research about recent treatment of diabetic macular edema

1. Recent Treatment Of BME
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Faculty of MedicineSohag University
Fourth year student
Sohag faculty of medicine
Assistant lecturer of ophthalmology
Faculty of medicine
Sohag University
Academic Year
2017-2018

2. Recent Treatment Of BME
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Introduction
As with all complications of diabetes, successful management of macular edema requires
good control of the diabetes itself.
The Early Treatment Diabetic Retinopathy Study (ETDRS) was the first study to provide a
treatment paradigm in this disease using laser therapy to reduce moderate vision loss in
patients with clinically significant macular edema by approximately 50%. Although
prevention of vision loss is important, visual improvement would be preferable.
Over the past few years, research has started to focus on the use of anti–vascular
endothelial growth factor (VEGF) therapy to treat diabetic macular edema (DME). As new
and promising treatment options emerge and prospective data begin to mount, it is
becoming clearer that anti-VEGF therapy will play an increasing role in the treatment of
DME.
A variety of intra vitreal medications are currently available, with others under study, Pars
plana vitrectomy may also be beneficial.
Although these treatments are very successful (In slowing or stopping further vision loss)
they do not cure diabetic retinopathy.

3. Recent Treatment Of BME
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Screening-A
According to preferred practice patterns of American academy of ophthalmology, the
recommended schedule for dilated eye examination by ophthalmologists is given in table
(1) ,detection of presence or severity of DR is possible.
Systemic management-B
Systemic control is crucial for management of any complications of DM including DR.
1- Control of diabetes and blood pressure
2- Control of hyperlipidemia
High plasma cholesterol may be associated with more sever hard exudates at macula.
a.hypercholesterolemiDR progression in diabetic withwas shown to retardSimvastatin
ty of hardand decreased severiregionsubfovealreduced lipid migration toOral atorvastatin
exudates in type 2 diabetics with dyslipidemia having CSME in a study by Gupta and
colleagues.
3- Control of nephropathy, anemia, obesity and cessation of smoking also important for
preventing DR and DME.
Ocular management of diabetic macular edema-C
1- Laser
Laser photocoagulation
The standard treatment for visual impairment
due to DMC.
Laser pattern used is determined according to fluorescein leakage pattern.
Patients with focal leaks from micro aneurysms are laser directly over these, while patient
responding DME-in nonPatients.are managed using gird laserdiffuse capillary leakswith
are laser on large ischemic areas in peripheral macula.
Figure 1

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Modifications of conventional laser
d laserrigModified
A 'C' shaped area around the macula is treated with low intensity small burns. This helps in
clearing the macular edema.
cropulse Diode laser photocoagulation (SMDLP)subthreshold mi
Diode laser is more compact, cheaper to maintain also cause less damage to retina than argon
laser, though pain associated with both treatments are comparable.
patterned scanned laser (PASCAL)
Optically pumped semiconductor laser (OPSL). Maximum 56 spots
in single predetermined pattern can be given in 0.6 seconds.
Available patterns single spot, arc, triple ring, square array, wedge,
line, and octant. Thus total time required to apply photocoagulation
is reduced.
Recently, the reults of DRCR.net protocol S were released demonstrating that there
continues to be research into use of focal laser, especially in the form of non-damaging,
laser therapy, although to date this form has shown only marginal benefit compared with
conventional laser. Although many physicians currently use non damaging laser, there
remains to be a clear consensus on its preferred use.
2- Pharmacotherapy
Pharmacologic treatments are being investigated in prospective trials currently.
(VEGF)vascular endothelial growth factor-Anti-A
 Ranibizumab: Intravitreal ranibizumab (0.3 mg) with prompt focal/grid laser (within one
week) has been found to be more effective compared with focal/grid laser alone for the
treatment of DME involving the central macula (OCT central subfield thickness of ≥250 um)
at 2-year follow-up (DRCRnet study).
Center involved-Color fundus picture shows macular thickening; Right-At presentation: Left–panel3: TopFigure
Color fundus picture with-Post ranibizumab treatment: Left–macular edema (430 μm). VA 20/60, N36. Bottom panel
l thickness of 180 μm. VA 20/30, N6Fovea-resolved macular edema; Right
Figure 2

5. Recent Treatment Of BME
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 Bevacizumab: Intravitreal Bevacizumab (1.25 mg) at 6 week intervals has been reported
to be more effective than modified ETDRS focal/grid laser in terms of improvement in
visual acuity at 12 months (BOLT study).
Intravitreal bevacizumab doses of 1.25 to 2.5 mg have shown improvement in best-corrected
visual acuity and in reducing macular thickness on OCT at 24 months in The Pan-American
Collaborative Retina Study Group.
 Aflibercept: intravitreal Aflibercept has been reported to be effective than focal/gird laser in
achievement at least two step DRSS. (VISTA and VIVID) trails.
Recent publication from the DRCR.net considered
that Aflibercept was more effective in regressing the
PDR than Bevacizumab or Ranibizumab.
B- Steroids
The beneficial effects of steroids in DME are due to the fact
that several inflammatory cytokines and chemokine's
involved in inflammatory cascade of DME are suspected to
steroids
Triamcinolone is a long acting steroid preparation. When
injected in the vitreous cavity, it decreases DMC and results
in an increase in visual acuity.
The effect of triamcinolone is transient, lasting up to three months, which necessitates
repeated injections for maintaining the
beneficial effect.
Best results of intravitreal Triamcinolone have
been found in eyes that have already
undergone cataract surgery.
few hard exudates, micro aneurysms and–Color fundus at presentation-At presentation: Left–: Top panel4Figure
Post bevacizumab–Cystoids macular edema (326 μm). VA 20/50, N12. Lower panel-area of retinal thickening. Right
fundus picture shows resolved macular edema; foveal thickness reduced to 187 μm. VA 20/30, N6Color-injections: Left
Figure 5
Figure 6
Figure7

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the result of DRCR.netprotocol U
This study was initiated to determine if patients with DME who have persistent vision loss
and edema following 6 months to 1 year of monthly anti-VEGF treatment could benefit
from adjunctive steroids.
Subjects were randomized to receive 1 or more Ozurdex dexamethasone implant, or sham
intravitreal steroids, both in combination with continued ranibizumab injections.
At 6 months, visual acuity was similar between groups, however, a significantly higher
proportion of steroid eyes showed flat retinas on OCT compared with control eyes.
Dr. Maturi also notes that a subgroup of pseudophakic eyes appeared to respond better to
treatment, suggesting steroids may benefit certain patients.
Medical follow-up
After laser treatment, the follow-up examination is at three months. If residual CSME is
noted, OCT and FA may be performed to evaluate the benefit and location of repeat laser
treatment.
Intravitreal injections (partially based on the DRCR net studies on ranibizumab): Patients
follow-up every 4 weeks for intravitreal anti-VEGF injections during the first 4 months. At 16
and 20 weeks follow-up, the injections are given only if the OCT central subfield thickness is
still >=250um.
3- Surgery
Instead of laser surgery, some people require
a vitrectomy to restore vision. A pars plana
vitrectomy is performed when there is a lot of
blood in the vitreous. It involves removing the
cloudy vitreous and replacing it with a saline
solution.
Studies show that people who have a vitrectomy soon after a large hemorrhage are more
likely to protect their vision than someone who waits to have the operation. Early
vitrectomy is especially effective in people with insulin-dependent diabetes, who may be at
greater risk of blindness from a hemorrhage into the eye.
Surgical follow up
Post-operative day (POD) #1, post-operative week (POW) #1, post-operative month (POM)
#1, POM #3, POM #6, POM#12.
Figure 8

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1- For prevention
Light treatment
A medical device comprising a mask that delivers green light through the eyelids while a person
sleeps.
The light from the mask stops rod cells in the retina from dark adapting, which is thought to reduce
their oxygen requirement, which in turn diminishes new blood vessel formation and thus prevents
diabetic retinopathy.
Richard Kirk presents the Noctura 400 Sleep Mask for Diabetic Retinopathy and Diabetic
Macular Oedema at the French Society of Ophthalmology Annual Conference 2017 in Paris.
: The optical coherence tomography before (left; 664 μm) and after (184 μm) vitreous surgery with internal9Figure
peeling; visual acuity improved from 20/200 to 20/25 despite the presence of minimal cystic changeslimiting membrane
nasal to the fovea
Figure 10

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2- For treatment
Novel therapies are being investigated. Strategies targeting molecules beyond VEGF are
being explored along with novel drug delivery mechanisms .
1- Designed ankyrin repeat protein
Novel molecules (DARPins ) targeting VEGF-A. these agents have
Higher potency and loner half-life (2 weeks)
2- Extended drug delivery
As monthly intravitreal anti-VEGF injections are burdens for pateints, implant of sustained
release delivery systems are more useful in treatment of chronic diseases as DME. They
based on passive,diffusion-controlled drug delivery mechanism, can be refilled in the office
as needed.
Encapsulated cells
Implants using encapsulated cells utilize an
RPE cell line that produce a soluble VEGF
receptor protein for at least 2 years.
Cells are encapsulated in a semi- permeable
membrane that allow selective passage of
molecules.
3- inhibitors of multiple growth factors
Squalamine, a small molecule anti-
angiogenic drug , targets VEGF along with
platelet –derived growth factor and bFGF.
4- tumor necrosis factor
TNF is an important cytokine that has been
implicated in many inflamatory diseases
including rhumatiod arthiritis… etc.
DME pateints showed significant improved
of visual acuity and reduction of retinal
thickness with intravenous injection of
infliximab (TNF inhabitor )(5mg/kg).
Large trials are needed to confirm efficacy of theses drugs in DME patients .
Figure 11
Figure 12

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3- For degenerated areas
Stem cell therapy
Clinical trials are under way or are being populated in preparation for study at medical centers in
Brazil, Iran and the United States. Current trials involve using the patients' own stem cells derived
from bone marrow and injected into the degenerated areas in an effort to regenerate the vascular
system.
DMEfor mangmentSummary
Figure 13

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References:
https://www.researchgate.net/publication/274086609_Recent_Advances_in_Management_of_
Diabetic_Macular_Edema
http://eyewiki.aao.org/Diabetic_Macular_Edema
4738;year=2016;volume=64;issue=1;spage=4;epage=13;aulast=Das-http://www.ijo.in/article.asp?issn=0301
-9475-47fd-d297-https://f1000researchdata.s3.amazonaws.com/manuscripts/13709/a75c8b2b
rs.pdf?doi=10.12688/f1000research.12662.1_Matthew_Powe-1117076d9335_12662_
treatment-https://emedicine.medscape.com/article/1224138
https://en.wikipedia.org/wiki/Diabetic_retinopathy#Management
https://www.youtube.com/watch?v=4jYNKjDsvJQ