Khayyam Durrani

Systemic therapy with conventional and novel immunomodulatory agents for ocular inflammatory disease.

Ocular inflammatory disease is the third leading cause of blindness in the United States. In addition to the conventional immunomodulatory agents, which include antimetabolites, alkylating agents, and antibiotics such as cyclosporine, many of which have been used in the treatment of this disease for decades, several new treatment modalities have emerged within the past 10 years. We review in detail the characteristics, safety, and efficacy of the conventional immunomodulators, the more novel agents such as the biologics, and investigational drugs that appear promising in the treatment of ocular inflammatory disease.

Prostate Specific Membrane Antigen (PSMA) Regulates Angiogenesis Independently of VEGF during Ocular Neovascularization

Background Aberrant growth of blood vessels in the eye forms the basis of many incapacitating diseases and currently the majority of patients respond to anti-angiogenic therapies based on blocking the principal angiogenic growth factor, vascular endothelial growth factor (VEGF). While highly successful, new therapeutic targets are critical for the increasing number of individuals susceptible to retina-related pathologies in our increasingly aging population. Prostate specific membrane antigen (PSMA) is a cell surface peptidase that is absent on normal tissue vasculature but is highly expressed on the neovasculature of most solid tumors, where we have previously shown to regulate angiogenic endothelial cell invasion. Because pathologic angiogenic responses are often triggered by distinct signals, we sought to determine if PSMA also contributes to the pathologic angiogenesis provoked by hypoxia of the retina, which underlies many debilitating retinopathies. Methodology/Principal Findings Using a mouse model of oxygen-induced retinopathy, we found that while developmental angiogenesis is normal in PSMA null mice, hypoxic challenge resulted in decreased retinal vascular pathology when compared to wild type mice as assessed by avascular area and numbers of vascular tufts/glomeruli. The vessels formed in the PSMA null mice were more organized and highly perfused, suggesting a more ‘normal’ phenotype. Importantly, the decrease in angiogenesis was not due to an impaired hypoxic response as levels of pro-angiogenic factors are comparable; indicating that PSMA regulation of angiogenesis is independent of VEGF. Furthermore, both systemic and intravitreal administration of a PSMA inhibitor in wild type mice undergoing OIR mimicked the PSMA null phenotype resulting in improved retinal vasculature. Conclusions/Significance Our data indicate that PSMA plays a VEGF-independent role in retinal angiogenesis and that the lack of or inhibition of PSMA may represent a novel therapeutic strategy for treatment of angiogenesis-based ocular diseases.

The Genetics of Adamantiades-Behcet's Disease

Adamanitiades-Behcets disease (ABD) is a relapsing systemic vasculitis that may involve the eyes, skin, and almost all other organ systems. Current research on the pathogenesis of ABD suggests a genetic basis for the disease, with certain MHC genes such as those coding for HLA-B51 being the most obvious candidates. Environmental factors such as infectious disease are thought to be responsible for triggering an immunological reaction and systemic features of the disease in genetically susceptible individuals. Identification of genes responsible for this susceptibility may lead to more definitive diagnostic tests and new approaches to the management of this potentially blinding condition.

Fundus Autofluorescence Imaging in Posterior Uveitis

Although the phenomenon of fundus autofluorescence has been known for decades, it has only recently been recognized as a measure of retinal pigment epithelial function and health. Characteristic fundus autofluorescence patterns have been described in eyes affected by inflammation of the posterior segment, and these patterns have provided insights into the pathogenesis of posterior uveitis entities. In addition, preliminary data indicate that fundus autofluorescence characteristics may serve as markers of disease activity, allow prediction of visual prognosis, and may help determine the adequacy of therapy. We provide an overview of the current state of fundus autofluorescence imaging technology and review our current knowledge of fundus autoflourescence findings and their clinical use in the posterior uveitis entities.

Adalimumab for Ocular Inflammation.

ABSTRACT Purpose: To evaluate adalimumab as an immunomodulatory treatment for non-infectious ocular inflammatory diseases. Methods: Characteristics of patients treated with adalimumab were abstracted in a standardized chart review. Main outcomes measured were control of inflammation, corticosteroid-sparing effect, and visual acuity. Results: In total, 32 patients with ocular inflammation were treated with adalimumab. The most common ophthalmic diagnoses were anterior uveitis, occurring in 15 patients (47%), and scleritis, occurring in 9 patients (28%). At 6 months of therapy, among 15 eyes with active inflammation, 7 (47%) became completely inactive, and oral prednisone was reduced to ≤10 mg/day in 2 of 4 patients (50%). On average, visual acuity decreased by 0.13 lines during the first 6 months of treatment. Adalimumab was discontinued because of lack of effectiveness in four patients within 6 months. Conclusions: Adalimumab was moderately effective in controlling inflammation in a group of highly pre-treated cases of ocular inflammatory disease.

Ocular rosacea, psoriasis, and lichen planus.

Although the number of dermatologic conditions with ocular manifestations is relatively limited, these entities have a high prevalence and represent a large proportion of clinic visits to both dermatologic and ophthalmic practices. This contribution will review oculocutaneous diseases that are not part of the allergic or autoantibody-mediated spectrum.

The efficacy and safety of adalimumab in ocular inflammatory disease

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Authors reply to Letter to the Editor- In response to: Comment on Durrani et al."s "Adalimumab for Ocular Inflammation".

Division of Ophthalmology, University of Connecticut Health, Farmington, Connecticut, USA, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA, Discovery Eye Center, MyungSung Christian Medical Center and MyungSung Medical School, Addis Ababa, Ethiopia, Massachusetts Eye Research and Surgery Institution, Waltham, Massachusetts, USA,, and Ocular Immunology and Uveitis Foundation, Waltham, Massachusetts, USA

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder most prevalent in females of African descent. Auto-antibody production in lupus results in end-organ damage by direct cytotoxicity and immune complex deposition. SLE can affect almost any ocular and adnexal structure. The most common ocular manifestation of SLE is keratoconjunctivitis sicca, which may occur in up to one-third of patients. Retinal involvement typically manifests as cotton wool spots and intraretinal hemorrhages. However, a subset of patients develop severe vaso-occlusive retinopathy, which may result in extensive capillary non-perfusion and retinal neovascularization, and is associated with a poor visual prognosis. The treatment of SLE typically includes systemic immunomodulatory therapy. In addition to conventional immunomodulators, the role of recently developed biologic response modifiers in the management of SLE and its ocular manifestations is currently under investigation.