Current Treatment Options

DME
Current Treatment Options

Dr. Zia-Ul-Mazhry
FCPS(Pak),
FRCS(Edin),
FRCS(Glasgow),
CIC Ophth- (UK)
Assistant Professor
Central Park Medical college Lahore
Consultant Eye Surgeon &
Head of Department
WAPDA Teaching Hospital Complex Lahore.
Diabetic Macular Edema
• What is DME?
• How to diagnose, investigate and classify?
• When to treat?
• What are the available tools and how to use
them?
• The Follow UP
Dr. Mazhry frcs,fcps 2

Introduction
• Historical Background:
– Diabetic Macular Edema (DME) was unrecognized
before invention of the ophthalmoscope (Helmholtz,
1851).
– Jaeger in 1856 was the first to describe a “roundish or
oval yellow spots and extravasations which permeate
part or the whole thickness of the retina” in a patient
with positive urine glucose test for Diabetes Mellitus.
– That same year Von Graefe refuted any relationship of
the eye findings to diabetes.

Introduction
• Historical Background (cont’d):
– In 1869 Noyes established a causal relationship between
the changes described by Jaeger and Diabetes Mellitus
(DM).
– In 1872 Nettleship confirmed this theory in his treaties on
the issue (“Noyes’ glucosuric retinitis”).
– In 1875 Appolinaire in Paris reported these observations
and described in addition, the accumulation of lipid in the
retina which he designated “glucose induced amblyopia.”
– Diabetic Macular Edema (DME) was thereafter recognized
as a clinical entity.

A classification of diabetic
retinopathy
• Non-proliferative diabetic
retinopathy (NPDR)
– Mild non-proliferative diabetic retinopathy
– Moderate-to-severe non-proliferative
diabetic retinopathy
• Proliferative diabetic
retinopathy
– High risk
• Maculopathy
– Diffuse/focal
– Clinically significant macular oedema (CSME )
– Ischaemic Maculopathy

NPDR
Typically asymptomatic, but may
have decreased or fluctuating
vision with fluctuation in blood
sugars
NPDR can affect visual function

through 2 mechanisms, both
which affect the macula:
Variable degrees of
intraretinal capillary closure
resulting in macular ischemia
Increased retinal vascular

permeability resulting in
macular edema

Minimal NPDR
• At least 1
Microaneurysms (m)
• Microaneurysms
only
• Remainder of fundus
normal

Mild NPDR
• Microaneurysms (m)
and Dot
hemorrhages (h)
• May also
demonstrate
macular edema and
lipid exudate (e)

Moderate NPDR
• Cotton wool spots (w),
Retinal hemorrhages
(h) (Dot-blot, Flame),
and Microaneurysms
(m)
• Hemorrhages,
Microaneurysms in at
least 1 quadrant, and
cotton wool spots or
venous beading in 1
quadrant only
• Less than Severe

Diabetic Macular Edema (DME)
• Definition: Diabetic macular edema

is retinal thickening caused by the accumulation
of intraretinal fluid primarily in the inner and
outer plexiform layers. It is believed to be a result
of hyperpermeability of the retinal vasculature.
• Can be present with any level of diabetic
retinopathy (DR).

Pathogenesis
Normal retinal circulation is unique:
Retinal capillaries are non-fenestrated and capillary

endothelial cells have tight junctions; normal retinal
capillaries do not leak fluid, blood
No lymphatic system in the retina

In the presence of retinal pathology, leaking fluid can
accumulate and cause edema or swelling
Retina responds to ischemia by stimulating growth factors

to produce new vessels (called neovascularization)
Pathogenesis (cont.)
Thus, 2 key changes occur:
Vessel permeability
Damaged endothelial wall becomes more porous
Vessel leaks fluid, lipids, erythrocytes
Accumulation of the fluid results in edema (macular
edema if located within the central region of the retina)
Vessel closure
Supply of oxygen and nutrients are decreased
New fragile growth occurs (secondary to ischemia)
Microaneurysms
• focal dilatations of retinal capillaries,
• 10 to 100 microns in diameter, and.
• appear as red dots especially temporal to the fovea.
• first ophthalmoscopically detectable change in diabetic
retinopathy.
• Despite multiple layers of basement membrane, they are
permeable to water and large molecules, allowing the
accumulation of water and lipid in the retina.
• Since fluorescein passes easily through them, many more
microaneurysms are usually seen on fluorescein angiography
than are apparent on ophthalmoscopy

Hard exudates
( Intra-retinal lipid exudates )
• Accumulations of
lipids leak from
surrounding
capillaries and
micro aneurysms
• they may form a
circinate pattern.

Epidemiology :
• International
– The WHO estimates that more than 150 million people
worldwide have diabetes.
• Untreated,
– there is a 25-30% risk of developing clinically significant macular
edema (CSME) with moderate visual loss.
• USA
– 5.8 million people are known to have DM
– 4 to 5 million Americans have DM that has not been diagnosed
– 9% of diabetic population in US will have macular edema
– Of these, 200,000 patients with “macular edema alone” are at
risk of moderate visual loss
• (Aiello and Ferris, 1987).
Emmanouil Mavrikakis, MD, PhD, Consultant Vitreoretinal Surgeon, Ophthalmology Department,
Athens Medical Centre, Greece
Wai-Ching Lam, MD, FRCS(C), Associate Professor, Department of Ophthalmology and Vision
Sciences, University of Toronto; Baseer U Khan, MD, Staff Physician, Department of 15
Ophthalmology, University of Toronto, Canada Updated: Sep 29, 2009 Dr. Mazhry frcs,fcps
DME-Legal Blindness
• Mortality/Morbidity
– Diabetes is the leading cause of new blindness in the
United States, to which CSME has a significant
contribution.
– Untreated, 25-30% of patients with CSME exhibit a
doubling of the visual angle within 3 years.
– Treated, the risk drops by 50%.

Diagnosis-History
• Ocular history • Duration of the
• Diabetic history diabetes
– Specific inquiry should – Increased risk of
be made into risk diabetic retinopathy
factors for the • Age of patient
development of – Diabetic retinopathy is
diabetic retinopathy. more likely to present
• Type of diabetes in patients older than
– After 20 years of 40 years.
disease, nearly all
patients with type I
and 60% of patients
with type II have some
degree of retinopathy.

Diagnosis-History
• Diabetic control • Renal disease
– The Diabetes Control – Proteinuria is a good
and Complication Trial marker for the
(DCCT) clearly development of
demonstrated that diabetic retinopathy;
tighter control of blood thus, patients with
sugar is associated diabetic nephropathy
with reduced incidence should be observed
of diabetic retinopathy. more closely.
(Glycosylated
hemoglobin [HbA1c]
should be less than
7%.)

Diagnosis-History
• Systemic hypertension • Pregnancy
– Increased risk of – Diabetic retinopathy
retinopathy (diabetic can progress rapidly in
retinopathy with pregnant women,
superimposed especially those with
hypertensive preexisting diabetic
retinopathy) retinopathy.
• Triglycerides and lipids
– Normalization of lipid
levels reduces retinal
leakage and exudates
deposition.

DME Diagnosis-Physical
• Funduscopy under stereopsis and high
magnification should be performed on every
patient with diabetes to assess for diabetic
macular edema and diabetic retinopathy.
• An indirect ophthalmoscope does not provide
adequate magnification for the
ophthalmologist to diagnose diabetic macular
edema.

DME Diagnosis-Physical
• Important observations include:
– Location of retinal thickening relative to the fovea
– Presence and location of exudates
– Presence of cystoid macular edema

Diabetic Macular Edema(DME)
Focal/Diffuse
• Diabetic macular edema is defined as
retinal thickening within 2 disc
diameters of the center of the macula.
– Focal edema
• is associated with hard exudate rings
resulting from leakage from
microaneurysms.
– Diffuse edema
• results from breakdown of blood-retinal
barrier with leakage from microaneurysms,
retinal capillaries, and arterioles. Often
associated with cystoid macular edema

Clinically Significant Macular Edema
CSME diagnosed primarily at the slit lamp
• Retinal thickening at or within (to assess retinal thickening)
500 µm from the center of the
macula or
• Hard exudates at or within 500
µm from the center of the
macula if accompanied by
thickening of the adjacent
retina or
• A zone of retinal thickening, 1
disc area or larger in size,
located 1 disc diameter or less
from the center of the macula
– ETDRS demonstrated that eyes
with CSME benefited from
treatment with focal Argon
laser
Other physical findings
• Visual acuity
– is an important
parameter in following
the progression of
CSME, although it does
not aid in the diagnosis
of CSME because
patients may have a
visual acuity of 20/20.
• The status of the
posterior hyaloid;
– detached, taut,
thickened

Differential Diagnoses
– ARMD, Exudative
– Branch Retinal Vein Occlusion
– Central Retinal Vein Occlusion
– Hypertension Macular Edema
– Irvine-Gass
– Uveitis
– Other Problems to Be Considered
• Cystoid macular edema
• Hypotonic retinopathy
• Macular pucker
• Epinephrine use in aphakia

Workup
Imaging Studies
• Color stereo fundus photographs
– provide an opportunity to evaluate long-term
changes in the retina.

Workup
Imaging Studies-FFA
• Fluorescine angiography
– Fluorescein angiography is CSME diagnosed primarily at the slit
lamp (to assess retinal thickening)
useful in demonstrating the
breakdown of the blood-
retinal barrier by delineating
retinal capillary leakage and
capillary nonperfusion
– Fluorescein angiography is
not relevant in aiding in the
diagnosis of CSME but should
be performed if treatment of
CSME is being considered.
Workup
Imaging Studies
• Fluorescine
angiography
– Fluorescine angiography
distinguishes and
localizes areas of focal
versus diffuse leakage,
thereby guiding the
placement of laser
photocoagulation.
– The proximity of the
leakage to the foveal
avascular zone should
be noted.
Fluorescine angiography
• Focal leakage:
• Well defined areas of leakage; e.g.,
microaneurysms
• FFA will clearly show the source of
leakage
• Diffuse leakage:
• Poorly demarcated widespread
leakage
• Destruction of the inner blood
retinal barrier.
• FFA will show widened
intercapillary spaces, with diffusely
dilated capillary bed, and diffuse
leakage.
• RPE dysfunction
Workup
Imaging Studies
• Optical coherence
tomography
– Optical coherence
tomography (OCT) captures
reflected light from retinal
structures to create a cross-
sectional image of the
retina, which is comparable
to histologic sections as
seen with a light
microscope.
Sciences, University of Toronto; Baseer U Khan, MD, Staff Physician, Department of Dr. Mazhry frcs,fcps 30
Ophthalmology, University of Toronto, Canada Updated: Sep 29, 2009
Workup
Imaging Studies
• Optical coherence tomography
– It has been able to demonstrate a moderate
correlation between retinal thickness and best-
corrected visual acuity, and it has been able to
demonstrate 3 basic structural changes of the
retina from diabetic macular edema (DME), that
is,
• retinal swelling, cystoid edema, and serous retinal
detachment.
Sciences, University of Toronto; Baseer U Khan, MD, Staff Physician, Department of Ophthalmology,
University of Toronto, Canada Updated: Sep 29, 2009 Dr. Mazhry frcs,fcps
Workup
Imaging Studies
• Optical coherence
tomography
– OCT is not currently required to
establish a diagnosis and is not
prescribed by current practice
guideline; however, OCT has
gained widespread acceptance
as an additional modality to
help identify and evaluate
macular pathology.4
– Quantitative measurement of
macular thickness and
subjective analysis of the foveal
architecture allow a precise and
reproducible way to monitor
macular edema.
Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular
edema with optical coherence tomography. Am J Dr. Mazhry frcs,fcps
Ophthalmol. Jun 1999;127(6):688-93
Treatment
• Medical Care
– Primary Care Physicians And Internists.
• optimizing
– diabetic and
– hypertensive
– renal
– and lipid control
– Diet
• Lifestyle modification
– Activity
• Lifestyle modification
– Optimizing diabetic, hypertensive, and lipid control has been

shown to positively impact diabetic retinopathy.
Chew EY, Klein ML, Ferris FL 3rd, et al. Association of elevated serum
lipid levels with retinal hard exudate in diabetic retinopathy. Early
Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch
Ophthalmol. Sep 1996;114(9):1079-84. 33 Dr. Mazhry frcs,fcps
Ocular Treatment
• Available Tools
– LASERs
– AntiVEGF Therapy
– Steroids

Focal/grid laser photocoagulation
• Focal/grid laser photocoagulation

– Goals
• Significant visual improvement is uncommon; the goal of macular
laser treatment is to reduce progression.
• Photocoagulation reduced the risk of moderate visual loss from
diabetic macular edema by 50%, from 24% to 12%, 3 years after
initiation of treatment.1
– Timing
• Laser treatment is most effective when initiated before visual acuity is
lost from diabetic macular edema; this emphasizes the need for
diligent monitoring and follow-up care.
• Laser treatment of diabetic macular edema should precede panretinal
photocoagulation (PRP) by at least 2-6 weeks because PRP before this
has been known to worsen diabetic macular edema.
• PRP should not be delayed in patients with very severe
nonproliferative diabetic retinopathy or high-risk proliferative diabetic
retinopathy.

Focal Photocoagulation for CSME
• Fluorescein angiography and Fundus photos are obtained prior to
initiation of laser therapy
• Ophthalmologist views the FA to guide treatment of CSME

– For focal leakage, direct laser therapy using green-only Argon
laser is applied to all leaking microaneurysms between 500 and
3000 µm from the center of the macula
– For diffuse leakage or zones of capillary nonperfusion adjacent
to the macula, a light-intensity grid pattern using green-only
Argon laser is applied to all areas of diffuse leakage more than
500 µm from the center of the macula and 500 µm from the
temporal margin of the optic disc
• Multiple sessions spread out over many months are frequently

necessary for resolution of DME

Laser Treatment for CSME
Laser photocoagulation continues to be a well-proven therapy to reduce the risk of vision
loss from diabetic macular edema.
• Focal:
– 50-100  spots to Area(s) of leakage can be identified by
areas of discrete examination (areas of retinal thickening) or by
leakage fluorescein angiography.
• Grid:
– 100-200  spots in
areas of diffuse
leakage
• “Focal-Grid”:
– combination of the Important to avoid foveal avascular zone
above Avoid confluent burns

Prognosis
Macular laser Rx
• ETDRS showed that in eyes with CSME, focal laser
photocoagulation reduces the risk of moderate visual
loss by 50% or more.
• It also reported an increase in the chance of
improvement on the final BCVA.
• However, in all the studies, 15%-24% of eyes had
moderate visual loss despite focal laser Rx.
• These eyes generally had diffuse diabetic macular
edema (DDME) or poor macular perfusion.

LASER Photocoagulation for CSME
• Side Effects and Complications of Focal Laser
– Paracentral scotomata
– Transient increased edema/decreased vision
– Choroidal neovascularization (new abnormal
blood vessel growth beneath the retina)
– Subretinal fibrosis
– Photocoagulation scar expansion
– Inadvertent foveolar burns

Anti VEGF Therapy
• Intravitreal anti-VEGF agents
• VEGF increases retinal vascular permeability, causes
breakdown of the blood-retina barrier, and results in
retina edema.
• VEGF is up-regulated in diabetic retinopathy.
• Three currently available anti-VEGF agents are:
– pegaptanib sodium,
– ranibizumab, and
– bevacizumab

Anti VEGF Therapy
• Pegaptanib sodium
– is a pegylated aptamer directed against the VEGF-A165 isoform. It was the first FDA approved
ophthalmologic anti-VEGF agent for the treatment of choroidal neovascularization (CNV) from
age-related macular degeneration , it appeared to improve anatomic and visual outcome in
patients with diabetic macular edema (DME).10 Phase 3 trials of pegaptanib sodium for diabetic
macular edema are being conducted.
• Ranibizumab
– is a recombinant humanized antibody fragment that is active against all isoforms of VEGF-A.
Intravitreal ranibizumab is FDA approved for the treatment of exudative ARMD. The RESOLVE
study (phase 2, placebo-controlled, randomized, multicenter study) evaluated the effect of
ranibizumab in patients with diabetic macular edema. The RESOLVE study is now concluded,
and final data should be available soon. The RESTORE study (phase 3, laser-controlled,
randomized, multicenter study) is designed to confirm the efficacy and safety of ranibizumab
0.5 mg as adjunctive therapy added to laser photocoagulation and/or as monotherapy in
patients with diabetic macular edema. The Diabetic Retinopathy Clinical Research Network is
planning two phase 3, prospective, randomized multicenter trials of ranibizumab for diabetic
macular edema.
• Bevacizumab
– is a full-length recombinant humanized antibody that is active against all isoforms of VEGF-A. It
is FDA approved as an adjunctive systemic treatment for metastatic colorectal cancer. Small,
nonrandomized pilot studies have documented some efficacy against diffuse diabetic macular
edema. The Diabetic Retinopathy Clinical Research Network conducted a phase 2, prospective,
randomized, multicenter clinical trial to determine the safety and possible benefits of this
agent. They concluded that intravitreal bevacizumab can reduce diabetic macular edema in
some eyes, but the study was not designed to determine whether the treatment was
beneficial.11 A phase 3 trial would be needed for that purpose.

Intravitreal Steroids
• Intravitreal triamcinolone acetonide
• Intravitreal triamcinolone acetonide (IVTA) has been shown
to significantly reduce macular edema and to improve visual
acuity, particularly when the macular edema is
pronounced.6,7,8
• Some studies advocate IVTA as primary therapy, whereas
others label it as adjunctive therapy to macular
photocoagulation.9
• Action is maximal at 1 week, lasting 3-6 months.
• Patients should be counseled about the risk (30-40%) of
increased intraocular pressure, of which virtually all can be
medically controlled.
• Other adverse effects include a less than 1% chance of
retinal detachment, cataract, and endophthalmitis

Role of Vitrectomy Surgery
• Pars plana vitrectomy
– It is widely recognized that there have been recent advancements in
small-gauge vitreoretinal surgery.
– Many studies14,15 suggest that vitreomacular traction or the vitreous
itself may play a role in increased retina vascular permeability.
Removal of the vitreous or relief of vitreous traction with vitrectomy
may, in some patients, be followed by resolution of macular edema
and corresponding visual rehabilitation. However, this treatment may
be applicable only to a specific subset of eyes with diabetic macular
edema.
– Patients with refractory CSME and a taut posterior hyaloid face who
have not responded to macular laser treatment may benefit from a
vitrectomy with possible significant improvement in visual acuity.14
– In eyes with diffuse diabetic macular edema without posterior
vitreous detachment, vitrectomy with posterior vitreous detachment
may be effective in resolving the diabetic macular edema and may
lead to an increase in visual acuity.15

Case Study EM

Case Study EM

Case Studies - Patient EM
• 59-year-old African-American male
• Type 2 DM x 11 yrs
• LEE: 1.5 yr
• Pt complaint “having trouble seeing”
• PMHx:
– Uncontrolled HTN
– + proteinuria
– Last HbA1c = 11.1%
• Meds: insulin, antihypertensive

Patient EM
• Cholesterol levels within normal limits

• Current Albumin/Creatine level =
231.6 µg/mg (Normal: 0 - 20 µg/mg)
• Triglycerides and LDL levels calculated
but non- fasting

Case Study EM
Exam Findings
• VA OD 20/30+ OS 20/30
• Sensorimotor exam normal
• No distortion with Amsler grid
• Early NSC, PSC OU; early CC, vacuoles OS
• IOP 14mmHg OU

Case Study EM
Plan
• Laser treatment for macular edema within

one to two weeks
• Control of BP and BG

Case Study EM
Treatment
• Focal laser treatment
– OD at 3 weeks
– OS at 7 weeks
• 4 month follow-up

Case Study EM
Notes
• HTN, renal disease and dyslipidemia can affect onset
and progression of retinopathy
• Co-management with other health care providers
• Lesions that may indicate nondiabetic etiology
– Venous caliber abnormalities
– Parapapillary cotton wool spots of similar onset
– Flame-shaped hemorrhages
– Diffuse retinal edema
– White centered hemorrhages (Roth’s spots)

Case DG
• 35-year-old Caucasian male
• Type 1 DM 23 years
• VA: OD-20/30; OS-20/40
• Denies hypertension, renal disease,
hypercholesterolemia/dyslipidemia

Patient DG
• Diagnosis:
– Moderate NPDR OU
– DME not CSME OD
– Clinically Significant Macular Edema OS
• Plan:
– FA to identify treatable lesions OS
– Focal laser photocoagulation OS

Prevention of Diabetic Retinopathy
• Prevention of diabetic retinopathy requires prevention of

diabetes
• Patients at higher risk (i.e. family history, ethnicity) of

developing diabetes can adjust modifiable risk factors
Healthy diet
Exercise
Blood pressure control
Tobacco cession
Weight reduction (if obese)

Role of Hypertension in DME
• WESDR - diabetic patients with HTN had
3 x incidence of DME.
• UKPDS__rigorous BP control with ACE-
inhibitor or -blocker reduced the risk of
the two-step progression of DR
significantly.

Role of Renal Disease in DME
• Gross proteinuria associated with 95% increased
risk of DME (WESDR)
• Case reports of reduction of diabetic macular
edema after dialysis
• Type 1 patients with microalbuminuria have
three-fold risk of PDR compared to those
with normal levels
Role of Serum Lipids in DR
• Elevated serum lipids are associated with
increased risk of retinal hard exudates
• Increased amounts of hard exudates are
associated with increased risk of visual
impairment
• Elevated lipids, most notably triglycerides, are
a risk factor for development of high-risk PDR
ETDRS Report # 18 and 22

Role of Vitreous in DME
• Vitreomacular traction is believed to

be a contributor to the multifactorial
etiology of DME.
• The role of the posterior hyaloid in a
subset of eyes with diffuse macular
edema has become increasingly
recognised (Schepens et al, 1984).
• Nasrallah et al observed that a
posterior hyaloid separation was more
common in diabetic eyes without M.E
than with M.E (55% v/s 20.0%).
(Nasrallah et al, Ophthalmology vol 90: 1988)

Vitrectomy Surgery
• New Indication:
– Persistent Diabetic Cystoid Macular Edema
– Vitrectomy surgery is often helpful in cases
withdetectable posterior hyaloid traction, epiretinal,
membrane, or macular striae.
– May also be beneficial in other cases of persistent or
worsening cystoid macular edema
– Considered for diffuse leakage or exudate in foveal
center with vision 20/70 or worse.

Cataract Surgery in Diabetics
• Various studies suggest that DR may progress following

cataract surgery
• Patients who undergo cataract surgery with CSME, Severe

NPDR, or PDR should be considered for photocoagulation
prior to cataract removal
• If density of cataract precludes adequate evaluation of the

retina or precludes treatment, prompt post-operative retinal
evaluation and treatment can be considered

Follow-Up Based Upon Retinopathy Findings
Retinal Abnormality Suggested Follow-Up

Normal or rare Annually
microaneurysms
Mild NPDR Every 9 months
Moderate NPDR Every 6 months
Severe NPDR Every 4 months
CSME Every 2-4 months (careful
f/u)
PDR Every 2-3 months (careful
f/u)
DRCR Network Overview
• Funding:
– National Eye Institute-sponsored cooperative
agreement initiated September 2002
• Objective:
– The development of a collaborative network to
facilitate multicenter clinical research on diabetic
retinopathy, diabetic macular edema and
associated conditions.

DRCR Diabetic Retinopathy
Clinical Research
• The Diabetic Retinopathy Clinical
Research Network reported results DRCR.net
from a multicenter, randomized
clinical trial, comparing focal/grid >150 sites overall
laser photocoagulation and >90 community
intravitreal triamcinolone for the
treatment of diabetic macular >450 total PIs
edema. They concluded that over a >1000 study personnel
2-year period focal/grid laser 40 States
photocoagulation is more effective
and has fewer adverse effects than www.DRCR.net
1-mg or 4-mg doses of preservative
free intravitreal triamcinolone for
most patients with diabetic macular
edema.13
Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for
diabetic macular edema. Ophthalmology. Sep 2008;115(9):1447-9, 1449.e1-10.
65
Dr. Mazhry frcs,fcps

DRCR
CURRENTLY RECRUITING STUDIES
• Randomized trial comparing intravitreal

triamcinolone acetonide and laser
photocoagulation for DME
• Evaluation of vitrectomy for DME
• Observational study of development of DME
following scatter laser photocoagulation
• Subclinical DME study

A Randomized Trial Comparing Intravitreal Triamcinolone
Acetonide and Laser Photocoagulation for Diabetic Macular
Edema
• To determine whether intravitreal triamcinolone acetonide

injections at doses of 1mg or 4mg produce greater benefit,
with an acceptable safety profile, than macular laser
photocoagulation in the treatment of diabetic macular
edema.
• To compare the efficacy and safety of the 1mg and 4mg
triamcinolone acetonide doses

Study Design
• Phase 3, multicenter, randomized clinical trial
• Randomization to one of three treatment groups:
• Standard of care group: conventional treatment
consisting of modified ETDRS photocoagulation
• Intravitreal injection of 1mg of triamcinolone acetonide
• Intravitreal injection of 4mg of triamcinolone acetonide
• Duration of follow-up: Three years

• Injection volume always = 0.05ml

Intraocular Formulation
®
Comparison with Kenalog -40
Ingredient Allergan Form Kenalog® -40
Triamcinolone Acetonide 2 and 8% 4%
Benzyl Alcohol - 0.99%

Polysorbate 80 - 0.04%
Sodium Chloride To Isotonicity To Isotonicity
Sodium Phosphate 0.34% -

Sodium Hydroxide/ to pH 7.3 to pH 5.0 -7.5
Hydrochloric Acid

Formulation and Packaging
Preservative & endotoxin free
Isotonic and pH Balanced
Single-unit Dosing
Allergan
• Sterile, prefilled (0.05ml),
single-dose, ready-to-use
syringe with attached 27-
gauge needle.
• Shelf-stable and requires no
shaking to re-suspend.
• Homogeneous, white
suspension, easily delivered.

Clinical Experience
• >75 active sites in >20 states

• >40 sites with pending certification
• First patient 7/14/04

• >300 patients enrolled

Evaluation of Vitrectomy for Diabetic
Macular Edema
• To provide information on the following outcomes in eyes
with DME that undergo vitrectomy: visual acuity, retinal
thickening, resolution of traction (if present), surgical
complications.
• To identify subgroups in which there appears to be a benefit
of vitrectomy and subgroups in which vitrectomy does not
appear to be beneficial.

Subclinical Diabetic Macular Edema
Study
• Primary Objective: To determine the incidence of progression
of subclinical diabetic macular edema (DME)
– Subclinical DME—no edema involving the center of the fovea as
determined by biomicroscopy but with center point thickness on OCT of
at least 200 microns but less than or equal to 299 microns
– Progression—increase in center point thickness of at least 50 microns to
> 300 microns
• Secondary Objectives:
– To evaluate factors predictive of the presence of subclinical macular
edema
– To determine indicators of risk for progression of subclinical DME

STUDIES IN FOLLOW-UP PHASE
• Pilot study of laser photocoagulation for
diabetic macular edema
• Pilot study of peribulbar triamcinolone
acetonide for diabetic macular edema

Pilot study of laser photocoagulation for
• Compare laser treatment as we now use it

(called “standard method”) with a similar laser
treatment that is milder in intensity, but more
extensive in number (called “mild macular
grid” method)

Pilot study of peribulbar triamcinolone acetonide for
• To estimate the incidence of improvement of DME following a

posterior peribulbar 40 mg triamcinolone acetonide injection
compared with laser.
• To estimate the incidence of improvement of DME following
an anterior peribulbar 20 mg triamcinolone acetonide
injection compared with laser.
• To estimate the incidence of intraocular pressure elevation
and other complications with each type of injection.
• To provide preliminary data comparing the incidence of
improvement of DME with a peribulbar triamcinolone alone
versus peribulbar triamcinolone followed by laser
photocoagulation.

UPCOMING STUDIES
• A Phase 2 Evaluation of Anti-VEGF Therapy for
Diabetic Macular Edema: Avastin
– 200 patient, phase 2 randomized, multi-center clinical
trial.
– Provide preliminary data on the dose and dose interval
related effects of intravitreally adminstered Avastin on
retinal thickness and visual acuity in subjects with
Diabetic Macular (DME) to aid in planning a phase 3 trial.
– Provide preliminary data on the safety of intravitreally
administered Avastin in subjects with DME.

COMPLETED STUDIES
• Temporal Variation in OCT Measurements of Retinal
Thickening in Diabetic Macular Edema
– Determine the proportion of eyes that demonstrate a
potentially meaningful change in central retinal thickening
measured on OCT throughout the day.
– Establish the time course of change for the eyes that
experience diurnal change in central retinal thickening.
– Evaluate intra-observer and inter-observer variability on OCT
measurements.

Eye Research
• Determine basic mechanisms of disease

• Identify potential therapeutic targets
• Develop specific novel therapies
• Evaluate at subcellular, cellular & organism level
• Rigorous clinical trials
• Opportunity to make today’s standard-of-care obsolete
tomorrow

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DME

Current Treatment Options

Dr. Mazhry frcs,fcps 2

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NPDR can affect visual function

Increased retinal vascular

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• Definition: Diabetic macular edema

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Retinal capillaries are non-fenestrated and capillary

No lymphatic system in the retina

Retina responds to ischemia by stimulating growth factors

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– Optimizing diabetic, hypertensive, and lipid control has been

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• Focal/grid laser photocoagulation

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• Ophthalmologist views the FA to guide treatment of CSME

• Multiple sessions spread out over many months are frequently

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• Cholesterol levels within normal limits

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• Laser treatment for macular edema within

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• Prevention of diabetic retinopathy requires prevention of

• Patients at higher risk (i.e. family history, ethnicity) of

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ETDRS Report # 18 and 22

• Vitreomacular traction is believed to

(Nasrallah et al, Ophthalmology vol 90: 1988)

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