Down syndrome and the eye: Ocular characteristics and ocular assessment.

The trisomy of chromosome 21, the smallest autosome, is associated with significant systemic manifestations in addition to intellectual disability. The triplication of this chromosome, known as Down syndrome (DS) is also associated with several manifestations in the eye, and ocular adnexae. People with DS have a variety of ophthalmic conditions, some of which require intervention. The variable systemic and ophthalmic presentations in DS can make the delivery of eye care challenging. We highlight common ophthalmic presentations in people with DS, as well as the practical implications of delivering eye examinations for this complex needs population. We aim to aid clinicians involved in the ophthalmic care of people with DS in both clinical and research settings.

Iris reconstruction: A perspective on the modern surgical armamentarium.

The surgical reconstruction of eyes with iris defects is almost invariably complex and challenging. A number of prosthetic iris devices are available including large-incision, rigid diaphragm, aniridic intraocular lens style devices, small-incision devices incorporating a capsular ring, and flexible, customized, small-incision iris prostheses. The surgical techniques for rehabilitation are dictated by the configuration of the iris defect, the presence of concurrent ocular pathology, and the functional complaint of the patient. Successful rehabilitation requires careful surgical planning and appropriate patient selection. Nonetheless, endowed with the modern surgical armamentarium, the reconstructive surgeon may achieve significant functional and cosmetic improvement.

The Sheep Cornea: Structural and Clinical Characteristics.

PURPOSE: The aim of this study was to perform qualitative and quantitative analyses to characterize the corneas of young, healthy sheep. MATERIALS AND METHODS: Eight healthy male sheep, 10 months to 1 year of age, were included as experimental subjects. Central corneal thickness was measured using a handheld pachymeter, and an Easygraph corneal topographer provided topographic maps. Microstructural imaging of corneal layers was achieved by using the Heidelberg Retina Tomograph III Rostock Corneal Module in vivo corneal microscope (IVCM). An Ocular Response Analyzer (ORA) provided quantitative measurements of intraocular pressure (IOP), corneal hysteresis (CH), and corneal resistance factor. Tissue histology and immunohistochemistry were carried out to obtain detail on the corneal layers. RESULTS: Light microscopy and immunohistochemical labeling revealed a stratified epithelium, a limbus with numerous limbal crypts, a thick basement membrane, a thin Bowman's layer, a thick corneal stroma with a dense population of keratocytes, and a thick, hyper-reflective Descemet's membrane. Using IVCM, the cell density of the basal layer was noted to be significantly higher than that of other epithelial cell types. The density of keratocytes was significantly higher (P value = 0.0223) in the anterior compared to the posterior stroma. The endothelial cells were organized in a characteristic honeycomb pattern. The mean and standard deviation values for central corneal pachymetry were 623.14 ± 19.5 µm and 616.37 ± 34.87 µm for the left and right eyes, respectively. ORA-derived mean values for IOPcc and CH for the left and right eyes were 14.93 ± 1.73 mm Hg and 15.16 ± 2.02 mm Hg and 3.56 ± 0.72 mm Hg and 3.73 ± 0.49 mm Hg, respectively. CONCLUSIONS: The anatomical and clinical characteristics of the sheep cornea, as outlined in this study, make the sheep a suitable and relevant model for corneal research. This study provides researchers with important data on the suitability of sheep as a model for ophthalmic experiments.

Evolution of Keratoconus: From Diagnosis to Therapeutics.

This review describes the evolution of the diagnosis and treatment of keratoconus from the earliest written description to present day. The first description was provided in 1736 by Benedict Duddell who described the prominent corneas of a fourteen-year-old boy. Throughout the 19th century, a variety of surgical procedures were proposed to manage the disease, such as surgically repositioning the pupil away from the cone, iris incarceration to produce a slit-like pupil, cauterization of the cone to produce a scar, and full thickness elliptical excision of the cone. Despite the ingenuity of these procedures, many led to serious complications. In 1936, Ramon Castroviejo revolutionized surgical management by performing the first corneal transplant for keratoconus. The advent of refractive surgery in the 1990s brought about a sudden and critical need for better understanding of keratoconus and corneal ectatic disease. Topographic analysis allowed for earlier detection of keratoconus, prior to clinical signs and symptoms. Tomographic analysis provided analysis of the anterior and posterior surfaces of the cornea and allowed for even earlier detection. The Belin/Ambrosio Enhanced Ectasia Display on the Pentacam incorporates anterior and posterior elevation, pachymetric map, best fit sphere and enhanced reference surface to provide an overall "D" value that is predictive of ectatic disease. This display allows refractive providers to quickly and accurately screen potential refractive surgery candidates to identify those at risk for ectasia and early subclinical keratoconus. Corneal crosslinking was revolutionary in the treatment of keratoconus. There have been several randomized controlled trials that have found it to be safe and effective to halt ectatic progression. Crosslinking was recently approved by the FDA for progressive keratoconus. Currently, there is no clear definition of ectasia progression. Providers must be able to clearly, objectively and consistently diagnose progressive disease to institute timely treatment in the population with the greatest potential benefit. The new Belin ABCD grading system and progression analysis incorporated into the Oculus Pentacam software provides an objective way of assessing progression over time. Keratoconus diagnosis and management have grown tremendously since the first description in 1736, but there is still much to learn about keratoconus and its management.

Sphere-forming cells from peripheral cornea demonstrate the ability to repopulate the ocular surface.

BACKGROUND: The limbus forms the outer rim of the cornea at the corneoscleral junction and harbours a population of stem cells for corneal maintenance. Injuries to the limbus, through disease or accidents such as chemical injuries or burns, may lead to significant visual impairment due to depletion of the native stem cells of the tissue. METHODS: Sphere-forming cells were isolated from peripheral cornea for potential use as transplantable elements for limbal stem cell repopulation and limbal reconstruction. Immunocytochemistry, live cell imaging and quantitative PCR were used to characterize spheres and elucidate activity post implantation into human cadaveric corneal tissue. RESULTS: Spheres stained positively for stem cell markers ∆NP63α, ABCG2 and ABCB5 as well as the basal limbal marker and putative niche marker, notch 1. In addition, spheres also stained positively for markers of corneal cells, vimentin, keratin 3, keratocan and laminin, indicating a heterogeneous mix of stromal and epithelial-origin cells. Upon implantation into decellularized corneoscleral tissue, 3D, polarized and radially orientated cell migration with cell proliferation was observed. Cells migrated out from the spheres and repopulated the entire corneal surface over 14 days. Post-implantation analysis revealed qualitative evidence of stem, stromal and epithelial cell markers while quantitative PCR showed a quantitative reduction in keratocan and laminin expression indicative of an enhanced progenitor cell response. Proliferation, quantified by PCNA expression, significantly increased at 4 days subsequently followed by a decrease at day 7 post implantation. CONCLUSION: These observations suggest great promise for the potential of peripheral corneal spheres as transplantable units for corneal repair, targeting ocular surface regeneration and stem cell repopulation.