DIABETIC MACULAR EDEMA

GENERAL INFORMATION ABOUT DIABETIC MACULAR EDEMA WITH 2 PATIENT CASES, TREATED WITH 2 DIFFERENT TREATMENT TECHNIQUES.
CLASSIFICATION (CSME)
RISK FACTORS
CAUSES
SIGNS AND SYMPTOMS
MANAGEMENT AND TREATMENT OPTIONS
DIAGNISTIC TESTS, BLOOD AND URINE TEST
SCORING SYSTEM
PATHOLOGY
DIFFERENTIAL DIAGNOSIS
PROGNOSIS
EPIDEMIOLOGY
DESCRIPTION OF 2 CASES, THEIR DIAGNOSTIC RESULT AND DETAILS ABOUT TREATMENTS PERFORMED.

1. Applying for：
Administration Specialist
General information:
Macular edema is the build-up of fluid in the macula, an area in the
center of the retina. The retina is the light-sensitive tissue at the back of
the eye and the macula is the part of the retina responsible for sharp,
straight-ahead vision. Fluid buildup causes the macula to swell and
thicken, which distorts vision.

Classification:
 Cystoid macular edema (CME) involves fluid accumulation in the
outer plexiform layer secondary to abnormal perifoveal retinal
capillary permeability. The edema is termed "cystoid" as it appears
cystic; however, lacking an epithelial coating, it is not truly cystic.










Diabetic macular edema (DME) is fluid accumulation and retinal
thickening within the macula as a result of diabetes mellitus.

2.  Who Gets It:
Your chances of DME go up when:
 Your blood sugar, blood pressure, and cholesterol stay high.
 You smoke.
 You don't stay active.
You're more likely to get DME if you:
 Have had diabetic retinopathy for a long time
 Are pregnant
 Are African-American or Hispanic
Types of DME: There are two main ones:
1. Focal DME is small spots of fluid leaking.
2. Diffuse DME has leaks and swelling throughout your macula.
Your eyesight may be worse with diffuse DME.


3. SIGNS & SYMPTOMS:
Often asymptomatic in the earliest stages
COMMON symptoms include:
 blurriness in the center of your vision
 blind spots or patches
 straight lines that look wavy
 colors that look dull or washed out

 may affect your ability to read, write, drive, and recognize faces.
 More severe disease results in visual distortion, loss of color perception
& loss of detail vision.
 May result in ‘legal blindness’ but not total blindness, unless concomitant
proliferative retinopathy with tractional retinal detachment.




CAUSES:
DME begins when the blood glucose is not well regulated. High blood
sugar consistently harms the whole bodily organs, like heart, and the
retina's tiny blood vessels.
Without healthy blood vessels, your retina can't work the way it's
supposed to.
Your body tries to help out by making more of a protein called vascular
endothelial growth factor, or VEGF. But too much of it weakens those
blood vessels. In time, they can tear and leak blood and fluid into your
retina. Your

4. retina will swell and get thicker, a condition called diabetic retinopathy.
The leaking fluid also causes swelling in the macula, the place in the
center of the retina that gives you sharp, clear vision.
So DME is a fluid buildup that makes your macula swollen because
of diabetes.
Diabetes is the main cause of macular edema. But it can happen for
other reasons, too, including cataract surgery or other operations on
your eyes, macular degeneration, swelling in the uvea (the middle part of
your eye), and blocked veins in your retina or damage from radiation.
Some medicines for diabetes, cancer, and multiple sclerosis can cause
macular edema.

DIAGNOSIS:
 CLINICAL PRESENTATION :
i. Patients with DME present with a range of visual symptoms depending on
the degree to which the fovea is involved and the chronicity of the
edema.
ii.If the macula center is not involved patients are rarely symptomatic.
iii. Some patients with central macular involvement have excellent acuity
and no visual complains, presumably because of only recent involvement
of the center.
iv.Patients may complain of loss of color vision, poor night vision and
washing-out of vision in bright sunlight with poor dark -light
adaptation.
v. Metamorphopsia is oten seen.

5. The definition of clinically significant macular edema (CSME) is the
most significant outcome of the ETDR (Early Treatment Diabetic
Retinopathy Study), sets the standard of care for managing diabetic
macular edema, is that it established a method for classifying and
diagnosing DME and determining when treatment is required.
Clinically Significant Macular Edema (CSME) is seen when one of
the following occurs:
1) Retinal thickening at or within 500 microns or 1/3 disc diameter
of center of macula.
2) Hard exudates at or within 500 microns of the center of the
macula with adjacent retinal thickening.
3) Retinal thickening GREATER than 1 disc diameter in size which is
within 1 disc diameter from the center of the macula.
It is important to bear in mind that a classification relying on a reti
nal biomicroscopic patient examination, not fluorescein
angiography, is the determination of the existence of CSME.

6.  BLOOD AND URINE TEST:
 Random blood sugar test;
A random blood glucose test means that you draw blood, regardless of
the moment you last eat. The diabetes is indicated by results equal or
above 200 milligrams (mg / dL) per decilitre.
 Fasting blood sugar test :
Fasting blood sugar tests means that you have blood drawn after you
have fasted, which usually means not eating for 8 to 12 hours:
 NORMAL : less than 100 mg/dL
 PREDIABETIC : between 100 and 125 mg/dL
 DIABETES : Results equal to or greater than 126 mg/dL after two
tests
 Oral glucose tolerance test :
The oral glucose test (OGTT) takes place over the course of two hours.
Your blood sugar is tested initially, and then you’re given a sugary drink.


7. After two hours, your blood sugar levels are tested again:
 NORMAL : Results of less than 140 mg/dL
 PREDIABETIC : Results between 140 and 199 mg/dL
 DIABETIC : Results equal to or greater than 200 mg/dL
 Urine testing for diabetes :
The diagnosis of diabetes is not always based on urine tests. They are
often used by doctors if they believe you may have type 1. If the fat
tissue is used for energy rather than blood glucose, the brain generates
ketone organs. Urine for these ketone organs can be tested by
laboratories.
If ketone bodies are present in moderate to large amounts in the urine,
this could indicate your body is not making enough insulin.


To check for vision loss.
The doctor uses a range of visual diagrams to learn how well you see
from various distances.

8.  IMAGING:
 Optical Coherence Tomography (OCT):-
This analysis demonstrates the retinal layers and estimates the
thickness of the retina. It can assist demonstrate a retinal indication
of some retinal illnesses such as Wet Age -related Macular
Degeneration (Wet AMD) and Diabetic Macular Edema (DME) if liquid
is in or under the retinal retina.

 Fluorescein Angiography:-

The dye is injected in a venous in your arm during this test. This color
allows your eye doctor to check for leakage in the vessels of your eye
or retina changes.

9.  Fundus Photography:-
This test lets your eye doctor look closely at your retina by taking
pictures of the back of the eye.


 Dilated (slit-lamp) eye exam:-
The doctor will use eye drops to make your pupils bigger (dilated). This lets
in more light so it's easier for them to see inside your eye. Then doctor looks
at the retina -- the place at the back of your eye where light hits -- for
problems like leaking blood vessels and swelling. They can also spot bleeding
in your macula. That's the part of your retina that gets damaged by DME.

10.  SCORING SYSTEM:-

11.  PATHOLOGY:
Normal retinal circulation is unique: retinal capillaries are non-fenestrated and
capillary endothelial cells have tight jonctions; normal capillaries do not leak
fluid, blood. There is no lymphatic system in the retina, so 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).
DME is the result of microvascular changes in diabetes leading to incompetence
of vessels, edema. Hypoxic state stimulate VEGF causing more edema.
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)

Photomicrograph of cystoids
spaces and subretinal fluid in the
retina of a diabetic patient with
severe DME

12.  DIFFERENTIAL DIAGNOSIS:

 Branch Retinal Vein Occlusion (BRVO)
 Central Retinal Vein Occlusion (CRVO)
 Exudative (Wet) Age-Related Macular Degeneration (AMD)
 Hypertension
 Pseudophakic (Irvine-Gass) Macular Edema
 Uveitis Evaluation and Treatment


MANAGEMENT:


 Laser Photocoagulation:-
i. laser photocoagulation had been the mainstay of treatment for DME
for almost for the past 25 years.

13. ii. The mechanisms of action of focal/grid laser are not well understood and are
not discussed in this review. However, the technique involves placement of
light, small (around 50 micron) laser burns only within thickened areas of the
macula, including direct (focal) treatment of microaneurysms as well as spots
scattered approximately two to three burn widths apart (grid) within other
areas of edema not accounted for by microaneurysms.
iii. In addition to the traditional argon or diode laser used for macular
photocoagulation, several newer laser technologies are being evaluated. One
of these is a navigated laser photocoagulator (NAVILAS) that integrates a
scanning laser slit camera with fluorescein angiography and employs
computer aided steering of the laser.
iv. Other newer laser technologies include subthreshold diode-laser micropulse
technology and selective retina therapy (SRT), which aims at minimizing
retinal and RPE tissue damage.
 Corticosteroids:-
i. Given the apparent role of inflammation in the pathogenesis of DME,
steroids have more recently been utilized for the treatment of DME. Their
mode of action may be largely through their ability to inhibit the
expression of VEGF.
ii. Intravitreal Triamcinolone, Fluocinolone acetonide.
 Anti VEGF Therapy:-
i. The VEGF family is a sub-group of growth factors that include VEGF-A,
B, C, D, E and placental growth factor (PlGF).
ii.Because of its central role in the pathogenesis of DME, VEGF was a logical
target for therapy. Several anti-VEGF agents are available.

14. iii. The first anti-VEGF agent used in ophthalmology was pegaptanib.
iv. Another anti-VEGF agent that has been developed and is pending FDA
approval for neovascular age-related macular degeneration is VEGF
trap-eye.
v. Bevacizumab, Ranibizumab, Aflibercept.
PROGNOSIS:
 Presence of an enlargement of the foveal avascular zone (FAZ), which
may be associated with poor visual prognosis.
 The evolution of DME is slow. It may wax and wane, probably under
the effect of systemic factors, such as high blood pressure and
glycemia.
 In the control group of the ETDRS trial, only 15% of patients with
CSME had significant visual loss after a 3-year follow-up (Early
Treatment Diabetic Retinopathy Study Research Group, 1985)
 The long-term prognosis of DME, however, is poor in eyes with
persistent macular edema.
 Factors of poor visual prognosis include long duration of edema,
severe macular nonperfusion, subfoveal plaque exudates, or
subfoveal fibrosis.
EPIDEMIOLOGY:
 DME occurs in approximately 14% of diabetics and can be found in
both type I and type II patients (Girach and Lund-Andersen, 2007).

15.  The reported risk factors for occurrence and progression of DME are
duration of diabetes, degree of metabolic control, elevated glycosylated
hemoglobin A1c, severity of DR, hypertension, low socioeconomic
status, and older age.
 Additional risk factors for progression of DME have been reported
including dyslipidemia, microalbuminuria, and proteinuria.
 Pregnancy may cause progression of DME and PDR with postpartum
regression in some patients and persistent edema in others.
 Elevated plasma levels of IL-6 were also strongly related to the severity
of macular edema (Girach and Lund Andersen, 2007).
REFERENCES:
www.webmd.com
www.ncbi.nlm.nih.gov
www.looktoyourfuture.com
www.mayoclinic.org
www.aao.org
http://www.jcor.in
http://www.djo.harvard.edu
nei.nih.gov
Macular Edema A Practical Approach (Volume Editor
Gabriel Coscas Créteil, Paris)

16. DETAILED DESCRIPTION :
A 52 year old man with a 9 year history of diabetes (as controlled as
possible).
He had diabetic retinopathy, his both eyes have artificially implanted
lenses.
He has a history of quite unmanagable DME.
Intravitreal Injection of Anti-VEGF Ranibizumab

1. Anesthesia: A subconjuctival injection of Lidocaine was given.
2. Povidone-iodine : A brown solution applied on the eyelids and
surrounding area to decrease the bacterial colonization, risk of
developing endophthalmitis and mark the working area.
3. Insert sterile speculum : To prevent needle from being inserted
in the eyelids, and prevention against blinking a speculum was
inserted.
4. Cover the face with cloth with a hole to expose eye and brow region.

17. 1. Injection Volume : 0.05 mL of Ranibizumab in a 30 gauge needle.
2. Location : The patient was asked to look up or away from the site
of injection. The injection was given 3 - 3.5 mm away from the
Limbus.



3. After the injection administration, a sterile cotton swab was placed
on the injection site to prevent reflux.

 POST- TREATMENT -
1. Re-treatment criteria were the persistence or relapse of leakage
combined with visual acuity (VA) deterioration.
2. Exactly same procedure of intravitreal injection after 1 month.
3. Follow up: 1 and 3 months after treatment

18. A 77-year-old man presented with blurred vision to 20/40 in his left
eye from clinically significant macular edema (CSME)

FA of the Left Eye: confirmed the presence of leaking
microaneurysms centered supranasal to the fovea.

OCT : minimal thickening in the right macula, but identifies foveal-
involving macular edema and subfoveal fluid in the left eye.

The patient was extremely averse to needles, and he also had
difficulty returning to the office for regular visits.

DIAGNOSIS: - CSME (Clinically Significant Macular Edema)

RECOMMENDATION : -
Fundus Photography - This test lets your eye doctor look closely at
your retina by taking pictures of the back of the eye.

19. 1. A whitening of microaneurysms with 50 - to 100-μm spots for a
duration of 0.1 s.
2. Repeat focal burns are applied, if needed, to obtain the desired
effect, especially for microaneurysms larger than 40 μm.
3. Retreatment is required if macular edema persists and the
above-mentioned criteria are not met.
4. Clusters of microaneurysms could be treated with larger and
confluent spots (200–500 μm), if lesions are not located within
750 μm from the center of the macula.

 Post-operative treatment :
1. Investigate long-term visual acuity and macular thickness on OCT
post-treatment.
2. Additional treatment is recommended if 4 months following
initial treatment, residual CSME with treatable lesions is seen
on examination.
3. Intervals between laser sessions need to be at least 4 months.

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