Alberto Jorge Betinjane

Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil.

PurposeAxenfeld-Rieger syndrome is a genetically heterogenous, autosomal dominant disorder that is characterized by anterior segment defects, glaucoma, and extraocular anomalies. This study examined the two genes known to cause Rieger syndrome, PITX2 and FOXC1, for mutations in five Brazilian families with Axenfeld-Rieger syndrome. MethodsFive families with a total of 23 persons affected by Axenfeld-Rieger syndrome were recruited for this study. A sequencing-based mutation screen was undertaken for the PITX2 and FOXC1 genes. Linkage analysis was used to study one large family for which no mutations were detected in the PITX2 or FOXC1 genes. ResultsTwo of the five families harbored mutations in the PITX2 gene, but none of the families had a detectable FOXC1 mutation. Haplotypic analysis of three Rieger syndrome regions in a large family with Axenfeld-Rieger syndrome excluded linkage to the 4q25 (PITX2), 6p25 (FOXC1), and 13q14 (RIEG2) regions. ConclusionsIt appears that the PITX2 gene is responsible for a significant portion of Axenfeld-Rieger syndrome in the Brazilian population. Furthermore, there is also evidence for the presence of genetic heterogeneity of the disorder within the Brazilian population. Finally, a large family with Axenfeld-Rieger syndrome has been identified that does not appear to harbor any of the three known loci. Axenfeld-Rieger syndrome gene segregation in this family likely represents a novel locus.

Visual impairment secondary to congenital glaucoma in children: visual responses, optical correction and use of low vision AIDS

INTRODUCTION Congenital glaucoma is frequently associated with visual impairment due to optic nerve damage, corneal opacities, cataracts and amblyopia. Poor vision in childhood is related to global developmental problems, and referral to vision habilitation/rehabilitation services should be without delay to promote efficient management of the impaired vision. OBJECTIVE To analyze data concerning visual response, the use of optical correction and prescribed low vision aids in a population of children with congenital glaucoma. METHOD The authors analyzed data from 100 children with congenital glaucoma to assess best corrected visual acuity, prescribed optical correction and low vision aids. RESULTS Fifty-five percent of the sample were male, 43% female. The mean age was 6.3 years. Two percent presented normal visual acuity levels, 29% mild visual impairment, 28% moderate visual impairment, 15% severe visual impairment, 11% profound visual impairment, and 15% near blindness. Sixty-eight percent received optical correction for refractive errors. Optical low vision aids were adopted for distance vision in 34% of the patients and for near vision in 6%. A manual monocular telescopic system with 2.8 × magnification was the most frequently prescribed low vision aid for distance, and for near vision a +38 diopter illuminated stand magnifier was most frequently prescribed. DISCUSSION AND CONCLUSION Careful low vision assessment and the appropriate prescription of optical corrections and low vision aids are mandatory in children with congenital glaucoma, since this will assist their global development, improving efficiency in daily life activities and promoting social and educational inclusion.

Color Doppler imaging of the superior ophthalmic vein in different clinical forms of Graves’ orbitopathy

PurposeTo compare color Doppler imaging (CDI) parameters of the superior ophthalmic vein (SOV) in patients with Graves’ orbitopathy (GO) and in normal controls.MethodsForty-three GO patients and 14 normal controls underwent CDI of the SOV. Patients had either fibrotic (lipogenic or myogenic) or congestive orbitopathy. The findings for each group were compared.ResultsFifty-eight orbits with fibrotic orbitopathy, 28 with congestive orbitopathy, and 28 from controls, were studied. In the congestive group, SOV flow was detected in 13, undetectable in 11, and reversed in four orbits; in the fibrotic group, it was present in 41 and undetectable in 17 orbits. In normal controls, SOV flow was detected in 25 and undetectable in three orbits. The differences among the three groups were significant. There was also a significant difference between controls and the congestive GO orbits but not between the fibrotic group and the other two groups. Fibrotic myogenic orbitopathy patients displayed a significantly smaller SOV flow than patients with lipogenic orbitopathy.ConclusionsSOV was significantly reduced in orbits with congestive GO or with myogenic fibrotic GO, but not in orbits with fibrotic lipogenic orbitopathy. SOV congestion may be a contributing pathogenic factor in both congestive and fibrotic myogenic Graves’ orbitopathy.

Genotype-Phenotype Correlations in CYP1B1-Associated Primary Congenital Glaucoma Patients Representing Two Large Cohorts from India and Brazil.

Background Primary congenital glaucoma (PCG), occurs due to the developmental defects in the trabecular meshwork and anterior chamber angle in children. PCG exhibits genetic heterogeneity and the CYP1B1 gene has been widely implicated worldwide. Despite the diverse mutation spectra, the clinical implications of these mutations are yet unclear. The present study attempted to delineate the clinical profile of PCG in the background of CYP1B1 mutations from a large cohort of 901 subjects from India (n=601) and Brazil (n=300). Methods Genotype-phenotype correlations was undertaken on clinically well characterized PCG cases from India (n=301) and Brazil (n=150) to assess the contributions of CYP1B1 mutation on a set of demographic and clinical parameters. The demographic (gender, and history of consanguinity) and quantitative clinical (presenting intraocular pressure [IOP] and corneal diameter [CD]) parameters were considered as binary and continuous variables, respectively, for PCG patients in the background of the overall mutation spectra and also with respect to the prevalent mutations in India (R368H) and Brazil (4340delG). All these variables were fitted in a multivariate logistic regression model using the Akaike Information Criterion (AIC) to estimate the adjusted odds ratio (OR) using the R software (version 2.14.1). Results The overall mutation spectrum were similar across the Indian and Brazilian PCG cases, despite significantly higher number of homozygous mutations in the former (p=0.024) and compound heterozygous mutations in the later (p=0.012). A wide allelic heterogeneity was observed and only 6 mutations were infrequently shared between these two populations. The adjusted ORs for the binary (demographic) and continuous (clinical) variables did not indicate any susceptibility to the observed mutations (p>0.05). Conclusions The present study demonstrated a lack of genotype-phenotype correlation of the demographic and clinical traits to CYP1B1 mutations in PCG at presentation. However, the susceptibility of these mutations to the long-term progression of these traits are yet to be deciphered.

Correlations between different tonometries and ocular biometric parameters in patients with primary congenital glaucoma

PURPOSE To identify the correlation between the difference of intraocular pressure measurements (IOP) obtained using the Goldmann applanation tonometer (GAT) and three others tonometers (Handheld applanation tonometer - HAT, Dynamic contour tonometer - DCT and Tono-Pen®) with biometric characteristics (corneal diameter, pachymetry, keratometry and axial length) in patients with congenital glaucoma. METHODS A cross-sectional study was performed on 46 eyes from 46 patients with congenital glaucoma. IOP measurements were obtained in all patients using GAT, HAT, DCT and Tono-Pen®. Keratometry, pachymetry, biometry and corneal diameter measurements were performed after the IOP measurement. The order of the tonometries was randomized. The correlations between the differences of IOP values of GAT and the other tonometers (Delta-IOP), and the different biometric parameters were studied. RESULTS Tono-Pen® Delta IOP revealed moderate positive correlation to keratometry (r=0.41, p=0.004). The other Delta-IOPs showed no correlation with any of the biometric characteristics evaluated. CONCLUSIONS IOP differences between GAT (gold standard) and GAT, HAT, DCT or Tono-Pen tonometers seem not to correlate with majority of ocular biometric characteristics. The only exception was the keratometry, which correlated in a positive and moderate way with Tono-Pen® Delta-IOP. This result suggests that the differences of IOP values of Tono-Pen® and GAT increase with the steepness of the cornea.

Perimetria automatizada em pacientes com glaucoma congênito primário

PURPOSE: To identify and characterize defects using the automated perimetry test in patients with primary congenital glaucoma. METHODS: Automated visual fields and charts of 81 eyes (48 patients) with congenital glaucoma were retrospectively analyzed, 15 being normal eyes (group N) and 66 eyes with primary congenital glaucoma (group G). Eyes of group G were grouped in eyes without perimetric changes and with early defects, characterized by MD> -6 dB (group G I= 41 eyes), and eyes with mild/advanced perimetric defects characterized by MD < -6 dB (group G II= 25 eyes). Main outcome measures: reliability indices, global indices, GHT report, foveal threshold index and descriptive visual field defects. RESULTS: The majority of patients showed good reliability. In group G I, 68% had normal visual fields; 22% showed localized defects and 10% showed general reduction of sensitivity. In group G II, 56% of the visual fields showed general reduction of sensitivity and 44% showed localized defects. The most common localized change was inferior paracentral scotoma. Eyes with normal visual fields in group G I had foveal threshold and MD values lower than normal eyes. The hemifield test was normal in 68% of eyes in group G I, and was abnormal in 100% of eyes in group G II. CONCLUSIONS: Automated perimetry test was able to show typical defects of glaucoma contributing to initial evaluation and giving reliable parameters for the follow-up of eyes in patients with congenital glaucoma.

Ultrasonographic findings in patients examined in cataract detection-andtreatment campaigns: a retrospective study

INTRODUCTION: A cataract is defined as an opacity of any portion of the lens, regardless of visual acuity. In some advanced cases of cataracts, in which good fundus visualization is not possible, an ultrasound examination provides better assessment of the posterior segment of the globe. OBJECTIVES: This study aims to evaluate the ultrasonographic records of patients with advanced cataracts who were examined during cataract campaigns. METHODS: The ultrasonographic findings obtained from 215 patients examined in cataract campaigns conducted by the Hospital das Clínicas Department of Ophthalmology of the Faculdade de Medicina da Universidade de São Paulo between the years of 2005 and 2007 were evaluated, and the utility of this exam in changing the treatment procedures was studied. RESULTS: A total of 289 eyes from 215 patients were examined. Of the eyes examined, 77.5% presented with findings in the vitreous cavity and the posterior pole. A posterior vitreous detachment with no other complications was observed in 47.4% of the eyes. The remaining 30.1% presented with eye diseases that could result in a reduced visual function after surgery. The most frequent eye diseases observed were diffuse vitreous opacity (12.1% of the eyes) and detachment of the retina (9.3% of the eyes). DISCUSSION: In many cases, the ultrasonographic evaluation of the posterior segment revealed significant anomalies that changed the original treatment plan or contra-indicated surgery. At the very least, the evaluation was useful for patient counseling. CONCLUSION: The ultrasonographic examination revealed and differentiated between eyes with cataracts and eyes with ocular abnormalities other than cataracts as the cause of poor vision, thereby indicating the importance of its use during ocular evaluation.

Ultrasonographic Echometry in the Control of Congenital Glaucoma

Ocular echometry is of greatest clinical significance in children, in whom the most significant changes in the dimensions of the different ocular structures occur. Ocular echometry, therefore, has particular value in the diagnosis and assessment of surgical therapy effectiveness in congenital glaucoma. In spite of the essential significance of tonometry by applanation in the clinical study of the disease, echometry allows for invaluable information as to the magnitude of the pathologic effects induced by an abnormal intraocular pressure in a given time interval. Echometry, therefore, can provide an assessment of the dynamics and magnitude of ocular changes caused by an anomalous intraocular pressure in eyes with congenital glaucoma.

Estudo comparativo entre imagens ultra-sonográficas obtidas com sondas de 10MHz e 20 MHz na avaliação de anormalidades do segmento posterior do globo ocular

The ultrasound is an important method in the evaluation of abnormalities of the posterior segment of the eye. PURPOSE: To compare the advantages and disadvantages of 10 and 20 MHz probe on B- scanning ultra-sonography in evaluation of vitreous and posterior pole diseases, providing recommendations for their use. METHODS: Patients from Hospital das Clinicas of the University of Sao Paulo (HC-FMUSP), attended between February 2006 and April 2007, were submitted to ultrasound exams using CINE-Scan® (Quantel Medical Inc) B-scan with 10 and 20MHz probe. The patients were examined by three experienced ophthalmologists, in horizontal dorsal position, after instillation of tetracaine 1% drops, first with the probe in direct contact with eyelids, and then with the probe placed directly in contact with the sclera or cornea. Theimages obtained were compared immediately during and after the examination. RESULTS: The 20 MHz probe reveled a superior resolution to study details, like shape and limits, on the posterior pole, and the 10 MHz probe provided better evaluation on vitreous humor. There were no differences if the exam was performed on eyelids or directly on sclera with the 10 MHz probe, but with the 20 MHz probe, the images had better resolution when the probe was used in direct contact with the eye. CONCLUSIONS: The 10 and 20 probes have different ideal range of reach, as different better specific means of image achieving.

Results of Goniotomy and Trabeculotomy as the Initial Surgical Procedure in the Treatment of Congential Glaucoma

Since 1968, we have been studying patients with congenital glaucoma according to the classification of gonioscopic features proposed by BUSACCA and CARVALHO (1, 2). Three gonioscopic pictures have been considered: persistence, metaplasia, and aplasia of the reticular system of the pectinate ligament, depending on the intensity of the dysplasic process.