More than 50% of patients with uveal melanoma end up developing metastases. Currently, there is no standard first-line treatment that facilitates proper management of the metastatic disease.
A ...systematic review of the last 40 years in PubMed with an exhaustive and strict selection of studies was conducted, in which the unit of measurement was overall survival (OS) expressed in Kaplan-Meier curves or numerically.
After the selection process, 110 articles were included. Regional therapies, such as intra-arterial liver chemotherapy (OS: 2, 9-22 months), isolated liver perfusion (OS: 9, 6-27, 4 months), or selective internal radiation therapy (OS: 18 months in monotherapy and 26 months in combination with other therapies) showed some superiority when compared to systemic therapies, such as chemotherapy (OS: 4, 6-17 months), immunotherapy (OS: 5-19, 1 month), immunosuppression (OS: 11 months), or targeted therapy (OS: 6-12 months), without being significant.
The results of this review suggest that there are no important differences in OS when comparing the different current treatment modalities. Most of the differences found seem to be explained by the heterogenicity of the different studies and the presence of biases in their design, rather than actual extensions of patient survival.
Retinopathy of pre-maturity (ROP) is a retinal disease that causes arrest of vascularization of the retina and can result in retinal detachment and blindness. Current screening protocols may not be ...sufficiently accurate to identify all at-risk patients. The aim of this study is to validate a method for improved identification of newborns at risk of ROP. We conducted a prospective clinical trial of pre-term newborns <32 weeks of gestation and/or <1,500 g birth weight during a 6-year period in a tertiary care hospital. We applied our new method based on measurement of insulin-like growth factor 1 (IGF1) levels at 3 weeks of age and the presence of sepsis during the first 3 weeks of life. Our screening protocol allowed exclusion of 121 (79.1%) patients for whom American Academy of Pediatrics (AAP) guidelines recommended screening, had a negative predictive value of 100%, and correctly identified all patients with ROP. Following retrospective assessment of our data based on these findings, we propose further restriction of the current AAP indications for screening to <1,100 g and <28 weeks of gestation in order to improve diagnostic efficacy while ensuring optimal use of restriction of human and material resources.
Although intravitreal administration of anti-infectives represents the standard treatment for infectious endophthalmitis, the knowledge about their pharmacokinetics is still limited. In this review, ...we aimed to summarise the factors influencing the pharmacokinetics of the anti-infective agents. We have conducted a comprehensive review of the preclinical pharmacokinetic parameters obtained in different studies of intravitreal injections of anti-infectives performed on animals, mainly rabbits. The two aspects with the biggest influence on pharmacokinetics are the distribution in the vitreous humour and the elimination through the posterior segment. The distribution can be affected by the molecular weight of the drug, the convection flow of the vitreous, the condition of the vitreous humour depending on the age of the patient, the possible interactions between the drug and the components of the vitreous, and the presence of vitrectomy. Meanwhile, the elimination includes the metabolism of the drug, the clearance via the anterior and posterior routes, and the possible inflammation of the eye resulting from the disease. Understanding the pharmacokinetics of the anti-infectives used in clinical practice is essential for a correct application. The information provided in this review could offer guidance for selecting the best therapeutic option according to the characteristics of the drugs.
The detection of metastases in patients with a diagnosis of uveal melanoma (UM) is a controversial issue. While only 1% of the patients have detectable metastases at the time of diagnosis, up to 30% ...of them will develop liver metastases within 5 years of treatment. UM spreads hematogenously, therefore, blood biomarkers may be helpful for prognosis and monitoring the disease progression. Despite the great progress achieved thanks to the genetic analysis of UM biopsies, this is an invasive technique and is limited by the heterogeneity of the tumor. The present review considers the current understanding in the field regarding biomarkers for the diagnosis and prognosis of UM and its metastasis, primarily to the liver. General covered topics include non-conventional markers such as proteins previously identified in cutaneous melanoma and UM cell lines, circulating tumor cells, microRNAs (miRNA), and circulating DNA, and how each may be critical in the development of novel blood biomarkers for UM.
Brachytherapy with iodine-125 (
I) has been extensively used as a conservative treatment for uveal melanoma (UM). Surgical technique for correct placement of episcleral radioactive plaques (ERP) in ...UM cases with posterior choroidal location and/or small size can be difficult and inaccurate. In this study, the correct positioning of plaques was assessed by intra-operative ultrasound control.
This was a longitudinal, retrospective study of consecutive 20 patients with UM (small-medium size and/or posterior location) who received
I brachytherapy. Location of plaques was adjusted by intra-operative ocular ultrasonography control. To perform ocular intra-operative ultrasonography, a 10 MHz probe was used to longitudinal and transverse bases in corresponding dummy plaques.
The study included 8 males and 12 females, with a mean age of 66.3 years (SD = 14.53), 5 right eyes (RE) and 15 left eyes (LE). In ultrasound examination, 4 UMs were of mushroom morphology and the rest nodular. Means of the size of UM by ultrasound were (mm): Lb: 10.60 (SD = 2.24) × Tb: 9.88 (SD = 1.54) × H: 4.02 (SD = 1.44) (3 cases corresponding to small size of collaborative ocular melanoma study (COMS), and 17 cases to medium). The plaques used were between 14 and 20 mm in diameter, with an average distance between the edge of greater base of the tumor and the edge of plate of 2.44 mm (SD = 0.34). It was necessary to surgically reposition the plaque in 4 cases (20%).
Intra-operative ultrasound control improves the accuracy of radioactive plaque placement for the treatment of medium-small UMs in posterior location. Probably, this technique should be applied in all cases of brachytherapy, regardless of the isotope chosen and the location of tumor mass, in order to perfectly adjust therapeutic position.
Epiretinal membrane (ERM) formation is a known postoperative complication following retinal detachment (RD) repair surgery. Prophylactic peeling of the internal limiting membrane (ILM) during surgery ...has been shown to reduce the risk of developing postoperative ERM formation. Some baseline characteristics and degrees of surgical complexity may act as risk factors for ERM development. In this review we aimed to investigate the benefit of ILM peeling in patients without significant proliferative vitreoretinopathy (PVR) who underwent pars plana vitrectomy for RD repair. A literature search using PubMed and various keywords retrieved relevant papers from which data were extracted and analyzed. Finally, the results of 12 observational studies (3420 eyes) were summarized. ILM peeling significantly reduced the risk of postoperative ERM formation (RR = 0.12, 95% CI 0.05-0.28). The groups did not differ in final visual acuity (SMD 0.14 logMAR (95% CI - 0.03-0.31)). The risk of RD recurrence (RR = 0.51, 95% CI 0.28-0.94) and the need for secondary ERM surgery (RR = 0.05, 95% CI 0.02-0.17) were also higher in the non-ILM peeling groups. In summary, although prophylactic ILM peeling appears to reduce the rate of postoperative ERM, this benefit does not translate into consistent visual recovery across studies and potential complications must be considered.
We performed a systematic review and meta-analysis to determine whether the use of local antibiotics is a beneficial prophylactic treatment for endophthalmitis in patients treated with anti-VEGF ...agents. We searched the MEDLINE and EMBASE databases, and the Cochrane Library over the period January 2007 to December 2016. The search terms used included "Endophthalmitis", "Antibiotic" and "Intravitreal injection". Studies in which the patients were treated exclusively with intravitreal injections of anti-VEGF were selected. Eight studies fit the inclusion criteria, which included a total of 276,774 injections; 109,178 (39.45%) were associated with the use of antibiotics and 114,821 (60.55%) were not associated with the use of antibiotics. Our meta-analysis indicated a significant risk for endophthalmitis that was 1.70 times greater with the use of antibiotics than that without antibiotics, with a confidence interval of 1.08 to 2.66 (p = 0.02). A meta-regression indicated that the location (operating rooms versus outpatient clinics) of injection did not have a significant effect on the incidence of endophthalmitis. The prophylactic use of antibiotics when administering anti-VEGF intravitreal injections may contribute to a greater incidence of endophthalmitis. This finding, in addition to reducing costs, would eliminate a treatment that has been shown to be unnecessary and even harmful to patients.
Current Situation and Challenges in Vitreous Substitutes Mondelo‐García, Cristina; Bandín‐Vilar, Enrique; García‐Quintanilla, Laura ...
Macromolecular bioscience,
August 2021, 2021-08-00, 20210801, Letnik:
21, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Vitreo‐retinal disorders constitute a significant portion of treatable ocular diseases. These pathologies often require vitreo‐retinal surgery and, as a consequence, the use of vitreous substitutes. ...Nowadays, the vitreous substitutes that are used in clinical practice are mainly divided into gases (air, SF6, C2F6, C3F8) and liquids (perfluorocarbon liquids, silicone oils, and heavy silicone oils). There are specific advantages and drawbacks to each of these, which determine their clinical indications. However, developing the ideal biomaterial for vitreous substitution continues to be one of the most important challenges in ophthalmology, and a multidisciplinary approach is required. In this sense, recent research has focused on the development of biocompatible, biodegradable, and injectable hydrogels (natural, synthetic, and smart), which also act as medium and long‐term internal tamponade agents. This comprehensive review aims to cover the main characteristics and indications for use of the extensive range of vitreous substitutes that are currently used in clinical practice, before going on to describe the hydrogels that have been developed recently and which have emerged as promising biomaterials for vitreous substitution.
Nowadays, there are many drawbacks associated with the different agents used in clinical practice for vitreous substitution. The development of the ideal biomaterial for vitreous substitution remains one of the most important challenges in ophthalmology. In this sense, recent research has focused on the development of biocompatible, biodegradable, and injectable biomaterials, which constitute a promising alternative for vitreous substitution.
The GNAQ and GNA11 genes are mutated in almost 80–90% of uveal melanomas in a mutually exclusive pattern. These genes encode the alpha subunits of the heterotrimeric G proteins, Gq and G11; thus, ...mutations of these genes result in the activation of several important signaling pathways, including phospholipase C, and activation of the transcription factor YAP. It is well known that both of them act as driver genes in the oncogenic process and it has been assumed that they do not play a role in the prognosis of these tumours. However, it has been hypothesised that mutations in these genes could give rise to molecularly and clinically distinct types of uveal melanomas. It has also been questioned whether the type and location of mutation in the GNAQ and GNA11 genes may affect the progression of these tumours. All of these questions, except for their implications in carcinogenesis, remain controversial. Uveal melanoma has a distinctive genetic profile, and specific recurrent mutations, which make it a potential candidate for treatment with targeted therapy. Given that the most frequent mutations are those observed in the GNAQ and GNA11 genes, and that both genes are involved in oncogenesis, these molecules, as well as the downstream signalling pathways in which they are involved, have been proposed as promising potential therapeutic targets. Therefore, in this review, special attention is paid to the current data related to the possible prognostic implications of both genes from different perspectives, as well as the therapeutic options targeting them.
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