Diabetic retinopathy: causes, symptoms, diagnosis, treatment

Diabetic retinopathy is a microvascular complication of diabetes mellitus, which damages the retinal capillaries, causes chronic ocular tissue ischemia, and leads to the formation of new abnormal vessels. The disease remains silent for a long time: in the early stages, a person sees "as usual," although changes in the retina are already occurring. Therefore, international standards recommend regular ophthalmological screening for all people with diabetes, including adolescents and pregnant women. Early detection allows for intervention before irreversible vision loss occurs. [1]

Clinically, there are non-proliferative stages (when vessels have not yet "grown" into the vitreous) and proliferative stages (when, due to severe ischemia, the retina "begs" for new vessels). A separate and very important topic is diabetic macular edema: this is the accumulation of fluid in the macula, causing blurred and distorted vision. Today, effective ocular injections of drugs against vascular endothelial growth factor, laser techniques, and vitreous surgery are available for the treatment of macular edema and the proliferative stage. [2]

Despite the arsenal of treatments, the key to preserving vision is timely examination and risk factor management. Modern screening programs utilize not only ophthalmoscopy and fundus photography, but also telemedicine and, in some countries, autonomous artificial intelligence systems that use photographs to determine whether an urgent visit to an ophthalmologist is necessary. These systems do not replace a doctor, but they help reach patients who have never seen an ophthalmologist. [3]

Finally, it's important to understand that diabetic retinopathy isn't just a "eye issue." Retinal damage correlates with overall vascular risk and reflects what's happening to microvessels throughout the body. Therefore, a well-designed plan can not only preserve vision but also reduce the risk of cardiovascular events. This is another reason to adhere to modern surveillance standards. [4]

Code according to ICD-10 and ICD-11

In the International Classification of Diseases, 10th revision, "diabetic retinopathy" is listed as a separate ophthalmological category and as a complication of diabetes mellitus. The World Health Organization's ICD-10 "core" list for ophthalmologists uses code H36.0 "Diabetic retinopathy." National clinical and statistical versions (e.g., ICD-10-CM in the USA) more often code "diabetes with ophthalmological complications" with an extension to a specific variant of retinopathy and the presence of macular edema (e.g., E11.311 - type 2 diabetes mellitus with unspecified diabetic retinopathy with macular edema). [5]

In the International Classification of Diseases, 11th revision, retinopathy is classified under "Diseases of the Retina" and coded as 9B71.0 "Diabetic Retinopathy," with clarifications on stage, lateralization, and clinical features (e.g., 9B71.01 - proliferative diabetic retinopathy). The ICD-11 system supports post-coordination: the retinopathy code alone is insufficient; the type of diabetes is additionally specified, followed by clarifications on macular edema and vision loss. This improves the accuracy of reporting and allows for automatic linking of ophthalmologist and diabetologist findings. [6]

Table 1. Codes that actually appear in documents

System	Block	Example/meaning	Comments
ICD-10 (WHO)	H36.0	Diabetic retinopathy	Used by ophthalmologists as a diagnosis of the eye. [7]
ICD-10-CM (USA)	E10.3-E14.3	Diabetes with ophthalmologic complications	Next, the type of retinopathy and macular edema are specified, for example E11.311. [8]
ICD-11 (WHO)	9B71.0	Diabetic retinopathy	Possible clarifications: 9B71.01 - proliferative form; add the code for the type of diabetes. [9]

Epidemiology

According to a global meta-analysis of 59 population-based studies, diabetic retinopathy occurs in 22–25% of adults with diabetes, of which approximately 6% have vision-threatening forms (proliferative stage and/or clinically significant macular edema). In 2020, an estimated 103 million adults were living with retinopathy, and by 2045, this number is expected to increase to approximately 160 million. These estimates include countries with varying screening availability but clearly show a trend: the number of cases is increasing in line with the increasing prevalence of diabetes. [10]

According to estimates from the International Consortium on Vision Impairment, in 2020, 1.07 million people were blind due to diabetic retinopathy, and another 3.28 million had moderate or severe visual impairment. This makes retinopathy one of the leading causes of preventable vision loss in working-age people. Regional differences are significant: a high burden is observed in countries with rapidly increasing diabetes incidence and low screening coverage. [11]

National figures vary depending on the healthcare system and screening discipline. For example, US data show that about a quarter of people with diabetes have retinopathy, yet many never receive an annual fundus examination. This is an excellent example of how the introduction of telemedicine and autonomous artificial intelligence in primary care can reduce the gap between recommendations and reality. [12]

In adolescents, the risk increases rapidly with the duration of the disease and poor glycemic control. This is why pediatric recommendations recommend starting initial ophthalmological examinations within a few years of the onset of type 1 diabetes and immediately with type 2 diabetes in adolescents. The frequency of follow-up depends on the findings at the initial examination. [13]

Reasons

The primary cause of diabetic retinopathy is chronic hyperglycemia: high blood glucose levels trigger a chain of biochemical reactions in the retinal vessels that damage cell membranes, proteins, and the extracellular matrix. Important factors include the formation of advanced glycation end products, oxidative stress, and activation of intracellular signaling pathways that disrupt endothelial function and promote inflammation. This is the common "ground" for all stages of the disease. [14]

Early on, pericytes—the supporting cells of capillaries and the "framework" of microvessels—die. Where pericytes are lost, the vascular wall loses stability, microaneurysms form, plasma leakage increases, and local edema develops. Simultaneously, endothelial cells die and capillaries close, leading to poorly reversible retinal ischemia. [15]

When tissue experiences oxygen starvation, it increases production of vascular endothelial growth factor and a number of proinflammatory mediators. These signals increase vascular permeability (contributing to macular edema) and stimulate the growth of new, but fragile and "abnormal" vessels—this is the proliferative stage, fraught with hemorrhages and retinal detachment. [16]

Macular edema adds its own drama: the integrity of the internal blood-retinal barrier is disrupted, fluid accumulates in the macula, and the architecture of the photoreceptors is distorted—the image becomes blurry, dark spots, and line distortions appear. Inflammation, leukocyte adhesion to the endothelium, and thickening of the capillary basement membrane contribute to the edema. [17]

Risk factors

The most powerful and proven risk factors are the duration of diabetes and the quality of glycemic control. The longer a person lives with elevated glucose levels and the more frequent the "swings" with high levels, the higher the risk of retinopathy and its progression. This risk applies to both type 1 and type 2 diabetes. [18]

Blood pressure and lipid profiles have a significant impact. Elevated blood pressure exacerbates microvascular stress, while atherogenic lipoproteins and high triglycerides are associated with exudates and macular edema. Therefore, ophthalmological guidelines list blood pressure and lipid control alongside glucose as part of a vision protection "package." [19]

Chronic inflammation, smoking, kidney disease, pregnancy (especially with initially poor control), and rapid correction of sharply elevated glycemia (the so-called "early deterioration," known to ophthalmologists at the start of intensive insulin therapy and some new metabolic drugs) are all significant. This is not a reason to abandon treatment, but a signal to monitor the retina more frequently during sudden changes in sugar levels. [20]

Finally, heredity also plays a role, but the genetic contribution cannot yet be reduced to a simple test. More importantly for practice, almost all of the risk factors listed are modifiable, meaning they can and should be addressed in parallel with ophthalmological treatment. [21]

Table 2. What most strongly “pushes” retinopathy

Factor	Why does it increase the risk?	What to do
Duration of diabetes	Long-term exposure to hyperglycemia and variability	Early and regular eye screening.[22]
High glucose and swings	Oxidative stress, glycation, inflammation	Individual glycemic goals and their stability.
Hypertension and dyslipidemia	Microangiopathy and exudation	Blood pressure < target values, lipid correction. [23]
Smoking, kidney disease	Increased vascular and inflammatory background	Tobacco cessation, nephroprotection.

Pathogenesis

The pathogenesis of diabetic retinopathy can be conceptualized as three interconnected layers. The first layer is the metabolic cascades of hyperglycemia: advanced glycation end products are formed, protein kinase C, polyol, and hexosamine pathways are activated, and oxidative stress increases. These processes damage the endothelium, pericytes, and basement membrane of retinal capillaries. [24]

The second layer is cellular events: death of pericytes and endothelial cells, loss of tight junctions between cells, thickening of the basement membrane, and adhesion of leukocytes to the vascular wall. The result is microaneurysms, vascular permeability, foci of ischemia, and gradual closure of capillaries. It is this stage that lays the foundation for macular edema and the transition to the proliferative stage. [25]

The third layer is the retina's response to oxygen deprivation: increased production of vascular endothelial growth factor and other molecules increases permeability and stimulates the growth of fragile new vessels. These vessels bleed easily, pulling on connective tissue membranes, leading to hemorrhages into the vitreous body, tractional retinal detachment, and the threat of sudden vision loss. [26]

A separate mechanism is disruption of the internal blood-retinal barrier in the macula. Inflammation and endothelial dysfunction "unzip" the intercellular junctions, allowing plasma to leak into the tissue, resulting in macular edema. This is why, in addition to antiangiogenic drugs, anti-inflammatory glucocorticosteroid implants are also used, especially in cases where the edema is poorly responsive to antiangiogenic therapy. [27]

Symptoms

In the early stages, symptoms are absent. This isn't a paradox, but a characteristic of the retina: a significant portion of the visual field compensates for "silent" defects, and a person doesn't notice the problem until the process affects the center of the retina or a hemorrhage occurs. Therefore, the absence of complaints doesn't mean the absence of the disease, and one should rely on a routine examination, not on sensations. [28]

When the macula is involved, a person notices blurring, "wavy" lines, decreased contrast, and impaired reading. These are typical complaints of diabetic macular edema. In everyday life, people describe it as "the screen has become blurry" or "letters are floating," especially towards the end of the day. At this stage, it is especially important to quickly confirm the diagnosis and begin treatment. [29]

In the proliferative stage, sudden "black curtains" or "floating spots" before the eyes may occur—this is a vitreous hemorrhage. Sometimes this resolves, but more often it signals severe neovascularization and the risk of tractional retinal detachment, requiring urgent evaluation by a vitreoretinal surgeon. [30]

Less commonly, the onset is manifested by a "stress situation"—a sudden loss of vision in one eye due to tractional detachment. This outcome can be avoided by continuing annual screening and treating retinopathy before its severe stages. This is the key practical conclusion from current recommendations. [31]

Classification, forms and stages

Clinically, a gradation is used between non-proliferative retinopathy (mild, moderate, severe) and proliferative retinopathy. The severity of the non-proliferative form is determined by the number of microaneurysms, hemorrhages, exudates, and signs of ischemia (e.g., venous anomalies, intraretinal microvascular anomalies). The proliferative form is the presence of newly formed vessels on the optic disc or elsewhere, often with preretinal or vitreous hemorrhages. [32]

Diabetic macular edema is also described, with or without central macula involvement. This is a separate severity axis, determining the need and urgency for injections of anti-vascular endothelial growth factor medications or glucocorticosteroid implants. Edema is confirmed by optical coherence tomography. [33]

For scientific and telemedicine programs, the scale from early diabetes eye treatment studies (the so-called "seven-field" fundus photography system) is retained, but in real-world practice, ultra-wide-angle imaging and optical coherence tomography angiography are increasingly being used to assess the periphery and blood flow without dye injection. These techniques are consistent with the classical scale in terms of diagnostic accuracy. [34]

Finally, for state statistical purposes and payment of medical care, stages are linked to ICD codes. This is important for data exchange between ophthalmologists and endocrinologists, including notations regarding the presence or absence of macular edema. [35]

Table 3. How to briefly read the stage in the conclusion

Axis	What does it mean?	Example of wording
Nonproliferative retinopathy	There is microvascular damage, but no neovascularization.	"Moderate nonproliferative retinopathy in both eyes"
Proliferative retinopathy	There are new fragile vessels, high risk of hemorrhage	Proliferative retinopathy of the right eye
Macular edema	Fluid accumulation in the macula	"Diabetic macular edema with central involvement"

Complications and consequences

Vitreous hemorrhages block the light pathway and dramatically impair vision. They often recur until the proliferative process is suppressed with laser and/or injections of drugs against vascular endothelial growth factor. Surgical removal of the vitreous is sometimes required, especially if the opacity persists for weeks. [36]

Tractional retinal detachment occurs due to connective tissue membranes "stretching" the retina during neovascularization. If the detachment affects the macula or threatens it, urgent vitrectomy is required. For small detachments, the surgeon and patient jointly decide on the timing of the intervention. [37]

Diabetic macular edema is a common cause of vision loss in people with nonproliferative retinopathy. Even with preserved peripheral vision, the edema causes the central vision to deteriorate, leading to decreased reading speed and the ability to process fine details. The good news is that modern treatment often restores this function. [38]

Without treatment, proliferative retinopathy can lead to neovascular glaucoma, when new vessels close the anterior chamber angle and increase intraocular pressure. This is one of the most severe complications, requiring combined care by an ophthalmologist-retinologist and a glaucoma specialist. [39]

When to see a doctor

Anyone with diabetes should undergo an initial ophthalmological examination according to the following standards: for type 2 diabetes, immediately upon diagnosis; for type 1 diabetes, 3-5 years after onset, and then annually (the interval may vary depending on findings). Pregnant women with diabetes should undergo an examination in the first trimester and then as needed. [40]

Schedule an eye exam immediately if you experience blurring, "wavy" lines, flashes of light, "floating spots," "black curtains," or a sudden drop in vision in one eye. These symptoms may indicate macular edema, hemorrhage, or retinal detachment. It's not every week that counts, but sometimes every day. [41]

If there's a sudden change in blood sugar lowering therapy or a rapid improvement in very high blood sugar levels, your doctor may recommend an unscheduled retinal examination: this is to detect the rare phenomenon of "early deterioration." This risk is lower than the risk of continuing to live with high blood sugar levels, but monitoring is still necessary. [42]

If an ophthalmologist is far away, use screening routes: fundus photography followed by evaluation by a specialist or, where available, an autonomous artificial intelligence system trained to recognize signs of retinopathy. A positive result is not a diagnosis of surgery, but a reason to see an ophthalmologist. [43]

Diagnostics

Step 1. Data collection and basic examination. The doctor clarifies the patient's diabetes history, glucose fluctuations, concomitant illnesses, and medications. Visual acuity is tested, intraocular pressure is measured, and the anterior segments of the eye and pupillary responses are examined. This establishes a "context" for risk and provides a starting point for dynamic comparison. [44]

Step 2. Fundus examination. After dilating the pupil, the ophthalmologist examines the retina, recording microaneurysms, hemorrhages, hard and cotton-wool exudates, venous anomalies, intraretinal microvascular anomalies, and signs of neovascularization. Fundus photographs are taken for documentation; increasingly, ultra-wide-angle images are used, which capture up to 200° of the retina in a single frame. [45]

Step 3. Optical coherence tomography. To confirm or rule out macular edema, macular tomography is performed—this is a micron-precision "slice" of the retina. If blood flow needs to be assessed, tomographic angiography is used, which allows capillary plexuses to be visualized without the use of dye and early perfusion abnormalities to be identified. [46]

Step 4. Fluorescein angiography and additional methods. When it is necessary to clarify areas of ischemia and leakage or plan laser treatment, dye angiography is performed; in the proliferative stage, this helps assess the activity of newly formed vessels. Telemedicine allows for initial screening using an artificial intelligence algorithm, already approved in the US for autonomously determining the need for an ophthalmologist referral. [47]

Table 4. Diagnostic tools - who is responsible for what

Method	What does it show?	When needed
Examination with pupil dilation	All the main signs of retinopathy	Base on every visit. [48]
Fundus photography (including ultra-wide-angle)	Documentation, peripheral changes	Screening and dynamics, telemedicine. [49]
Optical coherence tomography	Macular thickness, edema, traction	Confirmation of macular edema, treatment monitoring.
Tomographic angiography	Blood flow in the capillary plexuses	Early perfusion changes and treatment strategy. [50]

Differential diagnosis

Not all bloodspots and exudates on the fundus are due to diabetic retinopathy. Similar symptoms can occur with hypertensive retinopathy, retinal vein occlusion, inflammatory vasculitis, and sickle cell disease. Differences are based on vessel configuration, lesion location, and history (for example, sudden painless vision loss and honeycomb-like edema are more common with venous occlusion). [51]

In macular edema, it is important to distinguish diabetic macular edema from inflammatory or postoperative edema. Optical coherence tomography and angiography are helpful; in diabetes, multiple microaneurysms, lipid exudates, and characteristic fluid distribution within the retinal layers are more often visible. [52]

In patients without known diabetes, vitreous hemorrhages are differentiated into retinal tears, other types of neovascularization, and trauma. The optical media may be obstructed, so ultrasound is sometimes required to rule out detachment. In questionable cases, the final diagnosis is confirmed by the progression and response to treatment. [53]

Finally, complaints of "floaters" and flashing lights may be associated with posterior vitreous detachment, a normal age-related condition. However, in a person with diabetes, this scenario does not rule out retinopathy, so it's best to get tested rather than guess. [54]

Treatment

The foundation of modern therapy is retinal support using three "pillars": ocular injections of drugs against vascular endothelial growth factor, laser techniques, and vitreoretinal surgery—each at its own time and as indicated. Antiangiogenic drugs reduce macular edema and calm newly formed vessels; lasers stabilize ischemic zones and reduce the retina's need for pathological vascular growth; surgery removes blood and traction when they interfere with vision or threaten the macula. [55]

For diabetic macular edema, injections of anti-vascular endothelial growth factor (VEGF) drugs are the first choice in most cases. Several molecules are used; a new one is a bispecific drug that simultaneously targets VEGF and angiopoietin-2, which allows for longer injection intervals without loss of efficacy in some patients. For patients who find it difficult to visit the clinic frequently, a high-dose formulation of another anti-VEGF drug is available, allowing for reduced visit frequency after the saturation phase. [56]

If macular edema is caused by a significant inflammatory component or is poorly responsive, intraocular glucocorticosteroid implants are used, which gradually release the medication into the eye. This is convenient when frequent visits to the clinic are impossible, but the risks of increased intraocular pressure and accelerated cataract formation should be kept in mind; these issues are addressed in consultation with an ophthalmologist-retinologist and glaucomatologist. [57]

For proliferative retinopathy, the treatment strategy is decided between panretinal laser photocoagulation and injections of anti-vascular endothelial growth factor (VEGF) drugs (or a combination of both). Panretinal laser has historically proven its ability to prevent vision loss and remains the standard, especially if there are concerns about the regularity of visits. Anti-VEGF drugs may provide better functional results with consistent injections but require discipline and a reminder system. The choice is discussed with the patient, taking into account lifestyle, availability, and concomitant diagnoses. [58]

Vitrectomy—a surgical procedure to remove the vitreous—is indicated when blood does not resolve, when membranes pull on the retina, threatening the macula, in cases of combined tears, and in neovascular glaucoma to control the source of ischemia. Modern microinvasive surgery can shorten recovery times, but the decision on the timing of surgery is individual: sometimes it is appropriate to wait and see if the blood resolves, while other times delay is dangerous for the macula. [59]

All ocular treatments work best when systemic factors are controlled: glycemia, blood pressure, lipids, and smoking cessation. These aren't just general statements: patients with good control have a reduced risk of macular edema recurrence and retinopathy progression. Management should be team-based—the ophthalmologist and endocrinologist coordinate goals and medications to simultaneously reduce ocular and systemic risks. [60]

In real life, not everyone can get an ophthalmologist appointment in a timely manner. That's where telemedicine screening programs come in: a photo of the eye fundus is taken at a clinic or pharmacy, an algorithm recognizes signs of retinopathy, and the patient receives a referral. Approved autonomous artificial intelligence systems have already proven their ability to safely "filter" the flow and increase screening coverage at the primary level, especially in regions with a shortage of ophthalmologists. [61]

Imaging technologies have also advanced. Ultra-wide-angle imaging provides a glimpse into the periphery, where significant lesions associated with the risk of progression are hidden; tomographic angiography allows for quantitative assessment of blood flow and perfusion even before gross changes appear on images. These tools help personalize the strategy: for some, laser therapy for peripheral ischemic zones, for others, an emphasis on injections, and for others, tight dynamic monitoring. [62]

Finally, an ophthalmologist will always explain: while we treat the eye, we also protect the person. Improving sleep, nutrition, physical activity, and smoking cessation are not "supplements" but factors that reduce inflammation and improve microcirculation. Such measures increase the chances of long-term remission after any eye treatment. [63]

Table 5. What we treat with what - a practical map

Situation	First line	Alternatives and additions
Macular edema with central involvement	Anti-vascular endothelial growth factor injections (including bispecific molecule)	Glucocorticosteroid implant for poor response/contraindications; focal/lattice laser as indicated. [64]
Proliferative retinopathy	Panretinal laser photocoagulation or injections against vascular endothelial growth factor	Combination of methods taking into account commitment and anatomy. [65]
Blood does not dissolve, traction, threat to the macula	Vitrectomy	Premedication with anti-vascular endothelial growth factor injection; postoperative laser. [66]

Prevention

The primary prevention method is regular screening and risk factor monitoring. Screening is not a consumer "option," but a necessary medical service: for type 2 diabetes, the first eye examination is mandatory immediately; for type 1 diabetes, it is 3-5 years after onset, and then usually annually. The interval is shortened if changes or pregnancy are detected. [67]

Strict glycemic control reduces the risk of retinopathy and slows its progression, especially if achieved early. Add to this control blood pressure and lipids, quitting smoking, and normalizing body weight and activity. These same measures will protect the heart and kidneys—all microvascular "targets" benefit simultaneously. [68]

If access to an ophthalmologist is limited, telescreening can be used: a fundus photo can be taken at a primary care clinic and a report can be obtained—either by a human or by autonomous artificial intelligence, which has already been approved by the regulator as a means of independently detecting signs of retinopathy. A positive result is a reason for a targeted visit, while a negative result does not cancel a scheduled examination in a year. [69]

Pregnant women with diabetes are especially advised to manage their blood sugar levels before conception and undergo an ophthalmological examination in the first trimester. In some women, rapid normalization of very high blood sugar levels can temporarily worsen retinopathy—this phenomenon is known and can be monitored with more frequent visits. [70]

Forecast

With timely detection and treatment, the prognosis is favorable: the vast majority can slow the progression and maintain useful vision for years and decades. This is especially true for macular edema—modern injections often restore visual acuity and allow for longer intervals between visits after the saturation phase. [71]

Untreated proliferative retinopathy is the main risk of sudden vision loss due to hemorrhages and detachment. Panretinal laser photocoagulation and/or anti-vascular endothelial growth factor injections significantly reduce this risk, and if complications arise, modern vitreous surgery offers the chance to restore transparency of the optical media and straighten the retina. [72]

Long-term prognosis depends not only on ophthalmic procedures but also on systemic control: consistently achieving target glycemia, blood pressure, and lipids means fewer new foci of ischemia and edema, and fewer injections and surgeries. Therefore, ophthalmologic and diabetic plans should go hand in hand. [73]

Finally, even in severe stages, one shouldn't give up: technology is advancing, with drugs with longer-lasting effects and new biomarkers enabling early detection of deterioration. Regular visits are an opportunity to take advantage of these advances. [74]

FAQ

Is it true that retinopathy "necessarily" leads to blindness?
No. With regular screening and modern treatment, most people can maintain their vision and activity. It's not the retinopathy itself that's dangerous, but late visits and missed appointments. [75]

If my blood sugar is normal, can I have my eyes checked less frequently?
The interval is determined individually. Even with good control, early changes can still appear, so follow your ophthalmologist's recommendations following your most recent examination. [76]

Are eye injections painful?
The procedure is performed under local anesthesia and is usually well-tolerated. Most people report only short-term discomfort. It's important to follow the schedule—it determines the outcome. [77]

Can laser injections be substituted?
For macular edema with central involvement, drugs against vascular endothelial growth factor are preferable. Laser remains an important tool for proliferative retinopathy and peripheral ischemic areas; methods are often combined. [78]

How reliable are smart cameras and algorithms?
Regulatory-approved autonomous systems have proven highly accurate in selecting patients for referral to an ophthalmologist. This is a screening, not a replacement for an in-person visit: a positive result is a reason to visit a specialist. [79]

Table 6. Important yeses and nos for the patient

Situation	Do	Do not do
The first year after diagnosis of type 2 diabetes	Get an ophthalmological examination immediately	Postpone "until symptoms appear"
Diabetic macular edema	Follow the injection schedule and come for check-ups.	"Stretching" intervals without agreement
Proliferative retinopathy	Discuss laser and injections while weighing lifestyle considerations	Refusing "due to fear of injections"
Ophthalmologist unavailable	Take a telescreening (photo of the fundus)	Rely only on how you feel