Running title: DEX implant for retinal vein occlusion
Efficacy of Dexamethasone Intravitreal Implant For Refractory Macular Edema
Caused by Retinal Vein Occlusion
Rehan M. Hussain, M.D.,
1
Thomas A. Ciulla, M.D., M.B.A
1,2
, Lauren M. Ciulla
2
,
Bethany Sink
2
, Alon Harris, Ph.D.
1
1
Department of Ophthalmology, Indiana University School of Medicine, 1160 W.
Michigan St, Indianapolis, IN 46202
2
Retina Service, Midwest Eye Institute, 200 W. 103
rd
St, Indianapolis, IN 46290
Corresponding Author:
Thomas A. Ciulla, M.D., M.B.A.
Volunteer Clinical Professor of Ophthalmology
Indiana University School of Medicine
Retina Service, Midwest Eye Institute
200 W. 103
rd
Street
Indianapolis, IN 46290
Thomasciulla@gmail.com
Phone: 317-817-1822
Fax: 317-817-1898
TC received contracted research funding from Acucela, Alcon, Ophthotec,
Thrombogenics, and Xoma within the past year. He currently has an employment
relationship with Ophthotech. AH would like to disclose that he receives remuneration
from CIPLA, Stemnion, Biolight, Nano Retina, AdOM, Science Based Health, Isarna
Therapeutics, and ONO Pharmaceuticals for serving as a consultant. AH also holds an
ownership interest AdOM, Oxymap and Nano Retina. All relationships listed above are
pursuant to IU's policy on outside activities. None of the other authors have any financial
disclosures. There are no conflicts of interest to report.
No funding was received for this work.
___________________________________________________________________
This is the author's manuscript of the article published in final edited form as:
Hussain, R., Ciulla, T., Ciulla, L., Sink, B., & Harris, A. (2018). Efficacy of Dexamethasone Intravitreal Implant for
Refractory Macular Edema Caused by Retinal Vein Occlusion. Retinal Cases & Brief Reports, 12(4), 294–299.
https://doi.org/10.1097/ICB.0000000000000496
2
Key Words: BRVO, CRVO, corticosteroids, dexamethasone, macular edema, optical
coherence tomography, Ozurdex
Summary Statement: Dexamethasone intravitreal implant effectively reduced
recalcitrant macular edema caused by retinal vein occlusion. Visual acuity initially
improved with treatment. However at one year follow-up, it worsened compared to
baseline in both phakic and pseudophakic eyes. 50% of phakic eyes underwent cataract
surgery and 23% of eyes developed ocular hypertension.
Abstract
Purpose: To investigate efficacy of dexamethasone intravitreal implant (DEX) in treating
refractory macular edema (ME) caused by retinal venous occlusion (RVO).
Methods: Retrospective chart review.
Results: 22 eyes with refractory ME caused by RVO were treated with a mean of 2.2
DEX over 12 months. Patient had previously received a mean of 7 treatments (laser,
bevacizumab, and/or triamcinolone) for ME present for at least 4 months duration (mean
20.8 months 20.8 ± 17.6, range 4-72 months) prior to starting DEX. Mean baseline visual
acuity (VA) was 20/91 and mean central subfield thickness (CSFT) was 506 μm. DEX
improved mean BCVA to 20/75 and 20/66 at 7 week and 6 month follow-up, although it
worsened to 20/132 at 12 months. Mean CSFT improved to 292, 352, and 356 μm at 7
week, 6 month, and 12 month follow-up respectively. There was a statistically significant
association between number of DEX treatments and CSFT (p=3.28 x 10
-9
). There was a
statistically significant association between number of days followed and BCVA
(p=0.006). 6 of 12 (50%) phakic patients developed visually significant cataract requiring
3
surgery. 5 of 22 (23%) patients developed ocular hypertension (intraocular pressure >30),
and consequently did not undergo further treatment with DEX.
Conclusions: DEX resulted in sustained anatomic reduction of RVO-associated
refractory ME, although this did not translate into long term BCVA improvement in
either phakic or pseudophakic patients, possibly related to chronic structural alterations in
the retina despite reduction of edema.
4
Introduction
Vision loss from retinal vein occlusion (RVO) is frequently due to macular edema
(ME).
1
The pathogenesis of ME following RVO is related to a variety of factors,
including hydrostatic effects from increased venous pressure, inflammatory cytokines,
dysregulation of endothelial tight junctions, and increased amount of vascular
permeability factors, including vascular endothelial growth factor (VEGF).
2-4
Macular
laser photocoagulation, intravitreal anti-VEGF agents, and intravitreal corticosteroids are
commonly utilized treatments for macular edema caused by central retinal vein occlusion
(CRVO) or branch retinal vein occlusion (BRVO). However, there are certain patients
who develop refractory ME despite multiple treatments with the aforementioned
modalities.
The dexamethasone (0.7 mg) intravitreal implant (DEX implant; OZURDEX,
Allergan, Inc., Irvine, CA) was approved in 2009 to treat macular edema caused by
retinal vein occlusion. It is contained in a solid bioerodable polymer for sustained-release,
and can exert clinical effects for three to six months. The OZURDEX GENEVA study
showed that both the 0.35g and 0.7 mg DEX implant groups were both superior to sham
in preventing visual acuity loss, and improving the rapidity and incidence of visual acuity
recovery in treatment-naïve eyes with ME secondary to CRVO or BRVO.
5
The authors of
this present study performed retrospective review of 0.7 mg DEX implant used to treat
RVO-associated macular edema that had been refractory to multiple prior treatments.
Methods
5
This retrospective, uncontrolled chart review studied patients diagnosed with
refractory ME due to RVO, who were treated with their first DEX implant from March
2010 through July 2015. This project was reviewed by Indiana University’s IRB and
considered exempt. Fluorescein angiography was performed on each patient on initial
presentation to the clinic. Only patients diagnosed with CRVO or BRVO were included.
Refractory ME was diagnosed if the patients experienced persistent ME of at least
4 months duration despite at least 2 prior treatments, including any combination of
macular laser photocoagulation, intravitreal triamcinolone acetonide, intravitreal
bevacizumab, or intravitreal ranibizumab. In those patients who had undergone macular
laser treatment, a grid pattern had been applied to areas with diffuse leakage, between
500 and 3000 microns from the fovea; 532 nm laser was set to spot size of 50 microns at
0.05 to 0.1 sec.
Exclusion criteria included other causes of macular edema, such as diabetic
retinopathy or neovascular age-related macular degeneration. Patients were excluded if
the baseline best corrected visual acuity (BCVA) was better than 20/40, the central
subfield thickness (CSFT) on spectral domain optical coherence tomography (OCT) was
less than 300 microns, or if the foveal avascular zone (FAZ) was enlarged to greater than
1000 microns. A minimum of 6 months of follow-up was required to be eligible for the
study.
Patient charts were reviewed for eligibility, and data were extracted regarding the
patient’s age, gender, previous interventions, and CSFT. The BCVA, CSFT, intraocular
pressure (IOP), lens status, treatment dates from the initial visit and follow-up visits were
recorded. Snellen visual acuity was converted to logarithm of minimal angle of
