Diabetic retinopathy

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

• background (non-proliferative), in which pathology is limited intra-retinal;
• proliferative, in which pathology spreads over the surface of the retina or beyond it;
• Preproliferative, characterized by the inevitable proliferative form.

Diabetes mellitus is a common metabolic disorder characterized by prolonged hyperglycemia of varying severity, developing again in response to a decrease in the concentration and / or action of endogenous insulin. Diabetes mellitus can be insulin-dependent or insulin-independent, otherwise defined as type 1 or 2 diabetes. Diabetic retinopathy is more common in type 1 diabetes (40%) than in type 2 diabetes (20%) and is the 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 is important. Sugar In the detection of diabetes in patients under 30 years of age, the probability of developing diabetic retinopathy after 10 years is 50% and in 30 years 90% of cases. Diabetic retinopathy is rarely seen in the first 5 years of diabetes and during puberty, but occurs in 5% of patients with type 2 diabetes.

Insufficient control over metabolic processes in the body is a fairly common cause of the development and progression of diabetic retinopathy. Pregnancy quite often promotes rapid progression of diabetic retinopathy. Predisposing factors also include insufficient control of the underlying disease before pregnancy, dramatically 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 type 1 and type 2 diabetes mellitus. Nephropathy with acute course leads to a worsening of the course of diabetic retinopathy. Conversely, treatment of renal pathology (eg, kidney transplantation) may be accompanied by improvement in the condition and a good result after photocoagulation. Other risk factors for diabetic retinopathy are smoking, obesity, hyperlipidemia.

Benefits of intensive metabolic control

• Delayed development of diabetic retinopathy, but not prevention.
• Delay in the progression of latent diabetic retinopathy.
• Decrease in the rate of transition of pre-proliferative diabetic retinopathy to proliferative.
• Reducing the incidence of edema of the macula.
• Reduced need for laser coagulation.

The pathogenesis of diabetic retinopathy

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

Microvascular occlusion

• capillaries. Their changes are represented by loss of pericytes, thinning of the basement membrane, damage and proliferation of endothelial cells. Hematologic disorders are represented by deformation and increased formation of the symptom of "coins", a decrease in 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 first appears on the middle periphery. Two main manifestations of hypoxia of the retina include:

• arteriovenous shunts, accompanied by pronounced occlusion ("turning off") of the capillaries in the direction from the arterioles to the venules. It is not clear whether these changes are represented by new vessels or the opening of already existing vascular channels, so they are often referred to as intra-retinal microvascular anomalies.
• neovascularization is considered the cause of the action of angiopoietic substances (growth factors) formed in the hypoxic tissue of the retina when trying to revascularize it. These substances contribute to neovascularization of the retina and optic disc, and often - and irises (iris rubeosis). A number of growth factors have been identified, but the most important is the vascular endothelial growth factor.

Microvascular seepage

The breakdown of the internal hematoretinal barrier leads to leakage of plasma components into the retina. The physical exhaustion of the walls of the capillaries leads to local saccular protrusions of the vascular wall, defined as microaneurysms, with possible sweating or occlusion.

The manifestation of increased vascular permeability is the development of intra-retinal hemorrhages and edema, which can be diffuse or local.

• diffuse retinal edema is the result of pronounced expansion of capillaries and percolation;
• local retinal edema is the result of focal leakage from microaneurysms and dilated capillary sites.

Chronic local edema of the retina leads to the deposition of solid exudate in the area of transition of the healthy retina and edematous. Exudates formed by lipoproteins and macrophages filled with lipids surround the region of microvascular percolation in the form of a ring. After cessation of percolation, they either undergo spontaneous absorption into the surrounding preserved capillaries, or are phagocytosed; the process lasts for several months and even years. Chronic leakage causes an increase in exudates and the deposition of cholesterol. 

Non-proliferative diabetic retinopathy

Microaneurysms are localized in the inner nuclear layer and belong to the first clinically determined disorders.

Symptoms:

• gentle, rounded, red dots, which first appear temporally from the fovea. If they are surrounded by blood, they may not differ from point hemorrhages;
• assimilation of trypsin retina in diabetic retinopathy with periphovial microaneurysms:
• microaneurysms with a high cell content of cells;
• The PHAG reveals delicate hyperfluorescent points, which are non-corroborated microaneurysms, the number of which is usually greater than that of ophthalmoscopically visible ones. In the late phases, diffuse hyperfluorescence due to leakage of the liquid is visible.

Solid exudates are located in the outer plexiform layer.

Symptoms:

• wax-shaped, yellow foci with relatively distinct edges, forming aggregations and / or rings in the posterior pole. In the center of the ring of solid exudate (annular exudate) microaneurysms are often determined. Over time, their number and size increase, which poses a threat to the fovea with possible involvement in the pathological process;
• The PHAG reveals the hypofluorescence caused by the blocking of the background fluorescence of the choroid.

Retinal edema is primarily localized between the outer plexiform and inner nuclear layers. Later, the inner plexiform layer and the layer of nerve fibers can be involved, up to the entire thickness of the retina. Further accumulation of fluid in the fovea leads to the formation of a cyst (cystic macular edema).

Symptoms:

• Retinal edema is best determined by examining a slit lamp using a Goldmann lens;
• The PHAG reveals a late hyperfluorescence caused by leakage of the retinal capillaries.

Hemorrhage

• Intra-retinal hemorrhages appear from the venous ends of the capillaries and are located in the middle layers of the retina. These hemorrhages are pointlike, have a red color and an indefinite configuration;
• in the layer of retinal nerve fibers, hemorrhages arise from larger surface precapillary arterioles, which determines their shape in the form of "flame tongues".

Tactics of management of patients with non-proliferative diabetic retinopathy

Patients with nonproliferative diabetic retinopathy do not need treatment, however, an annual examination is necessary. In addition to optimal control over diabetes, it is necessary to take into account the accompanying factors (arterial hypertension, anemia and kidney pathology). 

Pre-proliferative diabetic retinopathy

The appearance of signs of threatening proliferation with nonproliferative diabetic retinopathy indicates the development of pre-proliferative diabetic retinopathy. Clinical signs of pre-proliferative diabetic retinopathy indicate a progressive ischemia of the retina, which is detected in the FLG in the form of intensive areas of hypofluorescence of the unperfused retina ("capillary exclusion"). The risk of progression to proliferation is directly proportional to the number of focal changes.

Clinical features of pre-proliferative diabetic retinopathy

Cotton-like foci are local areas of infarcts in the layer of retinal nerve fibers caused by occlusion of precapillary arterioles. The interruption of the axoplasmatic current with subsequent accumulation of the transported material in the axons (axoplasmic stasis) gives the foci whitish shade.

• signs: small, whitish, cotton-like surface foci that cover lower lying blood vessels, clinically determined only in the post-equatorial zone of the retina, where the thickness of the layer of nerve fibers is sufficient for their visualization;
• The PHAG reveals local hypofluorescence caused by the blocking of the background fluorescence of the choroid, often accompanied by neighboring regions of unperfused capillaries.

Intra-retinal microvascular disorders are represented by shunts from the retinal arterioles to the veins that bypass the capillary bed, and are therefore often identified near the interruption sites of capillary blood flow.

• signs: tender red strips connecting arterioles and venules, which look like local parts of flat, newly formed retinal vessels. The main distinguishing feature of intra-retinal microvascular disorders is their location within the retina, the impossibility of crossing large vessels and the absence of sweating on the PHAG;
• The PHAG reveals local hyperfluorocenosis associated with adjacent areas of capillary blood flow interruption.

Venous disorders: enlargement, loops, segmentation in the form of "beads" or "beads".

Arterial disorders: constriction, a sign of "silver wire" and obliteration, which gives them a similarity to the occlusion of the branch of the central artery of the retina.

Dark spots of hemorrhages: hemorrhagic infarcts of the retina, located in its middle layers.

Tactics of management of patients with pre-proliferative diabetic retinopathy

With pre-proliferative diabetic retinopathy, special surveillance is required because of the risk of developing proliferative diabetic retinopathy. Photocoagulation is not usually indicated, except when it is impossible to observe in dynamics or the pair eye sight is already lost due to proliferative diabetic retinopathy. 

Diabetic maculopathy

The main cause of vision impairment in diabetics, especially in type 2 diabetes, is foveal edema, solid exudate deposition or ischemia (diabetic maculopathy).

Classification of diabetic maculopathy

Local exudative diabetic maculopathy

• signs: a clearly limited thickening of the retina, accompanied by a full or incomplete ring of perifovealnyh solid exudates;
• The PHAG reveals late local hyperfluorescence due to sweating and good macular perfusion.

Diffuse exudative diabetic maculopathy

• signs: diffuse thickening of the retina, which can be accompanied by cystic changes. Obliteration with pronounced edema sometimes makes it impossible to localize the fovea;
• The PHAG reveals multiple point hyperfluorescence of microaneurysms and late diffuse hyperfluorescence due to sweating, which is more pronounced compared with clinical examination. In the presence of cystic macular edema, a patch in the form of a "petal of a flower" is defined.

Ischemic diabetic maculopathy

• signs: decreased visual acuity with a relatively preserved fovea; is often associated with pre-proliferative diabetic retinopathy. Dark bleeding spots can be detected;
• The PHAG reveals the unperfused capillaries in the fovea, the severity of which does not always correspond to the degree of decrease in visual acuity.

Other areas of non-perfusionable capillaries are often present in the posterior pole and on the periphery.

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

[7], [8], [9], [10], [11], [12]

Clinically significant edema of the macula

Clinically significant edema of the macula is characterized by the following:

• Retinal edema within 500 μm from the central fovea.
• Solid exudates within 500 μm from the central fovea if they are accompanied by a thickening of the retina around it (which may extend beyond 500 μm).
• Retinal edema within 1 DD (1500 μm) or more, i.е. Any zone of edema should fall within 1 DD from the central fovea.

Clinically significant edema of the macula requires laser photocoagulation regardless of visual acuity, since treatment reduces the risk of vision loss by 50%. Improvement of visual functions is rare, so treatment is indicated for prophylactic purposes. It is necessary to conduct PHAG before treatment in order to determine the areas and sizes of sweating. Detection of unperfused capillaries in fovea (ischemic maculopathy), which is a poor prognostic sign and contraindication to treatment.

Argon laser coagulation

Equipment

Local laser coagulation involves applying laser coagulants to microaneurysms and microvascular disorders in the center of the rings of solid exudates localized within 500-3000 microns from the central fovea. The size of the coagulum is 50-100 μm with a duration of 0.10 sec and sufficient power to provide gentle discoloration or darkening of the microaneurysm. Treatment of foci up to 300 μm from the central fovea is indicated with persisting clinically significant edema of the macula, despite earlier treatment and visual acuity below 6/12. In such cases, it is recommended that the exposure time be shortened to 0.05 seconds; b) Lattice laser coagulation is used in the presence of sites of diffuse thickening of the retina localized at a distance of more than 500 μm from the central fovea and 500 μm from the temporal margin of the optic nerve disc. The size of the coagulates is 100-200 microns, the exposure time is 0.1 sec. They should have a very light color, they are imposed at a distance corresponding to the diameter of 1 coagulate.

Results. Approximately 70% of cases it is possible to achieve stabilization of visual functions, in 15% - there is an improvement and in 15% of cases - the subsequent deterioration. The resolution of edema occurs within 4 months, so repeated treatment during this period is not indicated.

Factors for unfavorable prognosis

Solid exudates covering the fovea.

• Diffuse edema of the macula.
• Cystic edema of the macula.
• Mixed exudative ischemic maculopathy.
• Severe retinopathy at the time of examination.

Vitrectomy

The pars plana vitrectomy may be indicated for macular edema associated with tangential traction, which extends from a thickened and compacted posterior hyaloid membrane. In such cases, laser treatment is ineffective in contrast to the surgical removal of macular tract. 

[13], [14], [15], [16]

Proliferative diabetic retinopathy

It 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 are carotid occlusion, posterior vitreous detachment, high degree myopia and optic nerve atrophy.

Clinical features of proliferative diabetic retinopathy

Signs of proliferative diabetic retinopathy. Neovascularization is an indicator of proliferative diabetic retinopathy. Proliferation of the newly formed vessels can occur at a distance of up to 1 DD from the optic nerve disk (neovascularization in the region of the disc) or along the main vascular (neovascularization outside the disc). Both options are possible. It has been established that the development of proliferative diabetic retinopathy is preceded by non-perfusion of more than a quarter of the retina. The absence of an internal border membrane around the optic disc partly explains the propensity for neoplasm in this area. New vessels appear as endothelial proliferation, most often from veins; then they cross the defects of the inner border membrane, they lie in the potential plane between the retina and the back surface of the vitreous that supports them.

PHAG. For diagnostics it is not necessary, but reveals neovascularization in the early phases of angiogram and shows hyperfluorescence in the late phases caused by active sweating of the dye from neovascular tissue.

Symptoms of proliferative diabetic retinopathy

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

Neovascularization in the region of the disk

• Moderate - sizes less than 1/3 of the DD.
• Expressed - the size is more than 1/3 of the DD.

Neovascularization outside the disc

• Moderate - the size is less than 1/2 DD.
• Expressed - the size is more than 1/2 DD.

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

Fibrosis associated with neovascularization is of interest in that, with significant fibrotic proliferation, despite the low probability of bleeding, there is a high risk of traction retinal detachment.

Hemorrhages, which may be preretinal (subgialoid) and / or inside the vitreous humor, are an important risk factor for reducing visual acuity.

Characteristics of an increased risk of significant vision loss during the first 2 years in the absence of treatment are as follows:

• Moderate neovascularization in the area of the disk with hemorrhages is 26% of the risk, which is reduced to 4% after treatment.
• Expressed neovascularization in the area of the disk without hemorrhage is 26% of the risk, which after treatment is reduced to 9%.

Expressed neovascularization of the optic disc with elevation

• Expressed neovascularization in the area of the disk with hemorrhages is 37% of the risk, which after treatment is reduced to 20%.
• Expressed neovascularization outside the disk with hemorrhages is 30% risk, which after treatment is reduced to 7%.

If these criteria are not met, it is recommended to refrain from photocoagulation and examine the patient every 3 months. However, in fact, most ophthalmologists have resorted to laser photocoagulation already at the first signs of neovascularization.

Complications of diabetic eye disease

With diabetic retinopathy, serious complications that threaten vision occur in patients who did not undergo laser therapy, or its results were unsatisfactory or inadequate. Possible development of one or more of the following complications.

Hemorrhages

They can be in the vitreous body or in the retrogialoid space (preretinal hemorrhages) or combined. Preretinal hemorrhages are crescent shaped, forming a demarcation level with a posterior detachment of the vitreous humor. Sometimes, preretinal hemorrhages can penetrate the vitreous. For resorption of such hemorrhages, more time is required in comparison with preretinal hemorrhages. In some cases, the organization and compaction of blood on the posterior surface of the vitreous body takes place with the formation of a "ocher-colored membrane". Patients should be warned that hemorrhage can arise from excessive physical or other stress, as well as hypoglycemia or direct eye injury. However, often the appearance of a hemorrhage during sleep.

Traction retinal detachment

It appears with the progressive reduction of fibrovascular membranes in large areas of vitreous retinal fusion. The posterior detachment of the vitreous in patients with diabetes occurs gradually; usually it is incomplete, which is due to the powerful fusion 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 with a reduction in fibrovascular membranes that extend from the posterior segment, usually in combination with a massive vasculature, anterior to the base of the vitreous;
• bridged traction is a consequence of the reduction of fibrovascular membranes that extend from one half of the posterior segment to the other. This leads to tension in the area of these points and can cause the formation of tension bands, as well as the displacement of the macula either relative to the disc, or otherwise, depending on the direction of the traction force.

Other complications of diabetic retinopathy

Blurred films that can develop on the back surface of an exfoliated vitreous body, pull the retina from the top down in the area of the temporal arcades. Such films can completely cover the macula with subsequent deterioration of vision.

• The ocular bottom is unchanged.
• Moderate pre-proliferative diabetic retinopathy with small hemorrhages and / or solid exudates at a distance of more than 1 DD from the fovea.

Planned referral to ophthalmologist

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

Early referral to ophthalmologist

• Non-proliferative diabetic retinopathy with deposits of solid exudate and / or hemorrhage within 1 DD from the fovea.
• Maculopathy.
• Pre-proliferative diabetic retinopathy.

Urgent referral to ophthalmologist

• Proliferative diabetic retinopathy.
• Preretinal or vitreous hemorrhage.
• Rubyoz of the iris.
• Retinal disinsertion.

[17], [18], [19],

Treatment of diabetic retinopathy

Pancreatic laser coagulation

Treatment with panretinal laser coagulation is aimed at causing involution of newly formed vessels and preventing loss of vision due to vitreous hemorrhage or traction retinal detachment. The amount of treatment depends on the severity of proliferative diabetic retinopathy. With a moderate course of the disease, coagulates are applied consistently far apart from each other at low power, and with a more pronounced process or relapse, the distance between the coagulates should be reduced and the power increased.

It is better for beginner ophthalmologists to use a panfundoscope. Giving a greater increase than the three-mirror Goldmann lens. Since when using the latter, the probability of unsuccessful photocoagulation with adverse consequences is higher.

Coagulation application

• The size of the coagulum depends on the contact lens used. With a Goldmann lens, the size of the coagulum should be 500 μm, whereas with a pan-fungoscope - 300-200 μm;
• Exposure time is 0.05-0.10 sec with a power that allows to apply gentle coagulants.

Primary treatment of diabetic retinopathy is performed with application of 2000-3000 coagulants in a scattered order in the direction from the posterior segment with coverage of 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 volume of treatment during each session is determined by the pain threshold of the patient and his ability to concentrate attention. Most patients have enough local anesthesia with eye drops, but there may be a need for parabulbar or sub-tenon anesthesia.

The sequence of actions is as follows:

• Step 1. Near the disk; down from the lower arcade.
• Step 2. A protective barrier around the macula is produced to prevent the danger of interference on the vitreous. The main cause of stable neovascularization is inadequate treatment.

Signs of involution are the regression of neovascularization and the appearance of empty vessels or fibrous tissue, the contraction of the enlarged veins, the absorption of retinal hemorrhages, and the diminution of disc blanching. In most cases, retinopathy without negative dynamics maintains a stable vision. In some cases, pre-proliferative diabetic retinopathy recurs, despite a primary satisfactory outcome. In this regard, a repeated examination of patients with an interval of 6-12 months is necessary.

Pancreatin 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 shown.

Treatment for relapses

• repeated laser coagulation with application of coagulates in the intervals between previously produced points;
• Cryotherapy in the anterior region of the retina is indicated when it is not possible to perform repeated photocoagulation due to poor visualization of the fundus due to opacification of the media. In addition, it allows to affect the areas of the retina that have not undergone panretinal laser coagulation ..

It is necessary to explain to patients that panretinal laser coagulation can cause defects in the field of vision of various degrees, which is a valid contraindication for driving a motor vehicle.

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

With a significant proliferative diabetic retinopathy, it is recommended first to intervene in the lower half of the retina, as in the case of a vitreous hemorrhage, this area closes, which makes further treatment impossible.

Follow-up management tactics

Observation is usually 4-6 weeks. In the case of pronounced neovascularization, a disc may require several sessions with a total coagulation amount of up to 5,000 or more, even though it is difficult to achieve complete elimination of neovascularization and there may be a need for early surgical treatment.