Fabio Endo Hirata

Surgery with intraoperative botulinum toxin-A injection for the treatment of large-angle horizontal strabismus: a pilot study

Some patients with large-angle strabismus may refuse or may not meet the criteria for binocular surgical correction. A second option for these patients involves a monocular procedure, which can be performed under peribulbar anesthesia and offers certain advantages (1). Improved surgical outcomes for conventional procedures may enhance the effectiveness of monocular surgery. In theory, this enhancement could be achieved by the coadjuvant use of intraoperative botulinum toxin A (BT) (2). To date, few reports have described the intraoperative injection of BT (3-5). Owens et al. (3) performed supramaximal monocular recession-resection surgeries and successfully used intraoperative BT in three large-angle exotropia patients. Khan (4) successfully performed two-muscle horizontal rectus surgery with simultaneous BT injection in patients with severe large-angle esotropia. Additionally, seven patients underwent bilateral medial rectus recession and bilateral BT injection, and one patient underwent a unilateral recess/resection surgery with medial rectus BT injection. These results indicated that bilateral medial rectus recession with simultaneous BT injection is a safe and effective surgical procedure for patients with severe large-angle esotropia, although more extensive studies are required to confirm these findings. Oskan et al. (5) reported the results of 10 patients with large-angle horizontal deviations (eso- or exotropia) who received BT injections into one recessed muscle and concluded that such treatment may provide greater surgical success compared to conventional horizontal rectus muscle surgeries. The results of these uncontrolled studies have reinforced the hypothesis that long-term realignment of the eyes can be achieved with surgery plus BT administration. However, the effectiveness of the addition of intraoperative BT compared to surgery alone is unclear. In this pilot study, we used a prospective, controlled, and randomized double-blind methodology to examine the effectiveness of BT injection in combination with surgical treatment compared to surgical treatment alone for the correction of large-angle horizontal deviations under local anesthesia.

Association of LOC387715/ARMS2 (rs10490924) Gene Polymorphism with Age-related Macular Degeneration in the Brazilian Population

Abstract Background: An association between LOC387715/ARMS2 (rs10490924) gene polymorphism and AMD has been reported. The aim of this study was to evaluate whether this polymorphism is associated with AMD in a Brazilian cohort. Materials and Methods: In total, 126 unrelated AMD patients (mean age 74.17 ± 7.64) were compared with 86 healthy controls (mean age 71.82 ± 7.12). Study subjects were classified according to the International ARM Epidemiological Study Group definition for early and late-stage AMD. LOC387715/ARMS2 rs10490924 polymorphism was evaluated through polymerase chain reaction and direct sequencing. Results: The T allele frequency was significantly higher in AMD patients than in controls (39.6% compared to 20.3%). The odds ratio (OR) for AMD was 2.05 (95% CI 1.13–3.71) for heterozygotes (TG) and 8.32 (95% CI 2.30–45.99) for homozygotes (TT). Conclusions: These results suggest that there is a contribution of the rs10490924 SNP of the LOC387715/ARMS2 gene to AMD susceptibility in this sample of the Brazilian population.

Incidence of preoperative high blood pressure in cataract surgery among hypertensive and normotensive patients.

Incidence of preoperative rise in blood pressure (BP) in cataract surgery among hypertensive and normotensive patients. Objective: To study the incidence of preoperative rise in BP in cataract surgery among normotensive individuals and hypertensive patients with historic good BP control in a population without other major chronic diseases. Settings: Ophthalmology Service of a University Hospital. Materials and Methods: A prospective study with 822 patients older than 40 years of age, with cataract surgery indication, and without major chronic diseases other than hypertension. The patients were divided in two groups: hypertensive and normotensive. Preoperative data, physical exams and medical adverse events were recorded in an evaluation questionnaire. Results: The sample included 427 normotensive (52%) and 395 hypertensive patients (48%). The two groups had similar proportions of operations that were cancelled and not subsequently rescheduled, 2% (eight patients) in each group. The incidence of preoperative rise in BP was 3.7% in the normotensive group and 10.9% in the hypertensive group (P < 0.001). Conclusion: Hypertensive patients with historic good BP control and without other major co-morbidities present a larger incidence of preoperative rise in BP than normotensive individuals in cataract surgery.

Evaluation of CFH Y402H polymorphism and CFHR3/CFHR1 deletion in age-related macular degeneration patients from Brazil

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide. Considered a multifactorial disease, genetic and environmental factors corroborate for its development. Klein and colleagues mapped AMD to the 1q31 region in 1998 and variant Y420H (rs1061170) in the complement factor H (CFH) gene was the first variant related to AMD in this region. The substitution of tyrosine for histidine contributes to changes in how CFH interacts with heparin and C-reactive protein, affecting complement regulation mediated by the gene. Since its discovery this single nucleotide polymorphism (SNP) has been related to an increased risk for the disease in several populations from different ethnicities around the world. Furthermore, Spencer and co-workers suggested that the CFHR3/CFHR1 deletion leads to the loss of two complement regulators (CFHR1 and CFHR3), increasing regulation mediated by CFH, having a protective effect against AMD development. We aimed at evaluating the contribution of Y402H polymorphism in the CFH gene and CFHR3/CFHR1 deletion in the 1q32 region in relation to AMD’s etiology in a sample of the Brazilian population. A total of 175 subjects diagnosed with AMD (case group) and 165 without (control group) were analyzed. Both patients and control subjects were selected at the Clinical Hospital of the University of Campinas (UNICAMP), Campinas, São Paulo, located in the Southeast of Brazil. This study was approved by the Ethics Committee and all participants signed an informed consent. Details about ophthalmic examination, inclusion and exclusion criteria as well as classification were previously described. The Y402H variant was evaluated through PCR and enzymatic digestion, and the CFHR3/ CFHR1 deletion through PCR as published elsewhere. Statistical analysis was performed using SAS program (Statistical Analysis System, version 9.4, by SAS Institute Inc., 2002–2008, Cary, NC, USA). Chi-square and Fisher’s exact tests were used to compare categorical variables. Kruskal-Wallis and Mann-Whitney tests were used to compare quantitative variables. Univariate and multivariate logistic regression analysis were used to investigate risk factors for AMD. A p-value less than 0.05 was considered statistically significant. Hardy-Weinberg Equilibrium was employed to analyze genotype distribution in case and control groups. Overall, 340 individuals were involved in this study. Out of these, 130 patients (74.29%) had the advanced form of the disease (A) versus 45 patients (25.71%) with non-advanced AMD (NA). Sixty-six patients (37.71%) presented with the dry form and 109 (62.29%) with the wet form of AMD. Mean age was 74.44 ± 8.02 for cases and 71.36 ± 7.10 for controls. In the case group 42% were men against 47% in the control group and 45% were smokers in the case group against 25% in the control group.When the variables gender, smoking and genetic factors were evaluated in relation to the risk of developing AMD, no association was observed for gender and smoking. The C allele of the CFH Y402H SNP was more frequent in the case group than in the control group (47% compared to 31%) (p = .00002, chi-square test) and considered a risk factor for the disease. The genotype distribution was consistent with the Hardy-Weinberg Equilibrium (HWE) in both groups. The frequency of the CFHR3/CFHR1 deletion was higher in the control group (8.5%) than in the case group (1.7%) (p = .0097), suggesting a protective role against the disease. All possible combination of genotypes and respective odds ratios (OR) are depicted in Table 1. After stratifying AMD according to its subtypes, results were also significantly different between “wet vs. controls” (p = .0004) and “dry vs. controls” (p = .0004) for the CFH genotypes and allele frequency (p < .001). The highest OR was achieved for CC versus TT genotypes when comparing “wet versus controls.” Evaluating the role of the CFHR3/CFHR1 deletion in relation to AMD type, the risk for the absence of the deletion was higher in the wet type group compared to the control group (p = .0423). After the evaluation of theCFH genotypes in relation to the form of the disease results show that the CC genotype is significantly associated with both A and NA forms when compared to the control group, with the highest OR for the advanced form (p < .0001). Evaluating the role of the CFHR3/CFHR1 deletion in relation to AMD form, the presence of the deletion was not statistically different between groups. After the multivariate regression analysis only the CFH category CC/TC versus TT sustained the significance for all comparisons (Table 2).

Assessment of the effect of intravitreal triamcinolone acetonide on the chorioretinal and vitreous inflammatory reaction to cryotherapy in rabbits

PURPOSE: To evaluate the inflammatory response in the choroid, retina and vitreous in rabbit eyes underwent cryotherapy followed by intravitreal triamcinolone acetonide and to compare with those underwent cryotherapy followed by intravitreal injection of saline solution. METHODS: This is a prospective case-control study. Surgical procedures were performed in eleven rabbits. Two animals were excluded because they did not complete the postoperative period or had intraoperative or postoperative complications. All rabbits underwent superior temporal peritomy and transscleralcryotherapy in both eyes. After cryotherapy, animals received intravitreal injection of triamcinolone acetonide in one eye and saline solution in the fellow eye. Animals were sacrificed seven days after the procedure and their eyes were enucleated. Histological sections of eyeballs were prepared and the vitreous humor was aspirated. The count of inflammatory cells was performed by light microscopy. RESULTS: Histological sections of both eyes of nine rabbits were analyzed. Inflammatory cells were found only in the choroid. There was no statistically significant difference in the number of inflammatory cells between the two groups, regardless of cell type analyzed. CONCLUSION: This study showed no statistically significant difference between the use or absence of intravitreal triamcinolone acetonide in the inflammatory response to cryotherapy in rabbit eyes. Studies with larger samples are needed to confirm the trend of this paper.

Ocular findings in Brazilian identical twins with Cohen syndrome: case report

A case of identical male twins with Cohen syndrome who present multiple ophthalmic findings is reported. The patients were identical 16 year-old twin boys who showed down slanting eyelids, mild ptosis, high-grade myopia, small cortical lens opacities, posterior subcapsular cataracts, myotic and corectopic pupils with poor dilation due to focal iris atrophy and retinochoroidal dystrophy. Ophthalmologists must be aware of the ocular and systemic findings of Cohen syndrome in the evaluation of young patients with mental retardation and visual impairment.

Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients

ABSTRACT Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case–control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value < 1e–07), representing a 2.369-fold higher risk factor for the disease. Both the AA and AG genotypes were observed more frequently in the age-related macular degeneration group compared to the control group (p = 1.21e–07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.