Ocular Inflammatory Disorders Research Articles

Double trouble: a patient with both HLA-B27 anterior uveitis and HLA-A29 birdshot chorioretinitis.

BackgroundBirdshot chorioretinitis (BSCR) is a rare ocular inflammatory disorder associated with HLA-A29 and characterized by bilateral choroidal lesions, vitritis, macular edema, and retinal vasculitis. Ocular inflammation associated with HLA-B27 is typically a recurrent, unilateral, acute anterior uveitis (AAU) that is frequently associated with ankylosing spondylitis (AS). To date, there are no reports of patients with both HLA-A29-positive BSCR and HLA-B27 AAU/AS in the English literature.FindingsA 50-year-old man with a history of bilateral anterior uveitis, vitritis, retinal vasculitis, and cream-colored depigmented oval choroidal lesions was found to be HLA-A29 and HLA-B27 positive. His lumbar spine and sacroiliac joint films revealed fusion of the spine, known as `bamboo spine' compatible with the diagnosis of ankylosing spondyloarthropathy. He had chronic ocular inflammation that was difficult to control with systemic steroids and immunomodulatory agents.ConclusionsThis is the only report of a patient with both HLA-A29-positive BSCR and HLA-B27-positive AS and associated anterior uveitis. The severity of his disease suggests that patients who test positive for both HLA-A29 and HLA-B27 carry a poor visual prognosis. Prompt diagnosis and treatment with local or systemic corticosteroids or steroid-sparing agents may control the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12348-014-0028-6) contains supplementary material, which is available to authorized users.

Ocular manifestations of seronegative spondyloarthropathies.

This article reviews recent advances in the understanding of the ocular manifestations of seronegative spondyloarthropathies. Ocular inflammatory disorders are common and important disease manifestations in patients with seronegative spondyloarthropathy, with anterior uveitis being the most common. There is a strong association between affected patients and the human leukocyte antigen B27. Local corticosteroid treatment is usually effective, but chronic or refractory uveitis responds well to immunosuppressive drugs that are effective for arthritis. Recent studies have highlighted the possible benefits of a number of biologic agents, including tumor necrosis factor-alpha inhibitors in such patients. Uveitis is the most common ocular manifestation in patients affected by seronegative spondyloarthropathies. Both genetic and environmental factors play a role in its pathogenesis. As it tends to affect the young adult population, it carries a significant personal and population burden. Immunomodulatory therapy that also acts as a corticosteroid sparing therapy can be effective in controlling chronic uveitis in patients with spondyloarthropathy.

Periocular Corticosteroid Injections in Uveitis: Effects and Complications

To evaluate the benefits and complications of periocular depot corticosteroid injections in patients with ocular inflammatory disorders. Multicenter, retrospective cohort study. A total of 914 patients (1192 eyes) who had received ≥ 1 periocular corticosteroid injection at 5 tertiary uveitis clinics in the United States. Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained at every visit via medical record review by trained reviewers. Control of inflammation, improvement of visual acuity (VA) to ≥ 20/40, improvement of VA loss attributed to macular edema (ME), incident cataract affecting VA, cataract surgery, ocular hypertension, and glaucoma surgery. Among 914 patients (1192 eyes) who received ≥ 1 periocular injection during follow-up, 286 (31.3%) were classified as having anterior uveitis, 303 (33.3%) as intermediate uveitis, and 324 (35.4%) as posterior or panuveitis. Cumulatively by ≤ 6 months, 72.7% (95% CI, 69.1-76.3) of the eyes achieved complete control of inflammation and 49.7% (95% CI, 45.5-54.1) showed an improvement in VA from <20/40 to ≥ 20/40. Among the subset with VA <20/40 attributed to ME, 33.1% (95% CI, 25.2-42.7) improved to ≥ 20/40. By 12 months, the cumulative incidence of ≥ 1 visits with an intraocular pressure of ≥ 24 mmHg and ≥ 30 mmHg was 34.0% (95% CI, 24.8-45.4) and 15.0% (95% CI, 11.8-19.1) respectively; glaucoma surgery was performed in 2.4% of eyes (95% CI, 1.4-3.9). Within 12 months, among phakic eyes initially ≥ 20/40, the incidence of a reduction in VA to <20/40 attributed to cataract was 20.2% (95% CI, 15.9-25.6); cataract surgery was performed within 12 months in 13.8% of the initially phakic eyes (95% CI, 11.1-17.2). Periocular injections were effective in treating active intraocular inflammation and in improving reduced VA attributed to ME in a majority of patients. The response pattern was similar across anatomic locations of uveitis. Overall, VA improved in one half of the patients at some point within 6 months. However, cataract and ocular hypertension occurred in a substantial minority.

Oleanolic acid controls allergic and inflammatory responses in experimental allergic conjunctivitis.

Pollen is the most common aeroallergen to cause seasonal conjunctivitis. The result of allergen exposure is a strong Th2-mediated response along with conjunctival mast cell degranulation and eosinophilic infiltration. Oleanolic acid (OA) is natural a triterpene that displays strong anti-inflammatory and immunomodulatory properties being an active anti-allergic molecule on hypersensitivity reaction models. However, its effect on inflammatory ocular disorders including conjunctivits, has not yet been addressed. Hence, using a Ragweed pollen (RWP)-specific allergic conjunctivitis (EAC) mouse model we study here whether OA could modify responses associated to allergic processes. We found that OA treatment restricted mast cell degranulation and infiltration of eosinophils in conjunctival tissue and decreased allergen-specific Igs levels in EAC mice. Th2-type cytokines, secreted phospholipase A2 type-IIA (sPLA2-IIA), and chemokines levels were also significantly diminished in the conjunctiva and serum of OA-treated EAC mice. Moreover, OA treatment also suppressed RWP-specific T-cell proliferation. In vitro studies, on relevant cells of the allergic process, revealed that OA reduced the proliferative and migratory response, as well as the synthesis of proinflammatory mediators on EoL-1 eosinophils and RBL-2H3 mast cells exposed to allergic and/or crucial inflammatory stimuli such as RWP, sPLA2-IIA or eotaxin. Taken together, these findings demonstrate the beneficial activity of OA in ocular allergic processes and may provide a new intervention strategy and potential therapy for allergic diseases.

Examining the choroid in ocular inflammation: a focus on enhanced depth imaging.

The choroid is the vascular layer that supplies the outer retina and is involved in the pathogenesis of several ocular conditions including choroidal tumors, age related macular degeneration, central serous chorioretinopathy, diabetic retinopathy, and uveitis. Nevertheless, difficulties in the visualization of the choroid have limited our understanding of its exact role in ocular pathology. Enhanced depth imaging optical coherent topography (EDI-OCT) is a novel, noninvasive technique that is used to evaluate choroidal thickness and morphology in these diseases. The technique provides detailed objective in vivo visualization of the choroid and can be used to characterize posterior segment inflammatory disorders, monitor disease activity, and evaluate efficacy of treatment. In this review we summarize the current application of this technique in ocular inflammatory disorders and highlight its utility as an additional tool in monitoring choroidal involvement in ocular inflammation.

Expert Panel Recommendations for the Use of Anti–Tumor Necrosis Factor Biologic Agents in Patients with Ocular Inflammatory Disorders

To provide recommendations for the use of anti-tumor necrosis factor α (TNF-α) biologic agents in patients with ocular inflammatory disorders. Ocular inflammatory diseases remain a leading cause of vision loss worldwide. Anti-TNF-α agents are used widely in treatment of rheumatologic diseases. A committee of the American Uveitis Society performed a systematic review of literature to generate guidelines for use of these agents in ocular inflammatory conditions. A systematic review of published studies was performed. Recommendations were generated using the Grading of Recommendations Assessment, Development, and Evaluation group criteria. Numerous studies including controlled clinical trials have demonstrated that anti-TNF-α biologic agents (in particular infliximab and adalimumab) are effective in the treatment of severe ocular inflammatory disease. Based on these studies, the expert panel makes the following recommendations. Infliximab and adalimumab can be considered as first-line immunomodulatory agents for the treatment of ocular manifestations of Behçet's disease. Infliximab and adalimumab can be considered as second-line immunomodulatory agents for the treatment of uveitis associated with juvenile arthritis. Infliximab and adalimumab can be considered as potential second-line immunomodulatory agents for the treatment of severe ocular inflammatory conditions including posterior uveitis, panuveitis, severe uveitis associated with seronegative spondyloarthropathy, and scleritis in patients requiring immunomodulation in patients who have failed or who are not candidates for antimetabolite or calcineurin inhibitor immunomodulation. Infliximab and adalimumab can be considered in these patients in preference to etanercept, which seems to be associated with lower rates of treatment success.

Noninfectious Immune-Mediated Uveitis and Ocular Inflammation

Noninfectious uveitis encompasses a diverse group of ocular inflammatory disorders that share an underlying immune etiology and may be associated with systemic disease or confined primarily to the eye. Uveitis is commonly classified by anatomical location of inflammation into anterior, intermediate, posterior, and panuveitis. The treatment of noninfectious uveitis consists of corticosteroids, immunosuppressive agents, and surgically placed steroid implants. We review the epidemiology, immunopathology, and clinical features of several noninfectious immune-mediated uveitides, including HLA-B27 acute anterior uveitis, juvenile idiopathic arthritis, intermediate uveitis, sarcoidosis, Behcet's disease, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, and white dot syndromes. We also discuss the stepwise approach to medical treatment of immune-mediated uveitis as well as the characteristics, safety, and efficacy of immunosuppressive agents used to treat ocular inflammatory disease.

Biologic Therapy For Ocular Inflammatory Diseases: An Update

Uveitis comprehends a wide and heterogeneous group of intraocular inflammatory conditions potentially sight-threatening and vari - able therapeutic strategies have been proposed. Classical treatment with steroids and conventional immunosuppressive agents is often used as first-step. However, a number of patients may not respond properly or tolerate these medications with well-known side ef - fects. Over the last two decades, advances in the understanding of the pathogenesis of autoimmune uveitis, as well as improved bio- technology, have enabled the development of a new class of drugs called biologics, which provide selective targeting of the immune mediators of the inflammation cascade. Biologic therapies were introduced as a new option for patients with autoimmune rheumatic conditions refractory to conventional therapy and due to their success have posteriorly been used in ophthalmology to treat ocular inflammatory disorders. These new agents may potentially provide more effective and less toxic treatment than conventional therapy. Biologic therapies include a wide variety of drugs with different mechanisms of action, including monoclonal antibodies against cell surface markers, cytokines and their receptors, or recombinant forms of natural inhibitory molecules. Although some results are based on investigations with insufficient clinical trials, the majority of biologics indicate preferable outcomes on refractory uveitis, with remarkable promise to increase the possibility of long-term remission. The development of these new drugs is one of the most revo- lutionary advances in recent years, and the promise of shifting paradigms makes it an exciting time for uveitis specialists worldwide.

In situ gelling ophthalmic drug delivery system: Formulation and evaluation

ABSTRACTDesigning a drug delivery system to target the eye is an interesting and challenging endeavor faced by scientists because of the critical and pharmacokinetically‐specific environment that exists in the eye. Topical administration of ophthalmic drugs is used to alleviate the symptoms and signs caused by ocular surface inflammatory disorders, to treat infections, for glaucoma or intraocular inflammation (uveitis). However, the responsiveness toward the conventionally developed drug delivery system is limited because of the presence of several types of barriers in the eye that impede the effective passage of many drugs leading to minimal dose absorption. Ion activated in situ gelling ocular systems undergo phase transition in the presence of cations (present in the tear fluid), thus enhancing the residence time of drug in the cornea. In the present study natural polysaccharides (pectin alone or in combination with sodium alginate) or a pectin derivative (thiolated pectin [TP] alone or in combination with sodium alginate) were used to formulate in situ gelling eye drops. The formulations were evaluated for their gelling capacity, rheological studies, spreadability, bioadhesion strength, and in vitro drug release. Thiolation of pectin was observed to result in an increase in the gelling behavior, viscosity, and bioadhesive strength. The formulations comprising pectin alone (P7), combination of pectin and sodium alginate (P5SA1) or TP6 demonstrated good in vitro release characteristics. The optimized formulations displayed a significant decrease in the intraocular pressure as compared to the marketed formulation upon instillation in rabbit eye. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39788.

Diagnostic techniques for inflammatory eye disease: past, present and future: a review

Investigations used to aid diagnosis and prognosticate outcomes in ocular inflammatory disorders are based on techniques that have evolved over the last two centuries have dramatically evolved with the advances in molecular biological and imaging technology. Our improved understanding of basic biological processes of infective drives of innate immunity bridging the engagement of adaptive immunity have formed techniques to tailor and develop assays, and deliver targeted treatment options. Diagnostic techniques are paramount to distinguish infective from non-infective intraocular inflammatory disease, particularly in atypical cases. The advances have enabled our ability to multiplex assay small amount of specimen quantities of intraocular samples including aqueous, vitreous or small tissue samples. Nevertheless to achieve diagnosis, techniques often require a range of assays from traditional hypersensitivity reactions and microbe specific immunoglobulin analysis to modern molecular techniques and cytokine analysis. Such approaches capitalise on the advantages of each technique, thereby improving the sensitivity and specificity of diagnoses. This review article highlights the development of laboratory diagnostic techniques for intraocular inflammatory disorders now readily available to assist in accurate identification of infective agents and appropriation of appropriate therapies as well as formulating patient stratification alongside clinical diagnoses into disease groups for clinical trials.

Evaluation of Ocular and General Safety Following Repeated Dosing of Dexamethasone Phosphate Delivered by Transscleral Iontophoresis in Rabbits

To evaluate the toxicokinetics and tolerability (local ocular and general toxicity) of the anti-inflammatory agent, dexamethasone phosphate (a prodrug of dexamethasone) delivered to the eye in rabbits by transscleral iontophoresis. Female rabbits (n=6/group) received dexamethasone phosphate (40 mg/mL ophthalmic solution, EGP-437) transsclerally to the right eye (OD) using the Eyegate(®) II ocular iontophoresis delivery system once biweekly for 24 consecutive weeks at current doses of 10, 14, and 20 mA-min and current levels up to, and including -4 mA for 3.5-5 min. The study included 2 control groups (n=6/group): (1) a noniontophoresis control [an ocular applicator-loaded citrate buffer (placebo) without current] and (2) an iontophoresis control (a citrate buffer plus cathode iontophoresis at 20 mA-min, -4 mA for 5 min). Recoverability was evaluated 4 weeks following the last dose in 2 animals per group. The left eye (OS) was untreated and served as an internal control for each animal. Ocular and general safety of dexamethasone phosphate and dexamethasone were assessed. Other evaluations included toxicokinetics, ophthalmic examinations, intraocular pressure (IOP) measurements, electroretinographs, clinical observations, body weight, hematology and serum chemistry, gross necropsy, organ weight, and microscopic histopathology. The biweekly transscleral iontophoresis with either the citrate buffer or dexamethasone phosphate at cathodic doses up to, and including 20 mA-min and currents up to, and including -4 mA for 24 weeks was well-tolerated. Transient signs of conjunctival hyperemia and chemosis, mild corneal opacity, and fluorescein staining of the cornea were noted and attributed to expected ocular reactions to the temporary placement of the ocular applicator and application of iontophoresis. There were no dexamethasone phosphate-, dexamethasone-, or iontophoresis-related effects on IOP, electroretinography, or histopathology. Reductions in body weight gain, anemia, decreased leukocyte and lymphocyte counts, compromised liver function, enlarged liver, and reduced spleen weight were consistent with systemic corticosteroid-mediated pharmacology, repeated use of anesthesia, stress, and sedentariness, and unlikely to be related to iontophoresis application. The results of this investigation suggest that repeated transscleral iontophoresis with dexamethasone phosphate may be safe for use as a treatment for inflammatory ocular disorders that require prolonged and/or repeated corticosteroid therapy.

THU0417 Uveitis Associated with Bisphosphonate Treatment: A Case Series of 18 Patients.

BackgroundClinical trials suggested that bisphosphonates (BP) were safe and well tolerated drugs, but post-marketing studies have shown their association with rare adverse events but potentially serious, including inflammatory ocular disorders,...

Analysis of a Novel Protocol of Pulsed Intravenous Cyclophosphamide for Recalcitrant or Severe Ocular Inflammatory Disease

To analyze the success rate of pulsed intravenous (IV) cyclophosphamide (CyP) for noninfectious ocular inflammatory disease and to identify risk factors for failure of therapy. Retrospective, interventional, noncomparative cohort study. One hundred ten eyes of 65 patients. Through a computer search of the Massachusetts Eye Research and Surgery Institution's database, we identified patients who were treated with IV CyP between May 2005 and April 2012. We obtained demographic and clinical information through review of the electronic health record of each patient. Clinical response, corticosteroid-sparing effect, recurrence rate, calculated "risk factors" for failure, visual acuity, and adverse reactions. Pulsed IV CyP achieved complete remission of inflammation (for ≥ 2 visits) in 54 patients (84.4%). Sustained remission of inflammation occurred in 70% of patients within 3 months, 86.6% of patients within 6 months, and 91.7% within 9 months. The mean time to achieving quiescence was 3.5 months. The success rate in reducing corticosteroid to prednisone ≤ 10 mg/d within 6 months, while maintaining control of ocular inflammation, was 89.7% (95% confidence interval [CI], 81.1-93.5%). The mean duration of clinical remission for those patients who had a positive response to CyP was 32.67 months (95% CI, 25.91-39.43). Relapse of vasculitis was observed in 1 patient (1.5%) after completing the course of therapy. Early initiation of therapy during the course of the disease was correlated with a lesser rate of recurrence (P = 0.028). The most common adverse effects were nausea (29%) and transient lymphopenia (26%). The mean best-corrected visual acuity (BCVA) improved from 0.59 ± 0.66 at baseline to 0.30 ± 0.54 at 6 months of follow-up (P<0.001). The mean follow-up period was 31.61 ± 20.47 months. Pulsed IV CyP employing our protocol results in an extremely high rate of sustained complete remission in patients with recalcitrant and fulminant, vision-threatening ocular inflammatory disorders, with an excellent safety profile in the hands of physicians trained and skilled in the art of this therapy. It also allows tapering and discontinuing corticosteroids in most patients. Early initiation of therapy may decrease the risk of relapses. The authors have no proprietary or commercial interest in any materials discussed in this article.

Interleukin-6 in the pathogenesis of posterior capsule opacification and the potential role for interleukin-6 inhibition in the future of cataract surgery

Posterior capsule opacification (PCO) is a debilitating and relatively common complication of cataract surgery despite modern medical and surgical advances. The pathophysiology of this condition has largely been attributed to peptide mediators, such as transforming growth factor-beta (TGFβ), epidermal growth factor (EGF) and matrix metalloproteinases (MMPs), with the inhibition of these and other related molecules showing promising results. Studies have also shown that the levels of interleukin-6 are elevated in the eyes following cataract surgery and in various ocular inflammatory disorders that predispose to PCO development. This review proposes, utilizing ocular and extra-ocular disease models, several potential pathways through which IL-6 may modulate the activity of TGFβ, EGF, MMP-2/-9 and immune cells to promote PCO. Among the IL-6-mediated pathways discussed are the transactivation of EGF receptor, the up-regulation of TGFβ and MMP-2/-9, and the loss of ocular immune privilege through trans-signaling, down-regulation of T-regulatory cells (Tregs) and up-regulation of Th17 cells. After establishing both the potential role of ocular IL-6 in the development of PCO and the apparent upstream activity of IL-6 in relation to the known mediators of PCO, the author hypothesizes that intraoperative anti-IL-6 therapy may be of great benefit in reducing all parameters of PCO pathogenesis. This review also provides a strong basis for carrying out multiple experimental studies with IL-6 inhibitors to further elucidate the specific pathways by which IL-6 may promote PCO as well as to better determine what role inflammation may play in this disease process.

Update on the Principles and Novel Local and Systemic Therapies for the Treatment of Non-Infectious Uveitis

Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non-infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to play the role of corticosteroid-sparing agents. These can be organized in four other steps: cyclosporine and methotrexate in a second one; azathioprine, mycophenolate and tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a last one with cyclophosphamide and chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non-infectious posterior uveitis.

Virological Analysis in Patients with Human Herpes Virus 6–Associated Ocular Inflammatory Disorders

To determine whether human herpes virus 6 (HHV-6) genomic DNA and mRNA can be detected in ocular samples from patients with inflammatory disorders, and whether viral replication is involved in the development of inflammation in the eye. After informed consent was obtained, ocular fluid samples (aqueous humor and vitreous fluids) were collected from 350 patients with uveitis or endophthalmitis. Corneal samples were also collected from 65 patients with corneal infections. Multiplex PCR was performed to screen ocular samples from the patients for HHV-1 to HHV-8. Samples were also assayed for HHV-6 DNA using quantitative real-time PCR. Primers for nested RT-PCR were designed to detect amplification of mRNA (HHV-6 A IE1 U90). PCR results indicated a total of seven patients with uveitis or endophthalmitis (7/350, 2% +) and a single patient with corneal inflammatory disease were positive for HHV-6 DNA (1/65, 1.5% +). These eight patients had high copy numbers of HHV-6 DNA, with values ranging from 4.0 × 10(3) to 5.1 × 10(6) copies/mL. Real-time PCR analysis indicated that two of these cases were HHV-6 variant A and six cases were variant B. In addition, HHV-6 mRNA was clearly detected in vitreous cells collected from one of the patients, suggesting that viral replication may occur in the eye. Our results indicate that HHV-6 infection/reactivation is implicated in ocular inflammatory diseases.

Release profile and transscleral permeation of triamcinolone acetonide loaded nanostructured lipid carriers (TA-NLC): in vitro and ex vivo studies

Nanostructured lipid carriers (NLC) have been developed for sustained release of triamcinolone acetonide (TA), a corticosteroid commonly indicated for macular edema, neovascularization, and other ocular inflammatory disorders. TA-NLC were prepared by high-pressure homogenization and characterized for in vitro release by dialysis bag. Ex vivo permeation profile was assessed using rabbit sclera isolated and mounted in Franz diffusion cells. TA-NLC were placed in episcleral donor compartment and choroidal side was perfused with HEPES buffer. Tissue sections underwent drug wash-out, following analysis by validated RP-HPLC of drug content and perfused fractions collected over 24 hours. Drug release followed one-order kinetics and permeability studies confirmed that TA is able to diffuse across rabbit sclera in sustained profile, following zero-order kinetics. Strong tissue binding was observed, providing a drug depot. These findings are of potential use when designing future TA therapy strategies for ocular diseases of posterior segment. From the Clinical EditorIn this study of triamcinolone acetonide loaded nanosize lipid carriers, potential ophthalmological applications are investigated including its trans-scleral permeation and release profile. Future in vitro studies are anticipated to establish this novel lipid carrier as a future therapeutic option for ocular diseases of the posterior segment.

Road to remission: a comprehensive review of therapy in uveitis

Introduction:Although uveitis remains the third leading cause of preventable blindness in the US, the care and management of patients with uveitis and ocular inflammatory disease sit poised to make evolutionary if not revolutionary changes in the years ahead. This review serves to highlight important advances in the pharmacologic options available for the treatment of uveitis and ocular inflammation.Areas covered:Advances in steroid therapy (both topical and extended delivery), updates in the clinical safety of systemic immune modulation, and the emerging therapies for uveitis and ocular inflammatory disease are some of the areas covered in this review.Expert opinion:Corticosteroids have been the mainstay in the care of patients with ocular inflammatory disorders for many years. Indeed, some physicians still use only steroids for treating inflamed eyes. However, the mission is remission of all corticosteroids in order to prevent the complications associated with long-term corticosteroid use. The goal is to achieve quiescence through aggressive use of corticosteroids to extinguish the fire and then move along to achieve steroid-free remission through immunosuppressant agents.

Adalimumab (Humira™): a promising monoclonal anti-tumor necrosis factor alpha in ophthalmology

Tumor necrosis factor alpha (TNF-α) is a key soluble mediator involved in the inflammatory cascade of many disorders including uveitis. Among the anti-TNF-α agents, one of the most used in immune-mediated diseases, such as inflammatory arthropathies, is adalimumab (Humira™, Abbott Pharmaceutical Inc.), a fully humanized antibody. The purpose of this review is to analyze the main pharmacological and clinical aspects of adalimumab and its efficacy both in systemic and ocular inflammatory disorders. Adalimumab was effective in treating several autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. In recent years, adalimumab has been used successfully in refractory cases of intraocular inflammation. Moreover, this biological agent showed good safety and efficacy profiles in ocular use including childhood uveitis. Switching from other anti-TNF-α agents to adalimumab may offer several advantages, such as easier administration, better patient compliance, and lower rate of adverse events. Adalimumab is a promising drug for the therapy of uveitis, although further studies are needed on its application in uveitis.

Recent Patents and Emerging Therapeutics in the Treatment of Allergic Conjunctivitis

Ocular allergy is an inflammatory response of the conjunctival mucosa that also affects the cornea and eyelids. Allergic conjunctivitis includes seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC). In general, allergic conditions involve mast cell degranulation that leads to release of inflammatory mediators and activation of enzymatic cascades generating pro-inflammatory mediators. In chronic ocular inflammatory disorders associated with mast cell activation such as VKC and AKC constant inflammatory response is observed due to predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines. Antihistamines, mast-cell stabilizers, nonsteroidal anti-inflammatory agents, corticosteroids and immunomodulatory agents are commonly indicated for the treatment of acute and chronic allergic conjunctivitis. In recent years newer drug molecules have been introduced in the treatment of allergic conjunctivitis. This article reviews recent patents and emerging therapeutics in the treatment of allergic conjunctivitis.