A review on recent advancements in ophthalmology devices: Currently in market and under clinical trials

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Abstract

The complex anatomical features of the eye and the presence of different ocular barriers has led to complications in the development of an effective treatment strategy for posterior segment diseases like diabetic retinopathy, age-related macular degeneration, retinal pigmentosa, etc., thus demanding the need for novel and innovative approaches. There are various treatment options available in the market which includes the new implants and drug delivery systems apart from the therapeutic agents which are benefiting the patients with modern improvements, enhanced formulations, targeted and long-term delivery. But they all still have numerous drawbacks which need to be addressed. This review article discusses and highlights the recent developments made in the ophthalmology which are in the market currently and under clinical trial. This review also suggests a possible alternative system that can be an effective and practical option for the treatment of posterior segment ophthalmic diseases.

Introduction

According to the survey conducted by the World Health Organization (WHO) in 2015, approximately 217 million people who are aged above 18 years or older globally are suffering from different ophthalmic diseases that can cause impairment in vision which can eventually lead to irreversible blindness [1]. Some of the ophthalmic diseases and disorders that are associated with the eye are glaucoma, cataract, diabetic retinopathy, age-related macular degeneration, keratoconus, retinal detachment, uveitis, retinal pigmentation, etc. [2]. Many of these diseases could also be inherited genetically [3]. The prevalence of vision impairment is increasing over the past decades with change in the lifestyle, environment, genetic and hereditary conditions, and also with an increase in age [4]. Fig. 1 shows the statistics of different eye diseases affecting the majority of the population worldwide. Uncorrected refractive errors like myopia, hyperopia, and astigmatism affect 49% of the population globally. Vision acuity in these conditions is restored with the help of glasses or through contact lenses. The most commonly affected ocular disorder is cataract followed by age-related macular degeneration and glaucoma as shown Fig. 1. However, other eye-related diseases like corneal occlusions, diabetic retinopathy, age related macular degeneration, glaucoma makes up 19% of the affected population (“GBVI - Global Cause Estimates • IAPB Vision Atlas,”).

In order to overcome the disorders caused by different ophthalmic diseases, different treatment strategies have been employed, of which ophthalmic implants and drug delivery systems have shown significant impact in changing and restoring normal lifestyle of the people affected by ocular diseases. Hence, this review discusses and sheds light upon the various implants and drug delivery systems that have been designed and developed to overcome the complications and severity associated with ophthalmic diseases to restore the normal functionality of eye and vision.

The human eye being one of the most complex organs of our body can be divided into two segments namely anterior and posterior segments. It is 24 mm in diameter and occupies 25% of the space of eye-socket while remaining is filled by extraocular muscles, vessels, nerves, connective tissue and fat that protect and give support to the eye [6]. The anterior segment of the eye is made of the cornea, iris, crystalline lens, and ciliary muscle while the posterior segment is made up of aqueous/vitreous humor, retina, choroid, macula and optic nerve (Fig. 2 (A)).

The cornea is the first layer of the eye which acts as a defensive barrier and also helps in transmission and focusing of the light into the eye. It is composed of collagen fibrils which are net-like structures and cover the entire surface of the cornea providing transparency and support. From Fig. 2 (B) below, we can notice that cornea is made up of various layers like the epithelium layer, Bowman's layer, Descemet's membrane, and endothelium. These layers help in providing nutrients and maintaining hydration. Endothelium layer of the cornea is in direct contact with the aqueous humor [7,8]. Aqueous humor is a transparent fluid that fills the area between the cornea and the crystalline lens and also provides the nutrients necessary. In order to block the excess amount of light entering the eye, there is the presence of iris, which also gives color to the pupil. The dilation and constriction of the pupil are controlled by iris depending on the intensity of light entering the eye. The light entering is focused on the retina with the help of the crystalline lens. The lens can change shape depending on the amount of light entering. The light received from the lens is focused on the retina through vitreous humor. Vitreous humor is a gel-like fluid that fills the posterior segment of the eye. The shape of the eye and the integrity of the retinal layer is maintained by vitreous humor through the maintenance of constant pressure [9]. Once the light is received by the retinal tissue, it transmits the signal to the brain through a series of retinal layers like an inner limiting membrane nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer limiting membrane, receptor layer and retinal pigment epithelium [6,8,10]. The light received by the retina is focused on macula lutea. The macula is connected to the optic nerve which sends nerve signals to the occipital lobe of the brain where final processing of neural signals from the retina to the formation of vision takes place [6,10,11].

The complex anatomical and physiological structure make the eye vulnerable to various diseases and disorders. Owing to its complexity the treatment of ocular diseases of both anterior and posterior segment is difficult [12]. One such difficulty in the treatment of ophthalmic diseases is the presence of different ocular barriers for drug delivery. There are five different barriers they are tear film barrier, corneal barrier, conjunctival barrier, blood-aqueous barrier, and blood-retinal barrier [13]. Tear film barrier is made of mucin, water, and lipids and acts a barrier for entry of foreign objects to the cornea and conjunctiva [14]. The corneal barrier is comprised of three layers containing epithelium, stroma, and endothelium cells. This barrier prevents the drug absorption from reaching to the anterior segment after topical administration [15]. The conjunctival barrier has the mucous membrane, conjunctival epithelium and vascularized connective tissue in layers thus preventing the drug absorption after administering topically [16]. The blood-aqueous barrier is made of capillary endothelium and ciliary endothelium forming a tight junction. It is located in the anterior segment of the eye and allows small molecules to pass through it for reaching aqueous humor [17]. Blood-retinal barrier is formed by retinal pigment epithelium and endothelial membrane thus creating a tight junction which restricts the entry of the drug from blood (administrated through systemic route) for reaching retina or aqueous humor [13]. Posterior segment diseases are most often complicated for treatment due to the presence of these barriers. Hence, to overcome this limitation repeated frequent intravitreal injections containing drug or implantation of drug delivery devices or implants are employed [18]. But this treatment option leads to severe complications such as infection, inflammation, retinal detachment and other adverse effects that will eventually lead to the death of photoreceptors and blindness in long-term [19]. Therefore, to overcome the ocular barriers and the severe adverse effects of intravitreal administrations unique and novel drug delivery systems are currently in development [20]. Some of these drug delivery systems and ophthalmic implants that are developed recently and the ones which are currently in development for the treatment of different ocular diseases to restore normal vision are discussed in this review article.

Section snippets

Ophthalmic devices

Ocular implants and drug delivery systems have gained immense interest in the recent era due to their efficient applications in restoring the normal vision acuity [21]. These devices can be non-biodegradable, biodegradable or stimuli-responsive systems that can be placed inside the eye for the release of the medication or to correct a deformity. In the recent years, drug delivery systems have gained a lot of importance due to their ability to release the medication or drug in a controlled and

Other ophthalmic drug delivery devices

So far we have discussed the different types of implants for various ophthalmic diseases, but there are also currently various drug delivery devices for the treatment of multiple diseases like uveitis, diabetic retinopathy, and AMD. These implants can be implanted in different parts of the eye as shown in Fig. 4, and they are discussed below (see Table 1).

Durasert™ is an injectable drug delivery system developed by Eye Point Pharmaceuticals, the USA for the sustained release of small molecules

Nanoparticles and hydrogel as drug delivery systems

There are different types of drug delivery systems that are currently in use, some of them are liposomes, microspheres, hydrogels, nanoparticles, cyclodextrins, etc. [121]. Of all the drug delivery systems nanoparticle-mediated drug delivery systems have gained immense interest due to the benefits they offer. Nanoparticles offer high biocompatibility, increased bioavailability of the drug in the target site and controlled release for a more extended period [25,122]. A review by Bisht et al.,

Outlook

The development and innovations of various implants and drug delivery systems have led to improving the quality of patients in restoring vision. Nevertheless, they are bound to multiple complications or side effects as mentioned in the article. However, in order to avoid these complications, there is a need for the development of novel therapeutical options. For example, the treatment of posterior segment diseases is more complicated than the anterior segment diseases. More researchers are

Conclusion

Treatment of ophthalmic diseases is a significant concern and a potential clinical problem that is persisting throughout the world. In order for the patients to regain the functional vision, there are various ocular therapies which include new novel drugs, implants, drug delivery system which has benefitted in restoring the vision. Even with robust development of new devices and implants, there is an increasing demand for the longevity of implants, patient compliance, non-invasive surgical

Conflicts of interest

The authors declare no conflict of interest.

Acknowledgments

The authors acknowledge the Blazer Foundation for supporting the Regenerative Medicine and Disability (RMDR) Lab at the Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford. The financial support from the MBT program at the Department of Biomedical Science is also acknowledged.

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