## 1 Introduction  
Anatomically, the eye can be compartmentalized into a fibrous tunic layer (sclera, cornea, and conjunctiva), vascular tunic or uvea (choroid, ciliary body, and iris), and an inner coat (retina) [1; 2; 3]. The retina, which is made of photoreceptor cells, is a light-sensitive layer of nervous tissue, and is known to be one of the most metabolically active tissues in the human body. The retina is the organ that is responsible for the interpretation and control of our vision, it converts light energy into electrical impulses, which is then transmitted to the brain by the optic nerve [4; 5]. The outer retina (OR) is the innermost layer of the light-sensitive eye and it is in this structure that the first stage of visual processing occurs [6]. The photoreceptor (PR) cells are anatomical and functional neurons specialized in photon capture and are responsible for the release of electrical responses [7]. The retinal pigment epithelium (RPE), located on the external side of the PR cells, is primarily responsible for supporting the primary visual functions, such as the phagocytosis of the external segments of the PR, retinal recycling (vitamin A), absorption of scattered light, and bidirectional transepithelial transport between the retina and the choriocapillaris, choroid, and the systemic blood circulation [8; 9]. These cells have specialized functions in supporting cells and tissue homeostasis, as well as maintaining a healthy retina. Although the retina is a highly specialized and optimized system, organisms do not depend on it for immediate survival, and therefore, it is prone to failure when invaded [10]. For the treatment of eye diseases, the optimal route for drug administration depends on the target tissue, duration of contact, and the disease itself. Diseases of the anterior eye (glaucoma, inflammations, and infections) are treated with eye drops, but due to the complex anatomy and dynamic physiological defense mechanism of the eye, it is known that less than 5% of the eye drop reaches the posterior chamber of the eye, and negligible penetration is seen through the anterior chamber [11; 12; 13]. The eye drops for topical ocular drug delivery have limited success because the drug concentration that hits these tissues is too low. This route has been less explored for treating diseases occurring at the back of the eye [14; 15; 16; 17]. For this reason, novel routes and innovative drug delivery systems for intraocular drug delivery injection or transscleral implants have been investigated to reduce the pre-corneal loss. However, it is necessary to consider that both intraocular injections and transscleral implantation are invasive and involve a high risk of side effects. The parenteral administration via the subconjunctival route delivers the drug underneath the conjunctival membrane, allowing the dose to reach the retina. The first drug delivery route across the transmembrane is via subconjunctival injection. There is thus a growing interest in new ocular drug delivery systems that facilitate the access of the drug to its target, or that can extend its duration of action. However, frequent injections can lead to adverse events, such as intraocular bleeding, infection, and retinal detachment. Transscleral drug delivery has been exploited as an alternative approach over intravitreal injection for drug delivery to the posterior segment of the eye. For the development of ophthalmic medicines, it is crucial to know how to design the drug release profile, absorption, distribution, metabolism, and excretion kinetics [18]. Drug delivery systems that use polymers or lipids are capable of releasing a drug in a controlled manner based on the physiology and pharmacokinetics of the eye. Since the eye has many membranes, tissues, and fluid flows, it is difficult to quantitatively estimate its effect on drug administration.