Diabetic Retinopathy

Outline: •Diabetic Retinopathy (DR) •Central Serous Choroidopathy (CSC) •Age-related Macular Degeneration (AMD)

Diabetic Retinopathy 糖尿病视网膜病变

Survey: Diabetic retinopathy is the leading cause of new cases of blindness in the United States in patients between the ages of 20 and 74. In the developing Western countries, at least 12﹪ of all blindness is due to diabetes. In the United States, a diabetic patient has more than a 20fold chance of becoming blind compared to a nondiabetic counterpart.

1 、 Risk factors

• The duration of insulin-dependent diabetes is the main factor in the appearance of diabetic retinopathy. When diabetes is diagnosed before age 30 years, the risk of developing retinopathy is about 2﹪ per year. After 7 years and 25 years, 50% and 90% of diabetic patients, respectively, will have some form of retinopathy. After 25 to 50 years of diabetes, 26% will have the proliferative form.

1 、 Risk factor

• Puberty (adolescence) and pregnancy both stimulate development of retinopathy. The 10-year rate of vision loss to less than 20/40 is about 10% in juvenile diabetics, insulin-dependent disease, and 24% in adult-onset, non-insulin- dependent diabetes. The Diabetes Control and Complications Trial (DCCT) showed that intensive insulin treatment to control blood sugar levels tightly decreased the risk of developing severe nonproliferative or proliferative retinopathy and reduced the need for laser surgery by about 50%.

2 、 Types of diabetes • (1)Type 1 (juvenile onset ) diabetes cases are autoimmune (pancreatic [ 胰 腺 ]destruction) and have a high risk for developing severe proliferative retinopathy.

2 、 Types of diabetes • (2) Type 2 (adult onset ) diabetes cases have normal to high insulin production but insulin-resistant receptor cells. There are more type 2 patients with blinding sequelae( 后遗 症 ) because of the greater number of type 2 diabetic patients.

3 、 Medical evaluation

• Every diabetic patient deserves the benefit of a comprehensive evaluation, with careful attention paid to determine the presence of symptoms of diabetic retinopathy such as decreased vision, distortion of vision, loss of color vision, and the presence of floaters. The duration of diabetes and the method of control of diabetes should be assessed. The presence of associated systemic disease should be noted. Hypertension is present in 20% of insulin-dependent diabetes and in 58% of non-insulin-dependent diabetes. Optimal （最佳） medical control is key to minimizing ocular and systemic complications

4 、 Clinical appearance • Diabetic retinopathy is classified into four groups • (1)Background retinopathy (nonproliferative retinopathy) • (2)Preproliferative diabetic retinopathy • (3) Proliferative diabetic retinopathy • (4) Diabetic maculopathy

(1) Background retinopathy (nonproliferative retinopathy)

• The diabetic lesions （损害） of background retinopathy are dilated （扩大） veins, intraretinal hemorrhages, microaneurysms, hard exudates, edema, and CWSs (cotton wool spots). Dot-blot hemorrhages, retinal edema, and hard exudates result from increased vascular permeability. Microaneurysms cluster around areas of capillary nonperfusion.

dot or blot haemorrhages

microaneurysms

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hard exudates forming a ring or circinate 漩涡状的 pattern around a leaking microneurysm

soft excudates in posterior fundus in moderate DR

• DR FA (fluorescein angiography )

(2)Preproliferative diabetic retinopathy

• Preproliferative diabetic retinopathy represents the most severe stage of background retinopathy (nonproliferative retinopathy). Preproliferative retinopathy is categorized by the presence of many intraretinal hemorrhages and microaneurysms, intraretinal microvascular abnormalities (dilated vessels within the retina), and venous beading. There is wide spread capillary closure. Approximately 10% to 50% of patients with preproliferative retinopathy develop proliferative retinopathy within a year.

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Splinter 片 haemorrhages and intraretinal microvascular abnormalities

(3) Proliferative diabetic retinopathy

• Proliferative diabetic retinopathy occurs in 5% of patients with diabetic retinopathy. In the proliferative stage, vascular abnormalities appear on the surface of retina or within the vitreous cavity, starting postequatorially. Visual loss can be severe. New blood vessels grow on the surface of the retina and the optic nerve and are usually attached to the posterior hyaloid （透明） surface of the vitreous body causes traction on the retinal neovascularization, resulting in vitreous hemorrhage and/or traction retinal detachment .

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Retinal Detachment

(4) Diabetic maculopathy

• Diabetic maculopathy may result from increased vascular permeability with or without intraretinal lipoprotein deposits (hard exudates), or, less commonly, from ischemia due to closure of foveal capillaries. Diabetic maculopathy may be seen in any phase of retinopathy except for very early background disease.

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DR macular

5 、 Pathology

Histology of eyes with diabetic retinopathy shows loss of intramural 壁内的 pericytes 外膜细 胞 and extensive capillary closure in trypsin 胰 岛素 -digest flat preparations of the retina. The blood-retinal barrier is compromised mainly by defects in the junctions between abnormal vascular endothelial cells. The most widely accepted working hypothesis for the pathogenesis 发病机理 of proliferative retinopathies such as diabetes, retinopathy of prematurity (ROP 早产儿视网膜病 ), and CRVO is that retina rendered ischemic by widespread capillary closure elaborates VEGF, which stimulates retinal neovascularization and/or rubeosis 潮红 of the iris.

6 、 Management

• Diabetic retinas are best examined using a binocular viewing system which provides moderate magnification such as a slitlamp at 10× in conjunction with a 90-D （ diopter ） lens to allow the stereoscopic 立体 vision. It is important to have the patient look in various fields of gaze so the more peripheral retina to the equator can be inspected, because approximately 27% of retinal abnormalities are found outside the central 45-degree area. Indirect ophthalmology provides a view of the retina at, and anterior to, the equator. Color photography is used to document the progress or regression of retinopathy following treatment. Fluorescein angiography defines areas of leakage and ischemia, and confirms the presence of neovascularization of the retina or disk.

• DR neovascularization of disc

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DR neovascularization

6 、 Management

• Diabetic eyes should be inspected for rubeosis with a slitlamp before the pupil is dilated because fine vessels on the iris are almost impossible to see once mydriasis 瞳孔扩大 is induced. Gonioscopy 前房角镜检查 is necessary if new vessels are seen on the surface of the iris with the slitlamp. To properly inspect the retina, wide pupillary dilation is needed.

6 、 Management • (1)Three major clinical trials have been carried out by the National Eye Institute to determine the retinal history of nonproliferative and proliferative diabetic retinopathy, as well as guidelines for treatment.

6 、 Management

• (a) The Diabetic Retinopathy Study (DRS) showed that scatter argon laser photocoagulation (panretinal photocoagulation 激光光凝 ) reduced the incidence of severe visual loss (vision less than or equal to 5/200) by half or more in eyes with neovascularization on the disk or within one disk diameter of the disk. A similar reduction in the rate of severe visual loss was obtained in eyes with neovascularization elsewhere associated with vitreous hemorrhage.

• laser pan-retinal photocoagulation

6 、 Management • (b) The Early Treatment Diabetic Retinopathy Study showed that eyes with clinically significant macular edema benefited from focal argon laser to discrete 不连续 areas of leakage and grid 格子 photocoagulation to areas of nonperfusion or diffuse leakage. Moderate visual loss was defined as a doubling of the visual angle: e.g., going from 20/20 to 20/40.

6 、 Management • Laser treatment reduced the risk of such visual loss by 50% or more, increased the chance of improved vision, and had only minor visual field effect. Focal photocoagulation for vision-threatening macular edema should be given before scatter photocoagulation (PRP) for approaching high-risk proliferative retinopathy. Aspirin had no clinical effect. Observation only was indicated for eyes with mild to moderate nonproliferative retinopathy

6 、 Management • (c) The Diabetic Retinopathy Vitrectomy Study showed that type 1 diabetic patients with recent, severe vitreous hemorrhage associated with vision equal to or more than 5/200 undergoing early vitrectomy 玻璃体切除 (within 6 months) had a notably better chance of attaining 20/40 or better vision than those whose vitrectomy was deferred a year. Type 2 or mixed diabetic patients did not benefit from early vitrectomy for severe vitreous hemorrhage. Patients with severe proliferative retinopathy with vision equal to or greater than 10/200 had a better chance of attaining 20/40 or better vision if they had early vitrectomy than those managed with conventional therapy.

6 、 Management • (2) Follow-up and management guidelines for diabetic retinopathy, as recommended by American Academy of Ophthalmology . • (a) Normal or rare microaneurysms: annual examination, good diabetic control. • (b) Mild nonproliferative diabetic retinopathy (NPDR ) (few hemorrhages and microaneurysms in one field or several fields, but no macular edema or exudates): examination every 9 months, good diabetic control.

6 、 Management

• (c) Moderate NPDR (hemorrhages and/or exudates in all fields, intraretinal microvascular abnormalities [IRMAS] or CWSs): examination every 6 months, good diabetic control. • (d) Severe NPDR (one or more of the following: severe number of retinal hemorrhages and microaneurysms, moderate IRMAs, venous beading): examination every 4 months. • (e) Macular edema at any time: examination every 3 to 4 months, focal laser if clinically significant edema develops.

splinter haemorrhages and intraretinal microvascular abnormalities

6 、 Management • (4) Non-high-risk proliferative diabetic retinopathy occurs when there are any new vessels but the eye does not yet have high-risk characteristics (HRC) as defined by the DRS. These eyes should be followed every 2 to 3 months. In patients with bilateral non-high-risk proliferative retinopathy, PRP should be considered in one eye.

6 、 Management • (3) Clinically significant macular edema includes any of the following features: • (a) Thickening of the retina at or within 500μm of the center of the macula. • (b) Hard exudates at or within 500μm of the center of the macula. • (c) Zones of retinal one disk area or lager, any part of which is within one diameter of the center of the macula. Appropriate argon laser photocoagulation reduces the risk of visual loss substantially.

6 、 Management • (5) Proliferative retinopathy with HRC. • Panretinal laser photocoagulation is the treatment of choice for this stage, which is characterized by one or more of the following. • (a) Neovascularization on or within one disk diameter of the disk greater than one-fourth to one-third of the disk area. • (b) Vitreous or preretinal hemorrhage associated with less extensive neovascularization of the disk (NVD) or neovascularization elsewhere (NVE) onehalf disk area or more in size.

6 、 Management • (6) Laser application. • The risk of severe visual loss in patients with HRC is substantially reduced by means of panretinal laser photocoagulation done with the argon green laser. If nuclear sclerotic cataract or vitreous hemorrhage is present, there is less wavelength absorption with yellow or red lasers, such as the Krypton. The goal is to achieve regression of exiting vessels and inhibition of new vessel growth. Treatment is commonly done in two to four stages separated by 1 or more weeks. Typically, 400 to 600 burns of 500μm diameter are placed in the retinal periphery in one session. They come to within 500μm of the disk on the nasal side.

6 、 Management

• To preserve central vision, none are place within two disk diameters of the center of the macula. To preserve peripheral field, burns are placed one to one-half burn width apart. The duration of each burn is 0.1 to 0.2 Seconds and the power is adjusted to achieve definite retinal whitening. Flat new vessels away from the disk receive confluent 融合性的 ; burns. Areas of significant fibrosis, traction retinal detachment, and vitreous or preretinal hemorrhage are avoided. If proliferative diabetic retinopathy continues to be active despite panretinal laser photocoagulation in all quadrants 象限 , additional laser spots may be added between, or anterior to, the old laser scars.

6 、 Management • Panretinal cryoablation 冷冻消融 [ 术 ] is useful in selected patients. If a blinding vitreous hemorrhage occurs despite these measures or before laser can be given, pars plana 睫状体扁平部 vitrectomy should be performed within 6 months in type 1 diabetics. Intraoperative laser photocoagulation is often performed when these patients undergo pars plana vitrectomy. If B-scan ultrasonography suggests an underlying traction retinal detachment of the macula, vitrectomy should be done in all patients. Of course, when a recent traction macular detachment or a combination traction and rhegmatogenous 孔源性的 retinal detachment is present even when there is no vitreous hemorrhage, vitreous surgery is indicated.

rhegmatogenous 孔源性的 retinal detachment

6 、 Management • PRP is not necessary in phakic 人工晶体 eyes if there is peripupillary rubeosis 红变 but no abnormal new vessels on the trabecular meshwork 小梁网 . Such eyes should be followed every 3 months. If there are new vessels in the angle, the eye is aphakic 无晶体眼 , or the eye is pseudophakic eye 人工晶状体眼 with a broken posterior capsule, prompt PRP is needed to prevent neovascular glaucoma even when proliferative diabetic retinopathy with HRC is absent.

6 、 Management

• Focal macular laser therapy for clinically significant macular edema commonly uses 100 to 200 μm spot sizes and 0.1 seconds duration. The goal is to change the color of leaking microaneurysms through direct treatment; grid treatment （核）栅极治疗 is given to areas of diffuse leakage and ischemia. Leaks within 500μm of the center of the macula are usually not treated with the laser unless previous treatment has failed, vision is less than 20/40, and treatment will not damage the perifoveal 中 心凹周的 capillary network on the edge the foveal avascular 无血管 zone.