Intravitreal injections (IVI) have become the standard of care for the management of many retinal diseases, and they represent an integral part of a current day retina practice. Since 2004, the number of IVI has been increasing exponentially due to the introduction of efficacious drugs to treat a variety of retinal conditions, in particular neovascular age-related macular degeneration (AMD) and retinal vascular diseases.^1,2 This growth trend is expected to continue and accelerate. The prevalence of AMD and diabetic retinopathy are rising.^3,4 With our rapidly expanding patient population in need of IVI, it is as important as ever to focus on the patient experience, as well as efficiency and costs associated with this common procedure.

Intravitreal injections can represent a significant burden for patients, due to psychological stress and potential pain and discomfort associated with the procedure, as well as the patient and caregiver time spent in the office. Although IVI are so commonly performed across all retina practices, the technique of the injection varies among providers. Universally, the techniques are aimed at preventing infectious endophthalmitis, a serious complication with a potentially devastating visual outcome despite prompt recognition and treatment. Although rate of infectious endophthalmitis per injection is low, reported between 0.09% and 0.029% across prospective and retrospective studies, cumulative per-patient risk is higher due to multiple injection events over time.^5,6 Furthermore, all providers are concerned with maximizing patient comfort to ensure compliance with the treatment regimen. This article will review current approaches used by retina specialists aimed at optimizing patient safety and comfort, while minimizing procedure time and allowing for an efficient clinic flow.

CHOICE OF ANESTHETIC AGENT

Needle entry is reported as the single most uncomfortable step of the IVI procedure, although pain scores are shown to decrease with consecutive injections over time.^7,8 Many anesthetic agents are available to provide pain relief during this step. Topical anesthetic drops such as proparacaine hydrochloride, tetracaine hydrochloride, and lidocaine are easily accessible and can be quickly administered by physician or supporting staff. Pledgets or cotton tipped swabs soaked in an anesthetic solution can also be used for topical anesthesia at the injection site. Comfortpack is a lidocaine pledget system available in a convenient single-use individual sterile packaging.

In addition, topical lidocaine and tetracaine gel formulations are available and offer the benefit of extended contact with the ocular surface and are less prone to dilution by the tear film.⁹ Several in vitro studies suggested that anesthetic gels impaired the antiseptic qualities of povidone iodine (PI) if instilled after the initial gel application.⁵ Some retina specialists avoid gel anesthetics due to this possible concern. However, in vivo studies have not shown significant evidence to indicate that gel use leads to increased rates of endophthalmitis.⁹

Subconjunctival injection of lidocaine ranging from 1% to 4% has been proposed as an anesthetic option for patients with higher pain sensitivity; however, the subconjunctival injection itself contributes additional pain.¹⁰ The authors do not use subconjunctival anesthetic injections in preparation for any intravitreal injections. For this method, it is prudent to use a new anesthetic bottle for each patient due to concern for introducing bacteria into the subconjunctival space prior to passing the intravitreal needle in this area and possibly seeding the vitreous cavity with bacteria. A recent well-designed systematic review found no significant difference between the available topical anesthetic options or subconjunctival anesthetic injections in reducing patient pain scores.⁹ Realistically, considerations of practice flow and cost effectiveness also play a role in guiding the choice of anesthetic method, and the authors routinely use topical proparacaine drops followed by a series of 3 cotton-tipped applicator pledgets placed in the upper eyelid fornix (1 nasal and 1 temporal) soaked in 4% lidocaine solution as a convenient and effective anesthetic approach.

STERILE DRAPING AND EYELID RETRACTION

Sterile drape is rarely applied as part of the sterile injection technique, and can be associated with significant patient discomfort during the procedure.⁷ Eyelid retraction, on the other hand, is essential when performing an IVI to prevent any contact with endophthalmitis-causing bacteria found on the eyelid margin. According to an American Academy of Ophthalmology survey, eyelid speculum retraction is most commonly used by 92% of survey respondents.¹¹ Alternatively, many surgeons utilize manual eyelid retraction techniques with the goal to increase patient comfort and shorten procedure time.¹² A recent study by Raevis et al comparing eyelid retraction techniques of unimanual eyelid retraction to cotton-tipped applicator retraction and speculum retraction found that speculum use was associated with the highest patient-reported pain score.¹³ However, speculum retraction remains recommended by expert panels, and it may be necessary for patients who squeeze eyelids heavily during the injection procedure.¹⁴

A single-use disposable device, Invitria, has been adopted by some retina specialists to provide lid displacement, as well as globe stabilization, and an injection port precisely oriented to ensure a reproducible trans-pars plana ocular penetration at a fixed angle and injection depth.¹⁵ It has been proposed that downward pressure from the device may block pain signals from the ciliary nerves and provide additional mechanical anesthesia during the procedure.¹⁶ Studies have shown that Invitria allows for significantly shorter procedure time without compromising patient comfort, as compared to conventional freehand techniques.^15-17 However, an individualized cost analysis is important to weigh the expenses associated with this single-use device against the benefit of saved procedural time for each practice.

TOPICAL ANTISEPSIS

Povidone iodine is the most widely used antiseptic agent in preventing postinjection endophthalmitis.¹⁸ Large epidemiologic studies have shown that PI has powerful broad-spectrum microbicidal activity, with no reports of resistance in the setting of topical ophthalmic use.^19-21 Although PI is very efficacious, it can lead to irritation and mild corneal epithelial toxicity after the injection.²² There are reports of contact dermatitis secondary to PI, but no reported cases of associated anaphylaxis.²⁰ Some patients may have concerns regarding a possible reaction to ophthalmic PI; Raevis et al propose that applying a drop of topical PI onto a patient’s hand or forearm for 5 minutes to assess for any local reaction may be helpful to provide reassurance, alleviate anxiety, and improve compliance.² Furthermore, a topical solution of lower concentration may be used for patients particularly sensitive to PI-induced irritation, because topical PI has been shown to have high bactericidal activity when applied for 30 seconds at a concentration as low as 2.5%.^19,23

Most physicians use 5% PI on the ocular surface; studies have shown that at this concentration PI is more efficacious when applied for 30 seconds rather than only 15 seconds, while irrigation with PI or repeated applications are more effective than a single instillation.¹⁹ The authors use a series of 3 cotton-tipped swabs saturated with 10% PI solution, applied in a sweeping motion from the limbus to the fornix in the quadrant of the IVI, ensuring at least 30 second contact of PI with the conjunctival surface. This method allows for precise and easy PI application, and effective antisepsis. On the other hand, routine periocular lid scrubs with PI are not recommended due to concerns for dislocating bacteria from the eyelid margin onto the conjunctiva, and increasing conjunctival bacterial counts.¹⁹

Alternatively, topical aqueous chlorhexidine gluconate 0.1% has been proposed as an equally efficacious and safe alternative that may provide greater patient comfort.^24,25 However, concerns including bacterial resistance to chlorhexidine, reduced activity against fungi, possible contamination during manufacturing, and the need for more data on chlorhexidine safety and efficacy in ocular antisepsis need to be addressed prior to adopting this agent for more widespread use.²¹ Another important strategy to theoretically decrease the risk of endophthalmitis, based on the research of McCannel et al, is minimizing oropharyngeal droplet transmission by avoiding talking or wearing surgical masks during the injection.^26,27

NEEDLE GAUGE AND INJECTION LOCATION

Small-gauge needles are used for IVI to provide maximum patient comfort and minimize scleral structural damage, vitreous incarceration, and reflux.²⁸ Although several trials did not find a significant difference in patient pain scores with the use of 27-, 30-, or 32-gauge needles, the 30- and 32-gauge needles are typically preferred by retina specialists.^8,29 As far as the location of the injection, there is a general consensus that the injections should be made at the pars plana between 3.5 mm and 4.0 mm from the limbus. However, the preferred quadrant varies among different providers. Although IVI can be performed safely 360° through the pars plana, the choice of exact injection location should be patient-specific, in particular avoiding sites of filtering bleb or shunt or scleral patch in eyes with prior glaucoma surgery, as well as avoiding sclerotomy sites in previously vitrectomized patients.¹⁹

SUMMARY

Intravitreal injections have become a common and frequently performed treatment for many patients with retinal disease. Real-world data show that variable-frequency injection regimens are commonly adopted in an attempt to reduce the burden, risks, and costs of repeated IVI.³⁰ However, clinical studies also suggest that lower number of annual injections may lead to poorer visual outcomes than those seen in randomized controlled trials with fixed, frequent injection regimens.^31,32 Although clinical trials of new, longer-acting agents and sustained-release systems are promising,³⁰ IVI will likely continue to be a frequent treatment in many patients’ lives. Simultaneously managing a busy clinic flow while maximizing patient comfort is key to taking care of patients with retinal diseases and ensuring compliance with frequent injection regimens in the modern era. The methods discussed above highlight the flexibility of the field and the continued efforts of industry and clinicians in advocating for the best possible patient experience while effectively and efficiently treating retinal diseases. RP

REFERENCES

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