Table 1 Routes of drug delivery to the posterior segment of the eye

Systemic

Oral

Simplicity of use

Systemic

adverse effects

[8]

IV

Low cost

Good

Patient compliance

Minimal systemic adverse effects

Low ocular bioavailability

(1-2%)

Intravenous administration of PLA-PEG chains with cell-penetrating peptide nanoparticles enhanced light-triggered local delivery of drug to the infected choroid ^*

Intravenous nanoparticles loaded with doxorubicin dramatically reduced the size of neovascular lesions ^*

[12]

Topical

Ointment

Low cost

Therapeutic doses can’t be delivered to the retina owing to the existence of dynamic and static barriers

A dexamethasone-eluting contact lens achieved sustained therapeutic levels of dexamethasone to the retina 200-fold greater than hourly administered dexamethasone drops ^*

[127]

Eye drops

Simplicity of use

Low therapeutic efficacy with amount less than 5% of the drugs diffusing through the eye following administration

An in situ thermosensitive hydrogel decreased laser-induced choroidal neovascularization in the posterior segment of the eyes of rats and pigs^*

[100]

Gels

Low systemic side effects

DEXTENZA^®, a dexamethasone intra-canalicular inserted into the lower lacrimal punctum, showed good effectiveness in treating pain and ocular inflammation during eye surgery along with ocular itching accompanied by allergic conjunctivitis ^**

[126]

Eye

Drops with nano/micro systems

Easily fabricated

Good patient compliance

[103]

Peri-ocular

Injections or implants inserted within the orbital rim of the eyeball (ex: sclera)

Less invasive, with less risks and retinal impairment, compared to intravitreal injections.

Lower concentrations are attained as compared to intravitreal injections/ implants

An iontophoretic hydrogel device improved the transport of intraocular nanoparticles and macromolecules to posterior eye segments via trans-scleral channels up to 300 times ^*

[127]

Intra-cameral

Implants or injections administered to the anterior segment of the eyeball

Cost-effective and efficient

The optimal drug’s dosage is administered.

Reduced systemic and ocular surface adverse effects in comparison with topical administration

Circumvents the challenging barrier of the cornea.

Possibility of triggering toxic anterior segment syndrome.

Endothelial cells of the cornea may be harmed.

Invasive method.

DURYSTA™, an FDA approved biodegradable intra-cameral implant, containing bimatoprost for the management of ocular hypertension patients ^**

DEXYCU^™, the first FDA-approved anti-inflammatory drug for use after cataract surgery using dexamethasone intra-cameral injectable suspension ^**

[128]

Suprachoroidal

Microneedles

Higher bioavailability than periocular routes

Potential tissue damage

XIPERE^®, an injectable suspension of triamcinolone acetonide administered into the suprachoroidal space (SCS) ^**

Microinjector^®, an FDA-approved delivery system, given to SCS^®, and used for the management of uveitis macular edema ^**

[13]

Suprachoroidal injected in situ gel

Targeting with high bioavailability in the retinal pigment epithelium and choroid.

Fabrication difficulty

In rabbit eyes, a microneedle-based device aided by iontophoresis boosted posterior targeting with efficiency more than 30% compared to nanoparticles in the SCS ^*

[77]

Intravitreal

Injection

Increased drug concentrations in vitreous and retinal regions.

Painful

Ozurdex^®,

an intravitreal FDA approved dexamethasone biodegradable implant used for the management of uveitis and diabetic macular edema ^**

[124]

Implant

Minimal systemic side effects

-Frequent injections can cause complications

-Difficulty in implant's

application and removal

-Implant may result in acidity in the

microenvironment

ILUVIEN^®, an approved non-biodegradable, injectable corticosteroid implant comprising Fluocinolone acetonide used for the management of macular edema^**

[122]