Medical hypothesis discovery and innovation in ophthalmology

Editorial/ No abstract

Presbyopia occurs after 40 years of age in humans with a progressive loss of accommodation. Accommodation depends on the contraction of the ciliary muscle and iris, lens changes and convergence.  The parasympathetic system regulates the degree of ciliary muscle and iris contraction necessary to modify the shape and position of the lens and its stimulation is effective through the activation of muscarinic receptors that are present in both structures. The hypothesis proposed here suggests the correction of accommodation in emmetropic presbyopic patients using a pharmacological treatment that includes a cholinergic agent combined with non-steroidal anti-inflammatory drugs (NSAIDs). This drug combination can restore near vision without affecting distance vision. It is important to note that the pharmaceutical form used was devoid of any inflammatory or other collateral effects.

As the number of contactâ€lens wearers rises worldwide, Pseudomonas aeruginosa (PA) keratitis is attracting more attention as a major public health issue. Corneal lesions of PA, being the most intimidating complication of contactâ€lens wearer, can progress rapidly in spite of local antibiotic treatment, and may result in perforation and the permanent loss of vision. One of the explanations proposed for the evasion of the pathogen from immune responses of the host as well as antibacterial treatment is the fact that invasive clinical isolates of PA have the unusual ability to invade and replicate within surface corneal epithelial cells. In this manner, PA is left with an intracellular sanctuary. Endophthalmitis, albeit rare, is another ophthalmic infection faced by the challenge of drug delivery that can be potentially catastrophic. The present hypothesis is that nanoparticles can carry antiâ€pseudomonas antibiotics (e.g. ceftazidime) through the membranes, into the “hidden zone†of the pathogen, hence being an effective and potent therapeutic approach against pseudomonas keratitis and endophthalmitis.

To fabricate donor corneal substitutes based on carbodiimide cross-linked porcine collagen, to study their in vitro and in vivo properties, and to elaborate new implantation techniques for the donor corneal collagen-based substitutes, this study had been performed. Bioengineered substitutes of corneal stroma (BSCS) were fabricated by cross-linking porcine type I collagen with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide and N-hydroxysuccinimide, as previously described. Their refractive indices were measured using an Abbe refractometer. The mechanical properties were evaluated by their ability to tolerate interrupted stitches placed during deep lamellar keratoplasty performed on isolated rabbit eyes. BSCS were then implanted into one cornea of 8 rabbits and were followed-up for 12 months. Our BSCS had refractive indices of 1.24-1.3 (human cornea 1.37-1.38), and tolerated the placement of 12 interrupted stitches well. A new technique, the BSCS “stitchless†implantation, was developed. When implanted into rabbit corneas, BSCS remained stably integrated and clear during the 12 month follow-up. Non-intensive opacities within corneal layers (grade 1.5 on a scale of 0 to 4) were observed in 2/8 eyes during the 1st postoperative week, and in one eye the opacity resolved. In the 2nd eye a fine opacity (grade 1) remained. Light microscopy confirmed the integrity of the implants and the absence of inflammation in corneal stroma. The current data suggest that the BSCS fabricated in the Ukraine by cross-linking collagen is a good alternative to human donor corneas if medical grade porcine collagen is used. In addition, the new “stitchless†technique of BSCS implantation may decrease corneal substitute damage and accelerate its epithelialisation.

An integrated model for keratectasia risk assessment has received much attention over many years. The objective of this article is to propose a more complete, conceptual model by which high risk individuals can be screened, even with no topographic irregularity or corneal thinning. In this model, corneal ectasia results from the fatigue effect of cyclic shear stress and tensile stress, caused by eye rubbing and fluctuating intraocular pressure (IOP), respectively, on corneal microstructures. The model clarifies the importance of the magnitude of shearing force applied by eye rubbing, the amplitude of IOP fluctuations, the frequency of eye rubbing and IOP fluctuations, the geometry of the cornea, the temperature of the cornea, and the effects of oxidative stress on the cornea in keratectasia development. Therefore, preoperative screening strategies based on these concepts can be designed to assess the risk of keratectasia at an early stage, and select the best candidates who can benefit from keratorefractive surgeries.

Letter/ No abstract