Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment.

The aim of this study was to quantify the proportion of regulatory T cells (Treg ) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)(+) Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4(+) T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3(+) Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3(+) Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3(+) Treg cells.

Interleukin-6 blockade in ocular inflammatory diseases.

Interleukin-6 (IL-6) is a key cytokine featuring redundancy and pleiotropic activity. It plays a central role in host defence against environmental stress such as infection and injury. Dysregulated, persistent interleukin (IL)-6 production has been implicated in the development of various autoimmune, chronic inflammatory diseases and even cancers. Significant elevation of IL-6 has been found in ocular fluids derived from refractory/chronic uveitis patients. In experimental autoimmune uveitis models with IL-6 knock-out mice, IL-6 has shown to be essential for inducing inflammation. IL-6 blockade can suppress acute T helper type 17 (Th17) responses via its differentiation and, importantly, can ameliorate chronic inflammation. Tocilizumab, a recombinant humanized anti-IL-6 receptor antibody, has been shown to be effective in several autoimmune diseases, including uveitis. Herein, we discuss the basic biology of IL-6 and its role in development of autoimmune conditions, focusing particularly on non-infectious uveitis. It also provides an overview of efficacy and safety of tocilizumab therapy for ocular inflammatory diseases.

Acute macular neuroretinopathy associated with migraine.

Acute macular neuroretinopathy (AMN) is an uncommon entity that affects the outer layer of the retina and usually presents itself as an acute paracentral scotoma. It is mostly seen in young women and the course is usually self-limited. The diagnosis is established by a multimodal image, with optical coherence tomography (OCT) being the preferred technique. The origin is thought to be linked to a possible dysregulation in the flow of the deep vascular plexus of the retina or the choriocapillaris. A clinical case of an AMN in a young woman associated with a migraine attack is presented, highlighting the importance of considering this disease in the differential diagnosis of visual disorders associated with migraines. A physiological and pathological basis between migraine and NMA is suggested.

Role of vitrectomy for syphilitic uveitis in a tertiary hospital in Spain.

Diagnosis and treatment of ocular syphilis can be challenging due to the wide spectrum of clinical presentations of this sexually transmitted disease. In some cases of syphilitic panuveitis, pars plana vitrectomy (PPV) can be useful in management since it plays an important role in improving fundus examination allowing treatment of possible retinal associated lesions when vitreous inflammation is intense. We present 3 cases of patients with ocular syphilis that underwent a therapeutic PPV, vitreous sample was taken and analyzed in two of them.

The retinal bacillary layer detachment: Clinical features and outcomes in posterior uveitis.

PURPOSE: To describe the clinical characteristics, presentation and response to treatment in posterior uveitis patients with bacillary layer detachment (BLD) seen on optical coherence tomography (OCT). MATERIALS AND METHODS: Retrospective review of patients with posterior uveitis and SD-OCT scans consistent with BLD. Data collected included demographics, uveitic etiology, treatment and duration of follow-up. Outcome measures included macular volume, central subfoveal thickness and visual acuity. RESULTS: Sixteen patients (20 eyes) were included. Twelve were female (75%). The mean age was 43.68 ± 14.7 years. The most frequent etiology of the uveitis was Vogt-Koyanagi-Harada (VKH) disease (n=10), followed by sympathetic ophthalmia (n=2). BLD was bilateral in four patients. Eight patients were treated with intravenous methylprednisolone boluses. Immunosuppressive therapies were required in 8 patients. The mean follow-up was 70 months (range: 2.0-216.0). CONCLUSION: BLD was observed in a series of posterior uveitis cases of various etiologies, showing functional and structural resolution with treatment in most cases.

Tuberculosis-Related Uveitis in Patients under Anti-TNF-alpha Therapy: A Case Series.

Tumor necrosis factor inhibitors (anti-TNF) have emerged as an effective treatment in noninfectious uveitis (NIU). Anti-TNF may increase the predisposition to infectious disease as tuberculosis (TB). TB-related uveitis in the context of an uveitogenic concurrent systemic immune-mediated disease under anti-TNF treatment remain a diagnostic challenge, deserving special focus on this rare context. Retrospective chart review of patients on anti-TNF drugs for systemic immune-mediated diseases that developed a multicentric microbiologically confirmed active TB with concurrent intraocular involvement.Three patients were recorded. Screening for TB before starting anti-TNF resulted negative in two patients. The other patient had received anti-tuberculous treatment in the past. All showed a microbiologically confirmed extraocular TB after unexpected atypical reactivation of the uveitis shifting to chronic granulomatous pattern.Specialists should be aware of TB reactivation, even with previous negative screening, when ocular uveitis signs and activity do not match with the expected pattern in a patient on anti-TNF drugs.

Multimodal imaging in acute idiopathic blind spot enlargement syndrome.

Two cases are reported of acute idiopathic blind spot enlargement syndrome (AIBSE) that presented with peripapillary white spots in the fundus. AIBSE belongs to the acute zonal occult outer retinopathy (AZOOR) complex. Conditions of this AZOOR complex may overlap. Typically, in AIBSE, a peripapillary hyperautofluorescence is seen in the autofluorescence. En-face OCT angiography at the ellipsoid level showed hyper-reflective spots around the optic disk in both cases. One case showed a reversible enlargement of the blind spot in visual field. AZOOR complex is an inflammatory disorder that affects the outer retina, and can now be confirmed with structural optical coherence tomography. In the cases presented, there was a reversible severe loss of the outer retina.

Atypical toxoplasmic retinochoroiditis in patients with malignant hematological diseases. / Retinocoroiditis toxoplásmica de presentación atípica en pacientes con enfermedades hematológicas malignas.

In immunocompromised patients, toxoplasmosis may have atypical presentation with bilateral, extensive or multifocal involvement. We report a case series of atypical toxoplasmic retinocoroiditis in patients with malignant hematological diseases who are usually immunosuppressed. Four patients were diagnosed of atypical toxoplasmic retinochoroiditis, all of them had immunosuppression (100%) and half of them (50%) had received a bone marrow transplant. The polymerase chain reaction for toxoplasma was positive in 75% of cases, and in one case (25%) the diagnosis was made with clinical and serological criteria. One patient presented ocular toxoplasmosis despite being on prophylactic treatment with atovaquone. Patients with atypical ocular toxoplasmosis and hematological diseases are generally immunocompromised, but they do not always have history of a bone marrow transplant. The presentation may be due to a primary infection or a reactivation of the disease. The aqueous humor and/or vitreous polymerase chain reaction allow confirming the diagnosis to perform a proper treatment.

Non-pharmacological complications associated with Intravitreal dexamethasone implant injection. / Complicaciones no farmacológicas asociadas a la inyección de implante intravítreo de dexametasona.

OBJECTIVE: Intravitreal dexamethasone implant (IID) is an effective and safe treatment for macular oedema as described in the literature. Ocular hypertension and cataracts are the most frequent complications. The indications of IID in the last few years have led to the retrospective reporting of rare complications, with potential visual impact related to the injection procedure. METHODS: A case series is presented of fifteen patients treated with IID for macular oedema who developed non-pharmacological complications related to the injection procedure or the implant itself, including, among others anterior chamber migration, intracrystalline injection, endophthalmitis, or segmentation. Differentiation was made between true complications and those that did not lead to any ocular damage. Epidemiological and baseline data were collected along with the treatment and outcome in each case. An analysis was made of multimodal imaging available. RESULTS: The incidence of complications was 0.65% in this series Anterior chamber migration was the most frequent complication (n=4), followed by intracrystalline injection, and endophthalmitis (n=2). The times between the injection and complications were variable. Visual impairment was the most common symptom (n=6). However, despite the complications found, IID was an effective treatment in most of the reported cases. CONCLUSIONS: Clinicians should be aware of these rare non-pharmacological complications so that they may be prevented and detected early, avoiding irreversible ocular damage.

[Central nervous system demyelinating disease-associated uveitis]. / Uveítis asociadas a enfermedad desmielinizante del sistema nervioso central.

OBJECTIVE: To describe the epidemiology, clinical features and visual prognosis in uveitis associated with demyelinating disease (DD) of the CNS. METHODS: A clinical, retrospective, and descriptive study was performed. Data regarding age at presentation, gender, time from onset was recorded, as well as, type of uveitis, complications, treatment and initial and final visual acuity (BCVA) on all patients with DD-associated uveitis diagnosed in our Unit between January 2009 and June 2011. RESULTS: Five women and 4 men were finally included (1.3% of 697 with uveitis). There was associated multiple sclerosis in 78% of cases. Mean age at presentation was 36.6 years for uveitis and 40 years for DD. The uveitis preceded the DD in 3 cases (33%). Typically, uveitis was bilateral (89%), chronic (89%), intermediate (89%), and associated with previous inflammation (29%), with synechiae (65%), and granulomatous (44%). The most frequent complications were cataract (71%) and macular oedema (53%). Besides local treatment, uveitis was managed with systemic steroids (78%), immunosuppressants (44%), and surgery (41% of eyes). After a mean follow up of 5 years, 47% of the eyes had a worse BCVA, among which, 12% lost ≥ 3 Snellen lines. The only patient treated with interferon (IFN), remained stable without treatment for the last 7 years. CONCLUSIONS: DD-associated uveitis typically affected young adult women with intermediate-anterior uveitis of chronic, bilateral and synechiae type. Complications are common and there is a risk of visual loss, despite treatment. IFN therapy may be an effective alternative to be investigated.

[Comparison of three optical coherence tomography devices, one time-domain and two fourier-domain, for the estimation of the retinal nerve fibre layer thickness]. / Comparación de tres instrumentos de tomografía de coherencia óptica, un time-domain y dos Fourier-domain, en la estimación del grosor de la capa de fibras nerviosas de la retina.

PURPOSE: To assess agreement between one system of time-domain optical coherence tomography (OCT) (Stratus) and two systems of fourier-domain OCT (Cirrus and 3D OCT-1000) for the measurement of the retinal nerve fibre layer thickness (RNFL). METHODS: Fifty eyes from 25 patients with neuro-ophthalmological disorders of the afferent visual pathway were included. A triple RNFL thickness OCT examination with Stratus, Cirrus and 3D OCT-1000 was performed on both eyes of every patient, on the same day and by the same technician. The average RNFL thickness by quadrants and clock sectors were compared with the Lin´s concordance correlation coefficient (CCC) and Bland-Altman plots. RESULTS: The average RNFL thickness, the temporal and nasal quadrants and corresponding clock sectors, was higher by 3D OCT-1000 (mean 90.02 microns), nevertheless, RNFL thickness of the superior and inferior quadrants and corresponding clock hours was higher when measured by Stratus device. The CCC agreement between Stratus and Cirrus was high (0.820), between Stratus and 3D OCT-1000 was moderate (mean 0.573) and between Cirrus and 3D OCT-1000 was moderate with a mean of 0.564 but too low in the nasal and temporal quadrants (0.362 and 0.347 respectively). CONCLUSIONS: The RNFL thickness measurements by Stratus, Cirrus and 3D OCT-1000 OCT are not equivalent. Although the agreement between Stratus and Cirrus was high, it was too low between 3D OCT-1000 and Stratus or Cirrus.

The immune response against herpesvirus is more prominent in the early stages of MS.

OBJECTIVE: To assess antibody levels against human herpesvirus type 6 (HHV-6), Epstein-Barr virus (EBV), and Chlamydia pneumoniae (CP) in serum from individuals in the early and late phase of MS. RESULTS: A strong association was found between anti-HHV-6 immunoglobulin M antibodies and early MS (clinically isolated syndromes at high risk for MS, and short duration active relapsing-remitting MS) when compared with healthy controls and secondary progressive MS. Moreover, in this group of patients, titers for anti-EBV immunoglobulin G were also elevated. The authors found no association between the levels of serum antibodies against CP and MS, nor did they detect the presence of DNA for these pathogens in the serum of patients with MS. Finally, serum from two patients with other inflammatory neurologic diseases also had elevated immunoglobulin M antibodies to HHV-6, indicating that the presence of this antibody is not specific to MS. CONCLUSION: An immune response against herpesviruses such as HHV-6 and EBV is associated with early MS.