Lux study: Contribution of a three-dimensional, high dynamic range, ultra-high-definition heads-up visualization system to a significant delivered light intensity decrease during different types of ocular surgeries.

OBJECTIVE: To explore the hypothesis that using a large, three-dimensional (3D), ultra-high-definition (4K), heads-up display (HUD) system in a real-life setting may be associated with a significant reduction in light intensity (LI) delivered during various types of eye surgery. METHODS: Single center, post-learning curve observational study of 142 independent consecutive cases: 73 cataracts and 69 vitrectomies (VR). For each group, the only variable setting was the LI. The LI delivered by each source was calibrated in lumens (lm). RESULTS: In the VR group, the delivered LI dramatically decreased from the 80% reference to 27.8%±13.2% (P<0.0001) (4.3 to 1.5lm). Among these surgeries, 91.3% needed 40% or less LI (2.3lm). The corneal transparency and quality of pupil dilation showed some correlation with the results. In the cataract group, the difference was even more spectacular, from 80% to 15%±11.3% (P<0.0001) (2.5 to 0.3lm). Among these surgeries, 80.8% required less than 20% LI (0.5lm). The surgical time, LI variations and type of cataract seemed to influence the results, down to 9.6%±5.4% (P<0.0001) (0.22lm) for nuclear cataracts, which represented 63% of the cataract sample. CONCLUSION: The digital signal amplification with this HUD system allows comfortable posterior as well as anterior segment surgery despite the decrease in incident light, suggesting an unprecedented reduction in the risk of phototoxicity compared to conventional systems as well as a likely improvement in patient comfort.

Patient experience of anti-vegf intravitreal injection.

Intravitreal anti-vascular epithelial growth factor (anti-VEGF) injections have revolutionised the treatment of macular diseases, but can be stressful for the patient. We surveyed 904 patients receiving injections at 5 centres in France regarding their feelings toward anti-VEGF injections. The mean age was 77.4 years, and the injections were performed mostly for age related macular degeneration (72%). Half of the patients had previously received>10 injections, 35.6% had received 3-10 injections, and 14.2% had received<3 injections. The mean (SD) stress score was 4.2 [on a scale from 1-10 (0=least stressful, 10=extremely stressful)]. Most patients (70%) reported low to moderate stress (score ≤5). The number of previous injections did not influence stress scores. Paradoxically, 61.2% of patients reported finding injections to be less stressful over time. Most patients found injections to be less traumatic than expected (64%) or just as they had anticipated (25%). Most patients (88%) were not bothered by the presence of other patients in the waiting room. Most patients (78.8%) preferred to be injected quickly before they had time to feel stressed about the procedure. Injections were generally well accepted; most patients would prefer to maintain their current schedule of injections and their current vision (55.7%), or would be willing to have more frequent injections for better vision (39.5%). Our results suggest that stress appears to be more related to the patient's psychological make-up than to the treatment experience or the number of injections received.

The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development.

Graft versus host disease (GvHD), which is the primary complication of allogeneic bone marrow transplantation, can alter the intestinal barrier targeted by activated donor T-cells. Chemical inhibition of the stress protein HSP90 was demonstrated in vitro to inhibit T-cell activation and to modulate endoplasmic reticulum (ER) stress to which intestinal cells are highly susceptible. Since the HSP90 inhibitor 17-allylamino-demethoxygeldanamycin (17AAG) is developed in clinics, we explored here its ability to control intestinal acute GvHD in vivo in two mouse GvHD models (C57BL/6BALB/c and FVB/NLgr5-eGFP), ex vivo in intestine organoids and in vitro in intestinal epithelial cultures. We show that 17AAG decreases GvHD-associated mortality without impairing graft versus leukemia effect. While 17AAG effect in T-cell activation is just moderate at the dose used in vivo, we observe a striking intestinal integrity protection. At the intestine level, the drug promotes the splicing of the transcription factor X-box binding protein 1 (XBP1), which is a key component of the ER stress. This effect is associated with a decrease in intestinal damage and an increase in Lgr5(+) stem cells, Paneth cells and defensins production. The importance of XBP1 splicing control is further confirmed in cultured cells and organoids of primary intestinal epithelium where XBP1 is either shRNA depleted or inhibited with toyocamycin. In conclusion, 17AAG has a protective effect on the epithelial intestinal barrier in mouse models of acute GvHD. This compound deserves to be tested in the therapeutic control of acute GvHD.

[Treatment of age-related macular degeneration: Expert opinion and therapeutic algorithm]. / Traitement de la dégénérescence maculaire liée à l'âge : avis d'experts et algorithme thérapeutique.

UNLABELLED: Intravitreal injections (IVT) of aflibercept are indicated in France for the treatment of neovascular age-related macular degeneration (AMD). An induction phase consisting of 3 monthly IVTs followed by follow-up visits and IVTs every other month during the first year is recommended. However, it may be necessary to adjust this schedule for some patients who might benefit from a more tailored approach, namely a follow-up visit immediately after the induction phase. The goal was to develop a treatment algorithm that would reflect current clinical experience and the opinions of experts on neovascular AMD. METHODS: A group of retinologists took positions on therapeutic questions regarding management of AMD using a nominal group technique (NGT). The results were combined to create a treatment algorithm. RESULTS: Seventy-nine percent of experts considered that the approved schedule was efficacious when fluid was completely resorbed after the induction phase. Ninety-four percent of experts recommended, after a successful induction phase, a monthly follow-up visit for 3 to 6 months in order to determine the rhythm of recurrence for each patient. Ninety-six percent of experts recommended that persistent fluid after the induction phase, even if visual acuity is improved satisfactorily, should be a criterion for systematic retreatment. CONCLUSION: The proposed algorithm (expert opinion) after the first year of use of aflibercept in France captures the complexity of the clinical cases that exist in daily practice and the necessity for regular follow-ups.

[Management of macular edema secondary to retinal vein occlusion]. / Prise en charge de l'œdème maculaire secondaire à une occlusion veineuse rétinienne.

BACKGROUND: In recent years, intravitreal injections have added to the treatment modalities available for macular edema (ME) secondary to retinal vein occlusion (RVO). This article aims to provide an update regarding the management of ME secondary to RVO. METHODS: A work group met in order to analyze the literature available on Embase/PubMed, regarding treatments for venous occlusion that have received market approval and are reimbursed in France. In total, 33 articles were selected. Consensus within the group for recommendations was based on this data from the literature review and clinical experience and was reported in this article. RESULTS: The management of ME secondary to branch retinal vein occlusion (BRVO) or central vein occlusion of the retina (CRVO) differs on a number of points. Methods of best practice were discussed separately for BRVO and CRVO, taking into account various ocular and associated parameters. DISCUSSION: Ranibizumab and dexamethasone implant are the first-line treatments for visual impairment due to ME secondary to RVO. The choice of either of these drugs may take into account various ocular and extraocular parameters. A change of treatment to one or the other or to laser may also be considered during follow-up.

Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells.

The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 supports survival is far from complete. In this work, we demonstrate both in rat and humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii) phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel different levels of CK2-dependent regulation of Par-4 between species. In rats, the phosphorylation by CK2 at the major site, S124, prevents caspase-mediated Par-4 cleavage (D123) and consequently impairs the proapoptotic function of Par-4. In humans, CK2 strongly impairs the apoptotic properties of Par-4, independently of the caspase-mediated cleavage of Par-4 (D131), by triggering the phosphorylation at residue S231. Furthermore, we show that human Par-4 residue S231 is highly phosphorylated in prostate cancer cells as compared with their normal counterparts. Finally, the sensitivity of prostate cancer cells to apoptosis by CK2 knockdown is significantly reversed by parallel knockdown of Par-4. Thus, Par-4 seems a critical target of CK2 that could be exploited for the development of new anticancer drugs.

Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity.

Heat shock protein 27 (HSP27) accumulates in stressed cells and helps them to survive adverse conditions. We have already shown that HSP27 has a function in the ubiquitination process that is modulated by its oligomerization/phosphorylation status. Here, we show that HSP27 is also involved in protein sumoylation, a ubiquitination-related process. HSP27 increases the number of cell proteins modified by small ubiquitin-like modifier (SUMO)-2/3 but this effect shows some selectivity as it neither affects all proteins nor concerns SUMO-1. Moreover, no such alteration in SUMO-2/3 conjugation is achievable by another HSP, such as HSP70. Heat shock factor 1 (HSF1), a transcription factor responsible for HSP expression, is one of the targets of HSP27. In stressed cells, HSP27 enters the nucleus and, in the form of large oligomers, binds to HSF1 and induces its modification by SUMO-2/3 on lysine 298. HSP27-induced HSF1 modification by SUMO-2/3 takes place downstream of the transcription factor phosphorylation on S303 and S307 and does not affect its DNA-binding ability. In contrast, this modification blocks HSF1 transactivation capacity. These data show that HSP27 exerts a feedback inhibition of HSF1 transactivation and enlighten the strictly regulated interplay between HSPs and HSF1. As we also show that HSP27 binds to the SUMO-E2-conjugating enzyme, Ubc9, our study raises the possibility that HSP27 may act as a SUMO-E3 ligase specific for SUMO-2/3.

[Reactivation of ocular toxoplasmosis after laser in situ keratomileusis]. / Réactivation d'une choriorétinite toxoplasmique après un traitement par LASIK.

Laser in situ keratomileusis (LASIK) is a safe and efficient refractive surgical procedure that provides excellent results in most cases. Several complications have been reported, most of them related to the posterior segment of the eye. Although they are quite rare, a growing number of vitreoretinal pathologic conditions after LASIK have been reported. To date no article has reported an inflammatory or infectious disease of the posterior segment after a LASIK procedure. We report a case of reactivation of toxoplasmic chorioretinitis that occurred 5 days after a LASIK procedure. Clinical outcome was spontaneously favorable after 1 month, with no loss of vision. Although a causal effect between LASIK and toxoplasmic chorioretinitis reactivation cannot be proven with a single case report, we stress the importance of dilated fundus examination in LASIK preoperative assessment: our case suggests that in the presence of preoperative toxoplasmic chorioretinitis scars, increased retinal monitoring is required.

[Progressive essential iris atrophy associated with chronic cystoid macular edema]. / Atrophie essentielle de l'iris associée à un oedème maculaire cystoïde chronique.

We describe a first clinical case associating progressive essential iris atrophy (iridocorneal epithelial syndrome, or ICE syndrome) and chronic cystoid macular edema. The clinical presentation and therapeutic progression suggest an inflammatory retinal barrier rupture as seen in Irvine-Gass syndromes. OCT or angiographic exploration should be systematically performed in cases of ICE syndrome to detect a subclinical macular edema.

[Bilateral anterior acute ischemic optic neuropathy complicating optic nerve head drusen. Apropos of a case]. / Neuropathie optique ischémique antérieure aiguë bilatérale compliquant des druses de la papille. A propos d'un cas.

A case of bilateral Anterior Ischemic Optic Neuropathy (AION) which is related to buried optic nerve head drusen is presented. Such an etiology has rarely been described and is poorly-documented in the literature. This etiologic diagnosis is brought by the imaging techniques: fluorescein angiography, B-scan ultrasonography and computed tomography. The pathogenesis may be related to the compressive effects encountered in a small scleral canal. The other complications of optic nerve head drusen are described and their similar mechanisms discussed.

[Anisocoria disclosing malignant lymphoma]. / Anisocorie révélatrice d'un lymphome malin.

Intraocular lymphoma is a rare disease. We present a patient in which anisocoria led to the diagnosis of iris lymphoma and systemic malignant non Hodgkin's lymphoma.

[Accuracy and reproducibility of the Eyesys corneal topographic analysis system]. / Fiabilité et reproductibilité du système d'analyse topographique cornéenne Eyesys.

Corneal topographic analysis has become quite useful for corneal surgery. Quantitative data on the quality and accuracy of the available instruments are not well known. We studied the accuracy and the reproducibility of the Eyesys machine using 4 calibrated balls: 8.99 mm, 7.93 mm, 7.10 mm, 6.13 mm. The machine is accurate (precision less than 0.1D for all the balls) and reproducible (4 measurements) with a SD less than 0.05 diopter for all the balls except for the 55.04's ball (0.06 to 0.1). We also studied reproducibility with six normal corneas using the same method. SD was 0.26 diopter for keratometry and 0.50 diopter for the astigmatism value.