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.     

Pharmacotherapy of systemic lupus erythematosus

The pharmacological management of systemic lupus erythematosus (SLE) is challenging owing to its unpredictable clinical course, the variable organ system involvement and the lack of clear understanding of disease pathogenesis. The widely used corticosteroids and immunosuppressive drugs, which can control disease activity, have serious, potentially fatal, side effects. In the last decade, a better understanding of lupus pathogenesis has led to the development of biological agents that are directed at biomarkers. However, these biologicals also exert side effects due to infections resulting from completely eliminating immune cells (e.g., B cells) or cytokine signals (e.g., interferon-α) or affecting molecular targets outside the immune system (CD40L on platelets). New biomarker-driven clinical trials are ongoing to evaluate the safety and efficacy of B-cell depletion, blocking of interferon signaling, inhibition of the mTOR pathway, and restoration of glutathione deficiency in lupus T cells.     

Pharmacotherapy of pompholyx

Pompholyx is an inflammatory vesicobullous disorder of the palms and soles. The condition is difficult to treat because of the peculiarities of the affected skin, namely, the thick horny layer and richness of sweat glands. The cornerstones of topical therapy are corticosteroids, although calcineurin inhibitors seem to be effective as well. Topical photochemotherapy with 8-methoxypsoralen is as effective as systemic photochemotherapy or high-dose ultra violet Type A-1 irradiation. Systemic therapy is often necessary in bullous pompholyx. Corticosteroids are used commonly, although no controlled studies have been published. For recalcitrant cases corticosteroids are combined with immunosuppressants. A new evolving treatment seems to be the intradermal injection of botulinum toxin.     

Pharmacotherapy of uveitis

Importance of the field: The term ‘uveitis’ covers a broad spectrum of ocular inflammation affecting the iris, ciliary body, and/or the choroid, all of which comprise the uveal tract. Severe cases of uveitis need be treated aggressively to prevent damage caused by chronic inflammation. Untreated or poorly managed cases can lead to ciliary body dysfunction, inadequate aqueous production, chorioretinal damage, and possibly blindness.

Areas covered in this review: There are many medications that can be used to treat uveitis. Corticosteroids are available in several formulations: topical drops, regional injections, oral and intravenous. Immunomodulatory agents that can be used for uveitis are antimetabolites, T-cell inhibitors, alkylating agents, and biologic response modifiers. These medications, their appropriate uses, and side effect monitoring will be detailed.

What the reader will gain: There is a stepladder approach to treatment of ocular inflammation. Corticosteroids are the treatment of choice for treating acute flares. Steroid free remission is the goal of therapy and can be achieved with the use of chemotherapeutic agents. Which medications are appropriate and how to escalate therapy will be reviewed.

Take home message: Chronic systemic corticosteroid therapy is not an acceptable long treatment plan for uveitis, unless all other medications have failed. Steroid sparing immunosuppressive therapy should be pursued as soon as acute flares of uveitis have been controlled.     

自动板层角膜刀浅板层角膜移植

目的探讨使用自动板层角膜刀行浅板层角膜移植的可行性。方法24只新西兰白兔分为供眼组（8只）,实验组（16只）。另2例（4只）为人体离体眼球（非正常N12）供临床应用。用自动板层角膜刀制作植片、植床,行浅板层角膜移植。结果手术损伤小,瘢痕少,创面愈合光滑,植片透明。结论术式有良好的临床应用前景。     

Long-term side effects of glucocorticoids

ABSTRACT

Introduction: Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible.

Areas Covered: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment.

Expert Opinion: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.     

Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia

Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases.

Materials and Methods: The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30?min, and after 10?min of ultraviolet A irradiation.

Results: Eleven eyes of eleven patients with progressive keratoconus (n?=?10) and iatrogenic corneal ectasia (n?=?1) were included in this study. The mean thinnest pachymetric measurements were 391.82?±?30.34?µm (320–434?µm) after de-epithelialization of the cornea, 435?±?21.17?µm (402–472?µm) following 30?min instillation of isotonic riboflavin solution without dextran and 431.73?±?20.64?µm (387–461?µm) following 10?min of ultraviolet A irradiation to the cornea.

Conclusion: Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.     

Pharmacological treatment for infectious corneal ulcers

Introduction: Cornea ulceration and infectious keratitis are leading causes of corneal morbidity and blindness. Infectious causes are among the most frequent and most severe. Management strategies for bacterial corneal ulcers have changed significantly over the last decades, however with a more limited progress in the treatment and management of nonbacterial, infectious ulcers.

Areas covered: This paper provides an overview of the current principles, strategies and treatment choices for infectious corneal ulcers in adults.

Expert opinion: Topical application with a broad-spectrum antimicrobial remains the preferred method for the pharmacological management of infectious corneal ulcers. Increasing reports of clinical failures and in vitro resistance to antibiotics to treat the most common infectious (bacterial) corneal ulcers are increasing concerns. New approaches for improvement in the pharmacological management of corneal ulcers should focus on strategies for a more rational and evidence-based use of current antimicrobials and development of products to modulate the host immune response and to neutralize microbial toxins and other immune modulators.     

Emerging drugs for the treatment of uveitis

Introduction: Uveitis is a potentially visually debilitating disease when untreated or poorly controlled. Chronic intermediate, posterior, or panuveitis often requires systemic immunosuppressive therapy to prevent such visual loss.

Areas covered: This review discusses existing treatments for ocular inflammation including corticosteroids, antimetabolites, alkylating agents, T-cell inhibitors, and biologic agents. Potential drugs being studied in clinical trials are introducing new routes for local corticosteroid delivery, and novel immunomodulators are exploring new targets of the inflammatory cascade.

Expert opinion: Treatment options for uveitis have expanded from even a decade ago. However, more clinical trials and research are needed to further our understanding of the mechanisms of ocular inflammation and the safety and efficacy of novel therapies.     

Pharmacotherapy options to treat asthma during pregnancy

Introduction: Pregnancy may be complicated by new onset or pre-existing asthma. This article reviews the recognition and management of asthma during pregnancy, paying close attention to the general principles of asthma medication use during pregnancy. Asthma is one of the most common potentially serious medical problems to complicate pregnancy, and asthma may adversely affect both maternal quality of life and perinatal outcomes. Therefore, optimal management of asthma during pregnancy is important for both mother and baby. This article reviews asthma pharmacotherapy during pregnancy, with an emphasis on gestational safety of commonly used medications.

Areas covered: In this review of asthma pharmacotherapy during pregnancy, the most pertinent recent publications are reported. Electronic databases such as PubMed were searched for terms pregnan* or perinat* or obstet* and asthma or wheeze and treatment.

Expert opinion: Although retrospective data have been reassuring, since pregnant women are generally excluded from clinical trials, there is a lack of adequate safety information for most medications taken during pregnancy. One of the most important needs for the future is the availability of further safety information for asthma medications used during pregnancy that can also account for asthma control.     

Pharmacotherapy in patients with idiopathic pulmonary fibrosis

Background: Based on the recognition of idiopathic pulmonary fibrosis as a fibroproliferative disease with the usual interstitial pneumonia histology, pharmacotherapies should be reconsidered. Objective: The aim of this study was to grasp the therapeutic efficacy of the drugs for idiopathic pulmonary fibrosis patients based on reports and the authors' own experiences. Methods: The study reviewed a spectrum of therapeutic strategies and the current problems in the drug treatments for idiopathic pulmonary fibrosis/usual interstitial pneumonia patients based on reported references. Results/conclusions: Unfortunately, the presence of usual interstitial pneumonia lesions increases the likelihood that idiopathic pulmonary fibrosis will resist various types of drug therapies. The most practical and critical points of therapeutic view are the following. First, for advanced idiopathic pulmonary fibrosis patients, small maintenance doses of drugs could reduce several adverse effects. Second, there needs to be early detection of pulmonary hypertension, which is an unfavorable prognostic factor and trial of vasodilators in patients with pulmonary hypertension. Third, for early stable patients, a large randomized controlled trial (using antifibrotic and immunomodulatory drugs) should be undertaken in order to obtain feasible results.     

Outcome of corneal transplantation

Corneal transplantation is a sight restoring surgery done for corneal blindness. The purpose of this retrospective preliminary study is to analyze the outcome of 54 corneal transplantations (for 32 females and 22 males) done in the Department of Ophthalmology between September 1998 and June 2002. The mean follow-up period was 13 months. Hundred percent (6/6) of the keratoconus (KC) and 85.4% of the nonkeratoconus grafts survived at a mean duration of 7.1 months and 16 months respectively. Seven of the 54 grafts (13%) have failed. The causes of graft failure were graft rejction in 4 and bacterial keratitis in 3 cases. Fifty of the 54 cases (92.6%) had a preoperative visual acuity of < 3/60. As a result of the transplantation, the percentage of blind eyes dropped from 92.6% to 21%. The data in this study confirms that corneal transplantation is a reasonably successful procedure in restoring sight for seleted cases of corneal blindness in Ethiopia.     

Epidermal growth factor receptor in corneal damage: update and new insights from recent reports

Agonist and antagonist drugs acting on epidermal growth factor receptor (EGFR) signaling are emerging as a new possibility for pharmaceutical study and clinical manipulation of some skin and corneal disorders. EGFR activation appears to be effective in reducing the time of reepithelialization after corneal wound healing, with potential uses in penetrating keratoplasty, refractive surgery, alkali burns, diabetic keratopathy, keratopathy following chemotherapy, cornea transplantation, and dry eye. Most of the studies show therapeutic advantages of human recombinant epidermal growth factor (hrEGF) eye drops without showing adverse effects. In contrast, EGFR inhibition delays epithelial cell proliferation and stratification during corneal regeneration.The aim of this review is to summarize the most seminal discoveries and recent advances so as to clarify the role of the EGFR system in corneal physiology and pharmacology. Epidermal growth factor eye drops could be a first-choice treatment for promoting regeneration in numerous epithelial defects in the medium to long term.     

植床带周边后板层的大植片穿透性角膜移植术临床观察

目的评价植床带周边后板层的大植片穿透性角膜移植术的临床疗效。方法24例24眼用植床带周边后板层的大植片穿透性角膜移植术为改良组,57例64眼用常规大植片穿透性角膜移植术为对照组,两组对照观察。结果1、视力：两组无差别。2、并发症：改良组术后浅前房1眼（4.2%）、虹膜前粘连2例（8.3%）、继发青光眼2例（8.3%）;对照组术后浅前房22眼（34.4%）、虹膜前粘连21例（32.8%）、继发青光眼22例（34.4%）。改良组并发症比对照组低（P〈0.05）。结论植床带周边后板层是大植片穿透性角膜移植术有效的改良方法。     

Acute rejection after heart transplantation

Acute rejection (AR) seems to be less common with current immunosuppressive strategies; however, it remains a major cause of morbidity and mortality in the first year following heart transplantation. Despite great interest in noninvasive methods for detecting rejection, the endomyocardial biopsy remains the standard method for AR identification and, recently, the cardiac biopsy grading system has been reviewed. Moreover, the availability of several immunosuppressive drug combinations has generated confusion in the minds of clinicians. This review will focus on recently published studies that are related to the clinical impact of AR, combination regimens of chronic maintenance immunosuppression and specific therapeutic options for treating AR.     

Evaluation and Treatment of Acute and Subacute Hearing Loss: A Review of Pharmacotherapy

Among various forms of hearing loss, there are acute (within 72 hrs) or subacute (weeks to months) presentations that may be reversible with early pharmacological intervention. The workup of a patient presenting with hypoacusia includes the usual history and physical examination in conjunction with an audiometric assessment in order to categorize the hearing loss as conductive, sensorineural, or mixed. Sudden sensorineural hearing loss and autoimmune inner ear disease are acute and subacute forms of sensorineural hypoacusia most likely to be reversed with prompt pharmacological intervention. Systemic or local corticosteroid therapy has the most evidence of benefit in patients with sudden sensorineural hypoacusia and is the best available first line therapy noted in clinical practice guidelines. Alternative immunosuppressant therapies have not been well studied, and many have serious toxicities that further complicate the benefit‐risk assessment. There are no randomized comparisons of corticosteroid dosing regimens that evaluated clinically important outcomes, so expert opinion must serve as the basis for dosing recommendations. Clinicians need to involve patients with hypoacusia in the shared decision‐making process, since partial or complete reversal of hearing loss can have substantial quality‐of‐life implications for affected patients.     

Immunosuppression trends in solid organ transplantation: The future of individualization,monitoring, and management

Immunosuppression regimens used in solid organ transplant have evolved significantly over the past 70 years in the United States. Early immunosuppression and targets for allograft success were measured by incidence and severity of allograft rejection and 1-year patient survival. The limited number of agents, infancy of human leukocyte antigen (HLA) matching techniques and lack of understanding of immunoreactivity limited the early development of effective regimens. The 1980s and 1990s saw incredible advancements in these areas, with acute rejection rates halving in a short span of time. However, the constant struggle to achieve the optimal balance between under- and overimmunosuppression is weaved throughout the history of transplant immunosuppression. The aim of this paper is to discuss the different eras of immunosuppression and highlight the important milestones that were achieved while also discussing this in the context of rational agent selection and regimen design. This discussion sets the stage for how we can achieve optimal long-term outcomes during the next era of immunosuppression, which will move from universal protocols to patient-specific optimization.     

Acute corneal toxicity of latanoprost with different preservatives

Purpose: To investigate the corneal toxicity of Xalatan and three latanoprost generics using transepithelial electrical resistance (TER) and scanning electron microscopy (SEM).

Methods: Corneal TER changes after a 60-s exposure to Xalatan (latanoprost 0.005% preserved with 0.02% BAC), and latanoprost generics (Latanoprost PF BAC free, Latanoprost Nitten SB containing sodium benzoate and Latanoprost Towa containing 0.01% BAC with sodium chloride polysorbate 80 as additive) were measured in living rabbits. Corneal damage was also examined by SEM. Hank’s balanced salt solution (HBSS) was used as a control.

Results: There was a significant decrease in the corneal TER after exposure of the cornea to Xalatan (p?<?0.01) and all latanoprost generics (p?<?0.01: Latanoprost PF, p?<?0.05: Latanoprost Nitten SB, Latanoprost Towa) as compared to HBSS. All latanoprost generics showed less TER decrease in the corneal TER as compared to Xalatan (p?<?0.01). SEM revealed that superficial cells of Xalatan-treated corneas were damaged and exhibited degenerated microvilli. Conversely, the superficial cells of corneas exposed to HBSS or all latanoprost generics appeared normal and had normal microvilli under SEM examinations.

Conclusion: The corneal toxicity of Xalatan is greater than that of latanoprost generics. Xalatan contains 0.02% BAC, which may be responsible for the corneal toxicity.     

冷冻干燥羊膜移植联合板层角膜移植治疗蚕蚀性角膜溃疡

目的观察冷冻干燥羊膜移植联合板层角膜移植在蚕蚀性角膜溃疡中的临床应用及效果。方法对12例12眼蚕蚀性角膜溃疡进行板层角膜移植术及病灶临近球结膜、球筋膜切除后进行羊膜移植术。结果术后12例患者临床症状全部消失．随访一年以上，无一例复发。结论冷冻干燥羊膜移植联合板层角膜移植治疗蚕蚀性角膜溃疡，可显著降低术后病变复发率，有较好的临床效果。     

The effect of sulfur mustard and nitrogen mustard on corneal collagen degradation induced by the enzyme collagenase

Objective: Sulfur mustard (SM) is an alkylating agent that can affect cornea and induce various complications. With regard to the role of the enzyme collagenase in dermatologic complications induced by SM and its role in other ocular disorders, we studied the effect of SM and nitrogen mustard (NM) on collagen degradation by collagenase.

Materials and methods: This study included 7 groups of samples: The negative control group contained collagen without collagenase and toxins, the control group contained collagen and collagenase without any toxin, the positive control groups of NM and SM contained collagen and NM or SM without collagenase, the experimental groups of NM and SM contained collagen that was affected by NM or SM and collagenase, and the control group of collagenase contained only collagenase without containing collagen or receiving toxins. After incubation for 3.5 hours, the amount of hydroxyproline and the protein content of the samples were measured. Data were analyzed by analysis of variance (ANOVA).

Results: The protein concentrations of the negative control group and the positive control groups of SM and NM were significantly lower than those for all other groups of the study. There was a significant difference in hydroxyproline concentration of control group and negative control group; however, there was no significant difference between experimental group of SM and the positive conrol group of SM. There was no significant difference between the negative control group and the positive control group of SM in the hydroxyproline concentration of sediment samples.

Conclusion: According to the results of this study, SM can affect the corneal collagen in a way in which collagenase cannot degrade it. In addition, it can be hypothesized that ineffective activity of this enzyme can result in increasing concentration of collagenase, which can lead to the destruction of the normal collagen of the cornea. The main result of this study confirms the hypothesis that SM inhibits the effect of collagenase on corneal collagen.