Ocular and eyelid involvement in collagen vascular diseases. Part I. Sjögren syndrome and systemic lupus erythematosus.

Collagen vascular disease is a heterogeneous group of autoimmune diseases that affect multiple organ systems. Sjögren syndrome, dermatomyositis, scleroderma, systemic lupus erythematosus, and sarcoidosis are collagen vascular diseases that often present with characteristic cutaneous manifestations. Although less known, various ocular manifestations that affect both external and internal structures of the eye can be seen in these conditions. Multidisciplinary management between dermatologists and ophthalmologists is essential in the early diagnosis and management of collagen vascular diseases affecting both the skin and eye. Part I of our series will discuss the ocular manifestations, their diagnosis, and therapeutic options in Sjögren syndrome and systemic lupus erythematosus.

Ocular and eyelid involvement in collagen vascular diseases. Part II. Dermatomyositis, scleroderma, and sarcoidosis.

Collagen vascular disease is a heterogeneous group of autoimmune diseases that affect multiple organ systems. Sjögren syndrome, dermatomyositis, scleroderma, systemic lupus erythematosus, and sarcoidosis are collagen vascular diseases that often present with characteristic cutaneous manifestations. Although less known, various ocular manifestations that affect both external and internal structures of the eye can also be seen in these conditions. Multidisciplinary management between dermatologists and ophthalmologists is essential in the early diagnosis and management of collagen vascular diseases affecting both the skin and eye. In part II of our series, we discuss the ocular manifestations, diagnosis, and therapeutic options of dermatomyositis, scleroderma, and sarcoidosis.

NONPARANEOPLASTIC AUTOIMMUNE RETINOPATHY VERSUS PERICENTRAL RETINAL DEGENERATION PHENOTYPE: WHICH CAME FIRST? A CASE REPORT.

PURPOSE: To report a case of nonparaneoplastic autoimmune retinopathy with phenotypical features of pericentral retinal degeneration (PRD) who responded to IV immunoglobulin therapy. METHODS: A case report. A 27-year-old man presented with recent subacute progressive nyctalopia and photopsia. RESULTS: Dilated fundoscopy demonstrated confluent yellow-white patches along the main temporal vascular arcades with sparing of the central island in the posterior pole. Color vision, fundus autofluorescence, fluorescein angiography, static visual field, and electroretinographic studies were inconclusive for retinal degeneration. Subsequent genetic testing for known mutations was negative. Workup for paraneoplastic autoimmune retinopathy was negative. Antiretinal antibodies were positive. The patient was diagnosed with nonparaneoplastic autoimmune retinopathy and was treated with IV immunoglobulin, which resulted in objective and subjective improvement on electroretinography, visual field, and optical coherence tomography of the retina. CONCLUSION: Nonparaneoplastic autoimmune retinopathy may present in a patient with the clinical phenotype of PRD. It is essential to rule out nonparaneoplastic autoimmune retinopathy in patients with subacute changes in the natural course of pericentral retinal degeneration because treatment with IV immunoglobulin may be helpful.

Adalimumab for Ocular Inflammation.

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.

An eye on nutrition: The role of vitamins, essential fatty acids, and antioxidants in age-related macular degeneration, dry eye syndrome, and cataract.

Visual impairment is a global epidemic. In developing countries, nutritional deficiency and cataracts continue to be the leading cause of blindness, whereas age-related macular degeneration (AMD) and cataracts are the leading causes in developed nations. The World Health Organization has instituted VISION 2020: "The Right to Sight" as a global mission to put an end to worldwide blindness. In industrialized societies, patients, physicians, researchers, nutritionists, and biochemists have been looking toward vitamins and nutrients to prevent AMD, cataracts, and dry eye syndrome (DES). Nutrients from the AREDS2 study (lutein, zeaxanthin, vitamin C, vitamin E, zinc, copper, eicosapentanoic acid [EPA], and docosahexanoic acid [DHA]) set forth by the National Institutes of Health remain the most proven nutritional therapy for reducing the rate of advanced AMD. Omega-3 fatty acids, especially DHA, have been found to improve DES in randomized clinical trials. Conflicting results have been seen with regard to multivitamin supplementation on the prevention of cataract.

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.

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.

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.

Adamantiades-Behcet disease: diagnosis and current concepts in management of ocular manifestations.

Adamantiades-Behcet disease is a relapsing systemic vasculitis that may involve the eyes, skin, and almost all other organ systems. The comprehensive ophthalmologist plays a key role by not only making the diagnosis but also by monitoring inflammatory status to guide systemic therapy. If left untreated, the disease has a high likelihood of causing blindness and death. Adamantiades-Behcet disease with retinal involvement is now considered an absolute indication for systemic immunomodulatory therapy. The diagnostic signs, potential complications, and treatment modalities currently available for ocular Adamantiades-Behcet disease are reviewed.

Effect of intravitreal injection of ranibizumab in combination with verteporfin PDT on normal primate retina and choroid.

PURPOSE: To evaluate the effect of intravitreal injection of a monoclonal antibody fragment (ranibizumab, also known as rhuFab V2 and Lucentis; Genentech, S. San Francisco, CA) directed against vascular endothelial growth factor (VEGF) in combination with verteporfin photodynamic therapy (PDT) on normal primate retina and choroid. METHODS: Eight cynomolgus monkeys were treated with intravitreal ranibizumab in one eye and placebo in the other, alternating with verteporfin PDT in both eyes on a weekly basis for 6 to 7 weeks. Treatment effects were evaluated by color fundus photography, fluorescein angiography, and light and electron microscopy. RESULTS: Over the course of the study, increasing retinal pigment epithelial changes, with corresponding window defects, developed in both eyes of all animals on fluorescein angiography over the course of the study. No complications attributable to the intravitreal injection of ranibizumab were observed. Histologic analysis revealed a similar reduction in choriocapillaris density in the irradiated area of eyes treated with PDT alone compared with those that received combination treatment. CONCLUSIONS: In this limited study of normal monkey eyes, no severe adverse effects from the combination of intravitreal ranibizumab and verteporfin PDT were demonstrated compared with PDT alone.

Psoriatic uveitis: a distinct clinical entity?

PURPOSE: To describe the clinical characteristics of uveitis occurring in patients with psoriasis and to compare them with patients with idiopathic anterior uveitis and HLA-B27-associated anterior uveitis. DESIGN: Case-control study. METHODS: The charts of 36 patients with a diagnosis of uveitis and psoriasis visiting the Immunology and Uveitis Service at the Massachusetts Eye and Ear Infirmary between January 2000 and December 2001 were reviewed. Clinical characteristics, therapy, and outcomes of uveitis were compared with 30 randomly selected patients with either idiopathic anterior uveitis or with HLA-B27-associated anterior uveitis. RESULTS: The mean age at presentation for uveitis was significantly higher in patients with psoriasis compared with nonpsoriatic groups (44.6 years in HLA-B27-psoriatic patients vs 35.9 years in HLA-B27- nonpsoriatic patients, P = .034; 52.7 years in HLA-B27+ psoriatic vs 35.7 years in HLA-B27+ nonpsoriatic patients, P = .001). Uveitis in patients with psoriasis also tended to be bilateral (62%) and prolonged (11.2 weeks). HLA-B27+ patients with psoriasis required supplemental therapy with oral nonsteroidal anti-inflammatory drugs (95% confidence interval [CI] 1.41 to 5.36, P = .003) for anterior uveitis more often than did the HLA-B27+ nonpsoriatic group. Patients with psoriasis and uveitis who were HLA-B27+ required oral NSAIDs (95% CI 1.51 to 9.79, P = .001) for anterior uveitis more often than did HLA-B27- psoriatic patients. CONCLUSION: Uveitis in patients with psoriasis may have distinguishing clinical features. Further epidemiologic studies are required to determine the strength of association between psoriasis without arthritis but with uveitis.

Pulse IV cyclophosphamide in ocular inflammatory disease: efficacy and short-term safety.

PURPOSE: To assess the efficacy and short-term safety of appropriately monitored pulse IV cyclophosphamide therapy in the treatment of patients with severe or treatment-resistant autoimmune ocular inflammatory disease. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Thirty-eight patients with severe or recalcitrant ocular inflammation of diverse etiologies. METHODS: Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Thirty-eight consecutive patients treated with pulse IV cyclophosphamide between January 1995 and March 2002 were analyzed. MAIN OUTCOME MEASURES: The control of inflammation, steroid-sparing effect, visual acuity, and adverse reactions. RESULTS: A positive response to treatment occurred in 68% of patients during the study period, with 55% achieving complete quiescence. A steroid-sparing effect was achieved in all patients previously on systemic steroid, allowing successful discontinuation of the drug in 41%. Visual acuity was maintained in 66% and improved in 21% of involved eyes. The most common side effects observed were fatigue (63%), nausea (32%), and headache (22%). None required a permanent discontinuation of therapy. CONCLUSIONS: Pulse IV cyclophosphamide is an effective therapeutic modality in patients with severe or treatment-resistant ocular inflammatory disease.