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AIMS: To compare effectiveness of subconjunctival triamcinolone acetonide injections and intravitreal injections of dexamethasone 700 µg implants in reducing central macular thickness (CMT) in uveitic and postoperative macular oedema (ME). METHODS: We conducted an open-label, French multicentre randomised comparative trial with a logarithmic CMT non-inferiority margin set at 0.06. Patients were adults with non-infectious inflammatory ME, without any contraindication to the treatments. They were randomised 1:1 to receive either triamcinolone or dexamethasone. The primary endpoint was the difference in CMT among treated eyes between baseline and 2 months, measured with spectral-domain optical coherence tomography. Secondary outcomes included visual acuity, laser flare, vitreous haze, duration of action, tolerance to injections and adverse events. RESULTS: Between January 2016 and January 2020, 106 patients were enrolled (54 in the triamcinolone group and 52 in the dexamethasone group). Subconjunctival triamcinolone injections seemed to be non-inferior to intravitreal dexamethasone injections, especially at month 3 (and nearly at month 1). Nevertheless, we could not demonstrate it, with a treatment effect at month 2 of 0.05 (0.01 ; 0.09) (p value=0.001). This was corroborated by post hoc analyses in the postoperative subgroup, for whom the non-inferiority was nearly demonstrated at month 2 with a treatment effect of 0.02 (-0.03 ; 0.08) (p=0.37). There was no significant difference in the occurrence of adverse effects. CONCLUSION: We could not demonstrate the non-inferiority of triamcinolone injections at month 2. Nevertheless, they showed some efficacity, particularly in treating postoperative ME, being as safe as dexamethasone injections, without any loss of chance if a therapeutic switch is necessary.
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Treatment decisions for neovascular age-related macular degeneration (nAMD) in the setting of individualised treatment regimens are adapted to disease activity. The main marker of disease activity and trigger for re-treatment with anti-vascular endothelial growth factor (anti-VEGF) agents is the presence of retinal fluid on optical coherence tomography (OCT). Recently, attention has focused on the impact of residual retinal fluid on nAMD management. Based on a literature review and the combined clinical experience of an international group of retinal specialists, this manuscript provides expert guidance on the treatment of nAMD according to fluid status and proposes an algorithm for determining when to administer anti-VEGF treatment according to residual fluid status. We explore the role of residual fluid in treatment decisions and outcomes in nAMD, taking into consideration fluid evaluation and, in particular, distinguishing between fluid in different anatomic compartments and at different stages during the treatment course. Current limitations to identifying and interpreting fluid on OCT, and the assumption that any residual retinal fluid reflects ongoing VEGF activity, are discussed.
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PURPOSE: To assess whether oculoplastic surgeries can be performed without any topical and systemic antibiotics, in a "100% antibiotic free" fashion. METHOD: We conducted a multicenter retrospective study between November 2017 and December 2022. Patients who underwent an oculoplastic procedure were screened. Patients who received preoperative or postoperative systemic antibiotics were excluded. Intraoperative IV antibiotics were allowed. Patients were divided into two groups: those who were treated with local antibiotics ointments (LATB group) and those who were treated without local antibiotics ointments (LATB free group) postoperatively. The primary outcome was the incidence of surgical site infections (SSI). The relationship between the use of local antibiotics and the occurrence of SSI was assessed using Fisher's exact test. The alpha risk was set to 5% and two-tailed tests were used. RESULTS: Among the 947 procedures included, 617 were included in the LATB group and 330 in the LATB free group. 853 and 80 procedures were classified Altemeier class 1 (clean) and class 2 (clean-contaminated) surgeries, respectively. Overall, 310 (32.73%) procedures were performed without any systemic nor topical antibiotics (100% antibiotic free fashion). SSI occured in four (4/617; 0.65%) and five (5/330; 1.52%) procedures in the LATB and LATB free group respectively, without any statistical difference between the groups (p = 0.290). A subgroup analysis was carried out by excluding the procedures performed under prophylactic intraoperative intravenous antibiotics and did not reveal any statistical difference between the two groups (p = 0.144). All SSI patients were treated with systemic antibiotics with favorable outcomes. Postoperative wound dehiscence was the only risk factor associated with postoperative SSI (p = 0.002). CONCLUSION: This study suggests that performing a "100% antibiotic free" oculoplastic surgery without systemic and topical antibiotics is reasonable in Altemeier class 1 and class 2 procedures.
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PURPOSE: To report new indications for deep temporalis fascia (DTF) grafts in the ophthalmic field. METHODS: Monocentric retrospective interventional case series study. All the patients who underwent a DTF graft in an unpublished new indication over the study period (May 2020-October 2023) were included. For each patient, gender, age, graft indication, outcomes, complications, and follow-up duration were collected. In most cases, the DTF graft was covered by a vascularized flap. RESULTS: Eight patients underwent a DTF graft over the study period. The indications were: radiotherapy-induced scleral necrosis in three cases, tendinoplasty to replace the inferior rectus muscle tendon invaded by a locally advanced conjunctival carcinoma in one case, Ahmed glaucoma valve tube exposure in one case, intraocular lens with scleral fixation exposure in one case, orbital cerebrospinal fluid fistula (orbitorrhea) in one case, and post-traumatic complete corneal graft loss in one case. The DTF graft was successful in 87.5% of cases after a mean follow-up of 11.4 months. No complications were observed. CONCLUSIONS: DTF graft is a highly versatile graft that can be easily harvested. New indications for DTF grafts may include the repair of radiotherapy-induced scleral necrosis, the creation of oculomotor tendon and the temporary packing of large ocular tissue loss in an emergency context. Further studies with a longer follow-up are needed to confirm our preliminary results.
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Fascia , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Fascia/trasplante , Procedimientos Quirúrgicos Oftalmológicos/métodos , Adulto , Estudios de Seguimiento , Músculo Temporal/trasplante , Colgajos Quirúrgicos , Anciano de 80 o más AñosRESUMEN
Metastatic uveal melanomas are highly resistant to all existing treatments. To address this critical issue, we performed a kinome-wide CRISPR-Cas9 knockout screen, which revealed the LKB1-SIK2 module in restraining uveal melanoma tumorigenesis. Functionally, LKB1 loss enhances proliferation and survival through SIK2 inhibition and upregulation of the sodium/calcium (Na+ /Ca2+ ) exchanger SLC8A1. This signaling cascade promotes increased levels of intracellular calcium and mitochondrial reactive oxygen species, two hallmarks of cancer. We further demonstrate that combination of an SLC8A1 inhibitor and a mitochondria-targeted antioxidant promotes enhanced cell death efficacy in LKB1- and SIK2-negative uveal melanoma cells compared to control cells. Our study also identified an LKB1-loss gene signature for the survival prognostic of patients with uveal melanoma that may be also predictive of response to the therapy combination. Our data thus identify not only metabolic vulnerabilities but also new prognostic markers, thereby providing a therapeutic strategy for particular subtypes of metastatic uveal melanoma.
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Melanoma , Neoplasias de la Úvea , Humanos , Calcio , Proliferación Celular , Melanoma/tratamiento farmacológico , Especies Reactivas de Oxígeno , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patologíaRESUMEN
Uveal melanoma (UM) is the most common intraocular tumour in adults, with dismal prognosis once metastases develop, since therapeutic options for the metastatic disease are ineffective. Over the past decade, novel cancer therapies based on immunotherapy have changed the landscape of treatment of different forms of cancer leading to many hopes of improvement in patient overall survival (OS). VISTA, LAG-3 and PRAME are novel promising targets of immunotherapy that have recently gained attention in different solid tumours, but whose relevance in UM remained to be comprehensively evaluated until now. Here, we studied the protein expression of VISTA, LAG-3 and PRAME using immunohistochemistry in representative whole tissue sections from primary UM cases in a cohort of 30 patients from a single centre (Nice University Hospital, Nice, France). The expression of each of these markers was correlated with different clinical and pathological parameters, including onset of metastases and OS. We demonstrated the protein expression of VISTA and LAG-3 in small lymphocytes infiltrating the tumour, while no expression of the proteins was detected in UM cells. For PRAME, nuclear expression was observed in UM cells, but no expression in tumour infiltrating immune cells was identified. Increased levels of VISTA expression in tumour infiltrating lymphocytes (TILs) were associated with nuclear BAP1 expression and better prognosis. Higher levels of LAG-3 in TILs were associated with higher levels of CD8-positive TILs. PRAME nuclear positivity in melanoma cells was associated with epithelioid cell dominant (>90%) UM histological subtype, higher mitotic numbers and a higher percentage of chromosome 8q gain. This study proposes VISTA as a novel relevant immune checkpoint molecule in primary UM and contributes to confirm LAG-3 and PRAME as potentially important immunotherapy targets in the treatment of UM patients, helping to expand the number of immunotherapy candidate molecules that are relevant to modulate in this aggressive cancer.
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Melanoma , Neoplasias de la Úvea , Adulto , Humanos , Antígenos de Neoplasias/genética , Aberraciones Cromosómicas , Inmunoterapia , Melanoma/genética , Pronóstico , Neoplasias de la Úvea/terapia , Neoplasias de la Úvea/genéticaRESUMEN
AIMS: To assess the efficacy and safety of a standardised hyperbaric oxygen therapy protocol (HBOT) monitored by fluorescein angiography (FA) in patients with retinal artery occlusion (RAO). METHODS: It is a prospective, non-comparative, monocentric study conducted between July 2016 and March 2022. All consecutive patients diagnosed with RAO within 7 days underwent visual acuity measurement, FA, macular optical coherence tomography (OCT) and OCT-angiography. They received two daily HBOT sessions (2.5 atmosphere absolute, 90 min) until revascularisation assessed by FA. Complete ophthalmic follow-up was scheduled at day 14, day 21 and at 1 month. The main outcome measure was a best-corrected visual acuity (BCVA) improvement defined as a decrease ≥0.3 logMAR at 1 month. RESULTS: Thirty-one patients were included and received a mean number of 33.9 (13-56) HBOT sessions. Retinal revascularisation was observed in 48.4% and 87.1% of patients at days 14 and 21, respectively. The mean BCVA on referral and at 1 month was 1.51 logMAR and 1.10 logMAR, respectively. Fifteen (48.4%) patients achieved the main outcome measure. Six (19.4%) patients experienced minor barotrauma that did not require HBOT discontinuation. The univariate analysis showed that antiplatelet-treated patients (p=0.044) and patients with a poor initial BCVA (p=0.008) were more likely to achieve a BCVA improvement. OCT-angiography was not sensitive enough to diagnose RAO or assess revascularisation. CONCLUSION: In RAO patients monitored by FA until spontaneous revascularisation of the central retinal artery, HBOT was effective and safe.
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Liquid biopsy and circulating tumor cell (CTC) screening has gained interest over the last two decades for detecting almost all solid malignancies. To date, the major limitation in terms of the applicability of CTC screening in daily clinical practice is the lack of reproducibility due to the high number of platforms available that use various technologies (e.g., label-dependent versus label-free detection). Only a few studies have compared different CTC platforms. The aim of this study was to compare the efficiency of four commercially available CTC platforms (Vortex (VTX-1), ClearCell FX, ISET, and Cellsearch) for the detection and identification of uveal melanoma cells (OMM 2.3 cell line). Tumor cells were seeded in RPMI medium and venous blood from healthy donors, and then processed similarly using these four platforms. Melan-A immunochemistry was performed to identify tumor cells, except when the Cellsearch device was used (automated identification). The mean overall recovery rates (with mean recovered cells) were 39.2% (19.92), 22.2% (11.31), 8.9% (4.85), and 1.1% (0.20) for the ISET, Vortex (VTX-1), ClearCell FX, and CellSearch platforms, respectively. Although paramount, the recovery rate is not sufficient to assess a CTC platform. Other parameters, such as the purpose for using a platform (diagnosis, genetics, drug sensitivity, or patient-derived xenograft models), reproducibility, purity, user-friendliness, cost-effectiveness, and ergonomics, should also be considered before they can be used in daily clinical practice and are discussed in this article.
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Melanoma , Células Neoplásicas Circulantes , Neoplasias de la Úvea , Humanos , Células Neoplásicas Circulantes/patología , Reproducibilidad de los Resultados , Melanoma/patología , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/patología , Biomarcadores de Tumor/metabolismoRESUMEN
Ophthalmic malignancies include various rare neoplasms involving the conjunctiva, the uvea, or the periocular area. These tumors are characterized by their scarcity as well as their histological, and sometimes genetic, diversity. Uveal melanoma (UM) is the most common primary intraocular malignancy. UM raises three main challenges highlighting the specificity of ophthalmic malignancies. First, UM is a very rare malignancy with an estimated incidence of 6 cases per million inhabitants. Second, tissue biopsy is not routinely recommended due to the risk of extraocular dissemination. Third, UM is an aggressive cancer because it is estimated that about 50% of patients will experience metastatic spread without any curative treatment available at this stage. These challenges better explain the two main objectives in the creation of a dedicated UM biobank. First, collecting UM samples is essential due to tissue scarcity. Second, large-scale translational research programs based on stored human samples will help to better determine UM pathogenesis with the aim of identifying new biomarkers, allowing for early diagnosis and new targeted treatment modalities. Other periocular malignancies, such as conjunctival melanomas or orbital malignancies, also raise specific concerns. In this context, the number of biobanks worldwide dedicated to ocular malignancies is very limited. The aims of this article were (i) to describe the specific challenges raised by a dedicated ocular malignancy biobank, (ii) to report our experience in setting up such a biobank, and (iii) to discuss future perspectives in this field.
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INTRODUCTION: Central vision loss due to diabetic macular edema (DME) is related to the macular edema itself but also, in some cases, to alterations of the foveal avascular zone (FAZ). The aim of this trial was to study changes in macular vessels in eyes with DME treated with aflibercept using optical coherence tomography angiography (OCTA). METHODS: This was a longitudinal, prospective, noncontrolled, single-arm study. The primary objective was the quantitative assessment of macular vessels over time in patients with DME treated with intravitreal aflibercept during a 48-week follow-up using OCTA. RESULTS: Twenty-six DME eyes from 26 patients were included (mean age, 64.6 years; women, 53.8%; prior anti-VEGF treatment, 46.1%). Each eye received a mean (SD) of 7.2 (2.2) injections. The following parameters of the FAZ did not change during the 48-week follow-up: the mean (SD) FAZ area varied from 0.19 (0.19) mm2 at baseline (n = 22) to 0.23 (0.20) mm2 at week 48 (n = 15), boundary from 1.54 (1.21) to 2.04 (1.20) mm, and circularity from 0.45 (0.33)% to 0.57 (0.20)%. There was no change in perfusion density and vessel density of the macula in the 3-mm circle. As expected, mean central retinal thickness, macular volume, and visual acuity improved during follow-up. CONCLUSION: No change in macular perfusion was observed in eyes with DME during a 48-week follow-up after intravitreal injections of aflibercept. Randomized controlled trials using OCT angiography in large populations with extended observation periods are needed to assess changes in macular vessels after intravitreal anti-VEGF treatment.
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Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Humanos , Femenino , Persona de Mediana Edad , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Tomografía de Coherencia Óptica/métodos , Inhibidores de la Angiogénesis , Estudios Prospectivos , Angiografía con Fluoresceína/métodos , Factor A de Crecimiento Endotelial Vascular , Inyecciones Intravítreas , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
PURPOSE: To compare the effect of antiseptics and antibiotics on the occurrence of Infectious Keratitis (IK) secondary to Corneal Foreign Body (CFB) removal. METHODS: Multicenter retrospective study conducted between June 2020 and June 2022 in patients referred for CFBs and treated with Picloxydine (Group 1) or Tobramycin (Group 2) for 7 days. A follow-up visit was scheduled on Day 3 (D3) and a phone call on D30. The primary outcome measure was the occurrence of IK. RESULTS: 307 patients (300 men) with a mean age of 42.8 (14.8) years were included. The mean (SD) time to consultation was 43.1 (45.6) hours. Picloxydine and Tobramycin were given to 155 and 152 patients. Half of patients (n = 154, 50.2%) were building workers and 209 (68.1%) did not wear eye protections. CFBs were mainly metallic (n = 292, 95.1%). Upon referral, rust was found in 220 patients (72.1%). A burr was used in 119 (38.9%) patients. IK occurred in 15 (4.9%) patients, 8 (5.3%) in Group 1 and 7 (4.5%) in Group 2 (p = 0.797). IK was successfully treated in all cases. Persistent rust was found in 113 patients (36.9%) on D3 without difference between burr or needle use (p = 0.278). On D3, corneal healing was delayed in 154 patients (47.2%), mainly in burr-treated patients (p = 0.003). The mean (SD) work stoppage duration was 0.32 (0.98) days. CONCLUSION: IK rate was 4.9%. The efficacy of antibiotics and antiseptics was similar on CFB removal. Using a burr was associated with a longer healing time. CFBs had a limited social impact.
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Antiinfecciosos Locales , Cuerpos Extraños en el Ojo , Queratitis , Masculino , Humanos , Adulto , Antibacterianos/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Estudios Retrospectivos , Tobramicina/uso terapéutico , Queratitis/inducido químicamente , Cuerpos Extraños en el Ojo/tratamiento farmacológicoRESUMEN
PURPOSE: Compare 0.30% sodium hyaluronate (0.30%HA) ocular gel with 0.18%HA eye drops in terms of improvement of ocular signs and symptoms, in patients with moderate to severe dry eye disease (DED). METHODS: This was a multicentric, randomized, investigator-masked, non-inferiority, comparative study conducted over 84 days. Three visits were scheduled, testing fluorescein corneal and conjunctival staining (Oxford and Van Bijsterveld scores), tear film break-up time (TBUT), Schirmer test, DED symptoms, 5-Item-Dry-Eye-Questionnaire (5-DEQ), patient and investigator satisfaction and frequency of instillation. RESULTS: At Day 35 (D35) and Day 84 (D84), both groups (n = 35 each) had a significant improvement in corneal staining (p < 0.001) with no inter-group difference. Van Bijsterveld score improved earlier (D35) for 0.30%HA suggesting a faster effect on conjunctival epithelium healing. There was no difference between the two concentrations in terms of TBUT or Schirmer improvements; however, the Schirmer test increase was only significant for 0.30%HA at D35 (p = 0.040). At D35 and D84, both groups showed similar improvements of DED symptoms and DEQ-5 score. Furthermore, treatment satisfaction was similar for the 2 formulations suggesting that daily use of 0.30%HA do not cause gel-related blurred vision disturbances. Frequency of instillation was similar for both groups. CONCLUSION: Our study demonstrates the non-inferiority of 0.30%HA gel compared to 0.18%HA solution in patients with moderate to severe DED. Because of its gel formulation and higher HA concentration providing prolonged comfort without causing visual disturbances, 0.30%HA gel might be adapted for bedtime use or during the day in more severe conditions.
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Síndromes de Ojo Seco , Ácido Hialurónico , Humanos , Conjuntiva , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/diagnóstico , Fluoresceína , Ácido Hialurónico/uso terapéutico , Soluciones Oftálmicas , LágrimasRESUMEN
PURPOSE: The purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France. METHODS: RAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here. RESULTS: Overall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02279537.
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Inhibidores de la Angiogénesis , Degeneración Macular , Humanos , Francia/epidemiología , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza VisualRESUMEN
Purpose: Reconstruction of the posterior lamella after eyelid tumor removal is challenging and not consensual. Tarsus is the most suitable graft, but is only available in small amounts. Herein, we aim to determine the most appropriate way to replace the tarsus by comparing the biomechanical, histological, and optical properties of five commonly used grafts. Methods: This study was conducted at the University hospital of Nice between June 2019 and June 2020. Five posterior lamella grafts (tarsus, conchal cartilage, sclera, hard palate, and dermis) were harvested in five fresh frozen cadavers. Biomechanical properties were assessed by tractometry. Collagen and elastin fibers were analyzed by using histological analysis and optical characterization with the second harmonic generation imaging. Results: The mean Young's modulus was 8.92 MPa (range, 2.90-22.90 MPa), 1.05 MPa (range, 0.39-1.76 MPa), 8.72 MPa (range, 2.0-23.50 MPa), 2.57 MPa (range, 0.41-4.35 MPa), and 1.44 MPa (range, 0.71-2.30 MPa) for the tarsus, the conchal cartilage, the sclera, the hard palate mucosa, and the dermis, respectively. The mean tensile strength was 3 MPa (range, 1.70-6.88 MPa), 0.54 MPa (range, 0.13-0.79 MPa), 2.87 MPa (range, 1.23-5.40 MPa), 1.4 MPa (range, 0.21-2.40 MPa) and 1.0 MPa (range, 0.46-1.43 MPa) for the tarsus, the conchal cartilage, the sclera, the hard palate mucosa, and the dermis, respectively. Hard palate mucosa was the closest to the tarsus regarding the ratio of elastin and collagen fibers. The average second harmonic generation intensity was 221 arbitrary units (a.u.) (range, 165-362 a.u.), 182 a.u. (range, 35-259 a.u.), 369 a.u. (range, 206-533 a.u.), 108 a.u. (range, 34-208 a.u.), and 244 a.u. (range, 195-388 a.u.) for the tarsus, the conchal cartilage, the sclera, the hard palate mucosa, and the dermis, respectively. The hard palate mucosa and the dermis were the closest to the tarsus regarding the collagen fiber size and orientation, respectively. Conclusions: By attributing 2 points for each characteristic (biomechanical, histological, and optical), the hard palate mucosa and the sclera seem to be the most suitable grafts to replace the tarsus. Translational Relevance: The aim of this article was to assess the biomechanical, histological and optical characteristics of five of the most commonly used tarsal grafts; this may be helpful in decisions for clinical practice.
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Introduction: We aimed to assess the efficacy and safety of a standardized hyperbaric oxygen (HBO2) therapy protocol in patients with retinal artery occlusion (RAO). Methods: A retrospective study was conducted in our tertiary care center from July 2016 to September 2019. Patients experiencing central RAO and branch RAO for less than seven days were included. Once the diagnosis was made, patients were urgently referred to the HBO2 department to receive a first 90-minute HBO2 session at a pressure of 2.5 ATA. Patients underwent two daily sessions seven days a week for at least 15 days. If no reperfusion was seen on fluorescein angiography on Day 15, treatment was continued for an additional week with an assessment on Day 21. The primary endpoint was BCVA improvement defined as a decrease by 0.3 logMAR at one month. Results: Twenty-eight patients were included during the study period. Fifty-seven percent of patients were treated more than 12 hours after the onset of the first symptoms. The mean BCVA was 1.5 logMAR at the time of referral and improved to 0.9 logMAR after HBO2 (p=0.001). A multivariate analysis identified a high blood pressure (p=0.039) and a low initial BCVA (p=0.005) as poor prognostic factors. Conclusion: Performing HBO2 sessions twice daily at a pressure of 2.5 ATA appears to be an effective and safe treatment for RAO.
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Oxigenoterapia Hiperbárica , Oclusión de la Arteria Retiniana , Humanos , Oxigenoterapia Hiperbárica/efectos adversos , Estudios Retrospectivos , Oclusión de la Arteria Retiniana/terapia , Oxígeno , Angiografía con FluoresceínaRESUMEN
To assess anatomical and functional outcomes after switching from dexamethasone implant (DEXi) to fluocinolone acetonide implant (FAci) in 113 diabetic macular edema eyes, a multicentric retrospective observational study was conducted. Seventy-five eyes (73.5%) were switched 1−8 weeks after their last DEXi. The mean best-corrected visual acuity improved to 59.8 letters at month 4 and remained stable during the follow-up. The mean central macular thickness (CMT) significantly decreased during the follow-up, with a minimum of 320.9 µm at month 3. The baseline CMT was higher in eyes that received the last DEXi >8 weeks versus <8 weeks before the first FAci (p < 0.021). After FAci injection, additional treatments were needed in 37 (32.7%) eyes. A longer diabetes duration (p = 0.009), a longer time between the last DEXi and the first FAci (p = 0.035), and a high baseline CMT (p = 0.003) were risk factors for additional treatments. The mean intraocular pressure was <19 mmHg at all timepoints, with no difference between eyes receiving the last DEXi ≤8 weeks or >8 weeks before the switch. Switching from DEXi to FAci in DME is effective and safe. A short time between the last DEXi and the first FAci reduced CMT fluctuations and the need for early additional treatments.
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Age-related macular degeneration (AMD) was described for the first time in the 1840s and is currently the leading cause of blindness for patients over 65 years in Western Countries. This disease impacts the eye's posterior segment and damages the macula, a retina section with high levels of photoreceptor cells and responsible for the central vision. Advanced AMD stages are divided into the atrophic (dry) form and the exudative (wet) form. Atrophic AMD consists in the progressive atrophy of the retinal pigment epithelium (RPE) and the outer retinal layers, while the exudative form results in the anarchic invasion by choroidal neo-vessels of RPE and the retina. This invasion is responsible for fluid accumulation in the intra/sub-retinal spaces and for a progressive dysfunction of the photoreceptor cells. To date, the few existing anti-AMD therapies may only delay or suspend its progression, without providing cure to patients. However, in the last decade, an outstanding number of research programs targeting its different aspects have been initiated by academics and industrials. This review aims to bring together the most recent advances and insights into the mechanisms underlying AMD pathogenicity and disease evolution, and to highlight the current hypotheses towards the development of new treatments, i.e., symptomatic vs. curative. The therapeutic options and drugs proposed to tackle these mechanisms are analyzed and critically compared. A particular emphasis has been given to the therapeutic agents currently tested in clinical trials, whose results have been carefully collected and discussed whenever possible.
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Envejecimiento , Degeneración Macular , Anciano , Humanos , Degeneración Macular/tratamiento farmacológico , Células Fotorreceptoras , Retina , Epitelio Pigmentado de la RetinaRESUMEN
The NOTCH signaling system regulates a variety of cellular processes during embryonic development and homeostasis maintenance in different tissues and contexts. Hence, dysregulation of NOTCH signaling is associated with a plethora of human cancers, and there have been multiple efforts to target key components of this pathway. In this review, we briefly highlight the latest research advances in understanding HES6, a poorly studied component of the NOTCH pathway. We summarize the role of HES6 in cancers with a focus on uveal melanoma. Finally, we discuss the ongoing efforts to target the NOTCH-HES6 axis in cancers.
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Melanoma , Neoplasias de la Úvea , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Femenino , Humanos , Embarazo , Proteínas Represoras/metabolismo , Transducción de SeñalRESUMEN
Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) have become the standard of care for age-related macular degeneration (AMD). Although most pivotal trials have used monthly injections, alternative strategies that enable the injections to be administered on a more flexible schedule, including pro re nata (PRN) and treat-and-extend (T&E) regimens, are being applied more frequently. This review sought to provide further scientific evidence about the visual outcomes and treatment burden among the currently available anti-VEGF agents and regimens, including aflibercept, ranibizumab, abicipar and brolucizumab. To this end, a systematic review of published randomized studies was conducted from the MEDLINE and EMBASE databases and the Cochrane library, and a meta-analysis was applied to the obtained data using single-means modeling to compare the efficacy and maintenance among the different available treatments and regimens at Years 1 and 2. Quality analysis identified the best-informed data for modeling purposes. Overall, 47 relevant publications were retrieved for the analysis. Superior efficacy, meaning that there were observed improvements in visual acuity (VA) and central retinal thickness (CRT), occurred with monthly versus PRN regimens, yet a higher IVI number was also observed. Conversely, the T&E regimens displayed similar efficacy to the monthly regimens, but with a reduced IVI number. Aflibercept T&E exhibited similar efficacy to ranibizumab T&E, but with significantly lower IVI numbers at both Year 1 (p < 0.0001) and Year 2 (p = 0.0011). Though all of the regimens resulted in maintained efficacy between Years 1 and 2, the required IVI number varied. The retrieved data did not enable other regimens or newer anti-VEGF agents such as brolucizumab to be compared. In conclusion, the T&E regimens were shown to be the most efficient, optimizing durable effectiveness whilst minimizing the IVI number in newly diagnosed exudative AMD, with aflibercept requiring the lowest IVI number.