Corneal Cross-Linking: The Evolution of Treatment for Corneal Diseases

Corneal cross-linking (CXL) using riboflavin and ultraviolet A (UVA) light has become a useful treatment option for not only corneal ectasias, such as keratoconus, but also a number of other corneal diseases. Riboflavin is a photoactivated chromophore that plays an integral role in facilitating collagen crosslinking. Modifications to its formulation and administration have been proposed to overcome shortcomings of the original epithelium-off Dresden CXL protocol and increase its applicability across various clinical scenarios. Hypoosmolar riboflavin formulations have been used to artificially thicken thin corneas prior to cross-linking to mitigate safety concerns regarding the corneal endothelium, whereas hyperosmolar formulations have been used to reduce corneal oedema when treating bullous keratopathy. Transepithelial protocols incorporate supplementary topical medications such as tetracaine, benzalkonium chloride, ethylenediaminetetraacetic acid and trometamol to disrupt the corneal epithelium and improve corneal penetration of riboflavin. Further assistive techniques include use of iontophoresis and other wearable adjuncts to facilitate epithelium-on riboflavin administration. Recent advances include, Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) for treatment of infectious keratitis, customised protocols (CurV) utilising riboflavin coupled with customised UVA shapes to induce targeted stiffening have further induced interest in the field. This review aims to examine the latest advances in riboflavin and UVA administration, and their efficacy and safety in treating a range of corneal diseases. With such diverse riboflavin delivery options, CXL is well primed to complement the armamentarium of therapeutic options available for the treatment of a variety of corneal diseases.

INFECTIOUS AND INFLAMMATORY COMPLICATIONSIN OPHTHALMOLOGYAMID COVID-19

Inflammatory complications of the organ of vision in the time of COVID-19 can be manifested as conjunctivitis, scleritis, episcleritis, keratitis, uveitis and optic neuritis. It is essential to collect anamnesis, examine the blood for the presence of COVID 19 and treat these patients with the help of infectious disease specialists. Correct diagnosis of inflammatory ocular complications in the presence of COVID 19 makes it possible to prevent ocular complications, such as: ulcers and corneal penetration; fusion and overgrowth of the pupil,which leadto secondary glaucoma; endoophthalmitis, panophthalmitis and optic nerve atrophy. Timely intensive medical care and adequate treatment of these complications lead to a decrease in disability in this category of patients.Keywords:Ophthalmology, COVID-19,complications, ulcers, endoophthalmitis, panophthalmitis, gastrointestinal tract, cavernous sinus thrombosis

Corneal Penetration of Low-Dose Atropine Eye Drops

Major studies demonstrating the inhibition of myopia in children and juveniles by low-dose atropine eye drops provide little information on the manufacturing process and the exact composition of the atropine dilutions. However, corneal penetration might significantly vary depending on preservatives, such as benzalkonium chloride (BAC), and the atropine concentration. Since there is a trade-off between side effects, stability, and optimal effects of atropine on myopia, it is important to gain better knowledge about intraocular atropine concentrations. We performed an ex vivo study to determine corneal penetration for different formulations. Atropine drops (0.01%) of different formulations were obtained from pharmacies and applied to the cornea of freshly enucleated pig eyes. After 10 min, a sample of aqueous humor was taken and atropine concentrations were determined after liquid–liquid extraction followed by high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). The variability that originated from variations in applied drop size exceeded the differences between preserved and preservative-free formulations. The atropine concentration in the anterior chamber measured after 10 min was only 3.8 × 10−8 of its concentration in the applied eye drops, corresponding to 502.4 pM. Obviously, the preservative did not facilitate corneal penetration, at least ex vivo. In the aqueous humor of children’s eyes, similar concentrations, including higher variability, may be expected in the lower therapeutic window of pharmacodynamic action.

STUDY OF ISOTONICITY AND OCULAR IRRITATION OF CHLORAMPHENICOL IN SITU GEL

Objective: The objective of this study was to find out the isotonicity of chloramphenicol ophthalmic in situ gel and to know the irritating effect of its in the eyes of test animals, so it can be to maximize absorption of the drug in the eye, minimize drug loss before corneal penetration and safe to used. Methods: This study were started by making four aseptic formulations of in situ gel preparations with a comparison of the baseline concentrations of different Poloxamer 407 and HPMC, F1 (5: 0.45), F2 (10: 0.45), F3 (5: 1) and F4 (10: 1). Four aseptic of in situ gel preparations, followed by a qualitative isotonicity test using blood cells to see the comparison between control and test preparations, and ocular irritation test using the draize test method to determine the presence or absence of the irritation. Results: The results obtained from the isotonicity test showed that the four preparations have normal blood cells that similar with isotonic control solution; therefore, it can be said that the preparations have been made isotonic. The results of the ocular irritation test using the draize test method showed for each category, such as cornea, iris, conjunctiva and edema were zero. A zero value on the cornea indicates no ulceration or opacity, and the iris, conjunctiva and edema were normal. Conclusion: Chloramphenicol in situ gel are isotonic and do not cause irritation to the rabbit's eyes, so they are safe to use and the formulation can be used for further research until the final goal is obtained.

Enhanced Corneal Penetration of a Poorly Permeable Drug Using Bioadhesive Multiple Microemulsion Technology

Corneal penetration is a key rate limiting step in the bioavailability of topical ophthalmic formulations that incorporate poorly permeable drugs. Recent advances have greatly aided the ocular delivery of such drugs using colloidal drug delivery systems. Ribavirin, a poorly permeable BCS class-III drug, was incorporated in bioadhesive multiple W/O/W microemulsion (ME) to improve its corneal permeability. The drug-loaded ME was evaluated regarding its physical stability, droplet size, PDI, zeta potential, ultrastructure, viscosity, bioadhesion, in vitro release, transcorneal permeability, cytotoxicity, safety and ocular tolerance. Our ME possessed excellent physical stability, as it successfully passed several cycles of centrifugation and freeze–thaw tests. The formulation has a transparent appearance due to its tiny droplet size (10 nm). TEM confirmed ME droplet size and revealed its multilayered structure. In spite of the high aqueous solubility and the low permeability of ribavirin, this unique formulation was capable of sustaining its release for up to 24 h and improving its corneal permeability by 3-fold. The in vitro safety of our ME was proved by its high percentage cell viability, while its in vivo safety was confirmed by the absence of any sign of toxicity or irritation after either a single dose or 14 days of daily dosing. Our ME could serve as a vehicle for enhanced ocular delivery of drugs with different physicochemical properties, including those with low permeability.

Surgical closure of giant traumatic macular hole with retinal graft

Aim: To present a case with a large traumatic macular hole that we repaired with a retinal graft. Case description: A 24-year-old male patient presented with corneal penetration and an intraocular foreign body caused by a work accident. Vitrectomy and intraocular foreign body removal were performed. One month after the surgery, the patient had macula on retinal detachment in the nasal and superior quadrant. In addition, a giant macular hole was formed. However, the macula was atrophic because of the trauma, and we could not repair the hole with classic macular hole surgery techniques. For this reason, we used a retinal graft to cover the macular hole, and we observed that the hole was closed in follow-up visits. Conclusion: Retinal grafts can be used in patients with giant macular holes. They may be useful especially in patients with atrophic macula in trauma cases.