Comparison of Corneal Tissue Profile of Pseudophakic and Phakic Donors

ABSTRACT Introduction Open-globe ocular injuries have increased in frequency in recent combat operations due to increased use of explosive weaponry. Unfortunately, open-globe injuries have one of the worst visual outcomes for the injured warfighter, often resulting in permanent loss of vision. To improve visual recovery, injuries need to be stabilized quickly following trauma, in order to restore intraocular pressure and create a watertight seal. Here, we assess four off-the-shelf (OTS), commercially available tissue adhesives for their ability to seal military-relevant corneal perforation injuries (CPIs). Materials and Methods Adhesives were assessed using an anterior segment inflation platform and a previously developed high-speed benchtop corneal puncture model, to create injuries in porcine eyes. After injury, adhesives were applied and injury stabilization was assessed by measuring outflow rate, ocular compliance, and burst pressure, followed by histological analysis. Results Tegaderm dressings and Dermabond skin adhesive most successfully sealed injuries in preliminary testing. Across a range of injury sizes and shapes, Tegaderm performed well in smaller injury sizes, less than 2 mm in diameter, but inadequately sealed large or complex injuries. Dermabond created a watertight seal capable of maintaining ocular tissue at physiological intraocular pressure for almost all injury shapes and sizes. However, application of the adhesive was inconsistent. Histologically, after removal of the Dermabond skin adhesive, the corneal epithelium was removed and oftentimes the epithelium surface penetrated into the wound and was adhered to inner stromal tissue. Conclusions Dermabond can stabilize a wide range of CPIs; however, application is variable, which may adversely impact the corneal tissue. Without addressing these limitations, no OTS adhesive tested herein can be directly translated to CPIs. This highlights the need for development of a biomaterial product to stabilize these injuries without causing ocular damage upon removal, thus improving the poor vision prognosis for the injured warfighter.

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Use of Polycaprolactone in Corneal Tissue Engineering: A Review

Materials Today Communications ◽

10.1016/j.mtcomm.2021.102402 ◽

2021 ◽

pp. 102402

Author(s):

Amin Orash Mahmoud Salehi ◽

Saeed Heidari Keshel ◽

Farshid Sefat ◽

Lobat Tayebi

Keyword(s):

Tissue Engineering ◽

Corneal Tissue

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Optimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffolds

Pharmaceutics ◽

10.3390/pharmaceutics13060832 ◽

2021 ◽

Vol 13 (6) ◽

pp. 832

Author(s):

Mohammad Mirazul Islam ◽

Dina B. AbuSamra ◽

Alexandru Chivu ◽

Pablo Argüeso ◽

Claes H. Dohlman ◽

...

Keyword(s):

Mechanical Properties ◽

Crosslinking Agent ◽

Collagen Scaffold ◽

Human Monocyte ◽

Subsequent Treatment ◽

Sodium Metabisulfite ◽

Corneal Tissue ◽

Dependent Manner ◽

Collagen Scaffolds ◽

Enzymatic Stability

Collagen scaffolds, one of the most used biomaterials in corneal tissue engineering, are frequently crosslinked to improve mechanical properties, enzyme tolerance, and thermal stability. Crosslinkers such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) are compatible with tissues but provide low crosslinking density and reduced mechanical properties. Conversely, crosslinkers such as glutaraldehyde (GTA) can generate mechanically more robust scaffolds; however, they can also induce greater toxicity. Herein, we evaluated the effectivity of double-crosslinking with both EDC and GTA together with the capability of sodium metabisulfite (SM) and sodium borohydride (SB) to neutralize the toxicity and restore biocompatibility after crosslinking. The EDC-crosslinked collagen scaffolds were treated with different concentrations of GTA. To neutralize the free unreacted aldehyde groups, scaffolds were treated with SM or SB. The chemistry involved in these reactions together with the mechanical and functional properties of the collagen scaffolds was evaluated. The viability of the cells grown on the scaffolds was studied using different corneal cell types. The effect of each type of scaffold treatment on human monocyte differentiation was evaluated. One-way ANOVA was used for statistical analysis. The addition of GTA as a double-crosslinking agent significantly improved the mechanical properties and enzymatic stability of the EDC crosslinked collagen scaffold. GTA decreased cell biocompatibility but this effect was reversed by treatment with SB or SM. These agents did not affect the mechanical properties, enzymatic stability, or transparency of the double-crosslinked scaffold. Contact of monocytes with the different scaffolds did not trigger their differentiation into activated macrophages. Our results demonstrate that GTA improves the mechanical properties of EDC crosslinked scaffolds in a dose-dependent manner, and that subsequent treatment with SB or SM partially restores biocompatibility. This novel manufacturing approach would facilitate the translation of collagen-based artificial corneas to the clinical setting.

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Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits

Pharmaceuticals ◽

10.3390/ph14050480 ◽

2021 ◽

Vol 14 (5) ◽

pp. 480

Author(s):

Martin Kallab ◽

Kornelia Schuetzenberger ◽

Nikolaus Hommer ◽

Bhavapriya Jasmin Schäfer ◽

Doreen Schmidl ◽

...

Keyword(s):

Single Dose ◽

Drug Concentration ◽

Vitreous Humor ◽

Controlled Study ◽

Eye Drops ◽

Corneal Tissue ◽

Single Administration ◽

Local Tolerability ◽

Dose Administration ◽

Retinal Tissue

The purpose of this study was to evaluate the ocular pharmacokinetics, bio-distribution and local tolerability of γ-cyclodextrin (γCD) based irbesartan 1.5% eye drops and candesartan 0.15% eye drops after single and multiple topical administration in rabbit eyes. In this randomized, controlled study, a total number of 59 New Zealand White albino rabbits were consecutively assigned to two study groups. Group 1 (n = 31) received irbesartan 1.5% and group 2 (n = 28) candesartan 0.15% eye drops. In both groups, single dose and multiple administration pharmacokinetic studies were performed. Rabbits were euthanized at five predefined time points after single-dose administration, whereas multiple-dose animals were dosed for 5 days twice-daily and then euthanized 1 h after the last dose administration. Drug concentration was measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the retinal tissue, vitreous humor, aqueous humor, corneal tissue and in venous blood samples. Pharmacokinetic parameters including maximal drug concentration (Cmax), time of maximal drug concentration (Tmax), half-life and AUC were calculated. To assess local tolerability, six additional rabbits received 1.5% irbesartan eye drops twice daily in one eye for 28 days. Tolerability was assessed using a modified Draize test and corneal sensibility by Cochet Bonnet esthesiometry. Both γCD based eye drops were rapidly absorbed and distributed in the anterior and posterior ocular tissues. Within 0.5 h after single administration, the Cmax of irbesartan and candesartan in retinal tissue was 251 ± 142 ng/g and 63 ± 39 ng/g, respectively. In the vitreous humor, a Cmax of 14 ± 16 ng/g for irbesartan was reached 0.5 h after instillation while Cmax was below 2 ng/g for candesartan. For multiple dosing, the observed Cmean in retinal tissue was 338 ± 124 ng/g for irbesartan and 36 ± 10 ng/g for candesartan, whereas mean vitreous humor concentrations were 13 ± 5 ng/g and <2 ng/g, respectively. The highest plasma concentrations of both irbesartan (Cmax 5.64 ± 4.08 ng/mL) and candesartan (Cmax 4.32 ± 1.04 ng/mL) were reached 0.5 h (Tmax) after single administration. Local tolerability was favorable with no remarkable differences between the treated and the control eyes. These results indicate that irbesartan and candesartan in γCD based nanoparticle eye drops can be delivered to the retinal tissue of the rabbit’s eye in pharmacologically relevant concentrations. Moreover, safety and tolerability profiles appear to be favorable in the rabbit animal model.

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Characterization of Ocular Surface Microbial Profiles Revealed Discrepancies between Conjunctival and Corneal Microbiota

Pathogens ◽

10.3390/pathogens10040405 ◽

2021 ◽

Vol 10 (4) ◽

pp. 405

Author(s):

Anna Matysiak ◽

Michal Kabza ◽

Justyna A. Karolak ◽

Marcelina M. Jaworska ◽

Malgorzata Rydzanicz ◽

...

Keyword(s):

Microbial Communities ◽

Ocular Surface ◽

Molecular Techniques ◽

Corneal Tissue ◽

Rna Seq ◽

Microbiome Composition ◽

Viral Sequences ◽

Pcr Techniques ◽

Unmapped Reads

The ocular microbiome composition has only been partially characterized. Here, we used RNA-sequencing (RNA-Seq) data to assess microbial diversity in human corneal tissue. Additionally, conjunctival swab samples were examined to characterize ocular surface microbiota. Short RNA-Seq reads, obtained from a previous transcriptome study of 50 corneal tissues, were mapped to the human reference genome GRCh38 to remove sequences of human origin. The unmapped reads were then used for taxonomic classification by comparing them with known bacterial, archaeal, and viral sequences from public databases. The components of microbial communities were identified and characterized using both conventional microbiology and polymerase chain reaction (PCR) techniques in 36 conjunctival swabs. The majority of ocular samples examined by conventional and molecular techniques showed very similar microbial taxonomic profiles, with most of the microorganisms being classified into Proteobacteria, Firmicutes, and Actinobacteria phyla. Only 50% of conjunctival samples exhibited bacterial growth. The PCR detection provided a broader overview of positive results for conjunctival materials. The RNA-Seq assessment revealed significant variability of the corneal microbial communities, including fastidious bacteria and viruses. The use of the combined techniques allowed for a comprehensive characterization of the eye microbiome’s elements, especially in aspects of microbiota diversity.

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Gamma-Irradiated Cornea in Combat-related Ocular Trauma

Military Medicine ◽

10.1093/milmed/usaa479 ◽

2020 ◽

Author(s):

Brian M Davis ◽

Carson Clabeaux ◽

Anton Vlasov ◽

Paul Houghtaling

Keyword(s):

Ocular Trauma ◽

Cost Savings ◽

Corneal Tissue ◽

Significant Cost ◽

Visual Rehabilitation ◽

Military Health ◽

Corneal Injury ◽

Gamma Irradiated ◽

The Military ◽

Penetrating Ocular Trauma

ABSTRACT Corneal injury is a known risk for deployed troops worldwide. To the authors’ knowledge, there has been no reported use of gamma-irradiated corneas in the setting of severe corneal trauma. Our report highlights the case of a 36-year-old active duty solider who sustained bilateral penetrating ocular trauma from a nearby ordnance explosion. We propose that ocular surgeons should consider utilizing gamma-irradiated corneas in (1) a situation where the corneal tissue is so damaged that it would be challenging to accomplish an adequate repair while providing the opportunity for future visual rehabilitation and (2) remote and/or deployed environments where storage of fresh donor tissue is limited. The long shelf life of gamma-irradiated corneas reduces the need for specialized storage equipment and the need for continuous resupply, both potentially leading to significant cost savings for the Military Health System.

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Nano-Scale Modifications of Amniotic Membrane Induced by UV and Antibiotic Treatment: Histological, AFM and FTIR Spectroscopy Evidence

Materials ◽

10.3390/ma14040863 ◽

2021 ◽

Vol 14 (4) ◽

pp. 863

Author(s):

Simona Cavalu ◽

George Roiu ◽

Ovidiu Pop ◽

Denisa A. Petricas Heredea ◽

Traian Octavian Costea ◽

...

Keyword(s):

Ftir Spectroscopy ◽

Antibiotic Treatment ◽

Amniotic Membrane ◽

Ocular Surface ◽

Enzymatic Digestion ◽

Uv Exposure ◽

Amniotic Membrane Transplantation ◽

Corneal Tissue ◽

Nano Scale ◽

Gentamicin Treatment

The efficiency of amniotic membrane (AM) transplantation in different types of ocular surface disorders is due to its outstanding properties such as antifibrotic, antibacterial, anti-inflammatory and antiangiogenic, working as a versatile scaffold to promote corneal tissue epithelialization. A proper preparation, preservation and clinical application are crucial for the best outcomes in the treatment of different severe ocular disorders, taking into account its fragility. In this context, by combining high-sensitivity tools such as atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy with histological and immunohistochemical examination, we aimed to investigate the ultrastructural modifications of the amniotic membrane (AM) upon UV exposure and/or antibiotic treatment, with relevance for clinical applications in ocular surface surgery. From the morphological point of view, we noticed a loss of cuboidal cells in the basal membrane, accompanied by the splitting of collagen fibers upon UV and/or gentamicin treatment, while structural alteration of proteins was evidenced by the FTIR quantitative analysis of the secondary structure. A decrease in α-helix and β-sheet content, accompanied by increased content in less ordered structures (turns, random and side chains), was noticed after all the treatments. At the nano-scale, AFM details showed modifications of collagen fibrils in terms of their thickness and network compaction upon gentamicin and/or UV treatment. The enzymatic digestion assay demonstrated that UV exposure significantly reduces the degradation rate of the AM, while gentamicin treatment promotes an accelerated enzymatic digestion upon UV exposure. In order to highlight the clinical impact of the research, a clinical case is presented showing the relevance of amniotic membrane transplantation in pterygium surgery.

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Significance of Crosslinking Approaches in the Development of Next Generation Hydrogels for Corneal Tissue Engineering

Pharmaceutics ◽

10.3390/pharmaceutics13030319 ◽

2021 ◽

Vol 13 (3) ◽

pp. 319

Author(s):

Promita Bhattacharjee ◽

Mark Ahearne

Keyword(s):

Tissue Engineering ◽

Chemical Structure ◽

Biochemical Properties ◽

Corneal Tissue ◽

Future Prospects ◽

Chemical Additives ◽

Injectable Hydrogels ◽

Corneal Regeneration ◽

Key Factor ◽

Fuchs Endothelial Dystrophy

Medical conditions such as trachoma, keratoconus and Fuchs endothelial dystrophy can damage the cornea, leading to visual deterioration and blindness and necessitating a cornea transplant. Due to the shortage of donor corneas, hydrogels have been investigated as potential corneal replacements. A key factor that influences the physical and biochemical properties of these hydrogels is how they are crosslinked. In this paper, an overview is provided of different crosslinking techniques and crosslinking chemical additives that have been applied to hydrogels for the purposes of corneal tissue engineering, drug delivery or corneal repair. Factors that influence the success of a crosslinker are considered that include material composition, dosage, fabrication method, immunogenicity and toxicity. Different crosslinking techniques that have been used to develop injectable hydrogels for corneal regeneration are summarized. The limitations and future prospects of crosslinking strategies for use in corneal tissue engineering are discussed. It is demonstrated that the choice of crosslinking technique has a significant influence on the biocompatibility, mechanical properties and chemical structure of hydrogels that may be suitable for corneal tissue engineering and regenerative applications.

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Photorefractive keratectomy for correction of myopia: Our one-year experience

Vojnosanitetski pregled ◽

10.2298/vsp1210852r ◽

2012 ◽

Vol 69 (10) ◽

pp. 852-857

Author(s):

Mirko Resan ◽

Miroslav Vukosavljevic ◽

Milorad Milivojevic

Keyword(s):

Visual Acuity ◽

Postoperative Complications ◽

Intraoperative Complications ◽

Mean Value ◽

Ablation Depth ◽

Laser In Situ Keratomileusis ◽

Photorefractive Keratectomy ◽

Corneal Tissue ◽

Surgical Method ◽

A Prospective Study

Background/Aim. Photorefractive keratectomy (PRK), after laser in situ keratomileusis (LASIK), is commonly performed refractive surgical method worldwide. The aim of this study was to examine the effectiveness and safety of PRK in correction of various strengths of myopia and to assess how much corneal tissue is being removed with one diopter sphere (Dsph) correction by using different optical zones (OZ). Methods. A prospective study with a follow-up period of 6 months included 55 patients of which 100 myopic eyes were treated by PRK method (one eye was included in 10 patients). Myopic eyes with a preoperative best corrected visual acuity (BCVA) = 1.0 (20/20) were analysed. In order to assess the effectiveness of PRK operated myopic eyes were divided into four groups according to the dioptric power: 1)? -1.75 Dsph (n = 26); 2) from -2 to -3.75 Dsph (n = 44); 3) from -4 to -6.75 Dsph (n = 23), and 4) ? -7 Dsph (n = 7). Myopic eyes with preoperative BCVA ? 0.9 (amblyopic eyes) were excluded from the study, as well as eyes with astigmatism > -1.5 Dcyl. To assess the effectiveness of PRK we examined the percentage of eyes in the mentioned groups, which derived uncorrected visual acuity (UCVA) 6 months after the intervention to the following: a) UCVA = 1.0 (20/20) and b) UCVA ? 0.5 (20/40). To assess the safety of PRK we examined the frequency of intraoperative and postoperative complications. To estimate how much corneal tissue was removed with one Dsph correction by using different OZ, we used preoperative and postoperative (after 6 months) central pachymetry values expressed in ?m and volume of cornea (central 7 mm) expressed in mm?. In that sense, we used only the myopic eyes with clear preoperative spherical refraction. The total number of these eyes was 27, of which 16 eyes were treated using a 6.5 mm OZ and 11 eyes using a 7 mm OZ. Results. Refractive spherical equivalent (RSE) for all eyes was in the range from -0.75 to -8.75 Dsph, and preoperative mean value of RSE with standard deviation (mean RSE ? SD) was -3.32 ? 1.83 Dsph. Six months after PRK, 91% of eyes had UCVA = 20/20, and 99% of eyes had UCVA ? 20/40. In the first group (? -1.75 Dsph) preoperative mean RSE ? SD was -1.34 ? 0.32 Dsph, six months after PRK, 96% of eyes had UCVA = 20/20, and 100% of eyes had UCVA ? 20/40. In the second group (from -2 to -3.75 Dsph) preoperative mean RSE ? SD was - 2.95 ? 0.57 Dsph, six months after PRK, 89% of eyes had UCVA = 20/20, and 100% of eyes had UCVA ? 20/40. In the third group (from -4 to -6.75 Dsph) preoperative mean RSE ? SD was - 4.93 ? 0.70 Dsph, six months after PRK, 100% of eyes had UCVA = 20/20. In the fourth group (? - 7 Dsph) preoperative mean RSE ? SD was -7.71 ? 0.67 Dsph, six months after PRK, 57% of eyes had UCVA = 20/20, and 86% of eyes had UCVA ? 20/40. There were no intraoperative complications while postoperative complications occurred in 2 patients - in both cases in one eye (2%). In that cases, epithelial defects were detected. In the group of eyes that were treated by 6.5 mm OZ mean RSE ? SD was -2.45 ? 0.99 Dsph, the ablation depth per 1 Dsph was 17.54 ? 5.58 ?m and ablated volume of central 7 mm cornea by 1 Dsph was 0.43 ? 0.18 mm?. In the group of eyes that were treated by 7 mm OZ mean RSE ? SD was -3.32 ? 2.26 Dsph, the ablation depth per 1 Dsph was 23.73 ? 6.91 ?m and ablated volume of central 7 mm cornea by 1 Dsph was 0.61 ? 0.31 mm?. Conclusion. PRK is effective and safe refractive surgical method for correcting myopia up to -8 .75 Dsph. OZ size is the main factor determining the depth of the excimer laser ablation of the corneal tissue volume consumed by 1 Dsph. Higher OZ value determines higher consumption of cornea tissue.

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The Mechanism of Ablation of Corneal Tissue by the Neodymium Doped Yttrium-Lithium-Fluoride Picosecond Laser

Cornea ◽

10.1097/00003226-199413060-00002 ◽

1994 ◽

Vol 13 (6) ◽

pp. 479???486

Author(s):

Daniel B. Brown ◽

William J. O??Brien ◽

Richard O. Schultz

Keyword(s):

Lithium Fluoride ◽

Picosecond Laser ◽

Corneal Tissue ◽

Yttrium Lithium Fluoride

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