Alejandra de-la-Torre

Severe South American ocular toxoplasmosis is associated with decreased Ifn-γ/Il-17a and increased Il-6/Il-13 intraocular levels.

In a cross sectional study, 19 French and 23 Colombian cases of confirmed active ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical, parasitological and immunological responses and relate them to the infecting strains. A complete ocular examination was performed in each patient. The infecting strain was characterized by genotyping when intraocular Toxoplasma DNA was detectable, as well as by peptide-specific serotyping for each patient. To characterize the immune response, we assessed Toxoplasma protein recognition patterns by intraocular antibodies and the intraocular profile of cytokines, chemokines and growth factors. Significant differences were found for size of active lesions, unilateral macular involvement, unilateral visual impairment, vitreous inflammation, synechiae, and vasculitis, with higher values observed throughout for Colombian patients. Multilocus PCR-DNA sequence genotyping was only successful in three Colombian patients revealing one type I and two atypical strains. The Colombian OT patients possessed heterogeneous atypical serotypes whereas the French were uniformly reactive to type II strain peptides. The protein patterns recognized by intraocular antibodies and the cytokine patterns were strikingly different between the two populations. Intraocular IFN-γ and IL-17 expression was lower, while higher levels of IL-13 and IL-6 were detected in aqueous humor of Colombian patients. Our results are consistent with the hypothesis that South American strains may cause more severe OT due to an inhibition of the protective effect of IFN-γ.

New clinical and experimental insights into Old World and neotropical ocular toxoplasmosis

Retinal lesions or other ocular manifestations are serious consequences of infection with the protozoan parasite Toxoplasma gondii. Whilst classically considered a consequence of congenital transmission, recent screening studies estimated that 2% of T. gondii seropositive persons in Europe and North America have retinal lesions, most of them persisting unnoticed. The situation is more dramatic in South America, probably due to the predominance of virulent strains. Some of these strains seem to exhibit ocular or neuronal tropism and are responsible for severe ocular lesions. Despite the medical importance, the physiopathological mechanisms have only recently begun to be elucidated. The particular immune-privileged situation in the eye has to be considered. Studies on French patients showed low or undetectable ocular parasite loads, but a clear Th1/Th17 type immune reaction. Suitable mouse models have appeared in the last few years. Using such a model, IL-17A proved to impair parasite control and induce pathology. In contrast, in South American patients, the parasite seems to be much less efficiently controlled through a Th2 type or suppressive immune response that favors parasite replication. Finally, several host genetic markers controlling immune response factors have been associated with ocular involvement of T. gondii infection, mainly in South America.

Ocular cytokinome is linked to clinical characteristics in ocular toxoplasmosis.

PURPOSE To determine the cytokine levels in aqueous humor (AH) of Colombian patients with active ocular toxoplasmosis (OT), and to correlate them with their clinical characteristics. METHODS 27 Cytokines/chemokines were assayed in 15 AH samples (nine patients with diagnosis of OT biologically-confirmed and six controls that underwent cataract surgery). Correlations were assessed between cytokine/chemokine levels, type of inflammatory response (Th1, Th2, Th17, Treg), and clinical characteristics. RESULTS Th2 predominant response was related to more severe clinical features. The presence of VEGF and IL-5 was related to higher number of recurrences. Growth factors (VEGF, FGF, PDGF-β), were related to higher number of lesions. Patients infected by type-I/III strains had a particular intraocular cytokine-pattern. CONCLUSIONS Th2 response was related to more severe clinical characteristics in patients infected by Type I/III strains. IL-5 and VEGF were associated with recurrences. We correlate for the first time, specific cytokine-patterns with clinical characteristics and with the infecting Toxoplasma strain.

Th1 and Th2 immune response to P30 and ROP18 peptides in human toxoplasmosis

Abstract We determined the specific lymphocyte proliferative response and cytokine profile production regarding Toxoplasma P30 (2017 from virulent and non-virulent strain) and ROP18 protein-derived peptides (from clonal lineages I, II and III) in 19 patients having ocular toxoplasmosis, five suffering chronic asymptomatic infection, nine with congenital toxoplasmosis and eight Toxoplasma negative people. A Beckman Coulter FC500 flow cytometer was used for determining antigen-specific T cells (CD3+ CD4+ or CD3+ CD8+ cells) in peripheral blood culture. IFN γ and IL10 levels were determined in culture supernatants. Specific CD4+ and CD8+ T cell response to total antigen and P30- and ROP18-derived peptides was observed in infected people. Ocular toxoplasmosis patients had a preferential Th2 response after antigenic stimulation. Non-virulent peptide 2017 was able to shift response toward Th1 in congenitally infected children and virulent peptide 2017 induced a Th2 response in chronically infected, asymptomatic people. An immune response in human toxoplasmosis after ex vivo antigenic stimulation was Th1- or Th2-skewed, depending on a patient’s clinical condition. Colombian ocular toxoplasmosis patients’ immune response was Th2-skewed, regardless of the nature of antigen stimulus.

Tubulointerstitial Nephritis and Uveitis Syndrome: Case Report and Review of the Literature

ABSTRACT Purpose: To review the literature on tubulointerstitial nephritis and uveitis (TINU) syndrome, and to report a case of a patient with relapsing polychondritis (RP) and TINU syndrome. Method: TINU syndrome is a rare oculorenal inflammatory disorder. It is more common in young women with autoimmune conditions, infections, systemic disease, and previous use of medications. We report the case of a 62-year-old woman with relapsing polychondritis and a 2-year history of acute, recurrent, asymmetric, bilateral, anterior, non-granulomatous uveitis accompanied by tubulointerstitial nephritis. Results: The patient was diagnosed with TINU syndrome associated with relapsing polychondritis. No cases of this association have been reported in the literature. The clinical features of TINU syndrome are discussed based on the published works. Conclusions: TINU is an uncommon syndrome; only about 200 cases have been reported in the literature related to infections, systemic disease, and previous use of medications such as antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs). We found that it can be associated with relapsing polychondritis; therefore, it is important to investigate symptoms of this disease since TINU syndrome can co-exist with it.

Pediatric Uveitis: Experience in Colombia

ABSTRACT Purpose: To describe the clinical features of uveitis in children treated at two ophthalmologic centers in Bogotá, Colombia, in a 13 year-period. Methods: Retrospective observational clinical record review of pediatric children with diagnosis of uveitis. Results: In total, 310 children were evaluated, 51.9% were female, mean age of 10.1 years. Posterior uveitis was the most common location (58.7%), of insidious onset (87.4%) and chronic course (78.1%). The most common etiology was infection (58.4%) caused by toxoplasmosis (76.8%). There was a statistically significant difference in visual acuity between anterior (20/68) and intermediate uveitis (20/70), compared with posterior uveitis (20/434) (p<0.05). Conclusions: This is the first study to report the clinical features of pediatric uveitis in Colombia, where infectious etiologies are the leading cause. It will improve awareness and knowledge of pediatric uveitis in developing countries, and contribute to the development of public health policies of pediatric visual health. Received 12 September 2015; revised 23 February 2016; accepted 25 February 2016; published online 18 May 2016

Bilateral Herpes Simplex Uveitis: Review of the Literature and Own Reports

ABSTRACT Purpose: Herpes simplex-associated uveitis is usually considered a unilateral eye disease, and rarely included in the differential diagnosis whenever there is bilateral involvement. We report three cases of bilateral herpetic anterior uveitis. Methods: We evaluated three patients who presented with clinical manifestations of bilateral uveitis suggestive of viral origin. Results: We found intraocular hypertension, cells in the anterior chamber, paralytic mydriasis, iris atrophy with transillumination defects, and variable anterior vitreous cellularity. According to the clinical findings, supported with herpes-specific antibody titers and aqueous humor PCR results in two of them, they were diagnosed with bilateral anterior herpetic uveitis. Conclusions: Our patients were initially misdiagnosed as having non-infectious uveitis and were treated with immunomodulatory medications, which could have favored the extension of infection bilaterally. Although uncommon, bilateral herpetic uveitis should always be considered in the differential diagnoses, when patients present with hypertensive uveitis in both eyes.

Postoperative Alcaligenes xylosoxidans endophthalmitis: report of two cases

We report two cases of postoperative Alcaligenes xylosoxidans endophthalmitis. A 78-year-old woman in good general health developed A. xylosoxidans endophthalmitis one month after an uncomplicated phacoemulsification procedure with posterior chamber intraocular lens. It was performed on her left eye, at another institution. Removal of the intraocular lens and capsule was performed because of recurrent inflammation after vitrectomy and intravitreal antibiotic injections. Her son, a 55-year-old man, developed A. xylosoxidans endophthalmitis in his left eye, two months after an uncomplicated phacoemulsification procedure with posterior chamber intraocular lens (it also was performed by the same surgeon). He also required vitrectomy with removal of the intraocular lens and capsule because of persistent disease. A. xyloso - xidans can cause chronic low-grade and progressive endophthalmitis after cataract extraction that is often resistant to corrective antibiotic therapy. This kind of case is rare. There have been only previously reported seven cases worldwide to the best of our knowledge.

Bilateral Iris Depigmentation and Ocular Hypotony as End-Stage Manifestations of Untreated Vogt-Koyanagi-Harada Disease.

Abstract Purpose: To describe severe bilateral iris depigmentation and persistent ocular hypotony as end-stage manifestations of untreated Vogt–Koyanagi–Harada disease. Methods: We present the clinical findings and diagnostic studies performed for three patients with bilateral iris depigmentation. Results: Vogt–Koyanagi–Harada disease in late recurrent stage was diagnosed in three patients with bilateral severe iris depigmentation and persistent ocular hypotony. Conclusions: Early diagnosis and treatment of inflammation are crucial factors in the clinical outcome of Vogt–Koyanagi–Harada disease. When left undiagnosed and untreated from early stages, severe iris depigmentation and ocular hypotony, uncommon manifestations of this disease, can develop.

Virus-Induced Anterior Uveitis (VIAU) in Immunocompromised Patients

ABSTRACT Purpose: To describe the clinical characteristics, diagnosis, and treatment of VIAU in immunocompromised patients. Methods: A critical review of literature was performed. Results: Diagnosis and treatment of VIAU in immunocompromised patients may be a challenge due to atypical clinical-courses, severe presentations, and more frequent recurrences. A conclusive diagnosis can be made by aqueous-humour PCR-analysis. Visual prognosis depends on early diagnosis and prompt treatment. Frequent ocular examinations are recommended in HIV patients with CD-4-counts below 100 in order to rule out opportunistic ocular coinfections. It is essential to bear in mind the potential side-effects of therapeutic interventions and consider the possibility of Immune Recovery Uveitis (IRU) in eyes with treated viral retinitis after the initiation of HAART. Conclusions: Early diagnosis and treatment of VIAU in immunocompromised patients can be achieved with high suspicion, recognizing clinical features, and obtaining specimens for molecular diagnostic testing in order to avoid usually severe ocular morbidity.