Degenerative retinal diseases are a major cause of visual impairment worldwide. With increasing life expectancy and longer exposure to risk factors, the demand for effective treatments has emerged as a vital challenge. In this context, intravitreal injections have established themselves as one of the most innovative and frequently used approaches in modern ophthalmology, especially for conditions such as age-related macular degeneration (AMD), diabetic retinopathy (DR) and non-ischemic macular edema.
What are intravitreal injections?;
Intravitreal injections are a method where drugs are injected directly into the vitreous body of the eye (inside the chamber in front of the retina). This local administration allows a high concentration of the drug in the target, avoiding systemic exposure and side effects of the rest of the body.
The drugs that are generally used fall into two main categories:
- Anti-VEGF (vascular endothelial growth factor replacement factors)
- Steroids and other anti-inflammatory intravitreal preparations
Depending on the condition, the patient's needs and the response, the most suitable substance or even an alternation between them can be chosen.
Degenerative retinal diseases treated with intravitreal injections
- Age-related macular degeneration (AMD)
The wet form of age-related degeneration is characterized by the development of abnormal neovessels under the retina, which leak fluids and blood cells causing swelling and changes in the macula. Anti-VEGF injections aim to inhibit this angiogenesis and reduce edema, allowing stabilization or even improvement of vision.
- Diabetic retinopathy (DR) and diabetic macular edema (DME)
In diabetic retinopathy, chronic hyperglycemia causes damage to the retinal microvessels, leading to leakage, ischemia and neovascularization. Diabetic macular edema is the most common cause of vision loss in diabetics and responds well to intravitreal injections of anti-VEGF and steroids, with reduction of edema and improvement of vision.
- Residual or resistant forms of oedema or neovascularisation
There are cases where the condition does not respond well to other treatment (such as laser photocoagulation or monitoring). Intravitreal injections are used as an alternative or adjunctive treatment in these cases.
Mechanism of action of intravitreal injections
Anti-VEGF agents
Ο VEGF (vascularendothelialgrowthfactor) is a protein that promotes the formation of new blood vessels (angiogenesis) and increases the permeability of the vessel walls. In retinal pathologies, increased VEGF expression contributes to leakage, edema and new vascular formations.
Intravitreal anti-VEGF injections (such as bevacizumab, ranibizumab, aflibercept and newer formulations) bind VEGF or inhibit its action, limiting the formation of abnormal neovessels and fluid leakage into the retinal network.
The result is the reduction of edema, the restoration of the normal anatomy of the macula and the achievement of functional improvement in vision or at least its stabilization.
Intravascular steroids and anti-inflammatory
- The inflammatory process plays an important role in many forms of retinal degenerative diseases.
- Intravitreal steroids (e.g. triamcinolone, dexacetazone in implants) help to reduce inflammatory tissue swelling, stabilize the cell membranes of vessels and reduce leakage.
- They are often combined with anti-VEGF therapies in difficult or refractory cases, or used when anti-VEGF is not indicated or not sufficient.
Advantages of intravitreal injections
Local, targeted action
They enable high concentration of the drug at the site of interest (retina) without significant systemic exposure and support safe use.
Dosage and timing flexibility
The dose and frequency of injections may be adjusted depending on the patient's response.
Efficiency
They have been shown to reduce swelling, stabilize or improve vision in many cases of degenerative diseases.
Complementary use
They can be combined with other treatment methods (such as laser therapy) or applied as a “rescue” when other treatments fail.
Minimally invasive
Although they enter the eye, the injections are relatively quick, painless (with local anaesthesia) and without much discomfort for the patient.
Limitations and risks
Although intravitreal injections offer significant advantages, they are not without risks and limitations:
Risk of endophthalmitis
There is a small, but real, risk of infection within the eye (endophthalmitis), a serious complication that requires immediate treatment.
Increased intraocular pressure (IOP)
Each injection may cause a temporary increase in intraocular pressure. In patients with glaucoma or predisposition to elevated pressure, IOP should be monitored.
Premature cataracts
In steroid treatments, there is a risk of accelerating the development of cataracts, especially in sensitive individuals.
Response and endurance
Some patients may not respond adequately to the first few injections (anti-VEGF resistance) or may experience recurrent swelling requiring ongoing invasive treatment.
Frequency of repetitions and costs
Intravitreal injections often require repeat injections with a defined interval (e.g. every 4-8 weeks or as needed). This can result in increased costs and burden in terms of time and monitoring.
Non-covered treatment areas
The peripheral area of the retina may not be adequately affected, and some pathological processes may require other treatments.
Administration strategies and treatment protocols
The strategy for administering intravitreal injections varies depending on the condition, stage, patient response and specialty guidelines. Some common approaches are:
Fixed programme (“fixedregimen”)
Some treatments start with a fixed number of injections (e.g. 3 monthly injections) and then continuous or adjusted administration.
Needs-based adaptation policy (ProReNata, PRN)
After initial phase, injections are given only when relapse or deterioration occurs, based on monitoring (visual acuity, OCT, vascular image).
The “treat-and-extend” method”
After the initial response, injections are given at gradually increasing intervals (e.g. +2 weeks) when the condition remains stable, with the aim of reducing the number of injections without loss of efficacy.
Combination treatment
In difficult or resistant cases, intravitreal injections are combined with other treatments (e.g. laser, photocoagulation, steroid injection).
Choosing the right strategy requires individualization per patient, based on monitoring visual acuity, macular morphology (OCT), vascular imaging (fluorescein angiography / OCT-angiography) and overall eye health.
Clinical benefits and results
Clinical studies and daily practice have demonstrated the following benefits from the use of intravitreal injections:
Stabilisation or improvement of vision
Many patients maintain their functional vision or even experience improvement (increase in visual acuity) after a series of injections.
Reduction of edema
The macular edema is often markedly reduced, as reflected on OCT images. This helps to reduce the deformity and disorder of the macula.
Avoiding disease progression
In many patients, intravitreal injections inhibit further deterioration of the disease, such as new blood vessel growth or worsening ischemia.
Reducing the need for other types of interventions
In the case of a successful response, the need for more invasive or radical procedures may be reduced.
Exploitation of new medicines and technology
With the development of new generations of anti-VEGF and steroid implants, treatments are becoming more effective, with longer-lasting effects and fewer injections.
Challenge of resistance and relapse
Despite the benefits, part of the treatment is still the management of resistance or relapse:
Intravitreal tolerance (tachyphylaxis / tolerance)
In some patients, after repeated injections, the response decreases. In these cases a change of anti-VEGF type, addition of steroids or protocol modification is considered.
Relapse of the disease
Despite treatment, swelling or new neovascular infiltrates may recur. Early detection and injection of «the resurgence point» is important to limit permanent damage.
Risk factors for non-response
Advanced stage of disease, long duration of disease before treatment, extensive peripheral pathology, coexisting vascular lesions or ischemia, advanced macular atrophy.
The management of resistance and relapse requires close monitoring, early diagnosis and flexibility in treatment strategy.
Role of imaging and monitoring
Successful use of intravitreal injections requires systematic monitoring with imaging tools:
OCT (Optical Coherence Tomography)
It measures the thickness of the macula, highlights the swelling and anatomical disorders (such as subconjunctival fluids, saccular cavities).
OCT is a «guidance tool» for assessing response and making a decision on reoperation.
OCT-angiography (OCTA)
It offers non-invasive imaging of the vascular networks of the macula without the use of contrast agent. It helps to identify neovessels, ischemia and areas with reduced perfusion.
Fluoroangiography
In some cases it is still used as the gold standard for the evaluation of leaks, neovessels and bleeding.
Bottom photography / visual acuity recording
Regular recording of visual acuity and documentation of the appearance of the fundus of the eye contribute to the clinical evaluation.
Linking clinical findings (vision) with imaging parameters is critical for optimizing treatment.
