ArticlePDF Available

Macular edema resolution assessment with implantable dexamethasone in diabetic retinopathy (MERIT): a pilot study

Taylor & Francis
Clinical Ophthalmology
Authors:

Abstract and Figures

Purpose This study aimed to evaluate the effect of dexamethasone implantation on the hard exudates (HEX) in patients with diabetic macular edema (DME). Study design This was a nonrandomized open-label single-center prospective trial. Methods This study included 15 eyes of 11 subjects with DME. Key inclusion criteria were naïve eyes with DME with HEX within 3 mm of fovea with center-involving DME; central macular thickness (CMT) >250 μm at baseline; best-corrected visual acuity (BCVA) between 20/400 and 20/40. Key exclusion criteria were previous intraocular surgery and history of panretinal photocoagulation (PRP) in past 4 months. The primary outcome measure was change in total HEX area at the macula (in mm²) measured by semiautomated algorithm. Secondary outcome measures were change in visual acuity, low-contrast visual acuity (LCVA), retinal sensitivity (RS) on macular microperimetry, and CMT. Results The total HEX area reduced from 1.5 mm² (±1.46 mm²) at baseline to 0.89 mm² (±1.062 mm²) at the final visit (p=0.185). The CMT improved significantly (p=0.03) from 488.67 μm (±240.66 μm) to 326.93 μm (±135.84 μm) at the final visit. Mean BCVA remained stable (p=0.95) (50.93±16.65 at baseline and 50.6±18.95 at final visit). The mean LCVA and RS showed insignificant improvement (p=0.31 and p=0.28, respectively). Conclusion Our pilot study demonstrated an improving trend in reduction of total HEX area and other anatomical outcomes, with limited functional outcomes. Larger randomized studies with a larger sample size with a control group are warranted to establish management protocols for DME with significant subfoveal HEX.
This content is subject to copyright. Terms and conditions apply.
© 2018 Chhablani et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php
and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you
hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission
for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
Clinical Ophthalmology 2018:12 1205–1211
Clinical Ophthalmology Dovepress
submit your manuscript | www.dovepress.com
Dovepress 1205
ORIGINAL RESEARCH
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/OPTH.S163681
Macular edema resolution assessment with
implantable dexamethasone in diabetic retinopathy
(MERIT): a pilot study
Jay Chhablani
Mahima Jhingan
Abhilash Goud
Kiran Kumar Vupparaboina
Taraprasad Das
Smt Kanuri Santhamma Retina
Vit reous Centre, LV Prasad Eye
Institute, Hyderabad, Telangana, India
Purpose: This study aimed to evaluate the effect of dexamethasone implantation on the hard
exudates (HEX) in patients with diabetic macular edema (DME).
Study design: This was a nonrandomized open-label single-center prospective trial.
Methods: This study included 15 eyes of 11 subjects with DME. Key inclusion criteria were
naïve eyes with DME with HEX within 3 mm of fovea with center-involving DME; central
macular thickness (CMT) .250 μm at baseline; best-corrected visual acuity (BCVA) between
20/400 and 20/40. Key exclusion criteria were previous intraocular surgery and history of
panretinal photocoagulation (PRP) in past 4 months. The primary outcome measure was change
in total HEX area at the macula (in mm2) measured by semiautomated algorithm. Secondary
outcome measures were change in visual acuity, low-contrast visual acuity (LCVA), retinal
sensitivity (RS) on macular microperimetry, and CMT.
Results: The total HEX area reduced from 1.5 mm2 (±1.46 mm2) at baseline to 0.89 mm2
(±1.062 mm2) at the final visit (p=0.185). The CMT improved significantly (p=0.03) from
488.67 μm (±240.66 μm) to 326.93 μm (±135.84 μm) at the final visit. Mean BCVA remained
stable ( p=0.95) (50.93±16.65 at baseline and 50.6±18.95 at final visit). The mean LCVA and
RS showed insignificant improvement ( p=0.31 and p=0.28, respectively).
Conclusion: Our pilot study demonstrated an improving trend in reduction of total HEX area
and other anatomical outcomes, with limited functional outcomes. Larger randomized studies
with a larger sample size with a control group are warranted to establish management protocols
for DME with significant subfoveal HEX.
Keywords: dexamethasone implant, Ozurdex, hard exudates, diabetic macular edema
Introduction
Diabetic macular edema (DME) constitutes a significant burden owing to the prolonged
and varied response to treatment. DME results mainly from hyperpermeability
of retinal vessels and microaneurysms associated with deposition of lipoproteins,
clinically manifesting as hard exudates (HEX), mostly deposited in the posterior pole,
often signifying the chronicity of the edema.1 Subfoveal migration of HEX could be
a challenging situation, with very poor visual outcome due to outer retinal structure
damage and may lead to subretinal fibrosis.
Various approaches, including laser photocoagulation, anti-vascular endothelial
growth factor (VEGF) therapy, surgical removal, and intravitreal triamcinolone have
been used to manage extensive HEX.2–7 Each of the treatment modalities has its chal-
lenges, such as the associated complications and limitations. Anti-VEGF therapy
has shown promising results in terms of both anatomical and visual outcomes and
Correspondence: Jay Chhablani
Smt Kanuri Santhamma Retina Vitreous
Centre, LV Prasad Eye Institute, Kallam
Anji Reddy Campus, 2 LV Prasad Marg
Banjara Hills, Hyderabad 500034,
Telangana, India
Tel +91 40 3061 2603
Fax +91 40 2354 8271
Email jay.chhablani@gmail.com
Journal name: Clinical Ophthalmology
Article Designation: Original Research
Year: 2018
Volume: 12
Running head verso: Chhablani et al
Running head recto: Hard exudates and dexamethasone implant
DOI: 163681
This article was published in the following Dove Press journal:
Clinical Ophthalmology
Clinical Ophthalmology 2018:12
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1206
Chhablani et al
has rapidly become the standard of care after pivotal trials
such as the RISE and RIDE.8 However, rapid reduction of
DME is associated with an increase in intraretinal exudates,
along with a shift to a more outer retinal location.9 On the
other hand, the RIDE and RISE trials have demonstrated
that the area of HEX in eyes with DME did not affect visual
prognosis and that HEX did not increase in ranibizumab-
treated eyes.10
Considering that DME could primarily be an inflam-
matory pathological process, intravitreal steroids have
also been used, and these have shown promising results
in the reduction of HEX and edema over a short term of
follow-up.4–6,11 Intravitreal triamcinolone is associated with
various possible complications such as endophthalmitis and
intractable glaucoma.12 The 2-year results of the Bevaci-
zumab or Dexamethasone Implants for DME (BEVORDEX)
study showed a reduction of HEX in patients with DME with
both intravitreal dexamethasone and bevacizumab, although
the reduction of HEX in center-involving DME (,500 μm)
was statistically significant with dexamethasone only.13
Many large-scale clinical trials such as protocol T14 did
not include eyes with extensive exudates involving foveal
area; therefore, clinicians lack any established protocol to
treat such cases. We designed a pilot study to document the
effect of continuous release of dexamethasone (using an
implantable device) on the HEX at fovea (primary objec-
tive) in patients with DME and to quantify the same. The
secondary objective was to study the functional impact of
implantable dexamethasone on the contrast sensitivity and
macular function.
Methods
A nonrandomized open-label single-center prospective con-
trolled trial was conducted on 15 eyes of 11 subjects with
a diagnosis of DME who presented to the LV Prasad Eye
Institute between April 2015 and February 2016. Written
informed consent was obtained from all subjects. The institu-
tional review board of Hyderabad Eye Research Foundation
approved the study (LEC12-14-109), and all the procedures
adhered to the tenets of the Declaration of Helsinki. The chart
review followed the previously set out guidelines, described
in earlier publications.15
Key inclusion criteria for the study were as follows:
1) naïve eyes with DME with HEX within 3 mm of fovea
with center-involving DME; 2) diagnosis of diabetes mellitus
(type 1 or type 2); 3) central foveal thickness .250 μm
at baseline; and 4) best-corrected visual acuity (BCVA)
between 20/400 and 20/40. The exclusion criteria included
the following: 1) any other associated ocular condition;
2) macular edema due to any other condition; 3) presence of
conditions such as macular ischemia, vitreomacular traction,
foveal atrophy, or pigment abnormalities; 4) substantial cata-
ract likely to decrease visual acuity by $3 lines; 5) history
of treatment for DME at any time; 6) history of panretinal
(scatter) photocoagulation (PRP) within 4 months prior
to enrollment; 7) history of major ocular surgery (includ-
ing vitrectomy, cataract extraction, scleral buckle, any
intraocular surgery, and so on) within the previous 4 months
or anticipated within the next 6 months following enrollment;
8) history of yttrium aluminum garnet (YAG) capsulotomy
performed within 2 months prior to enrollment; 9) aphakia;
10) intraocular pressure (IOP) $25 mmHg; 11) history
of open-angle glaucoma; 12) history of steroid-induced
IOP elevation that required IOP-lowering treatment; and
13) examination evidence of external ocular infection, includ-
ing conjunctivitis, chalazion, or significant blepharitis.
Data collected at the initial visit included demographics,
BCVA using the Early Treatment Diabetic Retinopathy Study
(ETDRS) visual acuity, low-contrast visual acuity (LCVA)
using COMPLog, color fundus photographs (7 fields),
infrared images (7 fields), autofluorescence images (7 fields),
optical coherence tomography (OCT) with central macular
thickness (CMT), fundus fluorescein angiography (FFA),
and microperimetry.
A comprehensive ocular examination was performed in
all cases. Ocular investigations included OCT and FFA. FFA
and fundus photography were performed using FF450 plus
Fundus Camera (Carl Zeiss, Jena, Germany) with VISUPAC.
Lens grading was performed as per standard Emery and
Little classification.16 Patients were not treated aggressively
with lipid-lowering medications, other than their regular
medications.
Color fundus photographs
Color fundus photographs (50° and 30°) were captured in
7 fields with a mydriatic fundus camera (Zeiss FF450; Carl
Zeiss Meditec).
FFA study
FFA was performed using fluorescein sodium 20%, and
imaging was performed using FF450 plus Fundus Camera
(Carl Zeiss Meditec) with VISUPAC in all visits.
Spectral domain OCT (SD-OCT)
The SD-OCT scans were obtained using Cirrus HD-OCT
(Carl Zeiss Meditec) after dilatation of the pupil with 0.8%
Clinical Ophthalmology 2018:12 submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1207
Hard exudates and dexamethasone implant
tropicamide and 5% phenylephrine eye drops at every visit.
The scanning protocol included high-definition (HD) 5-line
raster, HD single-line raster, enhanced depth imaging, and
macular cube. Central retinal thickness (CRT) was deter-
mined automatically and analyzed by OCT software, by
generating images using the Macular Cube 512×128 scan
over a 6×6 mm area, the cube being composed of 128 hori-
zontal examination lines of 512 A-scans each. The CRT was
obtained from the 1 mm CRT area as described in the ETDRS
fields corresponding to the CMT.
Microperimetry
Microperimetry was performed using the microperim-
eter (macular integrity assessment [MAIA™]; CenterVue,
Padova, Italy). Pupils of all patients were dilated before
examination. Goldmann III stimuli and a 4-2-1 staircase
strategy were used, and a test grid with 37 stimulus locations
covering an area of 10° was applied. The stimuli were pro-
jected on a white background with black illumination set to
1.27 cd/m2 and a stimulus presentation time of 200 ms. The
perimetric strategy of the microperimeter starts at an initially
defined threshold level for each stimulus. A 4-2-1 staircase
strategy is then carried out, and the weakest recognized value
is documented as the retinal sensitivity (RS) at each tested
site. Mean differential light sensitivity, in decibels (dB), of all
test locations was analyzed for the study. For assessment of
fixation, the fundus movements were tracked during exami-
nation while the patient gazed at the fixation target. The auto
tracking system calculated the horizontal and vertical shifts
relative to a reference frame and drew a map of the patient’s
eye movements during the examination. The recorded
fixation points were classified into 3 categories for fixation
analysis – stable, relatively unstable, and unstable. Fixation
was defined as follows: stable if .75% of the fixation
points were inside the 2°-diameter circle; relatively unstable
if ,75% were inside the 2°-diameter circle, but .75% were
inside the 4°-diameter circle; and unstable if ,75% of the
fixation sites were inside the 4°-diameter circle. Significant
improvement or worsening in microperimetry was defined
as a change in sensitivity of $1 dB, a change in stability of
fixation, or both.
Measurements of HEX by a
semiautomated algorithm
We used the semiautomated algorithm for HEX measurements;
this algorithm uses a 2-pronged methodology, involved per-
forming top-hat filtering, second-order statistical filtering,
and thresholding of the color fundus images.
In brief, a 2-pronged approach was adopted to detect both
bright and weak/faint HEX. In Step 1, to detect bright HEX,
top-hat17 filtering was first used on the gray scale image of
the color fundus photograph using a structuring element
(disk, where the radius of the disk is considered to be ¼ the
width of the image) to make background illumination more
uniform. Subsequently, adaptive histogram equalization17
was performed to further enhance the exudates from the back-
ground. Then, the enhanced image was binarized using an
empirically determined threshold (0.37) for segmenting the
exudates from the background, in which the brighter pixels
indicate the exudates. However, in addition to the exudates,
some outliers also were obtained due to reflections from the
optic disk and retinal vessels in the nerve fiber layer.
Next, in Step 2, we proceed to detect the weaker exudates
that may not have been detected in Step 1. Here, only the
green plane of the color fundus image is considered because
weak exudates are better contrasted in the green plane than in
the grayscale image or the red and blue planes. Then, similar
operations that were used in Step 1 were subsequently per-
formed but with different thresholds. Specifically, the radius
of the structuring element for performing top-hat filtering is
decreased to one quarter of the width of the image, and the
threshold for binarization is empirically determined as 0.25
for images obtained after the respective operations. Step 2
also resulted in a few outliers due to the same reasons men-
tioned earlier in Step 1.
Now, the results of Step 1 and Step 2 are combined, and
the outliers are removed manually using a rectangular selec-
tion box. Finally, the total area of the detected HEX is mea-
sured to facilitate monitoring of the treatment response.
Color fundus photographs were analyzed using this algo-
rithm by a single observer. Intraobserver reproducibility was
evaluated using the first 15 images and was found to correlate
well, with an intraclass correlation coefficient of 0.94.
Intravitreal injection of the
dexamethasone implant
All individuals who met the study criteria underwent intravit-
real injection of the dexamethasone (0.7 mg) implant into the
eye following all aseptic precautions in a sterile environment.
After topical anesthesia and Betadine® (Mhs Pharmaceuti-
cals Private Limited, Hyderabad, India) 10% preparation
of the eye, the implant was injected in the inferotemporal
quadrant. When 2 eyes of the same individual fit the study
criteria, the 2 eyes were injected at an interval of 3 days.
No postinjection prophylaxis or patching was recommended.
Injections were performed at baseline and at Month 4.
Clinical Ophthalmology 2018:12
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1208
Chhablani et al
Study visits
All patients were examined at baseline and at Days 60,
120, 180, and 240. Comprehensive examination, BCVA,
LCVA, fundus photography, SD-OCT, and microperimetry
were done at all visits. FFA was performed at baseline,
Day 120, and Day 240. All individuals were advised to get
the IOP measured locally at 2 weeks after the intravitreal
dexamethasone implant injection, to rule out any inadvertent
steroid-related rise in IOP.
Outcome measures
Primary outcome measure
The primary outcome of interest was the change in total area
of HEX at the macula (in mm2), measured by a semiauto-
mated algorithm.
Secondary outcome measures
The secondary outcome measures were changes in visual
acuity, LCVA, RS on macular microperimetry, and central
subfield thickness on SD-OCT.
Statistical analysis
Statistical analysis was performed using SPSS software
(version 16.0; SPSS, Chicago, IL, USA), with special
emphasis on the aforementioned information. Wilcoxon
signed-rank test was used for statistical analysis of various
outcome measures. The follow-up rate was 87%, and there-
fore, last observation carried forward (LOCF) analysis was
performed. Values of p,0.05 were considered statistically
significant.
Results
Fifteen eyes of 11 patients, 6 males and 5 females, were
included in the study. Mean age was 54.4±8.1 years.
All patients had type 2 diabetes mellitus. Three patients
were on antihypertensive medications, and 2 patients were
on lipid-lowering medications. None of the patients were
smokers. All eyes, but 1, were phakic. Phakic eyes had
grade I nuclear sclerosis in 5 eyes and grade 2 in 3 eyes; the
remaining 6 eyes had clear crystalline lens. A representative
case of the phakic eye is shown in Figure 1.
Anatomical outcome
The total area of HEX at the macula was 1.5 mm2 (±1.46 mm2)
at presentation. This reduced to 0.89 mm2 (±1.062 mm2) at
the final visit. This was a clinically significant decrease over
the short duration even though statistically insignificant
(p=0.185).
The CMT of the patients in our study improved signifi-
cantly (p=0.03) from a baseline of 488.67 μm (±240.66 μm)
to 326.93 μm (±135.84 μm).
Visual outcome
Mean BCVA at presentation was 50.93 (±16.65) ETDRS
letters. At the 8-month follow-up, BCVA remained stable
at 50.6 (±18.95) ETDRS letters; this was statistically not
significant ( p=0.95). The mean LCVA at presentation was
1.15 (±0.39) (approximate Snellen’s equivalent of 20/300),
which improved to 0.97 (±0.43) (approximate Snellen’s
equivalent of 20/200) at the final visit; this was statistically
not significant ( p=0.31).
Functional outcome
The average threshold microperimetry values improved from
6.99 dB (±8.897 dB) at presentation to 11.91 dB (±7.64 dB)
at final follow-up. This showed a trend toward an improve-
ment in the macular function over time despite the results
appearing statistically insignificant ( p=0.28).
Cataract progression
Among the phakic eyes, 1 eye with grade I nuclear sclerosis
at baseline had posterior subcapsular cataract and 4 eyes with
clear crystalline lens at baseline had early nuclear sclerosis
at the final visit.
Change in IOP
Mean IOP at baseline was 13.2±2.59 mmHg, which remained
stable till the final visit at 14.46±3.46 mmHg (p=0.26). One
patient had an increase in IOP (26 mmHg) at Month 2,
which was controlled using antiglaucoma medication till
the final visit.
Diabetic retinopathy grading
At baseline, 14 eyes had moderate nonproliferative diabetic
retinopathy (NPDR) and 1 eye had stable lasered prolifera-
tive diabetic retinopathy (PDR; lasering was done 9 months
before the enrollment). None of the eyes had change in their
diabetic retinopathy status till the final visit.
Table 1 shows a short summary of the results.
Discussion
Our study showed a trend toward decrease in total surface
area of HEX at the macula, along with an increase in RS,
following dexamethasone implantation. Though these results
were not significant, they bode well for long-term follow-up
of patients on these implants. A trend toward decreasing HEX
in DME has been described with both anti-VEGF injections10
Clinical Ophthalmology 2018:12 submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1209
Hard exudates and dexamethasone implant
Figure 1 Representative case of phakic eye.
Notes: (A) A 56-year-old male presented with moderate NPDR and center-involving macular edema with plenty of HEX. He underwent 2 intravitreal dexamethasone
implantations at baseline and at Month 4. (B) His visual acuity improved from 20/200 to 20/100 at Month 8, with reduction in HEX. Quantitative analysis of HEX showed a
reduction from (C) 1.9 mm2 to (D) 1.75 mm2. Spectral domain optical coherence tomography showed a reduction in subfoveal HEX (arrow) and reduction in central macular
thickness as can be seen at (E) baseline and (F) Month 8. Retinal sensitivity map shows improvement from (G) baseline to (H) Month 8.
Abbreviations: HEX, hard exudates; NPDR, nonproliferative diabetic retinopathy.
Table 1 Observations of the MERIT study at baseline and nal follow-up
Characteristics At baseline –
mean (±SD)
At 8 months –
mean (±SD)
p-value
BCVA in ETDRS letters 50.93 (±16.654) 50.6 (±18.95) 0.959
Contrast sensitivity (logMAR) 1.15 (±0.39) 0.97 (±0.43) 0.31
Central macular thickness (μm) 488.67 (±240.66) 326.93 (±135.84) 0.03
Hard exudates area (mm2)1.525 (±1.46) 0.89 (±1.06) 0.19
Average threshold retinal sensitivity (dB) 6.99 (±8.896) 11.91 (±7.64) 0.29
Abbreviations: BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; logMAR, logarithm of the minimum angle of resolution;
MERIT, macular edema resolution assessment with implantable dexamethasone in diabetic retinopathy.
Clinical Ophthalmology 2018:12
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1210
Chhablani et al
and steroids;11,13,18 however, in these cited studies, the quanti-
fication of HEX and assessment of RS as functional outcome
were not carried out.
In our study, we noted a significant decrease in the CMT
despite the short duration of follow-up; this demonstrates the
efficacy of the dexamethasone implant in treating DME, as
has been documented earlier.13,18 However, we did not notice
a significant change in the BCVA, LCVA, and RS. This
could be explained by the neuronal and structural damages
secondary to the chronic nature of the DME, cataract progres-
sion, and presence of subfoveal HEX.
Corticosteroids reduce the inflammation and lead to
recovery of blood–retina barrier, in addition to their anti-
VEGF property. Triamcinolone has been shown to cause
resorption of HEX in various small case series in eyes with
DME.3,5,6 Dexamethasone increases the vascular resistance
and reduces permeability, which contributes to faster resolu-
tion of HEX.
Khairallah et al6 report resolution of HEX after single
intravitreal triamcinolone injection at a mean of 8 months of
follow-up. Similarly, Avci and Kaderli3 and Ciardella et al5
also report resolution of HEX in chronic DME with improve-
ment in visual acuity. These studies have reported an increase
in IOP in 25%–40% of eyes, which required antiglaucoma
medications. None of these studies have evaluated functional
outcomes. Moreover, dexamethasone implants have less
frequent and transient episodes of increased IOP, which can
be managed successfully with topical medications.19
Contrast sensitivity and RS are considered to be comple-
mentary tools in functional vision evaluation in DME.20
Vujosevic et al21 have previously found macular microperim-
etry to be an excellent additional tool to add to BCVA and
CMT as a factor explaining visual function in patients with
DME; they had also demonstrated a significant change in
microperimetry results in patients with normalizing macular
thickness in center-involving DME. Mastropasqua et al22 have
found that RS, as measured by microperimetry, improved
after dexamethasone implantation as early as 1–4 months
after the injection. Similar findings have also been noted ear-
lier by Querques et al.23 Our study demonstrated an improve-
ment in functional outcome (RS) following dexamethasone
implantation, even in the presence of subfoveal exudates.
Limitations of our study include the small sample size
and lack of a control group. We did not evaluate SD-OCT
structural changes with various outcome measures. We are
unable to comment on comparative outcomes with anti-
VEGF therapy. We did not evaluate the distance of HEX
from the fovea, which could be an important parameter to
assess the foveal migration during follow-up.
The strength of this study was that we evaluated HEX
resolution as the primary outcome measure in a prospective
manner, along with the impact on the anatomical, visual,
and functional changes. We performed a quantitative assess-
ment of HEX using a validated semiautomated algorithm,
not subjectively as done in earlier studies. Our objective
approach could be used in the consideration of HEX as one
of the outcome measures in clinical trials on DME evaluating
various treatment modalities.
Conclusion
Our pilot study demonstrated reduction of total HEX and
improvement in RS, along with a reduction in CMT. Poor
visual outcomes were related to the persistence of subfo-
veal HEX; therefore, early consideration of dexamethasone
implantation in eyes with HEX close to the fovea may be
beneficial. Long-term studies with a larger sample size with
a control group are warranted to establish management
protocols for DME with significant subfoveal HEX.
Acknowledgment
The manuscript has not been presented at any meetings and
no funding was provided for the study.
Disclosure
The authors report no conflicts of interest in this work.
References
1. Singh A, Stewart JM. Pathophysiology of diabetic macular edema.
Int Ophthalmol Clin. 2009;49(2):1–11.
2. Yang CM. Surgical treatment for severe diabetic macular edema with
massive hard exudates. Retina. 2000;20(2):121–125.
3. Avci R, Kaderli B. Intravitreal triamcinolone injection for chronic
diabetic macular oedema with severe hard exudates. Graefes Arch Clin
Exp Ophthalmol. 2006;244(1):28–35.
4. Avci R, Kaderli B, Akalp FD. Intravitreal triamcinolone injection for
chronic diffuse diabetic macular oedema. Clin Exp Ophthalmol. 2006;
34(1):27–32.
5. Ciardella AP, Klancnik J, Schiff W, Barile G, Langton K, Chang S.
Intravitreal triamcinolone for the treatment of refractory diabetic macular
oedema with hard exudates: an optical coherence tomography study. Br
J Ophthalmol. 2004;88(9):1131–1136.
6. Khairallah M, Zeghidi H, Ladjimi A, et al. Primary intravitreal tri-
amcinolone acetonide for diabetic massive macular hard exudates.
Retina. 2005;25(7):835–839.
7. Takagi H, Otani A, Kiryu J, Ogura Y. New surgical approach for removing
massive foveal hard exudates in diabetic macular edema. Ophthalmology.
1999;106(2):249–256; discussion 256–247.
8. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic
macular edema: results from 2 phase III randomized trials: RISE and
RIDE. Ophthalmology. 2012;119(4):789–801.
9. Pemp B, Deak G, Prager S, et al; Diabetic Retinopathy Research Group
Vienna. Distribution of intraretinal exudates in diabetic macular edema
during anti-vascular endothelial growth factor therapy observed by
spectral domain optical coherence tomography and fundus photography.
Retina. 2014;34(12):2407–2415.
Clinical Ophthalmology
Publish your work in this journal
Submit your manuscript here: http://www.dovepress.com/clinical-ophthalmology-journal
Clinical Ophthalmology is an international, peer-reviewed journal
covering all subspecialties within ophthalmology. Key topics include:
Optometry; Visual science; Pharmacology and drug therapy in eye
diseases; Basic Sciences; Primary and Secondary eye care; Patient
Safety and Quality of Care Improvements. This journal is indexed on
PubMed Central and CAS, and is the official journal of The Society of
Clinical Ophthalmology (SCO). The manuscript management system
is completely online and includes a very quick and fair peer-review
system, which is all easy to use. Visit http://www.dovepress.com/
testimonials.php to read real quotes from published authors.
Clinical Ophthalmology 2018:12 submit your manuscript | www.dovepress.com
Dovepress
Dovepress
Dovepress
1211
Hard exudates and dexamethasone implant
17. Gonzalez RC, Woods RE. Digital Image Processing. Upper Saddle
River, NJ: Prentice Hall; 2008.
18. Scaramuzzi M, Querques G, Spina CL, Lattanzio R, Bandello F.
Repeated intravitreal dexamethasone implant (Ozurdex) for diabetic
macular edema. Retina. 2015;35(6):1216–1222.
19. Malcles A, Dot C, Voirin N, et al. Safety of intravitreal dexamethasone
implant (Ozurdex): the safodex study. Incidence and risk factors of
ocular hypertension. Retina. 2016;37(7):1352–1359.
20. Kim YH, Yun C, Kim JT, Kim SW, Oh J, Huh K. The correlation between
retinal sensitivity assessed by microperimetry and contrast sensitivity in
diabetic macular oedema. Br J Ophthalmol. 2014;98(12):1618–1624.
21. Vujosevic S, Midena E, Pilotto E, Radin PP, Chiesa L, Cavarzeran F.
Diabetic macular edema: correlation between microperimetry and opti-
cal coherence tomography findings. Invest Ophthalmol Vis Sci. 2006;
47(7):3044–3051.
22. Mastropasqua R, Toto L, Borrelli E, et al. Morphology and function
over a one-year follow up period after intravitreal dexamethasone
implant (Ozurdex) in patients with diabetic macular edema. PLoS One.
2015;10(12):e0145663.
23. Querques G, Lattanzio R, Querques L, et al. Impact of intravitreal dex-
amethasone implant (Ozurdex) on macular morphology and function.
Retina. 2014;34(2):330–341.
10. Domalpally A, Ip MS, Ehrlich JS. Effects of intravitreal ranibizumab
on retinal hard exudate in diabetic macular edema: findings from the
RIDE and RISE phase III clinical trials. Ophthalmology. 2015;122(4):
779–786.
11. Larsson J, Kifley A, Zhu M, et al. Rapid reduction of hard exudates
in eyes with diabetic retinopathy after intravitreal triamcinolone: data
from a randomized, placebo-controlled, clinical trial. Acta Ophthalmol.
2009;87(3):275–280.
12. Sutter FK, Simpson JM, Gillies MC. Intravitreal triamcinolone for
diabetic macular edema that persists after laser treatment: three-month
efficacy and safety results of a prospective, randomized, double-masked,
placebo-controlled clinical trial. Ophthalmology. 2004;111(11):
2044–2049.
13. Mehta H, Fraser-Bell S, Yeung A, et al. Efficacy of dexamethasone
versus bevacizumab on regression of hard exudates in diabetic
maculopathy: data from the BEVORDEX randomised clinical trial.
Br J Ophthalmol. 2015;100(7):1000–1004.
14. Diabetic Retinopathy Clinical Research Network, Wells JA,
Glassman AR, et al. Aflibercept, bevacizumab, or ranibizumab for
diabetic macular edema. N Engl J Med. 2015;372(13):1193–1203.
15. Gilbert EH, Lowenstein SR, Koziol-McLain J, Barta DC, Steiner J.
Chart reviews in emergency medicine research: where are the methods?
Ann Emerg Med. 1996;27(3):305–308.
16. Emery JM. Kelman phacoemulsification, patient selection. In:
Emery JM, MoIntyre DJ, editors. Extracapsular cataract surgery:
St. Louis, MO: CV Mosby; 1983:95–100.
... The most used intravitreal anti-VEGF agent's regimens, pro re nata and treat and extend, include at least three loading doses of intravitreal drugs and further frequent medical appointments and monthly injections to manage the ME, becoming a burden to the patient and relatives [7][8][9] . ...
Article
Full-text available
Introduction: Macula edema consists in one of the most common causes of visual impairment. Objective: To evaluate the safety and efficacy of continuous release of 0.7 mg dexamethasone (using implantable device) for treatment of macular edema. Methods: Cross-sectional observational study of 16 patients treated with 0.7 mg dexamethasone intraocular implant. Visual acuity, intraocular pressure and central macular thickness were recorded at baseline, 1-month and 3-month follow-up. Results: 15 eyes of 13 patients were included. Most eyes (n=9) improve visual acuity from baseline at 1-month follow-up; this improvement persisted through 3-monyh follow-up in six eyes. The central macular thickness decreased in the majority of the subjects at 1-month (n=12) and at 3-month (n=10) follow-up. Three eyes presented with elevated intraocular pressure. Conclusion: Dexamethasone implant can both reduce the risk of vision loss and improve anatomical features of macular edema due to several pathologies studied. This implant may be used safely and should be considered a therapeutic option to Brazilian Public Health System.
Article
Full-text available
Purpose: To compare retinal function by using fundus-guided microperimetry (MP) and multifocal electroretinography (mfERG) for detecting hydroxychloroquine (HCQ) maculopathy. Methods: Forty-six eyes of 25 patients referred to our clinical practice for HCQ maculopathy assessment and 3 groups of normal control subjects were evaluated by mfERG and MP. Macular structure was assessed using spectral-domain optical coherence tomography (SD-OCT). Ring ratios from the three innermost mERG rings were compared with average sensitivity of each MP ring at approximately equivalent distances from the fovea. HCQ toxicity was defined as an mfERG ring ratio or mean MP ring sensitivity >2 standard deviations below the normal mean. The sensitivity and specificity of MP to detect HCQ toxicity relative to mfERG were evaluated. Results: MP rings MR2 and MR3 were positively correlated with corresponding mfERG ring ratios (r = 0.52, P = 0.002 and r = 0.56, P < 0.001 respectively). Ring 2 and ring 3 measures of MP and mfERG were significantly worse in HCQ eyes than controls (P < 0.001). The sensitivity of MP to detect toxicity for MR1 through MR3 ranged from 33% to 88%, whereas specificity ranged from 72% to 85%. Through rings 1 to 3, the frequency of abnormal function ranged from 20% to 48% for MP, 11% to 35% for mfERG, and 41% to 45% for SD-OCT. Conclusions: The frequency of detection of HCQ toxicity with MP was greater than with mfERG. MP showed an overall good sensitivity and moderate specificity in detecting HCQ-induced functional deficits. Translational relevance: Results from this study may allow clinicians to improve screening accuracy for HCQ toxicity by using the alternative modality of MP.
Article
Full-text available
Purpose: To analyze the incidence, risk factors, and time course of intraocular pressure elevation after intravitreal dexamethasone implant (Ozurdex). Methods: The medical charts of 421 consecutive eyes (361 patients) receiving one or more Ozurdex implant between October 2010 and February 2015 were reviewed retrospectively. Ocular hypertension was defined as intraocular pressure of at least 25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were retinal vein occlusion (34%), diabetic macular edema (30%), postsurgical macular edema (17%), uveitis (14%), and other etiologies (5%). Results: Among 1,000 intravitreal injections, ocular hypertension was recorded for 28.5% of injected eyes over a mean follow-up period of 16.8 months (3-55). Intraocular pressure-lowering medication was required for 31% of eyes. Only three eyes with preexisting glaucoma required filtering surgery to manage postinjection intraocular pressure elevation. Early retreatment between the third and fourth month does not increase the risk of intraocular pressure elevation. Younger age, male sex, Type 1 diabetes, preexisting glaucoma treated with dual or triple therapy, and a history of retinal vein occlusion or uveitis were significant risk factors for ocular hypertension after dexamethasone implant injection (P < 0.05 for all the above). Conclusion: Episodes of ocular hypertension after Ozurdex implant were generally transient and successfully managed with topical treatment. An analysis of the risk factors may help to determine the risk-benefit ratio for individual patients treated with dexamethasone implants.
Article
Full-text available
Background: To investigate changes in macular morphology and function after an intravitreal dexamethasone implant for diabetic macular edema (DME). Methods: Twenty-seven eyes in 27 treatment-naive patients affected by DME were treated with intravitreal Ozurdex® injections (IVOI) and followed up 12 months to evaluate morphological and functional changes by means of best-corrected visual acuity (BCVA), microperimetry (MP1), multifocal electroretinography (mfERG), pattern electroretinography (PERG) and spectral domain optical coherence tomography (SD-OCT). Results: Both BCVA and retinal sensitivity improved significantly at one month after the IVOI (p = 0.031 and p<0.0001, respectively). After five months, the improvement of BCVA remained statistically significant compared with baseline values (p = 0.022); retinal sensitivity improvement was statistically significant for up to four months after the IVOI (p = 0.059). Moreover, central macular thickness significantly decreased for up to four months. Interestingly, PERG and mfERG values did not change significantly for up to four months post-IVOI, but then began to worsen. Conclusions: In eyes with DME, intravitreal dexamethasone implant determined morphological and functional improvement as soon as one month and for up to four months after the treatment.
Article
Full-text available
Objective To report the effect of bevacizumab versus dexamethasone on hard exudates (HEX) in diabetic macular oedema (DME). Design Post hoc analysis of 24-month data from the Randomised clinical trial of BEVacizumab OR DEXamethasone for diabetic macular oedema (BEVORDEX) phase 2 multicentre randomised clinical trial. Eyes with centre-involving DME resistant to or unlikely to benefit from macular laser therapy were included. Eyes were randomly assigned to bevacizumab every 4 weeks or Ozurdex dexamethasone implant (DEX) every 16 weeks, both as required. The 68 eyes from 48 patients that completed 24-month follow-up were analysed. Two masked graders assessed extent and location of HEX on baseline, 12-month and 24-month foveal-centred colour fundus photographs using validated grading software. Results Macular HEX was present in 60% of study eyes. Of these, 21 eyes were treated with DEX and 20 eyes with bevacizumab. Both treatments led to reduction in area of macular HEX at 12 months and 24 months. There was greater regression of HEX from the foveal centre in DEX-treated eyes (median change +890 µm, IQR=1040 µm) than bevacizumab-treated eyes (median change +7.0 µm, IQR=590 µm) at 12 months (p=0.04) but the difference was no longer statistically significant (p=0.10) by 24 months (DEX +1400 µm, IQR=1590 µm; bevacizumab +20 µm, IQR=2680 µm). Reassuringly, no study eye developed HEX at the foveal centre, a visually devastating consequence of diabetic maculopathy. Conclusions Bevacizumab and DEX were effective in reducing area of HEX in eyes with DME. DEX provided more rapid regression of HEX from the foveal centre although bevacizumab-treated eyes started to catch up by 24 months. Distance from the foveal centre as well as total area of macular HEX should be assessed when evaluating treatments for foveal-threatening HEX. Trial registration number NCT01298076; Post-results.
Article
Full-text available
Background: The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. Methods: At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year. Results: From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P=0.40), hospitalization (P=0.51), death (P=0.72), or major cardiovascular events (P=0.56). Conclusions: Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.).
Article
Full-text available
To evaluate the effect of monthly intravitreal ranibizumab on hard exudate (HE) area and the impact of HE on visual acuity (VA) outcomes in diabetic macular edema (DME) patients using data from 2 phase III clinical trials. Exploratory analyses of phase III, randomized, double-masked, sham-controlled, multicenter clinical trials. Adults with DME, baseline best-corrected VA 20/40 to 20/320 Snellen equivalent, and central foveal thickness of ≥275 μm. Between the 2 studies, 759 patients with DME were randomized to receive monthly 0.3 or 0.5 mg intravitreal ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) or sham injections. Hard exudate area was assessed from color fundus stereophotographs both on an ordinal scale and using continuous estimates of areas within the Early Treatment Diabetic Retinopathy Study grid. Data from 739 eyes were available for analysis. Mean baseline HE area was similar across treatment groups, ranging from 0.65 to 0.82 mm(2). Through month 24, the percentage of eyes without HE increased from 20.9% to 36.3% in the sham group and from 22.1% to 61.3% and 23.6% to 62.0% in the ranibizumab 0.3-mg and 0.5-mg groups, respectively. Resolution of HE became apparent sometime after month 6 in ranibizumab-treated eyes. At baseline, there was no meaningful correlation between VA and presence or absence of HE. After baseline, there also was no consistent correlation between presence or absence of HE and change in VA over time. In this exploratory analysis, monthly intravitreal ranibizumab resulted in significantly greater reduction of HE area compared with sham (P < 0.0001). In contrast to the rapid effects of ranibizumab on macular edema, changes in HE area were more gradual. Contrary to prior expectations, the presence and area of HE did not increase as DME resolved (either in the ranibizumab or sham groups). Importantly, baseline VA was not correlated with presence of HE, nor was the therapeutic benefit of ranibizumab on VA affected negatively by the presence of HE. These data suggest that in the context of intravitreal anti-vascular endothelial growth factor therapy, the presence of HE is not a prognostic indicator of poor visual outcomes. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Article
To evaluate the effects of repeated intravitreal dexamethasone implant. We reviewed the charts of 12 patients with diabetic macular edema, who received at least 2 intravitreal Ozurdex (0.7 mg) on an "as needed" basis. Main outcome measures included changes in best-corrected visual acuity, central macular thickness, retreatment interval, and incidence of side effects. A total of 15 eyes of 12 patients (6 men, 6 women; mean age 62 ± 12 years) were included. Retreatment was judged necessary after mean of 7.8 ± 4.1 months from the first Ozurdex (median, 6 months) (15 of 15 eyes), mean of 4.8 ± 0.9 months from the second Ozurdex (median, 5 months) (7 of 15 eyes), mean of 5.3 ± 1.5 months from the third Ozurdex (median, 5 months) (3 of 15 eyes), and mean of 5.6 ± 2 months from the fourth Ozurdex (median, 5 months) (3 of 15 eyes). Mean baseline best-corrected visual acuity was 0.67 ± 0.33 logMAR in the overall diabetic macular edema population; it significantly improved to 0.53 ± 0.31 logMAR after mean of 40.9 ± 18.2 days from the first Ozurdex (peaking efficacy) (P < 0.001), to 0.53 ± 0.29 logMAR after mean of 34.4 ± 9.0 days from the second Ozurdex (peaking efficacy) (P < 0.003), and stabilized to 0.62 ± 0.26 logMAR after mean of 29.8 ± 12.1 days from the third Ozurdex (peaking efficacy) (P = 0.05), to 0.5 ± 0.26 logMAR after mean of 36.3 ± 3.2 days from the fourth Ozurdex (peaking efficacy) (P = 0.2), and to 0.50 ± 0.26 logMAR after mean of 37.0 ± 2.6 days from the fifth Ozurdex (peaking efficacy) (P = 0.2). Mean baseline central macular thickness significantly decreased from 546 ± 139 μm to 292 ± 43 μm at 39.4 ± 17.9 days from the first Ozurdex (peaking efficacy) (P < 0.001), to 297 ± 47 μm at 33 ± 9.4 days from the second Ozurdex (peaking efficacy) (P < 0.001), to 293 ± 22 μm at 29.8 ± 12.1 days from the third Ozurdex (peaking efficacy) (P = 0.01), and stabilized to 309 ± 35 μm at 36.3 ± 3.2 days from the fourth Ozurdex (peaking efficacy) (P = 0.1), and to 295 ± 7 μm at 37.0 ± 2.6 days from the fifth Ozurdex (peaking efficacy) (P = 0.1). No serious adverse events were observed; three eyes developed a transient intraocular pressure increase, and cataract was extracted in one eye. Repeated intravitreal Ozurdex on an "as needed" basis with a variable retreatment interval may produce long-term clinically meaningful benefits in the treatment of diabetic macular edema, without other significant side effects than expected after intraocular corticosteroid treatment.
Article
Purpose: To evaluate changes in the distribution and morphology of intraretinal microexudates and hard exudates (HEs) during intravitreal anti-vascular endothelial growth factor therapy in patients with persistent diabetic macular edema. Methods: Twenty-four patients with persistent diabetic macular edema after photocoagulation were investigated in this prospective cohort study. Each eye was assigned to a loading dose of three anti-vascular endothelial growth factor treatments at monthly intervals. Additional single treatments were performed if diabetic macular edema persisted or recurred. Intraretinal exudates were analyzed over 6 months using spectral domain optical coherence tomography (SD-OCT) and fundus photography. Results: Before treatment, microexudates were detected by SD-OCT as hyperreflective foci in 24 eyes, whereas HEs were seen in 22 eyes. During therapy, HE increased significantly in number and size. This was accompanied by accumulation of microexudates in the outer retina. Enlargement of hyperreflective structures in SD-OCT was accompanied by enlargement of HE at corresponding fundus locations. A rapid reduction in diabetic macular edema was seen in all patients, but to varying degrees. Patients with hemoglobin A1c levels <7% and serum cholesterol <200 mg/dL formed fewer HEs and featured more edema reduction and visual acuity gain. Conclusion: Diabetic macular edema reduction during intravitreal anti-vascular endothelial growth factor therapy was accompanied by dynamic rearrangement of intraretinal exudates at corresponding locations in fundus photography and SD-OCT. Intraretinal aggregates of microexudates detectable as hyperreflective foci by SD-OCT may compose and precede HE before they become clinically visible.
Article
Aim To investigate the relationship between contrast sensitivity (CS) and retinal sensitivity (RS) assessed by microperimetry (MP) in diabetic retinopathy (DR) with clinically significant macular oedema (CSME). Methods A retrospective study was performed with 35 eyes of 35 patients with DR and CSME. Retinal thickness (RT) and MP were tested with the spectral SD-optical coherence topography/scanning laser ophthalmoscope system. Mean central RT at the fovea centre's 1 mm zone (CRT) and at the fixation centre's 1 mm zone (FCRT) was measured. RS was tested at the fixation centre, within 2° and 4° areas. CS was measured with six target sizes (6.3°, 4.0°, 2.5°, 1.6°, 1.0°, 0.64°) with a contrast glare tester. Results The mean CRT and FCRT were 344.3±136.2 and 359.9±135.5 μm, respectively. Mean log CSs (−log10) with the six target sizes ranged from 0.19 to 1.32. The mean RS at the fixation centre, within 2°, and within 4° area were 8.51±4.81 dB, 8.58±3.88 dB and 9.22±3.56 dB, respectively. RS at all tested areas were significantly correlated to log CS with all target sizes (range, r=0.366–0.755; p=0.0001–0.030). CRT and FCRT were not significantly correlated to log CS or RS. Conclusions CS and RS showed moderately significant correlations in CSME. However, neither CS nor RS was correlated with RT in patients with CSME. It could be that CS and MP are complementary to each other and are useful tools in the evaluation of functional vision.
Article
To investigate the impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and function in eyes with macular edema secondary to central retinal vein occlusion. Twelve treatment-naive patients with decreased visual acuity because of central retinal vein occlusion-related macular edema were enrolled in this prospective uncontrolled study. Patients were treated with intravitreal Ozurdex and followed up at 1 month and 3 months for the evaluation of morphologic and functional outcomes, by means of best-corrected visual acuity, microperimetry, multifocal electroretinography, and customized high-resolution enhanced depth imaging spectral-domain optical coherence tomography scans. Twelve eyes of 12 patients (10 men, 2 women; mean age 56.2 ± 13.0 years) were included for analysis. At 1 month, mean best-corrected visual acuity, retinal sensitivity (microperimetry), multifocal electroretinography parameters, central macular thickness, and specific neurosensorial retinal measurements improved significantly. We found a significant negative correlation between retinal sensitivity and central macular thickness at 1 month and 3 months (r = -0.831, P = 0.001; r = -0.881, P = 0.001; respectively). Moreover, retinal sensitivity was negatively related to both outer and inner retinal thickness in all four intervals from the fovea. From baseline to Month 1, change in outer retinal thickness was positively related to multifocal electroretinography N1R1 amplitude change (r = 0.698, P = 0.012), whereas change in central macular thickness was negatively related to multifocal electroretinography P1R1 amplitude change (r = -0.701, P = 0.011). At 3 months, improvement of mean retinal sensitivity and central macular thickness slightly decreased. In eyes with macular edema secondary to central retinal vein occlusion, intravitreal dexamethasone provides functional benefits that correlate well with ultrastructural macular changes.
Article
Objective: To examine the efficacy of surgical removal of foveal hard exudates in diabetic macular edema and to determine the expression of vascular endothelial growth factor (VEGF) in the excised specimens. Design: Cohort study. Participants: Seven eyes of six patients with massive subfoveal hard exudate due to diabetic macular edema were examined. The average age of the patient was 56 years (range, 46-60 years). Intervention: Pars plana vitrectomy for removal of massive foveal exudates was performed. Main outcome measures: Preoperative and postoperative visual acuity and complications were recorded; immunohistochemical staining for VEGF and other cell markers for macrophage and pigment epithelial cells in excised specimens was performed. Results: Postoperative best-corrected visual acuity improved by two or more lines of Snellen equivalent in five eyes (71%) (P = 0.0061). VEGF, identified by anticytokeratin and CD68 antibodies, was expressed in pigment epithelial cells and macrophages invading the hard exudates. Conclusion: Surgical removal of foveal hard exudates might be effective in low-vision patients with diabetic maculopathy. VEGF might play a role in the formation and persistence of foveal hard exudates in diabetic macular edema.