Relationship between Uveitis and Thyroid Disease: A 13-Year Nationwide Population-based Cohort Study in Taiwan.

Purpose: To investigate whether patients with thyroid disease are at increased risk of uveitis.Methods: Data was collected from the Taiwan National Health Insurance system and included patients newly diagnosed with thyroid disease from 2000 to 2012. The endpoint of interest was a diagnosis of uveitis.Results: In analyzing 21,396 patients with thyroid disease, yielding 85,584 matched comparisons, patients with thyroid disease to have a significantly higher cumulative incidence of uveitis when compared to the control cohort with the Kaplan-Meier analysis. This result was further confirmed by Cox regression analysis. The increased risk was persistent in both genders. The association between thyroid disease and uveitis was stronger in patients without diabetes or hypertension.Conclusion: Patients with thyroid disease were found to have a higher risk for uveitis. For certain age groups or patients without diabetes or hypertension, the role of thyroid disease might be more crucial for uveitis development.

Drug Retention Rate and Causes of Discontinuation of Adalimumab in Uveitis: Real-World Data from the Biotherapies in Uveitis (BioÚvea) Study Group.

PURPOSE: To study the drug retention rate (DRR), causes, and predictors of discontinuation of adalimumab (ADA) in a real-world uveitis setting. DESIGN: Multicentric, nationwide, registry-based, ambispective, observational study. PARTICIPANTS: Patients treated with ADA for noninfectious uveitis (NIU) in the Biotherapies for Uveitis (BioÚvea) Spanish registry from November 2016 to November 2017. METHODS: Demographics, clinical data, timing, and reasons for discontinuation, if occurred, were recorded. The DRR and drug retention time (DRT) were estimated using the Kaplan-Meier method. Median follow-up was analyzed by reverse Kaplan-Meier. Log-rank test was used for comparisons. Cox proportional-hazards model (PHM) and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events. MAIN OUTCOME MEASURES: Drug retention rate and DRT. RESULTS: A total of 392 patients were analyzed, including 218 women. Median age was 39 (interquartile range, 25) years. Nonanterior uveitis was recorded in 242 patients. Median follow-up was 49.07 (0.97-131.67) months, median DRT (survival) was 69.3 months, and 14 patients were lost to follow-up. The DRR at 6, 12, 24, and 60 months was 92.97%, 87.68%, 76.31%, and 54.28%, respectively. Adalimumab was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74 patients, adverse event in 34 patients, and sustained quiescence in 25 patients. Recorded adverse events included infections in 10 patients and malignant neoplasms in 3 patients. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. Adalimumab was prescribed as a second or greater biotherapy line in 76 patients who showed shorter DRT (P = 0.038). Starting ADA in nonbiotherapy-naive patients was a predictor for "discontinuation due to inefficacy," whereas undifferentiated uveitis was a predictor for "discontinuation due to adverse event." Drug retention time was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence. CONCLUSIONS: Drug retention rate of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show a significant influence on DRT. The use of ADA as a second or further biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.

A Review of the Course and Treatment of Non-Infectious Uveitis during Pregnancy.

Inflammatory conditions such as autoimmune uveitis often occur in women of childbearing age. During pregnancy, women may experience exacerbations of their disease in the first trimester. In the later stages of pregnancy, however, the uveitis tends to remain less active. The management of uveitis during pregnancy is a challenging task, forcing the physician to re-evaluate the patient's current therapy and offer alternative options that pose the least risk to the patient and fetus. This article will review treatments widely used for uveitis, including corticosteroid therapy, anti-metabolites, calcineurin inhibitors, and biologic therapy. It will evaluate the use of these medications in pregnancy and the postpartum state.

Juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4(+) T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management.

Autoimmune uveitis: clinical, pathogenetic, and therapeutic features.

Autoimmune uveitis (AU), an inflammatory non-infectious process of the vascular layer of the eye, can lead to visual impairment and, in the absence of a timely diagnosis and suitable therapy, can even result in total blindness. The majority of AU cases are idiopathic, whereas fewer than 20 % are associated with systemic diseases. The clinical severity of AU depends on whether the anterior, intermediate, or posterior part of the uvea is involved and may range from almost asymptomatic to rapidly sight-threatening forms. Race, genetic background, and environmental factors can also influence the clinical picture. The pathogenetic mechanism of AU is still poorly defined, given its remarkable heterogeneity and the many discrepancies between experimental and human uveitis. Even so, the onset of AU is thought to be related to an aberrant T cell-mediated immune response, triggered by inflammation and directed against retinal or cross-reactive antigens. B cells may also play a role in uveal antigen presentation and in the subsequent activation of T cells. The management of AU remains a challenge for clinicians, especially because of the paucity of randomized clinical trials that have systematically evaluated the effectiveness of different drugs. In addition to topical treatment, several different therapeutic options are available, although a standardized regimen is thus far lacking. Current guidelines recommend corticosteroids as the first-line therapy for patients with active AU. Immunosuppressive drugs may be subsequently required to treat steroid-resistant AU and for steroid-sparing purposes. The recent introduction of biological agents, such as those targeting tumor necrosis factor-α, is expected to remarkably increase the percentages of responders and to prevent irreversible sight impairment. This paper reviews the clinical features of AU and its crucial pathogenetic targets in relation to the current therapeutic perspectives. Also, the largest clinical trials conducted in the last 12 years for the treatment of AU are summarized and critically discussed.

Outcome of viscodilation and tensioning of Schlemm's canal for uveitic glaucoma.

OBJECTIVE: To evaluate the safety and efficacy of circumferential viscodilation and tensioning of Schlemm's canal (canaloplasty) in the treatment of uveitic glaucoma (UG). DESIGN: Pilot, retrospective, noncomparative case series. PARTICIPANTS: Nineteen uveitic eyes of 15 patients with UG. METHODS: The main outcome measure was surgical success. Secondary outcome measures included intraocular pressure, usage of ocular hypotensive medication, visual acuity, and sight-threatening complications. Patients were included when UG could not be controlled despite maximum tolerated medical therapy. Exclusion criteria were peripheral anterior synechiae and previous glaucoma surgery. RESULTS: Mean follow-up time from canaloplasty was 2.6 ± 1.1 years. Mean intraocular pressure decreased from 30.4 ± 8.4 mm Hg preoperatively to 13.8 ± 5.0 mm Hg at last follow-up (p < 0.001). The mean number of ocular hypotensive medications decreased from 3.7 ± 0.8 preoperatively to 0.4 ± 1.0 at last follow-up (p < 0.001). At last follow-up, the complete success, qualified success, and failure rates were 73.7%, 10.5%, and 15.8%, respectively. No canaloplasty-related permanent sight-reducing complications occurred. Preoperative best corrected visual acuity decreased more than 1 Snellen line in 1 eye due to exacerbation of uveitis 18 months postoperatively. CONCLUSIONS: Canaloplasty appears to be a relatively safe and effective initial surgical intervention in UG.

Risk factors for the development of macular edema in noninfectious uveitis.

PURPOSE: Macular edema (ME) is a vision-limiting complication of uveitis. The aim of the present study was to identify risk factors for the development of ME. METHODS: This was an observational, cross-sectional study including 350 patients with noninfectious uveitis. Data were acquired by using a questionnaire. Associations with ME were analyzed for age,alcohol consumption, coffee consumption, cardiovascular risk factors, and level of education. RESULTS: On univariate analysis, patients with ME were older (p<0.001, odds ratio [OR] 1.03) and had a longer history of uveitis (p=0.006, OR 1.03). Patients with university certificate or high school diploma had a significantly reduced risk (OR 0.25, p<0.001) to develop ME compared to patients with less education. For smoking, the number of pack-years was significantly but weakly associated with the presence of ME (p=0.02, OR 1.02). Smokers with a smoking history of more than 20 pack-years had a higher risk for ME (OR = 2.46, confidence interval 1.2-5.2). Daily coffee consumption predisposed to ME (p=0.02, OR 2.1). Arterial hypertension, body mass index, alcohol consumptions, and hypercholesterinemia were not associated with ME. Multivariate analysis confirmed age, coffee consumption,and low education to be risk factors for ME, whereas smoking was lost on multivariate analysis. CONCLUSIONS: Age, low level of education, daily coffee consumption, and possibly smoking are risk factors for ME in patients with noninfectious uveitis.

Association of systemic steroids and mycophenolate mofetil as rescue therapy for uveitic choroidal neovascularization unresponsive to the traditional immunosuppressants: interventional case series.

To study the efficacy of systemic steroids (SS) associated with mycophenolate mofetil (MMF) for the control of juxta/sub-foveal uveitic choroidal neovascularization (CNV) unresponsive to the traditional immunosuppressive agents. Patients with juxta/sub-foveal uveitic CNV unresponsive to the traditional immunosuppressive drugs were treated with SS and MMF. The study was designed as a prospective, consecutive, open-label, interventional case series. Visual gain and loss were defined as improving or worsening of two or more lines of best-corrected visual acuity (BCVA), respectively. CNV size outcome was dichotomized as "increased" or "stable/reduced", if increased >200 µm(2), or reduced ≥ 200 µm(2) or not modified by 200 µm(2), respectively. Nine cases (12 eyes) have been considered; ages ranged from 27 to 56 years. The mean follow-up time was 18.2 ± 2.9 months (min: 14 months, max: 23 months). At base-line, the mean BCVA was 0.3 ± 0.17, improving up to 0.57 ± 0.25 and to 0.63 ± 0.22 (P < 0.001, paired t-test) at the 6 and 12-month follow-ups, respectively. At the last follow-up, all the patients had stable/improved BCVA (P < 0.0001, Fisher's exact test) and stable/reduced lesion size (P < 0.0001, Fisher's exact test). None of the patients complained of any severe adverse event during the treatment. The combination of SS and MMF seems to be a promising strategy in order to control uveitic CNVs unresponsive to the traditional immunosuppressive agents. Further studies are needed to validate the data of this case series.

Biologic response modifier therapy for psoriatic ocular inflammatory disease.

PURPOSE: To evaluate the efficacy and safety of biologic response modifiers (BRMs) in the treatment of patients with psoriatic ocular inflammatory disease. METHODS: The records of 8 patients diagnosed with psoriatic ocular inflammatory disease who received adalimumab or infliximab were reviewed. Main outcome measures were control of intraocular inflammation, visual acuities, and adverse effects of therapy. RESULTS: The mean patient age was 53 +/- 15 years. Three patients had psoriatic panuveitis, 3 had psoriatic scleritis, and 2 patients had psoriatic anterior uveitis. The ocular inflammatory disease was bilateral in 7 patients. Four patients received adalimumab, and 4 received infliximab. Average time of therapy was 6.1 +/- 4.7 months. Six patients were treated concurrently with methotrexate. With respect to visual acuity, 2 patients demonstrated improvement, 2 patients demonstrated deterioration, and 4 patients remained stable. Seven patients achieved remission of their ocular inflammation. CONCLUSIONS: BMRs can be a useful adjunctive therapy for psoriatic ocular inflammatory disease.

The anti-inflammatory effects of Curcuma longa and Berberis aristata in endotoxin-induced uveitis in rabbits.

PURPOSE: To investigate the anti-inflammatory effect of topical application of Curcuma longa (C. longa) and Berberis aristata (B. aristata) aqueous extracts on experimental uveitis in the rabbit. METHODS: Anterior uveitis was induced in rabbits by intravitreal injection of lipopolysaccharide from Escherichia coli after pretreatment with C. longa and B. aristata aqueous extracts. Subsequently, the anti-inflammatory activity of C. longa and B. aristata was evaluated by grading the clinical signs and histopathologic changes and estimating the inflammatory cell count, protein, and TNF-alpha levels in the aqueous humor. RESULTS: The anterior segment inflammation in the control group was significantly higher than in both the extract-treated groups, as observed by clinical and histopathologic grading. The inflammatory cell count in the control group was 30.75 +/- 7.33 x 10(5) cells/mL, whereas it was 2.39 +/- 0.59 x 10(5) (P < 0.001 vs. control) and 11.56 +/- 2.44 x 10(5) (P = 0.001 vs. control) cells/mL in the C. longa- and B. aristata-treated groups, respectively. The protein content of the aqueous humor was 18.14 +/- 4.98, 3.16 +/- 0.55 (P < 0.001 vs. control), and 8.24 +/- 1.42 (P < 0.01 vs. control) mg/mL in the control, C. longa-, and B. aristata-treated groups, respectively. The aqueous TNF-alpha level in the control group was 976.29 +/- 66.38 pg/mL and was 311.96 +/- 28.50 (P < 0.0001 vs. control) and 654.09 +/- 47.66 (P < 0.001vs. control) pg/mL in the C. longa- and B. aristata-treated groups, respectively. CONCLUSIONS: Topical instillation of aqueous extracts of C. longa and B. aristata showed potent anti-inflammatory activity against endotoxin-induced uveitis in rabbits.

HLA-B27-associated uveitis: overview and current perspectives.

PURPOSE OF REVIEW: To review current knowledge about the pathogenesis, clinical presentation, and treatment of HLA-B27-associated uveitis, which is the most commonly identified cause of uveitis in community-based practice and an important cause of ocular morbidity. RECENT FINDINGS: Significant advances have been made in understanding the pathogenesis of HLA-B27-associated ocular and systemic disease, especially with regard to the genetic underpinning of these diseases. Increasing attention has also been focused on the use of alternative therapies in the treatment of HLA-B27-associated uveitis, with special attention to sulfa class antibiotics, historically have been used to treat the articular manifestations of the spondyloarthritides, and newer drugs that inhibit tumor necrosis factor-alpha. SUMMARY: The next several years promise to yield exciting new advances in understanding of the genetic epidemiology and treatment of HLA-B27-associated uveitis.

Long-term progression, prognosis, and treatment of patients with recurrent ocular manifestations of Reiter's syndrome.

PURPOSE: To investigate the spectrum of ocular involvement, to examine the clinical outcome, and to analyze the influence of treatment in patients with chronic ocular manifestations of Reiter's syndrome (RS) referred to a tertiary care ocular immunology service. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-five patients with RS evaluated at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary from 1981 through 2001. METHODS: Charts of patients were reviewed and data on age, gender, follow-up time, ocular symptoms, extraocular involvement, ocular complications, therapy, and visual acuities were recorded. MAIN OUTCOME MEASURES: Visual acuity, ocular complications, disease progression, clinical outcome, and systemic treatment. RESULTS: Twenty-five patients (20 male and 5 female) diagnosed with RS, with a mean age at presentation to our service of 37 years, were studied. The mean follow-up was 48.5 months. Eighty-five percent of patients tested were positive for human leukocyte antigen B27. Sixty-four percent of patients had a positive family history. All patients had oligoarthritis and enthesitis, most commonly affecting the back (56%), Achilles tendon (52%), and sacroiliac joint (24%). Eighty percent had a history of infection, most frequently urethritis (68%). Forty-four percent had a history of mucocutaneous lesions. All patients demonstrated ocular involvement at the time of diagnosis (68% with unilateral and 32% with bilateral disease), 84% had evidence of uveitis, 3% had scleritis, 2% had conjunctivitis, and 1% had pars planitis and iridocyclitis. During follow-up, the ocular complications included conjunctivitis (96%), anterior uveitis (92%), posterior uveitis (64%), keratitis (64%), cataract (56%), intermediate uveitis (40%), scleritis (28%), cystoid macular edema (28%), papillitis (16%), and glaucoma (16%). Systemic treatment for ocular inflammation was initiated in all patients. Ninety-six percent were treated with nonsteroidal anti-inflammatory agents. Eighty-eight percent were treated with corticosteroids, 64% requiring systemic prednisone. Immunosuppressive therapy was initiated in 52% of patients, with all receiving methotrexate. Seven patients required more than one immunosuppressive agent. The mean initial visual acuity was 20/25 in the right eye and 20/30 in the left eye. The mean final visual acuity was 20/25 in the right eye and 20/25 in the left eye. CONCLUSIONS: Reiter's syndrome may be associated with chronic recurrent ocular inflammation. Systemic therapy (including immunosuppressive treatment) typically is required to control the ocular inflammation and to prevent progressive visual loss.

Prevalencia del HLA-B27 en uveítis anteriores agudas idiopáticas. Cuadro clínico y factor pronóstico / Prevalence of HLA-B27 in idiophatic acute anterior uveitis. Clinical picture and pronostic factor

Antecedentes. La uveítis anterior aguda asociada al HLA-B27 es una enfermedad inflamatoria del ojo ampliamente conocida; la espondilitis anquilosante y la uveítis anterior aguda, bilateral alterna, no granulomatosa se asocia al HLA-B27 en un 30 por ciento de la población mexicana afectada con esta espondiloartropatía. Se han observado diferencias entre la uveítis anteriores agudas asociadas al HLA-B27 y aquellas que no lo presentan, considerándose como un factor pronóstico al antígeno B27. Objetivo. Determinar la prevalencia del antígeno HLA-B27 en la uveítis anteriores agudas idiopáticas y sus características clínicas, a fin de establecer la importancia del HLA-B27 en pacientes con uveítis en la población mexicana. Material y métodos. Se practicó examen oftalmológico completo y estudios de laboratorio a 30 pacientes que, de acuerdo a criterios de inclusión y exclusión, tuvieron el diagnóstico de uveítis anterior aguda no granulomatosa en la que no se demostró enfermedad sistémica asociadas a la uveítis. En caso necesario, se indicó tratamiento local con corticoesteroides y ciclopléjicos. La muestra de sangre para determinar HLA-B27 se envió al Servicio de Inmunología del Instituto Nacional de Nutrición Salvador Zubirán. Resultados. Se incluyeron 30 pacientes, 16 del sexo femenino y 14 del masculino, todos mestizos, edad entre 15 a 65 años con una media de 33.6 años. Ocho de los 30 pacientes tuvieron HLA-B27 positivo (26.7 por ciento). Los 22 restantes fueron HLA-B27 negativos; de éstos, 17 (72 por ciento) presentaron uveítis unilateral, once (50 por ciento) tuvieron recurrencias, 18 (81.8 por ciento) respondieron favorablemente al tratamiento tópico; la duración promedio del cuadro agudo fue de 24 días, la agudeza visual promedio fue 20/25. En los ocho pacientes con B27 positivo, los resultados porcentualmente fueron semejantes. La uveítis en los casos B-27 negativos presentaron: congestión ciliar en el 82 por ciento, depósitos retroqueráticos moderados en el 59 por ciento, celularidad leve en cámara anterior en el 72 porciento, sinequias en el 63 por ciento y la uveítis se consideró leve en el 72 por ciento...

Síndrome do olho vermelho: diagnóstico e tratamento clínico / Red eye syndrome: diagnosis and clinical treatment

A síndrome do olho vermelho possui inúmeras causas. O conhecimento do diagnóstico diferencial por parte do médico clínico facilitará a correta terapêutica até a avaliaçäo pelo especialista, principalmente no pronto-socorro. Os autores expöem, de forma simplificada, as principais causas, quadros clínicos e tratamento desta síndrome

[Vitrectomy in proliferative vitreoretinopathy. Anatomical and functional results in 501 patients]. / Vitrektomie bei proliferativer Vitreoretinopathie. Anatomische und funktionelle Resultate bei 501 Patienten.

BACKGROUND: Modern vitreoretinal surgery allows a successful management of most cases of retinal detachment (RD) due to proliferative vitreoretinopathy (PVR). Failure of a vitrectomy in these cases is generally caused by a recurrence of PVR. Little is known about the postoperative 'life cycle' of proliferative cellular processes within the periretinal space. An adequate retreatment of PVR recurrences may improve the anatomical and functional results of a vitrectomy. MATERIAL AND METHODS: The retrospective study comprises 501 consecutive eyes operated for non-diabetic traction RD. Conventional retinal surgery preceded the vitrectomy in 36% of the cases. PVR was staged according to the classification of the Retina Society (14) with supplemental stages for 'anterior loop' formation, epimacular and subretinal membranes. The mean follow up of 139 eyes with one single vitrectomy was 24.2 months. The time-course of recurrent PVR in 362 eyes (72%, mean follow-up 34.2 months) was analyzed. Silicone-oil tamponade was used in 343 (69%) eyes. RESULTS: Recurrent PVR occurred predominantly within 1 to 9 months (median 1.8 mos) after vitrectomy. Latencies of recurrences did not differ significantly between PVR-C and D stages. Reattachment of the retina was achieved in about 85% of PVR-C and 70% of PVR-D stages. Anatomical results were better in non-traumatic RD cases. Final visual acuity of eyes operated since 1990 was 5/200 or better in 78% C-stages and 65% D-stages (follow-up of > or = 12 months). The final visual acuity was 20/100 or better in 33% of all PVR-C cases and 9.5% of all PVR-D cases. Significantly improved visual results were achieved in eyes operated with silicone oil tamponade, and in the later series of 279 eyes operated since 1990. The rate of postoperative total blindness was reduced from 16.7% before 1990 to 3.6% after 1990. CONCLUSION: Blindness due to traction RD can be avoided by vitreoretinal surgery in about 75% of PVR-C and over 50% of PVR-D cases provided that PVR recurrences are detected early and treated adequately.

Role of oxygen radicals in experimental allergic uveitis.

The experimental autoimmune disease elicited by a large dose of retinal S antigen in guinea pigs is characterized by massive necrotizing uveitis and retinitis. Treatment of these animals with the antioxidants superoxide dismutase, catalase, and sodium benzoate resulted in marked reduction of uveal inflammation. The attenuated inflammation was characterized by a relatively well-preserved retina and retinal pigment epithelium along with a reduction of subretinal exudate and vitreous inflammation. These findings suggest that reactive oxygen metabolites may play a role in the destruction of ocular tissue and amplification of the inflammatory process in experimental uveitis.