**Background:** Ocular diseases, including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and diabetic macular edema (DME), are leading causes of visual impairment globally. Conventional treatments such as topical eye drops, intravitreal injections, and laser photocoagulation face significant limitations, including low bioavailability, poor patient compliance, and risks like retinal detachment and endophthalmitis. Biomaterial-based drug delivery systems have emerged to address these challenges by enhancing drug residence time, corneal penetration, and sustained release.
**Methods:** This narrative review discusses prominent ocular diseases and their conventional treatments, then categorizes and describes various biomaterial drug delivery systems. The review covers non-biodegradable implants (e.g., Port Delivery System with ranibizumab, iDose TR), biodegradable implants (e.g., Ozurdex, Durysta, Brimo DDS), hydrogels (e.g., ECE hydrogel for bevacizumab, peptide-based hydrogels), liposomes (e.g., latanoprost-loaded EggPC liposomes, triamcinolone acetonide-loaded liposomes), nanomicelles (e.g., CSO-VV-SA nanomicelles for dexamethasone, poloxamine nanomicelles for ethoxzolamide), DNA-inspired nanoparticles (e.g., Janus Base Nanotubes, nanopieces for siRNA), dendrimers (e.g., DenTimol, PAMAM dendrimers for ruboxistaurin), microneedles (e.g., Tower Microneedle, dissolvable polymeric microneedles), and drug-loaded contact lenses (e.g., vitamin E-loaded lenses with timolol, latanoprost-eluting contact lenses). The review references clinical trials and preclinical studies to illustrate progress.
**Key Results:** Key findings include: (1) The Port Delivery System with ranibizumab was FDA-approved in October 2021 for neovascular AMD, with vitreous hemorrhage reduced to 5.2% in Phase 3 after surgical optimization. (2) The fluocinolone acetonide intravitreal implant (ILUVIEN) releases drug at 0.25 µg/day initially (average 0.2 µg/day) for ~36 months; FAME Phase 3 trials showed significant visual acuity improvement from 3 weeks through 36 months. (3) Ozurdex (dexamethasone implant) improved ETDRS outcomes in persistent DME at 1, 3, 4, and 6 months post-injection, but ocular hypertension occurred in 26.9% of recipients. (4) Bimatoprost sustained-release implant (Durysta) provided rapid IOP reduction over 6 months in Phase 1/2 trials, with favorable safety over 24 months. (5) Brimonidine DDS in geographic atrophy showed consistently smaller lesion growth in Phase 2. (6) ECE hydrogel released 80% of bevacizumab in 20 days with no cytotoxicity on human RPE cells and preserved rabbit neuroretina for 2 months. (7) Latanoprost-loaded EggPC liposomes reduced IOP in rabbits for up to 90 days, with 60% drug release in 14 days. (8) DenTimol (dendrimeric timolol) reduced IOP by 30% in rats within 30 minutes, with 8% corneal permeation vs. 3.5% for timolol in 4 hours. (9) Dissolvable polymeric microneedles released 100% of pilocarpine within 30 minutes in PBS and 90% permeated cornea in 6 hours ex vivo. (10) Vitamin E-loaded contact lenses with timolol reduced IOP significantly in beagle dogs over 4 days.
**Clinical Implications:** Biomaterial-based systems offer promising alternatives to conventional therapies by reducing injection frequency, improving bioavailability, and enhancing patient comfort. FDA-approved devices like ILUVIEN, Ozurdex, Durysta, and the Port Delivery System demonstrate clinical translation. However, challenges remain, including potential for ocular hypertension with corticosteroids, need for surgical implantation, and limited long-term safety data for newer systems. Ongoing clinical trials (e.g., NCT03519386 for iDose TR, NCT04500574 for latanoprost-eluting contact lenses) will further establish efficacy and safety. The field is moving toward biodegradable, bioinspired materials and combination therapies to optimize outcomes.