[OCULAR SYPHILIS].

INTRODUCTION: Syphilis is also known as 'the great imitator' for its ability to mimic many diseases due to its extensive range of clinical manifestations. This review aims to provide an update on the clinical presentation, diagnosis and treatment of ocular syphilis. It manifests in a spectrum of ways that can occur at any stage of the disease, and may be the only presenting feature of systemic syphilis, with the most common finding being panuveitis. The diagnosis is usually aided by serology testing: nonspecific treponemal antibodies (for screening and follow-up) and specific treponemal antibodies for confirmation of the diagnosis. The treatment for ocular syphilis is similar to neurosyphilis and includes intravenous aqueous crystalline penicillin.

Outcome and risk of ocular complications of managing children with chronic anterior uveitis with topical rimexolone 1.

PURPOSE: To investigate the efficacy and safety of 1% rimexolone ophthalmic suspension in children with chronic anterior uveitis under real-life conditions in a tertiary center. METHODS: This is a retrospective longitudinal study. Medical records were analyzed at baseline, 1, 3, 6 and 12 months before and after switching to rimexolone for best-corrected visual acuity (BCVA), oral steroid use, number of flares, IOP and anti-glaucoma management. RESULTS: Twenty-four patients (41 eyes) diagnosed with either anterior uveitis (n = 25, 60.0%) or panuveitis (n = 16, 40%) were enrolled. The mean age was 10.5 years (4-16 years). The number of patients requiring oral prednisolone reduced from 8 patients (32.0%) at baseline to 3 patients (20.0%) at 12 months (P < 0.001). Following baseline, the median number of uveitis flares reduced from 2.0 (inter-quartile range (IQR) 1.0-2.75) to 1.0 (IQR 0.0-1.0) compared to the 12 months before baseline (P < 0.001). The mean IOP reduced from baseline (22.0 ± 7.3 mmHg) to 1 month (18.8 ± 8.7 mmHg, P = 0.01) and remained stable up to 12 months (15.9 ± 5.0 mmHg, P < 0.001). Average BCVA, dose of oral prednisolone and anti-glaucoma treatments did not change compared to the baseline. The development for IOP ≥ 30 mmHg was associated with a known corticosteroid response [odds ratio (OR) 6.8, P = 0.003] and a dose > 7.5 mg/day oral prednisolone (OR 4.4, P = 0.033). CONCLUSIONS: Rimexolone 1% ophthalmic suspension is an effective and safe topical steroid for pediatric anterior uveitis.

Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative.

BACKGROUND: In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is possibly its most devastating extra-articular manifestation. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment practices differ widely, within and between nations. OBJECTIVES: To provide recommendations for the diagnosis and treatment of JIA-associated uveitis. METHODS: Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of nine experienced paediatric rheumatologists and three experts in ophthalmology from Europe. Recommendations derived from a validated systematic literature review were evaluated by an Expert Committee and subsequently discussed at two consensus meetings using nominal group techniques. Recommendations were accepted if >80% agreement was reached (including all three ophthalmologists). RESULTS: In total, 22 recommendations were accepted (with >80% agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12 on treatment and 2 on future recommendations. CONCLUSIONS: The SHARE initiative aims to identify best practices for treatment of patients suffering from JIA-associated uveitis. Within this remit, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated by an evidence-informed consensus process to suggest a standard of care for JIA-associated uveitis patients throughout Europe.

A simple computer program to quantify red desaturation in patients with optic neuritis.

PURPOSE: Red desaturation is a subjective, sensitive test for patients with optic nerve disease. There is no quantitative clinical test to measure the severity of color desaturation. The current study introduces a simple PowerPoint presentation for quantification of red desaturation in patients with optic neuritis. METHODS: A Microsoft Office PowerPoint presentation was designed. A red square is shown on each half of the screen. The degree of desaturation on one side is increased in each successive slide. The patient holds a black cardboard divider between his/her eyes, such that each eye can see one-half of the screen. The patient uses the mouse to forward through the slides, thereby gradually increasing the desaturation of the red square presented to the normal eye until it matches the color of the red square seen with the tested eye. Desaturation is graded by the number of slide changes needed until subjective equal color between the eyes is perceived. The test was presented to normal volunteers and to patients with optic neuritis. The difference in saturation levels between the right and the left eyes in patients with optic neuritis vs controls was compared. RESULTS: A total of 83 patients were included. Patients with optic neuritis had significantly increased desaturation compared to controls (6.17 ± 3.3 vs 0.24 ± 2.8 respectively; p < 0.0001). CONCLUSIONS: This test is easy to create and efficiently quantifies the severity of red desaturation.

Uveitic Flare-Ups After Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) in Patients with Uveitic Glaucoma.

PURPOSE: To assess the risk of gonioscopy-assisted transluminal trabeculotomy (GATT) inducing an uveitic flare-up in patients with uveitic glaucoma (UG). METHODS: This retrospective study included consecutive UG patients who underwent GATT at a single medical center between June 2020 and September 2022. The main outcome measure was the occurrence of a surgery-related uveitic complication defined as either an uveitic flare-up defined by the Standardization of Uveitis Nomenclature (SUN) criteria, or the appearance of cystoid macular edema (CME) from 2 weeks to 3 months after surgery. RESULTS: A total of 25 eyes of 22 patients were included in the study. Age ranged from 10-78 and 64% were women. The most common uveitic etiologies were juvenile idiopathic arthritis (JIA, 24%) and herpetic infection (24%). A total of 48%of the patients were on systemic immunosuppressants prior and unrelated to surgery. Eight eyes (32%) had severe glaucomatous damage prior to surgery, and 20% of the patients had undergone previous glaucoma surgery. Two cases (8%) demonstrated uveitic flare-up in the early postoperative period: a case of mild anterior chamber reaction and a case of CME with persistent edema prior to surgery. Average intraocular pressure (IOP) was reduced from 26.7 mm Hg on four medications to 12.2 on 1.1 after 1 year. One patient required reoperation for IOP control. CONCLUSIONS: With careful pre and postoperative care, GATT seems to be a low-risk procedure for uveitic flare-ups in patients with UG.

Ocular Behçet Disease-Clinical Manifestations, Treatments and Outcomes According to Age at Disease Onset.

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments and outcomes between three age groups: juvenile (<18 years), adult (18-39 years) and late (≥40 years) disease onset. The study included 175 ocular BD patients (303 eyes) from Israel and Palestine: juvenile-onset (n = 25, 14.3%), adult-onset (n = 120, 68.6%) and late-onset (n = 30, 17.1%). Most patients in all groups were male. Systemic manifestations were similar in all groups. Systemic co-morbidities were more common in late-onset patients. Bilateral panuveitis was the most common ocular manifestation in all patients. Non-occlusive retinal vasculitis, peripheral vessel occlusions, cataract and elevated intraocular pressure were found more commonly among juvenile-onset eyes. Anterior uveitis and macular ischemia were most common among late-onset eyes, while branch retinal vein occlusion was most common in adult and late-onset eyes. All patients were treated with corticosteroids. Methotrexate, immunomodulatory combinations and biologic treatments were more commonly used for juvenile-onset patients. All groups had a similar visual outcome. Our study showed that patients with ocular BD have varied ocular manifestations and require different treatments according to age of disease onset, but visual outcome is similar.

Retinal vascular occlusions in ocular Behçet disease - a comparative analysis.

PURPOSE: The literature on retinal vascular occlusions in Behçet disease (BD) patients is limited. The aim of this study is to thoroughly investigate retinal vascular occlusions among ocular BD patients. METHODS: Retrospective, multicentre case-control study. Three-hundred and three eyes of 175 patients with ocular BD, from 13 hospitals in Israel and Palestine, were included. Patients were assigned into two groups according to the presence of retinal vascular occlusion. Epidemiology, systemic and ocular manifestations, treatments and outcomes were compared between the groups and risk factors for retinal vascular occlusions were identified. RESULTS: One hundred twenty-five patients (71.4%) were male. The mean age at presentation was 28.2 ± 0.86 years. Retinal vascular occlusions were found in 80 eyes of 54 (30.9%) patients, including branch retinal vein occlusion (51.3%), peripheral vessels occlusions (32.5%), central retinal vein occlusion (13.8%) and arterial occlusions (7.5%). Systemic manifestations were similar among both groups. Anterior uveitis was more common in non-occlusive eyes (p < 0.01). Non-occlusive retinal vasculitis (p = 0.03) and ocular complications were more common in occlusive eyes (p < 0.01). Treatments including mycophenolate mofetil, Infliximab or a combination therapy of anti-metabolite and calcineurin inhibitor were more commonly used by occlusive patients (p < 0.05). Occlusive patients underwent more cataract surgeries (p = 0.03). The occlusive group had worse mean best-corrected visual acuity (BCVA) throughout follow-up (p < 0.01). Risk factors for retinal vascular occlusions included male sex and Jewish ethnicity (p < 0.05). CONCLUSION: Retinal vascular occlusions were found in a third of ocular BD patients. Occlusive eyes had a worse prognosis. Risk factors for vascular occlusions were identified.

Association of retinal microvascular caliber with blood pressure levels.

BACKGROUND: The most common ophthalmologic manifestation of hypertension is hypertensive retinopathy. Our study was designed to evaluate the factors that determine retinal vessel caliber in hypertensive subjects. METHODS: During a 6-month period, retinal photographs were taken of participants during a routine yearly check-up. The photographs were evaluated by an ophthalmologist and the diameters of the individual retinal vessels were measured and summarized by a computer program. Data including patient's medical history, physical examination and laboratory evaluations were collected. The findings of the ophthalmologic examinations were analyzed with respect to the relevant systemic data. RESULTS: We evaluated 285 subjects (43 women) with an average age of 62 ± 9 years (range 33-87). Hypertension was reported in 204 (71.6%) subjects and diabetes mellitus in 60 subjects (21%). The arteriolar calibers were inversely related to age (R = - 017; p = 0.01). Retinal arteriolar and venular calibers were wider in smokers and in subjects with dyslipidemia. History of hypertension was not associated with any vascular changes. However, retinal arteriolar caliber was inversely related to blood pressure levels. Diuretic treatment was associated with narrow retinal venular caliber. CONCLUSION: The association between different cardiovascular risk factors and hypertensive retinopathy is complex. Effective blood pressure control has a beneficial effect on the vascular changes in the retina.

Steroid treatment suppresses the CD4+ T-cell response to the third dose of mRNA COVID-19 vaccine in systemic autoimmune rheumatic disease patients.

Prolonged steroid treatment has a suppressive effect on the immune system, however, its effect on the cellular response to mRNA vaccine is unknown. Here we assessed the impact of prolonged steroid treatment on the T-cell and humoral response to the SARS-CoV-2 spike (S) peptide following the third dose of the BNT162b2 vaccine in systemic autoimmune rheumatic disease patients. We found that CD4 T-cell response to the S peptide in patients on high-dose long-term steroid treatment showed significantly less S-peptide specific response, compare to low-dose or untreated patients. Remarkably, these results were not reflected in their humoral response, since almost all patients in the cohort had sufficient antibody levels. Moreover, S-peptide activation failed to induce significant mRNA levels of IFNγ and TNFα in patients receiving high-dose steroids. RNA-sequencing datasets analysis implies that steroid treatments' inhibitory effect of nuclear factor kappa-B signaling may interfere with the activation of S-specific CD4 T-cells. This reveals that high-dose steroid treatment inhibits T-cell response to the mRNA vaccine, despite having sufficient antibody levels. Since T-cell immunity is a crucial factor in the immune response to viruses, our findings highlight the need for enhancing the efficiency of vaccines in immune-suppressive patients, by modulation of the T-cell response.

Immunogenicity and safety of the mRNA-based BNT162b2 vaccine in systemic autoimmune rheumatic diseases patients.

BACKGROUND: The COVID-19 outbreak has led to the rapid development and administration of the COVID-19 vaccines worldwide. Data about the immunogenicity and adverse effects of the vaccine on patients with systemic autoimmune rheumatic diseases (SARDs) is emerging. AIM: To evaluate Pfizer/BioNTech (BNT162b2) mRNA-based vaccine second-dose immunogenicity and safety, and the relation between them, in patients with SARDs. METHODS: A total of one hundred forty tow adults who received two doses of the BNT162b2 vaccine were included in the study. The SARDs group included Ninety-nine patients and the control group (forty-three participants) comprised a mixture of healthy participants and patients who were seen at the rheumatology clinic for non-SARDs. Anti-SARS-CoV-2 IgG antibodies against the Spike protein were evaluated using a SARS-CoV-2 IgG immunoassay. A level of > 150 AU/mL was considered positive. An adverse effects questionnaire was given to the participants upon their first visit to the clinic after their BNT162b2 vaccination. RESULTS: Of the 142 participants, 116 were seropositive (81.7%) and 26 (18.3%) were seronegative. Of the seronegative participants, 96.2% were SARDs patients. The proportion of seropositivity in the SARDs patients treated with any immunosuppressant was significantly lower (69.9%) compared to the control group and SARDs patients not receiving immunosuppressants (96.8%). A significant negative correlation between seronegativity and treatment with rituximab, mycophenolate mofetil (MMF), and prednisone was found in the SARDs group (p = 0.004, 0.044, 0.007 respectively). No fever was observed following the BNT162b2 vaccine in seronegative patients, and the frequency of musculoskeletal adverse effects upon the second dose of the BNT162b2 vaccine was significantly higher in seropositive compared to seronegative patients and in the control group compared to the SARDs patients (p = 0.045, p = 0.02 respectively). CONCLUSION: A decline in the immunogenicity to the second dose of BNT162b2 mRNA is seen in patients with SARDs, especially in patients treated with rituximab, MMF, and prednisone. Adverse effects of the vaccine including fever and musculoskeletal symptoms might be a signal for the acquisition of immunity in those patients. KEY POINTS: • BNT162b2 mRNA vaccine is less immunogenic in SARDs patients compared to the control group. • Rituximab, prednisone, and mycophenolate mofetil significantly reduced immunogenicity to the vaccine. • There is a correlation between immunogenicity and adverse effects of the vaccine.

Acute posterior multifocal placoid pigment epitheliopathy associated with CN III palsy.

PURPOSE: To report a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) associated with cranial nerve (CN) III palsy. OBSERVATIONS: A 20-year-old woman developed bilateral anterior uveitis, which resolved with topical steroids. Three weeks later she exhibited posterior pole lesions in both eyes, corresponding with a diagnosis of APMPPE, as confirmed by multimodal imaging. Two days later the patient presented with right CN III palsy. The patient was started on oral prednisone, which was gradually tapered off. Signs and symptoms improved rapidly, with complete resolution within two months. CONCLUSION AND IMPORTANCE: Though rare, APMPPE may present with neurological involvement, as in this previously unreported association with CN III palsy. Unlike uncomplicated APMPPE cases, in patients with neurological manifestations systemic therapy is advocated.

Diagnostic value of imaging in horner syndrome in adults.

BACKGROUND: The yield of imaging in Horner syndrome has been explored only in children. This study evaluates the yield of imaging in adults. METHODS: This was a retrospective cohort study of 52 patients with Horner syndrome examined in 2 neuro-ophthalmology hospital clinics. Patients were divided into 3 groups according to the ability to determine the etiology at the time of the first neuro-ophthalmology consultation: group I, etiology of Horner syndrome known at the initial neuro-ophthalmologic examination; group II, etiology of Horner syndrome not known at the initial neuro-ophthalmologic examination, but sufficient information obtained to allow targeted imaging; and group III, etiology of Horner syndrome not known at the initial neuro-ophthalmologic examination, and sufficient information not obtained to allow targeted imaging. The yield of investigation and the frequency of the different etiologies were evaluated. RESULTS: In 32 (62%) patients, the etiology was already known at the initial neuro-ophthalmologic examination (group I). The most prevalent etiology was surgical trauma. In 11 (21%) patients, a targeted imaging workup was possible, revealing an etiology in 7 patients (group II). Carotid dissection and cavernous sinus mass were the most common etiologies. In 9 (17%) patients, a nontargeted imaging evaluation was necessary, revealing an etiology in only 1 patient, who had a previously undetected thyroid malignancy (group III). CONCLUSIONS: The etiology of Horner syndrome is usually known at the time of initial presentation to a neuro-ophthalmologist. When the etiology is not known and clinical information permits a targeted imaging evaluation, an etiology can usually be determined, most commonly a cervical carotid artery dissection or a cavernous sinus mass. When the etiology is not known and clinical information is insufficient to allow a targeted imaging evaluation, an etiology is rarely discovered. Even so, nontargeted imaging is warranted because life-threatening lesions, such as thyroid malignancies, may rarely be detected.

Bilateral simultaneous central retinal vein occlusion in hyperviscosity retinopathy treated with systemic immunosuppressive therapy only.

PURPOSE: To describe the clinical presentation and imaging features of a patient presenting with bilateral central retinal vein occlusion (CRVO), who was subsequently diagnosed with hyperviscosity retinopathy due to B cell lymphoproliferative disease, and had a good response to systemic immunosuppressive therapy. OBSERVATIONS: A clinical case report of an 87-year-old woman who presented with bilateral CRVO. Visual acuity, clinical examination, spectral domain optical coherence tomography (SD-OCT), color fundus photography and systemic evaluation were obtained. Ocular examination at presentation revealed bilateral CRVO, and OCT examination revealed significant central macular edema bilaterally. Six months after the diagnosis of hyperviscosity retinopathy and administration of systemic cyclophosphamide immunosuppressive therapy for B cell lymphoproliferative disease, most of the retinal hemorrhages resolved and partial resolution of the macular edema in the left eye was observed. CONCLUSION AND IMPORTANCE: This case describes the association between bilateral simultaneous CRVO and hyperviscosity. Under unique circumstances our patient received systemic therapy alone, without plasmapheresis. Although only limited therapy was applied, she didn't have deterioration or recurrent events; she had a small improvement in her macular edema and a significant improvement in her systemic functional state as well as reduction in her monoclonal IGM level.

Intravitreal Administration of Antiviral Agents in Silicone Oil-Filled Human Eyes.

PURPOSE: To report our experience with intra-silicone oil (SO) injection of antiviral agents for treatment of viral retinitis and to review the relevant literature. DESIGN: Two case reports and a literature review. PARTICIPANTS: Two patients with viral retinitis and SO tamponade. METHODS: Two patients with viral retinitis were treated with intravitreal injections of low-dose ganciclovir (2 mg/0.05 ml), foscarnet (1.2 mg/0.05 ml), or both after retinal detachment repair with SO tamponade, in addition to systemic antiviral therapy from 2014 through 2015. The literature on the use of intraocular antiviral agents in the setting of SO vitreous substitute was reviewed. MAIN OUTCOME MEASURES: Clinical outcomes after administration of intra-SO antiviral therapy. RESULTS: A patient with progressive outer retinal necrosis received 5 intra-SO injections of low-dose ganciclovir and foscarnet after surgery over 6 weeks. Another patient with acute retinal necrosis received weekly low-dose foscarnet injections into his SO-filled eye for 8 weeks after surgery. Significant retinitis regression with long-term retinitis control was achieved in both patients throughout follow-up. No articles reporting the administration of soluble antiviral agents into an SO-filled human eye were identified. CONCLUSIONS: Our preliminary findings indicate that administration of low-dose ganciclovir and foscarnet into an SO-filled eye may be used as adjunctive treatment for viral retinitis. Further studies are needed to confirm these results.