Ocular Relapse Research Articles

The Relationship between Fluorescein Angiography Leakage after Infliximab Therapy and Relapse of Ocular Inflammatory Attacks in Ocular Behçet’s Disease Patients

ABSTRACT Purpose: To clarify the relationship between fluorescein angiography (FA) leakage after infliximab therapy and ocular attack relapse in patients with ocular Behçet’s disease (BD). Methods: Patients with ocular BD were divided into two groups based on the presence (Group 1) or absence (Group 2) of ocular attacks after IFX therapy. FA leakage was evaluated by FA score in each of the optic discs, macula, large retinal vessels, and capillary vessels. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the relationship between FA score after IFX therapy and ocular attack relapse. Results: The areas under the curves obtained from the ROC curve of optic disc score and capillary vessels score after IFX therapy were 0.867 (95% confidence interval [CI]: 0.788–0.946) and 0.788 (95% CI: 0.649–0.927), respectively. Conclusions: FA leakage in the optic disc and capillary vessels after IFX therapy was strongly related to ocular attack relapse.

Effectiveness and safety of interferon α2a as an add-on treatment for refractory Behçet's uveitis.

Objective:The objective of this study was to investigate the effectiveness and safety of interferon (IFN) α2a as an add-on treatment for refractory Behçet’s uveitis (BU).Methods:In this retrospective cohort study, 30 refractory BU patients who received IFNα2a treatment in Peking Union Medical College Hospital between February 2015 and June 2018 were consecutively included. IFNα2a was used mainly as an add-on treatment for BU patients who underwent relapse under corticosteroids and conventional immunosuppressive agents. The primary outcome was treatment success rate before and after initiation of IFNα2a. Changes in ocular relapse rates, disease activity, corticosteroid- and immunosuppressant-sparing effects, as well as side effects were secondary outcomes.Results:A total of 30 patients (27 males and 3 females) with a mean age of 30.5 ± 8.7 years were included. Twenty-one patients (70%) were treated with at least 2 immunosuppressive agents before the initiation of IFNα2a. Treatment success was achieved in 26 patients (86.7%), and the median uveitis relapse rate decreased from 7.3 (range 2–12) to 0 (range 0–6) per patient-year (p = 0.000002) during a mean follow-up of 21.7 ± 7.5 months, corticosteroids were lowered in 25 cases (83.3%) and completely withdrawn in four (13.3%). In addition, immunosuppressive agents were reduced in number and dosage in 22 (73.3%) and 29 patients (96.7%), respectively, and were completely withdrawn in 12 cases (40%). No severe adverse events were observed and serum autoantibodies remained negative during the treatment of IFNα2a.Conclusion:IFNα2a is effective and relatively safe in refractory BU, with significant steroid- and immunosuppressant-sparing effects.

New concepts in the diagnosis and management of choroidal metastases.

The most frequent site of ocular metastasis is the choroid. The occurrence of choroidal metastases has increased steadily due to the longer survival of metastatic patients and the improvement of diagnostic tools. Fundoscopy, ultrasonography, and fluorescein angiography are now complemented by indocyanine green angiography and optical coherence tomography. Choroidal tumor biopsy may also confirm the metastatic nature of the tumor and help to determine the site of the primary malignancy. There is currently no consensus on the treatment strategy. Most patients have a limited life expectancy and for these complex treatments are generally not recommended. However, recent advances in systemic therapy have significantly improved survival of certain patients who may benefit from an aggressive ocular approach that could preserve vision. Although external beam radiation therapy is the most widely used treatment, more advanced forms of radiotherapy that are associated with fewer side effects can be proposed in select cases. In patients with a shorter life expectancy, systemic therapies such as those targeting oncogenic drivers, or immunotherapy can induce a regression of the choroidal metastases, and may be sufficient to temporarily decrease visual symptoms. However, they often acquire resistance to systemic treatment and ocular relapse usually requires radiotherapy for durable control. Less invasive office-based treatments, such as photodynamic therapy and intravitreal injection of anti-VEGF, may also help to preserve vision while reducing time spent in medical settings for patients in palliative care. The aim of this review is to summarize the current knowledge on choroidal metastases, with emphasis on the most recent findings in epidemiology, pathogenesis, diagnosis and treatment.

The Clinical Characteristics, Treatment, and Outcomes of Giant Cell Arteritis are Dependent on Histological Subtype

Objective: To determine the clinical outcomes of the two histopathological patterns considered positive for giant cell arteritis (GCA): active arteritis and healed arteritis. Methods: A retrospective chart review was performed of 22 patients with biopsy-proven GCA. Eleven patients had active arteritis and eleven patients had post-inflammatory alterations consistent with healed arteritis. We sought to compare presenting symptoms, ischemic ocular events, inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and platelet count), relapses, and dosage requirements of long-term steroids between the two groups. Results: 7 of 11 patients with active arteritis had an initial ocular ischemic event while 3 of the 11 patients with healed arteritis had an initial ischemic event to the eye. There was no statistical difference in initial ESR between the two groups, but CRP and platelet counts on initial presentation were statistically higher in the active group (p = 0.0002 and p <0.0001 respectively). Patients with active arteritis on biopsy required higher doses of steroids over a 2-year follow-up compared to the healed group: on average 11 mg/day to 1 mg/day at 1 year (p = 0.0008), and 7 mg/day to 0.5 mg/day at 2 years (p = 0.0208), respectively. During the follow-up period, 2 of the 11 patients in the active group demonstrated a recurrent ischemic event to the eye same or fellow eye while in the healed group there were no recurrent ischemic events. Conclusions: Patients with healed arteritis on pathological examination of temporal artery biopsy appear to have better prognoses and may require less aggressive treatment than those with active inflammation.

Long-Term Efficacy and Safety of Interferon Alpha-2a in the Treatment of Chinese Patients with Behçet’s Uveitis Not Responding to Conventional Therapy

ABSTRACTPurpose: To investigate the long-term efficacy and safety of interferon alpha-2a (IFNα-2a) in Chinese patients with Behçet’s uveitis (BU) refractory to conventional therapy.Methods: In a prospective observational cohort study, 127 patients were treated with an initial dosage of 3 million units per day in the first three months, followed by gradual tapering of the dose.Results: After 3 months of treatment, IFNα-2a was shown to be effective in 115 cases (91%). At the end of the 1-year follow-up, the frequency of ocular relapses decreased to 1.59 ± 1.68 per year (ranging 0–6) (p < 0.001), as compared to 5.09 ± 2.51 per year (ranging 3–15). Moreover, the frequency of oral ulcer relapses also decreased to 2.49 ± 1.84 per year (ranging 0–6) (p < 0.001), as compared to 8.20 ± 3.72 per year (ranging 2–10). Visual improvement or stability was observed in 32 patients (59%) in these 54 patients. During a mean follow-up of 11 months (range 3–33), the mean final VA (logMAR) had progressed from 1.0 logMAR to 0.8 logMAR in all treated patients.Conclusions: Long-term low dose of IFNα-2a is useful in treating Chinese BU patients who do not respond adequately to conventional therapy.

Ocular Lesions in Congenital Toxoplasmosis in Santa Isabel do Ivaí, Paraná, Brazil.

We verified clinical and psychopedagogic aspects of congenital cases with ocular sequelae, 13 years after toxoplasmosis outbreak in Santa Isabel do Ivaí, and current seroprevalence of this zoonosis in pregnant women. Audiologic and ophthalmologic evaluations were performed in congenital cases, in addition to collection of clinical and psychopedagogic data. In pregnant women, current seroprevalence was observed. Among affected teenagers, 2 of 5 are behind in school grade, and 4 of 5 reported learning difficulties, requiring psychopedagogic monitoring, as well as ocular complaints. We observed predominance of small, scarred, dispersed, type II chorioretinal lesions (hypopigmented halo and hyperpigmented central area), and 1 case of ocular relapse. All patients presented normal audiologic assessment. Among 131 pregnant women, 62 (47.3%) were seronegative and 39 (29.8%) were IgG reactive. Only 1 reported acquiring infection during the outbreak. This is one of the few studies in Brazil showing the outcome of congenital toxoplasmosis, a decade after infection, in one of the world's largest outbreaks.

Presumed Ocular Relapse of Diffuse Large B Cell Uterine Lymphoma Presenting Only as Vitritis after Continuous and Complete Remission

Presumed Ocular Relapse of Diffuse Large B Cell Uterine Lymphoma Presenting Only as Vitritis after Continuous and Complete Remission

Anakinra in the Treatment of Patients with Refractory Scleritis: A Pilot Study

ABSTRACTPurpose: This study aimed to evaluate the safety and efficacy of anakinra for severe and refractory scleritis.Methods: Ten patients with severe (i.e. at least 2 ocular relapses per year despite treatment) and refractory [i.e. at least to one disease modifying antirheumatic drugs (DMARDS)] scleritis were treated with anakinra (100 mg/day subcutaneously). Scleritis was associated with inflammatory systemic diseases in 60% of cases. The remission rate defined the primary outcome.Results: Ninety percent of patients were complete responders with a mean follow-up of 19.4 months after starting anakinra. The corticosteroids daily dose decreased from 18.3 ± 4.1 mg to 4.2 ± 4.9 mg, (p < 0.05), at initiation of anakinra and at end of follow-up, respectively. Associated immunosuppressants were stopped in all cases except one. Side effects were observed in 4 patients who did not need anakinra withdrawal.Conclusions: This pilot study suggests the efficacy of anakinra in patients with refractory scleritis.

Characterization of isolated retinal vasculitis. Analysis of a cohort from a single center and literature review.

Isolated retinal vasculitis (IRV) is an inflammatory condition of unknown etiology confined to the retinal vessels. In contrast to secondary retinal vasculitis (RV), IRV has not been well characterized. To describe and characterize isolated forms of RV. We performed a retrospective review (2006-2016) of IRV patients from a multidisciplinary Uveitis Unit. RV diagnosis was based on funduscopic and fluorescein angiography findings. To distinguish between secondary RV and IRV, evaluations included clinical assessment, several inflammatory, autoimmune and microbiological laboratory markers, and a chest radiography. Ophthalmological features at disease onset, therapeutic interventions, ocular relapses, visual outcomes and laboratory findings were recorded. Our cases were subsequently compared with those from a literature review. Among 192 patients with RV, 11 (5.7%) were diagnosed with IRV. Seven patients with initially presumed IRV were reclassified as secondary after further evaluation. IRV generally affected adult women. Bilateral ocular involvement and retinal phlebitis were common findings. 72% of patients presented with visual loss, which was severe in 27%. Treatments used included systemic glucocorticoids (82%), additional immunosuppressive agents (27%), intravitreal therapy (37%), panretinal photocoagulation (37%) and pars plana vitrectomy (26%). The annual relapse rate was 0.46. Although final visual acuity was considered good in 86%, 45% experienced worsening and only 27% improved. IRV is a rare sight-threatening condition. Despite intensive local and systemic immunosuppressive treatment, visual improvement is observed in only 27% of cases. When IRV is suspected, a differential diagnosis excluding a systemic disease is always warranted. A multidisciplinary approach and a guided clinical, laboratory and imaging evaluation have proven to be useful to distinguish retinal single-organ vasculitis from secondary forms of RV.

Evaluation of Tumor Necrosis Factor inhibitor therapy in Susac syndrome

PurposeTo analyze the effect of tumor necrosis factor inhibitor therapy on ocular relapses in patients with Susac syndrome.MethodsMulticenter retrospective case series of patients with ocular Susac syndrome treated with a TNF inhibitor (either infliximab or adalimumab). Diagnosis was based on neurologic, ophthalmic, otologic, biologic and imaging typical findings.ResultsFive patients were included. All were initially treated with a combination of corticosteroids and classical immunosuppressive drugs. In 4 of the 5 patients a TNF‐inhibitor (3 infliximab and 2 adalimumab) was started due to treatment failure. In these patients cortisone could not be decreased below a daily dose of 10 mg without the occurrence of relapses (with an average of 4.25 relapses over a mean follow‐up of 330 days) despite the use of a mean of 2.75 different immunosuppressive drugs. After introduction of an anti‐TNF agent the daily cortisone dose could successfully be tapered below 10 mg in all patients with a complete stop in 3 patients, with a mean number of 1.25 relapses during a mean follow‐up of 1,199 days. In the fifth patient, disease activity was well controlled with only steroid sparing immunosuppressive agents and only 1 relapse during approximately 5 years of follow up until these had to be stopped for a desired pregnancy. No relapse was documented during 60 weeks of follow‐up while on infliximab treatment afterwards.ConclusionsAnti‐TNF antibodies can be a valuable option for the treatment of ocular Susac syndrome and may especially be considered in those patients unresponsive to conventional immunosuppressive treatment.

Long-term Efficacy of Interferon in Severe Uveitis Associated with Behçet Disease

ABSTRACTPurpose: To retrospectively assess the frequency of ocular relapse and the possibility of long-term remission in patients treated with interferon (IFN) for severe uveitis associated with Behçet disease.Methods: All patients were treated with an initial dosage of 3 million IU IFN three times a week. The main outcome measure was the number of relapses per person per year before, during, and after IFN treatment.Results: Of 36 patients (67 eyes), 31 (86.1%) responded to IFN. The mean follow-up was 8.19 years. Twenty-one out of 36 patients discontinued IFN and 76% of these have not relapsed within 5.05 years after discontinuation. The mean relapse per person per year decreased significantly from 1.39 to 0.0496 (p = 1.82×10−10) during the treatment period and remained at 0.057 relapses per person per year after IFN discontinuation.Conclusion: IFN efficiently decreases the relapse rate and seems to permit long-term remission even after discontinuation.

Rituximab in the treatment of refractory scleritis in patients with granulomatosis with polyangiitis (Wegener's).

The purpose of this descriptive study was to evaluate the clinical response to rituximab (RTX) in patients with scleritis due to granulomatosis with polyangiitis (GPA), in patients who had proved refractory to treatment with systemic glucocorticoids and immunosuppressive agents. Retrospective analysis of interventional case series. Single referral center study. Eight patients (12 affected eyes) due to scleritis secondary to GPA, refractory to conventional treatment were included to receive RTX as therapy for remission induction. RTX was administered as a 1-g infusion every 2weeks, for a total of 2 g. Patient follow-up included clinical evaluation (systemic and ophthalmologic), B-cell subset (CD19, CD20, CD22) counts, proteinase-3 anti-neutrophil cytoplasmic antibody (PR-3 ANCA), and Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS-WG). Outcomes were response to treatment and achievement of remission, as well as number of ocular relapses. The main indication for treatment was refractory necrotising anterior scleritis. Four weeks after completion of treatment with RTX, all patients showed clear clinical improvement, with no further progression. In all patients, an absolute depletion of B cells was confirmed in the first 6 weeks after treatment. Seven patients (87.5%) achieved remission of inflammatory activity in 7months or less. However, three patients experienced ocular relapse, which comprised reactivation of the anterior scleritis, uveitis, and posterior scleritis, and two patients required a second dose of RTX, with immediate improvement. RTX is useful in the treatment of refractory necrotising scleritis in patients with GPA. Of note, in those who relapse after remission, RTX can be successfully used for retreatment.

Interleukin‐1 blockade in neuro‐Behçet's disease: a case‐based reflection

Interleukin‐1 blockade in neuro‐<scp>B</scp>ehçet's disease: a case‐based reflection

Ocular adnexal diffuse large B-cell lymphoma: a multicenter international study.

The clinical features of diffuse large B-cell lymphoma (DLBCL) subtype of ocular adnexal lymphoma have not previously been evaluated in a large cohort to our knowledge. To investigate the clinical features of ocular adnexal DLBCL (OA-DLBCL). This retrospective international cooperative study involved 6 eye cancer centers. During 30 years, 106 patients with OA-DLBCL were identified, and 6 were excluded from the study. The median follow-up period was 52 months. Overall survival, disease-specific survival (DSS), and progression-free survival were the primary end points. One hundred patients with OA-DLBCL were included in the study (median age, 70 years), of whom 54 (54.0%) were female. The following 3 groups of patients with lymphoma could be identified: primary OA-DLBCL (57.0%), OA-DLBCL and concurrent systemic lymphoma (29.0%), and ocular adnexal lymphoma relapse of previous systemic lymphoma (14.0%). Of 57 patients with primary OA-DLBCL, 53 (93.0%) had Ann Arbor stage IE disease, and 4 (7.0%) had Ann Arbor stage IIE disease. According to the TNM staging system, 43 of 57 (75.4%) had T2 tumors. Among all patients, the most frequent treatments were external beam radiation therapy with or without surgery (31.0%) and rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine sulfate, prednisone (CHOP) or rituximab-CHOP-like chemotherapy with or without external beam radiation therapy (21.0%). The 5-year overall survival among the entire cohort was 36.0% (median, 3.5 years; 95% CI, 2.5-4.5 years). Relapse occurred in 43.9% (25 of 57) of patients with primary OA-DLBCL. Increasing T category of the TNM staging system was predictive of DSS (P = .04) in primary OA-DLBCL, whereas the Ann Arbor staging system was not. However, when taking all 100 patients into account, Ann Arbor stage was able to predict DSS (P = .01). Women had a longer median DSS than men (9.8 years; 95% CI, 1.9-17.7 years vs 3.3 years; 95% CI, 1.6-5.0; P = .03). Most patients with primary OA-DLBCL were seen with Ann Arbor stage IE and TNM T2 disease. The 5-year overall survival was between 2.5 and 4.5 years, which is the 95% CI around the median of 3.5 years in this cohort. Increasing T category appears to be associated with decreased DSS among patients with primary OA-DLBCL. When taking all patients into account, sex and Ann Arbor stage also seem to be DSS predictors.

Isolated Ocular Relapse in Acute Lymphoblastic Leukemia

12-year-old girl with a history of acute lymphoblastic leukemia,but without previous evidence of central nervous system involvement, presented with sudden, painless loss of vision in both eyes 3 years after complete remission. Her best-corrected visual acuity was 1/6 in the right eye and 2/6 in the left eye.

Follicular lymphoma of the ocular adnexal region: a nation-based study.

To characterize the clinicopathological features of follicular lymphoma of the ocular adnexal region. Retrospective nation-based study of Danish patients with ocular adnexal follicular lymphoma from January 1st 1980 through December 31st 2009. Twenty-four patients with ocular adnexal follicular lymphoma were identified. Fourteen (58%) of the patients were females. The median age was 63 years (range: 42-96 years). Eleven (46%) of the patients had primary ocular adnexal lymphoma, seven (29%) had an ocular adnexal lesion in conjunction with a concurrent systemic lymphoma and six patients (25%) presented with an ocular adnexal relapse. The most frequently affected sites were the lacrimal gland (38%) and the orbit (33%). Thirteen patients (54%) presented with Ann Arbor stage IE lymphoma, four (17%) had stage IIE, two patients (8%) stage IIIE, and five patients (21%) had stage IV lymphoma. Radiotherapy was primarily used in patients with primary lymphoma and those with a stage IE/IIE relapse (82%), while stage IIIE/IV lymphomas most frequently received alkylating chemotherapy (67%). Complete remission was observed in 19 of the patients (79%), but of these 11(58%) had a relapse. The 10-year overall survival for the entire cohort was 59%. The translocation t(14;18) was detected in 16 patients (16/24, 76%). Recurrence was only observed in patients with the t(14;18) (p=0.05, log-rank). Ocular adnexal follicular lymphoma is more commonly found in elderly female patients. The lacrimal gland is relatively frequently involved. Radiotherapy is the treatment of choice for localized ocular adnexal follicular lymphoma providing a favourable prognosis for majority of patients.

Ocular adnexal follicular lymphoma: a multicenter international study.

The clinical features of the follicular subtype of ocular adnexal lymphoma (OAL) have not been previously evaluated in a large cohort. To characterize the clinical features of follicular OAL. We performed a retrospective multicenter study that involved 6 eye cancer centers from January 1, 1980, through December 31, 2010. A total of 105 patients with follicular OAL were identified, of which 7 patients were excluded because of missing clinical data. The median follow-up time was 52 months (range, 13-118 months). Overall survival, disease-specific, and progression-free survivals were the primary end points. Ninety-eight eligible patients with follicular OAL were included; 60 (61%) were women. The median patient age was 63 years (range, 32-96 years). Sixty-nine patients (70%) had primary OAL, 19 (19%) had OAL in conjunction with a concurrent systemic lymphoma, and 10 (10%) presented with an ocular adnexal relapse. The lacrimal gland (28%), conjunctiva (28%), and orbit (28%) were the most frequently involved sites. Of the 69 patients with primary follicular lymphoma, 38 (55%) presented with Ann Arbor stage IE lymphoma, and 31 (45%) had stage IIE lymphoma. Patients with disseminated lymphoma had stage IIIE (9 of 19 [47%]) and stage IV (10 of 19 [53%]) disease, whereas patients with a relapse of systemic lymphoma presented with stage IE (8 of 10 [80%]), stage IIE (1 of 10 [10%]), and stage IIIE (1 of 10 [10%]) disease. Patients with primary follicular lymphoma (n = 69) and those with isolated ocular relapse (n = 9) were treated with external beam radiation therapy (EBRT) (35 of 78 [45%]) or EBRT plus chemotherapy (22 of 78 [28%]). Patients presenting with stage IIIE-IV follicular lymphoma (n = 20) most frequently received chemotherapy (9 of 20 [45%]) or EBRT plus chemotherapy (4 of 20 [20%]). The 10-year overall survival for the entire study cohort was 60%. Primary patients treated with EBRT had a better disease-specific survival compared with patients receiving ERBT plus chemotherapy (10-year disease-specific survival, 94% vs 40%; P = .02 by log-rank test). Follicular OAL was more commonly found in elderly female patients. These tumors were equally noted to involve the conjunctiva, lacrimal gland, and orbit. Patients with ocular adnexal follicular lymphoma primarily treated with EBRT had a more favorable long-term disease-specific survival.

Isolated extramedullary ocular relapse of acute lymphoblastic leukemia after peripheral blood stem cell transplantation

Isolated extramedullary ocular relapse of acute lymphoblastic leukemia after peripheral blood stem cell transplantation

‘Hypopyon’ in the anterior chamber: unilateral ocular relapse of acute myeloid leukaemia in a 2-year-old girl

‘Hypopyon’ in the anterior chamber: unilateral ocular relapse of acute myeloid leukaemia in a 2-year-old girl

FRI0354 Efficacy of infliximab in the treatment of sight-threatening uveitis in behçet’s disease

BackgroundDespite intensive immunosuppressive therapy, permanent loss of vision resulting from relapsing ocular inflammation occurs frequently in Behçet’s disease. Since tumor necrosis factor (TNF) have a pathogenic role in Behçet’s uveitis,...