Corneas In Group Research Articles

Is central corneal thickness a constant during air puff indentation with Corvis ST?

AbstractPurposeCorvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) is the only commercial device that can capture corneal dynamic deformation in real time and provide a number of dynamic parameters, which include central corneal thickness (CCT). This study aimed to quantitatively analyse the change in CCT during air puff indentation using Corvis ST.MethodsSixty‐seven keratoconic eyes and 84 normal eyes were enrolled in this study. Dynamic videos were obtained from Corvis ST. An adaptive bilateral filtering method and a frame correlation method were used to remove noises. An adaptive threshold segmentation method was used to extract corneal boundary. The change in central corneal thickness, described as relative change rate of central corneal thickness (RCRCCT) and change speed of central corneal thickness (CSCCT) were compared between keratoconus group and normal cornea group.ResultsIt is shown that CCT would change and these two parameters were statistically significantly different between the keratoconus group and the normal cornea group RCRCCT, p = 0.014; CSCCT, p = 0.001.ConclusionsThe result of this study approved that CCT would change during air puff indentation. Further study is needed to develop more clinical applications based on these new findings, such as distinguishing keratoconus from normal cornea. image Fig. 1 Curves of changes in cornea and force over time. (A) Curve of corneal apex displacement and curve of air puff force; (B) A typical curve of the CCT changingover time. The red lineis the central corneal thickness‐time curve, the blue line is the force ‐time curve, and the green line is the fitting curveof force curve.

Effect of Base Curve on Silicone Hydrogel Contact lens Fitting Characteristics and Comfort

Purpose : To compare the fitting assessment and subjective comfort according to the base curves of silicone hydrogel lens. Methods : Thirty adults (60 eyes, mean age: 21.9 years) who had no ocular disease and no problem in wearing contact lenses were included. Contact lens fittings were performed with empirical and trial fitting methods. ln empirical fitting. base curve of contact lenses were selected based on K–reading (fitting contact lens with 8.5 mm base curve in the case of steeper than 7.8 mm. 9.0 mm base curve in the case of flatter than 7.8 mm), and in trial fitting, two base curves were fitted by a double blind method. The fitting characteristics were assessed with centration, movement, lag, push-up test and keratometer mire. The subjective comfort was evaluated through questionnaires with Likert 5-point scale. Results : It was shown that 91.67% of the subjects was acceptable to base curve determined by empirical fitting. However, 33.33% of steep curve group showed ideal fitting with 9.0 mm base curve and 25% of flat curve group showed ideal fitting with 8.5 mm base curve, and empirical and trial fitting showed 71.67%, 100% in success rate, respectively. It was appeared that 63.33% of subjects felt no difference in the comfort sensation of contact lenses with different base curves, but the comfort sensation with the 8.5 mm base curve (3.53 points) was significantly higher than 9.0 mm base curve (2.75 points), (t=4.528, p<0.001) and 27.78% of a flat cornea group felt comfortable with steeper fitting. Conclusion : In order to determine the base curve of silicone hydrogel contact lenses, it is suggested that evaluating the fitting condition is more important than subjective fitting condition of the wearer or empirical determination.

Electron Beam Irradiated Corneal Versus Gamma-Irradiated Scleral Patch Graft Erosion Rates in Glaucoma Drainage Device Surgery.

IntroductionPatch graft erosion and implant exposure is a known complication of glaucoma drainage device (GDD) surgery. Recently, electron beam (e-beam) irradiated corneal tissue ha s become available; however, limited data exist on the rates of erosion for e-beam irradiated corneal grafts compared to traditional scleral grafts after GDD surgery.MethodsThis retrospective study examines the records of 253 eyes from 225 adult subjects who underwent GDD surgery with either e-beam irradiated corneal or scleral grafts at the Casey Eye Institute by five surgeons between April 22, 2014 and October 11, 2017. Surgical procedures and the occurrence of graft erosion were determined using billing codes and verified by manual review of electronic health records.ResultsThe average age at the time of surgery was 61.3 ± 17.5 years (n = 200) and 60.8 ± 16.8 years (n = 53) for the e-beam irradiated cornea and sclera groups, respectively. The average follow-up time post-surgery was 416 ± 345 days and 495 ± 343 days for the e-beam irradiated cornea and sclera groups, respectively. There were no statistically significant differences in sex, age, follow-up time, and glaucoma diagnosis between the groups; however, the e-beam irradiated cornea group was statistically more likely to have an Ahmed implant as compared to the sclera group. No erosion events were noted in either group.Conclusione-Beam irradiated corneal grafts were used 3.8 times more frequently relative to scleral grafts, yet there were no cases of graft erosion in either group during the follow-up period.

Therapeutic ultrasound for improving the tropical corneal delivery of macromolecules

The goal of this project is to facilitate the delivery of topical drugs into the cornea and anterior segment of the eye using therapeutic ultrasound which could present a promising treatment for keratoconus and other corneal diseases. Each cornea is dissected and placed in a diffusion cell. smURFP-blue, a blue fluorescent chromophore, was used as the drug. The experimental groups of corneas were treated with 1 and 0.8 W/cm2 continuous ultrasound for 5 min at frequencies of 400 kHz and 600 kHz, respectively, then left in the diffusion cell for another 55 min. Fluorescence images of the fixed corneas were obtained to determine the relative amount of smURFP-blue that remained in the tissue. Safety of ultrasound application was tested by comparing the damage in the corneal layers. Spectroscopy measurements indicated no statistical difference in the presence of the chromophore in the receiver compartment in ultrasound- and sham-treatment groups. Preliminary results showed greater fluorescent intensity in the cornea when smURFP-blue is delivered with ultrasound compared to smURFP-blue added without ultrasound. The histology studies did not show any significant damage in ultrasound-treated corneas. This work may allow for the development of an inexpensive, clinically applicable, and minimally invasive ultrasound method for corneal drug delivery.

Yield of Display Modules of Corneal Tomography for Early Diagnosis of Corneal Ectasia.

The thesis deals with comparison of topographic corneal indexes and their importance for the diagnosis of corneal ectatic disease. The corneas with different stages of keratoconus, forme fruste keratoconus, pellucid marginal degeneration, corneal warpage syndrome, and physiological cornea with varying values of regular astigmatism were included in the tested group. The study was conducted in 2015-2018 at the European Eye Clinic Lexum Brno. The study group contained 208 eyes, 111 eyes with keratoconus, 31 eyes with forme fruste keratoconus, 23 eyes with pellucid marginal degeneration, 10 eyes with corneal warpage syndrome and 33 physiological eyes. 19 corneal parameters and indexes were monitored for these ectatic diseases, which were compared with healthy corneas with regular astigmatism. Asingle-factor ANOVA test, aStudent t-test were used for statistical analysis. Pearson&#39;scoefficients were used to assess the correlation. In all the observed tomographic parameters astatistically significant difference was found between the physiological and ectatic group of corneas. The parameters with the highest statistical difference were BEThLo, ISV, IHD, D, Rmin. Statistically significant indices were also found between the forme fruste keratoconus and physiological corneas. The best parameters for detecting the subclinical keratoconus were the back elevation at the thinniest point of the cornea (BEThLo), the difference between the thinniest and the central point of cornea (CP-TL), the maximum pachymetic progression index and the Db and D indexes (p 0.6) according to Pearson&#39;scorrelation coefficient. Statistically significant differences in the KK and PMD groups were found in the index of relative pachymetry, central pachymetry, CKI and Dp. Key words: Pentacam, corneal ectasia, keratoconus, pellucid marginal degeneration, corneal warpage syndrome, forme fruste keratoconus.

Implantable Collamer Lens ® for Management of Pseudophakic Ametropia in Eyes With a Spectrum of Previous Corneal Surgery

To assess the visual outcomes, predictability, and safety of the Implantable Collamer Lens (ICL) (STAAR Surgical, Inc., Monrovia, CA) for the management of residual pseudophakic refractive error. Forty-nine pseudophakic eyes of 40 patients in which myopic, hyperopic, or toric ICLs were implanted were retrospectively analyzed. Twenty-nine eyes had been implanted with a monofocal intraocular lens (IOL) and 20 eyes had a multifocal IOL. All IOLs were implanted in the capsular bag. Of the 49 eyes included, 6 had residual refractive error after phacoemulsification without corneal pathology or surgical alteration (virgin cornea group), 12 had LASIK or photorefractive keratectomy (PRK) (excimer laser group), 8 had radial keratotomy, 5 had intrastromal corneal ring segments (ICRS) implantation, 11 had penetrating keratoplasty, and 7 had deep anterior lamellar keratoplasty (DALK). Uncorrected and corrected (CDVA) distance visual acuity and manifest refraction were evaluated. The efficacy/safety indices were 0.92/1.10, 0.98/1.13, 1.04/1.11, 0.90/1.13, 0.79/1.17, and 0.71/1.23 for the virgin cornea, excimer laser, radial keratotomy, ICRS, penetrating keratoplasty, and DALK groups, respectively. No eye lost one or more lines of CDVA. The virgin cornea, excimer laser, and radial keratotomy groups showed better predictability and accuracy, with 96.2% spherical equivalent within ±1.00 diopters (D). The ICRS, penetrating keratoplasty, and DALK groups demonstrated approximately 50% spherical equivalent within ±1.00 D. There were no intraoperative or postoperative complications. Good refractive outcomes and a strong safety record support the use of the ICL for the correction of residual refractive error in pseudophakic eyes with previous corneal surgery. [J Refract Surg. 2018;34(10):654-663.].

Comparative Study of Ocular Pharmacokinetics of Gatifloxacin Between Continuous Lavage and Hourly Topical Instillation in Rabbits

To investigate the ocular pharmacokinetics and distribution of gatifloxacin between continuous lavage through the Morgan lens and repeated topical drop instillation in rabbits. Thirty-six healthy rabbits were randomly divided into 2 groups, and 0.3% gatifloxacin ophthalmic solution was instilled by continuous lavage using the Morgan lens onto the left eyes at 15 mL/h (or 50 μL of the same solution repeatedly administered topically every hour). The animals were killed at 2, 4, 8, and 12 hours in the Morgan lens group or at 12 and 24 hours in the topical instillation group. Aqueous humor specimens were collected from the anterior chamber first, and other ocular tissues and plasma were collected subsequently. Pharmacokinetic and pharmacodynamic indices, other than the minimum inhibitory concentration (MIC), were used as therapeutic parameters in ocular tissues. The highest concentration was found in the corneas in both groups. With continuous lavage, gatifloxacin reached an efficacious high concentration in 4 hours in the cornea, which is equivalent to about 23 times the concentration reached in the same tissue by hourly topical instillation for 12 to 24 hours. Using historic data as references, C/MIC90 was 105 (>10) and AUC0-t/MIC90 was 194 h (>125) in the cornea in the continuous lavage group at 4 hours, whereas these values were 5 and 73 hours for the topical hourly instillation group. Compared with hourly topical instillation, continuous lavage through the Morgan lens could achieve significantly higher concentrations in ocular tissues within a short period, especially in the cornea. Continuous lavage may be a much more efficient way to treat recalcitrant corneal infections.

Intérêt de la formule Holladay 2 dans le calcul de la puissance de l’implant intraoculaire pour les yeux de biométrie hors normes

To evaluate the benefit of the Holladay 2formula versus the 3rd generation formulae in calculating the IOL power in eyes with non-standard axial length or keratometry before cataract surgery. Retrospectiv study from January to December 2015. The inclusion critaeria were axial length (AL) <22mm or >26mm, or average keratometry <42D or >46D, dividing the patients in 4groups respectively. The 7parameters required to calculate the Holladay 2formula were collected. The final refractive result was turned into spherical equivalent to calculate the optimal power retrospectively. Then, the results obtained using the other formulae were compared with the optimal IOL power. One hundred and twenty-six eyes operated by two surgeons were included. In the high AL group (n=32), the SRK/T was the most accurate formula; regarding the low AL group (n=36), the Hoffer Q and Holladay 2formulae performed better; for the steep cornea group (n=27), the Hoffer Q, Haigis, Holladay 1and 2formulae were not different; last, the Holladay 1and 2were more accurate in the flat cornea group (n=33). In our study, the Holladay 2formula does not seem to be better than the others for calculating IOL power in non-standard eyes. Preoperative eye features in such non-standard cases should be taken into account before the surgery to choose the more suitable formula.

Assessment of the Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) scleral lens on visual acuity for corneal irregularity and ocular surface disease

PurposeTo describe changes in visual acuity in patients fit with the Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) with irregular corneas compared to those with ocular surface disease, as well as describe patient demographics and fitting indications for PROSE at an academic medical center. MethodsA retrospective chart review from 2010 to 2016 on a total of 825 eyes from 493 patients fitted with a PROSE lens, and grouped by etiology, either irregular cornea/dystrophy or ocular surface disease and associated sub-etiologies. We compared best corrected visual acuity (BCVA) before and after PROSE fitting. ResultsThe irregular cornea group (n = 262 eyes) included corneal scar (n = 57), dystrophy (n = 17), post-operative corneal irregularity (n = 70), and primary ectasia (n = 118). The OSD group included 563 eyes. For all etiologies combined, mean BCVA prior to PROSE fitting compared to after improved by 0.28 logMAR (p < .001). In the irregular cornea group, the mean BCVA improved by 0.46 logMAR (p < .001), while the improvement in BCVA for the OSD group was 0.20 logMAR (p < .001). All etiologies in the irregular cornea group demonstrated improvement in BCVA (p < .05) with the exception of post-PRK (n = 2). BCVA improvement was found for all sub-etiologies in the OSD subgroup (p < .05). ConclusionsPROSE treatment had a positive impact on visual acuity for a wide range of corneal irregularities and ocular surface disease, suggesting that PROSE lenses may offer improvements in visual acuity without risks inherent to surgery.

Comparison on dry eye symptom between scleral tunnel incision and transparent corneal incision in phacoemulsification

Objective To compare dry eye symptom between scleral tunnel incision and transparent corneal incision in phacoemulsification and IOL implantation. Methods The data of 200 eyes of 194 cases with cataract underwent phacoemulsification and intraocular lens implantation were collected. They were divided randomly into the transparent corneal incision group , 100 eyes of 98 cases, and scleral tunnel incision group, 100 eyes of 96 cases. The dry eye symptom and Schirmer I test (SⅠt) after surgery were compared between the two groups. Results The dry eye symptom scores of the two groups were increased and decreased after a period of time.The dry eye symptom scores of the two groups at 1, 7 and 14 days after surgery were significantly higher than those before operation (P 0.05). In scleral tunnel incision group the dry eye symptom scores at 1, 7 and 14 days after surgery were significantly higher than those in transparent corneal incision group (P<0.05). Postoperative SⅠt of two groups were firstly increased and then decreased, and two groups of corneal fluorescein staining scores were decreased after increased (P<0.01). In scleral tunnel incision group SⅠt scores at 1, 7, 14 and 30 days after surgery were significantly lower than those in the transparent corneal incision group (P<0.05). After surgery breakup time (BUT) of two groups were decreased at first and then increased (P<0.01). The BUT in scleral tunnel incision group was significantly higher than that of the transparent cornea group (P<0.01). Conclusion Through scleral tunnel incision phacoemulsification can effectively reduce the influence of stability of tear film in early postoperative period, but the symptom of dry eye is more severe than that with clear corneal incision. The dry eye symptom effect of two incisions is not obvious at the end of the follow-up time. Key words: Phacoemulsification; Lens, intraocular; Scleral tunnel incision; Transparent corneal incision; Dry eye

Ocular penetration of topically applied 1% tigecycline in a rabbit model.

To evaluate ocular penetration of topically applied 1% tigecycline. Forty-two New Zealand White rabbits were divided into 3 groups. A 50 µL drop of 1% tigecycline was administered in group 1. In groups 2 and 3, the drop was administered every 15min for 60min (keratitis protocol). Aqueous humor samples in groups 1 and 2 were collected under general anesthesia at 15, 30, 45, 60, 120, and 180min after the last drop. All animals in group 3 were euthanatized. Cornea, vitreous and blood samples were collected 60 and 120min after the last drop. Tigecycline concentrations were measured using high performance liquid chromatography-mass spectrometry (LC-MS/MS). The peak aqueous humor tigecycline concentration [mean 0.73±0.14 mg/L (SD) and 2.41±0.14 mg/L, respectively] occurred 45min after topical drug application in groups 1 and 2. Group 3 mean values in the cornea, and vitreous, were 3.27±0.50 µg/g, and 0.17±0.10 mg/L at 60min and 3.17±0.77 µg/g and 0.20±0.07 mg/L at 120min, respectively. Tigecycline serum concentrations were negligible. Tigecycline levels in the aqueous humor in groups 1 and 2, and in the cornea in group 3 exceeded the minimum inhibitory concentrations of most gram-positive organisms that cause bacterial keratitis and endophthalmitis.

Corneal endothelium and central corneal thickness changes in type 2 diabetes mellitus.

PurposeThis study was conducted to compare the corneal endothelial cell density (ECD), morphological features, and central corneal thickness (CCT) in type 2 diabetes mellitus (DM) with age-matched, nondiabetic control subjects using EM-3000 Specular Microscope.Study designThis was a prospective, hospital-based, nonrandomized, case–control, observational, and quantitative study.Subjects and methodsThe study included 57 patients (57 eyes) with type 2 DM and 45 control (nondiabetic) subjects (45 eyes). The corneal endothelial structure and CCT were examined in all eyes by noncontact specular microscopy using EM-3000 Specular Microscope. The endothelial structure was studied for ECD, coefficient of variation of cell area (CV), and percentage of hexagonal cells.ResultsThe study included 36 eyes without diabetic retinopathy (DR), 14 eyes with nonproliferative DR, and 7 eyes with proliferative DR. There were 26 eyes with a duration of ≤10 years and 31 eyes with a duration of >10 years. Also, there were 24 eyes with HbA1c ≤7.5% and 33 eyes with HbA1c >7.5%. ECD was significantly lower in the diabetic cornea than in control group (P=0.014). CV was higher in diabetic cornea (P=0.008). The diabetic cornea group had lower percentage of hexagonal cells than the control group, but the difference was not statistically significant (P=0.603). Also, diabetic cornea was thicker than control group, but not statistically significant (P=0.301).ConclusionThis study documented that type 2 DM causes a significant reduction of ECD and increased CV (polymegathism). Also, diabetic cornea has increased CCT and lower percentage of hexagonal cells than normal subjects, but without statistical significance.

New parameters in assessment of human donor corneal stroma.

To provide quantitative parameters for assessment of human donor corneal stroma by imaging stromal features of diseased and normal human corneas with full-field optical coherence microscopy (FFOCM), using confocal microscopy (CM) and histology as reference techniques. Bowman's layer (BL) thickness and keratocyte density were assessed exvivo in 23 human donor corneas and 27 human pathological corneas (keratoconus and other corneal disorders) with FFOCM, CM and histology. Stromal backscattering was assessed with FFOCM. Additionally, 10 normal human corneas were assessed invivo with CM. In FFOCM, the logarithm of the normalized stromal reflectivity was a linear function of stromal depth (R2 =0.95) in human donor corneas. Compared with keratoconus corneas, human donor corneas featured higher BL thickness (p=0.0014) with lower coefficient of variation (BL-COV; p=0.0002), and linear logarithmic stromal reflectivity with depth (higher R2 , p=0.0001). Compared with other corneal disorders, human donor corneas featured lower BL-COV (p=0.012) and higher R2 (p=0.0001). Using the 95% confidence limits of the human donor cornea group, BL thickness<6.5μm (sensitivity, 57%; specificity, 100%), BL-COV>18.6% (79%; 100%) and R2 <0.94 (93%; 71%) were revealed as indictors of abnormal cornea. In CM, keratocyte density decreased with stromal depth (r=-0.56). The mean overall keratocyte density (cells/mm2 ) was 205 in human donor corneas, 244 in keratoconus, 176 in other corneal disorders and 386 in normal corneas. Full-field optical coherence microscopy (FFOCM) provides precise and reliable parameters for non-invasive assessment of human donor corneal stroma during storage, enabling detection of stromal disorders that could impair the results of keratoplasty.

Effect of incision types for Artisan phakic intraocular lens implantation on ocular higher order aberrations.

To evaluate the effect of incision types for Artisan phakic intraocular lens (PIOL) implantation on ocular higher-order aberrations (HOAs). A retrospective review was conducted of the patients who had undergone Artisan PIOL implantation for the correction of myopia and followed up for at least 6mo. Patients are classified into 2 groups considering the incision type: cornea group with patients undergone clear corneal incision; sclera group with patients undergone sclera tunnel incision. All patients with postoperative astigmatism of under 1 diopter (D) were included to minimize the effect of residual astigmatism on postoperative HOAs. Visual acuity, special equivalents, astigmatism, predictability (±1 D from target refraction), HOAs (coma, trefoil, spherical aberration), and corneal endothelial counts were analyzed preoperatively and 6mo postoperatively. At the postoperative 6mo, all patients of both groups achieved uncorrected visual acuity of 16/20 or better, and significantly decreased the spherical equivalents compared with preoperative values. The predictability of refractive correction was 96% in the former, and 94% in the latter. Unlike the sclera group, preoperative astigmatism decreased significantly in cornea group at postoperative 6mo. The HOAs increased significantly at postoperative 6mo compared to the preoperative values in both groups, and the root mean square (RMS) total and trefoil wavefront aberration of cornea group were significantly higher than those of sclera group. Although corneal incision significantly reduces preexisting astigmatism, the postoperative 6mo of total RMS and trefoil aberration change may deteriorate the visual quality after Artisan PIOL implantation.

Corneal Resistance to Keratolysis After Collagen Crosslinking With Rose Bengal and Green Light.

The purpose of this study was to evaluate the resistance to degradation by collagenase A of corneas that have been crosslinked with Rose Bengal and green light (RGX). The ex vivo crosslinking procedure was performed on enucleated rabbit corneas. Corneas were deepithelialized after applying 30% alcohol. Corneas were stained with Rose Bengal (RB, 0.1%) for 2 minutes and then exposed to green light (532 nm) at 0.25 W/cm2 for times to deliver doses of 50, 100, 150, or 200 J/cm2 (n = 5 per group). Five corneas were pretreated with riboflavin solution (0.1% riboflavin) for 15 minutes and irradiated with ultraviolet A (UVA) light (370 nm, 3 mW/cm2) for 30 minutes. Five corneas underwent only de-epithelialization and were otherwise untreated. Five corneas were stained with RB without light exposure. The central corneas of each group was removed with a 8.5-mm trephine and incubated at 37°C in 0.3% collagenase A solution. Time to dissolution of each cornea was compared across treatments. Corneas treated with RGX were treated with light fluences of 50, 100, 150, and 200 J/cm2; these corneas dissolved completely at 8.3 ± 1.2, 11.1 ± 1.4, 12.4 ± 1.7, and 15.7 ± 1.8 hours, respectively. Corneas treated by riboflavin and UVA light dissolved at 15.7 ± 1.7 hours, and nontreated corneas dissolved at 6.1 ± 1.3 hours. Corneas treated with only RB (no green light) dissolved at 9.3 ± 1.7 hours. Compared with the untreated corneas, all of the RB groups and the riboflavin-UVA-treated group of corneas degraded statistically significantly slower than untreated corneas (P < 0.05). Crosslinking with RGX increased corneal resistance to digestion by collagenase comparable to that produced by riboflavin and UVA treatment.

Observation on ultrastructure and histopathology of cornea following femtosecond laser-assisted deep lamellar keratoplasty for acute corneal alkaline burns

To demonstrate the changes in ultrastructure and histopathology of the cornea in acute corneal alkaline burns after femtosecond laser-assisted deep lamellar keratoplasty. The New Zealand white rabbits treated with alkaline corneal burn were randomized into two groups, Group A (16 eyes) with femtosecond laser-assisted deep lamellar keratoplasty 24h after burn and Group B (16 eyes) without keratoplasty as controls. All eyes were evaluated with transmission electron microscopy (TEM) at 1, 2, 3, and 4wk follow-up, then all corneas were tested by hematoxylin and eosin staining histology. The corneal grafts in Group A were transparent, while those in Group B showed corneal stromal edema and loosely arranged collagen fibers. One week after treatment, TEM revealed the intercellular desmosomes in the epithelial layers and intact non-dissolving nuclei in Group A. At week 4, the center of the corneas in Group A was transparent with regularly arranged collagen fibers and fibroblasts in the stroma. In Group B, squamous cells were observed on the corneal surface and some epithelial cells were detached. Femtosecond laser-assisted deep lamellar keratoplasty can suppress inflammatory responses, prevent toxic substance-induced injury to the corneal endothelium and inner tissues with quicker recovery and better visual outcomes.

Two-Photon Fluorescence Microscopy for Determination of the Riboflavin Concentration in the Anterior Corneal Stroma When Using the Dresden Protocol.

To determine the riboflavin concentration gradient in the anterior corneal stroma when using the Dresden protocol with different dextran solutions. Three different groups of porcine corneas, five each, were compared regarding the riboflavin concentration in the anterior stroma. Before all experiments, stable hydration conditions were established for the corresponding solution. All groups were treated with 0.1% riboflavin in different dextran solutions (15%, 16%, 20%). After imbibition, two-photon microscopy was used to determine fluorescence intensity. For signal attenuation and concentration determination corneas were saturated and measured a second time by two-photon microscopy. Additionally, the distribution was calculated mathematically and compared to the empiric results. Riboflavin concentration is decreasing with depth for all dextran solutions. A nearly constant concentration could be determined over the first 75 μm. Analysis of the fit functions leads to diffusion coefficients of D = 2.97 × 10-7 cm2/s for the 15% dextran solution, D = 2.34 × 10-7 cm2/s for the 16% dextran solution, and D = 1.28 × 10-7 cm2/s for the 20% dextran solution. The riboflavin gradients of the 20% dextran group were statistically significantly different from 15% dextran starting at a depth of 220 μm and deeper (P = 0.047). The 16% dextran group differed statistically at a depth of 250 μm and deeper (P = 0.047). These results show a significant difference to those published previously. With correct settings two-photon microscopy is a precise way to determine the concentration of riboflavin in cornea. The measured gradient is excellently fit by a Gaussian distribution, which comes out as a solution of Fick's second law.

Absorption and distribution characteristics of terbinafine hydrochloride nanoemulsions in cornea after instillation

Background Nanoemulsions (NEs) is one of the most popular ophthalmic colloidal drug delivery system due to its long-term stability, low toxicity and irritancy, considerable capacity for solubilization of lipophilic drug molecules and great potential in bioavailability improvement.The cornea pathway is the main route of intraocular absorption after topical use of NEs.Though NEs possess numerous physiological and physicochemical advantages, the use of NEs cannot always obtain satisfactory results. Objective This study was to investigate the impacts of epithelium and stroma on the corneal permeation of topical ophthalmic terbinafine hydrochloride nanoemulsions (TH-NEs). Methods TH-NEs was prepared by the self-emulsification method.The size and Zeta potential of the oil droplets in the formulation were analyzed using a dynamic light-scattering particle size analyzer.The high performance liquid chromatography (HPLC) was used for the in vitro release study.Sixty New Zealand albino rabbits were randomly divided into intact cornea group and cornea epithelium debrided group.The cornea epithelium of the left eyes was debrided in the cornea epithelium debrided group.The TH-NEs were instilled into the lower conjunctival sac of left eyes.Six rabbits were executed from each group 15, 30, 60, 120 and 240 minutes after dosing, respectively.The corneas were collected and analyzed by HPLC.The fluorescein diacetate (FDA) was used to label the TH-NEs.Two C57BL/6 mice with left cornea epithelium debrided and 2 normal mice were used for the fluorescence tracing study.The fluorescence distribution of FDA labeled TH-NEs was observed by a two-photon laser confocal scanning microscope 30 minutes and 60 minutes after single instillation. Results The average size and Zeta potential of the oil droplets were 51.37 nm and -0.232 7 mV respectively, and 0.482% of encapsulated drugs was released from the TH-NEs after 12 hours.The peak concentrations of TH in the intact cornea and epithelium debrided cornea were (17.85±2.79)μg/g and (4.40±1.75)μg/g respectively, which occurred 15 minutes post-dose.The drug concentrations in the intact cornea were significantly higher than that in the debrided cornea 15, 30, 60 and 120 minutes after dosing, with significant differences between them (t=9.998, 8.658, 6.903, 7.576; all at P=0.000). The fluorescence was observed in the cornea epithelium when the cornea was intact.The fluorescence intensity in the superior layer of corneal epithelium was obviously higher than that in the deep layers of corneal epithelium 30 minutes and 60 minutes after dosing.No fluorescence was observed in the cornea stroma of both eyes. Conclusions The cornea epithelium is the main of absorption and distribution position of TH-NEs.The cornea stroma is the dominating permeation barrier for the intraocular transportation of the TH-NEs.The cornea stroma may stop the permeation of TH-NEs by molecular exclusion mechanism. Key words: Terbinafine hydrochloride; Nanoemulsions; Corneal epithelium; Corneal stroma; Tissue distribution

Pharmacokinetics of Meropenem for Use in Bacterial Keratitis.

To investigate the toxicity and corneal pharmacokinetics of meropenem as a potential antimicrobial for bacterial keratitis. Corneal epithelial cell and keratocyte toxicity was investigated using methyl thiazolyl tetrazolium (MTT) and LIVE/DEAD assays. The penetration of meropenem through the human cornea was measured using an artificial anterior chamber. In one group of corneas, the epithelial and endothelial layers were removed and in a second group these layers were left intact. We applied 50 μL (10 mg/mL) meropenem to the corneal surface and collected samples in the anterior chamber from 45 minutes up to 24 hours. Meropenem concentrations were estimated with a bioassay and HPLC. Meropenem had significantly higher cellular metabolic activity (MTT assay) at both 5 mg/mL and 2.5 mg/mL compared with moxifloxacin (P = 0.029 and P = 0.018, respectively), with 96% cell viability (LIVE/DEAD assay). The measured values for meropenem concentrations in corneal and aqueous samples were significantly higher using a bioassay than with HPLC (P = 0.004). For both intact and denuded corneas, the concentrations in the anterior chamber increased from 0.48 μg/mL (SD 0.89) and 0.89 μg/mL (SD 0.81) to 6.35 μg/mL (SD 0.81) and 13.48 μg/mL (SD 14.82) using HPLC, and from 0.68 μg/mL (SD 1.50) and 1.31 μg/mL (SD 1.55) to 47.03 μg/mL (SD 5.51) and 43.69 μg/mL (SD 27.22) measured with a bioassay. Meropenem has very low toxicity in vitro. It has good corneal penetration, achieving anterior chamber concentrations above MIC90 for bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, streptococci, coagulase-negative staphylococci, and the Enterobacteriaceae.

Measurement of Quantitative Viscoelasticity of Bovine Corneas Based on Lamb Wave Dispersion Properties

The viscoelastic properties of the human cornea can provide valuable information for clinical applications such as the early detection of corneal diseases, better management of corneal surgery and treatment and more accurate measurement of intra-ocular pressure. However, few techniques are capable of quantitatively and non-destructively assessing corneal biomechanics in vivo. The cornea can be regarded as a thin plate in which the vibration induced by an external vibrator propagates as a Lamb wave, the properties of which depend on the thickness and biomechanics of the tissue. In this study, pulses of ultrasound radiation force with a repetition frequency of 100 or 200 Hz were applied to the apex of corneas, and the linear-array transducer of a SonixRP system was used to track the tissue motion in the radial direction. Shear elasticity and viscosity were estimated from the phase velocities of the A0 Lamb waves. To assess the effectiveness of the method, some of the corneas were subjected to collagen cross-linking treatment, and the changes in mechanical properties were validated with a tensile test. The results indicated that the shear modulus was 137 ± 37 kPa and the shear viscosity was 3.01 ± 2.45 mPa·s for the group of untreated corneas and 1145 ± 267 kPa and was 0.16 ± 0.11 mPa·s for the treated group, respectively, implying a significant increase in elasticity and a significant decrease in viscosity after collagen cross-linking treatment. This result is in agreement with the results of the mechanical tensile test and with reports in the literature. This initial investigation illustrated the ability of this ultrasound-based method, which uses the velocity dispersion of low-frequency A0 Lamb waves, to quantitatively assess both the elasticity and viscosity of corneas. Future studies could discover ways to optimize this system and to determine the feasibility of using this method in clinical situations.