Feedback on ophthalmologic telemedicine in a nursing home. 1

Keywords: Telemedicine, teleophthalmology, preventative maintenance, screening, dependency

come

Introduction:

By late 2015, 728,000 individuals were living in homes for the elderly. 80% of them were in an assisted living facility (EHPAD) [START_REF] Muller | 728 000 résidents en établissements d'hébergement pour personnes âgées en 2015[END_REF]. Access to ophthalmologic care for assisted living residents is a public health problem. The assisted living population has a number of medical conditions. In fact, these patients have, on average, 7.9 chronic illnesses [START_REF] Makdessi | En EHPAD, les résidents les plus dépendants souffrent davantage de pathologies aiguës[END_REF]. Ophthalmic conditions are no exception to the rule.

The current structure of ophthalmology practices is geared toward time efficiency in visits, but the methods of consultation are not well-adapted to the management of dependent individuals. At the same time, in France, the number of ophthalmologists continues to decrease, while the need for eye care has increased by a factor of three over the past 30 years [START_REF]Work load of Ophtalmologists in France[END_REF]. To help alleviate this deficiency in medical coverage, the development of telemedicine in ophthalmology may provide an interesting solution. In other countries, this method of consultation is already used in various fashions, which may or may not include an interview with a physician [START_REF] Rathi | The Current State of Teleophthalmology in the United States[END_REF]. For diabetic retinopathy, telemedicine has already been proven effective by a number of studies for diabetic retinopathy screening in isolated patients [START_REF] Gupta | Evidence for Telemedicine for Diabetic Retinal Disease[END_REF][START_REF] Jani | Evaluation of Diabetic Retinal Screening and Factors for Ophthalmology Referral in a Telemedicine Network[END_REF]. For age related macular degeneration, the correlation between so-called "classic" visits and telemedicine visits is excellent [START_REF] Ghemame | Suivi en télémédecine des patients atteints de DMLA[END_REF]. More globally, ophthalmology telemedicine can diagnose a number of vitreoretinal diseases in isolated patients [START_REF] Host | Real-time teleophthalmology video consultation: an analysis of patient satisfaction in rural Western Australia[END_REF]. On patient satisfaction surveys, patients appear satisfied with this new means of consultation [START_REF] Murchison | Reaching the Unreachable: Novel Approaches to Telemedicine Screening of Underserved Populations for Vitreoretinal Disease[END_REF].

A randomized study in Sicily [START_REF] Luca | Tele-health-care in the elderly living in nursing home: the first Sicilian multimodal approach[END_REF] has shown the benefit of a telemedicine model for assisted living patients, which can significantly improve depression scores, psychiatric problems, quality of life scores, and the need for hospital admissions. However, ophthalmology was not part of the data analyzed in this study. Within this context, we performed ophthalmology telemedicine visits including measurement of visual acuity, intraocular pressure, optical coherence tomography and wide field fundus photography between an assisted living facility and our ophthalmology service at the University Medical Center.

Materials and methods:

From June 2018 to November 2018, we performed telemedicine visits with the residents of the assisted living facility at the Janzé (Ille-et-Vilaine) Medical Center. The telemedicine visits could be requested by the resident, the attending physician, an administrator, or a resident's family member.

The patient was examined by a technician with the help of an EHPAD caregiver.

We obtained written consent from each patient (or family member in the case of cognitive impairment) prior to performance of the various examinations. Each patient (or family member in the case of cognitive impairment) was verbally informed that their personal data might be recorded in an anonymous fashion for statistical purposes in a retrospective study.

Demographic data and general past medical history were systematically recorded, with attention to diabetes, hypertension and past ophthalmologic history. The technician then measured the refraction, intraocular pressure with an air-pulse tonometer, distance and near visual acuity, wide field fundus photography (DAYTONA©, Optos, Scotland), and macular and disc OCT (CIRRUS© Spectral Domain HD-OCT, Carl Zeiss Meditec, Germany). All data were transferred to a secure server developed by the Bretagne e-health cooperative.

Following this first technician visit, the patients had a videoconference from the EHPAD with an ophthalmologist at the University Medical Center ophthalmology service, who had previously reviewed the data transferred to the secure server. At the conclusion of the visit, the plan was given to the patient and the clinical care team, followed by a medication prescription via secure messaging as needed, or an appointment for a so-called "classic" visit or additional follow-up.

Nous avons procédé à l'analyse statistique de l'évolution de l'acuité visuelle des patients avant et après notre intervention. Chaque oeil a été analysé indépendamment de l'oeil adelphe. Nous avons procédé à l'analyse en vision de loin et vision de près. Nous avons converti toutes les mesures d'acuité en LogMar pour l'analyse. Elle a été réalisée grâce au test de Student pour échantillons appariés. Nous nous sommes également intéressés à la proportion de malvoyance chez ces patients, malvoyance définie comme une acuité visuelle inférieure ou égale à 3/10 (Échelle de Monnoyer).

L'analyse de celle-ci a été réalisée grâce au test exact de Fisher. Les analyses statistiques ont été effectuées avec l'aide du calculateur en ligne BiostaTGV (https://biostatgv.sentiweb.fr/).

We statistically analyzed the change in the patients' visual acuity from before to after our intervention. Each eye was analyzed independently of the fellow eye. We studied distance and near vision. We converted all the visual acuity measurements to LogMar format for the analysis. This was performed with a Student's t test for paired samples. We also studied the proportion of low vision among these patients, with low vision defined as visual acuity less than or equal to 3/10 (Monoyer scale). This was analyzed with Fisher's exact test. The statistical analyses were performed with the online BiostaTGV calculator (https://biostatgv.sentiweb.fr/).

The study falls within the MR-003 standard methodology.

Results:

Over the six-month study period, we conducted ophthalmology telemedicine visits with 67 patients (mean age 83 +/-8 years). These included 27 men (40%) and 40 women (60%). These telemedicine visits took place one afternoon per week. We were able to examine 5 patients per afternoon on average, with the mean duration of the visit being 40 minutes, 6 minutes of which represented "direct" telemedicine with the physician. The main past medical history reported included hypertension in 44 patients (66%), cognitive or behavioral difficulties in 33 patients (49%), cerebrovascular accidents in 19 patients (28%), and diabetes in 12 patients (18%). 32 patients (48%) did not provide a reason for the visit; these cases had been requested by the EHPAD physician as part of a dependency work-up. 25 patients (37%) complained of decreased vision. The other reasons for consultation are summarized in table 1. The telemedicine visit was able to be requested by the resident, the attending physician, an administrator, or the resident's family.

In 36 cases (54%), we were able to perform a complete visit, including measurement of visual acuity and intraocular pressure as well as performance of wide field fundus photography and OCT. The examinations that were not successfully completed in all cases were fundus photography in 45% (29 patients) and OCT in 53% (35 patients). We were able to measure the intraocular pressure in 95 eyes (71%). The mean pressure was 13.32 mmHg (+/-2.6 mmHg). In our series, no patients had elevated intraocular pressure. For eight patients, no examination could be performed. The main difficulties encountered in the performance of an optimal examination were intellectual impairment and lack of understanding of text, deafness or hearing loss, refusal to participate, and difficulties in positioning at the measurement devices.

During the telemedicine visit, we diagnosed an ophthalmologic condition in 37 patients (55%), and specific management was begun for 14 (37.8%) of them. Among the diagnoses found were cataracts at a surgical stage (14; 37.8%), ocular surface disease such as keratopathy and blepharitis (5; 13.5%), and atrophic AMD without exudative signs (5; 13.5%). We also diagnosed a retinal tear (1; 1.5%), posterior capsule opacification (2; 3%), suspicious eyelid lesion (1; 1.5%) and diabetic maculopathy (1; 1.5%).

In terms of visual acuity, of the 134 eyes studied, we were able to analyze 109 eyes (81%) for distance vision and 83 eyes (61%) for near vision. The mean distance LogMar visual acuity prior to updating the refraction was 0.67 (+/-0.76), or between 2/10 and 2.5/10 on the Monoyer scale. For near vision, the mean LogMar acuity prior to updating the refraction was 0.68 (+/-0.84), or between Parinaud 6 and Parinaud 8. After our intervention, the mean distance visual acuity was measured at 0.52 (+/-0.72) (p<0.0001; 95% CI [0.091-0.211]) (Figure 1). Similarly, after our intervention, mean near acuity was measured at 0.53 (+/-0.76) (p<0.0001; 95% CI [0.0737-0.2205]) (Figure 2). With regard to low vision, the proportion of low-vision eyes decreased in a statistically significant fashion from 54% to 39% (p=0.02; odds ratio 1.86; 95% CI [1.06-3.28]) after our intervention (Figure 3).

For each patient, the decision to begin a specific management and classic ophthalmologic follow-up was discussed in a multidisciplinary fashion with the clinical care team of the EHPAD within 7 days after our on-site visit. In this context, we prescribed artificial tears for 7 patients and a low-vision rehabilitation consultation for 2 patients. A preoperative consultation for lid surgery was scheduled for 2 patients, and for cataract surgery for 2 others. Two patients underwent YAG laser capsulotomy at the University Medical Center. Finally, the retinal tear was treated with an argon laser retinopexy at the University Medical Center, and a specialist consultation was scheduled for intravitreal anti-VEGF injections for management of the diabetic maculopathy case. 30 patients (45%) were given a prescription for corrective lenses. A future follow-up was scheduled for 12 patients (18%).

Discussion:

To our knowledge, this experiment in ophthalmology telemedicine in an assisted living facility is the only one in France to be carried out in this fashion. It gave the residents access to a complete ophthalmology visit, taking advantage of current diagnostic technology. For the residents, we are improving the conditions of the visit: we obviate the need for transportation, since our visits occur in their home; the time allotted to them is increased compared to classic ophthalmology visits, allowing for better cooperation. Finally, the videoconferencing interview preserves the doctor-patient human interaction, since the clinician and patient can speak directly. We informed the clinical care team of the eye health status of the residents within 7 days after our visit. This allowed the EHPAD care team to better adapt the resident's management and environment. In fact, low vision is a source of isolation, and it is critical to diagnose it. Thus, this new information plays a role in the overall management of the elderly patient.

In our experiment, the examination equipment was graciously loaned by the various suppliers, which allowed us to carry out the project much more simply. Indeed, given the number of patients seen, purchasing the equipment at an estimated cost of 150,000 euros would not have been a reasonable or economically viable alternative. Current systems for equipment rental are also still very expensive. Certain measurements such as intraocular pressure for glaucoma screening are not necessarily a must in these patients, due to the slow progression of the disease. Finally, the personnel on site were paid by the assisted living facility; therefore, we did not have to pay personnel. For this experiment, we incorporated a second step in the form of tele-expertise. All the equipment used is portable, including a refractor, slit lamp with video recorder, and non-mydriatic fundus camera. The measurement of visual acuity and acquisition of images was performed at the bedside by a technician. We hope to improve the efficiency of our visits by surmounting the obstacles presented by patient positioning at the various measurement devices (article in the process of being edited).

In France, there are five types of telemedicine defined by Article 78 of Law No. 2009-879 of July 2009, the so-called "HPST" (hospital, patient, health and place of service) law (Art. L6316-1 of the public health code) spelled out in Decree No. 2010-1229 of October 19, 2010. Teleconsultation permits a medical professional to provide a remote consultation through information and communication technology. The other types of telemedicine are: tele-expertise, remote monitoring, tele-assistance, and "regulation." Tele-expertise allows a medical professional to remotely solicit the opinion of one or several medical professionals through information and communication technology. This is primarily a medical act and non-simultaneous response (the patient and physician do not speak with each other). This takes place between two physicians either during or after the initial consultation. Remote monitoring permits a medical professional to remotely interpret data collected at the patient's home. Medical tele-assistance permits a medical professional to remotely assist another healthcare provider in performing a procedure. Medical "regulation" is the physician response to paramedics in an emergency setting. In France, there are telemedicine solutions in ophthalmology, but these do not address assisted living residents. We can cite the "Muraine" protocol [START_REF] Muraine | Mise en place du premier protocole français de[END_REF] and the optical rehabilitation program known as "RNO." The "Muraine" protocol allows ophthalmic technicians to perform vision examinations at a remote facility and then transmit the results for interpretation by an ophthalmologist. However, the patients in question are patients without disease who have seen an ophthalmologist within 5 months. These vision examinations may be performed in nursing homes, optician or ophthalmologist offices, but not in assisted living facilities (EHPADs) per se. The "RNO" protocol authorizes the technician to perform a vision examination in the office in the absence of the ophthalmologist, in the context of renewing or adjusting optical correction. Again, this protocol is not designed for patients in an assisted living facility.

Conclusion:

Ophthalmology telemedicine in the assisted living facility allows an isolated, dependent, poorly mobile population access to care. It permits screening and visual improvement for the residents, while also informing the clinical care team about the eye health of the resident. However, it still needs to be optimized to improve efficacy and efficiency. délégation de tâche en ophtalmologie avec télémédecine dans le pays de Bray en Haute-Normandie.

Revue

Figure 1 :Figure 2 :Figure 3 :

 123 Figure 1: Distribution of distance visual acuities

Table 1 :

 1 Summary of reasons for consultation

	Francophone	d'Orthoptie	-	Vol.	9	-	N°	4	-	p.	234-237	-

Acknowledgements:

This project was able to be completed thanks to Mr. Dubourg, director of cooperative projects at the Rennes University Medical Center, Mrs. Grimaud, director of the Janzé Medical Center, and financing from the Bretagne Regional Health Agency. We hereby extend our appreciation to them.

Disclosure of interest

The authors have no conflicts of interest to disclose.


A Baillif

Martel

Ken Martini

Edouard Fevrier

Sacha Nahon

Stéphanie Baillif

Arnaud Martel
email: martel.a@chu-nice.fr

Martel Arnaud

Bilateral swinging Ozurdex in a patient with bilateral anterior uveitis after cataract surgery

Keywords:

des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

IMAGE JFO

Title : bilateral swinging ozurdex in a patient with bilateral anterior uveitis post cataract surgery Titre : la danse bilatérale des ozurdex chez un patient présentant une uvéite antérieure bilatérale post chirurgie de cataracte We report the case of an 82-year-old patient who presented bilateral anterior uveitis following uneventful bilateral cataract surgery. Despite local steroid treatments, bilateral recurrence of the anterior uveitis with posterior synechia was noted. Bilateral ozurdex injection was performed with persistence of some cells in the anterior chamber. A new bilateral injection was performed during the same session. At one-month post injection, best corrected visual acuity improved (8/10 on both eyes). Intra ocular pression was 12 mmHg on both eyes. For the first time since cataract surgery, slit lamp examination revealed a quiet anterior chamber. However, bilateral eye examination was marked by an anterior and superior position of the two Ozurdex implants (Figure 1) located just behind the posterior capsule (Figure 2). Fundus examination was unremarkable. As demonstrated on the Video, eyes movements provoked an unexpected "dance" of the two Ozurdex implants. The patient did not complain of any visual disturbance.

A too anteriorly Ozurdex injection may be associated with iatrogenic cataract [START_REF] Fevrier | An iatrogenic posterior subcapsular cataract[END_REF] and anterior chamber migration [START_REF] Kang | The clinical outcomes of surgical management of anterior chamber migration of a dexamethasone implant (Ozurdex®)[END_REF]. However, in the case presented herein, the anterior location of the two implants probably helped us to achieve a full anterior chamber inflammation recovery without visual disturbance.

Conflict of interest : none

FIGURES LEGENDS:

Figure 1 : clinical photograph of the patient revealing bilateral anteriorly located Ozurdex implants. Figure 2 : Swept source anterior OCT (Anterion, Heidelberg, Germany) demonstrating the anterior location of the Ozurdex implant in the vitreous cavity just behind the posterior capsule.

VIDEO LEGENDS:

Vidéo 1 : bilateral swinging ozurdex.


Une OACR révélant un Pseudoxanthome élastique CRAO as presenting sign of pseudoxanthoma elasticum. Auteurs : Arnaud. Artus a, *, Paul. Codron a , Claire. Iscar a , Sophie. Bryselbout a , Issam. Chergui b , a Service d'Ophtalmologie, CHU Amiens Picardie, 1 rue du Professeur Christian Cabrol, 80054 Amiens, France b Service d'Ophtalmologie, CH Saint-Quentin, 1 avenue Michel de l'Hospital, 02321 Saint-Quentin, France


Keywords: UO2, PuO2, mixed oxides, syntheses, characterization, dissolution kinetics, plutonium content, powder

Several (U1-xPux)O2±δ powders with different morphologies and different plutonium contents were synthetized using a sol-gel route. All the powders were fully characterized to quantify their structural parameters. After understanding and verification of the morphological effects on mixed oxide dissolution, this study consists of quantification of effect of plutonium content on dissolution kinetics using nitric acid 8.5M at 95°C. Significant differences in dissolution kinetics were observed. Indeed, the plutonium content is a key parameter that has to be considered in studies of (U1-xPux)O2±δ dissolution kinetics. A kinetics law was established and validated for dissolutions within these particular experimental conditions.

Impact of the plutonium content on dissolution kinetics of (U 1-x Pu x )O 2±δ powders Yannis ZIOUANE a , Bénédicte ARAB-CHAPELET b , Gilles LETURCQ b a ORANO Projets -Research Hall of Beaumont-Hague, 30440 Beaumont-Hague b CEA, DES, ISEC, DMRC, University of Montpellier, Marcoule, France

Introduction

The dissolution of spent nuclear fuel in nitric acid is one of the main steps of nuclear fuel recycling by hydrometallurgical process. For this purpose, it is useful to fully understand and quantify the impact of fuel characteristics on dissolution kinetics. In this study, a focus on the impact of the plutonium content of the (U,Pu) oxide on dissolution kinetics was done. Only a few studies were focused on this effect, because of the high radioactivity of these materials and the difficulties to manipulate plutonium. Uriarte et al. [ 1 ] presented the differences in dissolution kinetics between UO2 and PuO2 in nitric medium. The authors described that dissolution kinetics, using nitric acid at 5 mol.L -1 , are approximately twenty million times faster for UO2 compared to PuO2. For the mixed oxide, they found that the more the mixed oxide contains plutonium the slower the dissolution kinetics. Lerch [ 2 ] also described a strong impact of the plutonium content on the kinetics and solubility of the oxides. The author studied oxides with Pu contents ranging from 15 to 25 percent. In this interval, the author proposed to model the impact of Pu amount on dissolution kinetics with a linear regression. Ikeuchi [ 3 ] studied the impact of Pu content ranging from 18 to 29% on spent fuel. Irradiated MOX (Mixed OXides) with Pu content of 18% was estimated to be similar to irradiated fuel LWR (Light-Water Reactor) of FBR axial blancket fuel in term of solubility, although it contains less plutonium in composition,. Above a plutonium content of 18%, the author indicated an exponential decrease of the dissolution kinetic rate with a linear increase of Pu content, and provided an empirical law also taking into account the acidity and temperature. Vollath [ 4 ] studied the (U,Pu) oxide dissolution at different Pu content, ranging from 0 to 100%, varying the acidity for a time period of 6 hours. The author observed no residue at the end of the dissolution of (U1-xPux)O2±Δ mixed oxide with a plutonium content up to 40%. Beyond this value, the percentage of residues increases exponentially until reaching about 100% when the Pu content is greater than 70%. All these authors did not consider the effect of the morphology of the material on dissolution kinetics. Indeed, for UO2 [ 5 ] and PuO2 [ 1 , 6 ] there are differences in dissolution kinetics which can vary by a factor of twenty depending on the morphology of the materials. Thus, no valid law has yet been determined describing the effect of the Pu content on dissolution kinetics. In 1967, studying the dissolution of non-irradiated PuO2 in hydrochloric acid and in nitric acid-calcium fluoride solvent system, Molen [ 7 ] described the effect of the solid-to-liquid ratio on the dissolution rate of plutonium oxide as a function of the morphology, and more particularly the mean crystallite size and the specific surface area, which in turn depends on porosity, pore size distribution, shape, size, and roughness. Among these two parameters, the author indicated that the specific surface area is the predominant parameter. Recently [ 8 ], the effect of morphology of the oxide on the dissolution rates has been quantified on CeO2 and validated on PuO2, evaluating the impact of each morphological parameter could have on the dissolution rates in nitric medium, over a wide range of morphological parameters. Statistically significant effects of crystallite sizes and specific surface area on the dissolution rates were formulated, in the same way Molen had presented. In addition, an empirical law describing how these parameters impact the dissolution kinetics rates was established. All these studies have in common the comparison of compounds with the same "initial mass of oxide/ initial volume of solution" ratio. For a given amount of solid, dissolution kinetic rate increases with higher specific surface area or lower crystallite size owing to more contact between solid particles and solution.

In the first part of this work, a study using different morphologies at the same Pu content has been conducted to validate this morphological law on the dissolution rates whatever the Pu content. In a last part, tests on mixed oxides permit to define an empirical model describing perfectly the effect of the Pu content on the dissolution rates taking care of the morphology of the samples. This paper presents our contribution done recently in Atalante facility at CEA Marcoule to understand the phenomena occurring during the dissolution of actinide oxides in nitric acid.

Experimental section

Synthesis of (U1-xPux)O2±δ powders

Sol-gel route

Synthesis of (U,Pu) oxides using sol-gel route require the use of low acidic and highly concentrated cationic solutions. A 2.9 M U(+VI) monometallic acid deficient uranyl nitrate (ADUN) solution was obtained in a glove-box under negative pressure through dissolution of uranium trioxide into uranyl nitrate solution till solubility limit was reached. After two weeks of stirring, the UO3 excess was filtered from the ADUN solution. The free acidity of the ADUN solution was very low as its pH was around 1.8.

In parallel, a 2.14 M Pu (+IV) monometallic nitrate solution was prepared by concentration/denitration process of a 0.24 M Pu(+IV) monometallic nitrate solution. In order to concentrate a Pu nitrate solution without concentrating the free nitric acidity, a distillation column was used with frequent additions of nitric acid solution of low acidity. Ideally, water should be used but the addition of water would cause Pu hydrolysis locally prior to the mixing of the solution. As shown in Figure 1, the more acidic the solution to be evaporated, the more acidic the vapor and the effective denitration [ 9 ]. Therefore, it is better to add small amount of low acidic solution frequently than larger amount less often, to keep the acidity of the solution to distillate as high as possible during the process of denitration. Addition of nitric acid solution of concentration below 0.5M causes Pu hydroxide colloids generation. Nitric acid of 0.5M was therefore used. As described in Figure 1, the acidity of the solution to evaporate has to be higher than 3M in order to evaporate more nitric acid than the 0.5M added. Using this method, a Pu solution with [Pu] =510g.L -1 and [HNO3] = 1.85 M was obtained.

Articles referring to the sol-gel method deal with the synthesis of microspheres [ 10 , 11 ]. In this paper, protocols were modified to synthesize powders as follows. For the different mixed oxides to produce, corresponding volumes of both solutions were then mixed with the desired stoichiometric ratio for the final oxide. Urea CO(NH2)2 and HMTA (hexamethylenetetramine) solution at low temperature (~5°C) were added to this mixed metal solution. The ratio [HMTA]/[U+Pu] used was equal to 2.0 [ 12 ] while [urea]/ [U+Pu] was 1.7. Once HMTA was dissolved into the cold nitrate solution, the solution was stirred and heated at 80°C. HMTA decomposed at high temperature causing an increase in pH and simultaneous hydrolysis of U and Pu. In a few minutes, solution turned to a gel. For a gel with a [Pu]/[U+Pu] ratio equal to 61% the ratios of the reagents were increased by 20% in order to change the pH of the gelation and therefore attempted to modify the morphology parameters of the final oxide to compare with a "61%" oxide made using the standard ratios. At room temperature, gel were washed with 2 M NH4OH allowing the elimination of the remaining organic matter provided by the reagents. The washed gels were calcined at 220°C for 30 min to remove residual ammonium nitrate and moisture. The dried gels were then calcined under reduced atmosphere Ar/H2 (95/5) to form the different oxides.

Thermal treatments

Heat treatments were performed up to 850°C with a rate of 20°C.min -1 for a majority of the gel. Compounds were maintained to this temperature for 90 min then cooled down to room temperature. A reducing atmosphere Ar/H2 (95/5) was used for these calcinations in order to reduce the uranium to its lower valence (+IV) and therefore have a solid solution (U1-xPux)O2±δ. These conditions are identical to those used by Ziouane et al. [ 5 ] for the UO2 synthesis. This study confirmed the complete reduction of U(+6) to U(+4). To have more than two morphologies with the same Pu content (i.e. 61%), a gel after its synthesis was separated into two batches: the first batch was calcined at 850°C and the other at 1000°C. It has already been shown [ 13 , 14 ] that the increase of the calcination temperature contributes to the densification of the material by decreasing the specific surface area and increasing the crystallite sizes. The powder containing 36% of plutonium was obtained after three calcination cycles including one at 1500°C. At this Pu content, the powder is highly reactive with respect to dissolution [ 4 ], all these cycles of calcination were carried out in order to make the powder more refractive to dissolution.

Characterization

XRD Analysis

XRD (X-Ray Diffraction) analyses of the synthesized powders were performed using a D8 Bruker Advance diffractometer (LynxEye detector) using Cu-Kα radiation (λ=1.5418 Å) especially equipped for radioactive material measurements. Gold was added as an internal standard to calibrate the angular positions of the observed XRD lines. Each powder pattern was recorded within an angular range from 5° to 80° in 2theta, with steps of 0.02° and a counting time of 0.6 s per step. The lattice parameters were determined by Le Bail refinement using the TOPAS software (TOtal Pattern Analysis Solutions) from BRUKER AXS [ 15 ] where only the profile parameters (cell dimensions, peak shapes, background, zero point correction) were refined. The microstrains and average crystallite sizes were calculated with the fundamental parameters method [ 16 ].

Specific surface area measurements

N2 adsorption/desorption isotherm was used for the determination of the biggest specific surface area (> 1 m².g -1 ) and the pore volume, Kr adsorption/desportion was used for smaller specific surface area. The specific surface area was calculated by the Brumauer-Emmett-Teller (BET) 5 point method [ 17 ] from around 1 g of each powder. Adsorption -desorption isotherms were measured at the boiling point of nitrogen (-196 °C) using a Micromeritics TriStar II Version 1.03 nuclearized.

Analysis of uranium and plutonium concentrations in solution by TIMS (Thermal Ionization Mass Spectrometry)

To determine precisely the

[ ] [

] stoichiometry of the synthesized oxides, a complete dissolution of the material was carried out in boiling HNO3/HF (4 M/0.05M) medium. A sample was taken when the powder was completely solubilized, the total dissolution liquor left over was then recycled to recover uranium and plutonium for further experiments using a partitioning column as described by Maillard et al. [ 18 ]. An isotopic analysis was then performed by thermo-ionization to produce ion beams in the TIMS mass spectrometer. The spectrometer used is a Thermo Fisher Scientific Triton. The method involves the evaporation and ionization by heating a dilute solution to be analyzed deposited on a metal ribbon using a micro syringe. The solution is then dried and installed in the source of the instrument. The ribbon is then heated by vacuum Joule effect, allowing the evaporation and ionization of the sample, to form an ion beam which is then analyzed in the mass spectrometer. Ion collectors detect the different beams produced by mass separation. The results are presented as isotopic ratios, given by the measured relative intensities of the different beams.

Dissolution

All the dissolutions described in this work were carried out in a glove box under negative pressure (Figure 2) and consisted of dissolving 300 mg of (U1-xPux)O2±δ powder in 15 mL of nitric acid of 8.5 mol.L -1 concentration. Solution was stirred at 300 rpm and maintained at 368.15 K. 2 h batch dissolutions were performed in a 60 mL maximum capacity reactor. These aggressive conditions are selected because of the refractory character of the oxides to dissolution in nitric medium. The lid of the reactor was equipped with a refrigerating column allowing the recombination of any nitrous vapors escaping from the reactor. The aim of these dissolution experiments was to understand how the Pu content impact dissolution kinetics. The different dissolution kinetics rates were recorded by alpha counting. This device allows determining the plutonium concentration in solution, the uncertainties applied to the experimental measurement are equal to 10% from pre-established standards. The congruence of uranium and plutonium has been verified and the mixed powders dissolve homogeneously. Considering their radioactivity all the liquid effluents of this study were recycled to recover Pu and U for a future study, using separation columns such those used by Maillard et al.

Results and discussion on (U1-xPux)O2± δ samples

Structure and morphology characterizations

Structural description

The Pu stoichiometry of the different samples determined by TIMS are reported on Table 1. For all powder samples, XRD patterns were characteristic of a fluorite-type (U1-xPux)O2±δ structure. Within the XRD detection limits, there was thus no additional phase. Table 1 also gathers the structural parameters of the different oxides. The lattice parameters vary with the Pu content according to the Vegard's law (3.1.1). This law was plotted in Figure 3 from the values presented by Young et al. [ 19 ] for UO2 and Freeman et al. [ 20 ] for PuO2. The experimental lattice parameters are nearly perfectly aligned with this law, indicating that they correspond to the theoretical lattice parameters calculated from the TIMS characterization. In the case of U0.39Pu0.61O2±δ (Expt. No. 850 a), there is a slight deviation from the line corresponding to a slight sub-stoichiometry of the compound, as shown in Table 1.

= -0.071 * [ ] [ + ]

+ 5.467

3.1.1

This deviation from Vegard's law can be explained by variation in oxygen. From the experimental lattice parameter, it is possible to calculate the oxygen stoichiometry of the oxide (U1-xPux)O2±δ from the empiric law (3.1.2) [ 21 ].The fourth column of the table 1 shows the results of this calculation for each material, leading to a perfect stoichiometry, with the uncertainty, for each compound. The oxides resulting from the same calcination temperature presents similar average crystallite sizes (Table 1). Furthermore, the average crystallite sizes seem to increase with the precursors calcination temperature, in accordance with data from the literature describing crystal growth during the sintering process [ 14 ].

The specific surfaces obtained are all of the same order of magnitude and small, but are also in accordance with the values already obtained in the literature for actinide oxides [ 22 ].It also appears from the table that the specific surface area of the oxides appear to be lower when the calcination temperature applied to obtain the oxide was higher.

Validation of the morphologic law

Ziouane et al. [ 8 ] presented the impact of powder morphology on dissolution kinetics of CeO2 and PuO2 defining an empirical law based only on the crystallite size and the specific surface area of the powder. To perfectly describe the effect of the Pu content, it is essential to validate that the effect of the morphology induced on dissolution is valid for (U1-xPux)O2±δ. Thus, three U0.39Pu0.61O2±δ were synthesized with different crystallite sizes and surface areas (Table 1). These oxides were dissolved under the same experimental conditions and the kinetics rates of dissolution are shown in Figure 4. The figure shows that at the same Pu content, the dissolution rate can vary by a factor of 4 only due to morphological differences. This report is not surprising because Ziouane et al. also observed the same behavior on CeO2 compounds: dissolution rate can vary by a factor close to twenty for CeO2 powders presenting different morphologies. The partial orders for the crystallite sizes and the specific surface area determined previously by the kinetic laws of CeO2 and PuO2 [ 1 ] are retained, -1 and 1/3 respectively. The resolution of the system of three equations with an unknown leads to the empirical law 3.2.1. A specific k value was found for U0.39Pu0.61O2±δ powders, independent of the powder morphology. This value expresses the possibility to describe satisfactorily the kinetics of dissolution from the morphological characteristics of the powders. Hence, this empiric morphologic law being verified for CeO2, PuO2 and here U0.39Pu0.61O2±δ, it applied to all uranium, plutonium mixed oxides making possible to dissociate, under same experimental conditions, the effects of the Pu content and the morphological effects.

) = * * +, ./ * 001 2.33 3.2.1

With y the dissolution kinetic rate in %dissolved.min -1 , k = 10 2.34 nm -1 .m -2/3 .g 1/3 .%dissolved 1 .min -1 for U0.39Pu0.61O2 being dissolved in nitric acid 8.5M at 95°C, Tc the crystallite size in nm, SSA the specific surface area in m 2 .g -1 .

Dissolution kinetics of (U1-xPux)O2± δ materials

The experimental conditions of dissolution of all samples of this study were kept constant (i.e. [HNO3] = 8.5M at 95°C, stirring rate of 300 rpm), in order to look at the specific effect of the Pu content on dissolution of (U1-xPux)O2±δ. The determination of the concentration of plutonium in solution allows calculation of the mass of dissolved oxide and thus the percentage of powder dissolved at each instant. All these percentages lead to a linear relationship between dissolution kinetic rate of oxide and Pu content. The dissolutions of oxides of different Pu content are illustrated in Figure 5. As it has already been reported in the scientific literature, increasing the Pu content leads to a decrease in kinetics. A factor close to one thousand is observed between the dissolution kinetics of U0.64Pu0.36O2±δ and PuO2. However here, the dissolution rate of the PuO2 appears faster than the dissolution rate of the U0.24Pu0.76O2±δ, the phenomenon can be explained by morphological parameters making the PuO2 powder more favorable to dissolution than the U0.24Pu0.76O2±δ (due to lower crystallite size and higher specific surface area of the PuO2 powder). The dissolution kinetics rate of the U0.64Pu0.36O2±δ powder is obtained only from two experimental points, because of a high reactivity of this powder. Table 1 presents similar morphological parameters for the studied compounds, with only a factor of 4 between the smallest and largest crystallites size and a factor of 15 between the lowest and highest specific surface area. Hence, there is a consequent effect of the Pu content on the dissolution kinetics. Some tests were carried out under similar experimental conditions on powders with lower Pu content (25% and less) but dissolution rates were too fast to be experimentally measured. It is then possible to quantify the effect of the Pu content of the oxide on its dissolution kinetics rate in nitric acid of 8.5M concentration at 95°C using the determined k value for the different Pu contents studied from Figure 5. The different k values are summarized in Table 2, column "experiment k". By plotting the logarithmic functions of the constant k according to the Pu content, a line is obtained (Figure 6) defining by the regression presented in equation 3.3.1, k value for the Pu content of 57% was not taken into account for this linear regression in order to be used as a validation point. This empiric law defines an effect of Pu content on dissolution kinetics following an exponential function for a range of Pu content between 36 and 100%. The phenomenon is similar to the findings of Ikeuchi [ 3 ] in the range of 18 to 29% Pu. 3.3.1 With %Pu the plutonium content of the oxide powder in percent and k in nm -1 .m - 2/3 .g 1/3 .%dissolved 1 .min -1 .

It may to be noticed that between the two limits of the tested interval (36% and 100% of Pu) the dissolution kinetics rate is multiplied by almost 7500. Looking at the validation point, the model k value for 57% of Pu, is 4.44 for an experiment value of 7.04, so a difference of only 37%. Considering k evolution with respect to Pu content, such little difference between model and experiment figures is acceptable as a slight uncertainty in Pu content could explain this result: a Pu content of 58% rather than 57% would induce a variation of k by 57% for example. Therefore, it is possible to conclude that the effect of the Pu content on the dissolution kinetics can be defined by a power function. As mentioned, the parameters of the function are valid for dissolution in nitric acid of 8.5M concentration at 95°C only. The future work of such study could be to look at the effect of acidity and temperature on the different parameters of the laws used, in order to define a general law modelling the dissolution of (U1-xPux)O2±δ irrespective of the morphologic properties of the powder, its composition (Pu content) and the dissolution conditions (acidity and temperature).

Conclusion

The characterization tools employed in this study were used to describe the Pu content and the morphology of the different powders. As the calcination temperature increases the crystallite size increases resulting in decrease in specific surface area, which is in agreement with literature data.

For the different morphologies of same oxide U0.39Pu0.61O2±δ, a kinetic law has been validated to describe the effect induced by the morphology on the dissolution rates. Although the physical relationship between the dissolution rates and the described morphological properties has not yet been described, mathematically there seems to be a close link between specific surface area, crystallite sizes and the dissolution kinetics of the oxide powders.

Present study indicates a decrease in dissolution kinetics with the increase in Pu content of (U,Pu) oxide. Despite a difference of a factor of about 7500 between the dissolution kinetics of U0,64Pu0,36O2±δ and PuO2, an empirical law could be established and validated describing the effect of the Pu content on dissolution rates at 8.5 mol.L -1 HNO3 concentration at 95°C.

Figure 1 :

 1 Figure 1 : Distillation of nitric acid, link between acidity of the solution to be evaporated and the acidity of the vapor produced.

  [ 18 ].

Figure 2 :

 2 Figure 2 : Photograph of a dissolution test with the stirred and heated solution in a glove-box under depression. The four nozzles on the reactor are used for the temperature regulation and control, the sampling of the solution and the refrigerating column.

Figure 3 :

 3 Figure 3: Evolution of the lattice parameter with Pu content in (U1-xPux)O2±δ solid solution, measured by XRD and compared with Vegard's law of (U1-xPux)O2 .

Figure 4 :

 4 Figure 4 : Dissolution of threeU0.39Pu0.61O2±δ powders in concentrated nitric medium 8.5 mol.L -1 for a dissolution temperature of the system equal to 95°C.

Figure 5 :

 5 Figure 5 : Dissolution of (U1-xPux)O2±δ powders with different Pu contents and different morphologies in the same experimental conditions ([HNO3]=8.5mol.L -1 at 95°C).

Figure 6 :

 6 Figure 6: Relation between the kinetic rate constant and the Pu content of the oxide at 8.5 mol.L -1 heated at 95°C. * = % .6.2 * 10 ./7.83.3.1 With %Pu the plutonium content of the oxide powder in percent and k in nm -1 .m - 2/3 .g 1/3 .%dissolved 1 .min -1 .

Table 1 : Structural parameters for each powders of (U1-xPux)O2±δ synthetized by sol-gel route and calcined at different temperature.

 1

	Compound	Calcination temperature (°C)	Lattice parameter (Ă)		O/ (U+Pu)	Average crystallites sizes (nm)	Specific surface area (m².g -1 )
	U0.64Pu0.36O2±δ	1500	5.4419 (1)		2.01 (2)	48 (1)	0.4 ± 0.3
	U0.43Pu0.57O2±δ	850	5.4276 (1)		1.99 (2)	49 (1)	0.4 ± 0.3
		850 a	5.4321 (1)		1.92 (2)	43 (1)	1 ± 0.1
	U0.39Pu0.61O2±δ	850 b	5.4228 (1)		2.01 (2)	33 (1)	1.5 ± 0.3
		1000 c	5.4241 (1)		2.00 (2)	69 (2)	0.9 ± 0.2
	U0.24Pu0.76O2±δ	850	5.4131 (1)		2.04 (2)	56 (2)	2.2 ± 0.2
	PuO2	850	5.3980 (1)		1.98 (2)	17 (1)	6.3 ± 0.5
			5.47
			5.46			Theoretical lattice parameters Experimental lattice parameters
		Lattice parameter (Å)	5.41 5.42 5.43 5.44 5.45
			5.40
			5.39
			0.0	0.2	0.4	0.6	0.8	1.0
				Plutonium content x of U 1-x Pu x O 2

Table 2 : k values for dissolution of (U1-xPux)O2±δ with varying Pu content, in nitric acid 8.5M at 95°C.

 2

	%Pu	Log %Pu	experiment k	Log k
	36	1.56	374	2.57
			0.19	-0.72
	61	1.79	2.53	0.40
			2.60	0.41
	76	1.88	1.58	0.20
	100	2.00	0.05	-1.30
	57	1.76	7.04	0.85

Y.B. Rao, R.B. Yadav, R.N. Swamy, B. Gopalan, S. Syamsundar, Determination of specific surface area of uranium oxide powders using differential thermal analysis technique, Journal of thermal analysis vol 44, pages 1439-1448, 1995.

Acknowledgements

This research was partly funded by ORANO, France. The authors specially thank C. Lavalette (ORANO) for encouraging this PhD work and for fruitful discussions. Another part was funded under the framework of the European H2020 GENIORS Project (Contract n: 730227).


Gauthier

P Goin

A-S Gauthier
email: asophiegauthier@yahoo.fr

Anne Gauthier

Sophie

atteinte de myélome multiple : à propos d'un cas

Présentation du cas

Discussion

Le myélome multiple est une hémopathie maligne caractérisée par la prolifération de plasmocytes tumoraux clonaux envahissant la moelle hématopoïétique, et produisant le plus souvent une immunoglobuline monoclonale détectable dans le sang et dans les urines [START_REF] Kumar | NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020[END_REF]. Les manifestations oculaires sont rares et séparées en deux groupes. Elles peuvent être secondaires à l'hyperviscosité sanguine ou directement liées à des infiltrations myelomateuses de l'os orbital ou de l'oeil [START_REF] Bradley | Epibulbar Plasmacytoma Masquerading as Subconjunctival Hemorrhage in a Patient With Multiple Myeloma[END_REF].

Toutes les structures de l'oeil peuvent être atteintes (3) mais les atteintes conjonctivales constituent un véritable challenge diagnostic car les lésions peuvent présenter un aspect trompeur s'il n'existe pas de masse tissulaire individualisable bien visible. Chez les patients déjà suivis pour myélome multiple, une atteinte oculaire peut-être le signe d'une maladie non contrôlée ou d'une récurrence. Le diagnostic de certitude repose sur l'analyse histologique. Il doit être rapidement confirmé afin de mettre en place une thérapeutique adaptée.

Légendes :

  Nous rapportons le cas d'une patiente de 50 ans, reçue en consultation aux urgences ophtalmologiques du CHU de Besançon pour survenue de plusieurs épisodes d'hémorragies sous conjonctivales suivis de l'apparition d'une lésion sous-conjonctivale. Cette patiente était prise en charge par le service d'hématologie depuis 1 an dans le cadre du traitement d'un myélome multiple IgG kappa. L'acuité visuelle à la prise en charge était chiffrée à 10/10 ème Parinaud 2 à droite et à gauche. Le tonus oculaire était normal. L'examen du segment antérieur a confirmé la présence de multiples tuméfactions palpébrales supérieures droites et d'un chémosis supérieur droit associé à une lésion sous-conjonctivale indurée sous-jacente (Figure 1). Le reste de l'examen des segments antérieurs et postérieurs était sans particularité. Un scanner orbitaire et cérébral non injecté a été réalisé dans le cadre du bilan étiologique. Il a été mis en évidence la présence d'un infiltrat orbitaire supérieur pré-septal droit (figure 2A), d'un épaississement tissulaire supéro-médial au contact du globe oculaire droit (figure 2 B, C), de multiples lésions osseuses d'origine myélomateuses. Un bilan hématologique complet a été réalisé. Il a été confirmé qu'il s'agissait de lésions d'origine myélomateuses survenues dans le cadre de la progression du myélome multiples en échappement thérapeutique. La patiente présentait alors de multiples plasmocytomes sous cutanée et hypodermiques d'apparition récentes. Un traitement chimiothérapeutique par endoxan® a été instauré. Les lésions ont initialement régressé avant de progresser de nouveau. La patiente a finalement été placée en soins palliatifs.

Figure 1 :

 1 Figure 1 : photographie du segment antérieur oeil droit

Figure 2 :

 2 Figure 2 : TDM orbitaire

Figure 1 :

 1 Figure 1 : photographie du segment antérieur oeil droit


Dr Ghemame Marwane
email: marwane.ghemame@gmail.com

Bon Valentin

Reilhac Astrid

Mouriaux Pr

Frédéric

Suivi en télémédecine des patients atteints de DMLA 1 Telemedicine monitoring for AMD patients 1 er

Keywords: DMLA, télémédecine, téléexpertise, suivi à distance, IVT AMD, remote consultation, telemedicine, intravitreal injection

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction :

Le suivi des patients de plus de 65 ans atteints de Dégénérescence Maculaire Liée à l'Age (DMLA) dans les pays développés est un problème de santé publique du fait du vieillissement de la population et la démographie médicale [START_REF] Haddad | Dégénérescence maculaire liée à l'âge. État des lieux[END_REF][START_REF] Wong | Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis[END_REF][START_REF] Hamard | Bulletin Académie Nationale de Medecine[END_REF]. En 2017, 59% des ophtalmologiques avaient plus de 55 ans et 36 millions d'actes de soins ophtalmologiques ont été réalisés annuellement [4]. De plus, les besoins en soins oculaires ont été multipliés par 3 en 30 ans [START_REF] Pouvourville | Work load of Ophtalmologists in France. Dans le cadre d'une étude des besoins de formation en ophtalmologistes en France, sur la période 2000-2020, analyser l'activité des ophtalmologistes libéraux en nombre de consultations[END_REF]. Les estimations prévoient une demande de 43 millions d'actes en 2025, laissant craindre une mauvaise couverture de la population [START_REF] Bour | Académie Française d'Ophtalmologie : les besoins en ophtalmologie d'ici[END_REF][START_REF] Bour | Rapport SNOF 2006 : l'ophtalmologie et la filière visuelle en France, perspectives et solutions à l'horizon 2025-2030[END_REF][START_REF] Augood | Prevalence of age-related maculopathy in older Europeans: the European Eye Study (EUREYE)[END_REF].

Le nombre de patients atteints de la DMLA est d'un million en France et cette maladie concerne un patient sur 4 après 75 ans [START_REF] Lafuma | Prevalence of visual impairment in relation to the number of ophthalmologists in a given area: a nationwide approach[END_REF][START_REF] Eye | Prevalence of Age-Related Macular Degeneration in the United States | Macular Diseases | JAMA Ophthalmology | JAMA Network[END_REF]. La DMLA est la première cause de cécité légale chez les patients âgés de plus de 65 ans dans les pays développés [START_REF] Augood | Prevalence of age-related maculopathy in older Europeans: the European Eye Study (EUREYE)[END_REF][START_REF] Millien | Etudes et résultats -DREES Direction Recherche Etude Evaluation des Statistiques[END_REF]. L'augmentation de sa prévalence est attendue dans les prochaines décennies, rendant essentiel le développement de techniques de diagnostic et de suivi. Ce suivi constitue une part importante des consultations en cabinet ophtalmologique où les délais d'obtention de rendez-vous peuvent êtres longs [START_REF] Soubrane | Impact de la dégénérescence maculaire néovasculaire : données françaises[END_REF]. Le cout de ce suivi [START_REF] Azzolini | A teleconsultation network improves the efficacy of anti-VEGF therapy in retinal diseases[END_REF] va donc s'accroitre significativement et se heurter aux limites financières du système de soins actuel, constituant un problème de santé publique. Par ailleurs, la réalisation d'une injection intra vitréenne (IVT) d'anti Vascular Endothelial Growth Factor (VEGF) dans le cas d'une DMLA exsudative est une urgence relative, nécessitant un accès aux soins rapide.

Dans ce contexte, la télémédecine constitue une solution de premier ordre, notamment en matière d'accès aux soins et de suivi des patients [START_REF] Brody | Computer use among patients with age-related macular degeneration[END_REF][START_REF]LOI n° 2017-1836 du 30 décembre 2017 de financement de la sécurité sociale pour[END_REF]. La télé-expertise correspond à l'avis d'un professionnel médical à un ou plusieurs autres professionnels médicaux via les technologies de

Déclaration d'intérêts

Les auteurs ne déclarent pas de conflits d'intérêt.

Introduction:

  Le suivi des patients atteints de Dégénérescence Maculaire Liée à l'Age (DMLA) dans les pays développés est un problème de santé publique du fait du vieillissement de la population et la démographie médicale. La télémédecine pourrait être un moyen d'améliorer ce suivi. Objectif : Comparer la concordance d'indication d'un traitement par Injection intra Vitréenne (IVT) d'anti VEGF au décours d'une consultation classique et d'une télé-expertise de patients atteints de DMLA exsudative. Matériel et méthodes : Il s'agit d'une étude prospective menée de Janvier 2017 à Avril 2017, monocentrique, incluant des patients suivis en Pro Re Nata pour une DMLA. La télé-expertise a été menée de façon anonyme par deux lecteurs sur la base du dossier médical regroupant l'acuité visuelle et des photographies du pôle postérieur. La concordance entre les indications d'IVT en suivi conventionnel par rapport au suivi en télé-expertise ainsi que les concordances inter observateurs ont été testées grâce au coefficient Kappa de Cohen via le logiciel SAS statistical software V9.4 (SAS Institute, Cary, NC). Résultats : 104 yeux correspondant à 57 consultations de 42 patients ont été analysés. La moyenne d'âge de l'échantillon était de 82,12 ans (écart type +/-6,4). Les prescriptions d'anti VEGF étaient similaires dans 97% des cas entre la consultation standard et la télé-expertise. Le coefficient Kappa était de 0,8861 [0,76 ; 1,00], p < 0,0001 pour la concordance d'indication d'IVT entre la consultation standard et la consultation en télé-expertise. Le coefficient Kappa était de 0,8441 [0,70 ; 0,99], p < 0,0001 pour la concordance d'indication inter observateur. Nous avons observé 5 cas discordants entre les 2 observateurs.

  photographie grand champ (DAYTONA©, Optos, Scotland) et les antériorités des examens selon le

« Cet article est issu d'une communication orale présentée lors du 124e congrès de la Société Française d'Ophtalmologie en mai