Diabetic retinopathy

Diabetic retinopathy is a microangionatis with primary involvement of precapillary arterioles, capillaries and postcapillary venules with possible involvement of larger caliber vessels. Retinopathy is manifested by microvascular occlusion and leakage. Clinically, diabetic retinopathy can be:

• background (non-proliferative), in which the pathology is limited intraretinal;
• proliferative, in which the pathology spreads across the surface of the retina or beyond it;
• preproliferative, characterized by an inevitable proliferative form.

Diabetes mellitus is a common metabolic disorder characterized by prolonged hyperglycemia of varying severity, developing secondary to a decrease in the concentration and/or action of endogenous insulin. Diabetes mellitus may be insulin-dependent or insulin-independent, otherwise defined as type 1 or type 2 diabetes. Diabetic retinopathy is more common in type 1 diabetes (40%) than in type 2 diabetes (20%) and is a leading cause of blindness in people aged 20 to 65 years.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ]

Risk factors for diabetic retinopathy

The duration of diabetes mellitus is important. When diabetes is detected in patients under 30 years of age, the probability of developing diabetic retinopathy after 10 years is 50% and after 30 years - 90% of cases. Diabetic retinopathy rarely manifests itself in the first 5 years of diabetes mellitus and during puberty, but occurs in 5% of patients with type 2 diabetes mellitus.

Insufficient control over metabolic processes in the body is a fairly common cause of the development and progression of diabetic retinopathy. Pregnancy often contributes to the rapid progression of diabetic retinopathy. Predisposing factors also include insufficient control of the underlying disease before pregnancy, abruptly initiated treatment in the early stages of pregnancy, and the development of preeclampsia and fluid imbalance. Arterial hypertension with insufficient control leads to the progression of diabetic retinopathy and the development of proliferative diabetic retinopathy in diabetes mellitus types 1 and 2. Acute nephropathy leads to worsening of the course of diabetic retinopathy. Conversely, treatment of kidney pathology (for example, kidney transplantation) can be accompanied by an improvement in the condition and a good result after photocoagulation. Other risk factors for diabetic retinopathy are smoking, obesity, and hyperlipidemia.

Benefits of Intensive Metabolic Control

• Delaying the development of diabetic retinopathy, but not preventing it.
• Slowing the progression of latent diabetic retinopathy.
• Reduction in the rate of transition of preproliferative diabetic retinopathy to proliferative.
• Reduction in the incidence of macular edema.
• Reducing the need for laser coagulation.

Pathogenesis of diabetic retinopathy

The pathogenesis of retinopathy is based on pathological processes in the retinal vessels.

Microvascular occlusion

• capillaries. Their changes are represented by the loss of pericytes, thinning of the basement membrane, damage and proliferation of endothelial cells. hematological disorders are represented by deformation and increased formation of the "royal columns" symptom, decreased platelet flexibility and aggregation, leading to a decrease in oxygen transport.

The consequence of the lack of perfusion of the retinal capillaries is its ischemia, which initially appears in the middle periphery. The two main manifestations of retinal hypoxia include:

• arteriovenular shunts, accompanied by a pronounced occlusion ("switching off") of capillaries in the direction from arterioles to venules. It is not clear whether these changes represent new vessels or opening of already existing vascular channels, so they are often referred to as intraretinal microvascular anomalies.
• Neovascularization is considered to be caused by the action of angiopoietic substances (growth factors) formed in the hypoxic tissue of the retina during an attempt to revascularize it. These substances promote neovascularization of the retina and optic disc, and often of the iris (rubeosis iridis). Many growth factors have been identified, but the most important is vascular endothelial growth factor.

Microvascular leakage

The breakdown of the internal blood-retinal barrier results in leakage of plasma components into the retina. Physical exhaustion of the capillary walls results in localized saccular protrusions of the vascular wall, defined as microaneurysms, with possible exudation or occlusion.

Manifestations of increased vascular permeability are the development of intraretinal hemorrhages and edema, which can be diffuse or local.

• Diffuse retinal edema is the result of marked capillary dilation and leakage;
• Localized retinal edema results from focal leakage from microaneurysms and dilated areas of capillaries.

Chronic localized retinal edema results in deposits of hard exudates in the area of transition from healthy retina to edematous retina. Exudates, formed by lipoproteins and lipid-laden macrophages, surround the area of microvascular leakage in a ring. After leakage ceases, they are either spontaneously absorbed into the surrounding intact capillaries or are phagocytosed; the process lasts for months or even years. Chronic leakage causes an increase in exudates and cholesterol deposition.

Non-proliferative diabetic retinopathy

Microaneurysms are localized in the inner nuclear layer and are among the first clinically detectable disorders.

Signs:

• soft, round, red spots, initially appearing temporally from the fovea. If surrounded by blood, they may not differ from pinpoint hemorrhages;
• Retinal trypsin uptake in diabetic retinopathy with perifoveal microaneurysms:
• microaneurysms containing cells at high magnification;
• FAG reveals delicate hyperfluorescent dots representing nonthrombotic microaneurysms, which are usually more numerous than those seen ophthalmoscopically. In the later phases, diffuse hyperfluorescence due to fluid leakage is seen.

Hard exudates are located in the outer plexiform layer.

Signs:

• waxy, yellow lesions with relatively clear edges, forming clusters and/or rings at the posterior pole. Microaneurysms are often identified in the center of the ring of hard exudate (annular exudate). Over time, their number and size increase, which poses a threat to the fovea with its possible involvement in the pathological process;
• FAG reveals hypofluorescence due to blocking of background choroidal fluorescence.

Retinal edema is primarily localized between the outer plexiform and inner nuclear layers. Later, the inner plexiform layer and the nerve fiber layer may become involved, resulting in full-thickness retinal edema. Further accumulation of fluid in the fovea results in cyst formation (cystoid macular edema).

Signs:

• Retinal edema is best demonstrated by slit lamp examination using a Goldmann lens;
• FAG reveals late hyperfluorescence due to retinal capillary leakage.

Hemorrhages

• Intraretinal hemorrhages arise from the venous ends of capillaries and are located in the middle layers of the retina. These hemorrhages are pinpoint, red in color, and of an indefinite configuration;
• In the retinal nerve fiber layer, hemorrhages arise from larger superficial precapillary arterioles, which causes their “flame” shape.

Tactics of management of patients with non-proliferative diabetic retinopathy

Patients with non-proliferative diabetic retinopathy do not require treatment, but annual examination is necessary. In addition to optimal control of diabetes, concomitant factors (arterial hypertension, anemia, and renal pathology) should be taken into account.

Preproliferative diabetic retinopathy

The appearance of signs of threatening proliferation in non-proliferative diabetic retinopathy indicates the development of preproliferative diabetic retinopathy. Clinical signs of preproliferative diabetic retinopathy indicate progressive retinal ischemia, revealed on FLG in the form of intense areas of hypofluorescence of the non-perfused retina ("switching off" of capillaries). The risk of progression to proliferation is directly proportional to the number of focal changes.

Clinical features of preproliferative diabetic retinopathy

Cotton wool lesions are localized areas of infarction in the retinal nerve fiber layer caused by occlusion of precapillary arterioles. Interruption of axoplasmic flow with subsequent accumulation of transported material in axons (axoplasmic stasis) gives the lesions a whitish tint.

• signs: small, whitish, cotton-like superficial lesions covering underlying blood vessels, clinically detectable only in the postequatorial zone of the retina, where the thickness of the nerve fiber layer is sufficient for their visualization;
• FAG reveals focal hypofluorescence due to blockage of background choroidal fluorescence, often accompanied by adjacent areas of nonperfused capillaries.

Intraretinal microvascular disorders are represented by shunts from retinal arterioles to venules that bypass the capillary bed, and are therefore often detected near areas of interruption of capillary blood flow.

• signs: delicate red stripes connecting arterioles and venules, having the appearance of localized areas of flat newly formed retinal vessels. The main distinguishing feature of intraretinal microvascular disorders is their location inside the retina, the impossibility of crossing large vessels and the absence of sweating on the FAG;
• FAG reveals focal hyperfluorescence associated with adjacent areas of interrupted capillary blood flow.

Venous abnormalities: dilation, looping, bead- or rosary-shaped segmentation.

Arterial abnormalities: narrowing, silver wiring and obliteration, which makes them similar to occlusion of a branch of the central retinal artery.

Dark hemorrhage spots: hemorrhagic retinal infarctions located in the middle layers of the retina.

Tactics of management of patients with preproliferative diabetic retinopathy

In preproliferative diabetic retinopathy, special monitoring is required due to the risk of developing proliferative diabetic retinopathy. Photocoagulation is usually not indicated unless follow-up is not possible or vision in the fellow eye has already been lost due to proliferative diabetic retinopathy.

Diabetic maculopathy

The main cause of visual impairment in patients with diabetes, especially type 2 diabetes, is foveal edema, deposition of hard exudate, or ischemia (diabetic maculopathy).

Classification of diabetic maculopathy

Localized exudative diabetic maculopathy

• signs: clearly defined retinal thickening, accompanied by a complete or incomplete ring of perifoveal hard exudates;
• FAG reveals late focal hyperfluorescence due to sweating and good macular perfusion.

Diffuse exudative diabetic maculopathy

• signs: diffuse thickening of the retina, which may be accompanied by cystic changes. Obliteration with pronounced edema sometimes makes it impossible to localize the fovea;
• FAG reveals multiple punctate hyperfluorescence of microaneurysms and late diffuse hyperfluorescence due to sweating, which is more pronounced compared to clinical examination. In the presence of cystoid macular edema, a "flower petal"-shaped area is identified.

Ischemic diabetic maculopathy

• signs: decreased visual acuity with relatively preserved fovea; often associated with preproliferative diabetic retinopathy. Dark hemorrhage spots may be present;
• FAG reveals nonperfused capillaries in the fovea, the severity of which does not always correspond to the degree of visual acuity loss.

Other areas of nonperfused capillaries are often present at the posterior pole and periphery.

Mixed diabetic maculopathy is characterized by signs of both ischemia and exudation.

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Clinically significant macular edema

Clinically significant macular edema is characterized by the following:

• Retinal edema within 500 µm of the central fovea.
• Hard exudates within 500 µm of the central fovea if accompanied by retinal thickening around it (which may extend beyond 500 µm).
• Retinal edema of 1 DD (1500 µm) or more, i.e. any area of edema must be within 1 DD of the central fovea.

Clinically significant macular edema requires laser photocoagulation regardless of visual acuity, as treatment reduces the risk of vision loss by 50%. Improvement of visual function is rare, so treatment is indicated for prophylactic purposes. It is necessary to conduct FAG before treatment in order to determine the areas and size of sweating. Identification of nonperfused capillaries in the fovea (ischemic maculopathy), which is a poor prognostic sign and a contraindication to treatment.

Argon laser coagulation

Technique

Local laser coagulation involves application of laser coagulates to microaneurysms and microvascular lesions in the center of hard exudate rings localized within 500-3000 μm from the central fovea. The coagulate size is 50-100 μm with a duration of 0.10 sec and sufficient power to ensure gentle bleaching or darkening of microaneurysms. Treatment of foci up to 300 μm from the central fovea is indicated for persistent clinically significant macular edema despite previous treatment and visual acuity below 6/12. In such cases, shortening the exposure time to 0.05 sec is recommended; b) lattice laser coagulation is used in the presence of areas of diffuse retinal thickening localized at a distance of more than 500 μm from the central fovea and 500 μm from the temporal edge of the optic nerve head. The size of the coagulates is 100-200 µm, the exposure time is 0.1 sec. They should have a very light color, they are applied at a distance corresponding to the diameter of 1 coagulate.

Results. In approximately 70% of cases, visual functions are stabilized, in 15% - there is an improvement, and in 15% of cases - subsequent deterioration. Edema resolution occurs within 4 months, so repeated treatment is not indicated during this period.

Factors for an unfavorable prognosis

Hard exudates involving the fovea.

• Diffuse macular edema.
• Cystoid macular edema.
• Mixed exudative-ischemic maculopathy.
• Severe retinopathy at the time of examination.

Vitrectomy

Pars plana vitrectomy may be indicated for macular edema associated with tangential traction that extends from a thickened and compacted posterior hyaloid membrane. In such cases, laser treatment is of little benefit compared to surgical removal of the macular traction.

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Proliferative diabetic retinopathy

Occurs in 5-10% of patients with diabetes. In type 1 diabetes, the risk is particularly high: the incidence rate is 60% after 30 years. Contributing factors include carotid artery occlusion, posterior vitreous detachment, high myopia, and optic atrophy.

Clinical features of proliferative diabetic retinopathy

Signs of proliferative diabetic retinopathy. Neovascularization is an indicator of proliferative diabetic retinopathy. Proliferation of newly formed vessels can occur at a distance of up to 1 dB from the optic disc (neovascularization within the disc) or along the main vessels (neovascularization outside the disc). Both options are possible. It has been established that the development of proliferative diabetic retinopathy is preceded by nonperfusion of more than a quarter of the retina. The absence of the internal limiting membrane around the optic disc partly explains the tendency for neoplasms to form in this area. New vessels appear as endothelial proliferations, most often from veins; they then cross defects in the internal limiting membrane, lie in the potential plane between the retina and the posterior surface of the vitreous body, which serves as a support for them.

FAG. Not required for diagnosis, but reveals neovascularization in the early phases of angiograms and shows hyperfluorescence in the late phases, caused by active sweating of dye from neovascular tissue.

Symptoms of proliferative diabetic retinopathy

The severity of proliferative diabetic retinopathy is determined by comparing the area occupied by newly formed vessels with the area of the optic nerve disc:

Neovascularization in the disc area

• Moderate - dimensions less than 1/3 DD.
• Expressed - dimensions more than 1/3 DD.

Extradiscal neovascularization

• Moderate - sizes less than 1/2 DD.
• Expressed - dimensions more than 1/2 DD.

Raised, newly formed vessels are less amenable to laser treatment than flat ones.

Fibrosis associated with neovascularization is of interest because with significant fibrous proliferation, despite the low probability of bleeding, there is a high risk of tractional retinal detachment.

Hemorrhages, which may be preretinal (subhyaloid) and/or intravitreal, are an important risk factor for decreased visual acuity.

Characteristics of increased risk of significant vision loss within the first 2 years if untreated include:

• Moderate neovascularization in the disc area with hemorrhages accounts for 26% of the risk, which decreases to 4% after treatment.
• Severe neovascularization in the disc area without hemorrhage accounts for 26% of the risk, which decreases to 9% after treatment.

Marked neovascularization of the optic disc with elevation

• Severe neovascularization in the disc area with hemorrhages accounts for 37% of the risk, which decreases to 20% after treatment.
• Severe extra-disc neovascularization with hemorrhage accounts for 30% of the risk, which decreases to 7% after treatment.

If the above criteria are not met, it is recommended to refrain from photocoagulation and examine the patient every 3 months. However, in reality, most ophthalmologists resort to laser photocoagulation at the first signs of neovascularization.

Complications of diabetic eye disease

In diabetic retinopathy, serious vision-threatening complications occur in patients who have not had laser therapy or whose results have been unsatisfactory or inadequate. One or more of the following complications may develop.

Hemorrhages

They can be in the vitreous body or in the retrohyaloid space (preretinal hemorrhages) or combined. Preretinal hemorrhages have a crescent shape, forming a demarcation level with the posterior detachment of the vitreous body. Sometimes preretinal hemorrhages can penetrate into the vitreous body. Such hemorrhages require more time to resolve than preretinal hemorrhages. In some cases, the blood is organized and compacted on the posterior surface of the vitreous body, forming an "ochre-colored membrane." Patients should be warned that hemorrhage can occur due to excessive physical or other stress, as well as hypoglycemia or direct eye injury. However, hemorrhage often occurs during sleep.

Traction retinal detachment

It occurs with progressive contraction of fibrovascular membranes in large areas of vitreoretinal adhesions. Posterior vitreous detachment in patients with diabetes occurs gradually; it is usually incomplete, which is due to powerful adhesions of the cortical surface of the vitreous with areas of fibrovascular proliferation.

The following types of stationary vitreoretinal traction lead to retinal detachment:

• anteroposterior traction occurs when the fibrovascular membranes that extend from the posterior segment, usually in conjunction with a massive vascular network, contract anteriorly to the base of the vitreous;
• Bridging traction is a result of contraction of the fibrovascular membranes that extend from one half of the posterior segment to the other. This results in tension in the area of these points and can cause the formation of tension bands, as well as displacement of the macula either relative to the disc or otherwise, depending on the direction of the traction force.

Other complications of diabetic retinopathy

Opacified films that may develop on the back of the detached vitreous pull the retina downwards in the temporal arcades. Such films may completely cover the macula, resulting in decreased vision.

• The fundus is unchanged.
• Moderate preproliferative diabetic retinopathy with small hemorrhages and/or hard exudates at a distance of more than 1 DD from the fovea.

Routine referral to an ophthalmologist

• Non-proliferative diabetic retinopathy with hard exudate deposits in the form of a ring along the main temporal arcades, but without a threat to the fovea.
• Non-proliferative diabetic retinopathy without maculopathy but with decreased vision to determine its cause.

Early referral to an ophthalmologist

• Nonproliferative diabetic retinopathy with hard exudate deposits and/or hemorrhages within 1 D of the fovea.
• Maculopathy.
• Preproliferative diabetic retinopathy.

Urgent referral to an ophthalmologist

• Proliferative diabetic retinopathy.
• Preretinal or vitreous hemorrhages.
• Rubeosis iridis.
• Retinal detachment.

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Treatment of diabetic retinopathy

Panretinal laser coagulation

Treatment with panretinal laser coagulation is aimed at causing involution of newly formed vessels and preventing vision loss due to vitreous hemorrhage or tractional retinal detachment. The extent of treatment depends on the severity of proliferative diabetic retinopathy. In moderate cases, coagulates are applied sequentially far from each other at low power, and in cases of more severe disease or relapses, the distance between coagulates should be reduced and the power increased.

Beginner ophthalmologists are better off using a panfundoscope, which provides greater magnification than the three-mirror Goldmann lens, since the latter has a higher probability of unsuccessful photocoagulation with adverse effects.

Application of coagulates

• the size of the coagulate depends on the contact lens used. With a Goldmann lens, the coagulate size should be 500 µm, while with a panfundoscope it should be 300-200 µm;
• exposure time - 0.05-0.10 sec at a power that allows applying gentle coagulants.

Primary treatment of diabetic retinopathy is performed with the application of 2000-3000 coagulates in a scattered manner in the direction from the posterior segment, covering the periphery of the retina in one or two sessions; panretinal laser coagulation, limited to one session, is associated with a higher risk of complications.

The amount of treatment during each session is determined by the patient's pain threshold and ability to concentrate. Local anesthesia with eye drops is sufficient for most patients, but parabulbar or sub-Tenon anesthesia may be necessary.

The sequence of actions is as follows:

• Step 1. Near the disc; below the inferotemporal arcade.
• Step 2. A protective barrier is created around the macula to prevent the risk of vitreous intervention. The main cause of stable neovascularization is inadequate treatment.

Signs of involution include regression of neovascularization and the appearance of empty vessels or fibrous tissue, contraction of dilated veins, absorption of retinal hemorrhages, and reduction of disc pallor. In most cases of retinopathy without negative dynamics, stable vision is maintained. In some cases, preproliferative diabetic retinopathy recurs despite the initial satisfactory result. In this regard, repeated examination of patients is necessary at intervals of 6-12 months.

Panretinal coagulation affects only the vascular component of the fibrovascular process. In the case of regression of newly formed vessels with the formation of fibrous tissue, repeated treatment is not indicated.

Treatment for relapses

• repeated laser coagulation with the application of coagulates in the spaces between previously produced points;
• Cryotherapy of the anterior retina is indicated when repeated photocoagulation is impossible due to poor visualization of the fundus caused by turbidity of the media. In addition, it allows for the treatment of areas of the retina that have not undergone panretinal laser coagulation.

It is necessary to explain to patients that panretinal laser coagulation can cause visual field defects of varying degrees, which is a justified contraindication for driving a car.

• Step 3. From the nasal side of the disc; completion of the intervention in the posterior pole area.
• Step 4. Laser coagulation of the periphery to the end.

In cases of severe proliferative diabetic retinopathy, it is recommended to first perform intervention in the lower half of the retina, since in the case of hemorrhage into the vitreous body, this area is closed, making further treatment impossible.

Subsequent tactics of patient management

Observation is usually 4-6 weeks. In case of pronounced neovascularization around the disc, several sessions with a total amount of coagulates up to 5000 or more may be required, despite the fact that complete elimination of neovascularization is difficult to achieve and early surgical treatment may be necessary.