Bita Manzouri

Pharmacotherapy of fungal eye infections.

Fungal eye infections are rare. Trauma associated with contamination by vegetative material, contact lens wear and long term corticosteroid use are common risk factors. The aims of treatment are to preserve visual function, which depends on the rapid diagnosis and efficient administration of appropriate antifungal therapy. This necessitates a clinical suspicion of fungal aetiology and the taking of appropriate smears and cultures as early as possible to identify the fungal organism. Currently there are three main classes of drugs available for use in fungal eye infections: polyenes, azoles as derivatives of imidazoles, and 5-fluorocytosine. Of the polyenes, amphotericin B, natamycin and nystatin are of clinical ophthalmic use. Based on better pharmacokinetic profiles and spectra of antifungal activity, the triazoles are the agents of choice. Successful treatment of fungal keratitis depends on early initiation of specific therapy consisting of topically-applied antifungal agents since topical administration is most likely to provide the best opportunity for achieving therapeutic corneal levels. Hence, the molecular weight of the various antifungal agents is of importance since it influences their ability to penetrate the corneal epithelium. Systemic administration may be necessary for resistant fungal ulcers. For fungal endophthalmitis, to preserve visual function and eliminate the fungal pathogen, topical, systemic and possibly intraocular antifungal therapy is used, although some do not recommend use of systemic agents for exogenous endophthalmitis.

Characterization of dendritic cell phenotype in allergic conjunctiva: increased expression of Fc ɛ RI, the high-affinity receptor for immunoglobulin E

PurposeDendritic cells (DCs) express the high-affinity receptor for IgE (FcɛRI) on their surface, which may enhance their ability to capture and internalize antigens for presentation to T-lymphocytes. The aim of this study was to determine if expression of FcɛRI+ DCs is increased in the conjunctivae of vernal keratoconjunctivitis (VKC) patients compared with those of normal controls.MethodsConjunctival biopsies were obtained from non-atopic and VKC patients. Double immunohistochemical staining was carried out using antibodies against FcɛRI and the CD1a antigen, a DC marker. The double-positive cells were counted in five representative fields of view for each conjunctival sample.ResultsFcɛRI+ CD1a+ cells were present in significantly higher numbers in VKC conjunctivae compared with normal controls (mean cell count of 21.3 in VKC vs5.0 in controls, P<0.005). In normal patients the FcɛRI-expressing DCs tended to be confined to the epithelial layer or the superficial substantia propria, but in the VKC samples these FcɛRI+ cells were mainly concentrated in the deeper substantia propria.ConclusionsFcɛRI+ DC numbers are elevated in the conjunctivae of VKC patients, a finding consistent with the results of other studies focusing on atopic conditions. Elevated expression of FcɛRI on DCs would facilitate antigen presentation and enhance T-cell priming, thereby contributing to ocular symptoms.

Topical cyclosporine in corneal transplantation.

Purpose: Corneal transplantation is the most commonly performed tissue transplantation boasting over a century of history, science, and tradition. One of the most promising immunomodulatory substances whose immunosuppressive effect has revolutionized solid organ transplantation is cyclosporine (CsA). We present a literature review on the role of topical cyclosporine in corneal transplantation. Methods: A review of the published literature using key databases that include MEDLINE and PubMed was undertaken. Published evidence base for the use of topical cyclosporine in corneal transplantation between 1986 and 2010 was evaluated and summarized. Results: There is some scientific evidence to support the use of topical cyclosporine in appropriately selected cases of corneal transplantation. Although some encouraging human case series and case–control studies have been published, to date most randomized controlled trials evaluating the effects of topical cyclosporine in graft rejection prophylaxis and treatment have failed to demonstrate statistically significant improved outcomes. Conclusions: Cyclosporine cannot currently be considered as an effective sole agent in prophylaxis and treatment of allograft rejection, and corticosteroids therefore remain the gold standard choice of therapy. Further studies are required to refine the role of cyclosporine in modern corneal transplantation.

Pharmacotherapy of allergic eye disease

Allergic eye disease is a term that refers to a number of disease processes that affect about one-fifth of the world’s population. Although the more advanced forms of the disease can be sight threatening, the most disabling effects are due to the clinical manifestations, and hence quality of life, with some patients having seasonal exacerbations of their symptoms, whereas others have symptoms that are present throughout the year. Recent increased understanding of the cellular and mediator mechanisms that are involved in the various disease manifestations has greatly facilitated the development of more effective treatment options. Newer topical medications are being used that have multiple actions, such as an antihistaminic effect coupled with mast-cell stabilisation, and which require reduced daily dosing due to their longer duration of action. With greater research into newer therapies and more effective modes of delivery, improved healthcare outcomes with a lower economic burden will be achieved for patients with allergic eye disease.

Ocular surface squamous neoplasia in an immunosuppressed patient with atopic keratoconjunctivitis

We describe a patient with severe atopic dermatitis and keratoconjunctivitis, who was prescribed both systemic and topical ciclosporin and who developed ocular surface squamous neoplasia (OSSN). To provide additional information on the incidence of the association between topical ciclosporin use and OSSN, we counted the total prescriptions for topical ciclosporin issued in our hospital between 2003 and 2006 (804 patients) and, for the same period, we reviewed the records of patients with OSSN for a history of treatment with ciclosporin or a history of atopy. No other case of OSSN in a patient with a history of topical ciclosporin use was identified, which makes it difficult to implicate topical ciclosporin as the causative factor.

Pharmacotherapy of corneal transplantation.

Introduction: Corneal transplantation is a surgical procedure in which damaged or diseased cornea is replaced by cadaveric corneal tissue. It is the most common form of solid-tissue transplantation in humans but its pharmacotherapy (in relation to graft rejection) has changed little for several decades. The mainstay of treatment of corneal graft rejection remains corticosteroids but these are variably effective and are associated with potentially serious adverse effects. Newer immunosuppressive drugs are increasingly being employed to manage high-risk grafts. However, these drugs are also not without side-effects, some of which can be severe and life-threatening. Areas covered: This review outlines the corneal transplant procedure and the treatment options available in the management of transplant rejection. Expert opinion: The surgical technique of corneal lamellar grafting has allowed for transplantation of smaller quantities of donor tissue to the recipient, thereby reducing the antigen load as a means of preventing a rejection episode. With greater understanding of the underlying molecular mechanisms involved in corneal transplant rejection pathology, potentially newer medications that will target specific cytokines or cells involved in rejection, whilst minimizing the potential side effects to the graft recipient, will be made available.

The Dendritic Cell in Allergic Conjunctivitis

The acquired immune response in health and disease is initiated when foreign antigens are processed and presented to T lymphocytes via antigen-presenting cells as peptides in the context of Class I and II major histocompatibility complex antigens. It is now clear that there are various types of antigen-presenting cells and that the phenotype of these cells (together with the milieu of the tissue or lymphoid organ) dictates the nature of the immune response to the antigen. Very little is known about the phenotype, distribution, and roles of dendritic cell subtypes that contribute to the pathophysiology of type I hypersensitivity reaction in the ocular surface. We review what has been learned from studies of both human ocular allergy and murine models and comment on how this compares to allergic reactions in other mucosal tissues.

Allergy and Contact Lenses

Allergic conjunctivitis is a response to environmental allergens, as well as a genetic predisposition of the patient. It is classified as either acute (seasonal allergic conjunctivitis) or chronic (perennial allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis). The immune mechanism of these diseases will be discussed, as well as the allergic response to contact lens wear.

The Role of Histamine in Ocular Allergy

Ocular allergy is a disorder affecting increasing numbers of individuals worldwide. Among the inflammatory mediators that contribute to ocular allergy, histamine is perhaps the best characterized. This monoamine is released by sensitized mast cells upon exposure to allergen and causes symptoms such as redness and tearing. Histamine may also recruit immune cells that can cause long-term damage to ocular surfaces. In this chapter we will discuss the known functions of histamine and histamine receptors in ocular allergy and will describe promising therapies targeting the histamine-signaling pathway.

Phototoxic maculopathy following uneventful cataract surgery in a predisposed patient

Operating microscope light induced foveal damage is a well recognised occurrence following ocular surgery including complicated cataract extraction, complex anterior segment procedures, and vitrectomy surgery.1 An increased risk of phototoxicity is associated with an operating time greater than 100 minutes, increased body and therefore retinal temperature, unfiltered blue light, and hyperoxaemia.2,3 We report a patient who developed a phototoxic lesion during routine cataract surgery possibly related to underlying systemic lupus erythematosus (SLE) and hydroxychloroquine treatment. We examine the measures taken to prevent recurrence with second eye surgery and the implications for routine cataract surgery are discussed. A 39 year old woman presented with blurred left vision and glare. One year previously she had been diagnosed with SLE for which she had been taking hydroxychloroquine 200 mg and prednisolone 5 mg daily for 18 months. She had bilateral subcapsular cataracts and underwent routine left phacoemulsification and lens implant surgery under general anaesthesia. Directly after surgery, the patient noted two confluent blind spots immediately below fixation in the left eye. When first seen by us the left visual acuity was 6/5, intraocular pressure was 16 mm Hg, and the eye was quiet with a well centred posterior chamber lens …