Table 1 Different administration routes for ocular drug delivery
Administration route | Approach | Target disease | Advantage | Challenge | Refs. |
|---|---|---|---|---|---|
Systemic | Systemic intravenous and oral administration | Endophthalmitis, uveitis, retinitis (acute retinal necrosis), cytomegalovirus retinitis, metastasis, malignancies, episcleritis, scleritis | Very effective for the simultaneous treatment of ocular and systemic diseases. Oral administration: non-invasive, good patient compliance, no requirement to apply strict sterile conditions, the large availability of pharmaceutical forms, high stability of drug | Systemic side effects, high dosing causes toxicity, blood-aqueous barrier, blood-retinal barrier, bioavailability < 2% | |
Topical | Topical usage | Anterior uveitis, conjunctivitis, keratitis, blepharitis, scleritis, episcleritis | Non-invasive, painless, ease of administration, patient compliance, localized drug effects, less drug entry into the systemic circulation | Tear renewal and large lacrimal clearance, blinking, nasolacrimal drainage, ocular dynamic and static barriers, low bioavailability | |
Intravitreal injection | Direct injection of drugs into the vitreous | AMD, posterior uveitis, branched retinal vein occlusion, central retinal vein occlusion, diabetic macular edema, cystoid macular edema, uveitic macular edema, cytomegalovirus retinitis, endophthalmitis | Attaining rapid therapeutics in the vitreous humor, limited systemic side effects, sustained drug levels, avoiding blood-retinal barrier | Cataract, retinal detachment, endophthalmitis, uveitis, retinal hemorrhage, vitreous detachment, subconjunctival hemorrhage, inflammation, cataracts, increased intraocular pressure, retinal toxicity, eye pain caused by invasive procedure | |
Periocular implants | Located eyeball's outer part and used the trans-scleral route for drug delivery | AMD and uveitis | Safer and less invasive than intraocular implants, more patient friendly, decreased complications, localized drug delivery. Biodegradable implants: capability to be metabolized, eliminated via a physiological pathway, ease of construction, ability to break down into non-toxic substances, and prevent inflammation after usage | Requires surgery, restricted by some static barriers (sclera, choroid, and RPE) and eliminated by lymph and blood flow in the surrounding tissues, final burst stage of the device and uncontrolled release of the remaining drug | |
Subconjunctival | Subconjunctival injection | Glaucoma, uveitis, AMD, corneal ulcer | Greater concentrations of drug in the anterior chamber than topical administration, less invasive compared to intravitreal injection, reduced adverse effects, such as cataracts, endophthalmitis, and retinal damage | Diminished bioavailability due to elimination through systemic circulation, subconjunctival hemorrhages, the possibility of glob preformation | |
Suprachoroidal | Injected into the supracervical space | Diabetic macular edema, macular degeneration, non-infectious uveitis and ocular oncology | Avoiding various ophthalmic barriers (e.g., cornea, conjunctiva and sclera), suprachoroidal space can act as a possible reservoir within the eye, sustained-release formulations, providing a safer way with larger immunogenic/biologic agents | Suprachoroidal hemorrhage, choroidal detachment, retinal detachment, subretinal hemorrhage | |
Sub-Tenon | Placing a formulation between the Tenon’s capsule and sclera | Chronic posterior uveitis, cystoid macular edema, diabetic macular edema | Increased permeation to the posterior eye segment, safer than intravitreal injections, no need to enter the eye and eliminating needle-associated risks, reducing drug passage to systemic circulation, prolonging the contact time with the sclera | Increased intraocular pressure, worsening cataracts, less efficacy in the treatment of uveitic macular edema in comparison with intravitreal injection, removal of the drug due to choroidal circulation, possibility of glob preformation, subconjunctival hemorrhage |