Injection of medication beneath the conjunctiva or the Tenon capsule allows drugs to bypass the conjunctival and corneal epithelial barriers and absorb passively down a concentration gradient across the sclera and into intraocular tissues (see Fig 15-1). Subconjunctival, sub-Tenon, and retrobulbar injections all allow medications to reach therapeutic levels behind the lens–iris diaphragm. The Tenon capsule is a lipophilic barrier, and if a hydrophilic drug is injected into the sub-Tenon space, it can penetrate intraocular tissue more quickly than topical application can. This approach is especially useful for drugs with low lipid solubility (such as penicillin), which do not penetrate the eye adequately when given topically. Subconjunctival injections create a reservoir of drug that can be slowly released into the tear film.
Injections can also be helpful in delivering medication closer to the local site of action—for example, posterior sub-Tenon injections of steroids for cystoid macular edema (CME) or subconjunctival injection of fluorouracil (5-FU) after trabeculectomy. Retrobulbar and peribulbar injections also act directly at the site of delivery. These techniques are typically used for delivery of ophthalmic anesthesia and are covered in BCSC Section 11, Lens and Cataract. Other examples of local, injectable medications are botulinum toxin, used in the treatment of benign essential blepharospasm and hemifacial spasm, as well as for strabismus; and retrobulbar alcohol, used as therapy for chronic pain in blind eyes. See BCSC Section 10, Glaucoma, for further discussion of local application of antifibrotic agents in filtering surgery.
Intraocular injection of drugs instantly delivers effective concentrations at the target site. Although this route of administration may reduce systemic adverse effects, ocular adverse effects, which can include transient ocular hypertension and inflammation/infection, may be more pronounced. Clinicians must take great care to avoid the use of preserved medications and to control the concentration of intraocular drugs so that the delicate internal structures of the eye are protected from toxicity. Also, clinicians should strictly adhere to standard aseptic technique for the preparation and injection of intraocular medication so that infection is prevented. There are 2 types of intraocular injections: intracameral, or injection into the anterior chamber; and intravitreal, or injection into the vitreous cavity. Examples of substances and medications delivered via intraocular routes are presented in Table 15-1.
Intracameral injection of an antibiotic, administered at the end of cataract surgery to prevent endophthalmitis, has been reported. These injections have the advantage of reducing the need for postoperative dosing of medications. Cefuroxime, a broad-spectrum cephalosporin, is commonly used for this purpose. However, single-dose solution of cefuroxime is unavailable in the United States, and strict aseptic compounding protocol for reconstitution and dilution needs to be followed. Vancomycin is effective against methicillin-resistant Staphylococcus aureus (MRSA) but also needs to be diluted before injection. Further, the theoretical risk of inducing drug resistance with indiscriminate use of vancomycin is a concern. Another option is diluting preservative-free topical moxifloxacin—a broad-spectrum, fourth-generation fluoroquinolone—for intracameral use. It is important that antibiotic solutions prepared for intracameral injection be free of preservatives or other additives. Cases of toxic anterior segment syndrome (TASS) have been reported after the use of antibiotics with preservatives or with dosing errors.
Table 15-1 Examples of Medications Delivered by Intracameral and Intravitreal Routes
A regulated, compounded preservative-free formulation of triamcinolone acetonide 15 mg/mL, moxifloxacin hydrochloride 1 mg/mL, and vancomycin 10 mg/mL is available for administration into the anterior vitreous after intraocular lens implantation through the zonule via the ciliary sulcus. Controlled studies on the safety and efficacy of this formulation are lacking. In 2017, the US Food and Drug Administration (FDA) received an adverse event report concerning a patient in whom bilateral hemorrhagic occlusive retinal vasculitis (HORV) developed after this formulation was administered in each eye at the conclusion of cataract surgery procedures performed 2 weeks apart. HORV is a rare but potentially blinding complication that has occurred in patients who received intraocular injections of vancomycin formulations at the end of otherwise uncomplicated cataract surgery.
Intravitreal injection is the most common form of intraocular drug delivery. These injections are most often used to manage patients with complications of diabetic retinopathy (diabetic macular edema) and age-related macular degeneration (choroidal neovascularization). They are also used in the treatment of uveitis, endophthalmitis, and other conditions. For example, for retinal vascular diseases, various agents are available that target vascular endothelial growth factor (VEGF). Intravitreal delivery can result in a relevant systemic concentration, as evidenced by the effects noted in fellow eyes in clinical trials. For discussion of individual agents used for intravitreal injection, see Chapter 16 in this volume and BCSC Section 12, Retina and Vitreous.
Ho AC, Scott IU, Kim SJ, et al. Anti-vascular endothelial growth factor pharmacotherapy for diabetic macular edema: a report by the American Academy of Ophthalmology. Ophthalmology. 2012;119(10):2179–2188.
Wen JC, McCannel CA, Mochon AB, Garner OB. Bacterial dispersal association with speech in the setting of intravitreous injections. Arch Ophthalmol. 2011;129(12):1551–1554.
Witkin AJ, Chang DF, Jumper JM, et al. Vancomycin-associated hemorrhagic occlusive retinal vasculitis: clinical characteristics of 36 eyes. Ophthalmology. 2017;124(5):583–595.
Yeh S, Albini TA, Moshfeghi AA, Nussenblatt RB. Uveitis, the Comparison of Age-related Macular Degeneration Treatments Trials (CATT), and intravitreal biologics for ocular inflammation. Am J Ophthalmol. 2012;154(3):429–435.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.