RESUMO
BACKGROUND: Abdominoplasty is a critical aesthetic and functional procedure for individuals who have undergone massive weight loss. Numerous techniques have been proposed to optimize aesthetic results while minimizing complications. METHODS: This prospective study examined 500 patients who underwent abdominoplasty during body-contouring procedures between 1 January 2018 and 31 December 2021 at a tertiary center. The Skin-Adipose Tissue-Muscle (SAM) protocol was employed to analyze the operative strategies and complication rates and compare them with the existing literature. Furthermore, patient satisfaction and aesthetic outcomes were measured one year post-operation using a comprehensive four-point questionnaire evaluated by the patients themselves and two independent surgeons. RESULTS: Participants had an average age of 34.8 years and a mean BMI of 31.1 kg/m2. The surgeries included 328 full abdominoplasties and 172 T-inverted abdominoplasties. Notable complications included wound infection (4%), wound dehiscence (8.6%), tissue necrosis (0.6%), seroma (8.4%), and hematoma (2.6%). A higher BMI was correlated with an increased risk of complications and lower patient satisfaction. Data analysis was performed using Stata version 18 software. CONCLUSIONS: The increasing prevalence of obesity highlights an urgent need for more bariatric surgeries and subsequent abdominoplasties to mitigate the effects of massive weight loss. A crucial link between elevated BMI and a heightened risk of postoperative complications, emphasizing the necessity for standardized surgical protocols tailored to individuals with higher BMI, was noted. Innovatively, future studies must further investigate the intricate dynamics between BMI and surgical risks. Exploring and establishing uniform, adaptive surgical guidelines promise to revolutionize patient care by significantly reducing complications and enhancing recovery and satisfaction following abdominoplasty.
RESUMO
PURPOSE: To validate the ability of theranostic imaging biomarkers in assessing corneal cross-linking (CXL) efficacy in flattening the maximum keratometry (Kmax) index. DESIGN: Prospective, randomized, multicenter, masked clinical trial (ClinicalTrails.gov identifier, NCT05457647). PARTICIPANTS: Fifty patients with progressive keratoconus. INTERVENTION: Participants were stratified to undergo epithelium-off (25 eyes) and epithelium-on (25 eyes) CXL protocols using an ultraviolet A (UV-A) medical device with theranostic software. The device controlled UV-A light both for performing CXL and assessing the corneal riboflavin concentration (riboflavin score) and treatment effect (theranostic score). A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epithelium-off and epithelium-on protocols, respectively. All eyes underwent 9 minutes of UV-A irradiance at 10 mW/cm2. MAIN OUTCOME MEASURES: The primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to classify eyes correctly and predict a Kmax flattening at 1 year after CXL. Other outcome measures included change in Kmax, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction and central corneal thickness 1 year after CXL. RESULTS: Accuracy and precision of the theranostic imaging biomarkers in predicting eyes that had >0.1 diopter (D) of Kmax flattening at 1 year were 91% and 95%, respectively. The Kmax value significantly flattened by a median of -1.3 D (IQR, -2.11 to -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 logarithm of the minimum angle of resolution (logMAR; IQR, -0.3 to 0.0 logMAR [P < 0.001] and -0.2 to 0.0 logMAR [P < 0.001], respectively). No significant changes in endothelial cell density (P = 0.33) or central corneal thickness (P = 0.07) were noted 1 year after surgery. CONCLUSIONS: The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epithelium-off and epithelium-on CXL protocols. Concentration of riboflavin and its UV-A light mediated photoactivation in the cornea are the primary factors determining CXL efficacy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
RESUMO
BACKGROUND: Deep inferior epigastric artery perforator (DIEP) flap is nowadays considered the gold standard in breast reconstruction. However, venous congestion is still a leading cause of free flap failure. Despite the conspicuous articles regarding the use of a secondary venous anastomosis, there is a lack in the literature regarding the prophylactic use of a secondary venous route to reduce the incidence of complications during breast reconstruction. METHODS: A double-center retrospective study based on women undergoing DIEP breast reconstruction was conducted, dividing patients into case group (DIEP flaps with double venous anastomosis) and control group (DIEP flaps with single venous anastomosis). Demographic and surgical data and complications were compared and statistically analyzed, and a reconstructive algorithm was proposed to improve the flap insetting. RESULTS: In total, 154 patients were included in the study, divided into case group (74 patients) and control group (80 patients). The median age at the time of surgery was 49.09 years (range: 29-68 years), slightly lower in group 1 when compared with group 2. The mean body mass index (BMI) was 25.52 kg/m2 (range: 21.09-29.37 kg/m2), in particular 25.47 kg/m2 (range: 23.44-28.63 kg/m2) in group 1 and 25.58 kg/m2 (range: 21.09-29.37 kg/m2) in group 2. No statistical differences were found between groups in terms of BMI and smoking and comorbidities history. The average operative times were 272.16 minutes (range: 221-328 minutes) in group 1 and 272.34 minutes (range: 221-327 minutes) in group 2, with no significant difference between groups, as well as ischemia time (44.4 minutes in group 1 [range: 38-56 minutes] and 49.12 minutes in group 2 [range: 41-67 minutes]). Statistical analysis showed a reduction in short-term complications and a statistically significant reduction for take-backs in the two groups. CONCLUSIONS: Our study suggests that venous supercharging of DIEP flap by performing dual venous anastomosis can be routinely and safely done prophylactically, and thus not only after intraoperative assessment of venous congestion, to avoid flap venous congestion and decrease the rates of re-exploration.
RESUMO
Adipose-derived mesenchymal stem cells (ASCs) are adult multipotent stem cells, able to differentiate toward neural elements other than cells of mesodermal lineage. The aim of this research was to test ASC neural differentiation using melatonin combined with conditioned media (CM) from glial cells. Isolated from the lipoaspirate of healthy donors, ASCs were expanded in a basal growth medium before undergoing neural differentiation procedures. For this purpose, CM obtained from olfactory ensheathing cells and from Schwann cells were used. In some samples, 1 µM of melatonin was added. After 1 and 7 days of culture, cells were studied using immunocytochemistry and flow cytometry to evaluate neural marker expression (Nestin, MAP2, Synapsin I, GFAP) under different conditions. The results confirmed that a successful neural differentiation was achieved by glial CM, whereas the addition of melatonin alone did not induce appreciable changes. When melatonin was combined with CM, ASC neural differentiation was enhanced, as demonstrated by a further improvement of neuronal marker expression, whereas glial differentiation was attenuated. A dynamic modulation was also observed, testing the expression of melatonin receptors. In conclusion, our data suggest that melatonin's neurogenic differentiation ability can be usefully exploited to obtain neuronal-like differentiated ASCs for potential therapeutic strategies.
Assuntos
Diferenciação Celular , Melatonina , Células-Tronco Mesenquimais , Melatonina/farmacologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Humanos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Tecido Adiposo/citologia , Neurônios/citologia , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Células de Schwann/citologia , Células de Schwann/metabolismo , Células de Schwann/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Adulto , Nestina/metabolismo , Nestina/genética , Proteína Glial Fibrilar Ácida/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/citologia , Neuroglia/metabolismo , Sinapsinas/metabolismoRESUMO
Seven human donor eye globes underwent corneal cross-linking using theranostic UV-A device with accessory corneal iontophoresis system for patterned delivery of a 0.22% riboflavin solution. Theranostic-guided UV-A light illumination assessed riboflavin distribution and treated corneas at 10 mW/cm2 for 9 min with a 5.0-mm beam size. Corneal topography maps were taken at baseline and 2-h post-treatment. Analysis utilized corneal topography elevation data, with results showing controlled riboflavin delivery led to a consistent gradient, with 40% higher levels centrally (248 ± 79 µg/cm3) than peripherally (180 ± 72 µg/cm3 at ±2.5 mm from the center). Theranostic-guided UV-A light irradiation resulted in significant changes in corneal topography, with a decrease in best-fit sphere value (-0.7 ± 0.2 D; p < 0.001) and consistent downward shift in corneal elevation map (-11.7 ± 3.7 µm). The coefficient of variation was 2.5%, indicating high procedure performance in achieving significant and reliable corneal flattening.
Assuntos
Córnea , Iontoforese , Riboflavina , Humanos , Córnea/metabolismo , Córnea/efeitos da radiação , Córnea/efeitos dos fármacos , Raios Ultravioleta , Nanomedicina Teranóstica , Sistemas de Liberação de Medicamentos , Terapia UltravioletaRESUMO
OBJECTIVE: To report variants in 26 candidate genes and describe the clinical features of Italian patients with keratoconus (KC). SUBJECTS/METHODS: Sixty-four patients with a confirmed diagnosis of KC were enrolled in this genetic association study. Patients were classified into two study groups according to whether they had a confirmed diagnosis of progressive or stable KC. A purpose-developed Next Generation Sequencing (NGS) panel was used to identify and analyse the coding exons and flanking exon/intron boundaries of 26 genes known to be associated with KC and corneal dystrophies. Interpretation of the pathogenic significance of variants was performed using in silico predictive algorithms. RESULT: The targeted NGS research identified a total of 167 allelic variants of 22 genes in the study population; twenty-four patients had stable keratoconus (n. 54 variants) and forty patients had progressive disease (n. 113 variants). We identified genetic variants of certain pathogenic significance in five patients with progressive KC; in addition, eight novel genetic variants were found in eight patients with progressive KC. Mutations of FLG, LOXHD1, ZNF469, and DOCK9 genes were twice more frequently identified in patients with progressive than stable disease. Filaggrin gene variants were found in 49 patients (76% of total), of whom 32 patients (80% of progressive KC group) had progressive disease. CONCLUSIONS: Targeted NGS research provided new insights into the causative effect of candidate genes in the clinical phenotype of keratoconus. Filaggrin mutations were found to represent a genetic risk factor for development of progressive disease in Italy.
RESUMO
PURPOSE: To estimate the prevalence of keratoconus in a population of subjects undergoing first eye examination in an eye clinic in Italy. METHODS: A single-center, cross-sectional, study was conducted involving patients who underwent first eye examination at an eye clinic in Rome between September 2021 and June 2022. The prevalence of keratoconus was determined by Placido-disk corneal topography using the maximum keratometry (Kmax) value and the Cone Magnitude and Location Index (CLMI) for keratoconus screening. Subjective analysis was performed by two experienced corneal specialists, who classified the outcome into two groups: normal and keratoconus. Risk factors, including family history of keratoconus, allergy or atopy, thyroid disease, eye rubbing habit and gender were also examined. RESULTS: A total of 512 subjects between 7 and 81 years old were evaluated. The inter-observer agreement to classify subjects in normal or keratoconus group was excellent (k = 1.0); the estimated prevalence in the specific population was 2.1%. Presence of positive family history (9% of keratoconus vs 5% normal), concomitant allergy or atopy (27% vs 9%) and eye rubbing habit (18% vs 4%) were associated with a higher risk of disease. CONCLUSION: This study reported a high estimated prevalence of keratoconus in a metropolitan area of Italy, as found in recent studies in the Mediterranean and Middle East countries. Screening for keratoconus is highly recommendable and easily feasible with corneal topography under expert supervision and may be indicated primarily in young population to improve early detection and prompt therapeutic management for halting disease progression.
Assuntos
Topografia da Córnea , Ceratocone , Humanos , Ceratocone/epidemiologia , Ceratocone/diagnóstico , Prevalência , Feminino , Masculino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Criança , Adolescente , Idoso , Adulto Jovem , Idoso de 80 Anos ou mais , Itália/epidemiologia , Fatores de Risco , População Urbana/estatística & dados numéricos , Córnea/patologia , Distribuição por IdadeRESUMO
PURPOSE: To assess the feasibility of theranostics to determine the riboflavin concentration in the cornea using clinically available ophthalmic formulations during epithelium-off (epi-off) and transepithelial (epi-on) corneal cross-linking procedures. METHODS: Thirty-two eye bank human donor corneas were equally randomized in eight groups; groups 1 to 3 and groups 4 to 8 underwent epi-off and epi-on delivery of riboflavin respectively. Riboflavin ophthalmic solutions were applied onto the cornea according to the manufacturers' instructions. The amount of riboflavin into the cornea was estimated, at preset time intervals during imbibition time, using theranostic UV-A device (C4V CHROMO4VIS, Regensight srl, Italy) and expressed as riboflavin score (d.u.). Measurements of corneal riboflavin concentration (expressed as µg/cm3) were also performed by spectroscopy absorbance technique (AvaLight-DH-S-BAL, Avantes) for external validation of theranostic measurements. RESULTS: At the end of imbibition time in epi-off delivery protocols, the average riboflavin score ranged from 0.77 ± 0.38 (the average corneal riboflavin concentration was 213 ± 190 µg/cm3) to 1.79 ± 0.07 (554 ± 103 µg/cm3). In epi-on delivery protocols, the average riboflavin score ranged from 0.17 ± 0.01 to 0.67 ± 0.19 (corneal riboflavin concentration ranged from 6 ± 5 µg/cm3 to 122 ± 39 µg/cm3) at the end of imbibition time. A statistically significant linear correlation (P ≤ 0.05) was found between the theranostic and spectrophotometry measurements in all groups. CONCLUSIONS: Real-time theranostic imaging provided an accurate strategy for assessing permeation of riboflavin into the human cornea during the imbibition phase of corneal cross-linking, regardless of delivery protocol. A large variability in corneal riboflavin concentration exists between clinically available ophthalmic formulations both in epi-off and epi-on delivery protocols.
Assuntos
Crosslinking Corneano , Fotoquimioterapia , Fármacos Fotossensibilizantes , Riboflavina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Colágeno/metabolismo , Substância Própria/metabolismo , Epitélio Corneano/metabolismo , Bancos de Olhos , Estudos de Viabilidade , Ceratocone/tratamento farmacológico , Ceratocone/metabolismo , Ceratocone/diagnóstico , Soluções Oftálmicas/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/administração & dosagem , Riboflavina/farmacocinética , Riboflavina/administração & dosagem , Doadores de Tecidos , Raios UltravioletaRESUMO
This retrospective study examines the implementation of Nexobrid, an enzymatic debriding agent developed from bromelain, for burn debridement in a major Italian burn center. With previous research showing encouraging results for Nexobrid in terms of reducing the need for surgical intervention and faster eschar removal, the current study aims to add to the growing body of evidence regarding its potential benefits and limitations. The patient database was utilized to identify patients who received Nexobrid treatment between October 2019 and June 2023. A retrospective analysis was conducted to gather demographic information, burn causes, procedural details, and patient outcomes. Of the 30 patients treated with Nexobrid, 10% did not require further surgical intervention, showcasing Nexobrid's potential to improve patient outcomes. However, over 80% of patients still required additional surgical intervention, demonstrating that Nexobrid's effectiveness varies across patients and should be considered a tool rather than a definitive solution in burn wound management. A few patients developed complications, and about 10% of patients succumbed to systemic complications. The study results reveal both the potential benefits and limitations of using Nexobrid in burn debridement. While it successfully eliminated the need for further surgical intervention in a small percentage of patients, the majority still required additional surgical procedures. These findings not only highlight Nexobrid's role as a tool in burn wound management but also point toward the discrepancies with previous studies. The authors suggest future research should include randomized controlled trials, direct comparisons between Nexobrid and traditional debridement methods, and studies incorporating larger and more diverse patient groups.
Assuntos
Unidades de Queimados , Queimaduras , Humanos , Estudos Retrospectivos , Desbridamento/métodos , Queimaduras/cirurgia , ItáliaRESUMO
PURPOSE: The aim of this study was to assess accuracy of the mean corneal stiffness ( kc , N/m) parameter to discriminate between patients with keratoconus and age-matched healthy subjects. METHODS: Dynamic Scheimpflug imaging tonometry was performed with Corvis ST (Oculus Optikgeräte GmbH, Germany) in patients with keratoconus (n = 24; study group) and age-matched healthy subjects (n = 32; control). An image processing algorithm was developed to analyze the video sequence of the Corvis ST air-puff event and to determine the geometric and temporal parameters that correlated with the corneal tissue biomechanical properties. A modified 3-element viscoelastic model was used to derive the kc parameter, which represented the corneal tissue resistance to deformation under load. Receiver operating characteristic curves were used to assess the overall diagnostic performance for determining the area under the curve, sensitivity, and specificity of the kc in assessing the corneal tissue deformation to the Corvis ST air-puff event in keratoconus and control eyes. The Corvis Biomechanical Index ( CBI ) was analyzed for external validation. RESULTS: The kc parameter was significantly different between keratoconus and controls ( P < 0.001), ranging from 24.9 ±3.0 to 34.2 ±3.5 N/m, respectively. It was highly correlated with CBI (r = -0.69; P < 0.001); however, the kc parameter had greater specificity (94%) than CBI (75%), whereas the 2 biomarkers had similar area under the curve (0.98 vs. 0.94) and sensitivity (96% vs. 92%) in predicting the occurrence of keratoconus. CONCLUSIONS: The kc parameter extracted by video processing analysis of dynamic Scheimpflug tonometry data was highly accurate in discriminating patients with clinically manifest keratoconus compared with controls.
Assuntos
Ceratocone , Humanos , Ceratocone/diagnóstico , Topografia da Córnea , Elasticidade , Córnea , Curva ROC , Biomarcadores , Manometria , Fenômenos BiomecânicosRESUMO
Electrical burns pose unique challenges in reconstructive surgery due to the extensive tissue damage they cause. The thumb is particularly susceptible to electrical burns, leading to severe functional impairment. This case series introduces the use of the temporal fascia free flap for thumb coverage in patients with electrical burn injuries. The study aims to assess the functional outcomes of this approach using the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Six male patients underwent thumb reconstruction using temporal fascia free flaps following electrical burn injuries. The extent of the injury was assessed, and necrotic tissue was debrided. Functional outcomes were evaluated using the DASH questionnaire 6 months postoperation. All procedures were conducted in accordance with ethical guidelines, and informed consent was obtained from all patients. All patients achieved successful transplants using temporal fascia free flaps. The average DASH score at the 6-month follow-up indicated satisfactory functional recovery. Patients reported improvements in thumb mobility and functionality, and the cosmetic appearance of the thumb was acceptable. The appearance of the scar in the donor area was well-received. The temporal fascia free flap proved to be an effective method for thumb reconstruction following electrical burn injuries. Its thin and flexible nature allows for optimal contouring and improved range of motion. Although one case of partial flap loss was observed, overall functional and aesthetic outcomes were satisfactory. Further research with larger sample sizes is warranted to optimize surgical techniques and postoperative care for better outcomes.
Assuntos
Queimaduras por Corrente Elétrica , Queimaduras , Retalhos de Tecido Biológico , Humanos , Masculino , Queimaduras por Corrente Elétrica/cirurgia , Polegar/cirurgia , Ombro , Queimaduras/cirurgia , Resultado do TratamentoRESUMO
Chest-wall perforator-based techniques to replace volume for breast conservative therapy allow excision of large breast areas with minimal sequalae, such as the nipple-areolar complex displacement, parenchymal indentation or contour deformity. Furthermore, chest wall perforator flaps facilitate the maintenance of breast symmetry, hence decreasing the need for contralateral surgery. Lateral intercostal flap was described in numerous variants among which the most famous are the propeller flap and the turnover version. The turnover version is the easiest and fastest version that allows the replacement of large amount of volume. In this paper, we evaluate patients reported outcomes, before and after surgery, collected through the Breast Q. This study was conducted on 21 patients who were admitted to the plastic surgery department. A prospectively maintained database was used to identify the patients and their records were assessed retrospectively. The pre/post operative patients data were collected. The Breast-Q questionnaire was administered before the surgery and at least 1 year after. No major surgical complications were reported. Mean Breast-Q scores were evaluated at least 1 year after surgery and radiotherapy and compared with pre-surgical scores. Among all the modules, no significant differences between the pre-surgical and post-surgical Breast-Q scores were observed. Until now, the lateral intercostal artery perforator flap has not been widely used, due to a difficult dissection and a challenging preoperative planning. According to the reported surgical technique, the execution is easy. This technique provides the same breast-related quality of life compared to preoperative values, reduces the mastectomy rate and increases the overall survival.
RESUMO
Microsurgical procedures are nowadays routinely performed worldwide in reconstructive surgery. The deep inferior epigastric artery perforator (DIEP) flap has become the gold standard in breast reconstruction due to its excellent outcomes and lower donor site morbidity. However, complications, including flap failure, still occur in DIEP flap breast reconstruction. Often, according to our experience, these complications result from pedicle disorders, which can be attributed to postoperative mobilization. In the present study, we evaluated the efficacy and safety of using a fibrin sealant as a method for pedicle stabilization to prevent pedicle mobilization in the postoperative period. With our technique, after the flap insetting and microsurgical anastomosis, the pedicle was stabilized by applying a fibrin sealant (TISSEEL™) around and over the entire pedicle. Our study included a homogeneous series of 70 patients who received a delayed DIEP flap breast reconstruction. A retrospective study was conducted to evaluate this novel technique compared to the conventional method. In our experience, the fibrin glue allowed us to reduce the strain for correct pedicle positioning and all subsequent efforts to avoid displacements in the postoperative period. Our preliminary results suggest that this method may lead to a reduction in overall complications attributable to pedicle disorders.
RESUMO
PURPOSE: To assess predictability of tissue biomechanical stiffening induced by UV-A light-mediated real-time assessment of riboflavin concentration during corneal crosslinking (CXL) of human donor tissues. SETTING: Studio Italiano di Oftalmologia, Rome, Italy. DESIGN: Laboratory study. METHODS: 20 sclerocorneal tissues were randomly stratified to undergo CXL with either the epithelium intact (n = 12) or removed (n = 8). Samples underwent corneal soaking with 0.22% riboflavin formulation (RitSight) with dosing time of t = 10 minutes and t = 20 minutes in epithelium-off and epithelium-on protocols, respectively. All tissues underwent 9-minute UV-A irradiance at 10 mW/cm 2 using theranostic device (C4V CHROMO4VIS). The device used controlled UV-A light irradiation to induce both imaging and treatment of the cornea, providing a real-time measure of corneal riboflavin concentration and treatment efficacy (ie, theranostic score) during surgery. Tissue biomechanics were assessed with an air-puff device (Corvis), which was performed before and after treatment. A 3-element viscoelastic model was developed to fit the corneal deformation response to air-puff excitation and to calculate the mean corneal stiffness parameter (k c ). RESULTS: Significant corneal tissue stiffening ( P < .05) was induced by the theranostic UV-A device in either CXL treatment protocol. Significant correlation was found between the theranostic score and the increase in k c ( R = 0.75; P = .003). The score showed high accuracy (94%) and precision (94%) to predict correctly samples that had improved tissue biomechanical strengthening. CONCLUSIONS: Real-time assessment of corneal riboflavin concentration provided a predictive and precise approach for significant improvement of tissue strength on individual corneas, regardless of CXL treatment protocol.
Assuntos
Crosslinking Corneano , Fármacos Fotossensibilizantes , Humanos , Córnea , Substância Própria , Reagentes de Ligações Cruzadas/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/uso terapêutico , Riboflavina/farmacologia , Resultado do Tratamento , Raios UltravioletaRESUMO
The Assessment of theranostic guided riboflavin/UV-A corneal cross-linking for treatment of keratoconus (ARGO; registration number NCT05457647) clinical trial tests the hypothesis that theranostic-guided riboflavin/UV-A corneal cross-linking (CXL) can provide predictable clinical efficacy for halting keratoconus progression, regardless of treatment protocol, i.e., either with or without epithelial removal. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that enables real-time monitoring of image-guided therapy. In this trial, the theranostic software module of a novel UV-A medical device will be validated in order to confirm its accuracy in estimating corneal cross-linking efficacy in real time. During CXL procedure, the theranostic UV-A medical device will provide the operator with an imaging biomarker, i.e., the theranostic score, which is calculated by non-invasive measurement of corneal riboflavin concentration and its UV-A light mediated photo-degradation. ARGO is a randomized multicenter clinical trial in patients aged between 18 and 40 years with progressive keratoconus aiming to validate the theranostic score by assessing the change of the maximum keratometry point value at 1-year postoperatively. A total of 50 participants will be stratified with allocation ratio 1:1 using a computer-generated stratification plan with blocks in two treatment protocols, such as epithelium-off or epithelium-on CXL. Following treatment, participants will be monitored for 12 months. Assessment of safety and performance of theranostic-guided corneal cross-linking treatment modality will be determined objectively by corneal tomography, corneal endothelial microscopy, visual acuity testing and slit-lamp eye examination.
Assuntos
Ceratocone , Fotoquimioterapia , Humanos , Adolescente , Adulto Jovem , Adulto , Ceratocone/diagnóstico , Ceratocone/tratamento farmacológico , Ceratocone/cirurgia , Medicina de Precisão , Crosslinking Corneano , Córnea/metabolismo , Raios Ultravioleta , Riboflavina/uso terapêutico , Fotoquimioterapia/métodos , Reagentes de Ligações Cruzadas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Topografia da Córnea , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
PURPOSE: The scope of this study was to investigate keratoconus progression using zonal average analysis of corneal tomography. METHODS: The corneal tomographies of patients participating in initial baseline and all scheduled follow-up visits up to 4 years were analyzed. Data were exported in custom software, which delineated 4 zones of analysis and calculated the average values of the anterior and posterior curvature and the average thickness for each zone at each visit. In particular, a 3.1 mm 2 area containing the K max , termed "keratoconus cone zone," was defined for assessing disease progression during the follow-up. RESULTS: A total of 201 patients were enrolled in this prospective study. At 4 years, 31% of the eyes (n = 62) had an average increase of ≥1.0 D in the keratoconus cone zone in baseline visit, whereas only 11% of the eyes (n = 22) had ≥1.0 D K max increase in the same period. The zonal anterior average curvature (+1.1 D; P < 0.001) and thickness (-14 µm; P < 0.001) values of the keratoconus cone zone progressed significantly during the follow-up. A high correlation was found between the 4-year changes of K max and central corneal thickness values and the change of the average anterior curvature and thickness values in the keratoconus cone zone. The posterior cornea did not show significant average changes (<-0.2 D; P > 0.05) during the follow-up. CONCLUSIONS: Single-point tomography indexes for keratoconus progression did not capture the overall structure and shape changes of the cornea. It would be recommended to update criteria for keratoconus management including the zonal average analysis of curvature and thickness values for tracking disease progression over observation periods longer than 1 year.
Assuntos
Ceratocone , Humanos , Ceratocone/diagnóstico por imagem , Estudos Prospectivos , Topografia da Córnea/métodos , Córnea/diagnóstico por imagem , Tomografia , Progressão da DoençaRESUMO
Theranostics is an emerging therapeutic paradigm of personalized medicine; the term refers to the simultaneous integration of therapy and diagnostics. In this work, theranostic-guided corneal cross-linking was performed on 10 human sclero-corneal tissues. The samples were soaked with 0.22% riboflavin formulation and underwent 9 minutes UV-A irradiance at 10 mW/cm2 using theranostic device, which provided both a measure of corneal riboflavin concentration and a theranostic score estimating treatment efficacy in real time. A three-element viscoelastic model was developed to fit the deformation response of the cornea to air-puff excitation of dynamic tonometry and to calculate the mean corneal stiffness parameter before and after treatment. Significant correlation was found between the theranostic score and the increase in mean corneal stiffness (R = 0.80; P < .001). Accuracy and precision of the theranostic score in predicting the induced corneal tissue stiffening were both 90%. The riboflavin concentration prior to starting the UV-A photo-therapy phase was the most important variable to allow corneal cross-linking to be effective. Theranostic UV-A light mediated imaging and therapy enables the operator to adopt a precise approach for achieving highly predictable biomechanical strengthening on individual corneas.
Assuntos
Ceratocone , Humanos , Ceratocone/diagnóstico por imagem , Ceratocone/tratamento farmacológico , Crosslinking Corneano , Medicina de Precisão , Reagentes de Ligações Cruzadas , Córnea/diagnóstico por imagem , Riboflavina/farmacologia , Riboflavina/uso terapêutico , Raios Ultravioleta , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Age-related macular degeneration (AMD) is a chronic multifactorial eye disease representing the primary cause of vision loss in people aged 60 years and older. The etiopathogenesis of the disease remains uncertain, with several risk factors contributing to its onset and progression, such as genotype, aging, hypertension, smoking, overweight, and low dietary intake of carotenoids. Since the aging populations of the industrialized world are increasing rapidly, the impact of AMD in the socio-economical life-developed countries is expected to increase dramatically in the next years. In this context, the benefits of prevention and early disease detection for prompt and effective treatment can be enormous to reduce the social and economic burden of AMD. Nutritional and lifestyle changes, including dietary intake of xanthophyll pigments, such as lutein and zeaxanthin, no smoking, and regular exercise, are known to protect from risk of AMD progression from early to advanced disease stages. In this review, we present the clinical outcomes of a pilot study on trans-scleral iontophoresis delivery of lutein in patients with AMD. Topical delivery of lutein directly to the macula may provide a more efficient method for enriching the macular pigment and for achieving greater patient compliance to therapy than oral administration and thus enhancing prevention strategies. Modern diagnostic methodologies shall address the major problem of accurately detecting the risk of transition from intermediate AMD to advanced AMD stages. Adaptive optics retinal imaging and resonance Raman spectroscopy are two highly promising technologies for the objective assessment of patients with AMD. In this review, we present some of their clinical applications for collecting quantitative measurements of retinal cellular changes and macular content of xanthophyll pigments, respectively. In conclusion, there is great expectation that technological advancements in AMD management will deliver improved screening, therapeutic prevention, and diagnostic systems in the coming decade through a pro-active strategy of "treatment for prevention" that will aim to reduce the global burden of vision loss caused by AMD in the elderly.
RESUMO
BACKGROUND: Riboflavin/UV-A corneal cross-linking (CXL) for treating keratoconus and iatrogenic corneal ectasia has been well-established as first treatment option to stabilize corneal tissue biomechanical instability. Although the plethora of clinical studies has been published into the field, there is no systematic review assessing the type and frequency of adverse events after CXL. METHODS: A systemic literature review on clinical safety and adverse events after CXL in patients with keratoconus and corneal ectasia was performed using PubMed. A literature search was performed for relevant peer-reviewed publications. The main outcome measures extracted from the articles were adverse events, endothelial cell density, corrected distance visual acuity and maximum simulated keratometry. RESULTS: The most frequent adverse events after CXL were corneal haze and corneal edema, which were mild and transient. The severe adverse events were infrequent (cumulative incidence: < 1.3%) after CXL. The clinical benefits of CXL highly outweighed the risks for the treatment of keratoconus and corneal ectasia. CONCLUSIONS: The severe adverse events with permanent sequelae are infrequent after CXL and all are associated with corneal de-epithelialization, such as infectious keratitis and corneal scarring.