Long-term outcomes of intraoperative triamcinolone injection versus postoperative oral prednisolone in congenital cataract surgery / Resultados de longo prazo do uso intraoperatório de triancinolona versus oral pós-operatório de prednisolona na cirurgia de catarata congênita

ABSTRACT Purpose: To compare the long-term ocular findings of children that were operated of congenital cataract before the age of two and that received an intraoperative intracameral triamcinolone injection or used postoperative oral prednisolone to modulate ocular inflammation. Methods: All patients who had previously participated in a clinical trial that analyzed the 1-year surgical outcomes of congenital cataract surgery utilizing intracameral triamcinolone (study group) or oral prednisolone (control group) were eligible to participate in this prospective cohort research. Patients' medical records were reviewed, and the children underwent a complete ophthalmologic exam on final follow-up. Biomicroscopic findings, intraocular pressure, central corneal thickness, the need for additional surgical interventions, and findings compatible with glaucoma were the primary end measures. Results: Twenty-six eyes (26 patients) were included (study group = 11 eyes; control group = 15 eyes). The mean follow--up was 8.2 ± 1.2 years and 8.1 ± 1.7 years in the study and control groups, respectively (p=0.82). All eyes presented a centered intraocular lens. There was no statistically significant difference between the groups with regards to the presence of posterior synechia (p=0.56), intraocular pressure (p=0.49), or central corneal thickness (p=0.21). None of the eyes fulfilled the glaucoma diagnostic criteria, presented secondary visual axis obscuration, or were reoperated. Conclusion: The long--term ocular findings of children that underwent congenital cataract surgery and received an intraoperative intracameral triamcinolone injection were similar to those that used postoperative oral prednisolone to modulate ocular inflammation. This suggests that intracameral triamcinolone may substitute oral prednisolone in congenital cataract surgery, facilitating the postoperative treatment regimen and compliance.

RESUMO Objetivo: Comparar os achados oculares em longo prazo de crianças que se submeteram à cirurgia de catarata congênita antes dos dois anos de idade e receberam uma injeção intracameral de triancinolona no intraoperatório ou usaram prednisolona oral no pós-operatório para modular a inflamação ocular. Métodos: Neste estudo prospectivo de coorte, todos os pacientes que participaram de um ensaio clínico anterior, que analisou os resultados cirúrgicos de 1 ano da cirurgia de catarata congênita usando triancinolona intracameral (Grupo de Estudo) ou prednisolona oral (Grupo Controle), eram elegíveis para participar. Os prontuários médicos dos pacientes foram revisados e as crianças foram submetidas a um exame oftalmológico completo no acompanhamento final. As principais medidas de desfecho foram: achados biomicroscópicos, pressão intraocular, espessura central da córnea, a necessidade de intervenções cirúrgicas adicionais e achados compatíveis com glaucoma. Resultados: Vinte e seis olhos (26 pacientes) foram incluídos (Grupo de Estudo = 11 olhos; Grupo de Controle = 15 olhos). O seguimento médio foi de 8,2 ± 1,2 anos e 8,1 ± 1,7 anos nos Grupos de Estudo e Controle, respectivamente (p=0,82). Todos os olhos apresentavam lente intraocular centrada. Não houve diferença estatisticamente significativa entre os grupos com relação à presença de sinéquia posterior (p=0,56), pressão intraocular (p=0,49) ou espessura central da córnea (p=0,21). Nenhum dos olhos preencheu os critérios diagnósticos para glaucoma, apresentou opacificação secundária do eixo visual ou foi reoperado. Conclusão: Os achados oculares em longo prazo de crianças que se submeteram à cirurgia de catarata congênita e receberam uma injeção intracameral de triancinolona no intraoperatório foram semelhantes aos que usaram prednisolona oral no pós-operatório para modular a inflamação ocular, sugerindo que a triancinolona intracameral pode substituir a prednisolona oral na cirurgia de catarata congênita, facilitando o tratamento pós-operatório e a adesão ao mesmo.

Response to correction of refractive errors and hypoaccommodation in children with congenital Zika syndrome.

PURPOSE: To describe the immediate response to correction of refractive errors and hypoaccommodation in children with congenital Zika syndrome (CZS). METHODS: Children born between May and December 2015 with a confirmed diagnosis of CZS and enrolled in a multidisciplinary early intervention program were included in this study. All children received a comprehensive ophthalmic examination, including dynamic retinoscopy and cycloplegic refraction. Children were prescribed their full correction if they met the criteria for refractive error, and additional plus 3.00 overcorrection for strabismus, accommodative dysfunction, and/or low vision. Monocular and binocular visual responses to Lea Grating Test at 30 cm, with and without eyeglasses, were measured on day 1 of glasses wear. RESULTS: A total of 60 children were evaluated (mean age at evaluation, 11.5 ± 1.1 months; range, 9.0-16.0 months). Lea Grating Test responses were abnormal in all children prior to spectacle correction. Hypoaccommodation was present in 17 of 21 children (81%). Overcorrection was prescribed for all children. Visual responses were subnormal even with glasses use; however, immediate improvement in binocular vision was found in 37 children (62%) and in 74 of 119 eyes (62.2%). For the monocular visual improvement, 27 of 115 eyes (23.5%) had structural abnormalities, and 44 of 115 eyes (38.3%) were structurally normal. There was a statistical difference between the cycloplegic refraction of the children in August and in November, including emmetropia (P = 0.001), hyperopia (P = 0.000), myopia (P = 0.007), and astigmatism (P = 0.004). CONCLUSIONS: Eyeglasses can improve visual acuity in children with CZS. Significant changes in their refractive status over time requires periodic updates.

Complex regulation of Hsf1-Skn7 activities by the catalytic subunits of PKA in Saccharomyces cerevisiae: experimental and computational evidences.

BACKGROUND: The cAMP-dependent protein kinase regulatory network (PKA-RN) regulates metabolism, memory, learning, development, and response to stress. Previous models of this network considered the catalytic subunits (CS) as a single entity, overlooking their functional individualities. Furthermore, PKA-RN dynamics are often measured through cAMP levels in nutrient-depleted cells shortly after being fed with glucose, dismissing downstream physiological processes. RESULTS: Here we show that temperature stress, along with deletion of PKA-RN genes, significantly affected HSE-dependent gene expression and the dynamics of the PKA-RN in cells growing in exponential phase. Our genetic analysis revealed complex regulatory interactions between the CS that influenced the inhibition of Hsf1/Skn7 transcription factors. Accordingly, we found new roles in growth control and stress response for Hsf1/Skn7 when PKA activity was low (cdc25Δ cells). Experimental results were used to propose an interaction scheme for the PKA-RN and to build an extension of a classic synchronous discrete modeling framework. Our computational model reproduced the experimental data and predicted complex interactions between the CS and the existence of a repressor of Hsf1/Skn7 that is activated by the CS. Additional genetic analysis identified Ssa1 and Ssa2 chaperones as such repressors. Further modeling of the new data foresaw a third repressor of Hsf1/Skn7, active only in the absence of Tpk2. By averaging the network state over all its attractors, a good quantitative agreement between computational and experimental results was obtained, as the averages reflected more accurately the population measurements. CONCLUSIONS: The assumption of PKA being one molecular entity has hindered the study of a wide range of behaviors. Additionally, the dynamics of HSE-dependent gene expression cannot be simulated accurately by considering the activity of single PKA-RN components (i.e., cAMP, individual CS, Bcy1, etc.). We show that the differential roles of the CS are essential to understand the dynamics of the PKA-RN and its targets. Our systems level approach, which combined experimental results with theoretical modeling, unveils the relevance of the interaction scheme for the CS and offers quantitative predictions for several scenarios (WT vs. mutants in PKA-RN genes and growth at optimal temperature vs. heat shock).