POLYPOIDAL LESIONS ASSOCIATED WITH CHOROIDAL NEVI.

PURPOSE: To investigate eyes with polypoidal lesions associated with choroidal nevi, their multimodal imaging characteristics, and long clinical follow-up. METHODS: Multicenter, retrospective case series study of patients with polypoidal lesions overlying choroidal nevi. Demographic and clinical information were recorded. Multimodal imaging including color fundus photography, optical coherence tomography, optical coherence tomography angiography, fundus fluorescein angiography, indocyanine angiography, and A- and B-scan ultrasonography were analyzed for nevus and polypoidal lesion characteristics. RESULTS: Fourteen eyes (14 patients; mean age: 70.3 ± 6.7 years) with polypoidal lesions overlying choroidal nevi were included. The mean follow-up duration was 50.0 ± 27.9 months (range 12-108). All nevi were pigmented on color fundus photography, flat on ultrasonography with a mean basal diameter of 3.8 ± 0.4 mm. In all but one eye, optical coherence tomography showed a shallow irregular pigment epithelium detachment overlying the nevus. A total of 11/14 eyes (78.6%) had exudative activity, 9 eyes received intravitreal anti-vascular endothelial growth factor injections, and one eye required intravitreal anti-vascular endothelial growth factor combined with photodynamic therapy. Mean visual acuity was 20/32 at baseline and 20/50 at final visit. CONCLUSION: We present the largest known cohort of eyes with polypoidal lesions associated with choroidal nevi with up to 9 years follow-up. The exudative degree of the polypoidal lesion in this condition is variable and treatment decisions should be taken on an individual basis. We hypothesize that choroidal ischemia because of altered choroidal vasculature rather than Haller layer hyperpermeability plays a role in the formation of polypoidal lesions overlying nevi.

Gender related trends among Israeli ophthalmologists professional career and personal life performance.

BACKGROUND: Gender-diversity trends in ophthalmology in Israel have not been studied despite a high proportion of female ophthalmologists. Our purpose was to evaluate gender-related trends in ophthalmology professional career and personal life performance in early and advanced careers in Israel. METHODS: A survey based on a nationwide voluntary anonymous web questionnaire was distributed to the members of the Israeli Ophthalmological Society. The questionnaire included questions referring to professional career and personal life performance. Gender differences were analyzed. RESULTS: Out of 252 respondents, 116 (46%) were women, with a mean age of 47.97 + -11.3 and 53.18 + -12.4 (P = 0.01) years, respectively. Marital status, post-residency fellowship performance or duration, an additional academic degree, academic appointments, and managerial positions were similar between genders. Fellowship predominance of males was found in cornea/cataract/refractive and of females in strabismus, pediatric ophthalmology, and neuro-ophthalmology (P < 0.01, P = 0.032, respectively). Men had significantly more publications and appointments in peer review journals and work hours (P = 0.04 and P = 0.02, P = 0.027, respectively). Both genders responded similarly regarding work satisfaction, combination between family life and work. More women felt inequity during and post-residency in clinical (P = 0.011, P = 0.001, respectively) and surgical work (P = 0.001, P = 0.035, respectively). More women experienced inappropriate remarks from patients and sexual harassment (P = 0.001, P < 0.001, respectively), and supported the need for affirmative action (P < 0.0001). CONCLUSIONS: Several gender disparities were found among ophthalmologists in Israel, including subspecialties distributions, publications, appointments in peer review journals, working hours, work inequity sense, harassment events, and support the need for affirmative action.

Risk factors and clinical significance of prechoroidal cleft in eyes with neovascular age-related macular degeneration in Caucasian patients.

OBJECTIVE: The objective of the study was to investigate the prevalence, risk factors and clinical significance of prechoroidal cleft (PC) among neovascular age-related macular degeneration (nAMD) patients in a Caucasian population. DESIGN: A retrospective observational cohort study. METHODS: A total of 140 patients with naive nAMD were treated with anti-vascular endothelial growth factor (VEGF) injections and a follow-up of ≥24 months. Optical coherence tomography (OCT) scans were graded for the presence of PC, central subfield foveal thickness (CSFT), maximal retinal thickness (MRT), pigment epithelial detachment (PED), presence of intraretinal fluid (IRF), subretinal fluid (SRF) and subretinal hyper-reflective material (SHRM) at baseline, 3, 6, 12 and 24 months. Best corrected visual acuity (BCVA) and anti-VEGF treatments were recorded. RESULTS: Out of 140, 21 eyes (15%) developed PC. BCVA improved significantly from 0.68 ± 0.56 to 0.62 ± 0.59 logMAR after 24 months (p = 0.008). The change in BCVA was not related to the presence of cleft (p = 0.208). Multivariate analysis confirmed that higher baseline CSFT (p = 0.011, OR = 1.004, 95%, CI 1.001-1.007) and the presence of multi-layered PED (p < 0.001, OR = 21.153, 95%, CI 5.591-80.026) were both predictive for development of PC. Eyes with PC received more injections than eyes without PC. CONCLUSION: Prechoroidal cleft was found in 15% of Caucasian nAMD patients treated with anti-VEGF injections and was related to greater retinal and PED height, as well as presence of multi-layered PED. Eyes with PC required more anti-VEGF injections. The presence of PC correlates with disease activity, and intensive anti-VEGF suppression can preserve vision.

[SOLVING A MEDICAL MYSTERY THROUGH THE EYES OF A YOUNG PATIENT WITH BUDD-CHIARI SYNDROME AND A NEW VISION LOSS].

INTRODUCTION: Budd-Chiari syndrome is a heterogeneous group of disorders characterized by venous drainage obstruction of the liver and is extremely rare. The clinical manifestations are usually ascites, varicose veins and in severe cases - hepatic insufficiency. Behcet's disease is a chronic, idiopathic, inflammatory disease that manifests as obstructive vasculitis and affects a variety of organ systems. Ocular involvement occurs in approximately 70% of the patients, and is a major clinical criterion in the diagnosis. Rarely, Behcet's disease can be a cause of Budd-Chiari syndrome. In these cases, the diagnosis has a crucial impact on the treatment and prognosis of the patients since patients with Budd-Chiari syndrome secondary to Behcet's disease, will usually improve under systemic medications with no need for surgery. In addition, in these patients there is a higher chance for developing hepatocellular carcinoma so they need to have a tight and a long follow-up. DISCUSSION: In this article we discuss a case of a young patient with Budd-Chiari syndrome, who was examined due to acute vision loss in his left eye. Left eye examination revealed panuveitis presenting with anterior uveitis, intermediate uveitis and an occlusive retinal vasculitis. The ocular examination raised suspicion that the diagnosis was Behcet's disease. Actually, Budd-Chiari syndrome was part of the presentation of Behcet's disease, which was not diagnosed until he was examined by us. The patient was treated with corticosteroid therapy and biological treatment with adalimumab, an anti-TNF drug. During follow-up, a complete resolution of the intraocular inflammation was achieved, as well as stabilization of its general condition, with the disappearance of the clinical signs indicative of liver failure.

Ocular Adverse Events Induced by Immune Checkpoint Inhibitors: A Comprehensive Pharmacovigilance Analysis.

PURPOSE: Characterize ocular adverse events (oAEs) caused by immune checkpoint inhibitors (ICIs). METHODS: Retrospective analysis of 41,674 cancer patients in the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database receiving anti-PD-1/PD-L1, anti-CTLA-4, or anti-PD-1+ anti-CTLA-4 combination. Reporting odds ratio (ROR) was used to approximate oAE rate across regimens and indications. RESULTS: The most common indications were lung cancer (27.3%) and melanoma (22.7%); 76.3% received anti-PD-1/PD-L1 monotherapy. 1,268 patients (3.0%) reported oAEs, namely vision disorders (30.8%), uveitis (15.1%), and retinal, lacrimal, and optic nerve disorders (10.7%, 9.0%, 8.4%). Melanoma showed the highest proportion of uveitis (117/9,471 cases; 1.2%). Addition of anti-CTLA-4 to anti-PD-1 increased the ROR of uveitis from 4.77 (95% CI 3.83-5.94) to 17.1 (95% CI 12.9-22.7). Among anti-PD-1/PD-L1 cases, uveitis was differentially reported in melanoma (ROR 14.7, 95% CI 10.7-20.2) compared with lung cancer (ROR 2.67, 95% CI 1.68-4.23). CONCLUSION: ICI-induced oAEs are rare, and uveitis is significantly associated with melanoma and anti-PD-1+ anti-CTLA-4 combination.

Consensus Recommendations for the Diagnosis of Vitreoretinal Lymphoma.

PURPOSE: To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL). METHODS: Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations. RESULTS: Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended. CONCLUSIONS: A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.

Efficacy and safety of intravitreal methotrexate for vitreo-retinal lymphoma - 20 years of experience.

Vitreo-retinal lymphoma (VRL) is the most common intraocular lymphoma and is highly associated with central nervous system (CNS) lymphoma (CNSL), both posing a therapeutic challenge. We investigated patients' characteristics, efficacy and safety of intravitreal methotrexate (MTX) injections and their outcomes over 20 years. The records of 129 patients diagnosed between 1997 and 2018 were retrospectively reviewed. Lymphoma involved both the CNS and vitreo-retina (49%), solely the CNS (37%) or solely the vitreo-retina (14%). In all, 45·5% of the patients with CNSL either presented with VRL or developed it after a mean (±SE) of 85·7 (7·3) months. In all, 66·0% of the patients diagnosed with VRL either presented with CNSL or developed it after a mean (±SE) 42·6 (7·6) months. The 81 patients with VRL (134 eyes) received a mean (±SD) of 19 (7) injections; however, only 5 (4) injections were needed to reach complete remission. Local recurrence occurred in two of the 81 patients. Overall, 80·2% of eyes had an initial moderate-severe visual loss, and >50% of them improved. Reversible keratopathy was the most prevalent side-effect. A total of 18·5% developed intraocular pressure (IOP) elevation due to angle neovascularisation after 16 injections, which could be reversed with prompt intravitreal injection of bevacizumab. Intravitreal MTX injections are a safe and effective treatment for VRL. Fewer injections (15) may offer similar results with fewer side-effects.

Occlusive retinal vasculopathy with macular branch retinal artery occlusion as a leading sign of atypical hemolytic uremic syndrome - a case report.

BACKGROUND: Hemolytic Uremic Syndrome (HUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, considered within the group of thrombocytic microangiopathies. Ocular complications in HUS are very rare. Here, we report an adult patient who suffered from acute onset of paracentral scotoma, caused by branch retinal artery occlusion (BRAO), as a leading symptom of atypical HUS. CASE PRESENTATION: A 39-year-old healthy male was lately diagnosed with essential hypertension and mild renal impairment. He complained about acute onset of central scotoma in his left eye. Fundus examination revealed marked narrowing of retinal vessels, cotton wool spots and few retinal hemorrhages in both eyes. The patient was diagnosed with bilateral ischemic retinal vasculopathy and acute macular BRAO in his left eye. Workup revealed thrombocytopenia, worsening renal failure. Renal biopsy showed signs of chronic thrombotic microangiopathy. The patient was diagnosed with atypical HUS (aHUS) and started on plasmapheresis, together with eculizumab. As his condition continued to worsen, he was put on renal replacement therapy. Due to a persistent monoclone of IgG1, the patient underwent bone marrow biopsy which revealed Monoclonal Gammopathy of renal significance, triggering a HUS and treatment was initiated accordingly. Two months after initial presentation, the patient developed neovascularization of the optic disc (NVD) in his left eye, and was treated with 3 monthly intravitreal bevacizumab injections with complete regression of the NVD. The patient suffered from myocardial infarction in the later course and was lost for follow-up. He returned 11 months after the last bevacizumab injection because of sudden loss of vision in his left eye caused by a dense vitreous hemorrhage. Biomicroscopy revealed a new NVD in his right eye. The patient underwent panretinal photocoagulation in both eyes with regression of neovascularization. Vision improved and remained 20/20 in both eyes. CONCLUSION: We present a case report showing retinal ischemia can be linked with aHUS. As clinal diagnosis might be challenging, physicians should be aware of the rare ocular manifestations of this devastating multi-organ disease. In case of retinal ischemia, panretinal photocoagulation should be initiated soon to avoid blinding complications.

Uveitis Induced by Biological Agents Used in Cancer Therapy.

Purpose: To report cases of uveitis induced by biological therapy given for cancer.Methods: Retrospective review of medical charts of patients.Results: Included were six patients aged 14-81 years. Three were treated with vemurafenib and one each with nivolumab, ipilimumab, and osimertinib. The oncological diagnoses were metastatic thyroid carcinoma, pleomorphic xanthoastrocytoma, metastatic melanoma, adenocarcinoma of the lung, and metastatic breast cancer. Ocular manifestations appeared 4-82 weeks after the biological treatment was initiated. The most common ocular presentation was anterior uveitis. Onset was sudden in all cases. The median duration of uveitis was 70 weeks. Treatment included topical or systemic corticosteroids; one patient received a single intravitreal steroid injection in one eye.Conclusions: Uveitis may rarely be induced by treatment with biological agents for cancer. Both oncologists and ophthalmologists should be aware of this potential side effect. Early detection and management can prevent permanent complications and save the patient's vision.

Bilateral Diffuse Uveal Melanocytic Proliferation in a Woman with Metastatic Scalp Squamous Cell Carcinoma Treated with Cemiplimab.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic intraocular syndrome that causes progressive visual loss in patients driven by an IgG factor associated with an underlying malignancy. The IgG factor - cultured melanocyte elongation and proliferation - was found in the IgG fraction of the serum of BDUMP patients. It has been shown to be involved in melanocytic proliferation. In this case report, we describe the first case of BDUMP related to metastatic cutaneous squamous cell carcinoma (cSCC) of the scalp. A 61-year-old woman complained of decreased vision in both of her eyes, while being treated with cemiplimab (an anti-PD-1 therapy) for metastatic cSCC. Fundus examination showed hypopigmented lesions in a leopard pattern and pigmentary clumps in both eyes. Further imaging confirmed the diagnosis of BDUMP. The patient was successfully treated with plasmapheresis. During follow-up, cataract progressed in both eyes, and she underwent cataract surgery with visual acuity improvement to 20/20. BDUMP is a challenging diagnosis especially in patients treated with anti-PD-1 immunotherapy as it can be confused with drug-related effects. It is crucial to distinguish between the cases in order to allow the appropriate treatment which includes continuation of systemic anti-PD-1 for the underlying malignancy and plasmapheresis therapy for BDUMP.

Acute Lymphoblastic Leukemia Relapse Limited to the Anterior Chamber of the Eye and Treated with Novel CAR T-Cell Therapy.

Acute lymphoblastic leukemia (ALL) is a malignant neoplasm of the blood stem cells, characterized by increased formation of immature lymphocytes. Ocular manifestations may vary with ocular, adnexal, and orbital involvement. In this case report, we describe the first case of extramedullary relapse of ALL limited to the anterior chamber of the eye treated with the novel chimeric antigen receptor T (CAR T)-cell therapy and provide a literature review of cases of ALL relapse in the anterior chamber. A 21-year-old male with a history of B-cell ALL presented with a unilateral blurry vision in his left eye. Ocular examination revealed the presence of cells +3 in the anterior chamber and a 1.5-mm hypopyon. Anterior chamber aspiration confirmed a B-ALL relapse. The patient was successfully treated with radiotherapy of his left eye and received CTL-019 transduced T cells (tisagenlecleucel; Novartis) with cytarabine as a bridging chemotherapy treatment. On the last examination, 18 months after the first presentation, the patient presented a complete ocular remission with no systemic or CNS involvement. ALL relapse may involve the anterior chamber of the eye, and an accurate diagnosis is crucial to enable a fast and appropriate treatment. Novel CAR T-cell immunotherapy, combined with ocular irradiation, may be considered in such cases.

Recurrent Neuroretinitis: A Unique Presentation of Behçet's Disease in a Child.

We describe a case of Behçet's disease (BD) in a young child that presented with recurrent neuroretinitis and developed retinal lesions during follow-up. A 4.5-year-old girl presented with fever of 39.5°C, erythema nodosum in her legs, bilateral knee arthritis, and perineum aphthae. On ocular examination, visual acuity was 20/25 in both eyes. Right eye examination was normal and the left eye (LE) showed mild anterior and intermediate uveitis, normal optic disc, and a macular star appearance. Laboratory workup demonstrated elevated C-reactive protein levels, a normal abdominal ultrasound, and a normal colonoscopy. The patient was diagnosed with BD. One month post initial presentation, the patient presented with visual acuity of finger counting in the LE with significant anterior uveitis, mild intermediate uveitis, and recurrent neuroretinitis. Under treatment of IV methylprednisolone, oral betamethasone, infliximab, and colchicine, a complete systemic remission was noticed, and uveitis became quiescent. On last examination, 4.5 years post first presentation, visual acuity was 20/25 in both eyes and the LE demonstrated a remnant of a juxtafoveal retinal scar. To the best of our knowledge, this is the first case of neuroretinitis presenting as a manifestation of pediatric BD. Ophthalmologists should be aware of these unique manifestations of ocular BD.

The importance of cytokines analysis in the diagnosis of vitreoretinal lymphoma.

PURPOSE: To evaluate the efficacy of the different diagnostic tests for vitreoretinal lymphoma (VRL). METHODS: A cohort of 150 patients with a presumed diagnosis of VRL. Vitrectomy samples were analysed for cytology, monoclonality [polymerase chain reaction (PCR)] and cytokine levels, and anterior chamber taps were analysed for cytokine levels. Vitreoretinal lymphoma (VRL) was diagnosed after confirming the clinical suspicion with vitreal or brain cytology. RESULTS: Vitreoretinal lymphoma (VRL) was diagnosed in 78 patients. Vitreal cytology was positive for 53/132 patients (40.2%), 36/53 had positive cytology from both the eye and the brain. Additional 25 patients had positive brain cytology. Vitreal PCR for monoclonality was positive for 32/91 patients (35.2%). Vitreal cytokine levels of interleukin (IL)-10/IL-6 were >1 for 47/110 patients (43.1%). For cytology, PCR and cytokine analysis, the respective sensitivity was 73.6%, 46.0% and 81.4%, and the accuracy of the tests was 85.6%, 60.4% and 80.9%, respectively. All three tests were available for 79 patients. In this subset, for cytology, PCR and cytokine analysis the respective sensitivity was 79.5%, 41.0% and 82.1%, respectively, and the accuracy of the tests was 89.9%, 60.8% and 81.0%, respectively. CONCLUSION: Cytokines analysis has an important role in the diagnosis of VRL. We suggest analysing cytokines levels in all cases suspected of VRL along with cytology and PCR analysis.

A Collaborative Retrospective Study on the Efficacy and Safety of Intravitreal Dexamethasone Implant (Ozurdex) in Patients with Diabetic Macular Edema: The European DME Registry Study.

PURPOSE: To evaluate the efficacy, effect profile, and safety of dexamethasone implant on diabetic macular edema (DME) in a real-life setting, further comparing results by DME duration, previous treatment status, and diabetic control. DESIGN: A multicenter, retrospective cohort of 340 DME eyes of 287 patients from 25 clinical sites from 8 countries. METHODS: Data were analyzed in 2 perspectives: per injection, in which all measurements were grouped and baseline was defined as the day of injection, and thus the pharmacodynamics of single injections could be assessed; and injection series, defined as 2 or more injections with 3 to 6 months between injections analyzing the outcome 3 to 6 months after the last injection. MAIN OUTCOME MEASURES: Primary outcome was improvement of 15 or more letters in best-corrected visual acuity (BCVA) from baseline. Secondary outcomes included improvement of 10 letters or more in BCVA, change in central macular thickness (CMT), and time to maximum improvement and safety. RESULTS: Overall, 762 injections were administered to 340 eyes of 287 patients. Injection series analysis included 171 series in 171 eyes of 150 patients, for a total of 444 injections, with a mean follow-up of 1.7±0.8 years. Of the 762 injections analyzed per injection, 22.7% achieved a 15-letter or more improvement, and 37.8% achieved a 10-letter or more improvement. Mean time to peak improvement was 81.9±39.7 days. Mean maximum change in CMT was -174±171 µm. Overall, 7.6% lost 15 or more letters. More eyes with early DME gained 10 or more letters and fewer eyes lost 10 or more letters compared with eyes with late DME (47.4% vs. 33.9% [P = 0.001] and 8.2% vs. 13.5% [P = 0.029], respectively). Patients with controlled diabetes showed greater CMT reduction (P = 0.0002). A higher percentage of treatment-naive patients gained 10 or 15 letter or more in BCVA (P = 0.001 and P = 0.006, respectively). Intraocular pressure elevation of more than 25 mmHg was found following 7.9% of injections; no endophthalmitis was reported. CONCLUSIONS: Dexamethasone implant is an effective and safe treatment for DME. Peak improvement was achieved 3 months after injection and dissipated thereafter. Clinicians and providers may consider shortening treatment intervals.

Disorganization of retinal inner layers as a biomarker in patients with diabetic macular oedema treated with dexamethasone implant.

PURPOSE: To investigate disorganization of retinal inner layers (DRIL) as a biomarker in eyes with diabetic macular oedema (DME) treated by intravitreal dexamethasone (DEX) implant. METHODS: Multicentre, retrospective study including eyes with DME treated with DEX implant and follow-up of 12 months after the first injection. OCT scans were evaluated for the presence of DRIL and other structural features. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline and at 2, 4, 6 and 12 months after treatment. Correlation between DRIL at baseline and outcomes after DEX treatment and the change in DRIL were analysed. RESULTS: A total of 177 eyes (177 patients; naïve, n = 131; refractory, n = 46) were included. Patients without DRIL at baseline gained significantly more vision and enjoyed greater reduction in CST over 12 months (both p = 0.03). DRIL at the boundary between the ganglion cell-inner plexiform complex and inner nuclear layer improved in 48/64 eyes (75%, p < 0.001), while DRIL between the inner nuclear layer and outer plexiform layer improved in 27/77 eyes (35%, p = 0.004). CONCLUSIONS: This is the first study to show that DEX implant has the potential to ameliorate DRIL. Patients without DRIL at baseline have a favourable outcome. DRIL may serve a robust biomarker in DME treated by DEX implant.

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

BACKGROUND: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome. METHODS: A national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004-2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys. RESULTS: The study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3-88). Median fever duration was 4 weeks (range, 2-9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4-445), 95% had complete recovery; 3 patients remained with ocular sequelae. CONCLUSION: This is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease.

Visual and Clinical Outcome of Macular Edema Complicating Pediatric Noninfectious Uveitis.

PURPOSE: To investigate the clinical course and visual outcome of macular edema (ME) in pediatric patients with chronic noninfectious uveitis. DESIGN: Retrospective case series. METHODS: The databases of the uveitis clinics of 4 tertiary medical centers in Israel and the UK were searched for all children treated for uveitic ME in the years 2005-2015. Data were collected from the medical records as follows: demographics, diagnosis, visual acuity, clinical and imaging findings, and treatment given specifically for ME. Findings at baseline and at 3, 6, 12, and 24 months were evaluated. RESULTS: The cohort included 25 children (33 eyes) of mean age 8.5 ± 3.4 years. The most common diagnosis was intermediate uveitis, in 14 children (7 idiopathic, 7 pars planitis). Uveitis was active at ME diagnosis in 28 eyes (84.8%). Median duration of follow-up was 48 months. Median time to resolution of ME was 6 months, with complete resolution in 25 eyes (75.8%) by 24 months. Baseline visual acuity was ≥20/40 in 8 eyes (24.2%), increased to 57.6% at 3 months (P < .0001), and remained stable thereafter. Treatment regimens included corticosteroids (systemically and/or locally), immunosuppression, and biologic therapies. No correlation was found between outcome and either structural characteristics of ME or specific treatment strategy. CONCLUSIONS: The prognosis of pediatric uveitic ME is favorable despite its chronic course. Larger randomized controlled trials are needed to define differences among treatment regimens.

Anterior Scleritis Associated with Pemphigus Vulgaris.

We present a rare co-occurrence of anterior scleritis developing in a patient with recalcitrant pemphigus vulgaris. We discuss the clinical and therapeutic implications of these two conditions and offer concise recommendations.

The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric uveitis of diverse etiologies.

PURPOSE: This study aimed to report the clinical outcome of children with uveitis treated with anti-tumor necrosis factor alpha (TNF-α) agents. METHODS: This included a retrospective cohort study. Children with uveitis treated with infliximab or adalimumab in 2008-2014 at five dedicated uveitis clinics were identified by database search. Their medical records were reviewed for demographic data, clinical presentation, ocular complications, and visual outcome. Systemic side effects and the steroid-sparing effect of treatment were documented. RESULTS: The cohort included 24 patients (43 eyes) of whom 14 received infliximab and 10 received adalimumab after failing conventional immunosuppression therapy. Mean age was 9.3 ± 4.0 years. The most common diagnosis was juvenile idiopathic arthritis-related uveitis (n = 10), followed by Behçet's disease (n = 4), sarcoidosis (n = 1), and ankylosing spondylitis (n = 1); eight had idiopathic uveitis. Ocular manifestations included panuveitis in 20 eyes (46.5%), chronic anterior uveitis in 19 (44.2%), and intermediate uveitis in 4 (9.3%). The duration of biologic treatment ranged from 6 to 72 months. During the 12 months prior to biologic treatment, while on conventional immunosuppressive therapy, mean visual acuity deteriorated from 0.22 to 0.45 logMAR, with a trend of recovery to 0.25 at 3 months after initiation of biologic treatment, remaining stable thereafter. A full corticosteroid-sparing effect was demonstrated in 16 of the 19 patients (84.2%) for whom data were available. Treatment was well tolerated. CONCLUSIONS: Treatment of pediatric uveitis with anti-TNF-α agents may improve outcome while providing steroid-sparing effect, when conventional immunosuppression fails. The role of anti-TNF-α agents as first-line treatment should be further investigated in controlled prospective clinical trials.