PURPOSE: To assess the feasibility of a study design that may determine whether subcutaneous administration of the interleukin-2 receptor antibody daclizumab can safely reduce the dependence on standard systemic corticosteroids or other immunosuppressive regimens in patients with sight-threatening, noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Prospective, multicenter, nonrandomized, noncomparative, open-label interventional trial. PARTICIPANTS: Fifteen patients, 5 each at 3 clinical centers, with noninfectious intermediate, posterior, or panuveitis, who require a currently stable immunosuppression regimen of systemic corticosteroids and/or other systemic treatments to control noninfectious intraocular inflammation. METHODS: After enrollment and baseline ophthalmic evaluations, 2 induction treatments were given 2 weeks apart using subcutaneous (SC) daclizumab at 2 mg/kg. Subcutaneous daclizumab maintenance treatments were then continued every 2 weeks at 1 mg/kg for 6 months. The initial immunosuppression load was tapered over 8 to 12 weeks in a staggered fashion beginning with the first induction treatment. Safety evaluations were performed at each treatment visit, with a primary efficacy evaluation at 12 weeks and a repeat efficacy evaluation at 26 weeks. MAIN OUTCOME MEASURES: Best-corrected visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] method) with a concurrent taper of concomitant systemic immunosuppression medication load (tabulated by use of a weighted scoring system) was assessed; target for success was defined as a 50% or greater reduction in concomitant immunosuppression load by 12 weeks while maintaining visual acuity within 5 ETDRS letters of baseline. Ocular inflammation was assessed at each visit with standardized grading scales. RESULTS: Ten of 15 patients (67%) receiving SC daclizumab treatments every other week successfully achieved the primary efficacy end point of reducing their concomitant immunosuppression load by at least 50% while maintaining their baseline visual acuity at 12 and 26 weeks. Subcutaneous daclizumab injections were well tolerated with no serious adverse events observed during the 6 months of treatments, although 3 patients experienced possibly related, nonserious adverse events. CONCLUSIONS: Subcutaneous daclizumab induction treatments at 2 mg/kg followed by 1 mg/kg maintenance treatments every other week seems safe and, in most cases, may reduce the concomitant immunosuppressive load required to treat noninfectious uveitis for 12 to 26 weeks.

OBJECTIVE: To characterize the fundus autofluorescence (FAF) findings in patients with white dot syndromes (WDSs). METHODS: Patients with WDSs underwent ophthalmic examination, fundus photography, fluorescein angiography, and FAF imaging. Patients were categorized as having no, minimal, or predominant foveal hypoautofluorescence. The severity of visual impairment was then correlated with the degree of foveal hypoautofluorescence. RESULTS: Fifty-five eyes of 28 patients with WDSs were evaluated. Visual acuities ranged from 20/12.5 to hand motions. Diagnoses included serpiginous choroidopathy (5 patients), birdshot retinochoroidopathy (10), multifocal choroiditis (8), relentless placoid chorioretinitis (1), presumed tuberculosis-associated serpiginouslike choroidopathy (1), acute posterior multifocal placoid pigment epitheliopathy (1), and acute zonal occult outer retinopathy (2). In active serpiginous choroidopathy, notable hyperautofluorescence in active disease distinguished it from the variegated FAF features of tuberculosis-associated serpiginouslike choroidopathy. The percentage of patients with visual acuity impairment of less than 20/40 differed among eyes with no, minimal, and predominant foveal hypoautofluorescence (P <.001). Patients with predominant foveal hypoautofluorescence demonstrated worse visual acuity than those with minimal or no foveal hypoautofluorescence (both P <.001). CONCLUSIONS: Fundus autofluorescence imaging is useful in the evaluation of the WDS. Visual acuity impairment is correlated with foveal hypoautofluorescence. Further studies are needed to evaluate the precise role of FAF imaging in the WDSs.

We present an interventional case report of exfoliating goblet cell hyperplasia mimicking pterygium. A 44-year-old male with bilateral lesions of the nasal bulbar conjunctiva extending over the cornea, consistent with pterygia, underwent surgical excision of the lesion in his left eye. Histopathologic examination revealed an exophytic lesion made up of proliferated goblet cells with benign cytologic features. Some of the goblet cells were atrophic and seemed to be desquamating from the lesion surface. Cytologic examination of a tear specimen collected from the right eye revealed the presence of exfoliated goblet cells admixed with mucin material. The lesion had not recurred three months after surgery. Exfoliating goblet cell hyperplasia, a condition not previously reported on the ocular surface, may mimic pterygium. Histopathologic examination is required to establish the diagnosis.

PURPOSE: To evaluate mycophenolate mofetil as a single noncorticosteroid immunosuppressive treatment for noninfectious ocular inflammatory diseases. DESIGN: Retrospective cohort study. METHODS: Characteristics of patients with noninfectious ocular inflammation treated with mycophenolate mofetil at 4 subspecialty clinics from 1995 to 2007 were abstracted by expert reviewers in a standardized chart review of every eye at every visit. Main outcomes measured were control of inflammation, corticosteroid-sparing effects, and discontinuation of mycophenolate mofetil (including the reasons for discontinuation). Survival analysis was used to estimate the incidence of outcomes, and to identify risk factors for each. RESULTS: Among 236 patients (397 eyes) treated with mycophenolate mofetil monotherapy, 20.3%, 11.9%, and 39.8% had anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis respectively; 14% had scleritis; 7.6% had mucous membrane pemphigoid; and 6.4% had other ocular inflammatory diseases. By Kaplan-Meier estimation, complete control of inflammation-sustained over consecutive visits spanning at least 28 days-was achieved in 53% and 73% of patients within 6 months and 1 year respectively. Systemic corticosteroid dosage was reduced to 10 mg of prednisone or less, while maintaining sustained control of inflammation, in 41% and 55% of patients in 6 months and 1 year respectively. Twelve percent of patients discontinued mycophenolate mofetil within the first year because of side effects of therapy. CONCLUSIONS: Given sufficient time, mycophenolate mofetil was effective in managing ocular inflammation in approximately half of the treated patients. Treatment-limiting side effects were observed in 12% of patients and typically were reversible.

PURPOSE: To determine the frequency of occurrence of limited clinical features which distinguish patients with Vogt-Koyanagi-Harada (VKH) disease from those with non-VKH uveitis. DESIGN: Comparative case series. PARTICIPANTS: We included 1147 patients. METHODS: All patients with bilateral ocular inflammatory disease presenting to any of 10 uveitis centers in the 3-month period between January 1 and March 31, 2006 (inclusive), were asked to participate. The clinical and historical features of disease were obtained from the participants via direct interview and chart review. Patients were stratified based on whether they were diagnosed with VKH disease or non-VKH uveitis for statistical analysis. MAIN OUTCOME MEASURES: Presence or absence of various clinical features in the 2 populations. RESULTS: Of 1147 patients, 180 were diagnosed with VKH disease and 967 with non-VKH uveitis. Hispanics and Asians were more likely to be diagnosed with VKH than non-VKH disease compared with other ethnicities. In acute disease, the finding of exudative retinal detachment was most likely to be found in VKH disease with a positive predictive value (PPV) of 100 and negative predictive value (NPV) of 88.4, whereas in chronic disease, sunset glow fundus was most likely to be found, with a PPV of 94.5 and NPV of 89.2. CONCLUSIONS: Numerous clinical findings have been described in the past as important in the diagnosis of VKH. The current study reveals that of these, 2 are highly specific to this entity in an ethnically and geographically diverse group of patients with nontraumatic bilateral uveitis. These clinical findings are exudative retinal detachment during acute disease and sunset glow fundus during the chronic phase of the disease. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.

PURPOSE: To evaluate the clinical outcomes of cyclosporine treatment for noninfectious ocular inflammation. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 373 patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to use cyclosporine as a single noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007 inclusive. METHODS: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage of cyclosporine and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. MAIN OUTCOME MEASURES: Control of inflammation, sustained control after reducing corticosteroid dosages, and discontinuation of therapy because of toxicity. RESULTS: Of the 373 patients (681 eyes) initiating cyclosporine monotherapy, 33.4% by 6 months and 51.9% by 1 year gained sustained, complete control of inflammation over at least 2 visits spanning at least 28 days. Approximately 25% more improved to a level of slight inflammatory activity by each of these time points. Corticosteroid-sparing success (completely controlled inflammation for at least 28 days with prednisone </= 10 mg/day) was achieved by 22.1% by 6 months and 36.1% within 1 year. Toxicity led to discontinuation of therapy within 1 year by 10.7% of the population. Patients aged more than 55 years were more than 3-fold more likely to discontinue therapy because of toxicity than patients aged 18 to 39 years. Doses of 151 to 250 mg/day tended to be more successful than lower doses and were not associated with a higher discontinuation for toxicity rate; higher doses did not seem to offer a therapeutic advantage. CONCLUSIONS: Cyclosporine, with corticosteroid therapy as indicated, was modestly effective for controlling ocular inflammation. Our data support a preference for cyclosporine adult dosing between 151 and 250 mg/day. Although cyclosporine was tolerated by the majority of patients, toxicity was more frequent with increasing age; alternative agents may be preferred for patients aged more than 55 years. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

BACKGROUND: The indications for enucleation have changed significantly over the past 60 years. We conducted a clinicopathologic study of enucleated globes to determine how and why the indications for enucleation have changed over time. METHODS: This retrospective review examined the pathology reports for 3,264 enucleated globes submitted to the Doheny Eye Institute between 1950 and 2006. Three years per decade were examined to generate a representative pool of specimens for each decade. Although the data for the 2000s were only available up to 2006, the data for this decade are drawn from 3 sample years as are all other decades. Pathology reports were reviewed for demographic information (age, sex, and ethnicity), clinical history prior to enucleation, and pathologic findings and diagnoses. Specimens were grouped according to the reason for enucleation into the following categories: atrophic/phthisis bulbi, congenital, glaucoma, infection, longstanding retinal detachment, trauma, tumor, uveitis, and other. RESULTS: During the study period, there were 3,264 enucleated globes. Overall, the total number of enucleations decreased over time from a peak of 1,014 in the 1960s to 275 in the 2000s. Glaucoma was the most common reason for enucleation during the 1950s (23%, 127 globes) and 1960s (31%, 315 globes). However, glaucoma steadily decreased over the following decades, and was responsible for only 8%(23 globes) of enucleations in the 2000s. Neovascular glaucoma (including glaucoma secondary to retinal vein occlusion and diabetic neovascularization) accounted for 21%(27 globes) of enucleations in the 1950s. By the 2000s, this number was 57%(13 globes). Trauma-related glaucoma accounted for 34%(43 globes) of all enucleations due to glaucoma in the 1950s, and 0%(0 globes) in the 2000s. Enucleation of globes with intraocular neoplasms accounted for 14%(79 globes) of total enucleations in the 1950s, 33%(120 globes) in the 1990s, and 51%(141 globes) in the 2000s. Uveal melanoma was the main intraocular neoplasm in the 1950s (77%, 60 globes), and retinoblastoma was the primary tumor in the enucleated globes of the 2000s (69%, 97 globes). CONCLUSIONS: Improved medical and surgical treatment of conditions that lead to end-stage eye disease have led to a decrease in total enucleated globes. This is particularly evident for glaucoma. Changing demographics in Los Angeles and referral patterns are most likely responsible for the increase in retinoblastoma. The absolute number of enucleations secondary to neoplasms has not decreased over time, despite an increase in globe-conserving treatments such as chemotherapy and radioactive plaques.

PURPOSE:: The purpose of this study was to determine whether fundus autofluorescence (FAF) and spectral domain-optical coherence tomography (SD-OCT) imaging allow better assessment of retinal pigment epithelium and the outer retina in subjects with chronic Vogt-Koyanagi-Harada disease compared with examination and angiography alone. METHODS:: A cross-sectional analysis of a series of seven consecutive patients with chronic Vogt-Koyanagi-Harada disease undergoing FAF and SD-OCT was conducted. Chronic disease was defined as duration of intraocular inflammation >3 months. Color fundus photographs were correlated to FAF and SD-OCT images. The images were later correlated to fluorescein angiography and indocyanine green angiography. RESULTS:: All patients had sunset glow fundus, which resulted in no apparent corresponding abnormality on FAF or SD-OCT. Lesions with decreased autofluorescence signal were observed in 11 eyes (85%), being associated with loss of the retinal pigment epithelium and involvement of the outer retina on SD-OCT. In 5 eyes (38%), some of these lesions were very subtle on clinical examination but easily detected by FAF. Lesions with increased autofluorescence signal were seen in 8 eyes (61.5%), showing variable involvement of the outer retina on SD-OCT and corresponding clinically to areas of retinal pigment epithelium proliferation and cystoid macular edema. CONCLUSION:: Combined use of FAF and SD-OCT imaging allowed noninvasive delineation of retinal pigment epithelium/outer retina changes in patients with chronic Vogt-Koyanagi-Harada disease, which were consistent with previous histopathologic reports. Some of these changes were not apparent on clinical examination.

PURPOSE: To evaluate the risk of and risk factors for hypopyon among patients with uveitis and to evaluate the risk of visual changes and complications after hypopyon. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with uveitis at 4 academic ocular inflammation subspecialty practices. METHODS: Data were ascertained by standardized chart review. MAIN OUTCOME MEASURES: Prevalence and incidence of hypopyon, risk factors for hypopyon, and incidence of visual acuity changes and ocular complications after hypopyon. RESULTS: Among 4911 patients with uveitis, 41 (8.3/1000) cases of hypopyon were identified at the time of cohort entry. Of these, 2885 initially free of hypopyon were followed over 9451 person-years, during which 81 patients (2.8%) developed hypopyon (8.57/1000 person-years). Risk factors for incident hypopyon included Behçet's disease (adjusted relative risk [RR]=5.30; 95% confidence interval [CI], 2.76-10.2), spondyloarthropathy (adjusted RR=2.86; 95% CI, 1.48-5.52), and human leukocyte antigen (HLA)-B27 positivity (adjusted RR=2.04; 95% CI, 1.17-3.56). Patients with both a spondyloarthropathy and HLA-B27 had a higher risk than either factor alone (crude RR=4.39; 95% CI, 2.26-8.51). Diagnosis of intermediate uveitis (+/- anterior uveitis) was associated with a lower risk of hypopyon (with respect to anterior uveitis only, adjusted RR=0.35; 95% CI, 0.15-0.85). Hypopyon incidence tended to be lower among patients with sarcoidosis (crude RR=0.22; 95% CI, 0.06-0.90; adjusted RR=-0.28; 95% CI, 0.07-1.15). Post-hypopyon eyes and eyes not developing hypopyon had a similar incidence of band keratopathy, posterior synechiae, ocular hypertension, hypotony, macular edema, epiretinal membrane, cataract surgery, or glaucoma surgery. Post-hypopyon eyes were more likely than eyes not developing hypopyon to gain 3 lines of vision (crude RR=1.54; 95% CI, 1.05-2.24) and were less likely to develop 20/200 or worse visual acuity (crude RR=0.41; 95% CI, 0.17-0.99); otherwise, visual outcomes were similar in these groups. CONCLUSIONS: Hypopyon is an uncommon occurrence in patients with uveitis. Risk factors included Behçet's disease, HLA-B27 positivity, and spondyloarthropathy. Intermediate uveitis cases (+/- anterior uveitis) had a lower risk of hypopyon. On average, post-hypopyon eyes were no more likely than other eyes with uveitis to develop structural ocular complications or lose visual acuity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Surgically induced necrotising scleritis (SINS) following sequential laser-assisted in situ keratomileusis (LASIK) and pterygium excision with conjunctival autograft. Purpose: To report a case of SINS occurring 1 month after uncomplicated pterygium excision with conjunctival autograft. Setting: Department of Ophthalmology, Singleton Hospital, Abertawe Bro Morgannwg University NHS trust, United Kingdom Method: A 70-year-old male presented with a 10 day history of redness and reduced vision in the right eye. Bilateral hyperopic LASIK and right eye pterygium excision with conjunctival autograft had been performed elsewhere, 6 months and 1 month prior to presentation. BCVA were 6/60 OD and 6/6 OS. A 2mm full thickness nasal corneal perforation with adjacent scleral melt (6.5x4mm) was evident. Tectonic full thickness corneal and scleral patch grafting with amniotic membrane graft overlay was performed with systemic immunosuppression (prednisolone 60mg od). Results: Recurrence of the corneascleral melt occurred one month postoperatively on reduction of prednisolone to 15mg od. This was initially managed successfully with cyclophosphamide 100mg and prednisolone 80mg. Two months postoperatively recurrent corneal perforation required the application of cyanoacrylate glue. At latest follow up four months postoperatively the corneal glue is insitu with no evidence of recurrent melt. Conclusions: SINS following pterygium excision with conjunctival autograft is rare with only 2 case reports in the literature. This is the first reported case of SINS occurring after pterygium excision with conjunctival autograft with preceeding LASIK.

PURPOSE: To present our experience with the diagnosis of benign masquerade syndromes, to evaluate the prevalence, clinical features and diagnostic tests. METHODS: A retrospective study of 42 patients treated for benign uveitis masquerade syndromes at our Department for DIAGNOSIS AND TREATMENT OF UVEITIS: 1st Faculty of Medicine in Prague, between 1996 and 2006, was performed. RESULTS: Seventy-nine patients with masquerade syndromes (7.1%) from all 1112 patients with uveitis were included. Malign masquerade syndromes were recognized in 37 patients (19 females and 18 males, mean age 55 years) and benign masquerade syndromes in 42 patients (23 females and 19 males, mean age 33.7 years). The most frequent cause of benign masquerade syndromes was a group of vascular anomalies (22 patients). The primary diagnosis was infectious or idiopathic uveitis in many cases.The most valuable diagnostic procedures were fluorescein angiography and analysis of intraocular fluids. CONCLUSION: Diagnosis of masquerade syndromes should be considered in all patients with idiopathic corticosteroid-resistant chronic uveitis. Timely diagnosis and treatment may improve the prognosis of masquerade syndromes.

The International Committee on Classification of Corneal Dystrophies, briefly IC (3)D, was founded with the sponsorship of the American Cornea Society and the American Academy of Ophthalmology in July 2005. This committee consists of 17 corneal experts (1) from USA, Asia and Europe. The goal of this group was to develop a new, internationally accepted classification of corneal dystrophies (CD) based on modern clinical, histological and genetical knowledge. The aim of the new classification should be to avoid wrong interpretations and misnomers of the different forms of CD. The IC (3)D extensive manuscript is in press as Supplement publication in the journal "Cornea". The 25 different CD are divided in four categories by clinical and genetical knowledge. Additionally, templates for each type of CD are included. Finally, many typical color slit-lamp photos are presented in the publication together with essential references and current genetical results in tabular form. As members of IC (3)D the authors present a clinical landmark survey of the different corneal dystrophies. The ophthalmologist is the first to examine and to diagnose a new patient with a probable CD at the slit-lamp. Our elaborated table of landmarks is supposed to be a "bridge" for the ophthalmologist to precisely define the corneal opacities of a presumed CD. This "bridge" makes it easier for them to study the IC (3)D Supplement publication and to get more information including adequate differential diagnosis.

The study was undertaken to define a role of immunological damage reactions in the pathogenesis of uveitis in the presence of rheumatic diseases on the basis of an in-depth analysis of the immunological characteristics of the disease. A complex immunological study was made in 76 rheumatic patients with uveitis in the acute phase of eye diseases. Among the patients, the males and females were 67.1 and 32.9%, respectively; their mean age was 41+/-6.4 years. The authors made CD typing of lymphocytes, by evaluating the processes of their activation and apoptosis, estimated the amount of the cytokines IL-4, IFN-gamma, TNF-alpha, and soluble TNF-alpha receptor in the serum and tear. The authors have established the following characteristics of an immune response in rheumatic patients with uveitis: a predominant impairment of cellular immunity with an increase in the processes of positive activation of lymphocytes and a reduction in the processes of their apoptosis; formation of Th1 deviation of systemic and local immune responses; elevated levels of the proinflammatory cytokine TNF-alpha in the blood and in the tear in particular. Humoral immunity was found to be activated with a rise in the levels of immunoglobulins of all classes and circulating immune complexes.

OBJECTIVES: To investigate the effect of corticotherapy on IL-8, IL-12, and nitric oxide (NO) production during idiopathic and Behçet active uveitis. METHODS: Peripheral venous blood was drawn from 70 patients with active uveitis before and during corticotherapy (32 with Behçet uveitis and 38 with idiopathic uveitis) and from 30 controls. Plasma was collected and peripheral blood mononuclear cells were separated immediately and cultured with or without Concanavaline A. IL-8 and IL-12 levels in plasma and culture supernatants were measured by specific enzyme-linked immunosorbent assay (ELISA). Nitric oxide levels were evaluated using a modified Griess method. RESULTS: Before therapy, the two groups of patients showed highly significant elevation of IL-8, IL-12, and NO levels compared to control subjects. During therapy, IL-8 and nitric oxide levels were significantly lower in active idiopathic and Behçet active uveitis both in vivo and in vitro. This effect was correlated with therapy duration. In contrast, while significant reduction of IL-12 levels was observed both in vivo and in vitro in idiopathic active uveitis during therapy, this effect was observed in vitro in Behçet active uveitis but not in vivo. CONCLUSION: Our results suggest that IL-8, IL-12, and NO are involved in the physiopathological mechanisms of idiopathic and Behçet uveitis. These three molecules showed different degrees of sensitivity to the inhibitory effect of corticoids, reflecting their different regulation by corticotherapy during active phases of the two diseases. According to our study, IL-8 can serve as a marker of inflammatory responses, while IL-12 should be used as a marker of the specific immune responses during active uveitis.

PURPOSE: To evaluate the concentration of sFas in serum of uveitis patients. MATERIAL AND METHODS: Serum samples were collected from 13 patients with uveitis and 12 controls. All patients have underwent ophthalmic and laboratory examinations. The sFas levels were determined by immunoenzymatic assay ELISA. RESULTS: We found statistically increased levels of sFas in serum of patients with uveitis compared with controls. CONCLUSIONS: Our results suggest a systemic nature of uveitis with persistent activation of the immune system. Apoptosis may play regulatory role in ocular inflammation of patients with uveitis.

Six cases with pathognomonic uveitis pathologies are presented and discussed using multiple-choice questions.

PURPOSE: Spondyloarthritis (SpA) encompass different diseases with common characteristics, ankylosing spondylitis (AS) being the most typical. Undifferentiated SpA may evolve into AS. In France, SpA and rheumatoid arthritis could have the same prevalence. AS has a profound impact on the quality of live and function of patients as well as social and economic consequences for the society. KEY POINTS: There is a mean delay of five to eight years between onset of symptoms and diagnosis of AS. This is due to the fact that radiographic sacroiliitis is delayed. The purpose of an earlier diagnosis is emphasized by the need for a better management, the new diagnostic method including magnetic resonance imaging and ultrasonography, and by the efficacy of anti-TNF therapy. The current criteria (New-York, Amor, ESSG) are classification but not diagnostic criteria. Their sensitivity is insufficient for an early diagnosis of SpA. Several groups are studying methods to ensure an early diagnosis. The group of Berlin has proposed, for patients suffering inflammatory chronic back pain, an algorithm using clinical, radiological and biological signs with, if necessary, search of HLA-B27 and MRI of sacroiliac joints. But this system is theoretical and the group of Maastricht found it of little effectiveness. Furthermore, it does not take account patients with symptoms beginning out of the spine. CONCLUSION: We believe that only the follow-up of cohorts constituted of patients with early SpA will enable us to improve our knowledge regarding diagnostic criteria and new tools for early diagnosis, as well as outcome, prognosis and early management of SpA and AS.