Silicone Oil Tamponade for Therapy of Primary Retinal Detachment in Patients Who Live at High Altitudes.

BACKGROUND: Uncomplicated rhegmatogenous retinal detachment (RRD) is mainly treated with vitrectomy and gas tamponade or, alternatively, scleral buckling surgery. However, gas tamponade inflates at high altitudes, causing significant complications. Silicone oil (SO) tamponade volume is unaffected by atmospheric pressure and may be used in patients who live or must undertake travel at high altitudes. PURPOSE: To determine the anatomical and functional outcomes after pars plana vitrectomy (PPV) with SO tamponade in primary uncomplicated RRD. METHODS: Twenty-eight consecutive cases of patients operated between January 2017 and December 2022 in Jules-Gonin University Eye Hospital in Lausanne were included in this retrospective study. All patients had a follow-up of at least 3 months after SO removal. RESULTS: Primary reattachment was achieved in all 28 eyes. Mean follow-up was 17.2 months (range: 3 - 51 months) after SO removal. Mean age at the time of intervention was 60 years (range: 21 - 80 years). Vision was stabilized or improved in 27 eyes (96%). One patient demonstrated a slight visual acuity decrease due to cataract formation at the last follow-up. In all patients, SO was removed 2 to 5 months after primary repair. In 14 of the 21 phakic patients, concomitant cataract surgery was performed. No surgical complications were encountered. Postoperatively, 5 (18%) patients had ocular hypertension, presumably steroid related, that was successfully controlled with topical treatment. CONCLUSION: PPV with SO injection seems to be a safe and efficient surgical approach in the treatment of primary uncomplicated RRD in patients living at high altitudes and was associated with good anatomical and functional outcome in our series. However, the need for a follow-up surgery to remove SO should be weighed in these cases.

Management of Coats-Like Disease in a Forty-Four-Year-Old Patient with FSHD Type I.

A forty-four-year-old female patient known for FSHD type I, with unremarkable past ocular history, complained of progressive visual acuity deterioration during a routine ophthalmological visit. Best-corrected visual acuity (BCVA) was 1.0 decimal Snellen equivalent bilaterally. Dilated fundus examination showed evidence of retinal Coats-like disease in the left eye, while the right eye showed significant retinal vascular tortuosity. Multimodal examinations (OCT scans and FA-fluorescein angiography) revealed large areas of retinal ischemia, thus confirming a retinal vascular disorder compatible with the diagnosis of Coats-like disease. Left eye laser photocoagulation of the ischemic areas was performed to avoid neovascular complications that had not been detected during follow-up visits (12 months), and BCVA in the left eye remained stable at 1.0 decimals Snellen equivalent. Coats-like disease in a patient affected by FSHD type I should always be screened even in the absence of any prior ocular diseases. Guidelines concerning the ophthalmological management of adults affected by FSHD are lacking. Based on this case, we recommend performing a yearly complete ophthalmological checkup with dilated fundus examination and retinal imaging. Patients should, furthermore, be encouraged to seek medical attention when noticing deterioration of visual acuity or other visual symptoms in order to avoid missing potential sight-threatening ocular complications.

Comparison of visual performances of enhanced monofocal versus standard monofocal IOLs in a mini-monovision approach.

PURPOSE: To compare visual performance and quality of life in patients who received either monofocal intraocular lenses (IOLs) or an enhanced monofocal IOL in a mini-monovision target approach. BACKGROUND: Monofocal lenses are the most common intraocular IOLs employed during cataract surgery because of their relatively low cost and good performance for distance sight. However, these lenses, generally, do not exonerate patients from spectacle use for near or intermediate tasks. On the other hand, enhanced monofocal IOLs (e.g., Tecnis Eyhance®) feature optical properties providing patients with good intermediate visual outcomes. Satisfactory near visual acuity results, regardless of IOL type, may be achieved through mini-monovision. We assessed visual performance outcomes between these IOLs, in a mini-monovision approach. METHODS: Retrospective case series of patients who underwent bilateral cataract surgery at our institution with implantation of Alcon SN60WF, J&J Tecnis DCB00 or J&J Tecnis Eyhance® DIB00 with a pre-operative mini-monovision target. The postoperative spherical equivalent was measured by a Nidek® auto-refractometer. Best-uncorrected binocular visual acuity (BUBVA) at far (3 m), intermediate (66 cm), and near (40 cm) distance and binocular contrast sensitivity (100%, 25%, and 5%, all at 1 m) were measured using Snellen and Pelli-Robson charts, respectively. Visual performance in daily life was evaluated with the Cataract VF-14 quality of life survey. RESULTS: 71 patients (35 in the monofocal IOL and 37 enhanced IOL group) were enrolled. Patients implanted with enhanced IOL exhibited statistically significant better BUBVA results at 66 cm and 40 cm distances compared to patients in the monofocal group. Additionally, patients in the enhanced IOL group presented a better contrast sensitivity in lower contrast conditions (5%) than patients with monofocal IOL. The quality of life survey showed statistically significant higher scores in daily activities without spectacles for patients with enhanced IOL. CONCLUSION: Enhanced monofocal IOLs, combined with a mini-monovision approach, provided patients with good visual performance at all tested distances, with superiority of enhanced monofocal IOLs at near and intermediate distances.

Functional Analysis of a Novel, Non-Canonical RPGR Splice Variant Causing X-Linked Retinitis Pigmentosa.

X-linked retinitis pigmentosa (XLRP) caused by mutations in the RPGR gene is one of the most severe forms of RP due to its early onset and intractable progression. Most cases have been associated with genetic variants within the purine-rich exon ORF15 region of this gene. RPGR retinal gene therapy is currently being investigated in several clinical trials. Therefore, it is crucial to report and functionally characterize (all novel) potentially pathogenic DNA sequence variants. Whole-exome sequencing (WES) was performed for the index patient. The splicing effects of a non-canonical splice variant were tested on cDNA from whole blood and a minigene assay. WES revealed a rare, non-canonical splice site variant predicted to disrupt the wildtype splice acceptor and create a novel acceptor site 8 nucleotides upstream of RPGR exon 12. Reverse-transcription PCR analyses confirmed the disruption of the correct splicing pattern, leading to the insertion of eight additional nucleotides in the variant transcript. Transcript analyses with minigene assays and cDNA from peripheral blood are useful tools for the characterization of splicing defects due to variants in the RPGR and may increase the diagnostic yield in RP. The functional analysis of non-canonical splice variants is required to classify those variants as pathogenic according to the ACMG's criteria.

Disentangling the complexity of tumor-derived extracellular vesicles.

The tumor microenvironment encompasses an intertwined ensemble of both transformed cancer cells and non-transformed host cells, which together establish a signaling network that regulates tumor progression. By conveying both homo- and heterotypic cell-to-cell communication cues, tumor-derived extracellular vesicles (tEVs) modulate several cancer-associated processes, such as immunosuppression, angiogenesis, invasion, and metastasis. Herein we discuss how recent methodological advances in the isolation and characterization of tEVs may help to broaden our understanding of their functions in tumor biology and, potentially, establish their utility as cancer biomarkers.

Dynamics in protein translation sustaining T cell preparedness.

In response to pathogenic threats, naive T cells rapidly transition from a quiescent to an activated state, yet the underlying mechanisms are incompletely understood. Using a pulsed SILAC approach, we investigated the dynamics of mRNA translation kinetics and protein turnover in human naive and activated T cells. Our datasets uncovered that transcription factors maintaining T cell quiescence had constitutively high turnover, which facilitated their depletion following activation. Furthermore, naive T cells maintained a surprisingly large number of idling ribosomes as well as 242 repressed mRNA species and a reservoir of glycolytic enzymes. These components were rapidly engaged following stimulation, promoting an immediate translational and glycolytic switch to ramp up the T cell activation program. Our data elucidate new insights into how T cells maintain a prepared state to mount a rapid immune response, and provide a resource of protein turnover, absolute translation kinetics and protein synthesis rates in T cells ( https://www.immunomics.ch ).

Biology and therapeutic targeting of tumour-associated macrophages.

Macrophages sustain tumour progression by facilitating angiogenesis, promoting immunosuppression, and enhancing cancer cell invasion and metastasis. They also modulate tumour response to anti-cancer therapy in pre-clinical models. This knowledge has motivated the development of agents that target tumour-associated macrophages (TAMs), some of which have been investigated in early clinical trials. Here, we provide a comprehensive overview of the biology and therapeutic targeting of TAMs, highlighting opportunities, setbacks, and new challenges that have emerged after a decade of intense translational and clinical research into these multifaceted immune cells. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles.

Extracellular vesicles (EVs), including exosomes, modulate multiple aspects of cancer biology. Tumor-associated macrophages (TAMs) secrete EVs, but their molecular features and functions are poorly characterized. Here, we report methodology for the enrichment, quantification, and proteomic and lipidomic analysis of EVs released from mouse TAMs (TAM-EVs). Compared to source TAMs, TAM-EVs present molecular profiles associated with a Th1/M1 polarization signature, enhanced inflammation and immune response, and a more favorable patient prognosis. Accordingly, enriched TAM-EV preparations promote T cell proliferation and activation ex vivo. TAM-EVs also contain bioactive lipids and biosynthetic enzymes, which may alter pro-inflammatory signaling in the cancer cells. Thus, whereas TAMs are largely immunosuppressive, their EVs may have the potential to stimulate, rather than limit, anti-tumor immunity.

The Self-Inactivating KamiCas9 System for the Editing of CNS Disease Genes.

Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expression of the Cas9 protein and high editing efficiency. In the first application, the gene responsible for Huntington's disease (HD) was targeted in adult mouse neuronal and glial cells. Mutant huntingtin (HTT) was efficiently inactivated in mouse models of HD, leading to an improvement in key markers of the disease. Sequencing of potential off-targets with the constitutive Cas9 system in differentiated human iPSC revealed a very low incidence with only one site above background level. This off-target frequency was significantly reduced with the KamiCas9 system. These results demonstrate the potential of the self-inactivating CRISPR/Cas9 editing for applications in the context of neurodegenerative diseases.