Biomechanical model of human cornea based on stromal microstructure

The optical characteristics of the human cornea depends on the mechanical balance between the intra-ocular pressure and intrinsic tissue stiffness. A wide range of ophthalmic surgical procedures alter corneal biomechanics to induce local or global curvature changes for the correction of visual acuity. Due to the large number of surgical interventions performed every day, a deeper understanding of corneal biomechanics is needed to improve the safety of these procedures and medical devices. The aim of this study is to propose a biomechanical model of the human cornea, based on stromal microstructure. The constitutive mechanical law includes collagen fiber distribution based on X-ray scattering analysis, collagen cross-linking, and fiber uncrimping. Our results showed that the proposed model reproduced inflation and extensiometry experimental data [Elsheikh et al., Curr. Eye Res., 2007; Elsheikh et al., Exp. Eye Res., 2008] successfully. The mechanical properties obtained for different age groups demonstrated an increase in collagen cross-linking for older specimens. In future work such a model could be used to simulate non-symmetric interventions, and provide better surgical planning.

Numerical model of the human cornea based on stromal microstructure: identification of mechanical properties for two age groups

The optical quality of the human eye mainly depends on the refractive performance of the cornea. The shape of the cornea is a mechanical balance between intraocular pressure and tissue intrinsic stiffness. Several surgical procedures in ophthalmology alter the biomechanics of the cornea to provoke local or global curvature changes for vision correction. Legitimated by the large number of surgical interventions performed every day, the demand for a deeper understanding of corneal biomechanics is rising to improve the safety of procedures and medical devices. The aim of our work is to propose a numerical model of corneal biomechanics, based on the stromal microstructure. Our novel anisotropic constitutive material law features a probabilistic weighting approach to model collagen fiber distribution as observed on human cornea by Xray scattering analysis (Aghamohammadzadeh et. al., Structure, February 2004). Furthermore, collagen cross-linking was explicitly included in the strain energy function. Results showed that the proposed model is able to successfully reproduce both inflation and extensiometry experimental data (Elsheikh et. al., Curr Eye Res, 2007; Elsheikh et. al., Exp Eye Res, May 2008). In addition, the mechanical properties calculated for patients of different age groups (Group A: 65-79 years; Group B: 80-95 years) demonstrate an increased collagen cross-linking, and a decrease in collagen fiber elasticity from younger to older specimen. These findings correspond to what is known about maturing fibrous biological tissue. Since the presented model can handle different loading situations and includes the anisotropic distribution of collagen fibers, it has the potential to simulate clinical procedures involving nonsymmetrical tissue interventions. In the future, such mechanical model can be used to improve surgical planning and the design of next generation ophthalmic devices.

Pressure-cornea-vascular index (PCVI) for predicting disease progression in normal tension glaucoma

It has been shown that the pressure-to-cornea index (PCI), which estimates the relative effects of intraocular pressure (IOP) and central corneal thickness (CCT), may differentiate between glaucoma and non-glaucoma states. The authors investigated the utility of the pressure-cornea-vascular index (PCVI) in predicting field-progression in patients with normal tension glaucoma (NTG).

The ocular pulse amplitude at different intraocular pressure: a prospective study

To investigate changes in ocular pulse amplitude (OPA) during a short-term increase in intraocular pressure (IOP) and to assess possible influences of biometrical properties of the eye, including central corneal thickness (CCT) and axial length.

Conjunctival Proliferation After a Mild Pepper Spray Injury in a Young Child

PURPOSE To report a case of conjunctival proliferation in a 2.5-year-old boy after initial evidence of a mild chemical injury after ocular exposure to pepper spray (oleoresin capsicum). METHODS Case report with ophthalmologic and histologic findings. RESULTS A child presented with mild conjunctival injection and chemosis without any corneal erosion after direct exposure to pepper spray. Three weeks later, a significant conjunctival proliferation was found at the limbus, which was refractory to treatment with topical corticosteroids. Finally, proliferative tissue was surgically excised without clinical recurrence during 2 months of follow-up. CONCLUSIONS We hypothesize that the young age of the patient may have been an important factor for the severe conjunctival proliferation in comparison to a mainly uncomplicated course of pepper spray injuries in most adults. We recommend the use of topical antiinflammatory treatment even in apparently mild pepper spray injuries, especially in young children.

Ocular penetration of caspofungin in a rabbit uveitis model

BACKGROUND: Little is known about the ocular penetration of echinocandin antifungals. We studied the ocular distribution of systemically administered caspofungin in a rabbit uveitis model. METHODS: Caspofungin (1 mg/kg per day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 days starting 24 h after induction of unilateral uveitis by intravitreal endotoxin injection. Caspofungin concentrations were determined by high-performance liquid chromatography in the cornea, aqueous humor, vitreous humor, and serum 4, 8, 16, and 24 h after administration of a single dose and 24 h after the last of seven doses. RESULTS: The mean caspofungin concentration in the aqueous of the inflamed eye 4 and 8 h after single-dose administration was 1.30 +/- 0.39 mug/ml and 1.12 +/- 0.34 mug/ml, respectively. Drug concentrations decreased to 0.24 +/- 0.09 mug/ml at 16 h and 0.26 +/- 0.14 mug/ml at 24 h. In the vitreous of inflamed eyes drug levels were undetectable at all time points. No drug was found in the aqueous of inflamed eyes 24 h after the last of seven repeated doses, and the vitreous only contained trace amounts. In the corneas of inflamed eyes concentrations reached 1.64 +/- 0.48 mug/g at 4 h, peaked at 2.16 +/- 1.14 mug/g at 8 h, and declined to 1.87 +/- 0.52 mug/g and 1.49 +/- 0.48 mug/g at 16 and 24 h, respectively. After repeated dosing, corneal concentrations of caspofungin were 0.8 and 1.0 mug/g and below the limit of detection in two of four animals. In non-inflamed eyes no drug was detectable in the aqueous and vitreous humor, and the corneas at any time point. CONCLUSIONS: In our model, caspofungin reached therapeutically relevant levels in the aqueous and cornea but not in the vitreous humor of inflamed eyes. Intraocular drug deposition was critically dependent on a disrupted blood-eye barrier. These findings suggest a limited role for caspofungin in the treatment of fungal endophthalmitis.

Combined pars plana phacofragmentation, vitrectomy, and Artisan lens implantation for traumatic subluxated cataracts

PURPOSE: To report on the outcome of combined pars plana phacofragmentation, vitrectomy, and Artisan lens implantation in the management of subluxated cataracts. METHODS: This prospective, interventional, nonrandomized case series included nine eyes of seven consecutive adult patients with traumatic lens subluxation. Pre- and postoperative data (complete manifest refraction, best spectacle-corrected visual acuity, slit-lamp examination findings, intraocular pressure, fundus status, numerical density of endothelial cells, corneal thickness, and complications) were collected prospectively for all patients. RESULTS: After a median postoperative follow-up of 12 months (range, 8-18 months), a mean spherical equivalent of -0.50 +/- 0.87 diopter (range, +1 to -1.50 diopter) was achieved. The mean logarithm of the minimum angle of resolution visual acuity improved from 1 (preoperatively) to 0.1 (postoperatively) (P = 0.007, Wilcoxon test). Median endothelial cell losses of 15 +/- 8% (P = 0.008) and 14 +/- 16% (P = 0.011) were registered at follow-ups of 1 month and 12 months, respectively. Postoperative complications included chronic intraocular inflammation and superior corectopia. CONCLUSIONS: Our procedure appears to be a safe, accurate, stable, and efficacious option for the management of traumatic subluxated cataracts in adults. However, longer-term data are needed to evaluate the corneal endothelium.

Fabry's disease: otoneurologic findings in twelve members of one family

Fabry's disease corresponds to an inherited disorder transmitted by an X-linked recessive gene. It generates a dysfunction of glycosphingolipid metabolism due to an enzymatic deficiency of alpha-galactosidase activity, resulting in glycosphingolipid deposits in all areas of the body. The clinical (heart, kidney, and central nervous system) manifestations are more severe in hemizygous boys than in heterozygous girls. They appear during childhood or adolescence: acroparesthesia, joint pain, angiokeratoma, corneal dystrophy, hypohydrosis or anhydrosis, and renal failure. The otoneurologic symptoms consist of hearing fluctuation, progressive unilateral or bilateral hearing loss, and episodes of vertigo or dizziness. Otoneurologic findings in 12 of 26 members of the same family are presented: the mother and 9 of her 12 children, as well as 2 of her 14 grandchildren: 4 healthy persons, 4 heterozygous female carriers, and 4 hemizygous male patients. Three of the male patients had fluctuation of hearing, sudden hearing loss, and episodes of vertigo and dizziness. The otoneurologic examinations showed a bilateral cochleovestibular deficit (n = 1), a right cochleovestibular deficit (n = 1), and a bilateral hearing loss combined with a right vestibular deficit (n = 1). Histopathologic evidence of glycosphingolipid accumulation in vascular endothelial and ganglion cells, as well as atrophy of the stria and spiral ligament, might explain the otoneurologic symptoms and findings.

Ocular pulse amplitude in healthy subjects as measured by dynamic contour tonometry

OBJECTIVES: To test whether dynamic contour tonometry yields ocular pulse amplitude (OPA) measurements that are independent of corneal thickness and curvature, and to assess variables of observer agreement. METHODS: In a multivariate cluster analysis on 223 eyes, the relationship between central corneal thickness, corneal curvature, axial length, anterior chamber depth, intraocular pressure, sex, age, and OPA measurements was assessed. Intraobserver and interobserver variabilities were calculated from repeated measurements obtained from 8 volunteers by 4 observers. RESULTS: The OPA readings were not affected by central corneal thickness (P = .08), corneal curvature (P = .47), anterior chamber depth (P = .80), age (P = .60), or sex (P = .73). There was a positive correlation between OPA and intraocular pressure (0.12 mm Hg/1 mm Hg of intraocular pressure; P<.001) and a negative correlation between OPA and axial length (0.27 mm Hg/1 mm of length; P<.001). Intraobserver and interobserver variabilities were 0.08 and 0.02 mm Hg, respectively, and the intraclass correlation coefficient was 0.89. CONCLUSIONS: The OPA readings obtained with dynamic contour tonometry in healthy subjects are not influenced by the structure of the anterior segment of the eye but are affected by intraocular pressure and axial length. We found a high amount of agreement within and between observers.

Detection of surfactant proteins A and D in human tear fluid and the human lacrimal system

PURPOSE: To evaluate the expression and presence of surfactant protein (SP) A and SP-D in the lacrimal apparatus, at the ocular surface, and in tears in healthy and pathologic states. METHODS: Expression of mRNA for SP-A and SP-D was analyzed by RT-PCR in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal ducts as well as in a spontaneously immortalized conjunctival epithelial cell line (HCjE; IOBA-NHC) and a SV40-transfected cornea epithelial cell line (HCE). Deposition of SP-A and SP-D was determined by Western blot, dot blot, and immunohistochemistry in healthy tissues, in tears, aqueous humor, and in sections of different corneal abnormalities (keratoconus, herpetic keratitis, and Staphylococcus aureus-based ulceration). Cell lines were stimulated with different cytokines and bacterial components and were analyzed for the production of SP-A and SP-D by immunohistochemistry. RESULTS: The presence of SP-A and SP-D on mRNA and protein levels was evidenced in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal duct samples. Moreover, both proteins were present in tears but were absent in aqueous humor. Immunohistochemistry revealed the production of both peptides by acinar epithelial cells of the lacrimal gland and epithelial cells of the conjunctiva and nasolacrimal ducts, whereas goblet cells revealed no reactivity. Healthy cornea revealed weak reactivity on epithelial surface cells only. In contrast, SP-A and SP-D revealed strong reactivity in patients with herpetic keratitis and corneal ulceration surrounding lesions and in several immigrated defense cells. Reactivity in corneal epithelium and endothelium was also seen in patients with keratoconus. Cell culture experiments revealed that SP-A and SP-D are produced by both epithelial cell lines without and after stimulation with cytokines and bacterial components. CONCLUSIONS: These results show that SP-A, in addition to SP-D, is a peptide of the tear film. Based on the known direct and indirect antimicrobial effects of collectins, the surfactant-associated proteins A and D seem to be involved in several ocular surface diseases.

Comparison of performance and patient satisfaction of two types of ERG electrodes

BACKGROUND: An age-controlled comparison concerning patient satisfaction and electrical performance of microfibres (DTL) and rigid contact lens (Henkes) corneal ERG electrodes was carried out. METHODS: 36 test persons underwent complete ophthalmological examination and were equally distributed into 3 age groups. Electroretinograms were recorded according to ISCEV standards. Randomly, in one eye a Henkes electrode was used and in the other eye a DTL electrode. Amplitudes of a- and b-waves and implicit times were measured and compared for the two electrode types. RESULTS: 34 of 36 test persons preferred DTL electrodes. Electrical performance concerning b-wave amplitudes was comparable. Statistically significant differences were detected only for scotopic combined cone-rod stimulation in the age groups 20 - 40 and 41 - 60 years between the different electrodes. Other recordings did not show differences. A statistically significant reduction of signal amplitudes with age was detected for scotopic isolated rod signals and combined cone-rod signals. Significance level was p < 0.05. No conjunctival or corneal erosions were found after ERG recordings for either electrode. CONCLUSIONS: Electrical performance is comparable between electrodes. For scotopic stimulations age was a significant influencing factor for signal amplitude and should be respected for normative values. DTL electrodes were preferred by the vast majority of patients. No adverse clinical effects were observed for either electrode. DTL electrodes should be preferred due to hygienic reasons (single use) and patient comfort.

Novel pressure-to-cornea index in glaucoma

BACKGROUND: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.

Noninvasive determination of intraocular pressure (IOP) in nonsedated mice of 5 different inbred strains

BACKGROUND: Noninvasive intraocular pressure (IOP) measurement in mice is critically important for understanding the pathophysiology of glaucoma. Rebound tonometry is one of the methods that can be used for obtaining such measurements. We evaluated the ability of the rebound tonometer (RT) to determine IOP differences among various mouse strains and whether differences in corneal thickness may affect IOP measurements in these animals. MATERIALS AND METHODS: Five different commonly used mouse strains (BALB/C, CBA/CAHN, AKR/J, CBA/J, and 129P3/J) were used. IOP was measured in eyes from 12 nonsedated animals (6 male and 6 female) from each strain at 2 to 3 months of age using the RT. IOPs were measured in all animals, on 2 different days between 10 AM and 12 PM. Subsequently, a number of eyes from each strain were cannulated to provide a calibration curve specific for that strain. Tonometer readings for all strains were converted to apparent IOP values using the calibration data obtained from the calibration curve of the respective strain. For comparison purposes, IOP values were also obtained using the C57BL/6 calibration data previously reported. IOP for the 5 strains, male and female animals, and the different occasion of measurement were compared using repeat measures analysis of variance. The central corneal thickness (CCT) of another group of 8 male animals from each of the 5 strains was also measured using an optical low coherence reflectometry (OLCR) pachymeter modified for use with mice. CCT values were correlated to mean IOPs of male animals and to the slopes and intercept of individual strain calibration curves. RESULTS: Noninvasive IOP measurements confirm that the BALB/C strain has lower and the CBA/CAHN has higher relative IOPs than other mouse strains while the AKR/J, the CBA/J, and the 129P3/J strains have intermediate IOPs. There is a very good correlation of apparent IOP values obtained by RT with previously reported true IOPs obtained by cannulation. There was a small but statistically significant difference in IOP between male and female animals in 2 strains (129P3/J and AKR/J) with female mice having higher relative IOPs. No correlation between CCT and IOP was detected. CCT did not correlate with any of the constants describing the calibration curves in the various strains. CONCLUSIONS: Noninvasive IOP measurement in mice using the RT can be used to help elucidate IOP phenotype, after prior calibration of the tonometer. CCT has no effect on mouse IOP measurements using the RT.

[Positive ibopamine provocative test in normal-tension glaucoma suspects]

BACKGROUND: Ibopamine is an alpha-adrenergic agent and causes an elevation of intraocular pressure in eyes with increased outflow resistance. It has been proposed as a test substance for the detection of early ocular hydrodynamic disorders. PATIENTS AND METHODS: A total of 64 normal-tension glaucoma suspect eyes without anti-hypertensive treatment were enrolled. A daily pressure curve was registered with measurements at 7:00 am, 8:00 am, 12:00 am, 17:00 pm using an applanation tonometer and a contour tonometer followed by instillation of ibopamine 2% in both eyes. Tonometry was performed every 15 minutes during the following hour. An IOP increase of > 2.0 mmHg was considered positive. RESULTS: The positive test group showed a significant pressure increase from 18.04 to 22.06 mmHg. Ocular pulse amplitude increased from 2.96 to 3.97 mmHg and was positively correlated with the pressure. Intraocular pressure was unchanged in the negative test group. Central corneal thickness was not significantly different in the two groups (p = 0.32). CONCLUSIONS: Ibopamine 2% eye drops have a positive pressure effect in 50% of suspected normal-tension glaucoma eyes and may differentiate between eyes with normal trabecular outflow capacity and eyes with increased resistance in the trabecular meshwork that are prone to pressure peaks and deterioration to glaucoma.

Topical caspofungin for treatment of keratitis caused by Candida albicans in a rabbit model

Candida albicans is the most frequent cause of fungal keratitis in temperate regions. Caspofungin has potent activity against Candida spp. in a variety of clinical settings. Little is known, however, about its activity against fungal keratitis. We compared the efficacy of topical caspofungin with that of topical amphotericin B (AMB) in a rabbit model of experimental keratomycosis. Keratitis was induced with a standardized inoculum of Candida albicans (SC 5314) placed on the debrided cornea. Twenty-four hours after infection, animals were randomly assigned to treatment with 0.15% caspofungin, 0.5% caspofungin, 0.15% AMB, and a saline control (n = 12 rabbits in each group). For the first 12 h, treatment was repeated every 30 min and, after a 12-h pause, was resumed at hourly intervals for another 12 h. The animals were examined and killed 12 h after administration of the last dose. Treatment effects were evaluated by clinical assessment, fungal culture, and histopathology. Drug treatment significantly reduced corneal fungal recovery from 3.78 log10 CFU in saline-treated animals to 2.97, 1.76, and 1.18 log10 CFU in animals treated with 0.15% caspofungin, 0.5% caspofungin, and 0.15% AMB, respectively. By histopathology, the mean hyphal density was significantly lower in the corneas of treated animals than in those of the controls; there was no difference in hyphal densities between the different treatment groups. The depth of corneal invasion was not significantly reduced by the antifungal treatments. By clinical assessment, keratitis progressed in animals treated with saline, whereas disease progression was inhibited by all drug treatment regimens. In our rabbit model, 0.5% caspofungin was as effective as 0.15% AMB for the topical treatment of Candida keratitis. The potential clinical efficacy of caspofungin awaits further investigation.