ANDRE AUGUSTO MIRANDA TORRICELLI
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/33 - Laboratório de Oftalmologia, Hospital das Clínicas, Faculdade de Medicina
LIM/33 - Laboratório de Oftalmologia, Hospital das Clínicas, Faculdade de Medicina
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article 39 Citação(ões) na Scopus Screening of Refractive Surgery Candidates for LASIK and PRK(2014) TORRICELLI, Andre A. M.; BECHARA, Samir J.; WILSON, Steven E.Purpose: The aim of this study was to evaluate exclusion criteria in screening patients for refractive surgery. Methods: Patients screened for initial refractive surgery by a single surgeon at the Cole Eye Institute (Cleveland Clinic) between 2007 and 2012 were reviewed. Exclusion criteria for patients who were not offered refractive surgery based on history and/or examination parameters were analyzed. Results: A total of 1067 refractive candidates were enrolled in the study. Five hundred nineteen (48.6%) were male and 548 (51.4%) were female with a mean age of 39 +/- 12 (range, 17-78) years. Refractive surgery was performed in 657 (61.6%) patients, and photorefractive keratectomy was considered the best option for 106 (9.9%) patients. Four hundred ten (38.4%) of all screened patients did not have refractive surgery, and 134 of these patients (12.6%) were considered to have contraindications for laser in situ keratomileusis and photorefractive keratectomy. Among the excluded patients, 69 (51.5%) were male and 65 (48.5%) were female with a mean age of 40 +/- 14 (range, 18-78) years. Abnormal corneal topography (34.3%) and low or insufficient corneal thickness (23.1%) were the most common reasons for exclusion. High myopia (10.5%) and (insipient or definite) cataract (9.7%) were also common reasons for exclusion. Other common factors for exclusion were high hyperopia (3.7%), need to wear reading glasses after surgery (3.7%), and severe dry eye unresponsive to treatment (3.7%). Conclusions: Abnormal corneal topography and low, or insufficient, corneal thickness remain the most common exclusion factors for corneal refractive surgery. Factors such as cataract, too high of correction, and severe dry eye are also common reasons for exclusion of patients.- Femtosecond Laser-Assisted LASIK Flap Complications(2016) SANTOS, Allisson Mario dos; TORRICELLI, Andre A. M.; MARINO, Gustavo K.; GARCIA, Renato; NETTO, Marcelo V.; BECHARA, Samir J.; WILSON, Steven E.PURPOSE: To discuss intraoperative and postoperative femtosecond laser-assisted LASIK flap complications and their management. METHODS: Review of published literature. RESULTS: Flap creation is a critical step in LASIK. The femtosecond laser has improved the overall predictability and safety of the lamellar incision, but complications can still occur during or after flap creation. Although many complications (eg, epithelial ingrowth and flap striae) were reduced with the femtosecond laser application, other specific complications have emerged, such as vertical gas breakthrough, opaque bubble layer, and transient light-sensitivity syndrome. CONCLUSIONS: The application of femtosecond laser technology to LASIK flap creation has increased greatly since its introduction. These lasers have improved the safety and predictability of the lamellar incision step. The majority of the femtosecond laser-assisted flap complications can be well managed without significant effects on refractive outcomes.
- Injury and and defective regeneration of the epithelial basement membrane in corneal fibrosis: A paradigm for fibrosis in other organs?(2017) WILSON, Steven E.; MARINO, Gustavo K.; TORRICELLI, Andre A. M.; MEDEIROS, Carla S.Myofibroblast-mediated fibrosis is important in the pathophysiology of diseases in most organs. The cornea, the transparent anterior wall of the eye that functions to focus light on the retina, is commonly affected by fibrosis and provides an optimal model due to its simplicity and accessibility. Severe injuries to the cornea, including infection, surgery, and trauma, may trigger the development of myofibroblasts and fibrosis in the normally transparent connective tissue stroma. Ultrastructural studies have demonstrated that defective epithelial basement membrane (EBM) regeneration after injury underlies the development of myofibroblasts from both bone marrow- and keratocyte-derived precursor cells in the cornea. Defective EBM permits epithelium-derived transforming growth factor beta, platelet-derived growth factor, and likely other modulators, to penetrate the stroma at sustained levels necessary to drive the development of vimentin + alpha-smooth muscle actin+ desmin+ (V+A+D+) mature myofibroblasts and promote their persistence. Defective versus normal EBM regeneration likely relates to the severity of the stromal injury and a resulting decrease in fibroblasts (keratocytes) and their contribution of EBM components, including laminin alpha-3 and nidogen-2. Corneal fibrosis may resolve over a period of months to years if the inciting injury is eliminated through keratocyte-facilitated regeneration of normal EBM, ensuing apoptosis of myofibroblasts, and reorganization of disordered extracellular matrix by repopulating keratocytes. We hypothesize the corneal model of fibrosis associated with defective BM regeneration and myofibroblast development after epithelial or parenchymal injury may be a paradigm for the development of fibrosis in other organs where chronic injury or defective BM underlies the pathophysiology of disease.
- Dry eye(2018) TORRICELLI, A. A.; RAMOS-ESTEBAN, J. C.; WILSON, S. E.Dry eye is the most common early and late postoperative complication after LASIK surgery. LASIK-induced dry eye is caused by a combination of decreased corneal innervation and chronic ocular inflammation. LASIK-induced dry eye is manifested clinically by the presence of fluctuation of visual acuity and punctate epithelial erosions but minimally decreased average tear production. LINE is the preferred term to describe this condition when it occurs after LASIK or LASIK enhancements in an eye with no symptoms or signs of dry eye prior to surgery. Some eyes likely have both LINE and underlying inflammatory dry eye disease. Optimization of the ocular surface is an important step to improving patient satisfaction after LASIK surgery. © Springer International Publishing AG 2018. All rights reserved.
- Regeneration of Defective Epithelial Basement Membrane and Restoration of Corneal Transparency After Photorefractive Keratectomy(2017) MARINO, Gustavo K.; SANTHIAGO, Marcony R.; SANTHANAM, Abirami; TORRICELLI, Andre A. M.; WILSON, Steven E.PURPOSE: To study regeneration of the normal ultrastructure of the epithelial basement membrane (EBM) in rabbit corneas that had -9.00 D photorefractive keratectomy (PRK) and developed late haze (fibrosis) with restoration of transparency over 1 to 4 months after surgery and in corneas that had incisional wounds. METHODS: Twenty-four rabbits had one of their eyes included in one of the two procedure groups (-9.00 D PRK or nearly full-thickness incisional wounds), whereas the opposite eyes served as the unwounded control group. All corneas were evaluated with slit-lamp photographs, transmission electron microscopy, and immunohistochemistry for the myofibroblast marker alpha-smooth muscle actin and collagen type III. RESULTS: In the -9.00 D PRK group, corneas at 1 month after surgery had dense corneal haze and no evidence of regenerated EBM ultrastructure. However, by 2 months after surgery small areas of stromal clearing began to appear within the confluent opacity (lacunae), and these corresponded to small islands of normally regenerated EBM detected within a larger area of the excimer laser-ablated zone with no evidence of normal EBM. By 4 months after surgery, the EBM was fully regenerated and the corneal transparency was completely restored in the ablated zone. In the incisional wound group, the two dense, linear corneal opacities were observed at 1 month after surgery and progressively faded by 2 and 3 months after surgery. The EBM ultrastructure was fully regenerated at the site of the incisions, including around epithelial plugs that extended into the stroma, by 1 month after surgery in all eyes. CONCLUSIONS: In the rabbit model, spontaneous resolution of corneal fibrosis (haze) after high correction PRK is triggered by regeneration of EBM with normal ultrastructure in the excimer laser-ablated zone. Conversely, incisional wounds heal in rabbit corneas without the development of myofibroblasts because the EBM regenerates normally by 1 month after surgery.
- The corneal fibrosis response to epithelial-stromal injury(2016) TORRICELLI, Andre A. M.; SANTHANAM, Abirami; WU, Jiahui; SINGH, Vivek; WILSON, Steven E.The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+alpha-smooth muscle actin+ desmin+ myofibroblasts. Myofibroblasts are specialized fibroblastic cells generated in the cornea from keratocyte-derived or bone marrow-derived precursor cells. The disorganized extracellular matrix components secreted by myofibroblasts, in addition to decreased expression of corneal crystallins in these cells, are central biological processes that result in corneal stromal fibrosis associated with opacity or ""haze"". Several factors are associated with myofibroblast generation and haze development after PRK surgery in rabbits, a reproducible model of scarring, including the amount of tissue ablated, which may relate to the extent of keratocyte apoptosis in the early response to injury, irregularity of stromal surface after surgery, and changes in corneal stromal proteoglycans, but normal regeneration of the epithelial basement membrane (EBM) appears to be a critical factor determining whether a cornea heals with relative transparency or vision-limiting stromal opacity. Structural and functional abnormalities of the regenerated EBM facilitate prolonged entry of epithelium-derived growth factors such as transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF) into the stroma that both drive development of mature myofibroblasts from precursor cells and lead to persistence of the cells in the anterior stroma. A major discovery that has contributed to our understanding of haze development is that keratocytes and corneal fibroblasts produce critical EBM components, such as nidogen-1, nidogen-2 and perlecan, that are essential for complete regeneration of a normal EBM once laminin secreted by epithelial cells self-polymerizes into a nascent EBM. Mature myofibroblasts that become established in the anterior stroma are a barrier to keratocyte/corneal fibroblast contributions to the nascent EBM. These myofibroblasts, and the opacity they produce, often persist for months or years after the injury. Transparency is subsequently restored when the EBM is completely regenerated, myofibroblasts are deprived of TGF beta and undergo apoptosis, and the keratocytes re-occupy the anterior stroma and reabsorb disordered extracellular matrix. The aim of this review is to highlight factors involved in the generation of stromal haze and its subsequent removal.
article 33 Citação(ões) na Scopus EBM regeneration and changes in EBM component mRNA expression in stromal cells after corneal injury(2017) SANTHANAM, Abirami; MARINO, Gustavo K.; TORRICELLI, Andre A. M.; WILSON, Steven E.Purpose: To investigate the production of the epithelial basement membrane (EBM) component mRNAs at time points before lamina lucida and lamina densa regeneration in anterior stromal cells after corneal injury that would heal with and without fibrosis. Methods: Rabbit corneas were removed from 2 to 19 days after -4.5D or -9.0D photorefractive keratectomy (PRK) with the VISX S4 IR laser. Corneas were evaluated with transmission electron microscopy (TEM) for full regeneration of the lamina lucida and the lamina densa. Laser capture microdissection (LCM) based quantitative real-time (RT)-PCR was used to quantitate the expression of mRNAs for laminin alpha-3 (LAMA3), perlecan, nidogen-1, and nidogen-2 in the anterior stroma. Results: After -4.5D PRK, EBM was found to be fully regenerated at 8 to 10 days after surgery. At 4 days after PRK, the nidogen-2 and LAMA3 mRNAs levels were detected at statistically significantly lower levels in the anterior stroma of the -9.0D PRK corneas (where the EBM would not fully regenerate) compared to the -4.5D PRK corneas (where the EBM was destined to fully regenerate). At 7 days after PRK, nidogen-2 and LAMA3 mRNAs continued to be statistically significantly lower in the anterior stroma of the -9.0D PRK corneas compared to their expression in the anterior stroma of the -4.5D PRK corneas. Conclusions: Key EBM components LAMA3 and nidogen-2 mRNAs are expressed at higher levels in the anterior stroma during EBM regeneration in the -4.5D PRK corneas where the EBM is destined to fully regenerate and no haze developed compared to the -9.0D PRK corneas where the EBM will not fully regenerate and myofibroblast-related stromal fibrosis (haze) will develop.- Corneal Molecular and Cellular Biology for the Refractive Surgeon: The Critical Role of the Epithelial Basement Membrane(2016) MARINO, Gustavo K.; SANTHIAGO, Marcony R.; TORRICELLI, Andre A. M.; SANTHANAM, Abirami; WILSON, Steven E.PURPOSE: To provide an overview of the recent advances concerning the corneal molecular and cellular biology processes involved in the wound healing response after excimer laser surface ablation and LASIK surgery. METHODS: Literature review. RESULTS: The corneal wound healing response is a complex cascade of events that impacts the predictability and stability of keratorefractive surgical procedures such as photorefractive keratectomy and LASIK. The generation and persistence of corneal myofibroblasts (contractile cells with reduced transparency) arise from the interaction of cytokines and growth factors such as transforming growth factor beta and interleukin 1 produced by epithelial and stromal cells in response to the corneal injury. Myofibroblasts, and the opaque extracellular matrix they secrete into the stroma, disturb the precise distribution and spacing of collagen fibers related to corneal transparency and lead to the development of vision-limiting corneal opacity (haze). The intact epithelial basement membrane has a pivotal role as a structure that regulates corneal epithelial-stromal interactions. Thus, defective regeneration of the epithelial basement membrane after surgery, trauma, or infection leads to the development of stromal haze. The apoptotic process following laser stromal ablation, which is proportional to the level of attempted correction, leads to an early decrease in anterior keratocyte density and the diminished contribution of these non-epithelial cells of components such as perlecan and nidogen-2 required for normal regeneration of the epithelial basement membrane. Haze persists until late repair of the defective epithelial basement membrane. CONCLUSIONS: Defective regeneration of the epithelial basement membrane has a critical role in determining whether a cornea heals with late haze after photorefractive keratectomy or with scarring at the flap edge in LASIK.
conferenceObject Abnormal epithelial basement membrane ultrastructure in corneas with haze after PRK in rabbits(2013) TORRICELLI, Andre; SINGH, Vivek; AGRAWAL, Vandana; WILSON, Steven