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PURPOSE To describe uveitis cases after the BNT162b2 mRNA SARS-CoV-2 vaccination. METHODS This is a multicenter, retrospective study. Vaccine-related uveitis diagnosis was supported by the classification of the World Health Organization Adverse Drug Terminology and the Naranjo criteria. RESULTS Twenty-one patients (23 eyes) with a mean age of 51.3 years (23-78 years) were included. Eight of the 21 patients had a known history of uveitis. The median time from previous to current attack was 1 year (0.5-15 years). There were 21 anterior uveitis cases, two with bilateral inflammation. Eight cases occurred after the first vaccination and 13 after the second vaccination. All but three presented as mild to moderate disease. Two patients developed multiple evanescent white dot syndrome after the second vaccination. The mean time from vaccination to uveitis onset was 7.5 ± 7.3 days (1-30 days). At final follow-up, complete resolution was achieved in all but two eyes, which showed significant improvement. One case of severe anterior uveitis developed vitritis and macular edema after the second vaccination, which completely resolved after an intravitreal dexamethasone injection. CONCLUSION Uveitis may develop after the administration of the BNT162b2 mRNA vaccine. The most common complication was mild to moderate anterior uveitis, while multiple evanescent white dot syndrome can also occur less frequently.

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.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.

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.A retrospective observational cohort study.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.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.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.

To describe herpetic ocular infections following SARS-CoV-2 vaccinations.A retrospective study of herpetic ocular infections after BNT162b2mRNA vaccination and a literature review.A cohort of five patients: three varicella zoster virus (VZV) and two herpes simplex virus (HSV) cases, as well as 19 literature cases: 9 cases of VZV and 10 cases of HSV post BNT162b2mRNA, AZD1222, mRNA-1273, and CoronaVac vaccinations. All cases presented within 28 days post vaccination. Most VZV and HSV cases (15/19) reported in the literature presented post first vaccine dose, while in our cohort 2 VZV cases presented post second dose and both HSV cases and one VZV case post third dose. The most common presentations were HZO with ocular involvement and HSV keratitis. All eyes had complete resolution; however, one had retinal detachment and three corneal scars.Herpetic ocular infections may develop shortly after SARS-CoV-2 vaccinations. Overall, the outcome is good.

Background Susac's syndrome, a rare autoimmune vasculo-occlusive disease, may pose a diagnostic challenge and result in a devastating ocular and systemic outcome. Our study identifies a new retinal finding and evaluates disease outcome. We aimed to assess clinical and imaging findings, systemic manifestations and disease outcome in patients with ocular Susac's syndrome under immunosuppressive/immunomodulation therapies. Methods Retrospective tertiary center study including patients with a diagnosis of Susac's syndrome with >12 months follow up. Medical record review including ocular, neurological and auditory clinical and imaging findings, and treatment modalities. Main outcome measures were clinical manifestations and disease outcome. Results Seven patients (14 eyes) with a mean age of 34.1 years were included. Mean follow-up was 31.9 months (12.4-72.4). All had bilateral ocular disease. Retinal microaneurysms, a new ocular finding, were demonstrated in 5 patients and persisted at the final visit. In 5 eyes, they further extended during follow-up. All were treated with immunosuppressive drugs and 5/7 additional immunomodulation therapy. At last examination, best corrected visual acuity was >20/40 in all eyes, 1/10 eyes had visual field deterioration, no eye had active ocular disease, all patients achieved neurological stability, and 1 patient had auditory deterioration. Conclusion Retinal microaneurysms, a new ocular finding in Susac's syndrome, were present in most of our patients, indicating ischemic retinal damage. Immunosuppressive and immunomodulation therapies seem to be highly effective in the control of disease activity.

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.

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.

BACKGROUND: Susac syndrome (retino-cochleo-cerebral vasculopathy, SuS) is an autoimmune endotheliopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss. In contrast to data regarding auditory function, data measuring vestibular function is sparse and the cervical vestibular-evoked myogenic potentials (cVEMPs). OBJECTIVE: To determine whether the video head impulse test (vHIT) can serve as a confirmatory assessment of vestibulocochlear dysfunction in cases of suspected SuS. METHODS: Seven patients diagnosed with SuS underwent pure tone audiometry, a word recognition test, cVEMPs and the vHIT. RESULTS: Five patients were diagnosed with definite SuS, and two with probable SuS. Two patients were asymptomatic for hearing loss or tinnitus, and no sensorineural hearing loss was detected by audiograms. Four patients complained of tinnitus, and three patients reported experiencing vertigo. Three patients had abnormal cVEMPs results. All seven patients’ vHIT results were normal, except for patient #2, who was one of the three who complained of vertigo. The calculated gain of her left anterior semicircular canal was 0.5, without saccades. CONCLUSIONS: This is the first study to describe the results of the vHIT and cVEMPs among a group of patients with SuS. The results suggest that the vHIT should not be the only exam used to assess the function of the vestibular system of SuS patients.

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.

Background Susac syndrome (SuS) is a rare condition characterized by a clinical triad of sensorineural hearing loss, branch artery occlusion and encephalopathy. This study reports an increased incidence of SuS in Israel. We describe the clinical characteristics of these patients, diagnostic procedures and the use and subsequent outcomes of newly published treatment guidelines. Methods This is a single center retrospective study. Patients who were diagnosed with SuS between July 2017 and August 2018 were enrolled in this study. Results Seven patients were diagnosed with SuS according to the diagnostic criteria in a time period of 13 months. The annual incidence was recently evaluated in Austria to be 0.024/100000, therefore, our case series represent at least a 5.4- fold increase in the annual incidence of SuS expected in Israel and a 7-fold increase in the annual incidence expected in our medical center. Mean time from the onset of the symptoms to diagnosis was three weeks and follow-up time was twenty four months. Recent exposure to cytomegalovirus was serologically evident in three patients and one patient had high titer of anti-streptolysin antibody. All patients underwent brain MRI, fluorescein angiography and audiometry. All patients were treated according to the newly recommended guidelines. All patients achieved clinical and radiological stability. Conclusions We report of an increased incidence of SuS in Israel. Infectious serological findings may imply a post infectious mechanism. The use of the recommended diagnostic procedures reduced the time to diagnosis. Newly published treatment guidelines led to favorable clinical outcomes.

BackgroundOcular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice.Methods192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy.ResultsFor 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing—usually PCR—in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim–sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim–sulfamethoxazole was prescribed to selected patients by 69.8%.ConclusionOur report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists.

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.

BackgroundFever 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.MethodsA 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.ResultsThe 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.ConclusionThis 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.

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.

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.

Characterize ocular adverse events (oAEs) caused by immune checkpoint inhibitors (ICIs).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.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).ICI-induced oAEs are rare, and uveitis is significantly associated with melanoma and anti-PD-1+ anti-CTLA-4 combination.

To report cases of uveitis induced by biological therapy given for cancer. Retrospective review of medical charts of patients. Included were six patients aged 14–81 years. Three were treated with v...

Purpose: To report the epidemiology, etiology, ocular characteristics, treatment and visual outcome of pediatric uveitis in Israel.Methods: Retrospective study from two tertiary uveitis centers.Res...

PURPOSE Ocular manifestations of syphilis have been reported in 2-10% of systemic infection. The purpose of this study was to report the incidence of ocular syphilis and various ocular manifestations, particularly optic nerve involvement, in newly diagnosed cases. METHODS This was a retrospective study. Medical records of newly diagnosed syphilis patients between January 2009 and January 2017 in a tertiary medical centre were reviewed. RESULTS There were 123 new systemic syphilis cases out of 569,222 (0.02%) admissions to the Tel Aviv Medical Center during the study period. Ninety-three of the 123 patients (76%) underwent ophthalmological examination. Twenty-three of the 93 patients (25%, mean age 48.6 ± 12.9 years, 20 males) had ocular syphilis, and in 12/23 (52%) patients, the ocular symptoms and findings prompted syphilis investigation. Eighteen of the 23 (78%) had optic nerve involvement, and the most common was inflammatory disc oedema. Older age (p = 0.0005) and tertiary stage disease (p = 0.0441) were associated with ocular manifestations and the presence of optic nerve findings. Human immunodeficiency virus (HIV) was associated with ocular but not optic nerve findings. Treatment included intravenous penicillin G, and four patients with severe optic neuropathy were also treated with systemic corticosteroids. Visual acuity significantly improved in most patients (p

To describe the demographics and clinical characteristics of patients with herpetic anterior uveitis (HAU), and compare characteristics by pathogen, recurrence, and association to iris atrophy.Multicenter, retrospective study of AU patients diagnosed clinically and by polymerase chain reaction (PCR).The study included 112 eyes in 109 patients: 54 (48.2%) HSV, 34 (30.4%) VZV, 2 (1.8%) CMV, and 22 (19.6%) unspecified diagnosis. HSV eyes, compared to VZV, had a higher recurrence rate, corneal involvement, KPs, iris atrophy, elevated IOP and posterior synechia (p 0.05). VZV patients had more frequent immunomodulatory treatments and history of systemic herpetic disease (p 0.05). Fifty-nine (52.7%) eyes had recurrent disease. Iris atrophy was associated with a higher prevalence of posterior synechia, dilated distorted pupil, and high IOP (p 0.05).Different HAU-causing Herpesviridae produce common clinical findings; therefore, PCR should be used more often to confirm specific diagnosis. Iris atrophy was associated with more severe disease.

Purpose: To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB).Methods: Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes.Results: The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes.Conclusion: A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity.

This study aimed to report the clinical outcome of children with uveitis treated with anti-tumor necrosis factor alpha (TNF-α) agents. 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. 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 Behcet’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. 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.

Purpose To evaluate the efficacy and safety of eplerenone for chronic nonresolving central serous chorioretinopathy (CSC). Methods Prospective, double-blind, randomized placebo-controlled study. Nineteen eyes of 17 patients with persistent subretinal fluid (SRF) due to CSC were enrolled and randomized to receive eplerenone 50 mg/day or placebo for 3 months, followed by a 3-month follow-up. The main outcome measure was change in SRF from baseline to 3 months of treatment. Secondary outcomes included change in SRF at any time-point, complete resolution of SRF, improvement in choroidal thickness and change in best-corrected visual acuity (BCVA). Results Thirteen eyes were treated with eplerenone and six with placebo. Both groups showed reduction in SRF throughout the treatment period, with a significant reduction at months 1, 3 and 5 only in the treatment group. Twenty-three per cent in the treatment group and 30.8% per cent in the placebo group experienced complete resolution of SRF. A significant improvement in BCVA was noted in the placebo group at 4 months, as well as a significant difference in BCVA between groups at 3 months in favour of the placebo group (p = 0.005). There was no significant difference in choroidal thickness in either group throughout the study period. No adverse events related to eplerenone were noted in the treatment group. Conclusion In this study, eplerenone was not found to be superior to placebo in eyes with chronic CSC.

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; naive, 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

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.

Purpose Aminobisphosphonates may cause orbital/ocular inflammation. Awareness of the clinical presentation and disease course is crucial. The purpose of this study was to analyse demographics, clinical presentation, disease course and treatment of aminobisphosphonate-associated orbital/ocular inflammation in a large series of patients. Methods A retrospective study of patients with aminobisphosphonate-associated orbital/ocular inflammation and a literature review to differentiate disease presentation and course between various aminobisphosphonates. Results Eight patients from our institution (6 women and 2 men, median age 62 years) were included. The used drugs were zoledronate, alendronate and risedronate. The most common clinical presentation was conjunctival hyperaemia/chemosis. Scleritis was the most common manifestation, followed by diffuse orbital inflammation and anterior uveitis. Ultrasound aided in diagnosis in all our patients. The aminobisphosphonate was halted in all patients, and some patients had anti-inflammatory treatment. Literature review included 68 patients (83 eyes), of them the most abundant drugs causing orbital/ocular inflammation were pamidronate (38 eyes) and zoledronate (35 eyes). Overall, among 76 patients, all drugs induced orbital disease, while uveitis was induced mostly by zoledronate and pamidronate, less by alendronate and not found among risedronate users. Time interval from drug administration to symptoms was hours to 28 days. Resolution was achieved in all patients, after 1-60 days from disease presentation, and the longer resolution period was found among alendronate users. Conclusion Orbital/ocular inflammation was mostly caused by intravenous aminobisphosphonates. Uveitis was not induced by risedronate. The putative aminobisphosphonate should be halted at the onset of orbital/ocular involvement and prognosis is favourable.

Purpose: To report a unique case of Behçet's disease that presented with atypical ocular manifestations. Methods: Case report. Results: A 23-year-old homosexual male presented with bilateral anterior uveitis, vitritis, neuroretinitis and a unilateral superior hemivein occlusion with frosted branch angiitis pattern. These were accompanied by systemic findings of recurrent oral aphthous ulcers, erythema nodosum, and neurological and gastrointestinal involvement. A positive HLA-B51 examination supported the diagnosis of Behçet's disease. Conclusion: Neuroretinitis and frosted branch angiitis may be the clinical manifestations of Behçet's disease and may present simultaneously.

PURPOSE To report a unique ocular manifestation of immunoglobulin G4-related disease (IgG4-RD) as choroidal effusion. METHODS Case report. RESULTS An 81-year-old man presented with clinical manifestations of choroidal effusion, confirmed by fluorescein angiography, ophthalmic ultrasound (posterior segment), high-frequency ultrasound biomicroscopy, Heidelberg Spectralis spectral domain optical coherence tomography, and enhanced depth imaging spectral domain optical coherence tomography. Systemic multi-organ findings included chronic pancreatitis, irregularity of the intrahepatic bile ducts, lymphadenopathy, aortitis, fibrotic changes of the lungs, hypophysitis, and sialadenitis. Extensive workup revealed elevated IgG4 serum levels, and lymph nodes biopsy showed reactive pattern with polyclonal IgG4 positive plasma cells. These findings were compatible with IgG4-related disease. Treatment with oral corticosteroids resulted in complete resolution of the choroidal effusion. CONCLUSION Choroidal effusion may be an ocular manifestation of IgG4-related disease. Oral corticosteroids is an effective treatment. Ophthalmologists should be aware of this possible finding.

To investigate the characteristics and long-term outcome of patients with noninfectious retinal vasculitis.This was a retrospective multicenter study. Main outcome measures included patients' characteristics, ocular findings, treatment modalities, and best-corrected visual acuity. All patients had at least 12-month follow-up time.Eighty-two eyes (45 patients) were included. Median follow-up was 46 months (range, 12-210 months). At presentation, 12 of the 45 patients (26.6%) had a known associated systemic or ocular disease. A diagnosis of a new systemic disease was found in additional 14 of 33 patients (42.5%) and birdshot chorioretinopathy in 3 of 33 patients (9.1%). The most common systemic disease was Behcet disease (17/24 patients; 70.8%). Laboratory tests had a low diagnostic value. The most common clinical findings were vitritis (58.5%) and perivascular sheathing (50.5%). Most patients were treated with immunosuppressive medications. Mean best-corrected visual acuity improved significantly during follow-up, patients with Behcet disease and worse visual acuity at baseline were more likely to have visual acuity improvement (P0.001).A new systemic or ocular disease associated with retinal vasculitis was found in more than half of the patients. Behcet disease was the most common newly diagnosed disease. Specific diagnosis leading to proper management is important to maintain favorable long-term visual outcome.

Purpose To evaluate retinal toxicity of intravitreal trimethoprim-sulfamethoxazole (TMP-SMX) in an albino rabbit model. Methods Albino rabbits (N = 10) were treated in the right eye with the maximum intravitreal dose of TMP-SMX mixture (1600 μg/8000 μg /0.1 mL), while 0.1 mL saline was injected into the vitreous of the left eye. Clinical examination and electrophysiological (electroretinogram [ERG] and visual evoked potentials [VEPs]) testing were conducted before injection, 3 days, 1, 2, and 4 weeks postinjection. Retinal structure and expression of glial fibrillary acidic protein (GFAP) were assessed from histology and immunocytochemistry respectively at the end of the follow-up period. Results Clinical examination was normal throughout the follow-up period. ERG responses from the experimental eyes were similar to those recorded from the control eyes, but the sum of oscillatory potentials decreased in the experimental eyes at 2 weeks postinjection. The VEP responses, elicited by stimulation of the experimental eyes, were abnormal having reduced amplitude and prolonged implicit time. Histological damage in the experimental eyes was expressed by thickness reduction of whole, outer, and inner nuclear layers. GFAP was expressed in retinal Muller cells of all experimental eyes, but none of control eyes. Conclusions A single intravitreal injection of TMP-SMX mixture (1600 μg/8000 μg, respectively) causes functional and structural damage to the inner retina and retinal output. Signs of retinal stress were also evident by GFAP expression in retinal Muller cells of all experimental eyes. Therefore, the use of TMP-SMX via intravitreal administration should be done with caution. Translational relevance These findings highlight the risk of retinal toxicity after intravitreal injection of trimethoprim-sulfamethoxazole and emphasize that this treatment should be carefully considered.

Delivery of pharmaceuticals to the posterior segment presents challenges that arise from the anatomy and clearance pharmacokinetics of the eye. Systemic and several local administration options [topical, periocular, intravitreal (IVT) and subretinal] are in clinical use, each with a unique benefit to risk profile shaped by factors including the administered agent, frequency of dosing, achievable pharmaceutical concentrations within posterior segment structures versus elsewhere in the eye or the body, invasiveness of the procedure and the inherent challenges with some administration methods. The use of the suprachoroidal space (SCS), which is the region between the sclera and the choroid, is being explored as a potential approach to target pharmacotherapies to the posterior segment via a minimally invasive injection procedure. Preclinical data on agents such as vascular endothelial growth factor inhibitors and triamcinolone acetonide (TA) indicate that administration via suprachoroidal injection results in more posterior distribution of the pharmacologic agent, with higher exposure to the sclera, choroid, retinal pigment epithelium cells and retina, and lesser exposure to the anterior segment, than observed with IVT administration. Based in part on these findings, clinical trials have explored the efficacy and safety of suprachoroidal administration of pharmacologic therapies in conditions affecting the posterior segment. Data on a proprietary formulation of TA administered by suprachoroidal injection show improvement in anatomic and visual outcomes in subjects with noninfectious uveitis, with the potential to mitigate the known risks of cataract and increased intraocular pressure (IOP) associated with the use of intraocular corticosteroids. Suprachoroidal administration appears to be a promising treatment modality and is also in the early stages of investigation for other possible applications, such as injection of antiglaucoma agents into the anterior SCS for long-lasting control of elevated IOP, and as a mode of delivery for gene- or cell-based therapies for retinal disorders.

PURPOSE To characterize cat-scratch disease (CSD) ocular manifestations and visual outcome and evaluate the effect of systemic antibiotics and corticosteroids on final visual acuity (VA). METHODS Multicentre retrospective cohort study. Medical records of 86 patients with ocular disease (107 eyes) of 3222 patients identified in a national CSD surveillance study were reviewed. RESULTS Mean age was 35.1 ± 14.2 years. Median follow-up was 20 weeks (range 1-806 weeks). Of 94/107 (88%) eyes with swollen disc, 60 (64%) had neuroretinitis at presentation, 14 (15%) developed neuroretinitis during follow-up, and 20 (21%) were diagnosed with inflammatory disc oedema. Optic nerve head lesion, uveitis, optic neuropathy and retinal vessel occlusion were found in 43 (40%), 38 (36%), 34 (33%) and 8 (7%) eyes, respectively. Good VA (better than 20/40), moderate vision loss (20/40-20/200) and severe vision loss (worse than 20/200) were found in 26/79 (33%), 35/79 (44%) and 18/79 (23%) eyes at baseline and in 63/79 (80%), 11/79 (14%) and 5/79 (6%) eyes at final follow-up, respectively (p

Several reports suggested a relation between uveitis and thyroid disease or dysfunction. However, no study has investigated the association between uveitis and thyroid dysfunction. The purpose of this study was to compare the prevalence of thyroid dysfunction in patients with and without non-infectious uveitis.This was a retrospective, case-control study.Two hundred thirty-five non-infectious uveitis patients (uveitis group) and 600 controls (control group) were included in the study, of whom 492 (58.9%) were females. No differences were demonstrated between the uveitis and control groups with regard to baseline characteristics, including age, sex, and the presence of systemic diseases such as diabetes, hypertension, and cardiac disease. Rheumatologic and gastrointestinal disease were more common in the uveitis group (p 0.001 and p = 0.007, respectively). Overall, thyroid dysfunction was noted in 61 (7.3%) patients, of whom 55 had hypothyroidism and six had hyperthyroidism. Seventeen out of 235 (7.2%) uveitis patients and 44/600 (7.3%) controls were diagnosed with thyroid dysfunction-a similar proportion in both groups (p = 0.96). Of these, all uveitis patients and 38 (86.4%) patients in the control group had a diagnosis of hypothyroidism (p = 0.63). A higher percentage of women was found among uveitis patients with thyroid dysfunction compared with uveitis patients without thyroid dysfunction (p = 0.002). The most common uveitis type was anterior uveitis. No significant difference was found in uveitis types between patients with or without a diagnosis of thyroid dysfunction.The prevalence of thyroid dysfunction was similar in both groups, and no association was found between non-infectious uveitis and thyroid dysfunction in this study. These findings suggest there is no need for routine thyroid function evaluation in patients with non-infectious uveitis.

Purpose: To report the long-term outcome of an intravitreal dexamethasone drug delivery system (DEX-DDS) injection for noninfectious uveitic macular edema. Methods: This was a retrospective study of 8 eyes (7 patients). Results: The mean follow-up time was 17.3 months. Macular edema resolved in all eyes at 3.9 weeks (range 1-6.9) postinjection. The central point thickness improved from 612 ± 143 to 250 ± 55 µm (p < 0.05). The mean best corrected visual acuity improved by 0.25 logMAR (p < 0.05) at 3.9 weeks (range 1-6.9) postinjection. In 5 eyes, macular edema did not recur after a mean follow-up of 14.5 months. In 3 eyes, macular edema relapsed after 4.7 months (range 3.6-6.3) and resolved again following further injections. Two eyes developed intraocular pressure elevation, which was well controlled with topical treatment. Conclusions: Intravitreal DEX-DDS injections resulted in resolution of macular edema and visual acuity improvement. Some eyes required repeated injections, but most eyes achieved long-term resolution. No significant complications were noticed.

Purpose: To evaluate retinal toxicity of intravitreal rituximab. Methods: Twelve albino rabbits were included in the study. 1 mg/0.1 mL of rituximab was injected to the right (experimental) eye of each rabbit, and 0.1 mL of saline was injected into the left (control) eye. Electroretinogram was recorded before injection and 3 hours, 4 days, 1 week, 2 weeks and 4 weeks after injection (12 rabbits), and visual evoked potential was recorded before injection and 4 weeks after injection (10 rabbits). Histology and glial fibrillary acidic protein immunocytochemistry (12 rabbits) were performed at 4 weeks after injection. Clinical examination was conducted at all time points in all rabbits. Results: The average dark-adapted electroretinogram b-wave Vmax ratios, and the average light-adapted b-wave amplitude ratios were approximately 1, and the average log σ difference was around zero throughout the follow-up period. The average visual evoked potential amplitude ratio and the average visual evoked potential implicit time difference were approximately 1 and 0, respectively. No histologic damage was seen, but glial fibrillary acidic protein was mildly expressed in 6 of 12 experimental eyes. Results of clinical examination were normal in all the eyes. Conclusion: Intravitreal injection of 1 mg rituximab does not cause functional or histologic signs of retinal toxicity in albino rabbits. Mild glial fibrillary acidic protein expression in Muller cells probably indicates a mild degree of retinal stress.

To study the potential toxic effects of intravitreal clindamycin on the retina of albino rabbits, by assessing functional and morphological retinal changes. Eight albino rabbits were included in the study. In each rabbit, 1 mg/0.1 ml clindamycin was injected into the vitreous of the right (experimental) eye, and 0.1 ml saline was injected into the vitreous of the left (control) eye. The electroretinogram (ERG) was recorded before injection, 3 days, 1, 2, and 4 weeks post-injection. The visual evoked potential (VEP) was recorded 4 weeks post-injection. Clinical examination was conducted at all time points. The eyes were enucleated at the termination of the follow-up period in order to prepare the retinas for histology in order to assess retinal structure. ERG and VEP responses that were recorded from the experimental eye at different times following intravitreal clindamycin injection were very similar to the corresponding responses that were recorded from the control eyes. Clinical examination was normal in all eyes, and no histological damage was observed. Intravitreal injection of 1 mg clindamycin does not cause functional or morphological signs of retinal toxicity in albino rabbits, during a period of 4 weeks post-injection. These findings support the clinical use of 1 mg intravitreal clindamycin.