA. The investigators stated that the safety profile was
acceptable and consistent with previous reports.
In a randomized, controlled, multi-center, double-masked, parallel-group, 12-month
trial, Callanan et al (2013) evaluated Ozurdex (dexamethasone intravitreal implant
[DEX implant]) 0.7 mg combined with laser photocoagulation compared with laser
alone for treatment of diffuse DME. A total of 253 patients with retinal thickening
and impaired vision resulting from diffuse DME in at least 1 eye (the study eye)
were enrolled. Patients were randomized to treatment in the study eye with DEX
implant at baseline plus laser at month 1 (combination treatment; n = 126) or sham
implant at baseline and laser at month 1 (laser alone; n = 127) and could receive up
to 3 additional laser treatments and 1 additional DEX implant or sham treatment as
needed. The primary efficacy variable was the percentage of patients who had a 10-
letter or more improvement in BCVA from baseline at month 12. Other key efficacy
variables included the change in BCVA from baseline and the area of vessel
leakage evaluated with fluorescein angiography. Safety variables included adverse
events and IOP. The percentage of patients who gained 10 letters or more in BCVA
at month 12 did not differ between treatment groups, but the percentage of patients
was significantly greater in the combination group at month 1 (p < 0.001) and month
9 (p = 0.007). In patients with angiographically verified diffuse DME, the mean
improvement in BCVA was significantly greater with DEX implant plus laser treatment
than with laser treatment alone (up to 7.9 versus 2.3 letters) at all time- points through
month 9 (p ≤ 0. 013). Decreases in the area of diffuse vascular leakage measured
angiographically were significantly larger with DEX implant plus laser treatment
through month 12 (p ≤ 0. 041). Increased IOP was more common
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with combination treatment. No surgeries for elevated IOP were required. The
authors concluded that there was no significant between-group difference at month
12. However, significantly greater improvement in BCVA, as demonstrated by
changes from baseline at various time points up to 9 months and across time based
on the area under the curve analysis, occurred in patients with diffuse DME treated
with DEX implant plus laser than in patients treated with laser alone.
Pacella et al (2013) evaluated the safety and effectiveness of Ozurdex in patients
with persistent DME over a 6-month follow-up period. A total of 17 patients (20
eyes) affected by DME were selected. The mean age was 67 + 8 years, and the
mean duration of DME was 46.3 + 18.6 months. The eligibility criteria were: age
greater than or equal to 18, a BCVA between 5 and 40 letters, and macular edema
with a thickness of greater than or equal to 275 μm; 13 patients had also previously
been treated with anti-vascular endothelial growth factor (VEGF) medication. The
mean ETDRS (Early Treatment Diabetic Retinopathy Study) value went from 18.80
+ 11.06 (T0) to 26.15 + 11.03 (p = 0.04), 28.15 + 10.29 (p = 0.0087), 25.95 + 10.74
(p = 0.045), 21.25 + 11.46 (p = 0.5) in month 1, 3, 4, and 6, respectively. The mean
logMAR (logarithm of the minimum angle of resolution) value went from 0.67 + 0.23
(at T0) to 0.525 + 0.190 (p = 0.03), 0.53 + 0.20 (p = 0.034), and 0.56 + 0.22 (p =
0.12) in month 1, 3, and 4, respectively, to finally reach 0.67 + 0.23 in month 6.
The mean central macular thickness (CMT) value improved from 518.80 + 224.75
μm (at T0) to 412.75 + 176.23 μm, 292.0 + 140.8 μm (p < 0.0001), and 346.95 +
135.70 (p = 0.0018) on day 3 and in month 1 and 3, respectively, to then increase
to 476.55 + 163.14 μm (p = 0.45) and 494.25 + 182.70 μm (p = 0.67) in month 4
and 6. The authors concluded that Ozurdex produced significant improvements in
BCVA and CMT from the third day of implant in DME sufferers, and this
improvement was sustained until the third month.
In a retrospective, interventional case-series study, Rishi et al (2013) evaluated the
safety and effectiveness of Ozurdex in patients with recalcitrant DME. Inclusion
criteria comprised patients presenting with recalcitrant DME, 3 or more months after
1 or more treatments of macular laser photocoagulation and/or intra-vitreal anti-
VEGF injections. Exclusion criteria included history of corticosteroid-responsive
IOP rise, cataract extraction, or other intra-ocular surgery within 3 months. The
main outcome measure was VA at 1 and 4 months after Ozurdex injection.
Secondary outcome measures included change in CMT on OCT and changes in
IOP following Ozurdex implant. Of 18 eyes (17 patients) with recalcitrant DME that
underwent Ozurdex implant, 3 eyes (2 patients) had follow-up of more than 3
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months post-injection. Mean age of patients was 56 years. Mean duration of
diabetes mellitus was 16.6 years. Systemic control of diabetes mellitus was good
as assessed by FBS/PPBS and HbA1c. The pre-operative mean CMT was 744.3
μm and improved to 144 and 570 μm at months 1 and 4, respectively. Pre-
operative mean BCVA was 0.6 logMAR units and improved to 0.3 and 0.46 logMAR
units at month 1 and 4, respectively. The mean follow-up was 4.3 months (range of
4 to 5 months). The authors concluded that Ozurdex appears effective in
management of recalcitrant DME. Moreover, they stated that the results of the
ongoing POSURDEX study will elaborate these effects better.
Non-Infectious Uveitis
Uveitis is inflammation of the uvea, the middle layer of the eye that consists of the
iris, ciliary body and choroid. Uveitis can have many causes, including eye injury,
inflammatory diseases or exposure to toxins. Uveitis is classified by location of
inflammation within the uvea: anterior uveitis refers to inflammation of the iris alone
(iritis) or the iris and ciliary body. Intermediate uveitis refers to inflammation of the
ciliary body. Posterior uveitis is inflammation of the choroid. Diffuse uveitis or
panuveitis is inflammation in all areas of the uvea.
In a review on new developments in corticosteroid therapy for uveitis, Taylor et al
(2010) stated that corticosteroids remain the mainstay of the management of
patients with uveitis. Topical corticosteroids are effective in the control of anterior
uveitis, but vary in strength, ocular penetration and side effect profile. Systemic
corticosteroids are widely used for the management of posterior segment
inflammation that requires treatment, particularly when it is associated with
systemic disease or when bilateral ocular disease is present. However, when
ocular inflammation is unilateral, or is active in 1 eye only, local therapy has
considerable advantages, and peri-ocular injections of corticosteroid are a useful
alternative to systemic medication and are very effective in controlling mild or
moderate intra-ocular inflammation. More recently, the injection of intra-ocular
corticosteroids such as triamcinolone have been found to be effective in reducing
ME and improving vision in uveitic eyes that have proved refractory to systemic or
peri-ocular corticosteroids. The effect is usually transient, lasting around 3 months,
but can be repeated although the side effects of cataract and raised intra-ocular
pressure are increased in frequency with intra-ocular versus peri-ocular
corticosteroid injections. This has led to the development of new intra-ocular
corticosteroid devices, which are designed to deliver sustained-release drugs and
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obviate the need for systemic immuno-suppressive treatment. The first such
implant was Retisert, which is surgically implanted (in the operating theater) and is
designed to release fluocinolone over a period of about 30 months. More recently,
Ozurdex, a "bioerodible" dexamethasone implant, which can be inserted in an office
setting, has completed phase III clinical trials in patients with intermediate and
posterior uveitis. This implant lasts approximately 6 months, and has been found to
be effective with a much better side effect profile than Retisert or intra-vitreal
triamcinolone injection, at least for 1 injection.
Williams et al (2009) evaluated the effects of a dexamethasone intravitreous drug
delivery system (dexamethasone DDS) in a randomized, prospective, single-
masked, controlled trial of patients with persistent (90 days or more) ME from
uveitis or Irvine-Gass syndrome (n = 41). Patients were randomized to surgical
placement of 0.35 mg or 0.7 mg dexamethasone DDS or observation. At day 90,
the primary outcome measure of a 10-letter or more BCVA improvement was
achieved in the 0.35 mg group, 0.7 mg group, and the observation group (p = 0.029
versus the 0.7 mg group) in 41.7 % (5/12), 53.8 % (7/13) and 14.3 % (2/14) of
patients, respectively. Improvement in VA persisted to day 180. A 15-letter or
more improvement was achieved in 53.8 % (7/13) of 0.7 mg patients versus 7.1 %
(1/14) of observed patients (p = 0.008). There were significantly greater reductions
in fluorescein leakage in treated patients than in observed patients.
Dexamethasone DDS was well- tolerated. Throughout the study, an increase in
intra-ocular pressure of 10 mm Hg or more was observed in 5 of 13 patients in the
0.7 mg group, in 1 of 12 patients in the 0.35 mg group, and in no patients in the
observation group. There were no reports of endophthalmitis. The authors
concluded that dexamethasone DDS may be a promising new treatment option for
patients with persistent ME resulting from uveitis or Irvine-Gass syndrome,
however, further investigation of its clinical value in this patient population is
warranted.
In September 2010, Allergan received FDA approval of its supplemental new drug
application of Ozurdex for the treatment of non-infectious uveitis affecting the
posterior segment of the eye. The approval was based on the findings of a single,
multi-center, masked, randomized study of 153 patients with non-infectious uveitis
affecting the posterior segment of the eye. After a single injection, the percent of
patients reaching a vitreous haze score of 0 (where a score of 0 represents no
inflammation) was statistically significantly greater for patients receiving Ozurdex
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versus sham at week 8 (primary time-point) (47 % versus 12 %). The percent of
patients achieving a 3-line improvement from baseline BCVA was 43 % for patients
receiving Ozurdex versus 7 % for sham at week 8.
Pars planitis, also called peripheral uveitis or intermediate uveitis) is a relatively
common ocular inflammatory condition. The major clinical findings are localized to
the vitreous and posterior pole. The hallmark of the disorder is the presence of
preretinal exudates over the inferior pars plana, referred to as snow banks.
"Therapy consists of oral or intra/periocular injected glucocorticoids. External
cryotherapy has also been used directly on the snowbanks. If these modalities fail,
systemic immunosuppression,
including methotrexate, azathioprine, cyclophosphamide, and cyclosporine, has
been used in some cases. Severe disease can often benefit from surgery to extract
a cataract and/or to remove vitreous debris" (Tolentino and Dana, 2019).
Coats' Disease
Martínez-Castillo et al (2012) reported a case of Coats' disease managed with
Ozurdex combined with retinal photocoagulation. A 46-year old female with 20/200
VA was diagnosed with Coats' disease with secondary retinal vaso-proliferative
tumor. An initial approach was performed with an intra-vitreal injection of the
sustained-release dexamethasone implant Ozurdex. After re-attachment of the
retina, the telangiectatic vessels were treated with laser photocoagulation. The
patient's VA improved to 20/25 after the intra-vitreal Ozurdex. No further
recurrences of exudation were evident through the 12-month follow-up. The
authors concluded that Ozurdex may be an effective initial therapeutic approach for
Coats' disease with immediate anatomical response and visual improvement. The
results of this case study need to be validated by well-designed studies.
IRVAN Syndrome
Empeslidis et al (2013) presented the short-term favorable clinical results with
Ozurdex in a patient with florid idiopathic retinal vasculitis, aneurysms, and
neuroretinitis (IRVAN) syndrome. The patient was a 26-year old man with
significant bilateral deterioration of vision due to vitreous hemorrhage and
neuroretinitis with a background of vasculitis and neovascularization. The patient
was initially treated with high doses of oral steroids (80 mg prednisolone), which
were gradually tapered, and also received extensive argon laser photocoagulation
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in ischemic areas in both eyes. Despite vigorous treatment and an initial positive
response to treatment, pars plana vitrectomy was eventually needed to address the
recurrent vitreous hemorrhages in the left eye. Consequently, VA improved from
0.1 to 0.2 (Snellen) and there was no relapse of vitreous hemorrhage. Persistent
ME was noted, however, and it was decided to treat with a dexamethasone 0.7 mg
intravitreal implant. Following the dexamethasone implant OS, VA improved
significantly from 0.2 to 0.5 (Snellen), the patient reported much less distortion, and
there was marked reduction in central retinal thickness from 467 to 234 microns.
The patient remained in remission without any exudation in the macula at 4 months
follow-up. The authors concluded that dexamethasone 0.7 mg intravitreal implant
appeared to be a safe and effective method in the treatment of ME in patients with
IRVAN syndrome and could possibly be a treatment option for other cases of
inflammatory induced ME.
Cystoid Macular Edema associated with Retinitis Pigmentosa
Saatci et al (2013) reported the effectiveness of Ozurdex in a patient with retinitis
pigmentosa (RP) and bilateral cystoid ME unresponsive to topical carbonic
anhydrase inhibitors. A 36-year old man with bilateral cystoid ME associated with
RP that was unresponsive to topical carbonic anhydrase inhibitors underwent
bilateral 0.7-mg Ozurdex 2 weeks apart. Spectral domain optical coherence
tomography revealed resolution of ME 1 week following each injection in both eyes
and his VA improved. However, ME recurred 2 months later in OS (left eye) and 3
months later in OD (right eye). Second implant was considered for both eyes. No
implant-related complication was experienced during the follow-up of 7 months.
The authors concluded that inflammatory process seems to play a role in RP.
Intravitreal dexamethasone implant may offer retina specialists a therapeutic option
especially in cases unresponsive to other treatment regimens in eyes with RP-
related ME.
Srour et al (2013) evaluated the anatomical and functional outcomes of Ozurdex in
patients with ME secondary to RP. A total of 3 patients (4 eyes), aged 24 to 46
years, presented with refractory ME secondary to RP were included in this study.
Ozurdex was administered to treat ME. The anatomical (CMT) and functional
(BCVA) outcomes as well as adverse events were recorded. All patients completed
6 months follow-up. After Ozurdex therapy, all patients showed regression of ME.
At baseline, mean CMT was 443 ± 185 μm (range of 213 to 619 μm); ME improved
to 234 ± 68 μm (range of 142 to 307 μm) at 1 month, to 332 ± 177 μm (range of 139
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to 513 μm) at 3 months, and to 305 ± 124 μm (range of 144 to 447 μm) at 6
months. Recurrent ME was recorded in 2 patients (both patients at 3 months from
Ozurdex therapy). Re-treatment with intravitreal Ozurdex was performed in 2
patients. Mean BCVA improved form 20/160 (range of 20/50 to 20/200) (baseline)
to 20/100 (range of 20/40 to 20/125) at 1 month, to approximately 20/125 (range of
20/100 to 20/200) at 3 months, and to approximately 20/125 (range of 20/100 to
20/160) at 6 months. No serious ocular and systemic adverse events were
observed during the study period. The authors concluded that Ozurdex provided
anatomic and functional improvements and may represent a valuable treatment
option for patients with ME secondary to RP. These preliminary findings need to be
validated by well-designed studies.
In a pilot study, Sudhalkar and colleagues (2017) determined the utility of the
intravitreal dexamethasone implant as therapy for cystoid macular edema (CME)
secondary to retinitis pigmentosa (RP) recalcitrant to carbonic anhydrase inhibitor
therapy over 2 years. This was a prospective, case-series study. Patients who
showed either an incomplete or no response to topical dorzolamide for at least 1
month and oral acetazolamide therapy for at least 15 days were recruited for the
study with informed consent. A complete anterior and posterior segment
examination was performed including fundus fluorescein angiography (FFA), OCT
scan and electroretinogram (ERG) to confirm the diagnosis. The dexamethasone
implant was injected using a standardized technique. Follow-ups were scheduled
on days 1, 7, and 30 and then monthly thereafter for 2 years. The primary outcome
measure was the change in corrected distance VA (CDVA) and central subfield
thickness (CST) at months 1, 6, 12, 18, and 24. The secondary outcome measure
was complications, if any. Appropriate statistical analysis was done. A total of 5
patients (2 men; 6 eyes; median age of 49 years) were recruited for the study. All
patients required at least 2 injections over 2 years. All patients demonstrated
significant improvement in CDVA (p = 0.004) as well as CST measurements (p = 0.0038)
over 2 years. No complications were noted. The authors concluded that
intravitreal dexamethasone implant provided significant improvement in CDVA and
CST measurements in patients with recalcitrant CME secondary to RP. This was a
small study (n = 5); its findings need to be validated by well-designed studies.
Furthermore, an UpToDate review on “Retinitis pigmentosa: Treatment” (Garg,
2017) states that “Cystoid macular edema can reduce central vision in later stages
of RP. The most successful treatment thus far is the oral carbonic anhydrase
inhibitor, acetazolamide. Acetazolamide increases fluid absorption across the
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retinal pigment epithelium. In the absence of macular edema, carbonic anhydrase
inhibitors do not improve vision or alter the course of electroretinography (ERG)
degradation in patients with RP”. It does not mention dexamethasone intravitreal
implant as a therapeutic option.
Cataract and MacularEdema
Sze and colleagues (2015) examined the safety and effectiveness of intra-vitreal
dexamethasone implant in patients with cataract and ME undergoing
phacoemulsification and intra-ocular lens (IOL) implantation. A total of 24 eyes with
ME secondary to DME and RVO were retrospectively reviewed. These eyes
underwent phacoemulsification with IOL implantation and intra-vitreal
dexamethasone implant 0.7 mg at the same setting between September 2012 and
September 2013. Demographic data, BCVA, CMT, (IOP, surgical time, and
complications were recorded. Twelve eyes had DME and 12 eyes had RVO (10
central RVO and 2 branch RVO). Median baseline logMAR BCVA was 1.0 (Snellen
20/200) and mean baseline CMT was 530.2 ± 218.9 µm. Median follow-up duration
was 13 months. At last follow-up, median VA improved significantly to 0.523
(Snellen 20/66) (p = 0.003) and CMT decreased to 300.7 ± 78.1 µm (p = 0.000).
Median surgical time was 23 minutes. There were no intra-operative complications.
In 12 eyes, ME recurred, requiring further treatment, and median time to
recurrences was 21 weeks. One eye had raised IOP after second dexamethasone
implant for recurrent ME. No major complication such as vitreous hemorrhage,
retinal detachment, or endophthalmitis occurred. The authors concluded that
combined cataract surgery with intra-vitreal dexamethasone implant appeared to be
safe and effective in treating patients with cataract and ME in this small case series.
Moreover, they stated that a larger prospective study with longer follow-up is
needed to demonstrate the long-term benefit of this combined procedure.
Post-Lensectomy-Vitrectomy Aphakia
Bansal et al (2012) reported the behavior of intra-vitreal Ozurdex implant in eyes
with post-lensectomy-vitrectomy (PLV) aphakia. These researchers carried out a
retrospective chart review of 3 eyes with PLV aphakia (3 patients with uveitis) who
received intravitreal injection of Ozurdex for cystoid macular edema (1 eye),
persistent inflammation (1 eye), and ocular hypotony (1 eye). Final outcome was
assessed in terms of effectiveness, stability, and tolerance of the implant.
Following implantation of the Ozurdex, an initial improvement was seen in all 3
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eyes. However, the implant migrated into the anterior chamber (AC) at 1 week in 2
eyes and at 5 weeks in 1 eye, and wandered between the AC and vitreous cavity
with changing postures of the patient. Two eyes developed corneal edema, of
which 1 eye underwent implant removal from the AC. The authors concluded that
Ozurdex implant should be contraindicated in eyes with PLV aphakia to avoid its
deleterious effect on the corneal endothelium.
Non-Arteritic Anterior Ischemic Optic Neuropathy
Alten and associates (2014) evaluated structural and functional outcomes of intra-
vitreal dexamethasone implant (IDI) in 3 patients presenting with non-arteritic
anterior ischemic optic neuropathy. Intra-vitreal dexamethasone implant was
administered once in 3 patients. Best-corrected visual acuity, perimetry, volume
spectral-domain OCT scan of the optic disc (ODV), retinal nerve fiber layer (RNFL)
scan and visually evoked potential (VEP) measurements were assessed at
baseline and after 1 and 3 months. Mean BCVA was 20/100 in patient 1 (patient 2:
20/100; patient 3: 20/50) at baseline, 20/60 (patient 2: 20/400) at 1 month and
20/80 (20/400; 20/60) at 3 months. Mean deviation in perimetry developed from
-4.90 dB (-22.09 dB; -8.68 dB) to -7.60 dB (-30.75 dB) and -14.23 dB (-30.59 dB;
-7.17 dB); ODV and RNFL decreased during follow-up; VEP measurements
showed a reduction in amplitudes during the entire observation period. The authors
concluded that all patients showed a reduction in papilla edema over time,
however, a functional improvement was not observed.
Proliferative Vitreoretinopathy
Banerjee and co-workers (2013) stated that proliferative vitreo-retinopathy (PVR) is
the commonest cause of late anatomical failure in rhegmatogenous retinal
detachment. Visual and anatomical outcomes remain poor despite advances in
vitreo-retinal surgical techniques with reported primary failure rates of up to nearly
50 %. Numerous adjunctive medications have been evaluated in clinical trials with
no agent gaining widespread acceptance and use. This study was designed to
investigate the benefits of using a slow-release dexamethasone implant delivered
intra-operatively in patients undergoing vitrectomy surgery for retinal detachment
with established PVR. For the study, 140 patients requiring vitrectomy surgery with
silicone oil for retinal detachment with established PVR will be randomized to
receive either standard treatment or study treatment in a 1:1 treatment allocation
ratio. Both groups will receive the standard surgical treatment appropriate for their
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eye condition and routine peri-operative treatment and care, differing only in the
addition of the supplementary adjunctive agent in the treatment group. The
investigated primary outcome measure was stable retinal re-attachment with
removal of silicone oil without additional vitreo-retinal surgical intervention at 6
months. The authors concluded that this is the first RCT to investigate the use of an
adjunctive slow-release dexamethasone implant in patients undergoing vitrectomy
surgery for retinal detachments with PVR.
Kuo and colleagues (2015) investigated a new sustained-release formulation of
dexamethasone (Ozurdex) for inhibiting PVR and its effect on the expression of
retinal glial reaction and inflammation in experimental PVR eyes. These
researchers used 30 pigmented rabbits for this study. One week after gas
compression, the eyes were injected with 5 × 10(4) retinal pigment epithelial cells
into the vitreous cavity to induce PVR. Concurrently, 1 eye also received an intra-
vitreal injection of Ozurdex; the other eye was used as a control. Proliferative vitreo-
retinopathy was graded by indirect ophthalmoscopy on days 1, 3, 7, 14, 21, and 28.
The expression of the retinal glial reaction and inflammation in experimental PVR
eyes were evaluated by Western blot analysis. Severity of PVR increased gradually
and peaked after 14 days, and no differences in PVR severity between the study
and control groups were observed at any time-point. The expression of glial
fibrillary acid protein (GFAP) increased on days 7 and 14 in both the PVR control
and study groups. While the use of Ozurdex in the study group showed less GFAP
expression, this difference was insignificant. The expression of tumor necrosis
factor (TNF)-α and interleukin (IL)-6 significantly increased on days 7 and 14 in
PVR control eyes. There was a significant difference in TNF-α between PVR
control eyes and Ozurdex-treated eyes on days 7 (p < 0.001) and 14 (p = 0.019).
Ozurdex in the study group showed lower IL-6 expression; however, this difference
was not significant on days 7 (p = 0.063) and 14 (p = 0.052). The authors
concluded that intra-vitreal injection of Ozurdex suppressed the expression of
inflammatory markers; however, it did not mitigate the severity of experimental PVR
in this animal model.
Radiation Maculopathy
Bui and colleagues (2014) stated that radiation maculopathy is the most common
cause of severe vision loss after radiotherapy of uveal melanoma. To-date, no
effective therapy exists. These researchers reported a novel approach to the
treatment of radiation maculopathy using Ozurdex (dexamethasone intra-vitreal
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implant). This was a retrospective case series of 2 patients who developed
radiation maculopathy after radiotherapy for uveal melanoma and was treated with
Ozurdex. Clinical outcomes included VA, central foveal thickness by OCT, IOP, and
cataract formation. Both patients were of Caucasian descent. Patient 1 received
charged-particle radiation, whereas patient 2 received iodine-125 brachytherapy for
medium-sized uveal melanoma located in the mid-peripheral retina. Radiation
maculopathy developed 47 months and 18 months after radiation exposure in
patient 1 and 2, respectively. Both patients initially received bevacizumab
monotherapy followed by alternating therapy with bevacizumab and intra-vitreal
triamcinolone. Secondary to a limited response, the patients were treated with
Ozurdex implants. One patient had visual improvement, and both patients
experienced a prolonged time frame of anatomical stability. Adverse effects
included a rise in the IOP, which was controlled by topical hypotensive agents and
posterior subcapsular cataract formation in patient 1. The authors concluded that
Ozurdex intra-vitreal implant provided a prolonged period of anatomical stabilization
in recalcitrant cases of radiation maculopathy in patients who have failed multiple
intra-vitreal bevacizumab injections and had only a partial response to intra-vitreal
triamcinolone. Moreover, they stated that larger prospective studies are needed to
determine the extent of visual benefit.
Macular Edema Secondary to Acute Retinal Necrosis
Majumder and colleagues (2016) reported 2 cases of acute retinal necrosis in
immunocompetent patients, complicated by CME and treated with Ozurdex
implant. Two patients diagnosed with acute retinal necrosis were treated with
intravenous acyclovir. Both of them developed CME following resolution of viral
retinitis. Ocular condition of the 1st patient was further complicated by central
serous chorioretinopathy. Under unavoidable circumstances, CME in both the
patients was treated with intravitreal dexamethasone implant with great caution.
Resolution of CME without recurrence of viral retinitis was noted in the long-term
follow-up. The authors concluded that the findings of this study should be
interpreted cautiously, and extreme caution should be exercised prior deciding the
management with a corticosteroid implant in patients with viral retinitis. However,
intravitreal dexamethasone implant can be a useful option in selected patients with
CME in acute retinal necrosis.
Lowering the Risk of Conjunctivitis in Individuals Receiving Cytarabine
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Matteucci and colleagues (2006) examined the effectiveness of dexamethasone
plus diclofenac eye drops as prophylaxis for conjunctivitis induced by high-dose
(HD) cytarabine (Ara-C). A total of 60 patients were randomized to receive either
dexamethasone (group A, n = 29) or dexamethasone plus diclofenac (group B, n =
31). Conjunctivitis was experienced by 13/29 (45 %) patients in group A, and 4/31
(13 %) patients in group B (p < or = 0.009); 12 out of 13 patients in group A who
developed ocular toxicity had grade 2 to 3 conjunctivitis whereas only 1 of 4
patients affected in group B experienced a similar grade of conjunctivitis. The
authors concluded that the incidence and severity of HD Ara-C-induced
conjunctivitis were significantly reduced by combined dexamethasone/diclofenac
prophylaxis. This was a small study, which showed that combined
dexamethasone/diclofenac prophylaxis provided better results than dexamethasone
prophylaxis in lowering the incidence of conjunctivitis in patients receiving
cytarabine. These findings need to be validated by well-designed studies. More
importantly, the study did not study Ozurdex (dexamethasone intravitreal implant).
Ozurdex for the Treatment of Acute Zonal Occult Outer Retinopathy (AZOOR)
Kuo and colleagues (2017) noted that acute zonal occult outer retinopathy
(AZOOR), a rare disorder affecting the outer retina, was first described by Gass in
1993 as a syndrome with rapid loss of 1 or more extensive zones of the outer
retinal segments. It is characterized by photopsia, minimal funduscopic changes,
and electroretinographic (ERG) abnormalities. The efficacy of systemic steroids in
treating AZOOR has been previously described and advocated by the concept of
autoimmune retinopathy. However, the use of intravitreal of sustained-released
steroid had not been mentioned to date. In this single-case study, a 34-year old
man had sudden onset of central scotoma and photopsia in the left eye. His visual
acuity (VA) continued to deteriorate. The visual field defect demonstrated bilateral
enlarged blind spots and altitudinal defects. Fluorescein angiography (FA) showed
non-specific retinal inflammation, and an ERG illustrated decreased amplitude of
the b wave in both eyes. Optical coherence tomography (OCT) examinations
revealed para-foveal loss of the photo-receptor inner/outer segment (IS/OS)
junction. Therefore, AZOOR was diagnosed. Although his vision did not improve
under the initial treatment of systemic corticosteroid and calcium channel blocker,
remarkable improvement was noticed after the intravitreal injection (IVI) of Ozurdex,
consistent with the recovered IS/OS junction disruption. These investigators stated
that during the 13-month follow-up, subject’s condition remained stable. However,
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these researchers could not rule out the residual or delayed effects from the
systemic steroid treatment received prior to the administration of Ozurdex or the
possibility of spontaneous recovery. Thus, they stated that the reliability of
intravitreal injection treatment with sustained released steroid need further
elucidation with future clinical research of AZOOR.
Barnes and associates (2018) reported on the use of intravitreal steroids in the
management of AZOOR. Retrospective case series of 9 eyes of 5 patients with
AZOOR who received intravitreal triamcinolone acetonide (IVTA), dexamethasone
intravitreal implant, and/or fluocinolone acetonide implant. Treatment response
was determined by reported symptoms and multi-modal imaging findings. Patients
were observed for at least 1 year following intravitreal steroid treatment (range of
14 months to 63 months). A total of 7 eyes received IVTA, 6 eyes received the
dexamethasone intravitreal implant, and 1 eye received the fluocinolone acetonide
implant. All patients experienced disease stability or improvement based on
symptomatic response and multi-modal imaging findings after intravitreal steroids; 1
eye developed central serous retinopathy, and another eye a choroidal neovascular
membrane; 5 of 9 eyes experienced ocular hypertension. All phakic eyes
developed cataracts. The authors concluded that intravitreal steroids effectively
achieved disease stability in patients with AZOOR. This was a small study (6 eyes
received Ozurdex) with relatively short-term follow-up (1 year).
Ozurdex for the Treatment of Macular Edema Secondary to Tuberculosis Uveitis
Hasanreisoglu and colleagues (2019) noted that tuberculosis-associated uveitis
remains a diagnostic and therapeutic challenge. After diagnosis of tuberculosis and
initiation of anti-tuberculosis therapy for tuberculosis uveitis, the clinical responses
are favorable. However, at 4 to 6 weeks of the therapy, there commonly occurs
paradoxical deterioration due to an increase in inflammation which is often
accompanied by cystoid macular edema (CME). Thus, adjuvant administration of anti-
inflammatory regimen should be considered. For this purpose, systemic and peri-
ocular steroids, systemic and intravitreal immunosuppressive agents have been
tested. Nevertheless, there is no report in the literature about intravitreal DEX
implants for the treatment of this inflammatory condition. These investigators
presented a case of tuberculosis uveitis whose ocular inflammation is partially
modified by systemic and peri-ocular steroid injections and then well-controlled by
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the intravitreal DEX implant. The authors concluded that intravitreal DEX implant
injection appeared to be a safe and potent option for the treatment of macular
edema secondary to tuberculosis uveitis.
Ozurdex for the Treatment of Cystoid Macular Edema (CME) Associated with Sympathetic Ophthalmia or Syphilis-Related Uveitis
In a retrospective, interventional, controlled study, Kakkassery et al (2017)
determined the safety, efficacy, and predictive outcome factors for intravitreal DEX
in pseudophakic cystoid macular edema (PCME). Patients included had to have
clinically significant PCME and have been treated with the DEX between 2012 and
2015. Charts and 1-year data were selected consecutively, and efficacy and safety
were abstracted; VA and central foveal thickness (CFT) were analyzed. A total of
19 patient data sets were analyzed. After treatment with DEX, mean VA increased
significantly by 0.2 logMAR (p = 0.034), while the mean CFT was reduced
significantly by 162.79 μm (p < 0.001); 5 patients receiving a combination of
DEX/bevacizumab have not experienced a higher mean VA gain or CFT reduction
compared to 14 patients receiving DEX alone. Decision rules, when to combine
DEX with bevacizumab, have not been defined before the study. Only post-
treatment VA gains in the non-hypertensive subgroup (n = 11) were significantly
better (p = 0.026). Analysis of data from diabetes patients (n = 4) versus non-
diabetics yielded no significant differences in efficacy. There have been no adverse
events (AEs) within follow-up time. The authors concluded that the use of DEX in
PCME showed significant improvements in VA and CFT. The VA appeared to
show greater improvements in patients without hypertension. Moreover, they
stated that the use of DEX implants in PCME should be further investigated in
larger patient populations to confirm these findings.
The authors stated that this pilot study had several drawbacks. The layout of a
retrospective study always includes a selection bias. The number of patients
screened was normally higher than the sample finally chosen for inclusion. The
small sample size (n = 14 with DEX alone) and geographic aspect represent a
further drawback. The drawbacks mentioned earlier could be assumed for all
retrospective data referenced above. Apart from 1 RCT, all datasets discussed
were also neither randomized nor controlled. The treatment decision especially for
an intravitreal administration of a DEX implant alone or with combined bevacizumab
had not been clearly defined and there might be a negative bias for the decision to
give additive bevacizumab. Also, the different group size of DEX implant alone or
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with combined bevacizumab weakened the significance of the data. Even more,
DEX implant with combined bevacizumab was more frequently used in PCME
patients with diabetes.
Lautredou et al (2018) reported the successful utilization of adjunctive repeat
intravitreal corticosteroid therapy for the treatment of CME in syphilis-related
uveitis. A HIV-positive patient with treated ocular syphilis who developed refractory
CME was treated with repeat intravitreal corticosteroid therapy including DEX
intravitreal implants. Treatment led to the resolution of CME and improvement in
VA. The authors concluded that intravitreal corticosteroid therapy may be a viable
adjunctive treatment for refractory CME in patients with treated syphilitic uveitis.
Corticosteroid-induced exacerbation of infection is unlikely in patients with an
adequate serologic treatment response. Moreover, these researchers noted that to
their knowledge there was only 1 case report in the literature where DEX implant
was used as adjuvant treatment for CME secondary to syphilitic uveitis.
Wocker and Januschowski (2019) presented the case of a 39-year old woman with
CME of the left eye in the context of sympathetic ophthalmia. The right eye
underwent several surgical interventions of both cornea and retina after ocular
trauma and was enucleated after first clinical signs compatible with sympathetic
ophthalmia and after exclusion of other infectious/non-infectious etiologies. The
patient was treated with para-bulbar triamcinolone injections and intravitreal
injections of a dexamethasone slow-release implant with a good clinical course with
respect to the macular edema. A steroid response did not occur over the treatment
period of more than 12 months. This was single-case study; its findings need to be
further investigated.
Ozurdex for the Treatment of Vasoproliferative Tumor
Temblador-Barba and colleagues (2018) reported the case of a 19-year old woman
who presented a vasoproliferative tumor. It caused complications, such as epi-
retinal membrane, macular edema, vitreous hemorrhage, and exudative retinal
detachment. The patient was treated with 3 injections of intravitreal bevacizumab,
an intravitreal DEX implant, tocilizumab, and double freeze-thaw cryotherapy. The
authors concluded that therapeutic options were: observation, if it is small, if it is a
peripheral lesion, and if there seems to be no threat to vision. If it requires
treatment, laser photocoagulation, intravitreal bevacizumab, trans-conjunctival
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cryotherapy, trans-pupillary thermotherapy, photodynamic therapy, brachytherapy
plaques and surgery are the different options available. Recently, tocilizumab and
intravitreal DEX implants have been reported to be beneficial.
Combined Intravitreal Anti-Vascular Endothelial Growth Factor (VEGF) and Ozurdex
In a retrospective cohort study, Lin and co-workers (2017) evaluated the safety and
efficiency in macular edema patients who concurrently received a single injection of
a dexamethasone intravitreal implant (DEX, 0.7 mg) and ranibizumab (2.3 mg).
Medical records from 2012 to 2016 were reviewed. Patients who received
concurrent DEX and ranibizumab injections with a follow-up period of at least 3
months were enrolled in the study group. An age- and gender-matched group
received ranibizumab injections and was designated the control group; BCVA, CMT
and IOP were included in the analysis. Steroid-induced ocular hypertension (SIOH)
is defined as either an elevation of more than 10 mmHg from baseline or a single
IOP measurement of more than 30 mmHg. A total of 26 patients were enrolled in
the current study with 13 patients in each group. Both the BCVA (p = 0.04) and
CMT (p < 0.01) achieved significant improvement after the follow-up period in the
study group. The IOP increased after the injection but no significant elevation was
observed throughout the follow-up period in the study group (p = 0.15). For SIOH, 1
patient in the study group had an elevated IOP of 10 mmHg (7.7 %) at 2 post-
operative months, and no single IOP measurement of more than 30 mmHg was
obtained; 5 patients (38.5 %) in the study group received medical treatment that
successfully retarded their IOP elevation, and no individuals required surgical
management. In the control group, there were no significant fluctuations
concerning BCVA, CMT, and IOP, and no ocular hypertension was observed.
According to the inter-group analysis, the CMT and BCVA recovered more
significantly in the study group than in the control group. The authors concluded
that concurrent injection of DEX and ranibizumab was a preliminary method that
showed effectiveness in treating ME. Furthermore, safety was also guaranteed,
with moderate levels of severity and transient IOP elevation being observed.
Moreover, they stated that a future large-scale study that include different anti-
angiogenic agents, such as aflibercept, is needed to evaluate the long-term safety
and effectiveness of this combined treatment.
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The authors stated that this study had several drawbacks. First, the small numbers
of patients, with only 13 patients in each group, would diminish the statistical power
of the study with a 22 % chance of type-II error. Second, the retrospective nature
could limit the consistency, and some data, including underlying diseases, may be
incomplete. Lastly, the concurrent ranibizumab injection in the study group might
influence the outcomes compared to previous studies.
Mehta and colleagues (2018) stated that he combination of steroid and anti- VEGF
intravitreal therapeutic agents could potentially have synergistic effects for treating
DME. On the one hand, if combined treatment is more effective than monotherapy,
there would be significant implications for improving patient outcomes. Conversely,
if there is no added benefit of combination therapy, then people could be potentially
exposed to unnecessary local or systemic side effects. Ina Cochrane review, these
investigators evaluated the effects of intravitreal agents that block VEGF activity
(anti-VEGF agents) plus intravitreal steroids versus monotherapy with macular
laser, intravitreal steroids or intravitreal anti-VEGF agents for managing DME.
They searched the Cochrane Central Register of Controlled Trials (CENTRAL)
(which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 1);
Ovid Medline; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and
the ICTRP. The date of the search was February 21, 2018. These researchers
included RCTs of intravitreal anti-VEGF combined with intravitreal steroids versus
intravitreal anti-VEGF alone, intravitreal steroids alone or macular laser alone for
managing DME. They included people with DME of all ages and both sexes. They
also included trials where both eyes from 1 participant received different
treatments. These investigators used standard methodological procedures
recommended by Cochrane; 2 authors independently reviewed all the titles and
abstracts identified from the electronic and manual searches against the inclusion
criteria. The primary outcome was change in BCVA between baseline and 1 year.
Secondary outcomes included change in CMT, economic data and quality of life
(QOL). They considered adverse effects including intra-ocular inflammation, raised
IOP and development of cataract.
There were 8 RCTs (703 participants, 817 eyes) that met inclusion criteria with only
3 studies reporting outcomes at 1 year. The studies took place in Iran (3 studies),
USA (2 studies), Brazil (1 study), Czech Republic (1 study) and South Korea (1
study); 7 studies used the unlicensed anti-VEGF agent bevacizumab and 1 study
used licensed ranibizumab. The study that used licensed ranibizumab had a
unique design compared with the other studies in that included eyes had persisting
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DME after anti-VEGF monotherapy and received 3 monthly doses of ranibizumab
prior to allocation. The anti-VEGF agent was combined with intravitreal
triamcinolone in 6 studies and with an intravitreal DEX implant in 2 studies. The
comparator group was anti-VEGF alone in all studies; 2 studies had an additional
steroid monotherapy arm, another study had an additional macular laser
photocoagulation arm. While the authors judged these studies to be at low risk of
bias for most domains, at least one domain was at unclear risk in all studies. When
comparing anti-VEGF/steroid with anti-VEGF monotherapy as primary therapy for
DME, these researchers found no meaningful clinical difference in change in BCVA
(MD -2.29 VA letters, 95 % CI: -6.03 to 1.45; 3 RCTs; 188 eyes; low-certainty
evidence) or change in CMT (MD 0.20 μm, 95 % CI: -37.14 to 37.53; 3 RCTs; 188
eyes; low-certainty evidence) at 1 year. There was very low-certainty evidence on
intra-ocular inflammation from 8 studies, with 1 event in the anti-VEGF/steroid
group (313 eyes) and 2 events in the anti-VEGF group (322 eyes). There was a
greater risk of raised IOP (Peto OR 8.13, 95 % CI: 4.67 to 14.16; 635 eyes; 8
RCTs; moderate-certainty evidence) and development of cataract (Peto OR 7.49,
95 % CI: 2.87 to 19.60; 635 eyes; 8 RCTs; moderate-certainty evidence) in eyes
receiving anti-VEGF/steroid compared with anti-VEGF monotherapy. There was low-
certainty evidence from 1 study of an increased risk of systemic AEs in the anti-
VEGF/steroid group compared with the anti-VEGF alone group (Peto OR 1.32, 95
% CI: 0.61 to 2.86; 103 eyes). One study compared anti-VEGF/steroid versus
macular laser therapy. At 1 year investigators did not report a meaningful
difference between the groups in change in BCVA (MD 4.00 VA letters 95 % CI:
-2.70 to 10.70; 80 eyes; low-certainty evidence) or change in CMT (MD -16.00 μm,
95 % CI: -68.93 to 36.93; 80 eyes; low-certainty evidence). There was very low-
certainty evidence suggesting an increased risk of cataract in the anti-VEGF/steroid
group compared with the macular laser group (Peto OR 4.58, 95 % CI: 0.99 to
21.10, 100 eyes) and an increased risk of elevated IOP in the anti-VEGF/steroid
group compared with the macular laser group (Peto OR 9.49, 95 % CI: 2.86 to
31.51; 100 eyes). One study provided very low-certainty evidence comparing anti-
VEGF/steroid versus steroid monotherapy at 1 year. There was no evidence of a
meaningful difference in BCVA between treatments at 1 year (MD 0 VA letters, 95
% CI: -6.1 to 6.1, low-certainty evidence). Likewise, there was no meaningful
difference in the mean CMT at 1 year (MD - 9 μm, 95 % CI: -39.87 μm to 21.87 μm
between the anti-VEGF/steroid group and the steroid group. There was very low-
certainty evidence on raised IOP at 1 year comparing the anti-VEGF/steroid versus
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steroid groups (Peto OR 0.75, 95 % CI: 0.16 to 3.55). No included study reported
impact of treatment on patients' QOL or economic data. None of the studies
reported any cases of endophthalmitis.
The authors concluded that combination of intravitreal anti-VEGF plus intravitreal
steroids did not appear to offer additional visual benefit compared with
monotherapy for the treatment of DME; at present the evidence for this is of low-
certainty. There was an increased rate of cataract development and raised IOP in
eyes treated with anti-VEGF plus steroid versus anti-VEGF alone. Patients were
exposed to potential side effects of both these agents without reported additional
benefit. The majority of the evidence came from studies of bevacizumab and
triamcinolone used as primary therapy for DME. There is limited evidence from
studies using licensed intravitreal anti-VEGF agents plus licensed intravitreal
steroid implants with at least 1 year follow-up. It is not known whether treatment
response is different in eyes that are phakic and pseudophakic at baseline.
Krick and Bressler (2018) presented some recent clinically relevant results from
Diabetic Retinopathy Clinical Research (DRCR) Network trials that may guide
management of DME or proliferative diabetic retinopathy (PDR). Among eyes with
DME and VA 20/50 or worse, aflibercept, on average, had greater improvement in
VA over 2 years compared with bevacizumab or ranibizumab. Aflibercept is
associated with higher rates of improvements in diabetic retinopathy severity
among eyes with PDR and vision-impairing DME at baseline compared with
bevacizumab or ranibizumab. Among eyes with persistent central-involved DME
after at least 6 anti-VEGF injections, no difference in mean VA improvement was
observed between eyes that received continued ranibizumab and sham injections
versus ranibizumab and intravitreal sustained dexamethasone drug-delivery
system, especially for phakic eyes. For eyes with PDR, ranibizumab was
associated with lower rates of developing PDR-worsening events compared with
pan-retinal photocoagulation, especially among eyes that did not receive
ranibizumab for central-involved DME at baseline. Ranibizumab was cost-effective
for PDR for eyes with, not without, vision-impairing central-involved DME,
highlighting challenges when safety and efficacy results were at odds with cost-
effectiveness results. The authors concluded that aflibercept for DME, in certain
circumstances, was more likely to have superior VA and anatomical outcomes
compared with bevacizumab or ranibizumab. No vision benefits were apparent,
especially for phakic eyes, by adding intravitreal corticosteroids for persistent DME
following anti-VEGF injections.
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Tsaousis and associates (2018) presented a case-series study of 3 women (mean
age of 48.33 ± 16.16 years) with punctate inner choroidopathy (PIC). These
researchers reported the outcomes after an essentially long follow-up period of up
to 14 years and provided evidence of the effectiveness of intravitreal injections of
bevacizumab (1.25 mg/0.05 ml) and dexamethasone (0.7 mg) in PIC patients with
choroidal neovascular membrane formation. This was a retrospective case series
of 3 patients with PIC who were treated with intravitreal injections of bevacizumab;
2 patients also received intravitreal dexamethasone. Once a choroidal neovascular
membrane (CNVM) developed, the outcome was poor with a BCVA of 6/60 or
counting fingers in the affected eyes. Patients were followed-up for 5, 14 and 8
years, respectively. The authors concluded that the use of dexamethasone 0.7 mg
in PIC yielded encouraging results and long periods of stability. When CNVM
complicated the primary disease, the prognosis was unfavorable, especially if the
macula integrity had already been considerably affected. On the contrary,
aggressive early therapy and continued monthly monitoring could prevent severe
fibrosis, as showed in previous reports. They stated that further studies with a
larger number of PIC patients are needed to examine the role of intravitreal
injections of dexamethasone 0.7 mg and anti-VEGF agents in PIC complicated with
CNVM. The main drawback of this study were its small sample size (n = 2 for
intravitreal dexamethasone implant plus intravitreal bevacizumab), the non-
randomized nature, and the lack of post-perspective study design.
Dextenza (dexamethasone ophthalmic insert)
On December 3, 2018, Ocular Therapeutix, Inc. announced the U.S. FDA approval
of Dextenza (dexamethasone ophthalmic insert) 0.4 mg for intracanalicular use for
the treatment of ocular pain following ophthalmic surgery.
Dextenza is a corticosteroid intracanalicular insert placed in the punctum and into
the canaliculus. The insert is designed to deliver a dexamethasone 0.4 mg dose to
the ocular surface for up to 30 days without preservatives. Dextenza resorbs and
exits the nasolacrimal system without the need for removal. Dextenza is intended
for single-use only.
FDA approval was based on results found in three randomized, multicenter, double-
masked, parallel group, vehicle-controlled trials in which patients received
Dextenza or its vehicle (placebo) immediately upon completion of cataract surgery.
In all three trials, Dextenza had a higher proportion of patients than the vehicle
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group who were pain free on post-operative Day 8. On post-operative Day 14, in
two of the three studies, Dextenza had a higher proportion of patients than the
vehicle group who had an absence of anterior chamber cells that was statistically
significant (Ocular Therapeutix, 2019).
Tyson et al. (2019) state that sustained-release intracanalicular dexamethasone
insert has been shown to be safe and effective for the treatment of postoperative
ocular inflammation and pain following cataract surgery. A prospective multicenter
randomized parallel-arm double masked vehicle-controlled phase 3 study was
conducted at 21 sites in the United States. A total of 438 adult patients with planned
clear corneal cataract surgery were randomized (1:1) to receive dexamethasone
insert or placebo, and the treatment was placed in the canaliculus of the eye
immediately after surgery (Day 1). The primary efficacy endpoints were complete
absence of anterior chamber cells at Day 14 and complete absence of pain at Day
8. The authors found that at Day 8, significantly more patients had an absence of
ocular pain in the dexamethasone insert arm compared with placebo (p < .0001). At
Day 14, significantly more patients had an absence of anterior chamber cells in the
dexamethasone insert arm compared with placebo (p < .0001). The
dexamethasone insert arm showed no increase compared with placebo in
incidence of all adverse events or ocular adverse events. Twice as many placebo
patients required rescue therapy, compared with treated patients at Day 14. The
study was able to successfully meet both primary endpoints. In addition, patients
receiving the dexamethasone insert experienced a decrease in inflammation after
surgery as early as Day 4 through Day 45, and a decrease in pain as early as one
day after surgery (Day 2) through Day 45. The study found that the dexamethasone
insert was well-tolerated, and the adverse events profile was similar to placebo.
Dextenza is contraindicated in patients with active corneal, conjunctival or
canalicular infections, including epithelial herpes simplex keratitis (dendritic
keratitis), vaccinia, varicella; mycobacterial infections; fungal diseases of the eye,
and dacryocystitis.
The most commonly reported adverse reactions (approximately 6-10% of patients)
were anterior chamber inflammation and elevations in intraocular pressure.
Dextenza and Allergic Conjunctivits
Torkildsen et al. (2017) report on the results of a phase 2, randomized, double-
masked, vehicle-controlled clinical trial evaluating the efficacy and safety of
Detenza in a model of allergic conjunctivitis. Fifty-nine subjects (n=28 Dextenza
group, n=31 vehicle group) with a positive conjunctival allergen challenge (CAC)
were randomized to receive Dextenza or PV (vehicle insert). Challenges occurred
over 42 days, with efficacy assessed at 14 (primary endpoint visit), 28, and 40 days
postinsertion. Outcome measures included the evaluation of ocular itching,
redness, tearing, chemosis, eyelid swelling, rhinorrhea, and congestion. At 14 days
postinsertion, Dextenza was statistically superior to PV, with least square mean
differences for ocular itching of -0.76, -0.97, and -0.87 at 3, 5, and 7 min post-CAC,
and for conjunctival redness of -0.46, -0.66, and -0.68 at 7, 15, and 20 min post-
CAC. Clinical significance, defined as a 1-U decrease from PV, was not met for
primary efficacy. Secondary endpoints, including number of subjects reporting
itching and conjunctival redness, indicated superior performance of Dextenza
compared with vehicle. Eleven Dextenza-treated (35.5%) and 10 vehicle-treated
(30.3%) subjects each experienced a single adverse event. The authors state that
this phase 2 study demonstrated preliminary efficacy and safety data of Dextenza
for the treatment of allergic conjunctivitis.
CPT Codes / HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":
Ozurdex:
CPT codes covered if selection criteria are met:
Other CPT codes related to the CPB:
HCPCS codes if selection criteria are met:
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J7312
Other HCPCS codes related to the CPB:
J2778
J9308
J9035
J9098
J9100
ICD-10 codes covered if selection criteria are met:
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Code Code Description
E08.311,
E08.3211
E08.3219,
E08.3311
E08.3319,
E08.3411
E08.3419,
E08.3511
E08.3559,
E09.311,
E09.3211
E09.3219,
E09.3311
E09.3319,
E09.3411
E09.3419,
E09.3511
E09.3559,
E10.311,
E10.3211
E10.3219,
E10.3311
E10.3319,
E10.3411
E10.3419,
E10.3511
E10.3559,
E11.311,
E11.3211
E11.3219,
E11.3311
E11.3319,
E11.3411
E11.3419,
E11.3511
E3559, E13.311,
Diabetic macular edema
H30.899
H34.8192
H34.823
H34.8392
H34.9
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
A18.54
B39.0 - B39.9 Histoplasmosis
D49.81
H00.039
H01.029
Blepharitis
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Code Code Description
H01.00A -
H01.00B
Unspecified blepharitis
H01.01A -
H01.01B
Ulcerative blepharitis
H01.02A -
H01.02B
Squamous blepharitis
H04.001 -
H04.029
Dacryoadenitis
H04.301 -
H04.329
Dacroyocystitis
H04.331 -
H04.339
Acute lacrimal canaliculitis
H04.411 -
H04.419
Chronic dacryocystitis
H04.421 -
H04.429
Chronic lacrimal canaliculitis
H05.011 -
H05.019
Cellulitis of orbit
H05.021 -
H05.022
Osteomyelitis of orbit
H05.031 -
H05.039
Periostitis of orbit
H05.041 -
H05.049
Tenonitis of orbit
H05.10 -
H05.129
Chronic inflammatory disorders of orbit
H10.011 - H10.9 Conjunctivitis
H16.001 -
H16.149
Keratitis
H25.0 - H26.9 Cataract
H27.00 - H27.03 Aphakia [rupture of the posterior lens capsule and anterior chamber
intraocular lens]
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Code Code Description
H32 Chorioretinal disorders in disease classified elsewhere [Ocular
histoplasmosis syndrome (OHS)]
H35.00 Unspecified background retinopathy [acute zonal occult outer
retinopathy (AZOOR)]
H35.021 -
H35.029
Exudative retinopathy [Coats' disease]
H35.20 - H35.23 Proliferative vitreo-retinopathy
H35.381 -
H35.389
Toxic maculopathy [radiation maculopathy]
H35.81 Retinal edema [not covered if secondary to idiopathic retinal vasculitis,
aneurysms, neuroretinitis (IRVAN) syndrome, or retinitis pigmentosa]
H35.89 Other specified retinal disorders [macular edema secondary to acute
retinal necrosis]
H40.30x+ -
H40.53x+
Glaucoma secondary to eye trauma, inflammation and other eye
disorders
H40.60x+ -
H40.63x+
Glaucoma secondary to drugs
H44.001 -
H44.009
Purulent endophthalmitis
H44.131 -
H44.139
Sympathetic uveitis
H47.011 -
H47.019
Ischemic optic neuropathy
H59.031 -
H59.039
Cystoid macular edema following cataract surgery
M72.6 Necrotizing fasciitis
Z96.1 Presence of intraocular lens [not covered for aphakic eyes with rupture
of posterior lens capsule and anterior chamber intraocular lens]
Dextenza (dexamethasone ophthalmic insert):
HCPCS codes covered if selection criteria are met:
C9048 Dexamethasone, lacrimal ophthalmic insert, 0.1 mg
ICD-10 codes covered if selection criteria are met:
G89.18
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
H10.45
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The above policy is based on the following references:
1. Kimura H, Ogura Y. Biodegradable polymers for ocular drug delivery.
Ophthalmologica. 2001;215(3):143-155.
2. McIntosh RL, Mohamed Q, Saw SM, Wong TY. Interventions for branch
retinal vein occlusion: An evidence-based systematic review.
Ophthalmology. 2007;114(5):835-854.
3. Mohamed Q, McIntosh RL, Saw SM, Wong TY. Interventions for central
retinal vein occlusion: An evidence-based systematic review.
Ophthalmology. 2007;114(3):507-519, 524.
4. Kuppermann BD, Blumenkranz MS, Haller JA, et al; Dexamethasone DDS
Phase II Study Group. Randomized controlled study of an intravitreous
dexamethasone drug delivery system in patients with persistent macular
edema. Arch Ophthalmol. 2007;125(3):309-317.
5. Hamid S, Mirza SA, Shokh I. Branch retinal vein occlusion. J Ayub Med Coll
Abbottabad. 2008;20(2):128-132.
6. Rehak J, Rehak M. Branch retinal vein occlusion: Pathogenesis, visual
prognosis, and treatment modalities. Curr Eye Res. 2008;33(2):111-131.
7. Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of
retinal vein occlusion: The Beaver Dam Eye Study. Arch Ophthalmol.
2008;126(4):513-518.
8. Fonrose M. Retinal vein occlusion. eMedicine Emergency Medicine
Ophthalmology. New York, NY: WebMD Medscape; August 25, 2008.
Available at: http://emedicine.medscape.com/article/798583-overview.
Accessed on September 9, 2009.
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9. Gewaily D, Greenberg PB. Intravitreal steroids versus observation for
macular edema secondary to central retinal vein occlusion. Cochrane
Database Syst Rev. 2009;(1):CD007324.
10. Grover DA, Li T, Chong CCW. Intravitreal steroids for macular edema in
diabetes. Cochrane Database Syst Rev. 2008;(1):CD005656.
11. Kooragayala LM. Central retinal vein occlusion. eMedicine Emergency
Medicine Ophthalmology Retina. New York, NY: WebMD Medscape; May
26, 2009. Available at: http://emedicine.medscape.com/article/1223746
overview. Accessed on September 15, 2009.
12. Parodi MB, Bandello F. Branch retinal vein occlusion: classification and
treatment. Ophthalmologica. 2009;223(5):298-305.
13. National Institutes of Health (NIH), National Eye Institute (NEI). New
treatment found to reduce vision loss from central retinal vein occlusion
Eye injections of corticosteroid medication may improve patients' vision.
NEI Press Release. Bethesda, MD: NEI; September 14, 2009. Available at:
http://www.nei.nih.gov/news/pressreleases/091409a.asp. Accessed on
September 14, 2009.
14. National Institutes of Health (NIH), National Eye Institute (NEI). Laser
treatment for vision loss from branch retinal vein occlusion is safer than
corticosteroid injections and equally effective. NEI Press Release.
Bethesda, MD: NEI; September 14, 2009. Available at:
http://www.nei.nih.gov/news/pressreleases/091409b.asp. Accessed on
September 14, 2009.
15. Johnson MW. Etiology and treatment of macular edema. Am J Ophthalmol.
2009; 147(1):11-21.
16. Haller JA, Dugel P, Weinberg DV, et al. Evaluation of the safety and
performance of an applicator for a novel intravitreal dexamethasone drug
delivery system for the treatment of macular edema. Retina. 2009;29 (1):46
51.
17. Allergan, Inc. Allergan receives FDA approval for Ozurdex™ biodegradable,
injectable steroid implant with extended drug release for retinal disease.
Press Release. Irvine, CA: Allergan; June 18, 2009. Available at:
http://agn.client.shareholder.com/releasedetail.cfm?ReleaseID=390519.
Accessed on September 15, 2009.
18. Allergan, Inc. Ozurdex™ (dexamethasone intravitreal implant). Prescribing
Information. 72212US10A. Irvine, CA: Allergan; June 2009. (Revised
September 2010). Available at:
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http://www.allergan.com/assets/pdf/ozurdex_pi.pdf. Accessed on
September 18, 2009.
19. Williams GA, Haller JA, Kuppermann BD, et al; Dexamethasone DDS Phase
II Study Group. Dexamethasone posterior-segment drug delivery system
in the treatment of macular edema resulting from uveitis or Irvine-Gass
syndrome. Am J Ophthalmol. 2009;147(6):1048-1054.
20. Ip MS, Scott IU, VanVeldhuisen PC, et al; SCORE Study Research Group. A
randomized trial comparing the efficacy and safety of intravitreal
triamcinolone with observation to treat vision loss associated with
macular edema secondary to central retinal vein occlusion: The Standard
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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan
benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial,
general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care
services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in
private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible
for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to
change.
Copyright © 2001-2019 Aetna Inc.
http://www.aetna.com/cpb/medical/data/700_799/0795.html 09/30/2019
AETNA BETTER HEALTH® OF PENNSYLVANIA
Amendment to Aetna Clinical Policy Bulletin Number: 0795
Dexamethasone Ophthalmic Implants (Ozurdex and Dextenza)
For the Pennsylvania Medical Assistance Plan, effective 1/1/20 medication coverage
requests for medications on the statewide preferred drug list will be reviewed using
the guidelines for determination of medical necessity developed by the Pennsylvania
Department of Human Services.
www.aetnabetterhealth.com/pennsylvania revised 09/13/2019
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