MARCONY RODRIGUES DE SANTHIAGO
Projetos de Pesquisa
Unidades Organizacionais
LIM/33 - Laboratório de Oftalmologia, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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conferenceObject Descemet's basement membrane modulation of corneal fibrosis(2019) WILSON, Steven E.; MEDEIROS, Carla S.; SAIKIA, Paramananda; OLIVEIRA, Rodrigo Carlos de; LASSANCE, Luciana; SANTHIAGO, Marcony R.- The Corneal Basement Membranes and Stromal Fibrosis(2018) MEDEIROS, Carla S.; MARINO, Gustavo K.; SANTHIAGO, Marcony R.; WILSON, Steven E.PURPOSE. The purpose of this review was to provide detailed insights into the pathophysiology of myofibroblast-mediated fibrosis (scarring or late haze) after corneal injury, surgery, or infection. METHOD. Literature review. RESULTS. The epithelium and epithelial basement membrane (EBM) and/or endothelium and Descemet's basement membrane (BM) are commonly disrupted after corneal injuries, surgeries, and infections. Regeneration of these critical regulatory structures relies on the coordinated production of BM components, including laminins, nidogens, perlecan, and collagen type IV by epithelial, endothelial, and keratocyte cells. Whether a cornea, or an area in the cornea, heals with transparency or fibrosis may be determined by whether there is injury to one or both corneal basement membranes (EBM and/or Descemet's BM) and delayed or defective regeneration or replacement of the BM. These opaque myofibroblasts, and the disordered extracellular matrix these cells produce, persist in the stroma until the EBM and/or Descemet's BM is regenerated or replaced. CONCLUSIONS. Corneal stromal fibrosis (also termed ""stromal scarring'' or ""late haze'') occurs as a consequence of BM injury and defective regeneration in both the anterior (EBM) and posterior (Descemet's BM) cornea. The resolution of fibrosis and return of stromal transparency depends on reestablished BM structure and function. It is hypothesized that defective regeneration of the EBM or Descemet's BM allows key profibrotic growth factors, including transforming growth factor beta-1 (TGF-beta 1) and TGF-beta 2, to penetrate the stroma at sustained levels necessary to drive the development and maintenance of mature opacity-producing myofibroblasts from myofibroblast precursors cells, and studies suggest that perlecan and collagen type IV are the critical components in EBM and Descemet's BM that bind TGF-beta 1, TGF-beta 2, platelet-derived growth factor, and possibly other growth factors, and regulate their bioavailability and function during homeostasis and corneal wound healing.
- Pathophysiology of Corneal Scarring in Persistent Epithelial Defects After PRK and Other Corneal Injuries(2018) WILSON, Steven E.; MEDEIROS, Carla S.; SANTHIAGO, Marcony R.PURPOSE: To analyze corneal persistent epithelial defects that occurred at 3 to 4 weeks after -4.50 diopter (D) photorefractive keratectomy (PRK) in rabbits and apply this pathophysiology to the treatment of persistent epithelial defects that occur after any corneal manipulations or diseases. METHODS: Two of 168 corneas that had -4.50 D PRK to study epithelial basement membrane regeneration developed spontaneous persistent epithelial defects that did not heal at 3 weeks after PRK. These were studied with slit-lamp photographs, immunohistochemistry for the myofibroblast marker alpha-smooth muscle actin (alpha-SMA), and transmission electron microscopy. RESULTS: Myofibroblasts developed at the stromal surface within the persistent epithelial defect and for a short distance peripheral to the leading edge of the epithelium. No normal epithelial basement membrane was detectable within the persistent epithelial defect or for up to 0.3 mm behind the leading edge of the epithelium, although epithelial basement membrane had normally regenerated in other areas of the zone ablated by an excimer laser where the epithelium healed promptly. CONCLUSIONS: A persistent epithelial defect in the cornea results in the development of myofibroblasts and disordered extracellular matrix produced by these cells that together cause opacity within, and a short distance beyond, the persistent epithelial defect. Clinicians should treat persistent epithelial defects within 10 days of non-closure of the epithelium to facilitate epithelial healing to prevent long-term stromal scarring (fibrosis).
- Intracorneal Ring Segments Implantation for Corneal Ectasia(2016) GIACOMIN, Natalia T.; MELLO, Glauco R.; MEDEIROS, Carla S.; KILIC, Alyin; SERPE, Cristine C.; ALMEIDA, Hirlana G.; KARA-JUNIOR, Newton; SANTHIAGO, Marcony R.PURPOSE: To provide an overview of the predictability, safety, and efficacy of intrastromal corneal ring segment (ICRS) implantation as a tool to improve visual acuity and its association with other techniques such as corneal collagen cross-linking (CXL), addressing biomechanical outcomes, models, surgical planning and technique, indications, contraindications, and complications in ectatic corneas. METHODS: Literature review. RESULTS: ICRSs have been used to regularize the corneal shape and reduce corneal astigmatism and higher order aberrations, improve visual acuity to acceptable limits, and delay, or eventually prevent, a corneal keratoplasty in keratoconic eyes. Changes in ICRS thickness and size, combination of techniques, and the addition of femtosecond lasers to dissect more foreseeable channels represent an improvement toward more predictable results. Several studies have shown, over time, the long-term efficacy and safety of ICRS treatment for keratoconus, with variable predictability, maintaining the early satisfactory outcomes regarding visual acuity, keratometry, and corneal thickness. It is just as important to ensure that the disease will not progress as it is to improve the visual acuity. Therefore, many studies have shown combined techniques using ICRS implantation and CXL. Also, further limitations of ICRS implantation can be addressed when associated with phakic intraocular lens implantation and photorefractive keratectomy. CONCLUSIONS: ICRS implantation has shown effectiveness and safety in most cases, including combined procedures. In properly selected eyes, it can improve both refraction and vision in patients with keratoconus.
- Intense Early Flattening After Corneal Collagen Cross-linking(2015) SANTHIAGO, Marcony R.; GIACOMIN, Natalia T.; MEDEIROS, Carla S.; SMADJA, David; BECHARA, Samir J.PURPOSE: To report two cases of significant flattening after corneal cross-linking (CXL) for keratoconus and discuss its potential explanations and implications. METHODS: Observational case report. RESULTS: One year after standard CXL protocol (3 mW/cm(2) for 30 minutes and total energy of 5.4 J/cm(2)), a 28-year-old woman presented a flattening of greater than 14 diopters and a 14-year-old boy presented a flattening of 7 diopters. CONCLUSIONS: Although rare, a significant flattening effect may occur during the first year after CXL, probably related to intense wound healing, increase in corneal elasticity, CXL effective depth, and central cone location. These cases suggest the necessity of a patient-specific approach and a better understanding regarding the actual mechanism behind its potent effect.
- Posterior stromal cell apoptosis triggered by mechanical endothelial injury and basement membrane component nidogen-1 production in the cornea(2018) MEDEIROS, Carla S.; LASSANCE, Luciana; SAIKIA, Paramananda; SANTHIAGO, Marcony; WILSON, Steven E.This study was performed to determine whether cells in the posterior stroma undergo apoptosis in response to endothelial cell injury and to determine whether basement membrane component nidogen-1 was present in the cornea. New Zealand White rabbits had an olive tip cannula inserted into the anterior chamber to mechanically injure corneal endothelial cells over an 8 mm diameter area of central cornea with minimal injury to Descemet's membrane. At 1 h (6 rabbits) and 4 h (6 rabbits) after injury, three corneas at each time point were cryopre-served in OCT for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemistry (IHC) for vimentin and nidogen-1, and three corneas at each time point were fixed for transmission electron microscopy (TEM). Uninjured corneas were controls. Stromal cells over approximately the posterior 25% of the stroma overlying to the site of corneal endothelial injury underwent apoptosis detected by the TUNEL assay. Many of these apoptotic cells were vimentin +, suggesting they were likely keratocytes or corneal fibroblasts. Stromal cells peripheral to the site of endothelial injury and more anterior stromal cells overlying the site of endothelial injury did not undergo apoptosis. Stromal cell death was confirmed to be apoptosis by TEM. No apoptosis of stromal cells was detected in control, uninjured corneas. Nidogen-1 was detected in the stroma of unwounded corneas, with higher nidogen-1 in the posterior stroma than the anterior stroma. After endothelial scrape injury, concentrations of nidogen-1 appeared to be in the extracellular matrix of the posterior stroma and, possibly, within apoptotic bodies of stromal cells. Thus, posterior stromal cells, likely including keratocytes, undergo apoptosis in response to corneal endothelial injury, analogous to anterior keratocytes undergoing apoptosis in response to epithelial injury.
- Accelerated corneal collagen crosslinking: Technique, efficacy, safety, and applications(2016) MEDEIROS, Carla S.; GIACOMIN, Natalia T.; BUENO, Renata L.; GHANEM, Ramon C.; MORAES JR., Haroldo V.; SANTHIAGO, Marcony R.Corneal collagen crosslinking (CXL) is an approach used to increase the biomechanical stability of the stromal tissue. Over the past 10 years, it has been used to halt the progression of ectatic diseases. According to the photochemical law of reciprocity, the same photochemical effect is achieved with reduced illumination time and correspondingly increased irradiation intensity. Several new CXL devices offer high ultraviolet-A irradiation intensity with different time settings. The main purpose of this review was to discuss the current use of different protocols of accelerated CXL and compare the efficacy and safety of accelerated CXL with the efficacy and safety of the established conventional method. Accelerated CXL proved to be safe and effective in halting progression of corneal ectasia. Corneal shape responses varied considerably, as did the demarcation line at different irradiance settings; the shorter the exposure time, the more superficial the demarcation line. (C) 2016 ASCRS and ESCRS
- Descemet's Membrane Modulation of Posterior Corneal Fibrosis(2019) MEDEIROS, Carla S.; SAIKIA, Paramananda; OLIVEIRA, Rodrigo Carlos de; LASSANCE, Luciana; SANTHIAGO, Marcony R.; WILSON, Steven E.PURPOSE. The purpose of this study was to evaluate the effect of removal of Descemet's basement membrane and endothelium compared with removal of the endothelium alone on posterior corneal fibrosis. METHODS. Twelve New Zealand White rabbits were included in the study. Six eyes had removal of the Descemet's membrane-endothelial complex over the central 8 mm of the cornea. Six eyes had endothelial removal with an olive-tipped cannula over the central 8 mm of the cornea. All corneas developed stromal edema. Corneas in both groups were cryofixed in optimum cutting temperature (OCT) formula at 1 month after surgery. Immunohistochemistry (IHC) was performed for alpha-smooth muscle actin (SMA), keratocan, CD45, nidogen-1, vimentin, and Ki-67, and a TUNEL assay was performed to detect apoptosis. RESULTS. Six of six corneas that had Descemet's membrane-endothelial removal developed posterior stromal fibrosis populated with SMA(+) myofibroblasts, whereas zero of six corneas that had endothelial removal alone developed fibrosis or SMA(+) myofibroblasts (P < 0.01). Myofibroblasts in the fibrotic zone of corneas that had Descemet's membrane-endothelial removal were undergoing both mitosis and apoptosis at 1 month after surgery. A zone between keratocan(+) keratocytes and SMA(+) myofibroblasts contained keratocan-SMA-vimentin(+) cells that were likely CD45(-) corneal fibroblasts and CD45(+) fibrocytes. CONCLUSIONS. Descemet's basement membrane has an important role in modulating posterior corneal fibrosis after injury that is analogous to the role of the epithelial basement membrane in modulating anterior corneal fibrosis after injury. Fibrotic areas had myofibroblasts undergoing mitosis and apoptosis, indicating that fibrosis is in dynamic flux.
- The Impact of Photorefractive Keratectomy and Mitomycin C on Corneal Nerves and Their Regeneration(2018) MEDEIROS, Carla S.; MARINO, Gustavo K.; LASSANCE, Luciana; SHANMUGAPRIYA, Thangavadivel; SANTHIAGO, Marcony R.; WILSON, Steven E.PURPOSE: To determine how photorefractive keratectomy (PRK) and mitomycin C (MMC) affect corneal nerves and their regeneration over time after surgery. METHODS: Twenty-eight New Zealand rabbits had corneal epithelial scraping with (n = 3) and without (n = 3) MMC 0.02% or -9.00 diopter PRK with (n = 6) and without (n = 16) MMC 0.02%. Corneas were removed after death and corneal nerve morphology was evaluated using acetylcholinesterase immunohistochemistry and beta-III tubulin staining after 1 day for all groups, after 1 month for PRK with and without MMC, and 2, 3, and 6 months after PRK without MMC. Image-Pro software (Media Cybernetics, Rockville, MD) was used to quantitate the area of nerve loss after the procedures and, consequently, regeneration of the nerves over time. Opposite eyes were used as controls. RESULTS: Epithelial scraping with MMC treatment did not show a statistically significant difference in nerve loss compared to epithelial scraping without MMC (P = .40). PRK with MMC was significantly different from PRK without MMC at 1 day after surgery (P = .0009) but not different at 1 month after surgery (P = .90). In the PRK without MMC group, nerves regenerated at 2 months (P < .0001) but did not return to the normal preoperative level of innervation until 3 months after surgery (P = .05). However, the morphology of the regenerating nerves was abnormal-with more tortuosity and aberrant innervation compared to the preoperative controls-even at 6 months after surgery. CONCLUSIONS: PRK negatively impacts the corneal nerves, but they are partially regenerated by 3 months after surgery in rabbits. Nerve loss after PRK extended peripherally to the excimer laser ablated zone, indicating that there was retrograde degeneration of nerves after PRK. MMC had a small additive toxic effect on the corneal nerves when combined with PRK that was only significant prior to 1 month after surgery.