Two-Decade Retrospective Analysis of Endogenous Endophthalmitis in Spain and Mexico: A Comprehensive Study.

Objectives: The aim of this study was to investigate endogenous endophthalmitis (EE) in Spain and Mexico, focusing on microbial patterns, antibiotic resistance, infection sources, risk factors, and patient outcomes. Methods: Over 20 years, 705 endophthalmitis cases were reviewed, and we identified 78 cases of EE in Santiago de Compostela, Spain, and Mexico City, Mexico. Microbial etiology, infection sources, antibiotic resistance, and treatment outcomes were compared between patients from Spain and Mexico. Results: Among the 78 EE cases, 47 (60.25%) were from Spain and primarily had bacterial infections (57.1%, mainly Staphylococcus and Streptococcus). In contrast, 31 cases (39.74%) were from Mexico and had a higher prevalence of fungal infections, particularly Candida (47.1%). Diabetes mellitus was a significant risk factor, and was more common in Mexico (61.3%) than in Spain (37.0%). The Spanish cohort exhibited notable antibiotic resistance, especially in Staphylococcus. Treatment typically involved systemic and intraocular antibiotics, with vitrectomy performed in 61.5% cases. Post-treatment, bacterial infections had higher success rates (approximately 50%) compared with fungal infections (approximately 30%). Evisceration was necessary in 9% cases, and the overall mortality rate was approximately 4.4%; it was slightly higher in Mexico than in Spain. Conclusions: The study highlights significant regional differences in EE between Spain and Mexico, particularly regarding microbial etiology and antibiotic resistance. The findings emphasize the need to adapt healthcare practices to specific regions to improve EE treatment outcomes, underscoring the importance of ongoing research and interregional collaboration to better understand and manage this complex condition.

SPECTRAL-DOMAIN OCT INSIGHTS INTO IDIOPATHIC EPIRETINAL MEMBRANE SURGERY OUTCOMES.

PURPOSE: This study aims to assess the prognostic value of a classification system that includes the presence of ectopic inner foveal layers (EIFL) and other anatomical variables identified in spectral-domain optical coherence tomography (SD-OCT) for idiopathic epiretinal membrane (ERM) surgery. METHODS: A descriptive-analytic, longitudinal, retrospective study was conducted on patients with idiopathic ERMs treated with pars plana vitrectomy (PPV) from January 2017 to December 2021. Clinical data and SD-OCT images were reviewed pre-surgery and 12 months post-surgery. The primary outcome measured was best corrected visual acuity (BCVA) before and after surgery, analyzing the impact of anatomical factors on BCVA in patients undergoing ERM surgery. RESULTS: The study included 342 eyes from 323 patients. Post-surgical evaluations showed significant reductions in central foveal thickness (CFT) across all ERM stages, with most stage 4 ERMs regressing to stage 3. The mean improvement in BCVA was significant for all stages, with earlier stages showing better results. Presence of macular edema (ME) and ellipsoid zone (EZ) disruption were significant predictors of post-surgical BCVA, while disorganization of the retinal inner layer (DRIL) showed association with visual recovery but was not conclusively predictive. CONCLUSION: The study highlights the importance of SD-OCT in assessing retinal changes in idiopathic ERMs, demonstrating the prognostic value of EIFL stage scheme and other anatomical variables like EZ disruption and ME presence on BCVA. These findings offer insights for surgical prognostication and the potential for personalized treatment strategies.

Impact of Driver Mutations on Metastasis-Free Survival in Uveal Melanoma: A Meta-Analysis.

The prognosis of uveal melanoma is significantly influenced by the risk of metastasis, which varies according to clinical and genetic features. Driver mutations can predict the likelihood of disease progression and survival, although the data in the literature are inconsistent. This meta-analysis aimed to evaluate the prognostic significance of driver mutations, including GNAQ, GNA11, BAP1, and SF3B1, in the advancement of uveal melanoma. A comprehensive search of databases yielded relevant studies, and data from 13 studies (848 eyes) were synthesized to assess the impact of these mutations on metastasis-free survival. The BAP1 mutation and negative immunohistochemistry were associated with a higher risk of metastasis (logHR = 1.44, 95% CI 1.05-1.83). GNAQ, GNA11, and SF3B1 mutations did not show a significant increase in risk. In summary, BAP1 has proven to reliably predict the likelihood of disease progression in uveal melanoma, while further studies are needed to establish the significance of other driver mutations.

Multiple neoplasms in patients with uveal melanoma: a systematic review.

PURPOSE: Uveal melanoma is the most prevalent intraocular malignancy in adults, derived from uveal tract melanocytes. This study focuses on the frequency and risk of second primary malignancies in UM patients. METHODS: A PubMed search (1980-2023) identified studies on SPM incidence in UM patients. From 191 references, 14 studies were chosen, focusing on UM, SPMs, and analysing data on demographics and types of neoplasms. RESULTS: Among 31,235 UM patients in 14 studies, 4695 had 4730 SPMs (15.03% prevalence). Prostate (15%), breast (12%), and colorectal (9%) cancers were most common. Digestive system malignancies were highest (19%), with colorectal cancer leading (51%). Breast and prostate cancers were prevalent in respective systems. Lung, bladder, and non-Hodgkin's lymphoma were also notable. The study observed an increasing trend in the frequency of SPMs over time, reflecting broader trends in cancer survivorship and the growing prevalence of multiple malignancies. CONCLUSION: The study highlights a significant presence of SPMs in UM patients, with an increasing trend in frequency over time, emphasizing prostate and breast cancers. This underscores the need for focused surveillance and tailored follow-up for UM survivors, considering their higher risk of additional malignancies. Future research should further investigate SPM aetiology in UM patients.

Bilateral Uveal Melanoma: An Insight into Genetic Predisposition in Four New Unrelated Patients and Review of Published Cases.

Background: Primary bilateral uveal melanoma (BUM) is an exceptionally rare form of uveal melanoma (UM). This study aimed to explore the potential existence of a genetic predisposition towards the development of BUM. Methods: We employed an exome sequencing approach on germline DNA from four unrelated patients diagnosed with BUM, seeking pathogenic or likely pathogenic variants indicative of a genetic predisposition to UM. Results: None of the patients exhibited pathogenic variants in the BAP1 gene. However, loss-of-function (LoF) variants in the TERF2IP and BAX genes were identified in two of the BUM patients. For patients BUM1 and BUM2, no pathogenic/likely pathogenic variants of significant clinical relevance to BUM were found to warrant inclusion in this report. Conclusions: Our findings suggest the presence of yet-to-be-discovered genes that may contribute to UM predisposition, as evidenced by the absence of pathogenic variants in known UM predisposition genes among the four BUM patients studied. The TERF2IP and BAX genes emerge as noteworthy candidates for further investigation regarding their role in genetic predisposition to UM. Specifically, the potential role of UM as a candidate cancer within the spectrum of cancers linked to pathogenic variants in the TERF2IP gene and other genes associated with the shelterin complex warrants further examination. Additional functional studies are necessary to support or challenge this hypothesis.

Foveal microvascular features following inverted flap technique for closure of large macular holes.

PURPOSE: To describe the anatomical and functional outcomes following use of the inverted flap technique (IFT) to close idiopathic macular holes (MH) of diameter greater than 400 µm. To compare the changes in the macular microvascularization following surgery in operated and healthy fellow eyes. METHODS: Retrospective study of 24 patients who underwent vitrectomy and IFT for large MH closure. The main variables were closure pattern, best corrected visual acuity (BCVA) and recovery of the external limiting membrane (ELM) and ellipsoid zone (EZ). Foveal avascular zones (FAZ) and vessel and perfusion densities, obtained by OCT angiography scans, were compared with those in healthy fellow eyes. RESULTS: Complete MH closure was achieved in 95.8% (23/24) of patients 6 months after surgery. There was a significant improvement in postoperative BCVA, from 1.0 to 0.4 logMAR (p < 0.001). The most frequent closure pattern was 1a (62.5%, 15/24), followed by 2c (12.5%, 3/24). The closure pattern was not correlated with height, minimum or maximum diameters or macular hole index (MHI) (p > 0.05). ELM and EZ recovery occurred in 87.5% and 83.3% of cases, respectively. FAZ were smaller in operated eyes than in the fellow eyes (p = 0.012). There were no differences in the vessel or perfusion densities between the operated and fellow eyes (p > 0.05). CONCLUSIONS: Use of the inverted flap technique for large MH closure provides a high rate of functional and anatomical recovery. We observed a reduction in the FAZ following surgery, with no differences in the macular microvascularization parameters, suggesting that the technique is safe.

Primary ILM peeling during retinal detachment repair: a systematic review and meta-analysis.

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.

PARK7/DJ-1 inhibition decreases invasion and proliferation of uveal melanoma cells.

INTRODUCTION: PARK7/DJ-1 is an oncogene that is associated with tumorigenesis in many cancers. Recent studies have demonstrated the importance of DJ-1 in the origin and development of uveal melanoma (UM). We present an analysis of the role of the DJ-1 protein in UM cells, especially in its effect on proliferation and migration. METHODS: UM cells from a primary tumor, Mel 270, and its liver metastasis, OMM2.5, were transfected with lentiviral-delivered shRNA against PARK7/DJ-1. Evaluation of cell migration and proliferation was performed using the xCELLigence real-time cell analyzer (RTCA). The effect of DJ-1 inhibition on the PTEN-Akt signaling pathway was also studied by immunoblotting. RESULTS: The silencing of PARK7/DJ-1 oncoprotein expression produced a significant decrease of phosphorylated Akt (S473) in Mel270 and in metastatic OMM2.5 UM cells with no alteration on tumor suppressor PTEN expression. The diminution of PARK7/DJ-1 expression significantly inhibited real-time proliferation and invasion of Mel270 and OMM2.5 and the invasion potential of the metastatic cells. CONCLUSION: DJ-1 appears to play a key role on the PTEN/Akt pathway in UM. DJ-1 inhibition appears to have a negative effect on proliferation and invasion of UM cells. This suggests DJ-1 as a potential therapeutic target in UM.

GNAQ and GNA11 Genes: A Comprehensive Review on Oncogenesis, Prognosis and Therapeutic Opportunities in Uveal Melanoma.

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.