Maria Cristina Martins

An Unusually High Prevalence of Ocular Toxoplasmosis in Southern Brazil

Because of the frequency of ocular toxoplasmosis and its occurrence in multiple siblings in southern Brazil, a population-based household survey was performed to better understand the epidemiologic characteristics of the disease in this region. Of 1,042 individuals examined, 184 (17.7%) were deemed to have ocular toxoplasmosis on the basis of conservative assessment of ophthalmic findings. Of those with ocular toxoplasmosis, 183 (99.5%) had specific IgG antibodies, compared with only 140 of 181 age-matched control subjects (77.4%; P less than .001). The prevalence of ocular toxoplasmosis was 0.9% in 1- to 8-year-olds, 4.3% in 9- to 12-year-olds, 14.3% in 13- to 16-year-olds, and 21.3% (95% confidence interval, 18.6% to 24.2%) in all individuals 13 years or older. The prevalence of ocular toxoplasmosis in this population was more than 30 times higher than previous estimates for the same condition elsewhere. The low prevalence in the young children we studied supplements previous data suggesting that, in this population, ocular toxoplasmosis is a sequela of postnatal rather than congenital infection.

A follow-up study of Toxoplasma gondii infection in southern Brazil ☆

PURPOSE To understand better the natural history of ocular toxoplasmosis by reexamining a well-characterized population in Southern Brazil. METHODS Ophthalmological examination and serologic tests for Toxoplasma gondii infection were performed in 1997 on 383 individuals who had undergone the same evaluation in 1990. RESULTS Of 109 seronegative subjects in 1990, 21 (19.3%) became seropositive by 1997, and 2 (1.5% of previously seronegative patients; 9.5% of those known to have seroconverted) developed ocular toxoplasmosis. Seroconversion occurred more frequently in individuals under 17 years of age (16 of 46 patients, 34.8%) than in those greater than 17 years of age (5 of 63 patients, 7.9%; p = 0.002). Of 131 seropositive individuals who did not have ocular lesions in 1990, 11 (8.3%) had typical toxoplasmic lesions in 1997. Of the 13 individuals with non-specific hyperpigmented small retinal lesions in 1990, 3 (23%) presented with typical lesions in 1997. CONCLUSIONS Acquired T. gondii infection can result in late development of ocular lesions. Small, non-specific hyperpigmented retinal lesions may represent sites of T. gondii infection in seropositive individuals.

An outbreak of Mycobacterium chelonae infection after LASIK

OBJECTIVE To describe an outbreak of mycobacterial keratitis after laser in situ keratomileusis (LASIK), including the microbiologic investigation, clinical findings, treatment response, and outcome. DESIGN Retrospective, noncomparative, interventional case series. PARTICIPANTS Patients (n = 10) who underwent LASIK surgery between August 22 and September 4, 2000, and developed mycobacterial infection. METHODS Patients were prospectively followed in relation to microbiologic investigation, clinical findings, treatment response, and outcome. MAIN OUTCOME MEASURES Most patients underwent bilateral simultaneous LASIK. Postoperative infection was signaled by the appearance of corneal infiltrates in the third postoperative week. The microbiologic workup was performed on cultures obtained either by direct scraping of the cornea or by lifting the flap. Medical therapy was instituted based on drug susceptibility testing. Surgical interventions such as corneal debridement and flap removal were performed during recurrences or when there was no satisfactory clinical response. RESULTS Cultures revealed Mycobacterium subspecies chelonae. Patients were treated with topical clarithromycin (1%), tobramycin (1.4%), and ofloxacin (0.3%). Oral clarithromycin (500 mg twice a day) was prescribed for those patients who did not respond clinically to topical treatment. Four eyes healed on this regimen. Flap removal was necessary in seven eyes. CONCLUSIONS This report highlights mycobacteria as an etiologic infectious agent after LASIK. Diagnosis can be difficult and is often delayed. The treatment mainstay is prolonged antibiotic therapy. Surgical debridement and flap removal may shorten the disease course.

Long-term results of topical mitomycin C 0.02% for primary and recurrent conjunctival-corneal intraepithelial neoplasia.

Purpose: To evaluate the efficacy, recurrence rate, and long-term complications of topical mitomycin C (MMC) 0.02% for conjunctival-corneal intraepithelial neoplasia (CCIN). Methods: A prospective, nonrandomized, noncontrolled study was conducted of patients with primary or recurrent CCIN treated with topical MMC 0.02%, four times per day, for 28 consecutive days. The main outcome measures were complete resolution of the neoplasia by slit-lamp examination and cytology 1 month after treatment, tumor recurrence, and long-term complications. Results: Between June 1999 and September 2005, 23 patients were included. Eighteen had primary CCIN (group 1) and 5 had recurrent CCIN (group 2). The mean follow-up was 46 months in group 1 and 54 months in group 2. All patients were treated with MMC 0.02% for 28 consecutive days. Complete resolution of the lesion was achieved in all patients after 1 month of treatment. Recurrence occurred in 1 patient (4.3%) after 24 months of treatment. Four patients developed corneal erosion (17.4%), 2 of them with primary CCIN and 2 with recurrent CCIN. Corneal erosion occurred 4 to 24 months after treatment and was treated successfully. The probability for corneal erosions by the log-rank test was equal for both groups (p = 0.1705). Conclusions: The use of topical MMC 0.02% for 28 consecutive days to treat primary or recurrent CCIN was effective and showed a low recurrence rate. Corneal erosion occurred in 17.4% of cases and can occur as late as 24 months after treatment.

Fundus autofluorescence of choroidal nevus and melanoma

Background: To describe autofluorescence patterns of choroidal melanocytic lesions using the Heidelberg Retinal Angiograph 2 system (HRA2). Methods: 20 patients with choroidal melanocytic lesions in the ocular fundus underwent ophthalmologic examination, fundus photography, autofluorescence and optical coherence tomography (OCT). Pathologic examination was performed on one enucleated eye with a large choroidal melanoma. Results: 15 patients had choroidal nevi and 5 had malignant choroidal melanoma (1 small, 1 medium and 3 large tumours). Choroidal nevi did not show any characteristic autofluorescence pattern, although secondary retinal pigment epithelium (RPE) changes, such as drusen and pigment epithelium detachment, appeared faintly hyperautofluorescent in 2 patients. Only the small malignant choroidal melanomas had prominent orange pigmentation, although all melanomas had an intense confluent hyperautofluorescent signal over the lesions. Pathology of one large malignant melanoma revealed lipofuscin underlying RPE. Conclusion: Most nevi did not have characteristic hyperautofluorescent features, but choroidal melanomas seemed to have a pattern of confluent hyperautofluorescence. Therefore, autofluorescence may be a useful non-invasive tool to assess lipofuscin in pigmented choroidal lesions, which may contribute to the diagnosis of malignancy. This hypothesis, however, remains to be confirmed in large prospective studies.

Subretinal bevacizumab detection after intravitreous injection in rabbits.

PURPOSE To evaluate subretinal detection of bevacizumab 2 hours after intravitreous injection of 1.25 mg in rabbit eyes. METHODS Anterior chamber paracentesis using a 30-gauge needle was performed in nine female Dutch-belted rabbits by removal of 0.05 mL of aqueous humor. Transscleral retinal detachment was performed with a modified 25-gauge infusion cannula connected to a bottle of physiologic saline solution (PSS). The animals were divided into experimental group 1, with intravitreous injection of 0.05 mL of (1.25 mg) with a 30-gauge needle (n = 6) and the control group 2, with intravitreous injection of 0.05 mL of PSS with a 30-gauge needle (n = 3). Two hours after the intravitreous bevacizumab or PSS injection, subretinal fluid was aspirated and immunoassayed to measure the level of bevacizumab. The rabbits were killed by intravenous pentobarbital injection. The eyes were enucleated and fixed in 10% formaldehyde. The pars plana site at which the transscleral cannula was introduced was analyzed by light microscopy, to exclude iatrogenic retinal tears. Eyes with accidental retinal tears were excluded. RESULTS Subretinal bevacizumab molecules were detected in the six eyes that received an intravitreous bevacizumab injection. No subretinal bevacizumab was detected in the control eyes. Light microscopy showed no evidence of retinal tears or holes in any rabbits used for the bevacizumab detection and control group. CONCLUSIONS Bevacizumab molecules were detected in the subretinal space after intravitreous injection of 1.25 mg of bevacizumab, possibly as the result of diffusion through the retina in a rabbit model.

Ocular and central nervous system paracoccidioidomycosis in a pregnant woman with acquired immunodeficiency syndrome

PURPOSE To describe an atypical case of central nervous system and ocular paracoccidioidomycoses simulating ocular toxoplasmosis in a pregnant woman with acquired immunodeficiency syndrome (AIDS). DESIGN Interventional case report. METHODS Case report. RESULTS A 25-year-old pregnant woman with AIDS, presented with a severe ocular inflammation in the right eye involving the choroid, retina, and the optic disk, which rapidly progressed to retinal detachment, iris neovascularization, and neovascular glaucoma. The left eye was normal. Magnetic resonance imaging (MRI) showed a focal hypodense contrast-enhanced ring lesion in the brain. Serum antibody titers were negative for Toxoplasma gondii, but the polymerase chain reaction was positive for the parasite in the vitreous sample. The patient responded partially to specific treatment for toxoplasmosis, and there was a small reduction in size of the brain lesion. She progressed to a blind painful eye, which was enucleated. Paracoccidioides brasiliensis was found in the histopathological studies of the eye and oropharynx. With the diagnosis of disseminated ocular paracoccidioidomycoses, the patient was treated with trimethoprim-sulfamethoxazole with a satisfactory outcome and reduction in size of the brain lesion. CONCLUSION Although ocular infection with ocular paracoccidioidomycoses is rare, this diagnosis should be considered when investigating ocular inflammation in a patient with AIDS.

Impaired glucose tolerance plus hyperlipidaemia induced by diet promotes retina microaneurysms in New Zealand rabbits

With the increasing prevalence of diabetes mellitus and metabolic syndrome worldwide, experimental models are required to better understand the pathophysiology and therapeutic approaches to preserve pancreatic beta cells, attenuate atherosclerosis and protect target organs. The aims of this study were to develop an experimental model of impaired glucose tolerance combined with hypercholesterolaemia induced by diet and assess metabolic alterations and target organ lesions. New Zealand male rabbits were fed high‐fat/high‐sucrose (10/40%) and cholesterol‐enriched diet for 24 weeks, when they were sacrificed. Biochemistry, fundus photographs with fluorescein angiography and pathological analyses were performed. Cholesterol‐fed and normal animals of same age were compared. Results: The animals with diet‐induced impaired glucose tolerance combined with hypercholesterolaemia gained weight, increased blood glucose, total cholesterol, LDL‐C and triglycerides and decreased HDL‐C (P < 0.05 vs. baseline). Fructosamine levels and the homeostasis model assessment of insulin resistance (HOMA‐IR) index were increased, while there was a reduction in the HOMA‐β (P < 0.05 for all vs. baseline). Histomorphologic findings of this model were aortic atherosclerosis, hepatic steatofibrosis and glomerular macrophage infiltration. Early clinical features of diabetic retinopathy with hyperfluorescent dots consistent with presence of retina microaneurysms were seen since week 12, progressing up to the end of the experiment (P < 0.0005 vs. baseline and 12 weeks). Our model reproduced several metabolic characteristics of human diabetes mellitus and promoted early signs of retinopathy. This non‐expensive model is suitable for studying mechanistic pathways and allowing novel strategic approaches.

Predictive index to differentiate invasive squamous cell carcinoma from preinvasive ocular surface lesions by impression cytology

Background/aims: In the literature, no cytological features have been identified that reliably differentiate invasive squamous cell carcinoma (SCC) from preinvasive lesions in impression cytology (IC) samples. The aim was to identify cytological features related to malignancy and apply them in a quantitative model to determine an index score with the best predictive power to differentiate SCC from preinvasive ocular surface lesions by IC. Methods: 39 patients with ocular surface epithelial lesions were enrolled. IC was obtained from all lesions before surgical excision. Specimens with atypical cells were evaluated regarding 11 cytological parameters based on the 2001 Bethesda system. Results: Histopathological diagnosis was pterygium in one case, actinic keratosis in nine cases, intraepithelial neoplasia in nine cases and SCC in 20 cases. Analysis of the receiver operating characteristic curve revealed that a predictive index score (cut-off point) ⩾4.25 presented the best relationship between sensitivity and specificity in identifying SCC (sensitivity of 95%, specificity of 93%, positive predictive value of 95% and negative predictive value of 93%). Conclusion: The scoring system model presented is suitable for clinical practice in differentiating SCC from preinvasive ocular surface lesions by IC and can be better evaluated with prospective use.

Ação do sal de cozinha sobre o Toxoplasma gondii

O baixo resultado encontrado por nos no isolamento do Toxoplasma gondii de embutidos de carne de porco procedentes de Erechim (RS) (uma positiva em 40 amostras) levou-nos a pesquisar a acao do sal de cozinha, presente nesses embutidos, sobre taquizoitas e cistos do parasita. Foram obtidos exsudatos peritoneais (taquizoitas) e macerados de cerebros (cistos) de camundongos previamente inoculados com cepas de Toxoplasma gondii isoladas do material de Erechim. A este inoculo foi acrescentado sal de cozinha refinado, comum, nas concentracoes de 2,2%, 2,5% e 3,0% habitualmente usadas no preparo dos embutidos. O tempo de exposicao ao sal foi de 24 e 48 horas, 3-5 e 7 dias, a 4oC, apos o qual, camundongos albinos, machos, foram inoculados, por via intraperitoneal, com 0,5 ml desses inoculos, padronizados quanto ao numero de parasitas. Os resultados mostraram que, nas concentracoes de sal a 2,2%, 2,5% e 3,0% e exposicoes de 24 e 48 horas, todos os camundongos inoculados com taquizoitas mais sal morreram, menos um, provavelmente nao infectado, (um sobrevivente em 28 inoculados). Na concentracao de 3,0% e exposicao durante 3-5 e 7 dias houve 10 sobreviventes em 37 animais inoculados (27%), sendo que com 5 e 7 dias, 7 de 15 camundongos sobreviveram (46,6%). Nos camundongos inoculados com cistos mais sal a 3,0% e exposicoes de 24, 48 e 72 horas, faltam anotacoes dos resultados; com exposicoes de 5 e 7 dias houve 17 sobreviventes e 3 mortos (85%). Camundongos-controles para cada grupo foram inoculados nas mesmas condicoes, porem sem o sal. A morte destes ocorreu em 100%, sempre, mais cedo do que a dos camundongos-testes. O toxoplasma foi recuperado do exsudato peritoneal e do cerebro dos camundongos recem-mortos e moribundos, mas nunca dos sobreviventes. Estes resultados evidenciam a acao inativante do sal de cozinha sobre o Toxoplasma gondii, na concentracao de 3%, durante um minimo de 3 dias e, possivelmente, explicam a raridade do isolamento do parasita nos embutidos de carne de porco salgada do inquerito de Erechim.