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Review Article

Diabetic Retinopathy: An Overview

Ajay Sharma, Trishna Taye, SB Rasel

Abstract: Diabetic Retinopathy (DR) is the most common micro vascular complication of diabetes mellitus and a major

cause of legal blindness.Both ocular & systemic factors are responsible for the pathogenesis of DR. The morbidity from

DR has a great impact on the society.Early diagnosis and prompt treatment reduces the complication and economic

burden .The major treatments for this condition have largely remained unchanged for long years: laser photocoagulation

for proliferative diabetic retinopathy and macular edema, under guidelines of the Early Treatment Diabetic Retinopathy

Study (ETDRS) . However, new therapeutic strategies have appeared, which raise the prospect that the years ahead will

see very significant additions to the options for treatment of diabetic retinopathy. Both corticosteroids and anti-VEGF

treatments are serving as additional options in the clinical management of Diabetic Retinopathy. The emergence of anti-

VEGF treatments strongly highlights the advent of rational drug therapy based on the identification of causative

mechanisms and molecular targets. Though Diabetic Retinopathy is irreversible, early diagnosis & prompt treatment

reduces the risk of visual loss, complications and economic burden on the society.

Key Words : Diabetic Retinopathy, Laser Photocoagulation, Macular oedema, Anti-VEGF

Introduction

Diabetes mellitus (DM) is a multi-factorial metabolic

disorder characterized by altered insulin production or

activity, clinically manifested as elevated blood glucose.

DM can be divided into type 1 or insulin dependent DM

(IDDM) and type 2 or non insulin dependent DM

(NIDDM).10% to 15% have IDDM and are generally

diagnosed before 40yrs of age, but the majority have

NIDDM and are generally diagnosed after 40yrs. DM

causes numerous long term systemic complications that

have considerable associated morbidity.

Diabetic retinopathy (DR) is a highly specific vascular

complication of both type 1 and type 2 DM. The

development and progression of Diabetic Retinopathy is

multi factorial and depends on the duration of DM among

other factors. The exact mechanism by which diabetes

causes retinopathy remains unclear, but several theories

have been postulated to explain the typical course and

history of the disease1, 2. The morbidity and suffering caused

by visual loss, the economic impact from diabetic

retinopathy is tremendous.

Epidemiology

According to the World Health Organization (WHO) the

total numbers of people with diabetes were 171 million in

2000, and are projected to rise up to 366 million in 2030.

80% of people with diabetes live in low and middle income

countries. India has 31.7 million diabetic subjects at

present1 .Projected figures for 2025 are 54 million. In the

Andhra Pradesh Eye Disease Study (APEDS) of self-

reported diabetics, the prevalence of DR was 22.4%2.In

the Chennai Urban Rural Epidemiology Study (CURES)

prevalence of DR was 17.6%.3 After 20 yrs of DM nearly

all patients with IDDM and more than 60% with NIDDM

have some degree of retinopathy. These figures clearly

indicate the magnitude of problem .

Risk factors for DR: The following are the risk factors

which can aggravate DR.

� Duration of Diabetes: Duration of diabetes is a major

risk factor associated with development of DR. After 5

yrs, 25% of type -1 DM patients have some form of

Diabetic Retinopathy, after 10 yrs, 60% and after 15 yrs

80% have DR4,5.

Severity of diabetes: Severity of hyperglycemia is a key

alterable risk factor associated with the development of

DR. Once retinopathy is present, duration of diabetes

appears to be a less important factor than hyperglycemia

for progression from earlier to later stages of retinopathy.6

� Hypertension : Studies, such as The Wisconsin

Epidemiological study of Diabetic Retinopathy (WESDR)

and UK Prospective Diabetes study (UKPDS), suggest that

1Ajay Sharma MS, FIVRS, 2Trishna Taye MS FIVRS,2SB Rasel FCPS, FIVRS1Head of Dept. 2Fellow, Vitreo-Retina departmnent,

Sankar foundation, Visakhapatnam, AP, India

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hypertension increases the risk and progression of DR and

Diabetic Macular Oedema (DME). Intensive management

of HTN has been demonstrated to slow retinopathy

progression.7,8

� Nephropathy: The presence of gross proteinuria at

baseline has been reported to be associated with 95%

increased risk of developing DME among type I patients

in the WESDR. The prevalence of PDR was much higher

in patients with persistent micro albuminuria.9

� Serum lipid: ETDRS has reported a positive correlation

between serum lipids and risk of retinal hard exudates in

type 2 DM. Recently, Gupta et al. have reported reduction

in edema, severity of hard exudates and sub-foveal lipid

migration in patients with type 2 diabetes and

dyslipidaemia, using a lipid-lowering drug, atorvastatin,

as an adjunct to macular photocoagulation10 .

� Pregnancy; Pregnant women with type 1 Diabetes, have

twice the risk of developing PDR than non-pregnant

women. Ideally, young mothers should be examined for

retinopathy before the onset of pregnancy11 .

� Other risk factors include anemia, smoking, cataract

surgery, obesity, cardiovascular disorder etc.

PATHOPHYSIOLOGY:

DR is predominantly a micro-angiopathy in which small

blood vessels are particularly vulnerable to damage from

hyperglycemia. Direct hyperglycemic effects on retinal

cells are also likely to play a role.

Various studies have shown that chronic hyperglycemia,

hypertension and hyperlipidemia contribute to the

pathogenesis of DR. Hyperglycemia damages retinal

vasculature in several ways and progression of DR is

generally related to the severity and duration of

hyperglycemia. The exact mechanism by which raised

glucose levels lead to vascular disruption seen in

retinopathy is poorly defined. However, various

biochemical pathways have been suggested to demonstrate

correlation between hyperglycemia and micro-vascular

complications of retinopathy. Among these pathways,

increased activity of protein kinase C (PKC) and glycation

of key proteins that lead to formation of advanced glycation

end products (AGEs) are more important than polyol

accumulation, oxidative stress, growth factor etc.

Six basic patho-physiologic processes are recognized in

the development of lesions of DR.

1. Loss of pericyte functions of retinal capillaries.

2. Out pouching of capillary walls to form micro aneurysms

3. Closure of capillaries and arterioles

4. Breakdown of blood/retinal barrier

5. Proliferation of new vessels and fibrous tissue.

6. Contraction of vitreous and fibrous proliferation with

subsequent vitreous hemorrhage and retinal detachment

due to traction.

DIAGNOSIS

The initial examination for a patient with diabetes includes

all features of the comprehensive adult medical eye

examination with particular attention to those aspects

relevant to DR.

HISTORY: An initial history should consist of the

following elements:

�Complaints (ocular and systemic) �Duration of diabetis4,6,

Past glycaemic control (hemoglobin A1c)6 and medication.

�Medical history; eg.:Obesity, renaldisease4, hypertention4,

serum lipids, pregnancy, past treatment.

EXAMINATION:

The initial examination should include the following

elements:

� Visual acuity � Slit lamp biomicroscopy

� Intraocular pressure � Dilated fundoscopy including

stereoscopic examination of the posterior pole

� For evidence of macular oedema

EXAMINATION SCHEDULE: Depends upon type of

DM

1. Type 1 DM: Many studies of patients with type 1 DM

reported a direct relationship between the prevalence and

severity of DM and duration of diabetes.12 The

development of vision threatening retinopathy is rare in

children before puberty. Among the patients with type 1

DM, substantial retinopathy may develop as early as 6-7

years after onset of disease4.Ophthalmic examination

should be performed beginning 3-5 years after diagnosis

of type 1 DM4 .

2. Type 2 DM: The time of onset of type 2 DM is often

difficult to determine and may precede the diagnosis by

number of years. 3% of patients whose diabetes is first

diagnosed at age 30 or later will have CSME or high risk

characteristics at the time of initial diagnosis of

diabetes4.About 30% of patients have some manifestations

of DR at the time of diagnosis. Ophthalmic examination

should be performed once at the time of diagnosis of type

2 DM.

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3. DIABETES ASSOCIATED WITH PREGNANCY:

DR can worsen during pregnancy due to metabolic

changes. Patients with DM who become pregnant should

be encouraged to have their eyes examined prior to

conception, and during early pregnancy, should be

counseled on the risk of development and progression of

DR, and should be counselled to make every attempt to

lower their blood glucose level to as near normal as

possible for their own heath and the health of the fetus.

Woman who developed gestational DM do not require eye

examination during pregnancy, because such individual

are not at increased risk for DR during pregnancy.

Table 1- Follow up schedule:

Diabetic type Recommended time of first

ExaminationRecommended follow up*

Type 1 3-5 yrs after diagnosis Yearly

Type 2 At the diagnosis Yearly

Prior to pregnancy type 1/2 Prior to conception & early in No retinopathy to mild or

the first trimester moderate NPDR;Every 3-12

months. severe NPDR or worse

;every 1-3 months

*Abnormal findings may dictate more frequent follow

up examination

CLINICAL FEATURES:

Symptoms:

In the initial stages of diabetic retinopathy, patients are

generally asymptomatic; in more advanced stages, patients

may experience symptoms of floaters, blurred vision and

progressive or sudden visual loss.

SIGNS:

Micro aneurysm: The earliest clinical sign of DR is a

micro-aneurysm. They are located in the inner nuclear layer

of the retina and appear as red dots.

Intra retinal hemorrhage: Dot blot hemorrhages are

located in the middle layers of the retina. Flame shaped

hemorrhages are located in the nerve fiber layers and

follow their course.

Hard Exudates: They are yellow waxy appearance mainly

located at the posterior pole

Cotton-wool spots: They result from nerve fiber layer

infarctions from occlusion of pre-capillary arterioles. They

are frequently bordered by micro-aneurysms and vascular

hyper permeability.

Retinal oedema: It is characterized by retinal thickening

which obscures the underlying RPE.

Intra retinal micro vascular abnormalities (IRMA): They

are either new vessel growth within the retina or, more

likely, pre-existing vessels that become shunts through

areas of non perfusion.

Venous caliber abnormality: They are indicators of severe

retinal ischemia. They can be venous dilatation, beading,

loop formation.

Neovascularization: May be on the disc (NVD), or

elsewhere on the retina(NVE).

Pre-retinal hemorrhages and vitreous hemorrhage:

Appear as pockets of blood within the potential space

between the retina and the posterior hyaloid phase. As

blood pools within this space, the hemorrhages may appear

boat shaped. Vitreous hemorrhage may appear as diffuse

haze or clump in the Vitreous gel.

Fibrovascular tissue proliferation and Traction retinal

detachments

DIABETIC MACULOPATHY: Maculopathy is a

disease of macula and can accompany any stage of DR

including background retinopathy. Maculopathy is a

serious condition and may affect central vision. It is

characterized by macular edema and ischemic

Maculopathy. Macular edema is due to extravasations of

plasma proteins due to damage of blood-retinal barrier.

Ischemic Maculopathy arises due to extensive micro

vascular occlusion and may cause severe loss of central

vision.

Diabetic Maculopathy is of the following types:

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Table 2- Classification of Diabetic Retinopathy (From ETDRS)

Severity Lesion Present

Non Proliferative

No Diabetic Retinopathy No retinal lesion

Microaneurysms only No lesions other than microaneurysms

Mild NPDR Microaneurysms plus retinal hemorrhages,hard exudates

Moderate NPDR Mild NPDR plus cotton-wool spots and/or IRMA

Severe NPDR Presence of one of the following features:microaneurysms plus venous

beading and /or H/MA standard photograph 2A in four quadrants,or

marked venous beading in two or more quadrants or moderate IRMA

(standard photograph 8A) in one or more quadrants)

Very severe NPDR Two or more of the above features described in severe NPDR

Proliferative

PDR without HRC New vessels and/or fibrous proliferations;or preretinal and /or vitreous

hemorrhage

PDR with HRC NVD standard photograph 10A ;or less extensive NVD, if vitreous or

preretinal hemorrhage is present;or NVE half disc area.if vitreous or

preretinal hemorrhage is present

Advanced PDR Extensive vitreous hemorrhage precluding grading ,retinal detachment

involving macula,or phthisis bulbi or enucleation secondary to a

complication of diabetic retinopathy.

1. Clinically Significant Macular Oedema (CSME).

2. Ischemic , with or without associated CSME

3. Cystoid macular edema

4. Non-CSME

CLINICALLY SIGNIFICANT DIABETIC

MACULAR OEDEMA (CSME):(figure 1)

The following are the criteria for CSME

1. Thickening of the retina located at or within

500microns from the center of the macula or

2. Hard exudates with thickening of the adjacent retina

located at or within 500microns from the center of

the macula or

3. A zone of retinal thickening, 1 disc area or larger in

size located at or within one disc area from the

center of the macula.

INVESTIGATIONS

Diabetic retinopathy is essentially a clinical diagnosis.

Investigations are required to aid the diagnosis, plan and

execute the treatment and document for review and

research purposes.

Fundus fluorescein angiography

ETDRS has documented the angiographic risk factors for

progression of NPDR to PDR.13FFA is used to classify

and treat DME into focal and diffuse variety and it also

aids in the diagnosis of CME.

Fig 1: Severe NPDR: Retinal hemorrhages ( red arrow)

seen extensively in all four quadrants. Dilated veins

indicating ischemia( Blue arrow). Also note hard

exudates( yellow arrow).

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Optical coherence tomography(OCT)

OCT generates cross-sectional image which provides us

with quantitative measurement of thickness in the

posterior pole area with reasonable accuracy, thus aiding

in establishing the diagnosis of CSME.14 Some important

features of Diabetic retinopathy are depicted in figures

2 to 4.

Management of DR:

The management of DR can be broadly classified into

1. Control of risk factors 2. Specific treatment

CONTROL OF RISK FACTORS :

Although specific treatment modalities for retinopathy

threatening vision have improved over years of clinical

and research experience, importance of preventive

measures (Good glycemic and blood pressure (BP)

control, smoking cessation, regular eye screening) cannot

be underestimated

Specific treatment: According to ETDRS

Normal or minimal NPDR : The patient with no DR or

minimal NPDR (e.g. with rare microaneurysm) should

be re examined annualy4, because within one year only

5% to 10% of them will develop DR. Existing retinopathy

will worsen by a similar percentage15,16,17. Laser, colour

fundus or angiography are not indicated .

Mild to moderate NPDR without macular edema

(figure5):Patients with mild to moderate NPDR should

have a repeat examination within 6-12 months; because

lesion progression is common15. Laser, surgery and FFA

are not indicated for this group of patients. Color fundus

photo may occasionally be helpful as a baseline for future

comparison and documentation.

Fig.2: CME: OCT showing Cystoid macular edema with

elevation of retinal sensory layers (white arrow) and

cystic spaces (yellow arrow)

Fig.3:OCT showing epiretinal membrane (white arrows)

Fig.4: OCT showing macular edema with pigment

epithelial detachment (white arrow).

Fig.5: PDR with CSME: Hard exudates ( yellow arrow)

with retinal thickening seen within 500 microns from the

foveal center, indicating CSME. Fibro-Vascular

proliferation( Red arrow) can be seen along the superior

temporal arcade.

40

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For patients of mild NPDR, the 4 years incidence of earlier

CSME or macular edema that is not clinically significant

is 12%.For moderate NPDR, this risk increased to 23%

for the patients of type1 and type 2 DM18 . Patients with

macular edema with no CSME should be rechecked within

3-4 months, because they are at risk of developing

CSME19..

Mild to Moderate NPDR with CSME: FFA should be

done prior to laser surgery to identify treatable lesions and

for identifying pathologic enlargement of FAZ (Foveal

Avascular zone) .The treatment of CSME has traditionally

been laser. The ETDRS results showed that the risk of

moderate visual loss is reduced by more than 50% for the

patients who undergo appropriate laser surgery,when

compared to untreated.

More recently data from the diabetic retinopathy clinical

research network (DRCR.net) and other studies have

demonstrated that intravitreal anti VEGF agents and

corticosteroids are effective treatments for CSME19,20 . The

visual acuity gain and reduction in macular thickness

following the administration of the combination of

intravitreal Ranibizumab, with prompt or deferred laser

were greater than the laser alone at 2 years of follow up.

When treatment for macular edema is deferred, as may be

desirable when the centre of macula is not involved or

immediately threatened, the patients should be observed

closely ( at least every 3-4 months) for progression.

SEVERE NPDR AND NON HIGH RISK PDR (figure

6): ETDRS data showed that severe NPDR and non high

risk PDR have a similar clinical course and subsequent

recommendation for treatment are similar .In eyes with

severe NPDR, the risk of progression to proliferative

disease is high. Half of severe NPDR will develop PDR

within 1 year, and 15% will be developing high risk

PDR18.The ETDRS compared early PRP with deferral of

PRP, defined as careful follow up (at 4 month interval)

and prompt PRP if progression to high risk PDR occurred.

When retinopathy is more severe, PRP should be

considered and should not be delayed if the eye has reached

the high risk proliferative stage18. If laser surgery is

indicated, full PRP is a proven surgical technique, and

partial PRP is not recommended 21.

HIGH RISK PDR (figure 7): The risk of severe visual

loss in patient of high risk PDR can be reduced

substantially by means of PRP as described in the ETDRS

and DRS .Most patients of high risk PDR should receive

PRP expeditiously22,23,24 .

HIGH RISK PDR NOT AMENABLE TO

PHOTOCOAGULATION (figure 8) : Victrectomy is

frequently indicated in patients with tractional macular

detachment specially of recent onset, combined tractional

and rhegmatogenous retinal detachment,vitreous

hemorrhage with rubeosis iridis and vitreous hemorrhage

precluding PRP.

Fig.6: PDR: Dilated and tortuous veins indicating

ischemia.(Blue arrows) Multiple new vessels seen

temporal to the fovea(Orange arrow)

Fig.7: High risk PDR: Massive NVD causing bleed and

preretinal hemorrhage seen in the peri papillary

area(Orange arrow). .Hard exudates( Yellow arrow) seen

in the superior macular area.

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Surgical management of DR

The indications for surgery are as follows

1. Persistent Vitreous hemorrhage (V.H)

2. Tractional Retinal detachment (R.D) involving macula

3. Combined tractional and Rhegmatogenous R.D

4. Dense persistent premacula, subhyaloid hemorrhage

5. Rubeosis iridis with V.H

Management of CSME:

The treatment technique is divided into two main

categories:

1. Focal laser: direct treatment of fluorescein leaks

2. Grid laser: treatment of diffuse areas of leakage or

non-perfused retinal thickening.

Pharmacotherapy

Pharmacological agents aim at preventing or reducing

the release of growth factors in response to retinal

ischemia from alterations in the structure and cellular

composition of the microvasculature.

Pharmacological agents:

a. Anti VEGF : 1. Pegaptanib sodium

2. Bevacizumab 3. Ranibizumab

b. Corticosteroids: Triamcinolone acetonide

Indications for Anti VEGF:1. Severe PDR25 . 2.Diabetic

macular edema26 . 3. Prior to PRP and in severe PDR27,28.

4. Rubeosis iridis and neovascular glaucoma29 .

42

Fig.8: PDR with TRD: Extensive fibro vascular

proliferation along major vessel (Blue arrow) and

tractional retinal detachment seen.

Recent advances

�Fenofibrate: Fenofibrate is a peroxisome proliferactor–

activated receptor (PPAR)-á agonist indicated for the

treatment of hypertriglyceridemia and mixed dyslipidemia.

Fenofibrate (200 mg once daily) reduced the need of laser

treatment for macular edema by 31% and for proliferative

retinopathy by 30%.

�Aflibercept: Aflibercept is currently being used in

clinical trials for both exudative Age related Macular

Degeneration and DME. Aflibercept has a higher binding

affinity than other anti-VEGF agents, which translates

into greater activity at lower biological levels and,

consequently, a longer duration of action.

�Sustained drug delivery system:

1) Triamcinolone acetonide (TA) implant (I-vation ).

2) Dexamethasone intravitreal implant (Ozurdex) 0.7 mg

for diabetic macular edema (DME) in pseudophakic

patients or phakic patients scheduled for cataract surgery.

3) Ocriplasmin (Jetrea; ThromboGenics, Belgium) has

been approved by the FDA for the treatment of

vitreomacular adhesion and has some efficacy in inducing

a PVD30.

Conclusion:

Diabetic Retinopathy may be present without any

symptoms. Visual loss due to Diabetic Retinopathy is

usually irreversible. Moreover the awareness of Diabetic

Retinopathy is low among the general public.

Patient access, careful medical and ophthalmological

follow-up, and timely laser photocoagulation are

fundamental to the successful elimination of blindness in

people with diabetes mellitus.

Method of Literature Search

This review was written based on Medline searches with

key words and References as appropriate and using articles

cited in the references of journal articles.

References

1. Wild S, Roglic G, Green A. Global prevalence of

diabetes, estimates for the year 2000 and projections

for 2030. Diabetes Care 2004;27:1047-53.

2. Dandona L, Dandona R, Naduvilath TJ. Population

based assessment of diabetic retinopathy in an urban

population in southern India. Br J Ophthalmol

1999;83:937-40.

INTERNATIONAL JOURNAL OF HEALTH RESEARCH IN MODERN INTEGRATED MEDICAL SCIENCES, ISSN 2394-8612 (P), ISSN 2394-8620 (O), Vol-2, Issue-1, Jan-Mar 2015

3. Rema M, Premkumar S, Anitha B. Prevalence of

diabetic retinopathy in urban India: The Chennai

Urban Rural Epidemiology Study (CURES) eye study.

Invest Ophthalmol Vis Sci 2005;46:2328-33.

4. Klein R,KleinBE, MossSE, etal. The Wisconsin

Epidemiologic study of diabetic retinopathy.

ii.Prevalence and risk of diabetic retinopathy when

age at diagnosis is less than 30 years. Arch

Ophthalmol 1984;102:520-6.

5. VermaR,TorresM,PenaF,etal.Prevalence of diabetic

retinopathy in adultsLatinos:The Los Angeles Latino

eye study .ophthalmology 2004;111:1298-306.

6. Davis MD, Fisher MR,Gangman RE, et al .Risk factor

for high risk proliferative diabetic retinopathy and

severe visual loss.ETDRS report number 18,.Invest

Ophthalmol Vis Sci 1998;39:233-53.

7. UK Prospective study group.Tight blood pressure

control and risk of macrovascular and risk of

microvascular complication in type 2

diabetes.UKPDS 38.BMJ 1998;317;703-13

8. Snow V , Weiss KB,Mottur-PilsonC.,The evidence

based tight blood pressure control I the management

of type 2 diabetes.Ann Intern Med 2003;138:587-92

9. Mathiesen ER, Ronn B, Storm B. The natural course

of microalbuminuria in insulin-dependent diabetes:

A 10-year prospective study. Diabetes Med

1995;12:482-7.

10. Gupta A, Gupta V, Thapar S, Bhansali A. Lipid-

lowering drug atorvastatin as an adjunct in the

management of diabetic macular edema. Am J

Ophthalmol 2004;137:675-82.

11. Klein BE, Moss SE, Klein R. Effect of pregnancy on

progression of diabetic retinopathy. Diabetes Care

1990;13:34-40

12. Klein R, Klein BE,MossSE,etal. The Wisconsin

Epidemiologic study of diabetic retinopathy.

ii.Prevalence and risk of diabetic retinopathy when

age at diagnosis is less than 30 years. Arch

Ophthalmol 1984;102:527 -32.

13. Early Treatment Diabetic Retinopathy Study Research

Group. Fluorescein angiographic risk factors for

progression of diabetic retinopathy: ETDRS report

number 13. Ophthalmology 1991;98:834-40.

43

14. Panozzo G, Gusson E, Parolini B, Mercanti A. Role

of OCT in the diagnosis and follow up of diabetic

macular edema. SeminOphthalmol 2003;18:74-81.

15. Klein R, Klein BE,MossSE,et al.The Wisconsin

Epidemiologic study of diabetic retinopathy 1X.Four

year incidence and progression of diabetic retinopathy

when age at diagnosis is less than 30

years.ArchOphthalmol 1989;107;237-45.

16. Klein R, Klein BE,MossSE,et al. The Wisconsin

Epidemiologic study of diabetic retinopathy X.Four

year incidence and progression of diabetic retinopathy

when age at diagnosis is 30 or more..ArchOphthalmol

1989;107;244-9.

17. Diabetes control and complication trial research

group.The effect of intensive treatment of diabetes

on the development of and progression of long term

complication in insulin dependent diabetes

mellitus.NEngl J Med.1993;329:977-86.

18. Early Treatment Diabetic Retinopathy Study Research

Group.Early photocoagulation for diabetic

retinopathy.ETDRS report number 9.Ophthalmology

1991;98:766-85.

19. Early Treatment Diabetic Retinopathy Study Research

Group.Early photocoagulation for diabetic macular

edema.ETDRS report number 1.Arch Ophthalmol

1985;103:1796-806.

20. Early Treatment Diabetic Retinopathy Study Research

Group.Early photocoagulation for diabetic macular

edema.Relationship of treatment effect to fluorescein

angiographic and other retinal characteristics at

baseline;ETDRS report number 19.Arch Ophthalmol

1995;113: 1144-55.

21. Writing team for the Diabetes control and

complication trial / Epidemiology of diabetes

interventions and complication research group.

Effective of intensive therapy on the micro vascul

arcomplication of type 1 diabetes mellitus. JAMA

2002;287:2563-9.

22. Diabetic Retinopathy Study Research Study

Group.Indication of photocoagulation treatment in

diabetic retinopathy; Diabetic retinopathy study

report number 14. Int OphthalmolClin 1987; 7:239-

53.

INTERNATIONAL JOURNAL OF HEALTH RESEARCH IN MODERN INTEGRATED MEDICAL SCIENCES, ISSN 2394-8612 (P), ISSN 2394-8620 (O), Vol-2, Issue-1, Jan-Mar 201544

23. Diabetic Retinopathy Study Research Study

Group.Four risk factors for severe visual loss in

diabetic retinopathy.The third report from diabetic

retinopathy study.ArchOphthalmol 1079;97:654-5.

24. Early Treatment Diabetic Retinopathy Study Research

Group.hemorrhages in diabetic retinopathy.Two years

results in a standard trial.Diabetic retinopathy

Earlyvictrectomy for severe vitreous victrectomy

study report 2.Arch Ophthalmol 1985;103:1644-52.

25. Injection of IVA as a preoperative adjunct before

vitrectomy surgery in the treatment of severe PDR.-

Rizzo S et al Graefes Arch Clinexp ophth.2008

Jun;246(6) 837-42

26. IntravitrealAvastin treatment of diffuse diabetic

macular edema in Indian population.KumarA,Sinha

S;IJO-2007;Nov-Dec;55(6);451-5

27. IVA prevention of PRP induced complications in

patients with severe PDR-Mason JO, YunkerJJ,

McGwin-Retina 2008 jul 29

28. TorelloM, Costa RA-Actaophth 2008 jun;86(4);

385-9

29. CeskslovOph 2008 Nov 64(6):234-6 {Actaoph 2008

sep-Jiang Y,LiangX,TaoY,Wang K}

30. Peter Stalmans, M.D., Ph.D., Matthew S. Benz, M.D.,

ArndGandorfer, M.D., Anselm Kampik, M.D.,

AnizGirach, M.D., Stephen Pakola, M.D., and Julia

A. Haller, M.D. for the MIVI-TRUST Study

Group,EnzymaticVitreolysis with Ocriplasmin for

Vitreomacular Traction and Macular Holes: N Engl J

Med 2012; 367:606-615August 16, 2012DOI:

10.1056/NEJMoa1110823