EPIDEMIOLOGY

Global Information

• Worldwide, diabetic retinopathy is the leading cause of blindness among working-aged adults.
• The global burden of diabetic retinopathy includes:
• 387 million people with diabetes mellitus (DM) in the world, estimated to increase to 592 million people in 2035.
• 93 million people with diabetic retinopathy
• Affects 1 out of 3 persons with diabetes mellitus
• Proliferative diabetic retinopathy (PDR): 17 million people
• Diabetic macular edema: 21 million people
• Vision-threatening diabetic retinopathy: 28 million people
• Prevalence of diabetic retinopathy is worldwide with only slight ethnic differences.
• Worldwide prevalence of DR in patients with type 1 DM is 77.3% and with type 2 is 25.1%.
• Changes in diet and lifestyle are suspected in the increase in DR prevalence.
• Earlier detection of DR in patients with diabetes, owing to better health care systems, contributes to the prevalence figures.
• 5%-8% of people with DR will need laser treatment.
• 3%-10% will have diabetic macular edema and 30% of them will have visual impairment.
• 0.5% of diabetic patients will need a vitrectomy.

Region-Specific Information (Middle East)

• Six of the 10 countries with the highest prevalence of diabetes in the world are in the Middle East (Bahrain, Kuwait, Lebanon, Oman, Saudi Arabia, and United Arab Emirates).
• The prevalence of diabetic retinopathy ranges from 19% in the UAE to 64% in Jordan (Table 1).

DIFFERENTIAL DIAGNOSIS

• Hypertensive retinopathy (Figure 1)
• Central retinal vein occlusion (Figure 2)
• Branch retinal vein occlusion (Figure 3)
• Ocular ischemic syndrome (Figure 4)
• Radiation retinopathy (Figure 5)
• Sickle cell retinopathy (Figure 6)
• Sarcoidosis (Figure 7)

PATHOPHYSIOLOGY/DEFINITION

Chart 1. Pathophysiology.

Risk Factors

Duration of Diabetes

Type 1 DM

1. 25% of patients will have DR after 5 years, 60% after 10 years and 80% after 15 years
2. 50% of patients under 30 years old will develop PDR if duration of DM is 20 years or more (WESDR)
3. 18% of patients after 15 years of diagnosis will develop PDR with no difference between type 1 and 2 (LALES-VER)

Type 2 DM

1. Patients >30 year 19 years, percentages are 84% and 53% respectively.
2. PDR will develop in 2% of patients if duration of DM is < 5 years and 25% if > 25 years

Glycemic control

1. Key modifiable risk factor
2. Recommendation: Hb A1c 7% or 6.5% in selected cases

High Blood Pressure

1. Slows progression of diabetic retinopathy

Blood Lipids

1. Slows progression of diabetic retinopathy

Pregnancy

1. Gestational diabetes does not require an eye examination during pregnancy and does not increase the risk of diabetic retinopathy.
2. Diabetic retinopathy can worsen during pregnancy; patients should have an eye examination before pregnancy and during the first trimester.
3. If a patient has no retinopathy or mild to moderate NPDR, examinations should be performed every 3 to 12 months.
4. If a pregnant patient has severe NPDR or worse, eye examinations should be performed every 1 to 3 months.
5. If neovascularization is detected during pregnancy, laser therapy should be performed.
6. Macular edema in pregnant patients can improve with delivery, no intravitreal anti-VEGF is recommended. Consider intravitreal steroids.
7. Diabetic retinopathy in a pregnant patient is not a contraindication for natural vaginal delivery.

Renal Impairment

Age

Clotting factors +

Renal Disease +

Physical Inactivity +

Inflammatory Biomarkers +

+ Encourage patients to be compliant with all medical aspects of their disease as these factors are associated with substantial cardiovascular morbidity and mortality.

PATIENT HISTORY

• Medical history
• Micro- and macrovascular complications
• Meds: Insulin, oral hypoglycemics
• Duration and type of diabetes
• HbAc1
• Ocular history

PHYSICAL EXAMINATION

• Visual acuity
• Intraocular pressure
• Slit lamp biomicroscopy
• Gonioscopy before dilating pupils
• Funduscopic examination of the posterior pole under dilated pupil
• Examination of peripheral retina and vitreous under dilated pupil
• Examination findings consistent with pathophysiology (Chart 1)

SIGNS/SYMPTOMS

• Asymptomatic
• Decreased vision
• Floaters
• Metamorphopsia
• Symptoms of retinal detachment
• Cotton-wool spots (Figure 8)

CLASSIFICATION

Classification of Diabetic Retinopathy

• See Table 2.

IRMA = intraretinal microvascular abnormalities; NPDR = nonproliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy
Source: American Academy of Ophthalmology Retina-Vitreous Panel. Preferred Practice Pattern® Guidelines. Diabetic Retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2014. Available at: www.aao.org/ppp.

Classification of Diabetic Macular Edema

• See Table 1

Source: American Academy of Ophthalmology Retina -Vitreous Panel. Preferred Practice Pattern® Guidelines. Diabetic Retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2014. Available at: www.aao.org/ppp.

• Diabetic macular edema (Figure 14)

Clinically Significant Macular Edema

• See Table 2

Source: Basic and Clinical Science Course, Section 12, American Academy of Ophthalmology, 2014-2015.

TREATMENT OF DIABETIC RETINOPATHY

• Treatment strategies are effective in 90% of cases to prevent severe visual loss.
• Most important factor in medical management of diabetic retinopathy is good glycemic control, which is associated with reduced risk of newly diagnosed retinopathy and of progression of existing retinopathy. Diabetes Control and Complications Trial-United Kingdom Proliferative Diabetic Retinopathy Study (DCCT-UKPDS).
• Adequate control of hypertension reduces progression of retinopathy and loss of vision (UKPDS)
• Encourage changes in lifestyles and good metabolic control in all diabetic patients
• Treatment options
• Laser therapy
• Anti-VEGF drugs (bevacizumab, ranibizumab, aflibercept)
• Surgery

TREATMENT OF DIABETIC MACULAR EDEMA

Available therapies are:

Laser Therapy

1. Focal laser : FDA approved based on ETDRS findings
2. Micropulse laser

Anti-VEGF Drugs

1. Aflibercept : 2mg every 8 weeks after 5 initial monthly injections: Approved by US Food and Drug Administration (FDA) in July 2014 based on VIVID-VISTA clinical trials results
2. Ranibizumab: 0.3 mg monthly Approved by FDA in August 2012 based on RISE- RIDE clinical trials results
3. Bevacizumab: Off-label use worldwide

Steroids

1. Intravitreal Injections
2. Intravitreal implants
• Ozurdex (Dexamethasone): 0.7 mg, re-treatment after 6 months of previous treatment. Approved by FDA in June 2014 based on the MEAD study.
• Iluvien (Flucinolone Acetonide): 0.19 mg last up to 36 months Approved by FDA in September 2014 based on the FAME study.

Anti-VEGF Drugs

Surgery

1. Consider in cases of vitreomacular traction

• Tractional retinal detachment (Figure 15)

CSME: clinically significant macular edema. ME: Non-clinically significant macular edema. NPDR: Nonproliferative diabetic retinopathy. PDR: Proliferative diabetic retinopathy. Anti VEGF: anti-vascular endothelial growth factor

Source: American Academy of Ophthalmology Retina -Vitreous Panel. Preferred Practice Pattern® Guidelines. Diabetic Retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2014. Available at: www.aao.org/ppp.

• Presence of CSME: See Figure 16, Figure 17, and Figure 18
• Treatment with focal laser photocoagulation. See Figure 19.
• Treatment with grid laser photocoagulation. See Figure 20.
• Panretinal photocoagulation (scatter) laser: See Figure 21.

CASE STUDY

History of Present Illness

A 68-year-old male patient complained of poor vision in his left eye. He had never had an eye examination before and was not aware of the recommendation for an annual eye exam.

Past Medical History

Diabetes mellitus type 2 diagnosed 1 year ago. He reported that his blood sugar was well controlled. His HbA1c was 5.9%.

Examination

• Visual acuity: 20/30 right eye, 20/60 left eye
• Extraocular movements: Full
• Intraocular pressure: 16 mm Hg OU
• Cornea: clear both eyes
• Anterior chamber: deep and quiet, with no neovascularization of the iris
• Lens: Nuclear sclerotic cataract both eyes (+)
• OD: moderate NPDR and no macular edema. (Figure 27A).
• OS: moderate NPDR with severe macular edema. (Figure 27B)

Treatment

1. Recommended that the patient undergo anti-VEGF treatment in his left eye.
2. The patient underwent 4 injections of aflibercept in the left eye monthly, followed up with OCT on each visit. Visual acuity improved to 20/20.

IMAGE LIBRARY

Differential Diagnosis

Figure 1. Hypertensive retinopathy. Note the disc edema, macular exudates, intraretinal hemorrhage with nerve fiber layer infarct, and venous congestion.

Figure 2. Central retinal vein occlusion (CRVO). CRVO in an eye with hand motions vision. The veins are dilated, and retinal hemorrhages are present. 

Figure 3. Branch retinal vein occlusion.

Figure 4. Ocular ischemic syndrome. A, Clinical photograph of an eye with ocular ischemic syndrome displaying features of conjunctival injection, cataract, and rubeosis irides. B, Gonioscopic appearance of neovascularization of the iridocorneal angle due to ocular ischemic syndrome. C, Fundus photograph of an eye with ocular ischemic syndrome showing features of venous dilation, midperipheral intraretinal hemorrhages, and attenuated arterioles. D, Fluorescein angiography image at 19 seconds (arterial phase) demonstrating a prolonged arm-to-retina circulation time and a patchy choroidal filling pattern.

Figure 5. Radiation retinopathy. Image of an eye that has undergone plaque brachytherapy for treatment of choroidal melanoma. The melanoma can be seen nasally, obscuring part of the disc.

Figure 6. Sickle cell retinopathy, with peripheral neovascularization (“sea fan” neovascularization) with autoinfarction.

Figure 7. Sarcoidosis, with retinal vascular sheathing.

Pathophysiology/Definition

Figure 8. Cotton-wool spot (capillary retinal arteriole obstruction).

Figure 9. Diabetic macular edema. A.Mechanism of diabetic macular edema, demonstrating development of thickening from a breakdown of the blood–retinal barrier. B. Spectral-domain optical coherence tomogram of diabetic macular edema. Note the foveal detachment.

Figure 10. Retinal neovascularization. (Image courtesy of Kellogg Eye Center, University of Michigan.)

Figure 11. Tractional retinal detachment. There is associated hemorrhage due to traction on fronds of neovascular ingrowth.

Management Classification

Figure 12. Moderate neovascularization elsewhere with preretinal hemorrhage. (Reproduced, with permission, from Schubert HD. 

Figure 13. Diffuse intraretinal hemorrhages (arrow) and microaneurysms in nonproliferative diabetic retinopathy.

Figure 14. Venous beading in nonproliferative diabetic retinopathy.

Figure 15. Intraretinal microvascular abnormalities (IRMAs) in nonproliferative diabetic retinopathy. Fluorescein angiogram showing microaneurysms, areas of nonperfusion, and intraretinal capillary remodeling.

Treatment

Figure 16. Clinically significant macular edema. Retinal edema located at or within 500 μm of center of macula.

Figure 17. Clinically significant macular edema. Hard exudates ≤500 μm of center of macular if associated with adjacent edema.

Figure 18. Clinically significant macular edema. A zone of thickening larger than 1 disc area within 1 disc diameter of the center of the macula.

Figure 19. Treatment with focal laser photocoagulation.

Figure 20. Treat with grid laser photocoagulation for diffuse clinically significant diabetic macular edema.

Management

Figure 21. Scatter panretinal photocoagulation

Figure 22. Vitreous hemorrhage w/decreased vision for more than 3 months.

Figure 23. Traction retinal detachment involving the macula.

Figure 24. Macular epiretinal membrane or displacement of macula.

Figure 25. Pars plana vitrectomy.

Figure 26. Proliferative diabetic retinopathy. (Top) Before treatment. (Bottom). One week after intravitreal injection with bevacizumab, the patient’s fundus examination showed much improvement.

REFERENCES

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CONTRIBUTORS

Executive Editor:
R. V. Paul Chan, MD, FACS, Weill Cornell Medical College, New York, New York

Section Editor:
North Africa/Middle East:
Ebtisam S. Kadhem Al-Alawi, FRCS, MRCOpht, DO, Salmaniya Medical Center, Bahrain

Assistant Editors:
Swetangi D. Bhaleeya, MD, Weill Cornell Medical College; New York, New York
Kristin Chapman, MD, Weill Cornell Medical College, New York, New York
Peter Coombs, MD, Weill Cornell Medical College; New York, New York
Michael Klufas, MD, Weill Cornell Medical College, New York, New York
Samir Patel, medical student, Weill Cornell Medical College; New York, New York

Region Contributor:
Mariam A. Hadi Almohsen, Senior Resident, Salmaniya Medical Complex, Bahrain

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