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The Bovine Corneal Opacity and Permeability test method (BCOP) is an in vitro test method that can be used to classify substances as 'ocular corrosives and severe irritants'. The BCOP uses isolated corneas from the eyes of cattle slaughtered for commercial purposes, thus avoiding the use of laboratory animals. Each treatment group (test substance, negative/positive controls) consists of a minimum of three eyes where the cornea has been excised and mounted to a holder. Depending on the physical nature and chemical characteristics of the test substance, different methods can be used for its application since the critical factor is ensuring that the test substance adequately covers the epithelial surface. Toxic effects to the cornea are measured as opacity and permeability, which when combined gives an In Vitro Irritancy Score (IVIS) for each treatment group. A substance that induces an IVIS superior or equal to 55.1 is defined as a corrosive or severe irritant.



1. Wavescan measurement.TopographyThe ability to measure the corneal front surface is an essential component of irregular corneal diagnosis and management. Taking measurements with a keratometer is insufficient, as it is limited to a 3mm to 4mm central zone and curvature measurement of two primary meridians. In addition, the mires of a keratometer are often unreadable as corneal irregularity worsens.

The gold standard for measuring front surface corneal irregularity is videokeratography or corneal topography. Corneal topographers are able to, in some cases, measure in excess of 10,000 data points across the entire corneal surface. A dioptric map of the corneal surface is the primary evaluative tool that a topographer offers the contact lens practitioner. Dioptric values are represented by a relative color-coded scheme. The clinician can use the resultant pattern to interpret, diagnose and classify the corneal irregularity.

There are two basic types of dioptric maps: sagittal and tangential. Sagittal maps, also called axial maps, are set up with algorithms that assume the cornea is spherical, which makes them less accurate for peripheral corneal evaluation and measurement. Tangential maps are based upon instant radius of curvature, making them inherently more accurate for diagnostic and lens fitting purposes.1

3. Oculus Pentacam.Some topographers are able to produce an elevation map of the cornea based on a reference sphere, which helps to predict areas of potential clearance or bearing for corneal GP lenses. In addition, many topographers have software that will allow the clinician to virtually fit a cornea GP lens based upon topographical results. Empirically fitting GP lenses this way has the potential to dramatically improve fitting efficiency. With this technology, the practitioner can virtually alter design parameters and observe how changes might affect the lens fit.

Each specific type of aberration can be mathematically represented by what is known as a Zernike polynomial. The common higher-order Zernike polynomials have names such as spherical, coma and trefoil. Typically, contact lens practitioners rely on GP or specialty soft contact lenses that are able to mask higher-order aberrations caused by front surface corneal irregularity.

Although most irregular corneal patients are able to achieve functional vision with these specialty lens designs, many of them will still have less than perfect visual acuity. Some patients, especially those with keratoconus, may complain of ghosting, halos and/or glare resulting from uncorrected back surface corneal irregularity that is not corrected for by their specialty lens.7,8

5. Bellin ambrosion BAD II ectasia.Optical Coherence TomographyOptical coherence tomography (OCT) is able to produce two-dimensional cross-sectional images of the anterior ocular surface. These high-resolution images allow for detailed analysis of the corneal layers. Diagnostically, this provides magnified visualization and biometric measurement. The OCT instruments being developed today have the ability to perform both anterior and posterior segment measures, which means that practitioners only need to purchase one instrument to gain two highly useful technologies. Examples of these combination systems include the Cirrus (Carl Zeiss Meditec), the RTVue (Optovue) and the 3D OCT (Topcon). Anterior segment OCT is still pending FDA approval. OCT imaging of the cornea and sclera has the potential to improve the evaluation and design of contact lenses (figure 2).17,18 Greg Gemoules, O.D., reported on nine patients that were successfully fit with scleral GP lenses utilizing sagittal depth and chord measurements obtained taken from a Visante OCT (Carl Zeiss Meditec).18

This technology is quite diverse in its clinical applications. Advantages include the ability to collect 360º imaging of the anterior segment, both anterior and posterior corneal elevation-based topography, global corneal pachymetry, anterior chamber analysis, anterior segment optical densitometry, IOL planning and contact lens design based on anterior segment tomography. As such, the applications are far reaching into areas of corneal analysis, cataract management, glaucoma analysis and IOL planning.

The most widely used application of Scheimpflug technology is the ability to detect corneal ectasia (figure 4). Due to the measurement of posterior corneal elevation and global pachymetry, abnormalities associated with ectasia are exquisitely detected, quantified and monitored. Specific software programs such as the Belin/Ambrosio II on Pentacam have the ability to clearly differentiate normal from ectatic corneas, thus allowing for earlier detection of ectasia and avoidance of performing keratorefractive procedures on patients who may be poor candidates (figure 5). Belin has recently utilized Pentacam to differentiate pellucid marginal degeneration from keratoconus with a pseudo-PMD anterior corneal topography through the analysis of global pachymetry.19

Advances in instrumentation have significantly improved the diagnostic and fitting success for irregular corneal management. Practitioners can utilize topography-based software that enables virtual contact lens fitting. Ultimately this can improve efficiency, especially for the novice contact lens practitioner.

Scheimpflug tomography allows for comprehensive corneal and anterior segment analysis with unique evaluation of the posterior corneal surface and global pachymetry, while aberrometry can quantify corneal irregularity. These measurements can then be used to add higher-order aberration control to contact lenses to improve visual outcomes. Ocular coherence tomography will improve design and fitting success for soft and scleral type lenses used for difficult cases.

Nonbite exposures. Nonbite exposures from animals very rarely cause rabies. However, occasional reports of nonbite transmission suggest that such exposures require assessment to determine if sufficient reasons exist to consider postexposure prophylaxis (104). The nonbite exposures of highest risk appear to be among surgical recipients of corneas, solid organs, and vascular tissue transplanted from patients who died of rabies and persons exposed to large amounts of aerosolized rabies virus. Two cases of rabies have been attributed to probable aerosol exposures in laboratories, and two cases of rabies have been attributed to possible airborne exposures in caves containing millions of free-tailed bats (Tadarida brasiliensis) in the Southwest. However, alternative infection routes can not be discounted (105--109). Similar airborne incidents have not occurred in approximately 25 years, probably because of elevated awareness of such risks resulting in increased use of appropriate preventive measures.

Human-to-Human Exposures. Human-to-human transmission can occur in the same way as animal-to-human transmission (i.e., the virus is introduced into fresh open cuts in skin or onto mucous membranes from saliva or other potentially infectious material such as neural tissue). Organ and tissue transplantation resulting in rabies transmission has occurred among 16 transplant recipients from corneas (n = eight), solid organs (n = seven), and vascular tissue (n = one). Each of the donors died of an illness compatible with or proven to be rabies (10,112--123). The 16 cases occurred in five countries: the United States (five cases: one corneal transplant transmission, three solid organ transmissions, and one vascular graft transmission), Germany (four cases), Thailand (two cases), India (two cases), Iran (two cases), and France (one case).

New parameters in assessment of human donor corneal stroma.Borderie M, Grieve K., Irsch K., Ghoubay D., Georgeon C., De Sousa C., Laroche L, Borderie VM. (2016) Acta Ophthalmologica, 95:297-306.

Fourier-domain optical coherence tomography imaging in corneal epithelial basement membrane dystrophy: a structural analysis.El Sanharawi, M., Sandali, O., Basli, E., Bouheraoua, N., Ameline, B., Goemaere, I., Georgeon, C., Hamiche, T., Borderie, V., and Laroche, L. (2015). Am J Ophthalmol 159, 755-763.

Full-field optical coherence tomography of human donor and pathological corneas.Ghouali, W., Grieve, K., Bellefqih, S., Sandali, O., Harms, F., Laroche, L., Paques, M., and Borderie, V. (2015). Curr Eye Res 40, 526-534.

Development of human corneal epithelium on organized fibrillated transparent collagen matrices synthesized at high concentration.Tidu, A., Ghoubay-Benallaoua, D., Lynch, B., Haye, B., Illoul, C., Allain, J.M., Borderie, V.M., and Mosser, G. (2015). Acta Biomater 22, 50-58.

Optical coherence tomography and confocal microscopy following three different protocols of corneal collagen-crosslinking in keratoconus.Bouheraoua N, Jouve L, El Sanharawi M, Sandali O, Temstet C, Loriaut P, Basli E, Borderie V, Laroche L.Invest Ophthalmol Vis Sci. 2014 Oct 28;55(11):7601-9. doi: 10.1167/iovs.14-15662 041b061a72

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