Treatment of Behçet Uveitis in Türkiye.

Objectives: Behçet uveitis (BU) is a potentially blinding disorder. The main determinant of visual prognosis is early and appropriate treatment that provides rapid suppression of inflammatory attacks, control of subclinical inflammation, and prevention of new attacks. Our study aimed to determine the Turkish uveitis specialists' approach regarding the treatment choices and management of special situations such as pregnancy, vaccination, and surgical planning in BU patients, and to increase information sharing and raise awareness of issues where knowledge is lacking. Materials and Methods: A web-based survey including 16 questions about the treatment approach in ocular involvement of Behçet's disease was sent via e-mail to uveitis specialists in Türkiye. Based on the answers of 49 ophthalmologists who responded to the survey, we evaluated the approaches of uveitis specialists in our country to initiating treatment, selecting therapeutic agents, monitoring, switching and stopping treatment, and special situations such as surgical planning, vaccination, and pregnancy in BU patients. Results: Uveitis specialists in our country mostly act in accordance with the guidelines in the decision to start treatment, selection of therapeutic agents, and monitoring the safety of treatment in BU. However, there is a lack of information about the therapeutic approach in pregnancy and vaccination practices. It was also observed that there is no consensus on the precautions to be taken before cataract surgery. Conclusion: Our study has shown that there is a need for more detailed and widespread information sharing on treatment in preparation for ocular surgery, safety monitoring, drug use during pregnancy, and vaccination in BU patients.

Surgical Treatment of Bullous Exudative Retinal Detachment Secondary to Atypical Bilateral Central Serous Chorioretinopathy

This study aimed to report the diagnostic process, treatment, and follow-up of a patient with bullous exudative retinal detachment (RD) associated with an atypical variant of bilateral central serous chorioretinopathy (CSCR). A 28-year-old woman was referred to our clinic for total bullous RD in the right eye with a vision level of light perception only. She had been previously diagnosed with idiopathic uveal effusion syndrome and treated with systemic corticosteroid therapy with no response, and was referred to us for scleral window surgery. Four-quadrant scleral window surgery with external drainage of the subretinal fluid was performed, resulting in a transient partial attachment of the retina. RD started to progress again within 3 weeks, which prompted comprehensive imaging together with more advanced systemic workup for systemic lupus erythematosus and other rheumatological and immunological diseases. Systemic corticosteroid therapy was initiated during this period but did not stop the progression and was discontinued after a short time. Fluorescein angiography and indocyanine green angiography revealed multifocal choroidal leakage foci and large choroidal vessels without any intraocular inflammation findings and led to the diagnosis of atypical CSCR. Pars plana vitrectomy (PPV), internal drainage of the subretinal fluid, endolaser to the focal leakage areas, and intravitreal aflibercept injection were performed. Visual acuity increased to 0.8 within 8 months after the surgery with no recurrence. Bullous exudative RD is a very rare and atypical form of CSCR, and a favorable outcome can be obtained with PPV and surgical drainage of subretinal fluid followed by laser photocoagulation.

Bilateral Acute Depigmentation of Iris (BADI) and Bilateral Acute Iris Transillumination (BAIT)Following Acute COVID-19 Infection.

PURPOSE: To report the presenting features and outcomes in patients who developed bilateral acute iris transillumination (BAIT) or bilateral acute depigmentation of iris (BADI) following acute COVID-19 infection. METHODS: Thirty two eyes of 16 patients were reviewed retrospectively. The severity of COVID-19 infection, use of antibiotics, time of onset of ocular symptoms; ocular signs, the course and surgical procedures were recorded. RESULTS: 24 eyes of 12 BAIT and eight eyes of four consecutive BADI patients were included. The mean time between infection and onset of ocular symptoms was 2.5±1.1 weeks. Nine patients were treated with oral moxifloxacin for COVID-19 prior to presentation. Trabeculectomy was performed in 7 eyes (21.8%) of 5 BAIT patients; in the postoperative follow-up, IOP was controlled without medication in 6 eyes, with medication in 1 eye. CONCLUSION: BADI and BAIT can also develop after COVID-19 infection. A significant proportion of BAIT patients may require glaucoma surgery.

How challenging can it be to treat Behçet uveitis?

A 20-year-old male Behçet uveitis (BU) patient presented with visual acuities (VAs) of hand movement in OD and counting fingers at 1 m in OS following treatment with corticosteroid monotherapy elsewhere. He had active intraocular inflammation OU along with macular hole and retinal detachment in OS. Infliximab (IFX) was started and vitreoretinal surgery was performed. He had infusion reaction with IFX, hepatotoxicity and depression with interferon, and resistance to adalimumab and tocilizumab therapies. Cytomegalovirus retinitis developed in OD following intravitreal dexamethasone implant and endophthalmitis developed in OS. At the 33rd month of follow-up, the patient was in clinical remission; however, there was persistent angiographic inflammation under certolizumab pegol, cyclosporine, mycophenolate mofetil, and low-dose prednisolone treatment. The left eye was phthisical and VA was 0.4 in OD. Immunomodulatory treatment is given based on the severity of inflammation in BU and needs to be closely monitored for efficacy and adverse effects.

Interferon Alpha-2a for the Treatment of Cystoid Macular Edema Secondary to Acute Retinal Necrosis.

PURPOSE: To report the results of interferon (IFN) α-2a treatment in patients with cystoid macular edema (CME) secondary to acute retinal necrosis (ARN). METHODS: We reviewed the records of seven patients (eight eyes) who received IFNα-2a for post-ARN CME. The initial dose of IFNα-2a was 3 MIU/day and it could be tapered down to 3 MIU twice a week. Efficacy was assessed by central macular thickness (CMT) on spectral-domain optical coherence tomography and visual acuity. RESULTS: Age range of seven patients (four men, three women) was 36-74 years. Mean CMT decreased from 477.9 ± 167.5 µm to 367.3 ± 120.5 µm at first week, and vision improved up to five lines in five eyes. CME relapsed after cessation of IFNα-2a in all and improved following reinstitution of treatment. Treatment was discontinued in one patient because of depression. Three patients electively discontinued treatment due to poor tolerability or lack of functional improvement. CONCLUSION: IFNα-2a is an effective therapeutic option for post-ARN CME, though side effects such as fatigue, elevated liver enzymes, neutropenia, and depression may limit tolerability. Lower initial doses may be a better tolerated.

COVID-19 and the Use of Immunomodulatory Agents in Ophthalmology

Immunomodulatory agents are often used in the systemic treatment of non-infectious uveitis. These drugs consist of corticosteroids, conventional immunosuppressives, and biological agents. As it is known that they suppress the immune system, the most important concern associated with immunomodulatory therapy (IMT) is the increased risk of infection. The World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although severe acute respiratory distress syndrome secondary to SARS-CoV-2 infection may develop in all people, patients who receive IMT may be at higher risk in terms of both the transmission of the infection and more severe disease course. Therefore, guidelines on the management of patients receiving IMT due to uveitis during the pandemic are needed. In this review, we examined the immunomodulatory drugs used in the treatment of uveitis in terms of infectious complications and the data of patients who received IMT during the COVID-19 pandemic and discussed recommendations for the use of these drugs. According to the latest information, patients who receive IMT may continue their treatment as long as there are no disruptions in regular complete blood count (especially white blood cell count >4,000/µL) and liver and kidney function tests. Patients diagnosed with COVID-19 should be managed with a multidisciplinary approach.

An Algorithm for the Diagnosis of Behçet Disease Uveitis in Adults.

Purpose: To develop an algorithm for the diagnosis of Behçet's disease (BD) uveitis based on ocular findings.Methods: Following an initial survey among uveitis experts, we collected multi-center retrospective data on 211 patients with BD uveitis and 207 patients with other uveitides, and identified ocular findings with a high diagnostic odds ratio (DOR). Subsequently, we collected multi-center prospective data on 127 patients with BD uveitis and 322 controls and developed a diagnostic algorithm using Classification and Regression Tree (CART) analysis and expert opinion.Results: We identified 10 items with DOR >5. The items that provided the highest accuracy in CART analysis included superficial retinal infiltrate, signs of occlusive retinal vasculitis, and diffuse retinal capillary leakage as well as the absence of granulomatous anterior uveitis or choroiditis in patients with vitritis.Conclusion: This study provides a diagnostic tree for BD uveitis that needs to be validated in future studies.

Behçet's disease uveitis: is there a need for new emerging drugs?

Introduction: Behçet's disease uveitis (BDU) is a potentially blinding disorder. Systemic treatment with disease-modifying anti-rheumatic drugs (DMARDs) is mandatory in patients with intraocular inflammation involving the posterior segment of the eye. Areas covered: This article discusses existing systemic treatment with corticosteroids and conventional and biologic DMARDs as well as adjunctive local therapy in BDU. An overview is provided for a wide range of biologic DMARDs that have shown promise or investigated in clinical trials. Most recently introduced biologic DMARDs and targeted synthetic DMARDs are also reviewed for their potential in the treatment of BDU. Expert opinion: The prognosis of patients with BDU has remarkably improved after the introduction of biologic DMARDs. An expanding therapeutic armamentarium will allow treatment of most refractory cases. The ultimate goal is to provide drug-free remission with preservation of 20/20 vision.

Multimodality Approach to the Diagnosis and Assessment of Uveitic Macular Edema.

Purpose: To provide an overview of the role of multimodality approach to the diagnosis and assessment of uveitic macular edema (UME). Methods: Review of literature. Results: Optical coherence tomography (OCT) has become the gold standard in the detection, quantification, monitoring of treatment, and determination of prognosis in UME. Fluorescein angiography provides essential information on blood-retinal barrier disruption as a result of intraocular inflammation and allows detection of associated retinal ischemia and neovascularization. Dye-less OCT angiography can reveal the presence of various qualitative and quantitative retinal microvascular changes mostly involving the deep capillary plexus. Reading acuity and retinal sensitivity assessed by microperimetry represent sensitive measures for visual dysfunction in UME and may supplement distance visual acuity in the follow-up of patients with UME. Conclusion: Conventional and new imaging modalities and ancillary tests complement each other in the diagnosis, assessment, and monitoring of patients with UME.

Long-term Results of Trabeculectomy With Mitomycin-C in Patients With Bilateral Acute Iris Transillumination.

PRéCIS:: The present study suggests that immediate trabeculectomy with mitomycin C (MMC) may be performed as a safe and effective intervention in the management of refractory ocular hypertension (OHT)/glaucoma in patients with bilateral acute iris transillumination (BAIT). PURPOSE: To report the long-term results of trabeculectomy with MMC in the management of OHT/glaucoma in patients with BAIT. MATERIALS AND METHODS: In total, 9 eyes of 6 patients with BAIT who underwent trabeculectomy with MMC between 2007 and 2015 were reviewed. Main outcome measures were control of intraocular pressure (IOP), the number of antiglaucomatous medications required to achieve the desired IOP, and complications. RESULTS: The postoperative follow-up time ranged between 2 and 9.5 years. IOP at presentation was >21 mm Hg in all patients. Maximum IOP with maximum antiglaucomatous medications during follow-up before surgery ranged between 36 and 55 mm Hg. At last visit, IOP ranged between 8 and 17 mm Hg, and 6 of 9 of the eyes required no antiglaucomatous medications. There was no failure in any patients according to the guidelines of the World Glaucoma Association. The most common complication was cataract formation in 7 eyes. CONCLUSIONS: The favorable outcomes observed during 2 to almost 10 years following surgical intervention are encouraging. Therefore, trabeculectomy with MMC provides long-term safe and effective results in OHT/glaucoma in patients with BAIT.

2018 update of the EULAR recommendations for the management of Behçet's syndrome.

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.

Tocilizumab for the Treatment of Behçet Uveitis that Failed Interferon Alpha and Anti-Tumor Necrosis Factor-Alpha Therapy.

PURPOSE: To report the results of tocilizumab (TCZ) treatment in patients with Behçet uveitis (BU) who had failed conventional, interferon alpha, and anti-Tumor necrosis factor-alpha therapy. METHODS: We reviewed the records of five patients with BU treated with monthly infusions of TCZ 8 mg/kg. Outcome measures were visual acuity, anterior chamber cells, laser flare meter (LFM) readings, vitreous haze, central macular thickness (CMT), and fluorescein angiography (FA) score. RESULTS: The clinical inactivity of BU and 20/50 or better vision were achieved in three female and two male patients treated with TCZ for 5-19 months. The mean LFM reading was reduced from 15.4 ± 2.7 to 5.0 ± 0.9 ph/ms; the mean CMT from 324.7 ± 36.6 µm to 280.2 ± 34.1 µm; and the mean FA score from 20.6 ± 5.4 to 9.3 ± 4.5 µm at the last visit. The only side effect was a slight elevation of the total cholesterol level in one patient. CONCLUSIONS: Tocilizumab may be a safe and effective therapeutic option for refractory BU.

Interferon Alpha for the Treatment of Cystoid Macular Edema Associated with Presumed Ocular Tuberculosis.

PURPOSE: To report the efficacy and safety of interferon (IFN) α-2a in patients with cystoid macular edema (CME) associated with presumed ocular tuberculosis (TB). METHODS: We reviewed the clinical records of 5 patients with presumed ocular TB who had been treated with IFN α-2a for recurrent CME during or after completion of anti-tubercular therapy. IFN α-2a was administered at an initial dose of 3 million IU per day and then tapered after the initial response. Treatment efficacy was assessed by central macular thickness (CMT) measurement using spectral-domain optical coherence tomography and visual acuity. RESULTS: Three patients were men, and 2 were women. Patients were aged between 38 and 66 years. Mean CMT was 483 ± 178.6 µm at baseline, 302.3 ± 56 µm at 1 week, 312.3 ± 49.5 µm at 1 month, and 286.2 ± 31.9 µm at 3 months. Mean LogMAR visual acuity was 0.6 ± 0.4 at baseline, 0.4 ± 0.3 µm at 1 week, 0.3 ± 0.3 at 1 month, and 0.3 ± 0.3 at 3 months. The treatment was interrupted for 10 days because of neutropenia after 2 weeks in 1 patient and discontinued in another after 10 days because of intolerance. Total treatment duration was 3-24 months in the remaining 4 patients. CONCLUSION: The present small case series suggests that IFN α-2a may be an effective and safe therapeutic option for CME that is associated with presumed ocular TB.

Review for Diagnostics of the Year: Multimodal Imaging in Behçet Uveitis.

Behçet disease is a chronic relapsing multisystem inflammatory disorder. Ocular involvement is characterized by a bilateral recurrent non-granulomatous panuveitis and retinal vasculitis. Posterior segment findings vary during the course of the disease, in parallel with the relapsing and remitting intraocular inflammation. Structural alterations occur with increased disease duration. Fluorescein angiography is the gold standard in revealing the extent and severity as well as the leaky and/or occlusive nature of retinal vasculitis. Multimodal imaging using color fundus photography, fluorescein angiography, and optical coherence tomography is essential in visualizing diagnostic features, detecting structural changes, and monitoring disease activity and response to treatment in patients with Behçet uveitis.

Systemic vasculitis and the eye.

PURPOSE OF REVIEW: The primary systemic vasculitides represent a spectrum of rare but life-threatening conditions that may also affect the eye in various forms. This article reviews recently published data on ocular manifestations of systemic vasculitis. RECENT FINDINGS: Early diagnosis and timely treatment has led to better visual outcomes in giant cell arteritis (GCA). Gene expression from orbital tissues could distinguish granulomatosis with polyangiitis (GPA) from sarcoidosis and Graves disease, but not from idiopathic orbital inflammation. Rituximab was an effective therapeutic option in ocular GPA. An ocular attack severity scoring system, flare levels, fluorescein angiography and optical coherence tomography parameters have been suggested as predictors of visual prognosis in Behçet disease. Efficacy of tumor necrosis factor-alpha inhibitors, interferon α and anti-interleukin-1 agents was shown in noncontrolled studies of ocular Behçet disease. SUMMARY: Widely used fast-track pathway care as well as ocular imaging to detect subclinical involvement may enable earlier diagnosis of GCA and prevention of permanent visual loss. Orbital inflammation may not remain idiopathic with advances in gene expression profiling of orbital tissues. With an increased availability and the use of biologic agents, visual prognosis will improve in patients with severe ocular complications of systemic vasculitides.

Reappraisal of the management of Vogt-Koyanagi-Harada disease: sunset glow fundus is no more a fatality.

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis. Aim of the study was to gather a body of evidence from the literature and from experts that systemic corticosteroid combined with non-steroidal immunosuppressive therapy should become the standard of care in initial-onset VKH disease. METHODS: Literature was reviewed and leading experts in VKH were consulted in different parts of the world in order to put forward a consensus attitude in the management of initial-onset VKH disease. RESULTS: There was a substantial body of evidence in the literature that early aggressive and sustained corticosteroid and non-steroidal immunosuppressive therapy in initial-onset VKH disease allows to achieve full control of choroidal inflammation, eliminating any subclinical choroidal inflammation, and substantially reduces recurrences with improvement of anatomical and functional outcomes. This was in agreement with experts' opinion and practice. ICGA was the method of choice to monitor disease evolution. CONCLUSION: Since the choroidal space is easily accessible to systemic therapy and because inflammation in VKH disease is exclusively originating from the choroidal stroma, early and sustained treatment right at the onset of the disease process with dual corticosteroid and non-steroidal immunosuppressive therapy can result in full "healing" in many cases preventing sunset glow fundus which results from depigmentation from chronic uncontrolled inflammation.

Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

Pediatric uveitis may be a serious health problem because of the lifetime burden of vision loss due to severe complications if the problem is not adequately treated. Juvenile idiopathic arthritis (JIA)-associated uveitis is characterized by insidious onset and potentially blinding chronic anterior uveitis. Periodic ophthalmologic screening is of utmost importance for early diagnosis of uveitis. Early diagnosis and proper immunomodulatory treatment are essential for good visual prognosis. The goal of treatment is to achieve enduring drug-free remission. The choice of therapeutic regimen needs to be tailored to each individual case. One must keep in mind that patients under immunomodulatory treatment should be monitored closely due to possible side effects. Local and systemic corticosteroids have long been the mainstay of therapy; however, long-term corticosteroid therapy should be avoided due to serious side effects. Steroid-sparing agents in the treatment of JIA-associated uveitis include antimetabolites and biologic agents in refractory cases. Among the various immunomodulatory agents, methotrexate is generally the first choice, as it has a well-established safety and efficacy profile in pediatric cases and does not appear to increase the risk of cancer. Other classic immunomodulators that may also be used in combination with methotrexate include azathioprine, mycophenolate mofetil, and cyclosporin A. Biologic agents, primarily tumor necrosis factor alpha inhibitors including infliximab or adalimumab, should be considered in cases of treatment failure with classic immunomodulatory agents.

Dexamethasone intravitreal implant (Ozurdex®) for pediatric uveitis.

PURPOSE: The purpose of this study was to investigate the safety and effectiveness of an intravitreally injected dexamethasone-containing implant (Ozurdex(®)) in the treatment of uveitis in children. METHODS: The study group included ten patients (14 eyes) aged 6.5-15 years (mean age 12 years) with intermediate or posterior uveitis who were treated with the Ozurdex implant at two tertiary medical centers between 2009 and 2014, following an insufficient response to standard uveitis therapy. All were followed for at least 6 months (mean 12.2 ± 4.9 months). Clinical data before and after treatment were collected retrospectively from the medical files. Outcome measures were best corrected visual acuity, vitreous haze, and macular thickness. Ocular complications were documented. RESULTS: Visual acuity improved in 12 eyes (86 %) and intraocular inflammation decreased in 13 eyes (93 %) from 1 week to 3 months after the first injection. Macular edema decreased in all eyes from 1 month to 3 months after the first injection. Five patients underwent repeated injections because of an increase in macular thickness at 3-6 month follow-up. Complications included cataract progression in one patient after one injection and cataract formation in two patients after two injections, and an elevation in intraocular pressure in two patients who responded well to topical treatment. CONCLUSIONS: Both single and repeated injections of a dexamethasone-containing implant are safe and effective for the treatment of noninfectious intermediate and posterior uveitis in children. The duration of the beneficial effect may be limited. More data are required to establish the safety profile of the implant in the pediatric age group.

Acute granulomatous iridocyclitis in a child with tubulointerstitial nephritis and uveitis syndrome.

BACKGROUND: Tubulointerstitial nephritis and uveitis [TINU] syndrome is a rare disorder that may also be underdiagnosed. Patients with TINU syndrome typically present with an acute bilateral nongranulomatous anterior uveitis following symptoms of systemic illness. FINDINGS: We report the case of a 15-year-old girl who presented with acute granulomatous iridocyclitis and was diagnosed with TINU syndrome based on renal biopsy findings. Both her uveitis and interstitial nephritis promptly responded to high-dose corticosteroid treatment, and there were no relapses during follow-up of 20 months. CONCLUSIONS: TINU should be included in the differential diagnosis of patients who present with acute granulomatous uveitis.

Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.