Intravitreal Injection Therapy: Current Techniques and Supplemental Services

Abstract

Purpose:

Intravitreal injection is the most frequently performed eye procedure in the world and is an essential component in the management of sight-threating retinal diseases and conditions. Given the seriousness and range of diseases treated and the risks of the procedure, retina specialists must weigh the pros and cons of each individual treatment. Complexities guiding injection treatment are multifaceted and involve patient-history review, careful examination, diagnostic testing selection and interpretation, customized medical decision-making, and follow-up considerations.

Methods:

This article by the Intravitreal Injection Task Force Committee of the American Society of Retina Specialists documents the intricacies and necessary components of the intravitreal injection procedure.

Results:

By expert consensus, the task force further recommends ancillary services and decision-making that may accompany intravitreal injection visits, when appropriate, to monitor response to treatment, adjust treatment, and manage additional considerations in the same or fellow eye.

Conclusions:

Retina specialists can optimize safety and therapeutic outcomes with individualized consideration and customization of intravitreal injection treatment for each patient.

Introduction

Intravitreal injection is the most common eye procedure worldwide ¹ and is increasing in use by 6% annually in the United States. ² Intravitreal injections have revolutionized retinal disease management and enabled dramatically improved prognosis to patients with potentially blinding retinal disease. Despite being common, intravitreal injection therapy is rarely “standard,” given the complexity of decision-making required for patients’ treatment. Intravitreal injection treatment is guided by individual patient’s factors, and therapy is tailored to achieve the best outcome for each patient.

Since the approval of the first antivascular vascular endothelial growth factor (anti-VEGF) injection therapy in 2005, ophthalmologists have come to learn through experience that real-world patients undergoing treatment of retinal disease are quite different from the patients who met the inclusion and exclusion criteria of the registration studies that led to commercial availability. Owing to the restrictive criteria of clinical trials, most patients are not candidates for trial inclusion. There are numerous conditions for which intravitreal injections are not Food and Drug Administration (FDA) approved yet studies have demonstrated benefit (eg, ocular histoplasmosis, polypoidal choroidal vasculopathy, retinal arterial microaneurysm, and cystoid macular edema [ME]). Furthermore, comorbid eye disease, systemic disease, or fellow eye disease may affect or add myriad complexities to a patient’s disease management. A variety of drugs are delivered by intravitreal injection, some FDA approved and some off-label.

Because of unique circumstances, most patients are not on a fixed treatment schedule and require examination of the eye(s) at customized intervals that deviate from the FDA label, including the “treat and extend” and “as-needed” treatment paradigms. Additionally, the number of FDA-approved medications is expected to increase over time, adding further complexity and agent-specific examination requirements to current treatment algorithms. Each of these options and variations adds significant management. Clinicians’ judgment aided by retinal diagnostic imaging allows therapy to be tailored to an individual patient’s condition, improving efficiency and decreasing the treatment's burden to patients and the cost to the health care system. ³ Therefore, a full spectrum of intravitreal injection therapy includes scheduled “standard” injections and also more complex variations that require a multifaceted approach and deliberations prior to injection. The purpose of this document is to review intravitreal injection therapy and to discuss considerations for which additional services are appropriate.

Methods

Vignette

This clinical vignette is an example of an intravitreal injection therapy that warranted supplemental medical decision-making at multiple times because of new abnormalities or worsening of disease in the same eye or fellow eye. For this patient, supplemental services allowed the physician to respond to clinical developments over time so that treatment could be customized for optimal care. Customization in turn allowed for safe deviation from the medication’s FDA label, management of concerns about the fellow eye, and reduction of unnecessary visits and injections as compared with standard monthly or bimonthly injection therapy.

A 77-year-old White woman developed a new paracentral scotoma in her right eye. Her initial visual acuity (VA) was 20/32 in the right eye and 20/16 in her left eye. Fundus examination revealed drusen, pigment clumping, and subretinal fluid (SRF) in her right macula. Drusen and pigment changes with no ME or hemorrhage were present in the left eye (Figure 1). Optical coherence tomography (OCT) and fluorescein angiography (FA) confirmed the presence of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) in her right eye and dry macular degeneration in the left eye (Figure 2). Based on examination and imaging results, the decision to treat with anti-VEGF therapy was made. After obtaining informed consent, the patient began monthly therapy with intravitreal aflibercept injections. A favorable response to treatment with resolution of the SRF by the third month was found on follow-up examination, which allowed the time frame for the next visit to be adjusted (Figure 3). After the first 3 monthly injections, aflibercept injections were transitioned to every other month, and she responded well to the reduced treatment frequency.

Figure 1.

Color fundus photographs and optical coherence tomography images of the (A and B) right and (C and D) left fundus at presentation.

Figure 2.

(A) Early and (B) late fluorescein angiogram images of the right eye confirm the presence of choroidal neovascularization at presentation.

Figure 3.

Response to intravitreal aflibercept. Optical coherence tomography images taken (A) before and after the (B) first, (C) second, and (D) third monthly aflibercept injection demonstrate resolution of subretinal and subretinal pigment epithelium fluid.

The patient continued treatment with aflibercept injections in her right eye every 2 months for the next 2 years. During this time, she developed metamorphopsia in her left eye. At a follow-up visit for possible intravitreal injection for the right eye, she was also examined to rule out new-onset neovascular macular degeneration in the left eye. She was found to have progressive changes related to dry macular degeneration that did not require intravitreal injection.

At 27 months after presentation, she remained asymptomatic with reduction of the scotoma. Despite not having any visual changes, she was found on dilated fundus examination thereafter to have a new retinal hemorrhage in the right eye, which indicated recurrent activity (Figure 4). FA confirmed the CNV complex was active and enlarged. Injection therapy was therefore readjusted to a shortened monthly interval and then eventually spaced to 4 to 6 weeks in the right eye.

Figure 4.

A new retinal hemorrhage was noted on dilated fundus examination at month 27, which indicated new choroidal neovascular activity.

Intravitreal Injections: Current Techniques

Prior to the intravitreal injection, a brief history is obtained to update status, to address any changes in vision or eye discomfort in the treated or fellow eye, and to screen issues related to comorbid eye disease (separate from the condition being treated with intravitreal injection). A limited eye examination is performed to rule out active infection or problem related to the treated condition.

Similar to other procedures, prior to the first intravitreal injection, informed consent is necessary to explain the risks, benefits, and alternatives of the procedure using vocabulary and concepts that are understandable to the patient and/or patient’s caregiver. Important risks to be covered during the informed consent process include endophthalmitis, ^{4 -6} silicone oil droplets, ^7,8 inflammatory reactions, ^9,10 and retinal detachment (RD). ¹¹ Reasonable alternatives to intravitreal injection are limited, but thermal laser photocoagulation, photodynamic therapy, and observation may be discussed depending on the individual circumstances of a particular patient. A thorough discussion regarding the different alternative intravitreal medications is often performed, especially given the growing number of available biologicals. Many retina specialists present the patient with a written summary and collect a signature to signify understanding and consent to the procedure. Finally, because intravitreal bevacizumab injections are not administered per the FDA label, informed consent often includes discussion of off-label usage of the medication.

If there are no concerns, following the informed consent process, the doctor and patient may proceed with the intravitreal injection as part of ongoing therapy. A pre-procedure verification process is conducted to ensure the correct drug is being injected into the correct eye on the correct patient.

Several anesthesia options are used to mitigate discomfort that can arise during and after the intravitreal injection procedure. The patient's comfort is paramount to reduce anxiety and improve compliance with treatment. ¹² Options for intravitreal injection anesthesia include topical anesthetic eye drops, a pledget soaked in anesthetic, viscous lidocaine, and subconjunctival or peribulbar block. ^13,14 Inherent pros and cons exist for each option, as well as different preferences among retina specialists and patients. For example, subconjunctival lidocaine injection provides excellent anesthesia and low infection rates ¹⁵ but is associated with temporary subconjunctival hemorrhage, ptosis, and diplopia. Viscous lidocaine may pose a possible increased risk of infection. ¹⁶

Preparation of the injection requires planning and meticulous attention to detail, as injectable drugs can be expensive and must remain sterile for patients' safety. The intravitreal drug is typically shipped overnight from a manufacturer, distributor, or outsourcing facility in temperature-controlled coolers. Verification of a reputable source of the medication is critical to avoid a counterfeit drug. ¹⁷ Retina specialists use prefilled syringes or draw medication from a vial into an injection syringe using a filter needle. For either option, the cap or filter needle is exchanged for a sterile 30-, 31-, 32-, or 33-gauge needle for injection. A short needle (1/2 inch [13 mm] or less) is safest to avoid through-and-through penetration of the globe and/or damage to the macula and optic nerve, especially in infants and smaller eyes. ¹⁸ Some steroid suspensions are injected using larger-gauge needles to avoid needle clogging. Administration of injections to multiple patients from a single-use vial is strictly prohibited and has been linked to endophthalmitis. ¹⁹ Care must be taken to avoid exposure to contaminants during the process, as errors in medication preparation have also been associated with endophthalmitis. ^{20 -22}

Air bubbles introduced into the syringe while loading the medication can cause bothersome floaters and inadvertent underdosing for the patient; however, flicking the syringe to dislodge air bubbles is not recommended given the association of increased incidence of silicone oil droplets ²³ and inflammatory reactions. ²⁴ Thus, careful attention to every step of procurement and preparation of intravitreal medication is necessary to minimize complications.

The eye, conjunctival sac, eyelids, and lashes house normal bacterial flora that can present a risk of infection to patients during intravitreal injection if the eye is not cleaned properly. Also, droplet contamination of the ocular surface or the needle with oropharyngeal flora from anyone near the treatment area has been described. The use of masks and/or minimizing speaking during the procedure has been recommended. Povidone iodine irrigation of the eye prior to injection is regarded as standard of care, as iodine was found to be the main factor in preventing endophthalmitis. ²⁵ However, aqueous chlorohexidine 0.5% is a reasonable alternative, ²⁶ especially for patients who are allergic to or cannot tolerate povidone iodine. Preoperative antibiotics are not necessary or helpful in preventing ocular infection and may inadvertently promote resistant bacteria on the ocular surface. ^27,28

Immobilizing the patient’s head, eyelids, and eye is helpful in creating a controlled environment for intravitreal injection. This lowers the risk of endophthalmitis as well as various traumatic complications, including cataract, ²⁹ RD, ¹¹ and corneal abrasion. ³⁰ The head is positioned firmly against a support, such as a pillow or headrest on the back of an examination chair or procedure table, and the patient should be well supported and comfortable when in the reclined position. Having patients and proceduralists wear masks and limit speaking during the procedure may decrease exposure to bacterial contamination. It is important for the physician to displace the eyelids and lashes away from the injection site via a sterile lid speculum ³¹ or by separating and holding the lids manually. ³² Additionally, the patient’s gaze is moved to optimize injection site exposure, which is usually the inferotemporal or supertemporal quadrant.

The pars plana is the preferred zone for the needle to penetrate the wall of the eye, avoiding damage to the anterior structures of the eye (including the lens and ciliary body) and posterior structures of the eye (including the retina and choroid). Measuring 3 to 4 mm posterior to the limbus with a caliper is a validated technique to locate the pars plana; however, some retina specialists can often locate the pars plana without use of a caliper. ¹¹ During the injection, the needle is oriented toward the optic nerve to avoid lens and anterior eye structures.

With the tip of the needle safely positioned in the vitreous cavity, steady depression of the syringe plunger to inject 0.05-to 0.1-mL volume is the safest way to deliver the drug, minimizing silicone oil droplets, ³ spikes in intraocular pressure (IOP), and vitreous reflux. ³³ After injection, the syringe/needle is withdrawn and safely disposed of in a sharps container to be incinerated. The lid speculum is removed and set aside to be sterilized for the next use, and the eye is rinsed with sterile saline or artificial tears to minimize ocular surface toxicity secondary to povidone iodine. ³⁴

Following the intravitreal injection procedure, the IOP should be monitored, and therapy for persistently elevated IOP is administered if indicated. The evidence for this guideline stems from research demonstrating that prolonged and pronounced IOP elevations can result in serious vision loss. ³⁵ Intravitreal injections can commonly be associated with transient or sustained IOP increases, and sustained IOP elevations are commonly associated with intravitreal corticosteroid injections. ³⁵

The IOP-lowering therapies can range from ocular hypotensive topical medications to anterior segment paracentesis. Apraclonidine works quickly in most cases as a single topical agent for elevated IOP or decreased vision of hand motion or light perception, and other glaucoma medications can be added if necessary. A prophylactic anterior chamber paracentesis is less commonly performed and reserved for cases in which fast IOP lowering is necessary in patients with preexisting glaucoma or at risk for optic nerve damage due to prolonged no light perception vision. IOP typically returns to the reference range in minutes, but a small percentage of patients have persisting severe, elevated IOP that can cause permanent damage to the optic nerve.

After injection, the eye should be checked for formed vision, optic nerve and retinal vessel perfusion, or IOP elevation. Patients with a known history of corneal abrasion or corneal erosion associated with corneal dystrophies can receive a brief corneal examination following injection to ensure the presence of an intact corneal surface. These individuals should also be advised to use frequent lubrication with artificial tears for the first few days after the procedure. In the presence of new complaints of photopsia or vitreous opacities, floaters, or bubbles after the procedure, a separate, additional dilated examination of the injected eye may be necessary to rule out potential injection-related complications such as vitreous hemorrhage, retinal tears, or detachment.

Once injection-related complications are ruled out, the patient may be discharged from the office with appropriate on-call services provided by the proceduralist, his or her physician group, or designee. The patient and caregivers should be given 24-hour emergency postprocedural contact information before leaving the office. This is important because of the small but measurable risk of serious adverse events during the recovery period. In general, the patient should contact the clinic or on-call service directly (rather than an emergency department, urgency center, or primary care) so that any emergency can be addressed as rapidly and efficiently as possible.

The patient and caregivers should be educated about the importance of avoiding eye rubbing, administering potentially contaminated eye drops the day of an injection, and recognizing signs and symptoms of serious ocular complications such as endophthalmitis, RD, corneal abrasion, and vitreous hemorrhage. These include increasing ocular pain, foreign-body sensation or discomfort, light sensitivity, severe and diffuse eye redness, worsening central or peripheral vision, or photopsia. ³⁶ Studies of ocular complications of intravitreal anti-VEGF injections have included corneal abrasion, lens injury, endophthalmitis (prevalence, 0.015%-0.083%), inflammation or uveitis, cataract progression, acute vision loss, central retinal artery occlusion, subretinal hemorrhage, retinal pigment epithelium tears, and RD (rate of 0.19%-3.9% per patient, 0.013% per injection). ^{6,37 -41} None of the adverse-event rates exceeded 0.21%. ³⁷ Patients on anticoagulation may be counseled about the high likelihood of injection-site subconjunctival hemorrhage that may enlarge during the following days and should be reassured that this presents a minimal risk to ocular structures.

Instructions of what to expect after intravitreal injection and what to do in case of emergency are reviewed, and the patient is scheduled for the next evaluation and/or treatment visit (eg, monthly for 2 years, per the ranibizumab FDA label if the patient is receiving on-label treatment). However, most patients are not on a fixed treatment schedule and will require examination of the eye(s) at customized intervals.

Supplemental Physician Services to the Intravitreal Injection Procedure

Some patients receiving intravitreal injections may require separate physician services to achieve an optimal outcome. A thorough but nonexhaustive list of examples of such distinct services and the scenarios that could demand such services are addressed as follows. For these situations, additional evaluation and management services (beyond what is included with the intravitreal injection) are generally appropriate and are the current standard of care.

Complex Medical History

In patients with a complex medical history, care should be coordinated with the patient’s entire medical team. Prior to the intravitreal injection procedure, medical history should be reviewed with the patient. In patients with arterial thromboembolic events such as recent stroke or myocardial infarction, the injecting physician may consider delaying the intravitreal injection or choosing a drug with less systemic absorption, based on clinical judgment. Some studies have reported no association between intravitreal anti-VEGF injections and cerebrovascular events or myocardial infarction, ^{42 -46} whereas other studies have reported that intravitreal anti-VEGF injections are associated with an increased risk of cerebrovascular accidents or myocardial infarctions. ^{47 -51}

Prior Ocular Surgeries

The injecting physician should consider other ocular factors in eyes scheduled for intravitreal injections, such as recent cataract or other ocular surgery. Factors such as the timing of an injection relative to another ocular procedure, type of ocular surgery, and history of ocular surgeries are all additional issues that the injecting physician needs to deliberate. For instance, patients with recent sutureless cataract surgery are at increased risk of wound rupture from the injection. Performing an intravitreal anti-VEGF injection soon following intraocular surgery can be a confounding variable when investigating the cause of a posttreatment infection, as the infection may have been acquired at cataract surgery and not at the time of intravitreal injection. The common bacterial pathogens differ between acute postintravitreal injection and postsurgery-related endophthalmitis; hence, determining the procedure source of the infection may be critical in guiding treatment and prognosis. ⁵²

Injecting physicians should avoid injecting the area of previous incisional glaucoma surgery, as this area is also at risk for wound dehiscence. In patients who have undergone prior retinal surgery with vitrectomy, intravitreal injections may need to be performed more frequently because of more rapid clearance of the drug. ⁵³

Glaucoma/Ocular Hypertension History

Acute increase in IOP is a well-known occurrence following intravitreal injection. ^54,55 Patients with preexisting glaucoma or ocular hypertension should be managed by their treating physician according to current standard of care. The injecting physician should use their best clinical judgment with intravitreal injections in patients with glaucoma or ocular hypertension. Intravitreal injections should not be denied or withheld from such patients as therapy may be imperative to preservation of vision. ³⁶ There is no evidence-based guidance on a specific IOP above which is unsafe to perform an intravitreal injection. Based on clinical judgment, the injecting physician will decide to lower IOP with topical medications or anterior segment paracentesis at the time of injection if necessary.

In addition to checking IOP prior to the injection, after the injection procedure the physician may check eye pressure or perfusion of the optic nerve with a dilated retinal examination and perform anterior chamber paracentesis as deemed clinically necessary. Alternatively, the injecting physician may choose to delay intravitreal injection if the IOP is poorly controlled and reschedule the procedure after the IOP is optimized by medical or surgical means. In patients with high-risk glaucoma and known pressure elevation after injection, preinjection paracentesis or preinjection topical or oral IOP-lowering medication should be considered.

Intraocular Pressure

IOP should be checked prior to injection. If the IOP is significantly elevated, the injecting physician may choose to delay the injection to another day. ³⁶ Alternatively, the injecting physician may proceed with injection if therapy is deemed necessary to vision preservation. Based on clinical judgment, the injecting physician will decide to lower IOP with topical medications or anterior chamber paracentesis at the time of injection if necessary. If neovascular glaucoma is suspected as the cause for ocular hypertension, the increased risk of hyphema with anterior chamber paracentesis must be considered.

Ocular and Adnexal Examination

The eyelids, adnexal area, conjunctiva, and cornea are carefully examined to evaluate for cellulitis, chalazion, hordeolum, blepharitis, conjunctivitis, and corneal infections or corneal ulcers. If there is an active external infection, postponing the injection until the infection has been treated and cleared is recommended unless, in the best judgment of the injecting physician, the benefits of the injection clearly outweigh the increased risk of endophthalmitis. Intravitreal injections are contraindicated in patients with active ocular and periocular infections.

In addition, the conjunctiva is inspected for signs of previous glaucoma surgery such as a bleb or tube shunt, as these areas should be avoided for the intravitreal injection's placement. The anterior segment is also carefully examined for scleral thinning that may be found in eyes with high myopia or previous scleritis; these areas of scleral ectasia should not be used for the site of the intravitreal injection.

The cornea should be examined for epithelial breakdown that can occur in conjunction with dry eye, exposure keratopathy, epithelial basement membrane dystrophy, and recurrent corneal erosional syndrome. This can be a cause for significant discomfort or corneal abrasions after the procedure and may necessitate treatment with artificial tears or ophthalmic ointments. The patient should be counseled prior to receiving the injection if any of these ocular findings are found at the pretreatment examination.

Intraocular Inflammation

A thorough dilated eye examination should be performed prior to injection to evaluate the presence of intraocular inflammation. Prior to beginning intravitreal injection therapy, the injecting physician should be aware of any prior intraocular inflammation, especially after intravitreal injections. The presence of active intraocular inflammation is a contraindication to certain intravitreal medications such as brolucizumab. ⁵⁶ Given that presentation of postinjection inflammation may occur months after brolucizumab, these patients should be thoroughly examined at every visit to rule out uveitis and occlusive vasculitis. ⁵⁶ As additional biologicals become available, the examination for inflammation such as anterior chamber cells and flare, vitritis, and retinal vasculitis may require additional, separate evaluations.

Retinal Examination

A dilated eye examination is often performed to evaluate the retina. The macula is carefully examined for the presence of ME, SRF, subretinal hemorrhage, pigment epithelial detachment, pigment epithelial tear, active CNV, or active exudation. The presence of new subretinal hemorrhage may necessitate surgical intervention or a change in drug and/or interval choice based on the judgment of the treating physician. In patients with diabetes, the presence of neovascularization, ME, SRF, retinal hemorrhages, microaneurysms, cotton-wool spots, disc edema, vitreous hemorrhage, or tractional RD as well as the severity of diabetic retinopathy are assessed. The peripheral retina is carefully examined for the presence of retinal tears, breaks, or detachments. If inflammation of the retinal vessels, choroid, or retina is present, then intravitreal medications such as brolucizumab are contraindicated. ¹³ After examination, the treating physician may require additional evaluation such as retinal imaging to decide on treatment.

Response to Therapy

If the eye has undergone a previous intravitreal injection, the response to therapy and any adverse events are assessed related to the medication and intravitreal injection. Persistence, improvement, or worsening of the ME, SRF, subretinal hemorrhage, or the pigment epithelial detachment is noted in addition to other findings such as VA and IOP. In patients with diabetes, neovascularization or vitreous hemorrhage is noted as well. The eye is carefully examined for active intraocular inflammation, and when present, intravitreal brolucizumab is contraindicated. ⁵⁶

Besides inflammation, intravitreal anti-VEGF injection can lead to the development of a retinal pigment epithelial tear in patients with pigment epithelial detachment and progressive traction or complex RD in patients with proliferative diabetic retinopathy, which can alter treatment course. ^57,58 The peripheral retina is inspected for retinal tears, breaks, or retinal detachments. ¹¹ If the patient is having a suboptimal response to the intravitreal medication, the injecting physician may decide to switch intravitreal medications. ⁵⁹ Often a multifactorial evaluation of VA, diagnostic imaging, and clinical examination is the standard of care, as suboptimal responses can be clarified by each of these separate measures.

Choice of Medication

When a patient undergoes an intravitreal injection, the injecting physician assesses the response to any previous medication injection and determines whether treatment with the same medication should be continued or changed. In addition, the injecting physician determines the time for the next follow-up examinationination and possible treatment. New clinical studies and/or changes in medical insurance coverage are also considered and may prompt the modification of ongoing therapy.

In patients with a suboptimal response to one intravitreal medication, the injecting physician may choose to change the intravitreal medication to produce a better therapeutic response. In addition, multiple studies have shown during anti-VEGF therapy the development of tachyphylaxis, a phenomenon in which repeated administration of a specific medication can result in a decreased therapeutic response. ^{59 -61} Based on separate examination and imaging, the injecting physician may determine that tachyphylaxis is occurring for a drug to which the patient previously had a good therapeutic response. In such instances, the injecting physician may consider increasing the frequency of injections of the same medication or switch to a new drug. The patient must then be evaluated for response to any changes made.

Fellow Eye

The fellow eye that is not receiving an intravitreal injection is also examined. For most retinal diseases that require intravitreal injection therapy, the other eye is also affected, including macular degeneration, diabetic retinopathy, myopic degeneration, and venous occlusive disease. One study of patients receiving intravitreal injections for unilateral wet AMD found a conversion rate of 24% from dry AMD to wet AMD in the fellow eye within 96 weeks. ⁶² The authors urged careful monitoring of the fellow eye in such patients, as illustrated in the earlier vignette. Earlier detection of conversion from dry AMD to wet AMD results in better visual outcomes. ⁶³

Imaging

After retinal examination, additional testing and imaging may be needed for the injecting physician to decide if intravitreal injection is indicated. The injecting physician may choose to perform additional evaluation such as retinal imaging with OCT, OCT angiography (OCTA), FA, or indocyanine green angiography (ICGA).

If no intraretinal fluid, SRF, or hemorrhage is found on examination, the injecting physician may perform angiography to assess the presence of growth of the CNV lesion, as nonleaking expansion of the CNV lesion has been described. ⁶⁴ If the lesion appears inactive, then the injecting physician may choose not to perform an intravitreal injection and instead have the patient return for follow-up examination and assessment. This as-needed treatment schema has been studied and was determined to be a reasonable option for many patients with neovascular AMD. Complete evaluation with examination and imaging is the standard of care at each visit with the possibility of avoiding unnecessary injections to control the disease. ⁶⁵

Different retinal conditions can produce features similar to exudative AMD. If polypoidal choroidal vasculopathy is suspected based on clinical examination, the treating physician may perform ICGA. ICGA can be helpful in identifying polyps in a patient with polypoidal choroidal vasculopathy, and the injecting physician may choose anti-VEGF treatment and/or alternative treatments such as thermal laser photocoagulation or photodynamic therapy depending on the location of the polyps and clinical judgment of the treating physician. In patients with drusenoid pigment epithelial detachments or vitelliform-like lesion on retinal examination, FA, OCTA, and fundus autofluorescence may be helpful in demonstrating the absence of CNV, thus avoiding the need for intravitreal injections.

Central serous retinopathy also produces SRF and pigment epithelial detachments and can mimic CNV. FA is helpful in distinguishing central serous retinopathy from CNV and thus avoiding the need for intravitreal injection. OCTA can reveal occult CNV in central serous retinopathy, confirming the need for intravitreal injections in these patients. ⁶⁶ Moreover, the natural history of many diseases treated with intravitreal injections leads to progressive vision loss when untreated, so monitoring and possible need for repeated imaging may be helpful to achieve optimal visual outcomes.

Not all older patients presenting with ME and features of AMD have wet AMD. Macular edema could be secondary to diabetes, pseudophakic cystoid ME, systemic or topical medications, uveitis, or other age-related diseases such as epiretinal membrane. Epiretinal membrane, if visually significant, is treated with vitreoretinal surgery. Uveitis causing ME can be treated with topical steroids, local steroid injections or local steroid implants, systemic steroids, or immunosuppressive medications. Thorough examination along with additional diagnostic testing such as FA or OCTA is helpful in distinguishing the cause of the macular fluid in these patients and the appropriate course of treatment.

Results

Myriad considerations contribute to the decision to treat a patient’s eye with an intravitreal drug injection, as detailed in this article. A high degree of clinical acumen, customized and appropriate ocular examination, as well as ancillary diagnostic testing, are all significant components that enable the physician to tailor intravitreal injection treatment plans needed to prevent vision loss. The processes that contribute to decision-making in intravitreal injection therapy are customized and multifaceted to minimize treatment burden.

Conclusions

This article underscores that intravitreal injection therapy may require a highly individualized and complex clinical analysis by the treating physician at each visit, and the treatment plan must be continually optimized to achieve the best outcomes to preserve a patient's vision.