Intravitreal injection

Intravitreal injection, also known as an intraocular injection, is a specialised medical procedure in which medication is delivered directly into the vitreous humour, the transparent, gel-like substance that fills the space between the lens and the retina at the back of the eye. This route of administration is specifically designed to target the posterior segment of the eye, enabling precise treatment of conditions that affect the retina, macula, or optic nerve—structures that are otherwise difficult to reach with topical or systemic therapies.

Intravitreal injections are most commonly used to treat sight-threatening retinal diseases, such as wet age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusions, among others. These conditions, if left untreated, can lead to irreversible vision loss. By injecting medication directly into the eye, clinicians can achieve high intraocular drug concentrations while minimising systemic exposure and associated side effects.

The procedure is typically performed under local anaesthesia in a sterile outpatient setting. Although it involves inserting a needle into the eye, it is generally well tolerated and considered safe when performed correctly. Advances in pharmacology—particularly the development of anti-VEGF therapies—have transformed the prognosis for many previously untreatable retinal diseases, making intravitreal injection a cornerstone of modern ophthalmic care.

Due to its effectiveness, this procedure has become one of the most frequently performed medical interventions in ophthalmology worldwide, with millions of injections administered annually.

History

The concept of delivering medication directly into the eye dates back to the early 20th century, but intravitreal injection as a routine clinical procedure only gained prominence in the latter half of the century.

Early ophthalmologists experimented with intraocular injections to treat infections and inflammatory conditions, but the technique was limited by concerns over ocular toxicity, infection risk, and the lack of safe, effective drugs suitable for intraocular use.

The development of vitreoretinal surgery in the 1970s and 1980s, along with advances in sterile technique and finer needles, paved the way for safer and more precise intravitreal injections.

A major turning point occurred in the early 2000s with the introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies. These drugs revolutionised the treatment of wet age-related macular degeneration (AMD), a leading cause of blindness. Prior to this, treatment options for wet AMD were limited and largely ineffective.

The landmark clinical trials demonstrating the efficacy and safety of intravitreal ranibizumab (Lucentis) and later aflibercept (Eylea) established intravitreal injection as a standard of care worldwide.

Since then, the procedure has expanded to treat a wide range of retinal diseases, including diabetic retinopathy, retinal vein occlusion, and uveitis. The development of sustained-release steroid implants and the use of intravitreal antimicrobials have further broadened its applications.

Today, intravitreal injections are among the most commonly performed medical procedures in ophthalmology, with millions administered annually worldwide, dramatically improving outcomes for patients with previously untreatable vision-threatening diseases.

Common Uses

Intravitreal injections are used to treat a variety of retinal, macular, and vitreous disorders, many of which can lead to progressive and permanent vision loss if left untreated. The procedure enables direct delivery of medications to the back of the eye, where these conditions originate. Below are the most common indications:

Wet Age-Related Macular Degeneration (Wet AMD)

Wet AMD is a chronic, degenerative eye disease that occurs when abnormal blood vessels grow under the retina and leak fluid or blood, causing rapid central vision loss. Intravitreal anti-VEGF injections are the gold-standard treatment, as they inhibit the growth of these abnormal vessels and help stabilise or improve vision. Early and regular treatment is crucial to preserving sight.

Diabetic Retinopathy and Diabetic Macular Oedema (DMO)

In patients with diabetes, prolonged high blood sugar levels can damage retinal blood vessels, leading to leakage, swelling, and the growth of new, fragile vessels. Diabetic macular oedema occurs when fluid accumulates in the macula, impairing central vision. Intravitreal injections of anti-VEGF agents or corticosteroids help reduce inflammation and fluid build-up, improving or stabilising visual acuity.

Retinal Vein Occlusion (RVO)

RVO, including central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), occurs when a vein in the retina becomes blocked, often leading to macular oedema and haemorrhage. This results in sudden or gradual vision loss. Intravitreal injections reduce retinal swelling and prevent further damage, typically using anti-VEGF drugs or corticosteroids.

Non-Infectious Posterior Uveitis

This inflammatory condition affects the uveal tract at the back of the eye and can cause damage to the retina and optic nerve. Corticosteroid injections into the vitreous humour help control intraocular inflammation in cases where systemic treatment is insufficient or contraindicated. Long-acting steroid implants may also be used for sustained control.

Infectious Endophthalmitis

Endophthalmitis is a severe, sight-threatening intraocular infection, often following eye surgery, trauma, or an injection itself. Intravitreal injections of broad-spectrum antibiotics or antifungals are administered urgently to control the infection and preserve vision. This is frequently performed in conjunction with a vitrectomy.

Cytomegalovirus (CMV) Retinitis

CMV retinitis is a serious retinal infection that primarily affects immunocompromised individuals, such as those with advanced HIV/AIDS or post-transplant patients. Intravitreal injections of antiviral agents like ganciclovir or foscarnet can help contain the infection locally, particularly when systemic antiviral therapy is inadequate or contraindicated.

Retinal Neovascularisation

The abnormal formation of new blood vessels on the retina, commonly seen in advanced diabetic retinopathy and other ischaemic conditions, can lead to vitreous haemorrhage and tractional retinal detachment. Intravitreal anti-VEGF agents help suppress neovascular growth, often used in conjunction with panretinal photocoagulation (PRP) laser therapy.

Macular Telangiectasia and Other Rare Disorders

Less common retinal conditions, such as macular telangiectasia (MacTel) or Coats’ disease, may also be managed using intravitreal medications, particularly when abnormal vessel leakage or neovascularisation is present.

Commonly Injected Medications

Intravitreal injections deliver a variety of medications tailored to the underlying ocular condition. The type of drug used depends on the disease being treated, its severity, and the patient's overall health. Most medications are administered using a fine-gauge needle and are designed to either reduce inflammation, inhibit abnormal blood vessel growth, treat infection, or manage oedema.

Anti-VEGF agents

Anti-vascular endothelial growth factor (anti-VEGF) drugs are among the most commonly injected medications in ophthalmology. They are primarily used to treat wet age-related macular degeneration, diabetic macular oedema, and retinal vein occlusion. These drugs work by blocking VEGF, a protein that promotes the growth of abnormal blood vessels and increases vascular permeability.

• Ranibizumab (Lucentis): A monoclonal antibody fragment specifically developed for intraocular use. It is approved for multiple retinal diseases and has a strong safety profile.
• Aflibercept (Eylea): A fusion protein that binds VEGF-A, VEGF-B, and placental growth factor (PlGF). It has a longer duration of action compared to some alternatives, allowing for less frequent dosing in many cases.
• Bevacizumab (Avastin): Originally developed for cancer therapy, this full-length monoclonal antibody is used off-label for ocular conditions. It is considerably more affordable and widely used globally despite not being specifically licensed for intraocular use.
• Brolucizumab (Beovu): A newer anti-VEGF agent with a small molecular size, allowing for high drug concentration per dose and potentially longer intervals between treatments. It has shown efficacy but has also been associated with a small risk of intraocular inflammation.

Corticosteroids

Corticosteroids are used to control intraocular inflammation and reduce macular oedema. They are particularly useful in treating non-infectious posterior uveitis, diabetic macular oedema, and macular oedema secondary to vein occlusion, especially in patients who do not respond to anti-VEGF therapy.

• Triamcinolone acetonide: A long-acting corticosteroid that can be injected directly into the vitreous cavity. It is effective but may increase the risk of cataract formation and elevated intraocular pressure.
• Dexamethasone implant (Ozurdex): A biodegradable implant that slowly releases dexamethasone over several months. It provides sustained anti-inflammatory effects and is commonly used in uveitis and macular oedema.
• Fluocinolone acetonide implant (Iluvien, Yutiq): A non-biodegradable implant that delivers fluocinolone over an extended period—up to 36 months. It is often reserved for chronic, recurrent cases of non-infectious posterior uveitis or diabetic macular oedema.

Antimicrobial agents

Intravitreal antibiotics and antifungals are used in cases of infectious endophthalmitis, a potentially blinding emergency. These medications are injected immediately upon suspicion of infection, often before culture results are available.

• Vancomycin: Targets Gram-positive organisms, including Staphylococcus aureus and Streptococcus species. It is often combined with a second agent.
• Ceftazidime: Effective against Gram-negative bacteria, including Pseudomonas. It is frequently used alongside vancomycin for broad-spectrum coverage.
• Amphotericin B: A potent antifungal agent used for fungal endophthalmitis. It has a narrow therapeutic index and must be administered carefully.
• Voriconazole: Another antifungal agent that may be used intravitreally for fungal infections, offering broader spectrum coverage with less retinal toxicity.

Antiviral agents

Used primarily in CMV retinitis and other viral infections of the retina, intravitreal antivirals deliver high drug concentrations directly to affected tissue, especially useful when systemic therapy is not viable or effective.

• Ganciclovir: A commonly used antiviral for CMV retinitis. It may be administered as direct injection or via sustained-release implant.
• Foscarnet: An alternative to ganciclovir, often used when resistance develops or when bone marrow toxicity is a concern with systemic therapy.

Emerging and experimental therapies

Research is ongoing into gene therapies, sustained-release drug delivery systems, and biologic agents that could eventually reduce or eliminate the need for frequent injections. Some investigational drugs aim to treat inherited retinal diseases or provide longer-lasting VEGF inhibition through viral vector delivery.

Procedure

The intravitreal injection procedure is typically performed in a clinical or outpatient setting under strict aseptic conditions. Despite the fact that it involves injecting a substance directly into the eye, the procedure is relatively quick, minimally invasive, and well tolerated when performed correctly.

Pre-procedure preparation

Before the injection, several preparatory steps are taken to ensure patient safety and comfort:

• Patient counselling and consent: The clinician explains the purpose of the injection, possible side effects, and potential risks. Informed consent is obtained.
• Positioning: The patient is usually seated in a reclined examination chair or placed in a supine position on a surgical table.
• Anaesthesia: A topical anaesthetic is applied using eye drops or gel to numb the ocular surface. In some cases, a subconjunctival injection of local anaesthetic may also be given.
• Antisepsis: The area around the eye and the ocular surface is thoroughly cleaned with an antiseptic solution, typically 5–10% povidone-iodine, to reduce the risk of infection. The use of iodine is considered critical in minimising the risk of endophthalmitis.
• Eyelid speculum: A sterile speculum is inserted to keep the eyelids open and prevent blinking during the procedure.

Injection technique

Once the eye is prepped and numbed, the clinician performs the injection with precision:

• Injection site: The needle is inserted into the pars plana, the relatively avascular area of the eye located approximately 3.5 to 4.0 mm posterior to the limbus, depending on whether the patient is phakic or pseudophakic (i.e. whether or not they still have their natural lens).
• Needle gauge: A fine-gauge needle (typically 27–32 gauge) is used to minimise discomfort and reduce tissue damage.
• Injection: The medication is injected slowly into the vitreous cavity, taking care to avoid touching the lens or retina. The entire process usually takes less than 10 seconds.
• Needle withdrawal: After the injection, the needle is carefully withdrawn and gentle pressure may be applied to the site with a sterile cotton-tipped applicator to prevent reflux.

Post-procedure care

After the injection, the following steps are typically taken:

• Visual check: The patient’s vision is briefly assessed to rule out immediate complications such as central retinal artery occlusion or significant haemorrhage.
• Intraocular pressure monitoring: In some cases, particularly when large volumes are injected or the patient has glaucoma, intraocular pressure is checked shortly after the injection.
• Post-injection instructions: Patients are advised to monitor for symptoms such as worsening vision, pain, or excessive redness. They are usually told to expect:
  • Mild irritation or a foreign body sensation
  • Blurry vision for a few hours
  • Small floaters or air bubbles (especially with certain medications)
• Topical antibiotics: Historically prescribed routinely, but current evidence suggests they are not necessary in most cases, and their routine use is declining due to concerns over resistance and lack of proven benefit.

Follow-up

Patients are typically scheduled for a follow-up visit within a few weeks, depending on the treatment protocol and the condition being managed. Some regimens, particularly those involving anti-VEGF agents, may require regular injections over a long-term period, ranging from monthly to every few months.

Risks and Complications

While intravitreal injections are considered safe and effective, especially when performed in a sterile environment by trained professionals, they are not entirely without risk. Most complications are rare and can be minimised through adherence to proper technique and post-injection monitoring. Complications can range from mild and transient to serious and vision-threatening.

Common and minor complications

These are typically self-limiting and resolve without intervention:

• Mild eye discomfort: A sensation of grittiness or irritation is common after the injection, usually lasting a few hours.
• Floaters: Small moving spots or shadows in the vision may occur due to tiny air bubbles or drug particles introduced during injection. These usually resolve within a few days.
• Subconjunctival haemorrhage: A small bleed under the conjunctiva (the white part of the eye) can occur at the injection site. It looks alarming but is painless and harmless, resolving in 1–2 weeks.
• Transient blurred vision: Temporary blurring may result from ocular surface irritation or the medication itself.
• Temporary rise in intraocular pressure (IOP): A mild, short-term elevation in pressure within the eye can occur after injection but usually resolves without treatment.

Less common but serious complications

These require prompt medical attention and may impact vision:

• Endophthalmitis: A rare but severe infection inside the eye, occurring in roughly 1 in 2,000 to 1 in 5,000 injections. Symptoms include increasing pain, redness, floaters, and vision loss. Urgent treatment with intravitreal antibiotics and sometimes vitrectomy is required.
• Retinal detachment: Separation of the retina from the underlying tissue, possibly triggered by vitreous traction or a retinal break. Symptoms include flashing lights, sudden floaters, or a shadow/curtain over part of the visual field.
• Traumatic cataract: Accidental contact of the injection needle with the lens can cause lens opacification, especially in phakic patients. Cataract surgery may be required in some cases.
• Lens injury: Direct mechanical damage to the crystalline lens may lead to visual impairment or need for surgical intervention.
• Vitreous haemorrhage: Bleeding into the vitreous cavity can obscure vision and typically occurs if retinal blood vessels are damaged during injection.
• Sustained elevation of intraocular pressure: Although often temporary, repeated injections—especially corticosteroids—can cause long-term IOP elevation, potentially leading to glaucoma.

Inflammatory complications

These may result from the drug itself or the body’s immune response:

• Sterile endophthalmitis (pseudo-endophthalmitis): A non-infectious inflammatory response to the injected drug, particularly seen with certain formulations. It presents similarly to infectious endophthalmitis but is less severe and often resolves spontaneously or with topical steroids.
• Intraocular inflammation: An immune-mediated reaction that can cause pain, redness, and visual changes. Most cases respond to corticosteroids but must be distinguished from infection.

Risk mitigation

Several strategies are employed to reduce the incidence of complications:

• Strict aseptic technique, including use of povidone-iodine antiseptic
• Use of sterile instruments and gloves
• Avoiding needle contamination by not touching lashes, lids, or conjunctiva
• Choosing the appropriate injection site and angle
• Post-procedure monitoring and clear patient instructions

Frequency

The frequency of intravitreal injections depends on several factors, including the underlying condition, the specific medication being used, the patient’s response to treatment, and the overall treatment strategy. Some therapies require frequent administration over long periods, while others are designed to last for several months or even years.

Anti-VEGF treatment regimens

Anti-VEGF drugs are typically used to treat wet age-related macular degeneration, diabetic macular oedema, and retinal vein occlusion. These medications often follow one of several dosing strategies:

• Loading phase: Treatment often begins with a series of monthly injections for 3 to 6 months to quickly suppress disease activity.
• Treat-and-extend: After disease stabilisation, the interval between injections is gradually extended (e.g. to every 6, 8, or 12 weeks) based on the patient’s response, with the aim of reducing injection frequency while maintaining control.
• Pro re nata (PRN) or "as needed": Injections are only given when there is evidence of disease activity on clinical examination or optical coherence tomography (OCT). This requires regular monitoring, typically every 4 to 8 weeks.
• Fixed dosing: In some cases, especially in clinical trials or certain treatment plans, injections are administered at fixed intervals (e.g. every 4 or 8 weeks) regardless of disease activity.

Corticosteroid implants

Steroid treatments are used for conditions such as non-infectious posterior uveitis and chronic macular oedema, especially when anti-VEGF therapy is inadequate or contraindicated.

• Triamcinolone acetonide: Often injected every 3 to 4 months, depending on the condition and intraocular pressure response.
• Dexamethasone implant (Ozurdex): Biodegradable, typically lasts 3 to 6 months, with re-treatment required accordingly.
• Fluocinolone acetonide implant (Iluvien/Yutiq): A non-biodegradable implant providing continuous drug release for up to 36 months. It is often used for long-term control in patients with chronic disease and a history of good response to steroids.

Antimicrobials and antivirals

For acute infections such as endophthalmitis or CMV retinitis, the frequency of intravitreal injections is determined by the severity of the infection and the pathogen involved.

• In endophthalmitis, multiple injections may be given over a period of days, often in combination with systemic antibiotics and possible surgical intervention.
• For CMV retinitis, antiviral injections may be given weekly or even more frequently, depending on disease progression and systemic therapy.

Long-term treatment considerations

Many retinal conditions, especially chronic degenerative diseases like wet AMD, require lifelong management. Although injection frequency may decline over time, complete cessation of therapy can lead to relapse. Ongoing monitoring and adjustment of treatment intervals are crucial.

Efforts are underway to develop longer-acting agents and sustained-release delivery systems to reduce the burden of frequent injections, both for patients and healthcare systems.

Alternatives

While intravitreal injection remains the preferred method for delivering medication directly to the posterior segment of the eye, especially for retinal diseases, several alternative or adjunctive treatments may be considered depending on the condition, severity, patient preference, and response to therapy.

Laser photocoagulation

Laser therapy uses focused beams of light to treat abnormal blood vessels or areas of retinal damage:

• Panretinal photocoagulation (PRP) is commonly used to manage proliferative diabetic retinopathy by reducing retinal oxygen demand and halting abnormal vessel growth.
• Focal/grid laser may be applied for diabetic macular oedema to seal leaking microaneurysms and reduce retinal swelling.
• Laser is also used in some cases of retinal vein occlusion and other vascular disorders.
• While effective, laser treatment may cause permanent scarring and peripheral vision loss, and is less frequently used now as a primary treatment for macular diseases compared to intravitreal injections.

Systemic or oral medications

For some inflammatory or infectious eye diseases, systemic therapy can be an alternative or supplement to intravitreal injections:

• Oral corticosteroids or immunosuppressants (such as methotrexate or mycophenolate mofetil) are used in non-infectious uveitis or autoimmune retinal conditions.
• Systemic antivirals or antibiotics may be indicated for infections like CMV retinitis or endophthalmitis, often combined with local therapy.
• However, systemic drugs may have limited ability to penetrate the eye in sufficient concentrations and carry a greater risk of systemic side effects.

Vitrectomy surgery

Vitrectomy is a surgical procedure to remove the vitreous gel and is sometimes indicated in:

• Severe or non-resolving vitreous haemorrhage.
• Retinal detachment repair.
• Cases of chronic or complicated endophthalmitis.
• Removal of epiretinal membranes or macular holes.
• Vitrectomy may be combined with intravitreal injections to improve drug delivery or address mechanical issues within the eye.

Sustained-release intraocular implants

In addition to standard intravitreal injections, long-acting drug delivery implants provide extended therapy without frequent injections:

• Steroid implants (e.g., Ozurdex, Iluvien) deliver corticosteroids over months or years.
• Research is ongoing into anti-VEGF implants and gene therapy vectors designed to provide continuous intraocular medication.

Observation and lifestyle modifications

In early or mild cases of some retinal diseases, particularly when vision is not significantly affected, careful monitoring with regular eye exams may be preferred before initiating invasive treatments.

Additionally, managing systemic risk factors such as blood sugar, blood pressure, and cholesterol levels plays a crucial role in slowing disease progression.