Novel infectious agents causing uveitis

In any patient with uveitis, an infectious cause should be ruled out first. The differential diagnosis includes multiple well-known diseases including herpes, syphilis, toxoplasmosis, tuberculosis, bartonellosis, Lyme disease, and others. However, clinician should be aware of emerging infectious agents as potential causes of systemic illness and also intraocular inflammation. Air travel, immigration, and globalization of business have overturned traditional pattern of geographic distribution of infectious diseases, and therefore one should work locally but think globally. This review recapitulates the systemic and ocular manifestations of several emergent infectious diseases relevant to the ophthalmologist including Rickettsioses, West Nile virus infection, Rift valley fever, Dengue fever, and Chikungunya. Retinitis, chorioretinitis, retinal vasculitis, and optic nerve involvement have been associated with these emergent infectious diseases. The diagnosis of any of these infections is usually based on pattern of uveitis, systemic symptoms and signs, and specific epidemiological data and confirmed by detection of specific antibody in serum. A systematic ocular examination, showing fairly typical fundus findings, may help establish an early clinical diagnosis, which allows prompt, appropriate management.     

Clinical Patterns and Causes of Intraocular Inflammation in a Uveitis Patient Cohort from Egypt

Purpose: To analyze the patterns and causes of intraocular inflammation in patients attending uveitis referral clinics in Egypt.

Methods: The study included 454 patients with uveitis examined both at the Department of Ophthalmology, Alexandria Faculty of Medicine, and tertiary uveitis referral clinics in Cairo and the International Eye Clinic in Upper Egypt, between August 2013 and March 2016. All patients had a comprehensive ocular examination and systemic work-up. Standard diagnostic criteria for uveitis syndromes were employed for all patients and ancillary ocular or systemic investigations were ordered as required by the suspected uveitis entity.

Results: The mean age at presentation was 30 years (range: 4–75). The male to female ratio was 1.1:1. Panuveitis was the most common anatomic pattern (43%), followed by anterior (40.7%), posterior (9%), and intermediate uveitis (7.3%). Anterior uveitis was most commonly attributed to pediatric parasitic anterior chamber granulomas (22.2%). Intermediate uveitis was most commonly idiopathic (81.8%). Toxoplasma retinitis was the most common cause of posterior uveitis (31.7%). Behçet disease was the most common cause of panuveitis followed by Vogt–Koyanagi–Harada (VKH) disease (45.6% and 22.1%, respectively). Among non-infectious etiologies, Behçet disease was the most frequent etiology (28.6%), while for infectious causes, herpetic uveitis was found to be the most frequent cause (39.8%).

Conclusions: In this uveitis patient population from Egypt, panuveitis was the most commonly encountered anatomic diagnosis. Behçet disease was the most common identified cause of uveitis followed by VKH disease. Herpes-related uveitides and parasitic granulomas represented the most evident causes of infectious uveitis.     

Chronic Anterior Uveitis Associated with Relapsing Polychondritis: A Case Report

ABSTRACT

Purpose: To report a case of chronic anterior uveitis associated with relapsing polychondritis (RP).

Case Report: A 43-year-old female patient presenting with bilateral progressive vision loss was diagnosed with bilateral anterior uveitis. According to her clinical signs and symptoms and biopsy results, RP was ultimately diagnosed. Her ocular inflammation was controlled with corticosteroids and systemic immunosuppressive treatment, and the symptoms related to RP improved.

Conclusion: Chronic uveitis is an inflammatory disease that may be associated with many systemic autoimmune diseases. RP should especially be considered in patients with bilateral chronic uveitis, and a relevant detailed history should be obtained for early and accurate diagnosis and treatment.     

Behçet Uveitis in the American Midwest

Purpose: Behçet disease is most common in Asia, the Middle East, and North Africa (Silk Road). The authors compare clinical presentation and course of Behçet uveitis in patients of Silk Road and non-Silk Road descent.

Methods: Retrospective review of patients evaluated at the University of Illinois January 1983–July 2010.

Results: Of 6134 new uveitis patients, 36 with available medical records met diagnostic criteria for Behçet disease. Ten (28%) were of Silk Road origin. Retinal vasculitis was the most common ocular manifestation, followed by panuveitis and retinitis. Ocular and systemic manifestations were similar between groups. Seventy-eight percent were treated with systemic immunosuppression, which reduced inflammatory attack rate.

Conclusions: Behçet disease is uncommon in the midwestern United States. Three-quarters of patients in this series were not of Silk Road descent. Physicians should consider the diagnosis of Behçet disease in any patient with retinal vasculitis or uveitis regardless of ethnicity.     

Ocular Involvement in Muckle-Wells Syndrome

ABSTRACT

Purpose: To present the ocular findings of the members of a family that has the diagnosis of Muckle Wells syndrome, a form of cryopyrin associated periodic syndrome (CAPS).

Materials and Methods: Nine patients with MWS were included in this study. Each study participant underwent a systemic evaluation, comprehensive ophthalmic examination, and auxillary testings.

Results: In this study, conjunctivitis was the most prominent ocular finding. Other relatively common ocular findings included band keratopathy, clinical signs of past uveitis, and corneal topography abnormalities. Nystagmus, corneal leukoma, and optic nerve pallor with epiretinal membrane were also detected. Rare ocular manifestations were posterior stromal corneal opacification with edema, anterior iris snychecia, and mild cataract.

Conclusion: MWS is a rare systemic autoinflammatory disorder that presents with a variety of ocular findings. Exacerbation of systemic and ocular findings with cold is a hallmark of the disease.     

Ocular Whipple Disease: Report of Three Cases

Purpose: To emphasize the different manifestations of ocular involvement in Whipple disease with challenge in establishing the diagnosis as clinical, laboratory, and histological features could mimic other uveitis entities.

Methods: Case reports of three patients.

Results: The first patient was an African male suffering from a chronic bilateral keratoconjunctitivitis that was initially misdiagnosed as a chronic allergic conjunctivitis. The second patient was an Italian female who presented with bilateral vitritis, whereas the third patient was an Italian male suffering from a chronic bilateral panuveitis. The diagnosis of ocular Whipple in the first and third case was made by a positive T. whipplei PCR from the ocular specimen, and the second patient had detection of T. whipplei from extraocular sites.

Conclusions: Whipple disease can have protean manifestations in the eye including an isolated ocular surface involvement manifested as keratitis.     

Ocular manifestation of systemic infections

Careful examination of external and internal ocular structures in patients with systemic infections may assist in early diagnosis and institution of appropriate therapy. Recent literature discussing ocular manifestations in the following systemic infectious diseases are reviewed: tuberculosis, Lyme borreliosis, cat scratch disease, toxocariasis, congenital toxoplasmosis, and invasive aspergillosis.     

Spectrum of Uveitis in A German Tertiary Center: Review of 474 Consecutive Patients

Abstract

Purpose: To analyze the spectrum of uveitis at a German tertiary center.

Patients and methods: A total of 474 consecutive patients with uveitis were classified according to the primary anatomic site of inflammation, examined for laterality of disease, and screened for etiologies.

Results: Out of the total, 253 patients (53%) had anterior uveitis, 90 patients (19%) had intermediate uveitis, 100 patients (21%) had posterior uveitis, and 31 patients (7%) had panuveitis. Fifty-six percent of the patients had bilateral involvement, predominantly in intermediate uveitis (ratio 4:1) and panuveitis (ratio 3.4:1). Regarding the etiology of all uveitis cases we found 17% infectious, 23% specific clinical entities, 20% associated with systemic disease (most commonly sarcoidosis with 11%), and 41% idiopathic uveitis.

Conclusions: Anterior uveitis was the most common anatomic site of intraocular inflammation. Using a tailored approach, screening for systemic etiologies is recommended, since 20% of all patients had associated systemic diseases.     

Oculo-renal Disorders in Infectious Diseases

Background: The aim of this article is to review the potential ocular and renal disorders in infectious diseases to which humans are susceptible and to determine prevalence of these diseases. Methods: Published cases of oculo-renal disorders associated with various infectious diseases were collected from the international literature by searching the MEDLINE database (PUBMED 1970–2004) for original reports and review articles published in English. Citations from papers retrieved were screened and retrieved papers were evaluated. Results: Based on the screened data, we propose a practical, structure-oriented checklist of such lesions divided into bacterial, viral, parasital, and fugal infections. Conclusion: The oculorenal manifestations of infectious diseases may be flagrant or subtle. Awareness of the signs and symptoms of infections allows early recognition and prompt, appropriate management. The clinical presentation and relative frequency of those manifestations are reviewed.     

Real-Time Multiplex PCR Analysis in Infectious Uveitis

ABSTRACT

Introduction: Infectious uveitis is a serious inflammatory condition that often causes grave ocular morbidity including permanent vision loss and damage to the structures of the eye. The most common causes of infectious uveitis include herpesviruses and Toxoplasma gondii. Traditionally, these infections have been identified and differentiated based on characteristic clinical examination findings; however, there is often overlap between these presentations and the unique cause of a given patient’s infection is not always clear. Therefore, a reliable and fast method for definitively diagnosing infectious uveitis would be helpful and potentially sight-saving. Several groups have recently found experimental success with real-time multiplex polymerase chain reaction (PCR) techniques.

Methods: A comprehensive review of the literature was undertaken to further understand the current state of real-time multiplex PCR and its clinical use. Search terms including “real time multiplex PCR”, “infectious uveitis”, and “uveitis diagnosis” were used. Appropriate English-language articles were included in this review.

Results: Publications from four main groups (two from the United States, one from Japan, and one from India) citing success with real-time multiplex PCR were compared and contrasted. All four groups used the same technique to develop a highly sensitive and specific multiplex PCR analysis and found that their tests maintained high sensitivity and specificity during validation testing. These tests confirmed clinical suspicions in the majority of cases of infectious uveitis, but there were also cases of clinical misdiagnosis that were corrected based on molecular pathogen detection. These patients were then initiated on appropriate antimicrobial therapy with subsequent clinical improvement.

Discussion: Real-time multiplex PCR is a highly sensitive and specific laboratory assay that allows for rapid and reliable molecular diagnosis of causative agents in infectious uveitis. This in turn facilitates swift initiation of effective therapy and prevents long-term ocular damage and vision loss.     

Role of Endoscopic Ultrasound in the Management of Tubercular Uveitis

Purpose: To evaluate the role and safety of endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC) in patients of tubercular uveitis.

Design: Interventional case series

Methods: Thirty patients suspected of tubercular uveitis that underwent EUS-FNAC were enrolled in the study. The patient details recorded were age, gender, systemic history, ocular complaints and clinical manifestations. The details of the investigations - skin test, X-Ray chest, CECT (contrast enhanced computed tomography) of chest and findings on EUS-FNAC were also recorded.

Results: Thirty patients with suspected tubercular uveitis showed mediastinal lymphadenopathy on CECT-chest and underwent EUS-FNAC. A total of 27 patients showed tubercular lymphadenitis and three patients showed reactive lymphadenopathy. Ziehl–Neelsen (ZN) staining was positive for acid-fast bacilli in four cases and culture was positive in one case. There were no noted complications of EUS-FNAC.

Conclusion: EUS-FNAC is a safe and efficacious procedure for confirming the diagnosis of tubercular uveitis and should be routinely employed wherever available.     

Uveitis Related to Juvenile Idiopathic Arthritis: Familial Cases and Possible Genetic Implication in the Pathogenesis

Purpose: To describe four cases of familial Juvenile Idiopathic Arthritis (JIA) associated uveitis.

Design: Retrospective observational case series.

Methods: Clinical data from patients who present familial JIA-associated uveitis are described and possible genetic influence in disease etiology is reviewed.

Results: Two sisters, 6- and 7-year-old, developed bilateral anterior uveitis related to oligoarticular JIA. Arthritis in both began by the age of 18 months; uveitis developed simultaneously in one of them and less than one year after arthritis in the other one. Both received topical and systemic treatment to control the ocular disease. Glaucoma occurred in both cases and bilateral cataract in one case. In the other family, a 2-year-old girl developed unilateral uveitis in the context of oligoarticular JIA which was diagnosed by 1-year-old. The disease became soon bilateral and she received topical and systemic immunosuppressive treatment. Her mother suffered from bilateral anterior uveitis associated to oligoarticular inflammatory disease during her infancy, later diagnosed as JIA-associated uveitis.

Conclusions: Familial cases of JIA uveitis, although not very common, support the possible role of genetic influence in the pathogenesis of the disease, with horizontal and vertical inheritance being possible. The evolution of ocular disease is similar to the non-familial cases, except for an earlier age of onset.     

Emerging infectious uveitis: Chikungunya,dengue, Zika and Ebola: A review

Recently recognized forms of uveitis include intraocular inflammations that occur during or following one of several emerging infectious diseases: chikungunya fever, dengue, Zika virus disease and Ebola virus disease. Anterior, intermediate, posterior and pan‐uveitis have been described in individuals infected with chikungunya virus. Persons who contract dengue or Zika viruses also may develop different types of uveitis in the course of the infection: maculopathy is a common manifestation of dengue eye disease, and Zika eye disease may cause hypertensive anterior uveitis or mimic a white dot syndrome. Up to one‐third of Ebola survivors develop aggressive uveitis, which is frequently associated with vision loss and complicated by cataract. There are no specific anti‐viral drugs for these forms of uveitis, and thus treatment is largely supportive. In this article, we summarize the systemic infectious diseases and virology, and describe the clinical presentations, outcomes and management of emerging viral forms of uveitis.     

A Focus on the Epidemiology of Uveitis

Purpose: Uveitis is a common, sight-threatening inflammatory ocular disease and includes multiple heterogeneous clinical entities. The prevalence of various types of uveitis depends upon multiple factors, such as age, sex, race, geographic distribution, environmental influence, genetics, and social habits. Epidemiologic research of uveitis is necessary to understand the etiology and immunopathogenesis of this group of diseases. The present study attempts to concentrate on the most recent information on the epidemiology of uveitis and compare it with previous knowledge.

Methods: An extensive literature search was performed in the Medline database (PubMed) and included surveys completed until 2015. Articles that reported prevalence and incidence were studied. References cited in the articles were also studied.

Results: The incidence and prevalence of uveitis differs based on age, anatomic location of the inflammatory process (anterior, intermediate, posterior uveitis, panuveitis), gender, histopathology (granulomatous, non-granulomatous), type of inflammatory process (acute, chronic, recurrent), and etiology (infectious, non-infectious). Prevalence differs by geographic location. Idiopathic anterior uveitis is the most common form of uveitis in the community. Infectious causes are common (30–60%) in the developing countries. Herpes and toxoplasmosis are the leading infectious causes of uveitis. Non-infectious uveitic conditions are generally more common in the developed world. An increase in the prevalence of infectious etiologies, including tuberculosis and syphilis, has been seen in developed countries. Introduction of new treatment options has also changed patterns of disease.

Conclusions: Introduction of new uveitis entities, changes in the incidence of already known disease and increased availability of diagnostic testing have all altered the epidemiology of uveitis in recent years. Knowledge of regional patterns of disease is essential. A more detailed classification of uveitis with the establishment of uniform diagnostic criteria and prospective population based studies would certainly benefit epidemiologic research and clinical practice.     

Ocular Manifestations of X-linked Chronic Granulomatous Disease: About Two Atypical Case Reports

Abstract

Purpose: Two atypical cases of ocular localizations of chronic granulomatous disease are reported.

Methods: The first case is about a 22-year-old woman carrier of the disease who developed active intraocular inflammation and choroidal granulomas successfully treated by steroids. The second is about a 2-year-old boy consulting for unilateral anterior uveitis and subsequent anterior chamber granuloma development as first signs of the disease.

Results: X-linked chronic granulomatous disease is a rare inherited primary immunodeficiency syndrome characterized by disorders of phagocytic cells resulting in recurrent infections and development of granulomas. Ophthalmological manifestations are not rare and are mainly represented by surface and intraocular inflammation with possible choroidal granulomas. The two cases reported here are atypical, one of active inflammation in a carrier and the other revealing the disease.

Conclusion: Ophthalmologists must be aware of chronic granulomatous disease and the possible ocular involvement of this disorder.     

A Review of Next-Generation Sequencing (NGS): Applications to the Diagnosis of Ocular Infectious Diseases

ABSTRACT

Purpose: To review the value of next-generation sequencing (NGS) in identifying the pathogens which cause ocular infections, thereby facilitating prompt initiation of treatment with an optimal anti-microbial regimen. Both contemporary and futuristic approaches to identifying pathogens in ocular infections are covered in this brief overview.

Methods: Review of the peer reviewed literature on conventional and advanced methods as applied to the diagnosis of infectious diseases of the eye.

Conclusion: NGS is a novel technology for identifying the pathogens responsible for ocular infections with the potential to improve the accuracy and speed of diagnosis and hastening the selection of the best therapy.     

Ocular Blood Flow Changes in Behçet Disease Patients with/without Thrombotic Disease

ABSTRACT

In this study, the authors aimed to evaluate ocular blood flow changes in Behçet disease (BD) with and without thrombotic disease. Ninety eyes of 90 patients with a diagnosis of BD (30 eyes with active uveitis, 23 eyes with inactive uveitis, 25 eyes without ocular involvement, and 12 eyes without ocular involvement and with a history of thrombosis) and 30 eyes of 30 age- and sex-matched control patients without any systemic disease with a total of 120 eyes were evaluated. In all cases, ophthalmic, central retinal, and ciliary artery flow parameters were measured with colour Doppler ultrasonography (CDU). The ocular blood flow parameters of all vessels in patients with active uveitis were found to be affected. All the flow parameters in the CRAs of the study groups were significantly different from the control group (p?<?0.001). Additionally, in non-ocular BD patients with thrombosis, blood flow parameters were affected more than the parameters in non-ocular BD patients without thrombosis and control patients. In conclusion, major haemodynamic changes were observed using CDU in the ophthalmic vessels of ocular Behçet patients. Also, CDU may detect ocular blood flow alterations before initial ocular clinical manifestations appear in BD patients     

Patterns of Uveitis among Patients Attending Jimma University Department of Ophthalmology,Jimma, Ethiopia

ABSTRACT

Introduction: Uveitis is an important cause of blindness and ocular morbidity in the world. The patterns of uveitis have not been well characterized in sub-Saharan Africa.

Purpose: To describe the characteristics of uveitis among patients presenting to Jimma University Department of Ophthalmology (JUDO) from July 2013 to December 2014.

Methods: This hospital-based prospective cross-sectional study included all new uveitis patients visiting JUDO outpatient department during the study period.

Results: Among 98 patients diagnosed with uveitis, anterior uveitis was found in 74.5% of patients. Majority of the patients, 83.7%, had unilateral uveitis. A uveitis syndrome was identified in 22.5% of cases; of these 15 (68.2%) were infectious. Herpes simplex uveitis was the commonest infectious cause (53.3%) while Toxoplasmosis was the most common cause of posterior uveitis (60%).

Conclusion: Anterior uveitis was the most common pattern found among uveitis patients. Herpes simplex and toxoplasmic chorioretinitis were the most common-identified infectious causes.     

Neuro-Sweet Disease Causing Orbital Inflammation

Abstract

Neuro-Sweet disease is a rare condition causing encephalitis or meningitis in addition to the erythematous skin plaques of Sweet syndrome. Neuro-Sweet disease has been associated with several ocular manifestations, including ocular movement disorders, episcleritis, conjunctivitis, uveitis, and optic disc oedema. The author reports a patient with orbital inflammation, cranial neuropathies, and a skin rash in the setting of myelodysplastic syndrome. Biopsy of her skin lesion confirmed the diagnosis of neuro-Sweet disease. To the author’s knowledge, this is the first reported case of neuro-Sweet disease causing orbital inflammation. Her ocular inflammation resolved with the use of systemic corticosteroid treatment.     

Review for Disease of the Year: Treatment of Viral Anterior Uveitis: A Perspective

Purpose: To define a clinically tailored therapeutic strategy for the treatment of viral anterior uveitis (VAU).

Methods: A PubMed search spanning the past 5 years was conducted using the MesH-terms “viral anterior uveitis” and “therapy.”

Results: The herpes simplex virus (HSV), the varicella zoster virus (VZV), and the cytomegalovirus (CMV) are the predominant pathogens in VAU. Other viruses, including rubella, chikungunya, and zika, have been linked with distinct forms of the disease. Depending on the causative agent and the host immunocompetence, the mainstay treatment for suspected VAU is a combination of topical or systemic antivirals and topical corticosteroids, supplemented with cycloplegics and intraocular-pressure-lowering medication.

Conclusions: Oral acyclovir, valacyclovir, and famciclovir are the mainstay of treatment for HSV- and VZV-induced infections. Brivudin serves as an alternative in insufficiently responsive cases. CMV-induced infections respond well to valganciclovir. A 3- to 12-month course of prophylactic treatment against recurrences is worth considering.