Table 1.
Comparison of Drug Delivery Modes for Retinal Diseases
| Drug Delivery Mode | Intravitreal Injection | Sub-Tenon's Injection | Suprachoroidal/Intrascleral Hollow Microneedle Injection | Topical Drops | Systemic Oral Pills |
|---|---|---|---|---|---|
| Pathway to target posterior segment | Direct | Transscleral | Transchoroidal | Transconjunctival/transscleral | Trans-RPE |
| Safety | |||||
| Risk | Highest injection risk | Minimal injection risk, mild systemic exposure | Minimal injection risk, minimal systemic exposure | Safest, but moderate systemic exposure | Minimal local exposure; highest systemic exposure |
| Adverse Events | Vitreous hemorrhage, retinal detachment, endophthalmitis | Subconjunctival hemorrhage | Subconjunctival hemorrhage, suprachoroidal hemorrhage | Conjunctival redness and irritation | Gastrointestinal upset |
| Efficacy | Most direct and effective; only mode that directly penetrates BRB | Much less bioavailable to the vitreous and retina due to anatomic barriers and several clearance mechanisms | 80-fold more bioavailable than sub-Tenon's injection; avoids subconjunctival/episclera clearance mechanism | Worst bioavailability and second worst duration of action; convenient and can be self-administered at home | Second worst bioavailability and worst duration of action; convenient and can be self-administered at home |
| Anatomic barrier(s) | Vitreous, retina | Subconjunctival/episclera, sclera, choroid, Bruch's membrane, RPE retina | Sclera, choroid, Bruch's membrane, RPE, retina | Conjunctival episclera, sclera, choroid, Bruch's membrane, RPE retina | Choroid, RPE, retina |
| Peak bioavailability | |||||
| Intravitreal | 100% | 0.01%–0.1% | 0.8%–70% | 0%–0.0004% | 0%–2% |
| Intra-aqueous humor | 3% | 0.008%–0.8% | 0.02%–2.1% | 0.0007%–5% | 1%–2% |
| Volume of distribution | Local | Local and systemic washout | Local | Local and systemic washout | Systemic and local |
| Clearance mechanism(s) | Outward vitreoretinal diffusion; aqueous humor flow | Subconjunctival/episclera; choriocapillaris | Choriocapillaris | Lacrimal tear flow, subconjunctival/episclera; choriocapillaris | Hepatic, choriocapillaris |
| Metabolism | RPE, ciliary body | Choroid, RPE, ciliary body | Choroid, RPE, ciliary body | Choroid, RPE, ciliary body | Hepatic, choroid, RPE, ciliary body |
| Duration of action | 21 Hours to 7 weeks | 6 Hours to 1 month | 18 Hours to 3 months | 30 Minutes to 4 hours | <30 Minutes |