Diabetic Retinopathy:
Symptoms, Prevention, and Treatment

Diabetic retinopathy is one of the most serious microvascular complications of diabetes, affecting the retina of the eye. The retina is a light-sensitive tissue located at the back of the eye, essential for vision, and requires a continuous supply of oxygen and nutrients. Blood supply to the retina is provided by the capillary network within it. In diabetes, elevated blood glucose levels lead to damage to this complex process, which can result in vision loss.

How Does Diabetic Retinopathy Develop?

In the initial phase of diabetic ophthalmic complications, the walls of the retinal capillaries become abnormally permeable (increased permeability). The following important elements of this process are known: the cells of the inner vessel wall begin to function abnormally (endothelial dysfunction), the vessel wall is remodeled (basement membrane thickening), and the number of pericytes—cells that play an important role around the small vessels—decreases. This combination of changes results in weakening of the retinal vessels, leading to the formation of microaneurysms.

From these damaged capillaries, fluid (edema), lipids, and other substances (lipid exudates) or blood can leak into the layers of the retina, causing dysfunction and damage to the photoreceptor cells. As the disease progresses, capillary dropout occurs, resulting in ischemia (lack of blood supply) in the retina.

In the late stages, when tissue hypoxia reaches a certain critical level, the retina attempts to grow new vessels in response (neovascularization). However, these vessels, also called neovascularization, are abnormal, form in inappropriate locations, and leak. This process can lead to further, more serious complications and even irreversible vision loss.

What Are the Symptoms of Diabetic Retinopathy?

In the early stages of diabetic retinopathy, it is often asymptomatic. Patients have difficulty noticing symptoms, and not infrequently only become aware of them when significant damage has already occurred. For this reason, regular ophthalmic examination is particularly important in diabetes. As the disease progresses, patients may experience a number of signs and symptoms, which can vary in severity.

The most common symptoms of eye problems associated with diabetes are as follows:

What Are the Stages of Diabetic Retinopathy?

Several stages of diabetic ophthalmic complications affecting the retina are distinguished. As a consequence of high blood glucose levels, without treatment these stages follow one another over time and lead to irreversible blindness.

1. Mild Non-Proliferative Diabetic Retinopathy (NPDR)

The earliest stage of diabetic retinopathy, characterized by the presence of bulge-like dilations of the small vessels (microaneurysms). Vision is usually not yet impaired at this stage.

2. Moderate Non-Proliferative Diabetic Retinopathy

As the disease progresses, the vessels in the retina dilate in more places and become increasingly damaged. This process leads to retinal hemorrhages, fluid leakage, deposition of other substances, and focal nerve fiber layer death (cotton-wool spots). Abnormalities and caliber variations also appear in the retinal veins. Vision loss may already occur at this stage due to fluid accumulation in the macular area.

3. Severe Non-Proliferative Diabetic Retinopathy

In this advanced stage, in addition to the above, many more capillaries become occluded, resulting in significant ischemia. The irregularity of the retinal veins is striking, and intraretinal microvascular abnormalities develop. More and more areas of the retina are deprived of nutrients and oxygen, increasing the risk of neovascularization (characteristic of the next stage). Vision loss is very common, as the macula, the site of sharp vision, is also frequently affected due to extensive retinal changes.

4. Proliferative Diabetic Retinopathy (PDR)

Due to capillary dropout, in addition to the previous changes, new, abnormal vessels begin to grow on the surface of the retina (neovascularization). These newly formed vessels develop in response to ischemia, but the process is defective and they cannot perform their intended function. Furthermore, the fragile vessels formed by neovascularization are prone to rupture, leading to vitreous hemorrhage and tractional retinal detachment, which, if left untreated, results in irreversible vision loss. Vision loss is very common at this stage and may be irreversible.

What Complications Can Diabetic Retinopathy Have?

In addition to diabetic retinopathy, diabetes can lead to other ophthalmic complications.

• Cataract: People with diabetes have a significantly higher risk of developing cataracts, which is the clouding of the lens of the eye. High blood glucose levels and their fluctuations play an important role in causing changes in the lens structure responsible for lens clouding to occur earlier than would be expected for the patient’s age.
• Glaucoma: People with diabetes are more likely to develop open-angle glaucoma, which causes progressive, irreversible damage to the optic nerve and vision loss. A special form that also occurs in diabetes is neovascular glaucoma. In this case, new vessels grow on the iris and in the angle of the anterior chamber, blocking the normal drainage site for fluid. In these cases, we often face intraocular pressure elevation that is difficult to treat.

Diabetic Macular Edema (DME): A Complication Affecting Sharp Vision

Diabetic macular edema (cystoid macular edema) is a common complication of diabetic retinopathy and is one of the leading causes of vision loss in people with diabetes.

Cystoid macular edema (CMO) develops when fluid leaks from damaged vessels into the macula, the central part of the retina responsible for sharp vision. The accumulation of fluid causes the macula to swell, resulting in dysfunction of the cells and blurring and distortion of central vision. In this case, reading or recognizing faces deteriorates, but any other task that requires central sharp vision also becomes more difficult.

Diabetic macular edema can occur at any stage of diabetic retinopathy and may be focal (affecting a localized area) or diffuse (affecting the entire macular region). Without treatment, macular edema can cause irreversible vision loss.

Prevention and Slowing of Diabetic Retinopathy

Although diabetic retinopathy cannot always be prevented, early detection and appropriate treatment of diabetes can significantly reduce the risk of developing diabetic retinopathy and slow its progression.

Management of the general condition plays an important role in preventing ophthalmic complications, which has several aspects.

• Strict glycemic control: Keeping blood glucose levels within the target range (generally HbA1c below 7%) is one of the most effective ways to prevent the development or progression of diabetic retinopathy.
• Blood pressure control: High blood pressure is one of the main risk factors for the progression of diabetic retinopathy. Keeping blood pressure at or below 130/80 mmHg can slow the progression of the disease.
• Lipid control: High cholesterol levels can worsen diabetic retinopathy and macular edema. Cholesterol-lowering medications, such as statins or fenofibrates, can help reduce this risk.
• Lifestyle modifications: Quitting smoking, eating a healthy diet, following a proper diet, and regular physical activity can help manage diabetes and its complications, including retinopathy.
• Regular ophthalmic examinations: People with diabetes should undergo a comprehensive ophthalmic examination at least once a year, which should include dilated fundus examination and macular OCT. This enables early detection and treatment of diabetic retinopathy, potentially preventing severe vision loss.

How Can Diabetic Retinopathy Be Treated?

Treatment of diabetic retinopathy is a complex task and involves treating multiple lesions, which may be present separately or simultaneously in the disease. Several treatment options are available to manage the condition, the primary goal of which is to prevent further vision loss. The choice of treatment depends on the severity of the disease, and these are often applied in combination or repeatedly. However, effective treatment and stabilization of the condition unfortunately do not always result in improved vision, as some of the retinal cells may already be damaged in the established disease. Predicting the extent of vision improvement is difficult and often impossible.

Treatment of diabetic macular edema (DME) is possible in two ways: with intravitreal injections or retinal micropulse laser treatment. In the case of macular edema, the primary goal is to eliminate the swelling at the site of sharp vision.

In the case of proliferative diabetic retinopathy, we aim to achieve occlusion of the abnormal neovascularization and reversal of the process. Currently, argon laser retinal treatment is the most suitable solution for this, either by conventional or navigated methods.

Late complications, such as tractional retinal detachment, are more difficult to treat and require major surgery (vitrectomy) under hospital conditions, with poorer chances of vision improvement. One of the goals of early treatments is to prevent the eye from reaching this latter state.

Argon Laser Treatment of the Retina

Laser photocoagulation has been the standard treatment for advanced diabetic retinopathy for many years. During this procedure, we sacrifice the peripheral parts of the retina that are less important for vision in order to preserve central vision and prevent the disease from progressing to more severe stages, and to reverse the more severe forms. During argon laser treatment, we create small burn injuries and scars on the periphery of the retina.

Panretinal Photocoagulation (PRP)

In proliferative diabetic retinopathy, treatment called panretinal photocoagulation (PRP) can achieve shrinkage of newly formed, abnormal vessels, thereby reducing the risk of vitreous hemorrhage and retinal detachment. Complete treatment of the retina can only be achieved with laser treatment performed on 4-6 occasions. Although this technique effectively prevents severe vision loss, certain side effects must be expected, such as visual field loss or constriction, night vision disturbances, and color vision disturbances.

Navigated Panretinal Photocoagulation (nPRP)

A more modern version of the treatment is navigated panretinal photocoagulation (nPRP), during which laser spots can be placed according to a predetermined pattern, so the resulting scars will be more uniform. Compared to conventional laser treatment, complete retinal treatment can be achieved in fewer sessions, so the desired effect is achieved more quickly. The procedure is also more comfortable, as it can be performed without placing a contact lens and the sensation of pain is significantly lower. The latter is due to the fact that 20% of the energy intensity compared to the conventional method is sufficient to achieve the desired effect.

Focal Photocoagulation

Argon laser treatment can also be used to reduce macular edema; treatment at this site is called focal photocoagulation. In this case, we place smaller laser spots in a localized area at or near the site of sharp vision to stop fluid leakage. Due to the risks of vision loss from the treatment and newer treatment options, we now very rarely use this procedure.

Intravitreal Injections and Implants

Anti-VEGF Injections

Vascular endothelial growth factor (VEGF) is a substance that plays a key role in the development of neovascularization and macular edema in diabetic retinopathy. Anti-VEGF agents are injected into the vitreous in the form of injections to block VEGF activity, thereby preventing the development of neovascularization and reducing macular edema. Anti-VEGF therapy, currently considered the gold standard, has revolutionized the treatment of DME and PDR, and has significantly improved visual outcomes in many patients; however, it is not the most ideal procedure, as it requires frequent and prolonged treatment in most cases.

Anti-VEGF injections must be administered monthly at the beginning, then every 2-3 months indefinitely, until the edema does not return. In favorable cases, a few treatments (at least 5) are sufficient for the macular edema to resolve permanently, but treatment often lasts for years due to recurrent macular edema.

Serious complications can also occur during injection treatments, such as purulent endophthalmitis, which is a severe, infection-related inflammation of the eye that often results in permanent vision loss even with treatment. However, with adherence to hygiene rules, its incidence is quite low.

Steroid Implants

The other group of injections includes steroid implants, which are delivered into the vitreous cavity in a small, absorbable reservoir. The implant gradually and evenly releases the active ingredient to the eye over 4-6 months, thus achieving a continuous effect. Although the advantage is that they need to be administered into the eye much less frequently, unfortunately their effectiveness is not ideal and complications are common (glaucoma, cataract development). For this reason, we generally use the treatment only in selected cases, as a reserve solution.

Micropulse Laser Treatment for Diabetic Macular Edema (MPL)

Micropulse laser treatment is an innovative alternative to conventional argon laser photocoagulation. Thanks to micropulse technology, the beneficial effect of the laser can be utilized without having to account for thermal damage (scarring) to healthy retinal tissue, as with conventional laser. The treatment is recommended in cases of mild or moderate macular edema, in which generally one treatment proves sufficient.

The advantage of micropulse laser treatment is that the entire treatment can be performed in one session and is painless. The procedure is safe and has no currently known complications. During the procedure, we do not create an external wound, so there is no risk of infection. With micropulse laser treatment, cystoid macular edema can be treated without damage to the photoreceptor cells, which is particularly important in the central areas critical for vision. If it becomes necessary later, there is no obstacle to repeating the micropulse treatment, as no scar forms on the retina during the treatment.

Anti-VEGF treatment and micropulse laser treatment can also be used in combination to increase effectiveness, stabilize the condition, and reduce the number of injections.

Vitrectomy: For Severe Diabetic Ophthalmic Complications

In advanced, proliferative diabetic retinopathy or in the case of vitreous hemorrhage that has not resolved for months, we must perform major surgery to stop or reverse vision loss.

Vitrectomy is performed under a microscope: we enter the eyeball through three needle-like openings and treat the diseased retina with various instruments. In the first steps of vitrectomy, we remove the vitreous gel. In the case of vitreous hemorrhage, we have thereby achieved the goal of the surgery, and we complete the operation by replacing the vitreous cavity with fluid.

Often, however, the abnormal vessels growing on the retina form thick neovascular membranes, which, when scarred, pull it along and cause tractional retinal detachment. In this case, we must cut through these abnormal tissues and peel them off the surface of the retina. Subsequently, we must reattach the retina evenly to the wall of the eyeball, which we must also fix with argon laser treatment.

It is not uncommon that even this is not sufficient in such cases, and the vitreous cavity must be filled with a substance that exerts a stronger pressing effect than fluid, silicone oil. We usually remove this substance from the eye after a few months, partly because vision can be at best only 20% through it, and partly because it can lead to further complications in the long term.

Anti-VEGF injection may also be administered before or during surgery, the purpose of which includes preventing bleeding from neovascularization and reducing macular edema.

What Is the Role of Vitamins in Diabetic Retinopathy?

Certain vitamins and nutrients have been shown to support retinal health, and according to some studies, may play a role in slowing the progression of diabetic retinopathy. These include the following:

• Alpha–lipoic acid: Antioxidant, anti-inflammatory, and improves endothelial function of small vessels.
• Vitamin A: Essential for maintaining retinal health and function.
• B vitamins: Vitamins B1, B2, B6, B9, B12 may have protective effects on the retina in diabetic retinopathy.
• Vitamins C, D, and E: Powerful antioxidants that help protect cells from oxidative stress and damage caused by high blood glucose levels.
• Lutein and zeaxanthin: Serve to protect the cells of the macula.
• N-acetylcysteine: As an antioxidant, it has a protective effect on retinal cells.

Although these vitamins may have beneficial effects on the disease, their routine use is not recommended, and in every case it is advisable to consult with your treating physician beforehand.

Summary

Diabetic retinopathy is a serious, progressive eye disease that can lead to irreversible vision loss if not detected and treated in time. Despite its insidious onset, diabetic retinopathy can be effectively managed with tight glycemic control, regular ophthalmic examinations, and appropriate treatment. Annual fundus examinations performed by a specialist are crucial for early detection of the disease, enabling timely intervention, such as laser treatment or anti-VEGF injections. In addition, lifestyle changes, proper blood pressure and cholesterol control, and the inclusion of vitamins in the diet can provide additional protective effects against this chronic disease.