Daniel V. Vasconcelos-Santos

Congenital Toxoplasmosis in Southeastern Brazil: Results of Early Ophthalmologic Examination of a Large Cohort of Neonates

OBJECTIVE To report results of early ophthalmologic examinations in a large cohort of newborns with congenital toxoplasmosis (CT) after neonatal screening. DESIGN Cross-sectional analysis of a cohort. PARTICIPANTS A total of 178 newborns with confirmed CT from 146,307 screened babies (95% of live births) from Minas Gerais state, southeastern Brazil. METHODS From November 2006 to May 2007, newborns underwent neonatal screening by immunoglobulin (Ig)M capture of dried blood samples. On all positive or suspected cases, confirmative serology was performed on babies and their mothers. Congenital toxoplasmosis was confirmed in newborns who had IgM and/or IgA and IgG, or IgG associated with suggestive ocular lesions (with IgM and IgG in the mother). Ophthalmologic evaluation consisted of indirect ophthalmoscopy with a lid speculum. Pediatric examination and radiologic studies of the central nervous system were also performed. In selected cases, biomicroscopy of the anterior segment, fundus photographs, or ultrasonography (B-scan) was performed. MAIN OUTCOME MEASURES Prevalence of retinochoroidal lesions, either cicatricial or active, and their location and associated findings, such as vascular sheathing, hemorrhage, vitreous opacities, and retinal detachment, were evaluated. The occurrence of cataract, microphthalmia, microcephaly, intracranial calcification, and hydrocephalus was also recorded. RESULTS Of 146,307 neonates screened, 190 had CT, yielding a prevalence of 1 in 770 live births, of whom 178 (93.7%) underwent standardized ophthalmologic examination at an average age of 55.6+/-16.6 days. Of these 178 infants, 142 (79.8%) had retinochoroidal lesions consistent with CT in at least 1 eye. Bilateral involvement was noted in 113 patients (63.5%). Macular involvement was seen in 165 eyes (46.3%) of 111 patients (62.4%). Active lesions were observed in 142 eyes (39.9%) of 85 patients (47.8%). These lesions were located in the macula of 75 eyes (21.1%) and were associated with retinal vascular sheathing in 44 eyes (12.4%). CONCLUSIONS A high prevalence of CT was encountered (1/770) with high rates of early retinochoroidal involvement ( approximately 80%) and many active lesions (in approximately 50%), indicating a possibly more severe ocular involvement by CT in Brazil than in other parts of the world. The hypotheses of higher parasite virulence and increased individual susceptibility are being currently investigated.

Genetic Characterization of Toxoplasma gondii Revealed Highly Diverse Genotypes for Isolates from Newborns with Congenital Toxoplasmosis in Southeastern Brazil

ABSTRACT Recent studies of Toxoplasma gondii isolates from animals in Brazil have revealed high genetic diversity. Many of these isolates are virulent to mice. It is speculated that these isolates may also be virulent to humans. However, there is very limited data regarding T. gondii strains from human infection. Therefore, it is not clear whether there is any association between parasite genotypes and disease phenotypes. In this study, a total of 27 T. gondii strains were isolated from humans with congenital toxoplasmosis in Minas Gerais state, Brazil. The genetic variability was assessed by restricted fragment length polymorphism in 11 loci (SAG1, 5′ plus 3′ SAG2, alternative [alt.] SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico). Genetic analysis of 24 strains revealed 14 different genotypes, including 7 previously identified from animals and 7 new types. The widespread genotype BrII accounted for 29% (7/24) of the isolates and was the dominant genotype involved in this study. This is the first report of genotyping of T. gondii isolates obtained from blood samples from newborns with congenital toxoplasmosis. Genotypic characterization of these isolates suggests high genetic diversity of T. gondii in this human population in Brazil. Future studies are needed to determine the source of contamination of this human population.

Clinical Features of Tuberculous Serpiginouslike Choroiditis in Contrast to Classic Serpiginous Choroiditis

OBJECTIVE To compare distinctive clinical features of presumed tuberculous serpiginouslike choroiditis (Tb-SLC) with classic serpiginous choroiditis (SC) in patients living in a region that is nonendemic for tuberculosis. METHODS Retrospective comparative analysis of clinical features of 5 patients with recurrent Tb-SLC and 5 with SC. RESULTS All patients with recurrent Tb-SLC primarily emigrated from areas highly endemic for tuberculosis and had been unsuccessfully treated with steroids/immunosuppressive agents. Results of uveitis investigations were negative except for positive tuberculin skin test results. These patients received oral tuberculostatic drugs, without recurrences (follow-up, 6-91 months). The ocular involvement in Tb-SLC was mostly unilateral, with multiple irregular serpiginoid lesions involving the posterior pole and periphery but usually sparing the juxtapapillary area. All 5 cases had inflammatory cells in the vitreous. Patients with SC were from areas nonendemic for tuberculosis, had negative uveitis workup findings (including tuberculin skin test results), and were successfully managed with steroids/immunosuppressive agents (follow-up, 6-72 months) with no recurrence. Ocular involvement in SC was usually bilateral, rarely multifocal, and primarily involved the posterior pole, especially around the optic disc and extending contiguously to the macula. No patient with SC presented with vitritis. CONCLUSION In areas nonendemic for tuberculosis, SC can be clinically differentiated from Tb-SLC. Patients with Tb-SLC come from highly endemic regions, show significant vitritis, and often present with multifocal lesions in the posterior pole and periphery. Cases of SC, in contrast, reveal minimal or no vitritis and frequently show bilateral involvement with larger solitary lesions extending primarily from the juxtapapillary area and sparing the periphery.

Strengths and Weaknesses of Diagnostic Tools for Tuberculous Uveitis

Diagnostic criteria for tuberculous uveitis encompass exclusion of other known etiologies of uveitis, suggestive clinical history and signs, supportive systemic investigations, positive response to empiric antituberculosis treatment and evidence of Mycobacterium tuberculosis or its DNA in ocular fluids/tissues. Recent advances in diagnostic tools for tuberculous infection, including molecular biology techniques for detection of M. tuberculosis DNA and interferon-gamma release assays, have improved the specificity of the diagnosis and the ability to ascertain exposure to the infectious agent. However even with such advances, establishing the diagnosis of tuberculous uveitis remains a challenging issue because each of these available investigations has its strengths and limitations and tuberculous infection can present with clinical features of any type of extraocular or intraocular inflammation. This article critically analyzes the role of these tests in supporting the diagnosis of tuberculous uveitis and proposes a practical diagnostic approach, based on a judicious combination of these tests.

Secondary ocular hypertension after intravitreal injection of 4 mg of triamcinolone acetonide: incidence and risk factors.

Purpose: To analyze the incidence of secondary ocular hypertension (SOH) after intravitreal triamcinolone acetonide (IVTA) injection and its risk predictors. Methods: Retrospective review of charts for 219 consecutive patients receiving a 4-mg IVTA injection. Results: One hundred fifty eyes of 150 patients who were followed for at least 3 months and met inclusion criteria were considered. Main indications for IVTA injection were neovascular age-related macular degeneration (79 eyes [52.7%]), choroidal neovascularization due to other etiologies (22 eyes [14.7%]), diabetic macular edema (14 eyes [9.3%]), central retinal vein occlusion (12 eyes [8.0%]), and branch retinal vein occlusion (8 eyes [5.3%]). SOH defined as intraocular pressure (IOP) of ≥21 mmHg was recorded for 32.0% of injected eyes at some point during a mean follow-up of 7.7 months. There was no association between SOH and age, sex, arterial hypertension, diabetes mellitus, indication for IVTA injection, prior cataract surgery, or concurrent photodynamic therapy. Although previous pars plana vitrectomy did not influence risk, peak IOP was lower in vitrectomized eyes (P = 0.044). Prior diagnosis of glaucoma was a significant risk factor for SOH (relative risk = 2.17; P = 0.004). In nonglaucomatous eyes, baseline IOP of ≥16 mmHg was associated with a higher risk of SOH (relative risk = 2.31; P = 0.003). Baseline IOPs of <12 mmHg, 12–14 mmHg, 15–17 mmHg, 18–20 mmHg, and >20 mmHg were associated with incidences of SOH of 11.1%, 25.4%, 40.0%, 46.2%, and 50.0% (P = 0.01), respectively. Conclusions: A 4-mg IVTA injection was associated with SOH in 32.0% of treated eyes. The risk of SOH was higher in eyes with previous glaucoma and higher baseline IOP. Peak IOP after IVTA injection was lower in vitrectomized eyes. Risk factor analysis may permit better individualization of the risk–benefit ratio for IVTA injection.

Retinal pigment epithelial changes in chronic Vogt-Koyanagi-Harada disease: fundus autofluorescence and spectral domain optical coherence tomography findings

Purpose: The purpose of this study was to determine whether fundus autofluorescence (FAF) and spectral domain-optical coherence tomography (SD-OCT) imaging allow better assessment of retinal pigment epithelium and the outer retina in subjects with chronic Vogt-Koyanagi-Harada disease compared with examination and angiography alone. Methods: A cross-sectional analysis of a series of seven consecutive patients with chronic Vogt-Koyanagi-Harada disease undergoing FAF and SD-OCT was conducted. Chronic disease was defined as duration of intraocular inflammation >3 months. Color fundus photographs were correlated to FAF and SD-OCT images. The images were later correlated to fluorescein angiography and indocyanine green angiography. Results: All patients had sunset glow fundus, which resulted in no apparent corresponding abnormality on FAF or SD-OCT. Lesions with decreased autofluorescence signal were observed in 11 eyes (85%), being associated with loss of the retinal pigment epithelium and involvement of the outer retina on SD-OCT. In 5 eyes (38%), some of these lesions were very subtle on clinical examination but easily detected by FAF. Lesions with increased autofluorescence signal were seen in 8 eyes (61.5%), showing variable involvement of the outer retina on SD-OCT and corresponding clinically to areas of retinal pigment epithelium proliferation and cystoid macular edema. Conclusion: Combined use of FAF and SD-OCT imaging allowed noninvasive delineation of retinal pigment epithelium/outer retina changes in patients with chronic Vogt-Koyanagi-Harada disease, which were consistent with previous histopathologic reports. Some of these changes were not apparent on clinical examination.

Long-Term, Multicenter Evaluation of Subconjunctival Injection of Triamcinolone for Non-Necrotizing, Noninfectious Anterior Scleritis

PURPOSE We sought to characterize the long-term outcomes and complications of subconjunctival triamcinolone acetonide injection (STI) for non-necrotizing, noninfectious anterior scleritis. DESIGN Retrospective, interventional, noncomparative, multicenter study. PARTICIPANTS Sixty-eight eyes of 53 patients from 9 participating hospitals in the United States, Singapore, and Australia. Only eyes with 6 or more months of follow-up were included. INTERVENTION Subconjunctival injection of 2 to 8 mg of triamcinolone acetonide was administered to eyes with non-necrotizing, noninfectious anterior scleritis. MAIN OUTCOME MEASURES Resolution of signs and symptoms, time to recurrence of scleritis, and side effect profile. RESULTS Median follow-up was 2.3 years (range, 6 months to 8.3 years). Sixty-six eyes (97.0%) experienced improvement of signs and symptoms after 1 injection. Twenty-four months after a single injection, 67.6% of eyes remained recurrence-free, whereas at 48 months, 50.2% were recurrence-free. Some 55.0% of patients who had adverse effects from systemic medications were off all systemic medications at last follow-up; 55.0% of patients who were taking systemic medications at the time of first triamcinolone acetonide injection were not taking prednisone and immunosuppressants at this time; 76.2% of patients still requiring systemic agents had associated systemic disease. Fourteen eyes (20.6%) had ocular hypertension not requiring intraocular pressure (IOP)-lowering therapy. Two eyes (2.9%) were treated with topical IOP-lowering agents alone, and 2 eyes required surgical intervention for glaucoma. None developed scleral necrosis or melt. CONCLUSIONS This retrospective, international study carried out at 9 hospitals suggests that STI can treat non-necrotizing, noninfectious anterior scleritis with side effects limited to elevated IOP in a few patients. Although no cases of scleral melt or necrosis were observed, we cannot definitively conclude that this may not occur after STI. Intraocular pressure should be closely monitored after STI. Subconjunctival triamcinolone acetonide injection may be useful as adjuvant therapy or to decrease systemic medication burden. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy.

OBJECTIVE To report a rare case of congenital toxoplasmosis from an immunocompetent mother with chronic infection who had reactivation of ocular disease during pregnancy. DESCRIPTION The newborn was asymptomatic at birth and identified by neonatal screening (IgM anti-Toxoplasma gondii in dried blood) among other 190 infants with congenital toxoplasmosis during a 7-month period. His mother had had a non-treated episode of reactivation of toxoplasmic retinochoroiditis during pregnancy, with stable IgG titers and negative IgM results. Results of IgM and IgG in the newborns serum, as well as IgG immunoblotting were positive and active retinochoroidal lesions were detected in his peripheral retina. The neonate was treated with sulfadiazine, pyrimethamine and folinic acid. At 14 months of life, the child remained asymptomatic, with regression of retinochoroidal lesions and persistence of IgG. COMMENTS It is possible that systematic neonatal screening in areas with high prevalence of infection may identify these cases.

Ultra-wide-field green-light (532-nm) autofluorescence imaging in chronic Vogt-Koyanagi-Harada disease.

BACKGROUND AND OBJECTIVE To assess the prevalence of peripheral fundus autofluorescence (FAF) abnormalities in chronic Vogt-Koyanagi-Harada disease (VKH). PATIENTS AND METHODS A retrospective review of cases at the Doheny Eye Institute between December 2009 and April 2010. Patients with chronic VKH who had ultra-wide-field FAF and pseudo-color imaging performed were included. All images were reviewed independently by two reading center certified retina specialists. RESULTS Twenty eyes of 10 patients were included in this analysis. Fourteen eyes of 7 patients (70%) showed peripheral changes on FAF images outside the posterior pole. Three different patterns were observed: multifocal hypofluorescent spots (n = 11 eyes), hyperfluorescent spots (n = 8 eyes), and a unique lattice-like pattern in both eyes of one patient. There were noticeable disparities between FAF and color images. CONCLUSION Peripheral FAF abnormalities are frequent in chronic VKH and are readily revealed by wide-field FAF imaging and manifesting with distinct patterns. Further investigation in prospective studies is warranted.

Biomarker analysis revealed distinct profiles of innate and adaptive immunity in infants with ocular lesions of congenital toxoplasmosis.

Toxoplasma gondii is the main infectious cause of human posterior retinochoroiditis, the most frequent clinical manifestation of congenital toxoplasmosis. This investigation was performed after neonatal screening to identify biomarkers of immunity associated with immunopathological features of the disease by flow cytometry. The study included infected infants without NRL and with retinochoroidal lesions (ARL, ACRL, and CRL) as well as noninfected individuals (NI). Our data demonstrated that leukocytosis, with increased monocytes and lymphocytes, was a relevant hematological biomarker of ARL. Immunophenotypic analysis also revealed expansion of CD14+CD16+HLA-DRhigh monocytes and CD56dim cytotoxic NK-cells in ARL. Moreover, augmented TCRγ δ + and CD8+ T-cell counts were apparently good biomarkers of morbidity. Biomarker network analysis revealed that complex and intricated networks underscored the negative correlation of monocytes with NK- and B-cells in NRL. The remarkable lack of connections involving B-cells and a relevant shift of NK-cell connections from B-cells toward T-cells observed in ARL were outstanding. A tightly connected biomarker network was observed in CRL, with relevant connections of NK- and CD8+ T-cells with a broad range of cell subsets. Our findings add novel elements to the current knowledge on the innate and adaptive immune responses in congenital toxoplasmosis.