ACUTE SYPHILITIC POSTERIOR PLACOID CHORIORETINITIS: MULTIMODAL IMAGING AND ELECTROPHYSIOLOGIC FINDINGS BEFORE AND AFTER TREATMENT.

PURPOSE: To describe the clinical course of acute syphilitic posterior placoid chorioretinitis (ASPPC) in the preplacoid stage, placoid stage, and after treatment with penicillin. METHOD: A retrospective case report of serial multimodal imaging and electrophysiology studies of a patient with ASPPC, with 18 months of follow-up. RESULTS: A 47-year-old man presented with bilateral panuveitis. The patient defaulted follow-up and returned when his vision deteriorated. Tests for neurosyphilis and retroviral disease were positive, and treatment was initiated. The earliest change on serial optical coherence tomography was loss of the signal from the reflective band corresponding to the ellipsoid zone. In the placoid stage, there was nodular thickening of the retinal pigment epithelium. The ellipsoid zone signals reappeared after treatment. Fundus fluorescein angiogram at presentation showed peripapillary vasculitis and disk leakage; indocyanine green angiography revealed multiple hypofluorescent spots in the peripapillary region and posterior pole that was not visible clinically. The angiographic abnormalities resolved after treatment. Electrophysiology demonstrated bilateral maculopathy and reduction of both a- and b-waves from dark-adapted and light-adapted responses at presentation. The b-waves (inner retina) recovered partially with treatment. CONCLUSION: To the best of our knowledge, this is the first case report of the multimodal imaging and electrophysiology findings in a patient with acute syphilitic posterior placoid chorioretinitis, before the development of the classic placoid lesion. Improvement of structural and functional pathology after systemic treatment is demonstrated.

Pathogenesis of ocular toxoplasmosis.

Ocular toxoplasmosis is a retinitis -almost always accompanied by vitritis and choroiditis- caused by intraocular infection with Toxoplasma gondii. Depending on retinal location, this condition may cause substantial vision impairment. T. gondii is an obligate intracellular protozoan parasite, with both sexual and asexual life cycles, and infection is typically contracted orally by consuming encysted bradyzoites in undercooked meat, or oocysts on unwashed garden produce or in contaminated water. Presently available anti-parasitic drugs cannot eliminate T. gondii from the body. In vitro studies using T. gondii tachyzoites, and human retinal cells and tissue have provided important insights into the pathogenesis of ocular toxoplasmosis. T. gondii may cross the vascular endothelium to access human retina by at least three routes: in leukocyte taxis; as a transmigrating tachyzoite; and after infecting endothelial cells. The parasite is capable of navigating the human neuroretina, gaining access to a range of cell populations. Retinal Müller glial cells are preferred initial host cells. T. gondii infection of the retinal pigment epithelial cells alters the secretion of growth factors and induces proliferation of adjacent uninfected epithelial cells. This increases susceptibility of the cells to parasite infection, and may be the basis of the characteristic hyperpigmented toxoplasmic retinal lesion. Infected epithelial cells also generate a vigorous immunologic response, and influence the activity of leukocytes that infiltrate the retina. A range of T. gondii genotypes are associated with human ocular toxoplasmosis, and individual immunogenetics -including polymorphisms in genes encoding innate immune receptors, human leukocyte antigens and cytokines- impacts the clinical manifestations. Research into basic pathogenic mechanisms of ocular toxoplasmosis highlights the importance of prevention and suggests new biological drug targets for established disease.

Chorio-retinal toxoplasmosis: treatment outcomes, lesion evolution and long-term follow-up in a single tertiary center.

BACKGROUND: Ocular toxoplasmosis is a common cause of ocular inflammation worldwide. The aim of this study is to characterize the clinical outcomes and lesion evolution of patients with ocular toxoplasmosis and to compare the primary and reactivation subgroups. METHODS: A retrospective population-based cohort study at one uveitis-specialized tertiary referral center. Patients presenting with active ocular toxoplasmosis between the years 2007-2016 were included. Primary ocular toxoplasmosis and reactivations were compared. RESULTS: Included were 22 patients, 64% female with a mean age of 29 ± 18 years, 59% (n = 13) were primary, 9% (n = 2) congenital and 32% (n = 7) reactivations. Visual acuity improved from 0.38 ± 0.44 to 0.20 ± 0.27 LogMAR (P = 0.026) after a mean of 37 ± 33 months. Initial lesion size was 2.38 ± 1.1 optic disc areas, reducing to 1.56 ± 1.24 following 2 months (34% reduction, P = 0.028) and to 1.17 ± 0.87 disc areas following one year (51% reduction, P = 0.012). Patients with macula-threatening lesions had worse visual acuity (0.50 ± 0.46 vs. 0.05 ± 0.07 LogMAR, P = 0.047). Primary and reactivation subgroups had similar presentations, visual outcomes and recurrence rates (all P > 0.05). CONCLUSIONS: In this population, primary ocular toxoplasmosis was the most common presentation. Lesion size reduced during the initial months with limited change thereafter and a third of cases recurred. Macula-threatening lesions were associated with worse visual acuity, and no significant differences were seen between the primary and reactivation subgroups.

Case report: a case of diffuse unilateral subacute neuroretinitis (DUSN) in a child.

BACKGROUND: Diffuse unilateral subacute neuroretinitis (DUSN) is a rare cause of posterior uveitis in the United Kingdom. It typically presents unilaterally in children and young adults but rarely bilateral cases have been reported. It is also rare to have multiple worms in the same eye causing the clinical picture. In this article, we present a challenging case of DUSN in a young girl unresponsive to conventional treatments suggesting the possibility of multiple worms being present in the same eye. CASE PRESENTATION: An 8-year-old girl presented with a 2-month history of headaches. On occasions the headaches were associated with redness and watering of her left eye. She denied any visual loss or visual symptoms. Her visual acuity was reduced to 6/30 in her left eye. Fundal examination revealed a unilateral chorioretinitis. Investigation did not reveal a specific cause for the chorioretinitis. Over 15 months her visual acuity improved to 6/9 but the fundal appearance changed and a diagnosis of DUSN was made. She was treated with focal laser, systemic anti-helminthic and immunosuppressive treatments but continued to develop new, active areas of chorioretinitis, raising the possibility of multiple worms in the sub-retinal space. There is also a concern as to other central nervous system (CNS) involvement given her significant and ongoing headaches. CONCLUSION: We present a challenging case of DUSN in a young girl; a condition that remains rare in the UK. She was unresponsive to both focal laser and systemic anti-helminthic and immunosuppressive treatments suggesting the possibility of multiple worms being present in the sub-retinal space. This case highlights the difficulties often encountered in the treatment of DUSN, even when a worm can be identified. Her visual prognosis is poor as there was ongoing recurrence of active chorioretinitis.

Coriorretinitis sifilítica: evolución final sin tratamiento / Syphilitic chorioretinitis: Final outcome without treatment

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Need for Quantitative Measurement Methods for Posterior Uveitis: Comparison of Dual FA/ICGA Angiography, EDI-OCT Choroidal Thickness and SUN Vitreous Haze Evaluation in Stromal Choroiditis.

BACKGROUND/PURPOSE: Quantitative methods for posterior uveitis are necessary for precise appraisal and follow-up of inflammation in practice and in clinical trials. The aim of this study was to assess fluorescein angiography (FA), indocanine green angiography (ICGA), and enhanced depth imaging optical coherence tomography choroidal thickness (EDI-OCT CT) in two stromal choroiditis entities, birdshot retinochoroiditis (BRC), and Vogt-Koyanagi-Harada disease (VKH), as well as to determine (1) disease patterns, (2) respective response to therapy, and (3) their potential utility in clinical trials in comparison to vitreous haze, the present standard outcome used in clinical trials. METHODS: This retrospective study included newly diagnosed patients with BRC and VKH, seen at the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland. Angiographic signs were quantified using an established dual FA/ICGA scoring system for uveitis at presentation and on follow-up. FA/ICGA score ratios were compared between diseases to determine disease patterns. EDI-OCT CT was determined using a spectral domain instrument. Vitreous haze was determined using the SUN (Standardization of Uveitis Nomenclature) method. RESULTS: Among 1872 uveitis patients seen from 1995 to 2016, 8 newly diagnosed BRC patients (16 eyes) and 6 newly diagnosed VKH patients (12 eyes) had sufficient data for study inclusion. Patients with BRC and VKH at initial onset had mean FA scores of 16.1 ± 7.0 vs. 4.6 ± 2.1 (p < 0.0001), respectively, while mean ICGA scores were similarly high in the two diseases, 18.9 ± 3.6 (BRC) vs. 20.8 ± 7.5 (VKH). After therapy, FA and ICGA scores decreased significantly for both entities (- 60% of FA score and 55% of ICGA score in BRC vs. - 72% of FA score and - 87% for ICGA score in VKH). EDI-OCT CT decreased significantly in the two entities. Vitreous haze was almost absent in VKH and low in BRC. CONCLUSION: Dual FA/ICGA scoring showed the diverse disease patterns of BRC and VKH; both the retina and choroid were involved at onset in BRC, whereas VKH was a pure choroidal disease with later spillover into the retina. Dual FA/ICGA allowed for the precise measurement of inflammation at onset and upon follow-up. EDI-OCT CT responded to therapy in both diseases but was found to be of limited use in this early/subacute disease phase because it lacked sensitivity to detect subclinical recurrences and was therefore only useful for long-term follow-up. Vitreous haze was low in both entities and thus useless as an inflammatory parameter.

Fungaemia caused by obstructive renal candida bezoars leads to bilateral chorioretinitis: a case report.

BACKGROUND: Renal fungal bezoars are remarkably rare and mostly occur in immunodeficient patients. Only a small number of cases with immunocompetent patients have been published so far. The published treatment approaches comprised systemic antimycotic therapy and surgical or minimal invasive removal of the fungal balls. In some cases irrigation of the renal duct system with amphotericin B was performed. By obstruction of the urinary tract bezoars can lead to infected hydronephrosis and severe urosepsis with high lethality. Fungaemia can cause fungal colonization in different distant organs. Fulminant chorioretinitis and irreversible visual impairment can be the consequence of ocular fundus colonization. The following report highlights that a co-operation between urologists and ophthalmologists is absolutely indispensible in case of fungaemia. CASE PRESENTATION: Hereinafter we describe a case of an immunocompetent 56 years old woman, presenting with flank pain and shivering. The diagnosis turned out to be difficult due to initially negative urine culture. The fungaemia caused by obstructive nephropathy led to bilateral candida chorioretinitis. The patient was treated with intravenous amphotericin b and the bezoar was removed by percutaneous "nephrolitholapaxy". After two months, a follow up revealed the patient felt well, chorioretinal lesions regressed and urine culture did not show any fungal growth. CONCLUSION: To the best of our knowledge, this is the first case reporting on obstructive renal bezoars, which lead to haematogenous fungus spread and bilateral chorioretinitis. It points out that extensive ophthalmologic examination should be performed in case of fungaemia even if the patient is not suffering from any visual impairment.

Congenital central toxoplasmic chorioretinitis - case study.

Congenital toxoplasmosis is a globally spread infectious disease caused by transplacental transmission of an intracellular parasitic protozoan Toxoplasma gondii. The infection can cause serious multi-organ complications, and in the case of vertical transmission, can lead up to fetal death - depending on the stage of pregnancy at the time of infection and the overall condition of the mothers immune system. Chorioretinitis, hydrocephalus and intracranial calcifications are a typical triad of symptoms associated with the disease. Toxoplasmic chorioretinitis in particular is the most common ocular manifestation. If the central retina is affected, it can cause a severe impairment of central visual acuity or lead up to blindness in the child. Prenatal screening of this disease is presently voluntary in the Czech Republic. This article reports on a case study of a toxoplasmic chorioretinitis in a newborn child observed from the active stage and the development of the affected retina over time. Further is also reported on the diagnostics and the treatment of multi-organ complications which occurred in this patient. Ophthalmologic examination was performed after diagnosis of hydrocephalus, which revealed severe changes of retina. Hydrocephalus was then properly treated. An overview of the diagnostic and therapeutic methods and the screening options available in the Czech Republic compare with other countries is also presented in the report. Key words: congenital toxoplasmosis, chorioretinitis, multi-organ complications, screening, hydrocephalus.

Safety and Efficacy of AAV5 Vectors Expressing Human or Canine CNGB3 in CNGB3-Mutant Dogs.

Achromatopsia is an inherited retinal disorder of cone photoreceptors characterized by markedly reduced visual acuity, extreme light sensitivity, and absence of color discrimination. Approximately 50% of cases are caused by mutations in the cone photoreceptor-specific cyclic nucleotide gated channel beta subunit (CNGB3) gene. Studies in CNGB3-mutant dogs showed that subretinal injection of an AAV vector expressing human CNGB3, which has 76% amino acid identity with canine CNGB3, driven by a 2.1 kb human red cone opsin promoter (PR2.1) and packaged in AAV5 capsids (AAV5-PR2.1-hCNGB3) rescued cone photoreceptor function, but at high doses was associated with an inflammatory response (focal chorioretinitis) consistent with immune-mediated toxicity. AAV vectors containing the PR2.1 promoter packaged in AAV5 capsids and expressing either the native canine CNGB3 (AAV5-PR2.1-cCNGB3) or the human CNGB3 (AAV5-PR2.1-hCNGB3) were evaluated at different dose levels in CNGB3-mutant dogs. The vector expressing canine CNGB3 achieved somewhat better rescue of cone function but unexpectedly was associated with a greater degree of retinal toxicity than the vector expressing human CNGB3. Very low-level T-cell immune responses to some AAV or CNGB3 peptides were observed in animals that received the higher vector dose. There was a more than twofold increase in serum neutralizing antibodies to AAV in one of three animals in the low-dose group and in two of three animals in the high-dose group. No serum anti-hCNGB3 antibodies were detected in any animal. The results of this study do not support the hypothesis that the focal chorioretinitis seen with high doses of AAV5-PR2.1-hCNGB3 in the initial studies was due to an immune response to human CNGB3.

Birdshot chorioretinopathy: current knowledge and new concepts in pathophysiology, diagnosis, monitoring and treatment.

Birdshot chorioretinopathy (BCR) is a rare form of chronic, bilateral, posterior uveitis with a distinctive clinical phenotype, and a strong association with HLA-A29. It predominantly affects people in middle age. Given its rarity, patients often encounter delays in diagnosis leading to delays in adequate treatment, and thus risking significant visual loss. Recent advances have helped increase our understanding of the underlying autoimmune mechanisms involved in disease pathogenesis, and new diagnostic approaches such as multimodality imaging have improved our ability to both diagnose and monitor disease activity. Whilst traditional immunosuppressants may be effective in BCR, increased understanding of immune pathways is enabling development of newer treatment modalities, offering the potential for targeted modulation of immune mediators. In this review, we will discuss current understanding of BCR and explore recent developments in diagnosis, monitoring and treatment of this disease. Synonyms for BCR: Birdshot chorioretinopathy, Birdshot retinochoroiditis, Birdshot retino-choroidopathy, Vitiliginous choroiditis. Orphanet number: ORPHA179 OMIM: 605808.

Coriorretinitis placoide sifilítica. Caso clínico / Syphilitic placoid chorioretinitis. A case-report

CASO CLÍNICO: Presentamos el caso de una mujer de 45 años sin antecedentes de interés y con una pérdida súbita de visión en su ojo izquierdo secundaria a una uveítis posterior bilateral. Tras despistaje, se diagnosticó de coriorretinitis placoide posterior aguda sifilítica, y recibió tratamiento con penicilina intravenosa. Discusión: Existen múltiples manifestaciones oculares de la sífilis que pueden simular cuadros y etiologías muy diversas. El tratamiento anti-treponémico normalmente produce una rápida y positiva respuesta en pacientes afectos. El diagnóstico precoz y certero de estos pacientes es por tanto crucial aunque, en ocasiones, los daños anatómicos y funcionales son irreversibles

CLINICAL CASE: We report the case of a 45-year-old woman, with unremarkable past medical history, who presented with acute visual loss in her left eye due to bilateral posterior uveitis. After the screening, she was diagnosed with acute syphilitic placoid chorioretinitis and was treated with intravenous penicillin. DISCUSSION: Clinical manifestations of ocular syphilis are extremely heterogeneous and may mimic several aetiologies. Anti-treponema treatment usually induces a quick and positive response in affected patients. Prompt and proper diagnosis of these patients is crucial, although anatomical and functional damage may persist

Coriorretinite esclopetária / Chorioretinitis sclopetaria

O objetivo deste trabalho é relatar um caso de trauma ocular por projétil de arma de fogo, que atingiu e se alojou na cavidade orbitária, desenvolvendo coriorretinite esclopetária. Foram abordados o mecanismo fisiopatológico, os principais achados clínicos e de exames complementares, além das opções de tratamento. As características do caso relatado reforçam a importância de uma abordagem multidisciplinar no trauma ocular.

The objective of this study is to report a case of ocular trauma by gunshot bullet, which struck and lodged in the orbit, developing chorioretinitis sclopetaria. We also addressed the pathophysiological mechanism, the main clinical findings and laboratory tests, and treatment options. The characteristic of this case enhances the importance of a multidisciplinary approach in the ocular trauma.

Endogenous Histoplasma capsulatum endophthalmitis in an immunocompetent patient.

PURPOSE: To report on a case of Histoplasma capsulatum endogenous endophthalmitis in an immunocompetent patient. METHODS: A 30-year-old patient was admitted with floaters and vision impairment of 1 month's duration. He had a history of adrenal insufficiency, together with nasal, septum, and soft palate lesions of 3 months; duration. Culture results from specimens of these lesions were positive for H capsulatum. He was human immunodeficiency virus negative and there was no evidence of immunodepression or history of immunosuppression. Fundus examination revealed multiple fluffy balls with a string of pearls appearance, 2+ vitreous haze, multiple foci of retinochoroiditis inferiorly in the peripheral retina, and a 6-disk area lesion of retinochoroiditis at the superotemporal periphery. Due to poor response to oral itraconazole, a vitrectomy was performed with an intraocular injection of amphotericin B 5 µg/0.1 mL and removal for a vitreous specimen for culture of bacteria and fungi. RESULTS: Vitreous specimen culture of the yeast at 28°C grew a white filamentous fungus colony, which was again cultured in a brain heart infusion agar medium, where it developed hyaline septate hyphae with microconidia and circular macroconidia with double wall, which was stained with a lactophenol dye at microscopic examination. The macroscopic morphology was consistent with H capsulatum. CONCLUSIONS: Although endogenous H capsulatum endophthalmitis is a rare entity, it should be considered as a possible etiology even in apparently immunocompetent hosts, especially in patients with history of disseminated disease.

Birdshot chorioretinopathy.

PURPOSE OF REVIEW: Birdshot chorioretinopathy remains incompletely understood, but new insights into its pathogenesis have been reported recently, and treatment and monitoring options have also expanded. Central visual acuity may remain good until the late stages of the disease, but loss of visual field and peripheral retinal function is common. RECENT FINDINGS: The underlying pathogenesis of the disease has long been believed to be T-cell driven, but examination of the IL-17 pathway has now further refined the potential underlying mechanism. New imaging techniques, including extended depth imaging of the choroid with optical coherence tomography, have demonstrated promise in detecting disease activity earlier, enabling targeted treatment to be given. Treatment options have expanded with the advent of the biological agents, and these may yet improve outcomes, particularly in refractory patients. SUMMARY: Laboratory research continues to investigate the underlying mechanisms of disease, but our understanding remains frustratingly incomplete for a disease with such a clear HLA association. Clinical research is increasingly being driven to improve the phenotyping of affected patients so that those at risk of visual loss can be identified early and treated more aggressively with individually targeted therapies such as the newer biological agents, but how successful this approach will ultimately prove to be remains to be seen.

Outcomes, impact on management, and costs of fungal eye disease consults in a tertiary care setting.

OBJECTIVE: To determine the frequency of clinical management changes resulting from inpatient ophthalmic consultations for fungemia and the associated costs. DESIGN: Retrospective case series. PARTICIPANTS: Three hundred forty-eight inpatients at a tertiary care center between 2008 and 2012 with positive fungal blood culture results, 238 of whom underwent an ophthalmologic consultation. METHODS: Inpatient charts of all fungemic patients were reviewed. Costs were standardized to the year 2014. The Student t test was used for all continuous variables and the Pearson chi-square test was used for categorical variables. MAIN OUTCOME MEASURES: Prevalence of ocular involvement, rate of change in clinical management, mortality rate of fungemic patients, and costs of ophthalmic consultation. RESULTS: Twenty-two (9.2%) of 238 consulted patients with fungemia had ocular involvement. Twenty patients had chorioretinitis and 2 had endophthalmitis. Only 9 patients (3.7%) had a change in management because of the ophthalmic consultation. One patient underwent bilateral intravitreal injections. Thirty percent of consulted patients died before discharge or were discharged to hospice. The total cost of new consults was $36 927.54 ($204.19/initial level 5 visit and $138.63/initial level 4). The cost of follow-up visits was $13 655.44 ($104.24/visit). On average, 26.4 patients were evaluated to find 1 patient needing change in management, with an average cost of $5620.33 per change in 1 patient's management. CONCLUSIONS: Clinical management changes resulting from ophthalmic consultation in fungemic patients were uncommon. Associated costs were high for these consults in a patient population with a high mortality rate. Together, these data suggest that the usefulness of routine ophthalmic consultations for all fungemic patients is likely to be low.

Interventions for toxoplasma retinochoroiditis: a report by the American Academy of Ophthalmology.

OBJECTIVE: To evaluate the available evidence in peer-reviewed publications about the outcomes and safety of interventions for toxoplasma retinochoroiditis (TRC). METHODS: Literature searches of the PubMed and the Cochrane Library databases were conducted last on July 20, 2011, with no date restrictions. The searches retrieved 275 unique citations, and 36 articles of possible clinical relevance were selected for full text review. Of these 36 articles, 11 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. RESULTS: Eight of the 11 studies reviewed were randomized controlled studies, and none of them demonstrated that routine antibiotic or corticosteroid treatment of TRC favorably affects visual outcomes or reduces lesion size. There is level II evidence from 1 study suggesting that long-term treatment with combined trimethoprim and sulfamethoxazole prevented recurrent disease in patients with chronic relapsing TRC. Adverse effects of antibiotic treatment were reported in as many as 25% of patients. There was no evidence supporting the efficacy of other nonmedical treatments such as laser photocoagulation. CONCLUSIONS: There is a lack of level I evidence to support the efficacy of routine antibiotic or corticosteroid treatment for acute TRC in immunocompetent patients. There is level II evidence suggesting that long-term prophylactic treatment may reduce recurrences in chronic relapsing TRC. Adverse effects of certain antibiotic regimens are frequent, and patients require regular monitoring and timely discontinuation of the antibiotic in some cases.

Toxoplasmosis: new challenges for an old disease.

More than a century after the identification of Toxoplasma gondii, major issues need to be addressed for the optimal management of ocular disease. Toxoplasmic retinochoroiditis is the main cause of posterior uveitis in several geographical areas. The parasite establishes a love-hate relationship with the eye, manipulating the immune response and inducing variable initial lesions and further relapses. It is now well established that most cases are acquired after birth and not congenital. The severity of the disease is mainly due to the parasite genotype and the host immune status. Diagnosis is based on clinical features, but may be confirmed by biological tools applied to ocular fluids. Combining several techniques improves the diagnostic yield in equivocal cases. Therapeutic management is the most important challenge. Even though evidence-based data on the efficacy of anti-parasitic drugs are still missing, new strategies with a good safety profile are available and may be proposed earlier during the course of the disease, but also in selected cases, to reduce sight-threatening relapses. Revisiting the therapeutic options and indications may be an important step towards long-term maintenance of the visual function and avoidance of major complications.