Management of Vernal Keratoconjunctivitis in Children in the United Kingdom: A Review of the Literature and Current Best Practice Across Six Large United Kingdom Centers.

Vernal keratoconjunctivitis (VKC) is a form of ocular allergy primarily affecting children. Considered a rare disease in Europe, its prevalence varies by geographic region and is poorly studied in the United Kingdom. There is considerable national variation in the management of VKC within the United Kingdom, risking misdiagnosis and delays to treatment for some children. This can significantly impact their quality of life, with the potential for lasting negative consequences. Based on discussions between experienced clinicians from six large centers across the United Kingdom, this article describes best practice recommendations for United Kingdom settings, including principles for diagnosis, referral, initial and long-term management, and supportive care. Recommendations include guidance on referral timing, which should depend on VKC severity, and a stepwise approach to treatment. Joint management by primary care and secondary care is recommended and the importance of supportive care, including emotional support and outreach to schools, is highlighted. Because frequent flareups are common in VKC, it is essential that families have access to the information they need to manage the disease and routes to access rapid care if needed. A thorough understanding of the nature of VKC, its triggers, and how best to manage it, by both patients and their families, is critical to ensuring appropriate management and to improving patient outcomes. [J Pediatr Ophthalmol Strabismus. 2023;60(1):6-17.].

Ocular Complications in the Prone Position in the Critical Care Setting: The COVID-19 Pandemic.

PURPOSE: Ocular complications are common in the critical care setting but are frequently missed due to the focus on life-saving organ support. The SARS-CoV-2 (COVID-19) pandemic has led to a surge in critical care capacity and prone positioning practices which may increase the risk of ocular complications. This article aims to review all ocular complications associated with prone positioning, with a focus on challenges posed by COVID-19. MATERIALS AND METHODS: A literature review using keywords of "intensive care", "critical care", "eye care", "ocular disorders", "ophthalmic complications," "coronavirus", "COVID-19," "prone" and "proning" was performed using the electronic databases of PUBMED, EMBASE and CINAHL. RESULTS: The effects of prone positioning on improving respiratory outcomes in critically unwell patients are well established; however, there is a lack of literature regarding the effects of prone positioning on ocular complications in the critical care setting. Sight-threatening ophthalmic disorders potentiated by proning include ocular surface disease, acute angle closure, ischemic optic neuropathy, orbital compartment syndrome and vascular occlusions. CONCLUSIONS: COVID-19 patients may be more susceptible to ocular complications with increased proning practices and increasing demand on critical care staff. This review outlines these ocular complications with a focus on preventative and treatment measures to avoid devastating visual outcomes for the patient.

Pharmacotherapeutic management of atopic keratoconjunctivitis.

INTRODUCTION: Atopic keratoconjunctivitis (AKC) is a form of allergic eye disease that can have sight threating implications. Prevalence is underestimated due to scarce published data and treatment is expanding as a result of limitations of current strategies. This article aims to provide an up-to-date overview of AKC and summarize current and upcoming management. AREAS COVERED: The authors provide history, immunopathogenesis, and summary of the clinical manifestations of AKC as well as presenting a review of the evidence in relation to treatment options including mast cell stabilizers, antihistamines, corticosteroids, and immunomodulatory drugs based on clinical trials. Future trends, drug targets, and novel delivery drug systems are also highlighted in this review. EXPERT OPINION: Previously established treatment strategies of AKC had relied on corticosteroids, but the side effects of long-term therapy resulted in the expansion into the use of immunomodulatory drugs such as tacrolimus and ciclosporin. However, these too provide limited success due to the suboptimal structural properties of the current molecules. The ideal molecule should generate maximum permeability across the multi-layered structure of the cornea, be able to be formulated into eye drops for ease of application with minimal dosing and for maximal clinical effect.

Supplementary IOLs: Monofocal and Multifocal, Their Applications and Limitations.

Supplemental intraocular lenses (IOLs) have been developed to replace IOLs designed for in-the-bag placement being used as "piggy-back" IOLs in the sulcus due to unacceptable complications. The new IOLs have unique platform designs to avoid these complications. As a result, a new nomenclature is needed to describe the 4 scenarios when supplemental IOL use is now indicated.

Systemic cyclosporine and corneal transplantation.

Corneal transplantation is the most commonly performed tissue transplant boasting over a century of history, science, and tradition. While favorable outcomes have been reported after penetrating keratoplasty, rejection remains a major cause of graft failure. The long-term survival rates of this relatively immunologically privileged tissue are only just comparable to those of vascularized organs. While corticosteroids treatment remains the gold standard for postoperative immunomodulation, other agents have been utilized in an ongoing effort to improve graft survival and patient outcomes. One of the most promising immunomodulatory substances whose immunosuppressive effect has revolutionized solid organ transplantation is cyclosporine (CsA). A calcineurin inhibitor, cyclosporine has been used as an immunosuppressive agent in corneal transplantation since the 1980's. Although some studies have shown beneficial effects of cyclosporine in both low- and high-risk corneal transplant patients the use of cyclosporine in rejection prophylaxis and treatment remain controversial and disputable. We herein present a literature review on the role of systemic cyclosporine in corneal transplantation.

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.

Papilloma development and long-term ciclosporin use in chronic ocular allergy with associated keratoconus.

PURPOSE: Conjunctival papillomata are squamous epithelial tumors with a strong association with human papilloma virus (HPV) types 6 and 11. They are benign conjunctival tumors that can be treated by surgical excision. We report a case where topical immunosuppressive therapy modified the local T-cell immunity in the conjunctiva resulting in papilloma development in a patient with keratoconus and a strong atopic history. METHODS: A case report of a 44-year-old man with a history of severe ocular and generalized atopy is presented. We present the problems encountered in management of his severe ocular allergy and how these impeded the management of his keratoconus. RESULTS: Conventional antiallergy topical medication was not producing symptom relief in this patient, and so topical immunosuppression was commenced using ciclosporin ointment 0.2%. This therapy modified the local T-cell immunity in the conjunctiva resulting in the development of papillomata which contributed to the intolerance of contact lens wear for visual rehabilitation of the keratoconus in the patient. These lesions were surgically removed but typically recurred and required further surgical excision. Adjunct cryotherapy was also performed at the time of the surgery to try to stem the recurrence of the papillomas. CONCLUSIONS: To the best of our knowledge and following a review of the published literature using key databases that include Medline and PubMed, this is the first report confirming the development of conjunctival papillomas secondary to HPV type 6 in a ciclosporin-treated patient.

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.

Bell's palsy in a 3-month-old infant: recommendations for management of pediatric cases.

Bell's palsy is an idiopathic unilateral paresis or paralysis of the facial nerve. The authors describe a 3-month-old infant with Bell's palsy and detail the investigation and management appropriate for the pediatric age group.

Characterisation of the phenotype and function of monocyte-derived dendritic cells in allergic conjunctiva.

BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells involved in initiating the immune response, presenting antigens to T cells and leading to T cell proliferation. In an immature state, DCs lack accessory signals required for T cell stimulation but are highly specialised to capture antigens. Full DC maturation changes the cell surface phenotype and facilitates stimulation of T cell proliferative responses. To examine the degree of DC maturity associated with vernal keratoconjunctivitis (VKC), the authors examined the phenotype and antigen-presentation capability of blood derived DCs from VKC patients and from normal controls. METHODS: Flow cytometry was used to identify the cell surface expression of markers of DC maturity (CD83, CD86, major histocompatibility complex class II) and mixed leucocyte reactions to assess DC induction of T cell proliferation. RESULTS: DCs derived from VKC patients were of a more mature phenotype than those from normal controls. However, these VKC DCs had reduced capability for induction of T cell proliferation compared with DCs from controls. CONCLUSION: The increased maturity of DCs in VKC patients correlates with the heightened immune responsiveness associated with this disorder. A number of mechanisms may underlie the impaired ability of DCs in atopy to stimulate T cell proliferation. This impairment of DC induction of T cell activation is likely to be one factor which contributes to the modified inflammatory response seen in VKC patients and the recognised susceptibility of these patients to viral infection.

Airbag-induced chemical eye injury.

Chemical injuries of the eye are a rare complication of airbag deployment and result from seepage of the chemical, causing inflation through vents in the airbag. We describe a severe case of bilateral alkali eye injury upon airbag contact in a road traffic accident. Delayed recognition and irrigation of the eyes exacerbated the injury with a resultant poor healing response of the left eye. Consequently, a left amniotic membrane graft was performed to promote corneal epithelial healing. The use of an amniotic membrane graft in the acute period after a chemical keratitis is unusual and reflects the severity of the corneal injuries sustained by this patient. This case illustrates the vision-threatening risk of alkali keratitis secondary to airbag deployment and highlights the importance of early recognition and management.

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.

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.

Dynamic changes in conjunctival dendritic cell numbers, anatomical position and phenotype during experimental allergic conjunctivitis.

Dendritic cells (DCs) are a subset of antigen-presenting cells (APCs) that are involved in the initiation and control of the immune response to antigens present at the interface with the environment. A limited number of groups have studied DCs in human and animal conjunctiva but no data is available concerning the different DC subsets present in the conjunctival tissue. The aims of this study are to characterize the phenotypes and numbers of DCs present in the murine model of allergic conjunctivitis using the technique of immunohistochemistry so as to aid the understanding of the mechanisms involved in allergic eye disease. A double immunofluorescence method was used to analyze the phenotypic distribution and density of DC subsets in the mouse conjunctival tissues of the allergic model using a panel of antibodies: CD11c, as a general marker of DCs, coupled with another DC subset marker such as Langerin for Langerhans cells (LCs), CD11b for myeloid DCs (mDCs) and mPDCA-1 for plasmacytoid DCs (pDCs). In the naïve conjunctiva, mDCs were consistently detected in the subepithelial layer and substantia propria. In the epithelium and the subepithelial layer, very few LCs and virtually no pDCs were observed. Following allergen challenge, there was a marked influx of mDCs and pDCs, but no LCs, into the subepithelial layer and throughout the substantia propria. These results indicate that conjunctival DC subsets may play an important role in the immune-regulatory processes involved in the inflammatory component of allergic conjunctivitis.

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.