Intricate homeostasis maintains the rich complexity and functionality of the ocular surface. Severe ocular surface diseases cause significant morbidities, including blindness. Ocular surface reconstruction strategies restore this homeostasis. Patients with limbal deficiency may benefit from limbal stem cell transplantation to alleviate persistent epithelial defects, maintain conjunctivalization regression and corneal avascularity, and restore vision. Amniotic membrane and other substrates function as tissue surrogates and substrates for expansion of stem cells. Maximum graft survivability necessitates aggressive and comprehensive preoperative management of inflammation, infection, microtrauma, dry eye conditions and HLA compatibility. Restoration of lacrimal gland function is important, as is implementation of aggressive immunosuppression. Future advancements in stem cell biology, tissue engineering, bioartificial microsystems or regenerative medicine will supplement the therapeutic armamentarium. The next decade will be an exciting time for corneal surgeons.
Introduction 1.1 The ocular surface -anatomy and pathologyThe corneal epithelium, conjunctival epithelium, and the lacrimal system constitute the ocular surface.A healthy corneal epithelium is essential for corneal health and visual function.The corneal epithelium is a 5-to 6-cell-thick layer that provides a defensive barrier against pathologic organisms.It exists in a dynamic equilibrium, with superficial cells being constantly shed into the tear film.Populations of pluripotent stem cells reside in the palisades of Vogt at the human corneoscleral limbus and generate transient amplified cells that centripetally migrate toward the central cornea.These transient amplified cells undergo terminal differentiation into epithelial cells and repopulate the corneal epithelium, i.e. the XYZ hypothesis (Thoft et al., 1983).Severe ocular surface disorders, such as infection, keratoconjunctivitis sicca, Stevens-Johnson syndrome, ocular cicatricial pemphigoid or chemical/thermal injuries, can progress to corneal scarring, conjunctivalization, neovascularization, or stromal melts.Depletion of the limbal stem cells may follow, resulting in impaired vision or eventual corneal blindness.According to the World Health Organization, corneal disorders, e.g.trachoma or onchocerciasis, constitute a significant cause of loss of vision and blindness in the world (Thylefors et al., 1995).The conjunctiva is a thin, transparent, mucus membrane, overlying a thin vascular stroma.It is divided into three geographic zones: bulbar, forniceal, and palpebral.The conjunctival nonkeratinized stratified epithelium contains mucin-producing goblet cells, which are important for tear film stability.Additionally, the conjunctiva participates in the ocular surface antimicrobial defense via the conjunctiva-associated lymphoid tissue, as well as secretory antimicrobial peptides, such as defensins (Haynes et al., 1999).Disorders of the conjunctiva include elastotic changes, fibrovascular proliferation, malignancies, and autoimmune conditions such as Stevens-Johnson syndrome or cicatricial pemphigoid.Complications include dysfunctional tear syndrome, keratinization, symblepharon formation, eyelid disfigurement, and eyelash misalignment.Patient discomfort, cosmetic imperfection, increased risk of infection, and visual impairment are some notable concerns.A normal tear film is essential for maintenance of the corneal and conjunctival epithelia.Composed of three layers, mucin, aqueous and lipid layers, the human tripartite tear film has antimicrobial, epitheliotrophic, mechanical, and optical properties.A wide range of physiologic or pathologic conditions, such as biologic aging, hormonal changes, chemical or thermal injuries, chronic inflammation, or autoimmune disorders, may disrupt the tear film and trigger a deleterious cascade, injuring ocular surface epithelia.Furthermore, suboptimal www.intechopen.comProgress in Molecular and Environmental Bioengineering -From Analysis and Modeling to Technology Applications 292 lacrimal functions may result in poor surgical outcomes, especially after penetrating keratoplasty or limbal stem cell transplantation.Traditionally, the eyelids and lacrimal gland were excluded from the definition of the ocular surface.It is evident that visual function and epithelial health would not be feasible without these structures.The eyelids are essential for ocular surface protection and tear film maintenance.Untreated eyelid deformities, lid malpositions, or eyelash misalignments can precipitate detrimental consequences to the integrity and function of the ocular surface epithelia.Thus, a functional ocular surface requires structurally and functionally intact eyelids and lacrimal gland. Ocular surface reconstitutionIn severe ocular surface disorders, the management strategies entail symptomatic relief, reconstitution of the anatomic and physiologic ocular surface, and treatment and prevention of recurrence of the causative condition.Here we will discuss strategies to restore the conjunctival epithelium, corneal epithelium, and lacrimal function.Figure 1 illustrates the management strategies.Injury or inflammation causes severe ocular surface disorder with conjunctival scarring, limbal stem cell deficiency, corneal opacity with neovascularization, lacrimal dysfunction, disorganized lashes, and lid malposition (a).Mainstay treatment options include antibiotics, anti-inflammatory agents, lubrication, and amniotic membrane transplantation, as well as removal of lashes and correction of lid changes (b).As progress is made in science and tissue bioengineering, tissue replacement and regeneration may be feasible to restore the ocular surface and vision (c). Conjunctival tissue reconstitution 2.1.1 Suppression of cicatricial changesCommonly, ocular surface diseases limited to the conjunctiva progress to excessive cicatricial changes and loss of normal epithelial anatomy.Cicatricial changes to the conjunctival epithelium generally result from poorly controlled fibroblastic activities, e.g.tissue injuries or persistent inflammation.In addition to disrupting the tear film, cicatricialization of the conjunctiva has important implications in glaucoma surgeries, where availablility of healthy conjunctiva is essential for good surgical outcomes.A widely adopted therapeutic strategy is pharmacologic suppression of the inflammatory cascade and the fibroblast activation pathway using corticosteroids and antimetabolites.Recently, research efforts have been directed toward transforming growth factor beta (TGF-) and its involvement in fibroblast proliferation.TGF-is a multifunctional cytokine, which plays an important role in tissue repair and regeneration.After injury, TGF-triggers a complex cascade involving monocyte and leukocyte chemotaxis, induction of angiogenesis, control of production of cytokines and inflammatory mediators, deposition of extracellular matrix materials, and prevention of their enzymatic degradation (Border & Ruoslahti, 1992; Massagué et al., 1992).Excessive TGF-activity has been associated with exuberant fibrotic changes in the eye and other organs.In a murine model, TGF-was associated with formation of granulation tissue (Roberts et al., 1986) and increased inflammatory cell activity, as well as with exuberant extracellular collagen type-III deposition (Siriwardena et al., 1999).Using immunohistochemistry, Razzaque et al (2003) found increased accumulations of type-I and type III collagens and heat shock protein 47, a collagen-binding protein in fibrotic conjunctiva of patients with ocular cicatricial pemphigoid compared to normal subjects.Up-regulation of these proteins was also detected when ex-vivo www.intechopen.com
We demonstrate seamless direct integration of a semiconductor nanowire grown using a bottom-up approach to obtain a vertical field-effect transistor (VFET). We first synthesize single crystalline semiconductor indium oxide (In2O3) nanowires projecting vertically and uniformly on a nonconducting optical sapphire substrate. Direct electrical contact to the nanowires is uniquely provided by a self-assembled underlying In2O3 buffer layer formed in-situ during the nanowire growth. A controlled time-resolved growth study reveals dynamic simultaneous nucleation and epitaxial growth events, driven by two competitive growth mechanisms. Based on the nanowire-integrated platform, a depletion mode n-channel VFET with an In2O3 nanowire constituting the active channel is fabricated. Our unique vertical device architecture could potentially lead to tera-level ultrahigh-density nanoscale electronic, and optoelectronic devices.
Inorganic single crystal nanowires and nanowalls which exhibit rich growth morphogenesis are shown. More specifically, these were grown on lattice-matched substrates, which facilitate their specific growth directions with respect to the substrates' planes. Structural and optical characterizations suggest high single crystallinity of these nanostructures and possible applications in nano-optoelectronics are discussed.
To measure the correlation between subjective symptom score, conventional clinical tests, and Fourier-domain optical coherence tomography (FD-OCT) of lower tear meniscus parameters in patients with dry eye disease.Eighteen patients with dry eye disease requiring medical therapy and/or punctal occlusion were recruited for this prospective, nonrandomized, observational case series. Severity of symptoms of dry eye disease was assessed using the Indiana University Dry Eye Questionnaire 2002. Clinical assessments were completed using slit-lamp biomicroscopy, rose bengal dye staining, fluorescein tear breakup time (TBUT), and a 5-minute Schirmer test with topical anesthesia. The lower tear meniscus was imaged using an FD-OCT system with 5-μm axial resolution and measured manually by a masked grader using computer calipers. Correlation was assessed using Spearman correlation coefficient (ρ).The mean (±SD) scaled symptom score was 58 ± 21, with a range of 0 to 100. Vital staining test averaged 1.7 ± 3.4, TBUT averaged 4.4 ± 1.8 seconds, and Schirmer tests averaged 10.2 ± 8.1 mm. As determined by optical coherence tomography, the meniscus height was 228 ± 153 μm, depth was 127 ± 79 μm, and cross-sectional area was 0.018 ± 0.021 mm. Optical coherence tomography meniscus area was negatively correlated with the symptom questionnaire score (P < 0.01) and positively correlated with Schirmer test results (P < 0.01). There was no significant correlation between symptom score and rose bengal staining, TBUT, or Schirmer test results (P > 0.01).Lower tear meniscus measurement with FD-OCT is an objective noninvasive test that correlates well with symptoms of dry eye disease and the Schirmer test.
As the prevalence of glaucoma continues to rise, clinicians and researchers are confronted with an age-old problem: how to reduce risk factors and preserve vision in glaucoma. Current management options revolve around a validated paradigm—intraocular pressure reduction. Active investigations to improve drug delivery efficacy and surgical outcomes are flourishing. This article aims to provide the interested readers with a review of recent discoveries in nanobiotechnology for the management of glaucoma. Targeted drug-delivery systems using mesoscale vectors demonstrate promising delivery profiles. The utility of nanoparticulate therapies to support retinal ganglion cell survival is being investigated. Studies to modulate tissue regeneration and remodeling and improve post-trabeculectomy outcomes are underway. Though these modalities promise new avenues to manage glaucoma, immediate market availability is not anticipated soon.
Penetrating keratoplasty is the most common type of tissue transplant in humans. Irreversible immune rejection leads to loss of vision and graft failure. This complex immune response further predisposes future corneal transplants to rejection and failure. A diverse armamentarium of surgical and pharmacologic tools is available to improve graft survival. In this review, we will discuss the various gene therapeutic strategies aimed at potentiating the anterior chamber-associated immune deviation to extend graft survival.
A 44-year-old woman presented with a painful red eye for 2 weeks. Ultrasound biomicroscopy and optical coherence tomography were instrumental in the diagnosis and management of this case of infectious scleritis associated with previous pterygium excision complicated by choroidal and retinal detachments.
