David Peralta
email: david.peralta@cea.fr

Jérémie Salomon

Jean-Frederic Martin

Eric De Vito

Jean-François Colin

Adrien Boulineau

Carole Bourbon

Benjamin Amestoy

Yvan Reynier

Jean-Frédéric Martin

Celine Tisseraud

Roger Pellenc

Jean-Louis Ferrandis

Didier Bloch

Sébastien Patoux

Influence of Al and F Surface Modifications on the Sudden Death Effect of Si-Gr/Li1.2Ni0.2Mn0.6O2 Li-Ion Cells

Keywords: Cathode, Lithium batteries, Coating, Lithium-rich materials

Introduction

The expected expansion of Electrified Vehicles (EV) in the coming years gives rise to the question of how to produce low-cost and environmentally friendly batteries. In 2020, global passenger car sales reached 1.9 M units BEV and 0.5 M units PHEV. It is forecasted that by 2030, BEV will increase to 7.3 M units and 0.8 M units PHEV [START_REF] Pillot | The Rechargeable Battery Market: Value Chain and Main Trends 2020-2030[END_REF]. Even if this new transport technology is a real opportunity to improve air quality in cities, the limitation of the dependence on critical and toxic materials such as cobalt is one of the key success to consider this technology as a green solution. Moreover, a significant increase of the acceptance of EVs can only come via both an increase of the driving range and a significant cost reduction. These two last specifications are at the origin of the current "high energy density race" and of the development of new high-energy cathode materials. Currently, the most promising materials that can cope with all these specifications belong to the lithium-rich layered oxides family.

Lithium-rich layered oxides are cobalt-free materials, and offer high specific energies and capacities (>250 mAh/g). The structure of these materials is a matter of debate in the scientific community. When some researchers describe the lithium-rich layered structure as a solid solution, others lean towards a composite structure built of LiMO2 and Li2MO3 domains (M = Mn, Ni) [START_REF] Thackeray | Advances in manganeseoxide 'composite' electrodes for lithium-ion batteries[END_REF][START_REF] Boulineau | Evolutions of Li1.2Mn0.61Ni0.18Mg0.01O2 during the Initial Charge/Discharge Cycle Studied by Advanced Electron Microscopy[END_REF][START_REF] Johnson | Synthesis, Characterization and Electrochemistry of Lithium Battery Electrodes: xLi2MnO3•(1-x)LiMn0.333Ni0.333Co0.333O2 (0≤ x ≤0.7)[END_REF][START_REF] Rossouw | Lithium manganese oxides from Li2MnO3 for rechargeable lithium battery applications[END_REF][START_REF] Lu | Lack of Cation Clustering in Li[NixLi1/3-2x/3Mn2/3-x/3]O2 (0 x ≤ 1/2) and Li[CrxLi(1-x)/3Mn(2-2x)/3]O2 (0 < x < 1)[END_REF][START_REF] Li | In Situ X-ray Diffraction Study of Layered Li-Ni-Mn-Co Oxides: Effect of Particle Size and Structural Stability of Core-Shell Materials[END_REF]. Complex electrochemical reactions result from this special structure. As an example, in the well-known Li1.2Ni0.2Mn0.6O2 composition, the manganese is at the 4+ oxidation state; so that only Ni 2+ could be oxidized at such level during electrochemical oxidation. Thus, considering the Ni 2+ /Ni 4+ redox couple, only 0.4 lithium can be removed from the structure, and this can only explain 126 mAh/g of the total specific capacity.

Many researchers worked to understand the reason of the extracapacity. Some authors demonstrated that a part of the oxygen of the structure can evolve in peroxo/superoxo-like species and can cycle reversibly [START_REF] Koga | Reversible Oxygen Participation to the Redox Processes Revealed for Li1.20Mn0.54Co0.13Ni0.13O2[END_REF][START_REF] Koga | Different oxygen redox participation for bulk and surface: A possible global explanation for the cycling mechanism of Li1.20Mn0.54Co0.13Ni0.13O2[END_REF][START_REF] Muhammad | Evidence of reversible oxygen participation in anomalously high capacity Li-and Mn-rich cathodes for Li-ion batteries[END_REF][START_REF] Sathiya | High Performance Li2Ru1-yMnyO3 (0.2 ≤ y ≤ 0.8) Cathode Materials for Rechargeable Lithium-Ion Batteries: Their Understanding[END_REF][START_REF] Sathiya | Reversible anionic redox chemistry in high-capacity layered-oxide electrodes[END_REF]. Despite its numerous advantages, the lithium-rich layered oxides suffer from a structure evolution when the cell is cycled above 4.3V [START_REF] Croy | Countering the Voltage Decay in High Capacity xLi2MnO3•(1-x)LiMO2 Electrodes (M=Mn, Ni, Co) for Li+-Ion Batteries[END_REF][START_REF] Croy | Li2MnO3-based composite cathodes for lithium batteries: A novel synthesis approach and new structures[END_REF][START_REF] Peralta | Role of the composition of lithium-rich layered oxide materials on the voltage decay[END_REF][START_REF] Zou | Probing and suppressing voltage fade of Li-rich Li1.2Ni0.13Co0.13Mn0.54O2 cathode material for lithium-ion battery[END_REF][START_REF] Yang | Mitigating voltage decay in high-capacity Li1.2Ni0.2Mn0.6O2 cathode material by surface K+ doping[END_REF]. This phenomenon induces a progressive fade of the cell working voltage and a loss in energy density during cycling. Other drawbacks such as low Crate capability and high first irreversible capacity could also be pointed out. Some studies highlight that surface treatments can enhance electrochemical performances of lithium-rich layered oxides. Metal oxide, phosphate and fluoride coatings are mainly used in the literature [START_REF] Zhang | Surface Modification of Li1.2Mn0.54Ni0.13Co0.13O2 Cathode Material with Al2O3/SiO2 Composite for Lithium-Ion Batteries[END_REF][START_REF] Zou | Improvement of electrochemical performance for Li-rich spherical Li1[END_REF][START_REF] Meng | Surface modification of Li-rich layered Li[END_REF][START_REF] Meng | Improving cycling stability and suppressing voltage fade of layered lithium-rich cathode materials via SiO2 shell coating[END_REF][START_REF] Chen | Effect of Li3PO4 coating of layered lithium-rich oxide on electrochemical performance[END_REF][START_REF] Zhang | Improvement of the Cycling Stability of Li-Rich Layered Mn-Based Oxide Cathodes Modified by Nanoscale LaPO4 Coating[END_REF][START_REF] Zhao | Design of surface protective layer of LiF/FeF3 nanoparticles in Li-rich cathode for high-capacity Li-ion batteries[END_REF][START_REF] Myung | Functionality of Oxide Coating for Li[Li0.05Ni0.4Co0.15Mn0.4]O2 as Positive Electrode Materials for Lithium-Ion Secondary Batteries[END_REF][START_REF] Zheng | The effects of TiO2 coating on the electrochemical performance of Li[END_REF][27][START_REF] Shi | Enhanced cycling stability of Li[Li0.2Mn0.54Ni0.13Co0.13]O2 by surface modification of MgO with melting impregnation method[END_REF][START_REF] Zhao | Enhanced Electrochemical Performance of Li [ Li0.2Ni0.2Mn0.6 ] O2 Modified by Manganese Oxide Coating for Lithium-Ion Batteries[END_REF][START_REF] Guan | Enhancing the electrochemical performance of Li1.2Ni0.2Mn0.6O2 by surface modification with nickel-manganese composite oxide[END_REF][START_REF] Sun | The Role of AlF3 Coatings in Improving Electrochemical Cycling of Li-Enriched Nickel-Manganese Oxide Electrodes for Li-Ion Batteries[END_REF][START_REF] Chen | Synthesis and performances of Li-Rich@AlF3@Graphene as cathode of lithium ion battery[END_REF][START_REF] Sun | AlF3 Surface-Coated Li[Li0.2Ni0.17Co0.07Mn0.56]O2 Nanoparticles with Superior Electrochemical Performance for Lithium-Ion Batteries[END_REF][START_REF] Kim | Effect of aluminum fluoride coating on the electrochemical and thermal properties of 0.5Li2MnO3•0.5LiNi0.5Co0.2Mn0.3O2 composite material[END_REF][START_REF] Qu | Enhanced Electrochemical Performance of Ni-Rich Cathode Materials with Li1.3Al0.3Ti1.7(PO4)3 Coating[END_REF][START_REF] Li | TiO2-coated LiNi0.9Co0.08Al0.02O2 cathode materials with enhanced cycle performance for Li-ion batteries[END_REF][START_REF] Zheng | Functioning Mechanism of AlF3 Coating on the Li-and Mn-Rich Cathode Materials[END_REF]. Among all these surface treatments, AlF3 appears as a very promising post treatment for lithium-rich layered oxide. Several publications report that AlF3 coatings can increase both the capacity and the C-rate capability of the cathode material [START_REF] Sun | The Role of AlF3 Coatings in Improving Electrochemical Cycling of Li-Enriched Nickel-Manganese Oxide Electrodes for Li-Ion Batteries[END_REF][START_REF] Chen | Synthesis and performances of Li-Rich@AlF3@Graphene as cathode of lithium ion battery[END_REF][START_REF] Sun | AlF3 Surface-Coated Li[Li0.2Ni0.17Co0.07Mn0.56]O2 Nanoparticles with Superior Electrochemical Performance for Lithium-Ion Batteries[END_REF][START_REF] Kim | Effect of aluminum fluoride coating on the electrochemical and thermal properties of 0.5Li2MnO3•0.5LiNi0.5Co0.2Mn0.3O2 composite material[END_REF]. Moreover, some authors claim that AlF3 treatment can alleviate the voltage fade issue of the cathode material [START_REF] Zheng | Functioning Mechanism of AlF3 Coating on the Li-and Mn-Rich Cathode Materials[END_REF]. However, a large part of the literature conclusions are based on Li-metal half-cells experimental results, and some significant discrepancies could be observed between half and full cells.

The purpose of this paper is to investigate the influence of AlF3 surface treatments in half-cells but also in Li-ion cells. It is observed that the capacity suddenly decays after 20 cycles due to manganese dissolution. A main part of this paper is dedicated to discussing the influence of the DMD process.

Experimental

Synthesis

All materials were synthesized by using commercial reactants: nickel sulfate hexahydrate (Sigma Aldrich®,NiSO4.6H2O, 99%), manganese sulfate monohydrate (Sigma Aldrich®, MnSO4 H2O, 99%), lithium carbonate (Sigma Aldrich®, Li2CO3, 99%) and sodium carbonate (Sigma Aldrich®, Na2CO3, 99.95%), aluminium nitrate nonahydrate (Acros Organic®, Al(NO3)3.9H2O) and ammonium fluoride (Prolabo®, NH4F, 98%). All reactants were used without further purification. Synthesis of Li1.2Ni0.2Mn0.6O2. In order to compare the coating influence with the best possible accuracy, the same batch of pristine material is used (1 kg batch). The synthesis protocol of Li1.2Ni0.2Mn0.6O2 is adapted from Peralta et al. to produce 1 kg of oxide [START_REF] Peralta | Role of the composition of lithium-rich layered oxide materials on the voltage decay[END_REF]. 6.25 mol of NiSO4.6H2O and 18.75 mol of MnSO4.H2O are mixed in 25 L of water. In another container, 25 mol of Na2CO3 and 5 mol of NH4OH are mixed in 25 L of deionized water. The transition metal ion solution is pumped directly into a 65 L CSTR reactor and the pH is kept at 7.5 during the whole synthesis by injecting the carbonate solution. Then, the final solution of the CSTR is aged for 7 h. Afterward, the carbonate of nickel and manganese (Ni0.25Mn0.75CO3) is recovered by filtration. The product is washed several times with hot water in order to remove residual sodium and sulfate species and finally, the carbonate is dried in an oven at 120 °C during one night. To obtain the final Li1.2Ni0.2Mn0.6O2 material, Ni0.25Mn0.75CO3 is intimately mixed with an excess (3.3%) of lithium carbonate (Li2CO3) and the mixture is fired at 900 °C during 24 h.

AlF3 treatment.

In the text, the coating ratio represents the molar ratio between the metal fluoride and the pristine materials. The same synthesis protocol is used to produce the different coating ratio. As an example, to produce 1% AlF3-treated Li1.2Ni0.2Mn0.6O2, 2.73 g of Al(NO3)3.9H2O are dissolved in 1L of water. Then 60 g of Li1.2Ni0.2Mn0.6O2 are dispersed in this solution and the resulting mixture is heated at 80 °C. Then a solution of 0.81 g of NH4F dissolved in 400 mL of water is added drop by drop in the first solution. The temperature is maintained during 5 hours then the product is recovered by filtration. The resulting powder is treated at 400 °C for 5 h.

Characterisation

XRD. Crystallinity of materials is controlled by X ray diffraction technique (XRD) using a Brüker AXS D8 diffractometer equipped with a Cu anticathode (Kα1,2).

Microscopy. Materials are observed by Scanning Electron Microscopy (SEM) by dispersing the powders on carbon tape using a LEO 1530 SEM. EDX mappings are performed using a FEI Tecnaï OSIRIS operating at 200 kV in STEM mode and equipped with SuperX EDX detector system. Surface analysis. After cycling, electrodes are retrieved from the cell and washed inside a glovebox with Dimethyl Carbonate. Their transfer is achieved by using an airtight vessel to a PHI VersaProbe II (Physical Electronics instrument) or a TOF.SIMS5 spectrometer (Ion Tof instrument). Charging effects are controlled during XPS analysis with a combination of low energy electron gun (negative charge) and low energy argon gun (positive charge). The X-ray source is an Al Kα monochromatic beam (1486.7 eV), the takeoff angle is set at 45°. High resolution spectra are acquired at an energy resolution of ∼0.6

eV. All spectra are calibrated by using F 1s as a reference binding energy for F in LiF (685 eV). TOF-SIMS characterisation are also achieved by using a load-lock compatible with the same air-tight transfer vessel as described above. Analyses were carried out in a positive polarity mode to achieve the elemental mappings of Mn and Ni at the electrodes surface. The primary ion beam is Bi + set at 30 kV.

Electrochemical characterisations. The first electrochemical tests are carried out using standard CR2032 type coin cells assembled in an argon-filled glove box. Electrodes are prepared by mixing Li1.2Ni0.2Mn0.6O2 (80 wt%), C65 (10 wt%) as conductive additive, and PVDF (10 wt%) as binder agent.

After grinding in hexane, the powder is dispersed in N-methyl-2-pyrrolidone, coated on an aluminium foil and then dried at 80 °C under vacuum for 48 h. Disks of 14 mm diameter are punched from the foil, and pressed at 650 MPa. The electrode is then used as positive electrode in a coin cell comprising lithium foil as the negative electrode, one Celgard 2400 and one Viledon® as separators soaked in electrolyte. Specific capacities and current rates are calculated based on a specific capacity of 316 mAh per gram of Li1.2Ni0.2Mn0.6O2. 10 cm² pouch cells are manufactured to evaluate cycle life in full cell configuration: they are assembled in a -20°C dew point dry room with one single layer positive electrode (3.2 x 3.2 cm active area), a separator (Celgard 2320 of 20 µm of thickness) and an oversized negative electrode (3.5 x 3.5 cm). The positive electrode is made with 92 %wt active material, 4% conductive additive and 4% PVDF, coated on 20 µm Al foil using a custom roll to roll equipment and NMP solvent. The negative electrode coated on 10 µm copper foil has 94%wt active material (95 wt% of graphite and 5 wt% of silicon nanoparticle), 2% conductive additive, 2% CMC and 2% SBR binder and is based on an aqueous formulation. After drying under vacuum at 55°C overnight, they are transferred in an argon atmosphere glove box for electrolyte filling with LiPF6 1M in EC/DMC/EMC (1/1/1 vol.) + 10% FEC (EC: Dimethyl carbonate, EC: Ethylene carbonate, EMC: Ethyl methyl carbonate, FEC: Fluoroethylene carbonate). The cathode loading is fixed at 10 mg/cm² and the anode loading is adjusted to 6 mg/cm² resulting in a maximum N/P of 1.05.

Gas Chromatography Mass Spectrometry (GCMS).

For electrolyte analysis, the GCMS (Agilent 7890 with column DB-200 122-2032 30 m x 0.25 mm 0.25 µ) is used with a split 100 injection mode at 280°C. The column ramp is 40°C to 200°C at 10°C/minute. The electrolytes are sampled in the pouch cells and diluted in acetonitrile. DMC and EMC are too volatile and their measured quantities are too dependent on the cell opening conditions for reliable results. For this reason, we only consider the FEC/EC ratio because the cyclic carbonates measures (integrated surface of total ion count peak calibrated with pure solvents) are less sensitive and permit to follow FEC consumption.

Results

Characterisation of lithium-rich pristine material

A 1kg-batch of Li1.2Ni0.2Mn0.6O2 is prepared by a coprecipitation method on a pilot reactor. The material is characterized by XRD and resulting unit cell parameters are very close to those observed in literature (see Figure 1a) [START_REF] Peralta | Role of the composition of lithium-rich layered oxide materials on the voltage decay[END_REF]. The compound crystallizes in the C2/m space group and no extra peak corresponding to any impurity phases is observed. All peaks, except for those between 20 and 25° correspond to a layered oxide structure based on a hexagonal α-NaFeO2 structure (space group 3 ).

The peaks between 20 and 25° result from the ordering of the lithium ions with the M ones in the transition-metal layers, and provide the structure with Li2MnO3-type features (space group C2/m). As expected for a synthesis based on a co-precipitation method, a SEM picture (Figure 1b) reveals that dense, spherical particles are obtained. Primary particles of ~200 nm are aggregated in dense secondary particles of ~ 6 µm diameter. The electrochemical performances of the as made Li1.2Ni0.2Mn0.6O2 are evaluated in half-cells in galvanostatic mode using 0.1 C rate between 4.8 V and 2.5 V. The first charge/discharge curve in Figure 1c has a classical shape and reveals performances at the state of the art (272 mAh/g in charge and 204 mAh/g in discharge -25 % of irreversibility). The capacity slowly increases up to 240 mAh/g during the first cycles and the voltage decay has two different slopes (Figure 1d). This phenomenon is already documented in literature and could be attributed to the activation of Li2MnO3 domains of the composite structure [START_REF] Peralta | Role of the composition of lithium-rich layered oxide materials on the voltage decay[END_REF][START_REF] Yu | Continuous activation of Li2MnO3 component upon cycling in Li1.167Ni0.233Co0.100Mn0.467Mo0.033O2 cathode material for lithium ion batteries[END_REF]. The electrochemical performances of the material are investigated in Li ion pouch cells using a silicon-graphite anode. Because of the slow activation process observed in half coin cells, it was decided to submit pouch cells to several conditioning methods at C/10. The first conditioning method consists in making 3 cycles between 4.7 V and 2.5 V (Vs Si-Gr). The second and the third methods consist in charging and maintaining the pouch cell at a constant voltage of 4.5 V (CC/CV until C/50) at room temperature (method 2) and at 45 °C (method 3). After the formation step, all cells are cycled between 4.4V and 2.5V at C/3 (Figure 2a&b). Best results are obtained with the cell formed with 3 cycles at 4.7

V (18 mAh Vs 16 and 14.7 mAh respectively for method 2 and 3). After 25 cycles, both capacities and average voltages of all cells suddenly fade. This surprising phenomenon will be called "sudden death effect" in this paper. The Figure 2c The first hypothesis in front of such a results was to incriminate the electrolyte stability. GCMS and gas release measurements were performed on the electrolyte just after the formation step and after cycling. GCMS results are summarized in the Table 1. There is a visible consumption of FEC (FEC/EC initial value is 0.3) during formation. This consumption is higher when the formation step includes high voltages or high temperature. However, high voltage does not promote gas formation while the 45°C method produces 3 times more gas than the room temperature methods. The FEC/EC ratio is evolving after 150 cycles but we cannot make reliable conclusions, as the capacity retention is not the same for the three conditioning methods. Room temperature condition for cycling does not promotes gas formation and values are the same as after formation. Looking at the chromatograms, no additional degradation product is detected in the electrolyte. Based on these observations we can support the assumption that the electrolyte decomposition is not the cause of the sudden death effect. It seems more credible to incriminate active materials of the cells. Because some Si-Gr anodes exhibit poor cycle lives, we test our anode in front of a commercial grade of NMC 622. No sudden death effect is observed and we can conclude that the Si-Gr material used in this study is not the cause of the quick capacity fade (Figure S1 in supplementary information file). Literature reports that elements from high manganese content materials can be dissolved in the electrolyte during cycling and these elements can migrate and poison the anode [START_REF] Zhan | Dissolution, migration, and deposition of transition metal ions in Li-ion batteries exemplified by Mn-based cathodes -a critical review[END_REF].

Characterisation of lithium-rich material after AlF3 treatment

The manganese dissolution is well documented in the literature concerning spinel materials. It is generally demonstrated that the dissolution is due to a surface mechanism. We decided to treat our material with AlF3 coatings in order to solve the sudden death effect. 60 g of Li1.2Ni0.2Mn0.6O2 is coated with different amounts of AlF3. No additional peak can be observed in XRD. The amount of AlF3 is certainly too low to be observed by XRD (Figure 3a), but the electrochemical behavior is clearly modified. An optimum is obtained with an AlF3 treatment of 1%: 280 mAh/g are obtained for the first discharge in comparison of 205 mAh/g obtained for the pristine material and the irreversible capacity decreases from 25 % to 11% (Figure 3 b&c). It can also be noticed that the AlF3 treatment does not solve the voltage decay issue (Figure 3d). we can conclude that we successfully modified the pristine material surface (Figure 4). The higher capacity is obtained with 1% of AlF3 which is in good agreement with the results obtained in coin cells (Figure 5a).

Capacities of all materials remain stable only during 25 cycles and then, decay quickly due to an increase of the cell polarization (Figure 5c). Similarly to our previous observation in coin cells, we can conclude that our AlF3 coatings do not solve the voltage decay issue (Figure 5b). Unfortunately, the sudden death effect is not suppressed by the surface treatment.

Pouch cells were cycled and anodes were characterized by XPS after 10 cycles and 20 cycles (just before the sudden death effect). First, it is important to note that Al is never observed at the anode side. From Table 2 it is noticed that the SEI is mainly composed of C, O and Li, F concentration remaining below 3%. However the balance between those elements is quite different after 20 cycles (compared to the situation after 10 cycles). After 10 cycles, C 1s spectrum exhibits several peaks. The low-binding energy peak observed after 10 cycles points out some trapped Li in graphite [START_REF] Cabanel | Determination of the diffusion coefficient of an inserted species by impedance spectroscopy: application to the H/H x Nb2O5 system[END_REF]. Graphite peak confirms that the SEI at that state is still thin (graphite photoelectrons are not screened). The peaks located between 285-288 eV range are related to organic degradation products like RO-CO2-Li, and the high energy peak to carbonates products [START_REF] Sharova | Comparative study of imide-based Li salts as electrolyte additives for Li-ion batteries[END_REF]. In that case, the balance is clearly in favour of the first category of products. The O 1s spectrum reveals the presence of Li oxides together with oxygen involved in the SEI (again, mainly Li alkyl carbonates species) [START_REF] Radvanyi | An XPS/AES comparative study of the surface behaviour of nano-silicon anodes for Li-ion batteries[END_REF][START_REF] Charton | Reactivity of Succinic Anhydride at Lithium and Graphite Electrodes[END_REF]. F 1s peak also exhibits 3 peaks. The low binding energy peak reveals the presence of LiF in low quantities, the other peaks being related to either lithium fluorophosphates degradation products or to traces of LiPF6 not perfectly washed out from the surface of the electrode [START_REF] Tatara | The Effect of Electrode-Electrolyte Interface on the Electrochemical Impedance Spectra for Positive Electrode in Li-Ion Battery[END_REF]. Mn and Ni are also detected. In the case of Ni though, the Ni 2p3/2 peak is overlapped with F KLL Auger transition, thus difficult to point out, even if a small peak can be pointed out at ~852 eV (though it could also be a Mn LMM Auger transition, it fits the detection of a Ni+ peak by TOF-SIMS as presented thereafter). The Mn 2p3/2 peak position at ~638 eV indicates that Mn is probably in a metallic form at this stage (Mn(0)) [START_REF] Biesinger | Resolving surface chemical states in XPS analysis of first row transition metals, oxides and hydroxides: Cr, Mn, Fe, Co and Ni[END_REF].

After 20 cycles: the C-Li peak disappears, while the carbonates peak is more intense. It is noteworthy that the carbonates peak is shifted to higher binding energy, which can be explained by a variation of chemical environment in the SEI. Carbonates can give rise to peaks at up to 292 eV [START_REF] Oswald | Binding energy referencing for XPS in alkali metal-based battery materials research (I): Basic model investigations[END_REF][START_REF] Jones | In situ x-ray photoelectron spectroscopy study of lithium carbonate removal from garnet-type solid-state electrolyte using ultra high vacuum techniques[END_REF]. This obviously underlines that the SEI is thicker and has a different composition (involving a higher carbonates concentration). O 1s peak also shows the disappearance of the Li-O contribution, which is probably related to the increase of the SEI thickness. At the same time, the F 1s spectrum shows a relative increase of the LiF contribution. All these observations point out an evolution of the composition of the SEI during the 10 last cycles. Mn and Ni are also now not detected after 20 electrochemical cycles.

In order to confirm the XPS detection of Mn and Ni, the surface of the cycled electrode is analysed with TOF-SIMS. Results are presented on Figure 7 Even though this is not a quantitative method, its higher sensitivity compared to XPS allows to detect very low amounts of Mn and Ni. After 10 cycles, Mn + and Ni + mass peaks are unambiguously detectable; their intensity are respectively at 2.5 104 and 2.103 counts. Such result confirm the presence of Mn and Ni at the surface of the electrode. Moreover, the mapping of both elements shows a relative homogeneity of their surface distribution. After 20 cycles, Mn + and Ni + mass peaks are still detectable, though at much lower intensities, falling down to respectively 800 and 100 counts. This explains why Mn and Ni are undetectable by using XPS: their surface concentration fall down below the XPS detection limit for each orbital (Mn 2p and Ni 2p).

Surface distribution is also more heterogeneous. These TOF-SIMS results unambiguously confirm the XPS results revealing the presence of Mn and Ni at the surface of the electrodes after 10 cycles, and the absence of detection after 20 cycles. The first important result to point out is the different SEI chemistries after 10 cycles and 20 cycles.

The detection of both manganese and nickel after 10 cycles suggests that these elements are dissolved in the electrolyte and migrate from the cathode side to the anode side. This phenomenon has been already reported in literature by several authors, first for spinel LiMn2O4 and more recently for 5V spinel material and Li-rich materials [START_REF] Numata | Advantages of blending LiNi0.8Co0.2O2 into Li1+xMn2-xO4 cathodes[END_REF][START_REF] Xu | Improving the Performance of Graphite/ LiNi0.5Mn1.5O4 Cells at High Voltage and Elevated Temperature with Added Lithium Bis(oxalato) Borate (LiBOB)[END_REF][START_REF] Yamamoto | Improvement of cycling performance in Ti substituted 0.5Li2MnO3-0.5LiNi0.5Mn0.5O2 through suppressing metal dissolution[END_REF][START_REF] Jiang | A design strategy of large grain lithium-rich layered oxides for lithium-ion batteries cathode[END_REF]. Transition metals are known to poison the anode surface [START_REF] Komaba | Influence of manganese(II), cobalt(II), and nickel(II) additives in electrolyte on performance of graphite anode for lithium-ion batteries[END_REF].

This migration probably happens during the first cycles. Then, the SEI grows on the electrode surface, which makes the detection of Mn and Ni impossible by XPS. The SEI growth is heterogeneous which makes Mn and Ni TOF-SIMS detection also more heterogeneous.

Now the remaining question is how nickel and manganese can be dissolved and migrate through the AlF3 modified surface (Al is never detected at the anode side). STEM-EDX mappings are performed on cathode primary particles to confirm the good homogeneity of fluor and aluminum species (Figure 8a).

Then cross sectional analyses are performed along a secondary particle (Figure 8b) and on the surface of the particles (Figure 8c). To fit with a perfect coating, it is expected that first the aluminum and fluor contents increase and then decrease (due to the pure AlF3 layer) and, only after, the manganese and nickel contents start to increase (due to material bulk). Curiously, no thin peaks of aluminum and fluor can be observed and manganese, nickel, aluminum and fluor start to be detected at the same time.

Moreover, classical coatings reported in literature have only several nanometers of thickness. In our case, aluminum and fluor could be detected during 200 nm.

Discussion

Surface doping/coating: Several publications describe AlF3 surface treatment as an adequate solution to solve the batteries cycle life issue and as a good solution to improve the cell electrochemical performances [START_REF] Sun | The Role of AlF3 Coatings in Improving Electrochemical Cycling of Li-Enriched Nickel-Manganese Oxide Electrodes for Li-Ion Batteries[END_REF][START_REF] Chen | Synthesis and performances of Li-Rich@AlF3@Graphene as cathode of lithium ion battery[END_REF][START_REF] Sun | AlF3 Surface-Coated Li[Li0.2Ni0.17Co0.07Mn0.56]O2 Nanoparticles with Superior Electrochemical Performance for Lithium-Ion Batteries[END_REF][START_REF] Zheng | Functioning Mechanism of AlF3 Coating on the Li-and Mn-Rich Cathode Materials[END_REF][START_REF] Zheng | The Effects of AlF3 Coating on the Performance of Li[END_REF]. Following a similar protocol to what is described in the literature, we produce here several materials with different AlF3 amounts. Concerning the electrochemical performances, our results are in good agreement with literature. The first irreversible capacity is lower and the specific capacity is higher. However, the cycle life is not improved in Li-ion cells. Using a similar process as ours, several authors observe the formation of a real layer of AlF3, whereas we observe that aluminium and fluor diffuse within the surface structure of the material. Rosina et al.

already evoke the possible migration of aluminium inside the Li-rich layered oxide structure and conclude that the AlF3 coating process finally leads to a fluorinated Al2O3 spinel-like phase [START_REF] Rosina | Structure of aluminum fluoride coated Li[Li1/9Ni1/3Mn5/9]O2 cathodes for secondary lithium-ion batteries[END_REF]. Liu et al. report similar conclusions by observing nanoislands of Al2O3 with Fluor [START_REF] Liu | Understanding the Role of NH4F and Al2O3 Surface Co-modification on Lithium-Excess Layered Oxide Li1.2Ni0.2Mn0.6O2[END_REF]. We continue to investigate why the results of this synthesis process can lead to such different results as a function of authors. We are now investigating possible side reactions during the heat treatment process, maybe induced by the choice of reactants. Another hypothesis can be the state of surface of the pristine material: maybe a fine layer of carbonate can react with AlF3 to create a special layer.

Several publications report that the diffusion of transition metal initially deposited at the cathode material surface may be triggered by a heat treatment at high temperature. As an example, He et al.

reported the diffusion of cobalt after a heat treatment of Co(OH)2-coated Mn2O3 and Li2CO3 at a temperature of 750°C [START_REF] He | Preparation of spherical spinel LiMn2O4 cathode material for lithium ion batteries[END_REF][START_REF] He | Preparation of co-doped spherical spinel LiMn2O4 cathode materials for Li-ion batteries[END_REF]. This leads to a spinel material LiMnO4 with a cobalt doped surface.

Other examples of surface doped active materials are reported in the literature especially with the titanium cation. In all case, this doping improves both electrochemical performances and cycle life. Lu et al. compared the electrochemical performances of a titanium coated and titanium surface doped LiMn2O4 cathode material and concluded that both treatments can limit the manganese dissolution [START_REF] Lu | Effectively suppressing dissolution of manganese from spinel lithium manganate via a nanoscale surface-doping approach[END_REF].

In all cases, surface doped materials have an enhanced cycle life and a higher capacity than the pristine material. Okudur et al. produced several titanium surface materials by applying different temperatures on a TiO2-coated LiNi0.5Mn1.5O4 [START_REF] Okudur | Ti surface doping of LiNi0.5Mn1.5O4-δ positive electrodes for lithium ion batteries[END_REF]. They highlighted that a low temperature of 500°C can be enough to make the titanium diffusion inside the surface structure of the lithium-rich layered oxide possible.

The effects observed in these different publications are similar of ours, except for cycling life and voltage fading. In all cases it seems that surface doped materials are promising and could be an alternative or a complement of classical coatings.

Manganese dissolution -migration -deposition process (DMD): The DMD mechanism is a welldocumented phenomenon in the literature especially concerning manganese-enriched spinel cathode like LiMn2O4 or LiNi0.5Mn1.5O4 oxides. However, several aspects of the fundamental mechanism of this phenomenon are still under debate especially concerning the oxidation state of Mn during the deposition step. When some authors report that metallic manganese is recovered on the anode side, others report that it is at the 2+ state. The link between capacity fade and the SEI modification is still under debate.

Here, we report our observation based on lithium-rich layered oxide and silicon-graphite anode cells.

Based on our characterisations, we assume that manganese and a very small amount of nickel are dissolved in the electrolyte during first cycles and migrate to the anode. The dissolution of manganese in the electrolyte is generally attributed to Mn 3+ in the material, which can disproportionate in Mn 4+ and Mn 2+ . Then Mn 2+ can be dissolved in electrolyte. It is commonly admitted that the dissolved manganese corresponds to a loss of active material in the LiMn2O4 material because capacity is due to the Mn 3+ /Mn 4+ redox. However this loss in active species in the cathode accounts for only 20-33 % of the overall capacity loss of spinel based cells [START_REF] Zhan | Mn(II) deposition on anodes and its effects on capacity fade in spinel lithium manganate-carbon systems[END_REF]. The largest part of the total capacity loss is due to the modification of the SEI due to the manganese deposition. If all authors agree that the SEI modification induced by manganese contributes to increase the cell resistance, two main mechanisms are still under discussion: SEI growth due to metallic Mn or ion exchange between Li + and Mn 2+ in the SEI [START_REF] Zhan | Dissolution, migration, and deposition of transition metal ions in Li-ion batteries exemplified by Mn-based cathodes -a critical review[END_REF]. Even if the mechanism seems similar with lithium rich layered oxides and silicon graphite anode, we observe some little differences. In our case, XPS reveals that dissolved TM do not deposit on the anode all along the cycling. Mn and Ni could be detected in the SEI only after 10 cycles and not any longer after 20 cycles. Our hypothesis is that TM are dissolved only during the first cycles and then they catalyse side reactions and a new SEI is formed on the first one and hide the SEI with Mn(0) and Ni(0). Considering the presence of Ni and Li in our formula, which promotes a 4+ oxidation state to Mn, it can be argued that the Mn 3+ content in the material may be too low to make the dissolution of TM during all cycling possible.

Conclusion

In lithium-ion pouch cells composed of Li1.2Ni0.2Mn0.6O2 and silicon graphite respectively for the cathode and anode, manganese and a very low amount of nickel are dissolved in the electrolyte and are deposited on the anode side only during the first cycles. After 10 cycles we observe that manganese is deposited on the anode side under its metallic form. Then, even if TM deposition stops after several cycles (because the few amount of Mn 3+ in the material formula), the TM deposited at the anode side degrades the electrolyte following new reactions. The product of this reaction is the creation of a thick carbonate based layer that completely covers the first SEI. At this step, it becomes difficult to detect the manganese at the anode surface. In the end, the resulting SEI completely insulates the anode and leads to an increase of cell resistivity. We assume that this phenomenon is the cause of the "sudden death effect" of our system. To solve this issue we tried to protect the Li1.2Ni0.2Mn0.6O2 particles by an AlF3 coating, following a classical synthesis procedure described in the literature. Our synthesis results in a surface doped material (with Al and F), which appears to be inefficient to block the TM dissolution. We are now working to compare the influence between a real coating and a surface doped material to solve the manganese dissolution issue. For a more general conclusion, more publications in this field with finely characterized particles surfaces are needed. First, to conclude about the electrochemical enhancement due to surface treatment but also to highlight why similar treatment can result in a coating layer or in a doped surface.

Figure 1 .

 1 Figure 1. Li1.2Ni0.2Mn0.6O2 physicochemical characterisations: (a) XRD pattern, (b) SEM image, (c)

  represents the difference between the average voltage in charge and discharge and provide some indications about the cells polarization. Curiously, the resistance of the cells suddenly increases after 25 cycles.

Figure 2 .

 2 Figure 2. Influence of different activation methods on Si-Gr/Li1.2Ni0.2Mn0.6O2 pouch cells cycle life:

Figure 3 .

 3 Figure 3. Characterisation of AlF3-treated Li1.2Ni0.2Mn0.6O2: (a) XRD patterns, (b) influence of the

Figure 4 .

 4 Figure 4. Chemical mappings obtained from STEM EDX experiments with the AlF3-treated materials

Figure 5 .

 5 Figure 5. Influence of AlF3 treatments on Si-Gr/Li1.2Ni0.2Mn0.6O2 pouch cells cycle life: (a) Capacity,

Figure 6 .

 6 Figure 6. XPS spectra of negative electrodes (Si-Gr/Li1.2Ni0.2Mn0.6O2 pouch cells) after

Figure 7 .

 7 Figure 7. TOF-SIMS mappings of the surface of electrodes for Mn + (left) and Ni + (right) after 10

Figure 8 .

 8 Figure 8. (a) Chemical mappings obtained from STEM EDX experiments performed with the 1% AlF3

Table 1 .

 1 GCMS results and gas released by electrolyte of pouch cells as a function of the activation

	process
	End of formation	End of cycling

Table 2 .

 2 Composition of the XPS probed volume (atomic%) as a function of cycling

	Cycle
		Li	C	O	F	P	Mn	Ni
	index
	10	44.7 26.6 26.5 1.6	0.3 0.3 Traces
	20	26.7 25.6 44.3 2.9	0.5 -	-

Acknowledgments

The study has been performed within the BEGREEN project. The authors gratefully acknowledge support from Pellenc Energy.


MD Roxane Bunod
email: roxane.bunod@hotmail.fr

Rachid Tahiri

MD Joutei Hassani

MD Mathieu Robin

MD, PhD Hong Liang

MS Ghislaine Rabut

MD, PhD Christophe Baudouin

MD, PhD Antoine Labbé

Apport de l'imagerie " en face " en tomographie par cohérence optique dans l'évaluation de la sévérité des ptérygions et sa corrélation avec la microscopie confocale in vivo

Keywords: Pterygium, en face optical coherence tomography, in vivo confocal microscopy, Fuchs patches

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

Pterygium is a common and benign ocular surface disorder characterized by a corneal invasion of altered limbal epithelial cells. Although the pathogenesis of pterygium is not completely understood yet, involved mechanisms include stromal fibroblasts activation, neovascularization, inflammation, and extracellular matrix modifications [START_REF] Girolamo | Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases[END_REF][START_REF] Hill | Pathogenesis of pterygium[END_REF] . The major role of chronic UV in the pathogenesis of pterygium is well established, supported by several studies and epidemiological data [3][START_REF] Coroneo | Pterygium as an early indicator of ultraviolet insolation: a hypothesis[END_REF][START_REF] Girolamo | UVB-mediated induction of interleukin-6 and -8 in pterygia and cultured human pterygium epithelial cells[END_REF][START_REF] Girolamo | UVB-Elicited Induction of MMP-1 Expression in Human Ocular Surface Epithelial Cells Is Mediated through the ERK1/2 MAPK-Dependent Pathway[END_REF][START_REF] Girolamo | UVB-Mediated Induction of Cytokines and Growth Factors in Pterygium Epithelial Cells Involves Cell Surface Receptors and Intracellular Signaling[END_REF] .

Clinical symptoms include eye redness, tearing, foreign-body sensation, aesthetic complaints or decreased visual acuity related to astigmatism and corneal-surface irregularities. The treatment can vary from conservative measures such as artificial tears, UV-protective sunglasses, anti-inflammatory drops to surgical techniques and immunosuppressive or antimetabolite adjuvant therapy [START_REF] Chu | Pterygium: new insights[END_REF] . Pterygium management remains challenging because of a high rate of recurrence after surgical treatment and ophthalmologists need to assess individual factors and characteristics to decide the best therapeutic strategy. With the improvement of new imaging techniques, sophisticated systems have been developed to improve pterygium evaluation. B-scan anterior segment optical coherence tomography (AS-OCT) has been widely used to investigate pterygium patterns [START_REF] Soliman | Spectral domain anterior segment optical coherence tomography assessment of pterygium and pinguecula[END_REF][START_REF] Welch | Pterygia measurements are more accurate with anterior segment optical coherence tomography -A pilot study[END_REF][START_REF] Gasser | Morphometric characterisation of pterygium associated with corneal stromal scarring using high-resolution anterior segment optical coherence tomography[END_REF] . With a higher resolution, in-vivo confocal microscopy (IVCM) allows the visualization of inflammatory cells, blood vessels, and normal cornea/pterygium limits [START_REF] Wang | In Vivo Confocal Microscopic Evaluation of Morphologic Changes and Dendritic Cell Distribution in Pterygium[END_REF][START_REF] Gheck | Apport de la microscopie confocale in vivo à l'étude des ptérygions[END_REF][START_REF] Shen | In Vivo Confocal Microscopy Observation of Cell and Nerve Density in Different Corneal Regions with Monocular Pterygium[END_REF][START_REF] Papadia | Anatomical and Immunological Changes of the Cornea in Patients with Pterygium[END_REF][START_REF] Labbé | An In Vivo Confocal Microscopy and Impression Cytology Evaluation of Pterygium Activity[END_REF] . More recently, en face OCT (EF-OCT) has been developed for anterior segment imaging. Based on OCT B-scan transversal section, reconstruction technique can rebuild frontal en face images. These coronal sections, also called C-scan, provide a new way to represent and analyze anterior segment tissues in vivo as a 2-dimensional. In a preliminary study, our group showed EF-OCT images of pterygium [START_REF] Joutei Hassani | En-face Optical Coherence Tomography as a Novel Tool for Exploring the Ocular Surface: A Pilot Comparative Study to Conventional B-Scans and in Vivo Confocal Microscopy[END_REF] . The study we present here aim to confirm the usefulness of EF-OCT in assessing pterygium severity and correlate IVCM findings.

Patients and methods

This observational single-center case series wtableas conducted at the Center for Clinical Investigation (CIC INSERM 1423) of the Quinze-Vingts National Ophthalmology Hospital, Paris, France. The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee CPP-Ile de France (number 10793). We prospectively included subjects with pterygium between April and September 2019.

Patients with recurrent pterygium were excluded.

After a written informed consent, all subjects underwent detailed ophthalmic examination, anterior segment photography, tear osmolarity measurement, Schirmer test, Break Up Time (BUT), IVCM, and EF-OCT imaging. Dry eye symptoms were assessed using OSDI questionnaire. A total of 12 questions about symptoms experienced over the previous week were administered to participants, with possible scores ranging from 0 to 48. Tear osmolarity was assessed using the TearLab device (TearLab Corp., San Diego, CA, USA). The Schirmer test was performed after topical anesthesia (oxybuprocaïne chlorydrate 0.4%, Thea, Clermont-Ferrand, France) by applying Whatman 41 filter paper strips (5 mmx30 mm) into the inferior-temporal part of the conjunctival sac. The wetted length was measured in millimeters after 5 minutes. To performed the BUT test, a drop of sodium fluorescein 0.5% (SERB, Paris, France) was applied in the inferior conjunctival sac and the patient was asked to blink several times to spread the fluorescein over the cornea. The tear film was then observed using the Cobalt blue light on the Goldmann slit lamp while the patient was asked not to blink. The time of appearance of the first dry spot was measured in second.

Clinical pterygium severity

Pterygium severity was graded according to the Modified Pterygium Classification System elaborated by Ke-Hung Chien et al. based on pterygium extension, vascularity, and thickness using slit-lamp examination [START_REF] Chien | Correlation of MicroRNA-145 Levels and Clinical Severity of Pterygia[END_REF] .

Severe Pterygium (SP) was defined as clinical severity score≥ 6 and/ or ocular surface disease index (OSDI) ≥ 30.

Mild Pterygium (MP) were defined as severity grading <6 and OSDI < 30.

En face OCT analysis

AS-OCT scans were acquired by a single trained operator using the RTVue Spectral Domain-OCT (SD-OCT) (Optovue Inc, Fremont, CA, USA) providing 26,000 A-scans per second with 5µm axial resolution and 15µm transversal resolution in tissue. Two different lenses were used for image acquisition: the Short Corneal Adaptor Module (CAM-S) which allows high-transverse-resolution imaging (10µm) with a scan size of 3x3mm and the Long Corneal Adaptor Module (CAM-L) which yields wide-field imaging (8 mm wide surface) with lower resolution (15µm). A high-density SD-OCT volume scan was acquired and 3D data were processed to generate C-scans. . AS-OCT volumes were visualized using the algorithm version A6, 2, 0, 68. The RTVue® OCT software automatically processed the OCT image. C-scans were automatically determined using the default thickness of 31 µm. The C-scan was manually swiped to explore the acquired volume and select en-face images allowing measurement of the FP maximum surface. C-scan images were qualitatively analyzed for shape and degree of reflectivity including pterygium stromal aspect, limit between the pterygium and the cornea and the adjacent cornea, the presence of hyperreflective spots (FP) in front of the tip of the pterygium. FP surface was measured (in mm 2 ) for each pterygium in a masked manner using the National Institutes of Health (NIH) ImageJ software (Bethesda, MD, USA).

IVCM analysis

IVCM was performed using the Heidelberg Retina Tomograph II/Rostock Cornea Module (Heidelberg Engineering GmbH, Heidelberg, Germany) confocal microscope by a single trained operator. Before examination, a drop of topical anesthetic (Novesine0.4% [oxybuprocaïne 0.4%] MSD-Chibret, Paris, France) and a drop of gel tear substitute (Lacrigel®, carbomer 0.2%, Europhta, Monaco) were instilled. The x-y position of the image and the section depth was controlled manually. Two-dimensional high-resolution optical sections covering an area of 400µm², with 2µm transversal resolution and 4 µm longitudinal optical resolution were acquired. IVCM analysis was focused on the corneal pterygium limits. IVCM allowed qualitative analysis of blood vessels, inflammatory cell infiltration, keratocyte activation and cornea/pterygium limits. Inflammatory cell infiltration were observed as infiltration of hyper-reflective cells whether in the corneal epithelium or corneal stroma in front of the pterygium head [START_REF] Labbé | An In Vivo Confocal Microscopy and Impression Cytology Evaluation of Pterygium Activity[END_REF] . Activated keratocytes were defined as keratocytes with hyperreflective cytoplasmic processes [START_REF] Hovakimyan | Morphological Analysis of Quiescent and Activated Keratocytes: A Review of Ex Vivo and In Vivo Findings[END_REF] . Cornea/pterygium limits were considered to be regular if the demarcation line between the pterygium and the cornea was sharp and linear. The limit was considered as blurry if the demarcation line was shattered at some points and irregular if the demarcation line was predominantly fragmented. Pterygium activity on IVCM was graded in four stages using a qualitative evaluation of pterygium activity characteristics previously described by our group (figure 1) [START_REF] Labbé | An In Vivo Confocal Microscopy and Impression Cytology Evaluation of Pterygium Activity[END_REF] :

-Stage 1: absence of blood vessel in the pterygium head, regular limit between cornea and pterygium without infiltrates or hyperreflective epithelial cells and few activated keratocytes within the corneal stroma adjacent to the pterygium head.

-Stage 2: linear blood vessels in the pterygium head, blurry limit between cornea and pterygium with mild infiltrates of hyperreflective cells (arrow) in the corneal epithelium and mild keratocytes activation within the corneal stroma adjacent to the pterygium head.

-Stage 3: blood vessel loops in the pterygium head, irregular limit between cornea and pterygium with moderate infiltrates of hyperreflective cells in the corneal epithelium and high keratocyte activation in the corneal stroma.

-Stage 4: numerous blood vessel loops in the pterygium head, irregular limit between cornea and pterygium with intense infiltrates of hyperreflective cells in the corneal epithelium and high keratocyte activation and hyperreflective cells in the stroma.

Statistical analysis

Results were expressed as standard error of the means (SEM). Statistical analyses were carried out using GraphPad Prism5 for Windows (GraphPad Software, Inc, San Diego, CA, USA). The paired Student t-test was used for quantitative data. P-values ≤0.05 were considered statistically significant.

Results

A total of 21 eyes of 17 patients with pterygium (11 men and 6 women) were included in the study (Table 1).

After assessment of clinical severity, patients were separated in two groups as follows: 11 eyes of 9 subjects with SP and 10 eyes of 8 subjects with MP. There were no significant differences in term of age (P=0. On EF-OCT pterygium stroma appears as a heterogeneous, hyperreflective lesion compared to normal cornea (figure 2). The contrast of reflectivity between the pterygium stroma and the adjacent hyperreflective and homogeneous cornea allows a clear visualization of pterygium corneal limits.

Mild pterygium group was characterized by a regular limit between the cornea and the pterygium and the absence of FP. On the contrary, severe pterygium group was characterized by irregular limits between cornea and pterygium and allowed clear visualization and evaluation of the FP surface as hyperreflective spots in front of the tip of the pterygium (figure 2 and3). FP surface measured with EF-OCT was significantly higher in the SP group (0.13 ± 0.06 mm2) than in the MP group (0.06±0.02 mm2) (P=0.003).

The pterygium-IVCM score was higher in SP group (2.36±0.81) than MP (1.20±0.42) (P= 0.0013). A larger FP

surface measured with EF-OCT was associated with higher score of activity on IVCM (linear regression r 2 =0.62, P<0.0001, figure 4).

Discussion

Evaluation of pterygium severity and progression greatly influence clinical decisions regarding the interval of follow-up and the type of surgical intervention. Since simple excision is associated with a higher rate of recurrence, various surgical techniques have been developed to prevent recurrence. The most common are excision associated with autologous conjunctival or limbal-conjunctival grafts, conjunctival flap or amniotic membrane graft [START_REF] Twelker | Evaluating Pterygium Severity: A Survey of Corneal Specialists[END_REF] . Alternately, adjuvant antimitotic treatment such as mitomycin C (MMC), 5-fluorouracil or even beta irradiation can also be used after excision to prevent cell proliferation. Intraoperative and postoperative MMC application has shown to be effective in recurrence prevention of primary and recurrent pterygium [START_REF] Lam | Intraoperative mitomycin C to prevent recurrence of pterygium after excision[END_REF][START_REF] Manning | Intraoperative Mitomycin in Primary Pterygium Excision[END_REF][START_REF] Raiskup | Mitomycin C for pterygium: long term evaluation[END_REF] . However, these adjuvant treatments are associated with potential sight-threatening complications such as scleral necrosis, corneal edema, corneal perforation, endophtalmitis [START_REF] Moriarty | Severe Corneoscleral Infection: A Complication of Beta Irradiation Scleral Necrosis Following Pterygium Excision[END_REF][START_REF] Rubinfeld | Serious Complications of Topical Mitomycin-C after Pterygium Surgery[END_REF] . . Evaluation of pterygium severity and activity appears to be indispensable to discuss the benefit-risk balance of the different treatments.

SD-OCT B-scan has been already for the qualitative and quantitative assessment of pterygium. On Bscan, pterygium appears as a mass of tissue separating the basal layer of corneal epithelium from the Bowman's membrane [START_REF] Soliman | Spectral domain anterior segment optical coherence tomography assessment of pterygium and pinguecula[END_REF] . Lluch et al. shown the correlation between the anomalous pterygium hyperreflectivity on OCT pattern and histological alteration including abnormal collagen arrangement, inflammatory cell infiltration and fibroblast subepithelial line [START_REF] Lluch | What biomarkers explain about pterygium OCT pattern[END_REF] . The cross-sectional B-scan images can also measure precisely the distance between the pterygium's apex and the limbus to provide a reproductible and accurate evaluation of pterygium extension [START_REF] Welch | Pterygia measurements are more accurate with anterior segment optical coherence tomography -A pilot study[END_REF] .

In a preliminary study, we had shown EF-OCT images of pterygium [START_REF] Joutei Hassani | En-face Optical Coherence Tomography as a Novel Tool for Exploring the Ocular Surface: A Pilot Comparative Study to Conventional B-Scans and in Vivo Confocal Microscopy[END_REF] . EF-SD-OCT allowed clear identification of the pterygium surface, borders and FP. These cell clusters, also known as Fuchs' flecks or Fuchs' islets, were first described by Ernst Fuchs as small spots visualized at the head of pterygium [START_REF] Fuchs | Ueber das Pterygium [Concerning the pterygium[END_REF] . Chui et al.

showed that FP corresponded to pterygium epithelial cells expressing putative limbal stem cell markers and hypothesize that they were at the origin of cell proliferation in pterygium [START_REF] Chui | Ophthalmic Pterygium[END_REF] . The presence of these islands of cells may represent a signal activation and proliferation related to UV damage [START_REF] Ip | Significance of Fuchs Flecks in Patients With Pterygium/Pinguecula: Earliest Indicator of Ultraviolet Light Damage[END_REF] . The presence of FP is a criterion for evaluating pterygium severity and is considered as a marker of pterygium progression [START_REF] Gheck | Apport de la microscopie confocale in vivo à l'étude des ptérygions[END_REF][START_REF] Labbé | An In Vivo Confocal Microscopy and Impression Cytology Evaluation of Pterygium Activity[END_REF][START_REF] Twelker | Evaluating Pterygium Severity: A Survey of Corneal Specialists[END_REF] . In the present study we showed that EF-SD-OCT yielded an accurate evaluation of FP surface of these patches and that highly active pterygium were associated with larger FP surface measured with EF-OCT.

IVCM offers a non-invasive method to study histologic characteristics of biological tissues in vivo [START_REF] Guthoff | In vivo confocal microscopy, an inner vision of the cornea -a major review[END_REF] . With IVCM, pterygium characteristics have been described, more particularly, in the transitional zone between the pterygium head and the healthy adjacent cornea [START_REF] Wang | In Vivo Confocal Microscopic Evaluation of Morphologic Changes and Dendritic Cell Distribution in Pterygium[END_REF][START_REF] Gheck | Apport de la microscopie confocale in vivo à l'étude des ptérygions[END_REF][START_REF] Papadia | Anatomical and Immunological Changes of the Cornea in Patients with Pterygium[END_REF][START_REF] Labbé | An In Vivo Confocal Microscopy and Impression Cytology Evaluation of Pterygium Activity[END_REF] . In a previous study, we identified IVCM characteristics associated with pterygium clinical activity [START_REF] Labbé | An In Vivo Confocal Microscopy and Impression Cytology Evaluation of Pterygium Activity[END_REF] . Inflammatory cells in the pterygium epithelium and stroma, blood vessels loops, irregular boundaries and the presence of FP were features associated with active pterygia, supporting the role of inflammation in pterygium pathogenesis [START_REF] Labbé | An In Vivo Confocal Microscopy and Impression Cytology Evaluation of Pterygium Activity[END_REF] l. We have used a qualitative evaluation of pterygium activity based on IVCM activity signs and found a significant positive correlation between FP surface on EF-OCT and the score of activity on IVCM. These findings confirm the significance of FP as a marker of activity and show that EF-OCT offers an interesting tool in clinical practice for assessing pterygium activity.

Compared to IVCM, EF-OCT brings some major advantages in clinical practice. First, SD-OCT device is widely available in ophthalmological centers much more than IVCM. Indeed, most of the OCT devices nowadays include an anterior segment module. EF-OCT image acquisition is achievable with limited experience whereas IVCM requires a trained operator to obtain high quality image. Moreover, the results are more operatordependent. EF-OCT is a rapid and non-contact technique which is beneficial for the patient as it avoids patient discomfort and contact with the cornea. The visualization window is also 100 times larger in EF-OCT than the surface analyzed by IVCM (4mm x 4mm versus 400 µm x 400µm), providing a better overall visualization of lesions with fewer image acquisitions. In contrast, a major limit of EF-OCT versus IVCM is the lower image resolution. However, recent SD-OCT technology has improved image resolution and further progress is expected in the future with the development of en face ultra-high-resolution (UHR) OCT [START_REF] Kieval | Ultra-High Resolution Optical Coherence Tomography for Differentiation of Ocular Surface Squamous Neoplasia and Pterygia[END_REF][START_REF] Wang | Ultra-High Resolution Optical Coherence Tomography for Imaging the Anterior Segment of the Eye[END_REF][START_REF] Shousha | Diagnosis and Management of Conjunctival and Corneal Intraepithelial Neoplasia Using Ultra High-Resolution Optical Coherence Tomography[END_REF] . RTVue software segmentation errors can cause incorrect EF-OCT reconstruction. Lastly, image acquisition can be biased because of image artifacts such as eyelashes shadowing or ocular movements. Despite these limitations, in our experience, EF-OCT is a reliable and reproducible imaging technique.

Our results suggest that the use of EF-OCT could be useful to assess pterygium severity by evaluating the extent of Fuchs patches. Associated with B-scan, AS-OCT acquisition also allows an accurate measurement of pterygium extension and detection of progression. AS-OCT associated with EF-OCT could be an interesting preoperative exam. There is a need for standardized method of grading pterygium severity to guide the treatment, thus EF-OCT could provide an interesting tool in clinical practice to assess pterygium severity.

Conclusion

EF-OCT could be useful to assess pterygium severity by evaluating the extent of FP. Higher FP surface on EF-OCT is correlated with higher clinical pterygium severity and pterygium activity on IVCM. By providing a simple, non-invasive and reproducible tool to analyze pterygium severity, EF-OCT could be a used as a complementary exam before surgery. Qualitative evaluation of pterygium activity based on IVCM characteristics of active pterygium we described in a previous study.

Stage 1: absence of blood vessel loops in the pterygium head (A), regular limit between cornea and pterygium without infiltrates or hyperreflective cells (E) and few activated keratocytes within the corneal stroma adjacent to the pterygium head (I).

Stage 2: linear blood vessels (*) in the pterygium head (B), blurry limit between cornea and pterygium with mild infiltrates of hyperreflective cells (arrow) in the corneal epithelium (F) and mild keratocytes activation within the corneal stroma adjacent to the pterygium head (J).

Stage 3: blood vessel loops (*) in the pterygium head (C), irregular limit between cornea and pterygium with moderate infiltrates of hyperreflective cells (arrow) in the corneal epithelium (G) and high keratocyte activation in the corneal stroma (K).

Stage 4 :

 4 numerous blood vessel loops (*) in the pterygium head (D), irregular limit between cornea and pterygium with intense infiltrates of hyperreflective cells (arrow) in the corneal epithelium (H) and high keratocyte activation and hyperreflective cells (arrow) in the corneal stroma (L).

Figure 2 .

 2 Figure 2. EF-OCT analysis of MP and SPMild pterygium (A: C-scan, B and C: B-scan). EF-OCT of mild pterygium is characterized by regular limits between the cornea and the pterygium. Note the absence of hyperreflectivity in front of the tip of the pterygium.Severe pterygium (E: C-scan, F and G: B-scan). EF-OCT of severe pterygium reveals irregular limits between cornea and pterygium and allows clear visualization and evaluation of the FP surface as hyperreflective spots in front of the tip of the pterygium (red circles).

Figure 3 .

 3 Figure 3. EF-OCT of FP in pterygiumEF-OCT showing the absence of FP (A to F). FP appear as hyper-reflective areas in the cornea adjacent to the tip of the pterygium (G to L). EF-OCT allows an evaluation of the surface of the FP.

Figure 4 .

 4 Figure 4. Correlation between IVCM activity and FP surface. Linear regression between IVCM activity and FP surface (n=21) showing significant positive correlation.

Table 1 . Population characteristics Figure 1. IVCM pterygium staging.

 1


Stanislas Roman
email: romanje@wanadoo.fr

MD Christophe Baudouin

Ph D Md

Dr Roman Stanislas

Flexible silicone artificial iris in cases of aniridia and iris deficiencies Iris artificiel en silicone flexible pour aniridies et déficiences iriennes

Méthodes: Des patients, atteints de déficiences iriennes se plaignant de photophobie ou d'un probleme esthétique et nécessitant une chirurgie de cataracte, ont recu le nouvel iris artificiel en silicone flexible Resultats: Quinze yeux de 14 patients on été evalué. L'âge moyen était de 49.5 années (+/-18.5). 50 % étaient aphaques, 22.4 % pseudophaques et 28.6 % phaques. L'étiologie était un traumatisme (57.1 %), un traumatisme chirugical (28.6 %) ou une aniridie congénitale (14.3 %). A 3 mois postoperatoire, sur une échelle de 0 à 10, la photophobie subjective moyenne s'est améliorée de 5.2 points (P = .002) et le résultat esthétique de 4.7 points (P = .001) . la perte endothéliale était de 16 % (P = .001). Entre 3 mois et 1 an postopératoire il n'y avait plus de perte endotheliale significative (P = .320). L' élévation de la pression intraoculaire était la complication principale (35.7 %). Deux patients souffrant d'un glaucome pré-existant ont nécessité une cyclodestruction. L'iris artificiel a dû être retiré pour un patient du fait d'une pression élévée et d'une douleur associée à une inflammation chronique. Les symptomes ont disparus après l'ablation de l'iris artificiel. Results: Fifteen eyes of 14 patients were evaluated. Mean age was: 49.5 (+/-18.5). 50 % were aphakic, 22.4 % pseudophakic and 28.6 % phakic. Etiology was trauma (57.1 %), previous surgical trauma (28.6 %) and congenital aniridia (14.3 %). Three months postoperatively, the mean subjective photophobia score improved by 5.2 points (P = .002) and the mean cosmesis score by 4.7 points (P = .001) on a 0 to 10 scale. Mean endothelial cell loss was 16 % (P = .001). There was no further statistically significant endothelial cell loss between the 3-month follow-up and the 1-year follow-up visit (P = .320). Elevated intraocular pressure was the main complication (35.7 %). Two patients with pre-existing glaucoma required cyclodestructive procedures. The artificial iris was removed in one eye because of chronic pain, elevated intraocular pressure and inflammation that resolved rapidly after removal.

Conclusion

Conclusion:

Implantation of the customized artificial iris is a very good option because of its outstanding cosmetic result. However, patients with pre-existing glaucoma are not good candidates. Patients should also be warned of possible chronic inflammation necessitating explantation.

Key words: artificial iris, aniridia, iris deficiencies

Aniridia and iris deficiencies can be congenital or acquired. They are often associated with other important ocular comorbidities. Acquired defects result from trauma, intraocular pressure (IOP) spikes (Urrets-Zavalia syndrome), intraocular inflammation or less frequently iridocorneal-endothelial syndrome. Both congenital and acquired pathologies result in iris deficiencies due to partial or total loss of iris tissue or simply mydriasis. Iris deficiencies cause cosmetic impairment, photophobia and decreased visual acuity. Cosmetic impairment and photophobia can be very debilitating. It is thus important to consider iris repair when planning cataract surgery, correction of aphakia or in disturbed pseudophakic patients. In cases of large iris defects when pupilloplasty is not possible, modified capsule tension rings (Morcher 50 F, 50 C and 96 C) or aniridia implants (Ophtec 311 brown, green and blue) and Morcher black 67 F and 67 G) were until recently the only possible options [START_REF] Sundmacher | Black-diaphragm intraocular lens for correction of aniridia[END_REF][START_REF] Reinhard | Black diaphragm aniridia intraocular lens for congenital and traumatic aniridia: long term follow-up[END_REF][3][START_REF] Menezo | Implantation of iris devices in congenital and traumatic aniridias: surgery solutions and complications[END_REF][START_REF] Miller | Outcomes of implantation of modified capsule tension rings with multiple black occluder paddles for eyes with congenital and acquired iris defects: report 3[END_REF][START_REF] Mavrikakis | Surgical management of iris defects with prosthetic iris devices[END_REF][START_REF] Miller | Safety and efficacy of black iris diaphragm intraocular lens implantation in eyes with large iris defects: Report 4[END_REF][START_REF] Roman | Artificial iris intraocular lenses in aniridia or iris deficiencies[END_REF][START_REF] Villemont | Management of aphakia-aniridia with scleral sutured artificial iris intraocular lenses[END_REF][START_REF] Weissbart | Management of aniridia and iris defects: an update on iris prosthesis options[END_REF][START_REF] Snyder | Prosthetic iris device implantation[END_REF] . The cosmetic result with these different devices is correct when the color of the fellow eye is black or brown but poor in cases of blue or green eyes. Furthermore, in cases of aphakia, it is necessary to enlarge the corneal incision to 9 or 10 mm. A relative new option for treatment is the use of a custom-made flexible silicone iris (Human Optics ArtificialIris ® or CustomFlex ® in the United States) that enables insertion through a small incision. To date, few studies have been published about this new otion [START_REF] Mayer | Pupillary reconstruction and outcomes after artificial iris implantation[END_REF] . This article reports our experience.

I. PATIENTS AND METHODS

This is a retrospective case series. The study was performed in conformance with the tenets of the Declaration of Helsinki. The Human Optics Artificial Iris® has received Conformité Européenne marking. No board approval was required. It is not to be mistaken with the esthetical artificial irises NewColorIris ® and BrightOcular ® used to change the color of a normal eye. They have not received the Conformité Européenne approval and should not be used because they often lead to very serious complications. All surgeries were performed by the same experienced surgeon (SR). Inclusion criteria were:

-age: 18 years and older -congenital or acquired iris deficiencies with no possibility of pupilloplasty correction -necessity of cataract surgery, aphakia correction (after failure of contact lens wear) or pseudophakic patients complaining of disturbing photophobia or cosmetic appearance.

Patients with ocular inflammation, retinal detachment dating less than 6 months or corneal epithelial disease (a common feature in some congenital aniridia) were excluded. Glaucoma patients with controlled intraocular pressure were not excluded.

All the patients had a complete preoperative examination. All eyes had a preoperative endothelial cell count (ECC), except case 7 and 10 because of corneal scarring and corneal decompensation respectively. Each patient was asked to subjectively assess his/her cosmetic appearance pre and postoperatively on a scale of 0 (very unsatisfied) to 10 (very satisfied) and his/her photophobia (0 = no photophobia to 10 = intolerable photophobia).

Follow-up was 1 day, 10 days, 1 month, 3 months, 1 year postoperatively. Surgical technique. The artificial iris (AI) was customized by Human Optics (Erlangen, Germany) for each patient based on the photographic documentation of the fellow eye. The AI is made of flexible silicone and has an overall diameter of 12.8 mm and a central pupil aperture of 3.35 mm. It comes in two versions: without fiber ('fiber-free') or with an embedded polymer fiber meshwork to prevent suture migration through the silicone ('withfiber'). The manufacturer recommends ordering the 'with-fiber' version when the AI is to be scleral-sutured. However, if needed, the 'fiber-free' version can be cautiously sutured. The advantage of the 'fiber-free' AI is increased flexibility. Two AI are delivered for each patient and it is possible to order both versions for the same patient. The AI must be cut with a trephine to the right dimension before insertion into the eye. In cases of an associated cataract surgery, a 'fiber-free' artificial iris downsized to 9 mm was planned to be placed in the capsular bag except for one patient with a subluxated lens where it was decided to scleralsuture a 'with-fiber' AI in the ciliary sulcus. In cases of pseudophakia or aphakia the trephine diameter was horizontal White-To-White (WTW) distance -1 mm and an iridectomy was made in the upper part of the AI. In cases of aphakia, the IOL (Alcon SN 60 WF) was to be sewn to the back of the AI and the resulting IOL-iris prosthesis complex was to be scleralsutured in the ciliary sulcus behind the iris remnants using a double-arm 9-0 polypropylene as described by Sptizer [START_REF] Sptizer | A new technique for treating postraumatic aniridia[END_REF] and Mayer [START_REF] Mayer | Artificial iris implantation in various iris defects and lens conditions[END_REF] . In cases of pseudophakia the AI was planned to be placed in the sulcus behind remnants of the iris tissue or to be scleral-sutured in the sulcus if the remnants were not considered sufficient.

One patient had a combined penetrating keratoplasty (PKP).

The iris was implanted through a small incision using either a forceps (4 mm) or an injector (Viscojet Medicel 2.2 mm) Statistical analysis. Descriptive statistics were presented as numbers (%) for qualitative variables and as median (minimum-maximum) for quantitative variables. To compare evolution of photophobia and cosmesis score and endothelial cell, the Wilcoxon signed-rank test was used. All tests were bilateral (cut-off 5%) and R version 3.5 (http://www.Rproject.org) was used for the statistical analyses. A P value of less than 0.05 was considered statistically significant.

II. RESULTS

Fifteen eyes of 14 patients were enrolled from July 2017 to September 2019. Table 1 shows preoperative data of each patient. Because of intraoperative difficulty, one eye was excluded from the study (see below). Mean age was: 49.5 +/-18.5. Seven eyes (50 %) were aphakic, 4 (28.6 %) phakic and 3 (21.4 %) pseudophakic. Two pseudophakic patients had a previous Ophtec 311 iris reconstruction and were not happy with the cosmetic result. The iris deficiencies etiologies were trauma (57.1 %), previous surgical trauma (28.6 %), and congenital (14.6 %). Surgical technique. In phakic patients, the initial plan to place the AI in the bag was abandoned in 3 cases (cases 13, 14 and 15). In cases 13 and 14 the capsular bag appeared too fragile even after a ring implantation and we preferred placing the AI in the sulcus behind the remnants of iris tissue, without scleral fixation in case 13 and with scleral fixation in case 14.

The former had to be repositioned and scleral-sutured 3 weeks after the initial surgery because of its migration forward in front of the remaining iris tissue causing sudden elevated IOP. In case 15, an Argentinian flag occurred during capsulorhexis and damaged the anterior capsule of the capsular bag. We could manage to implant the IOL in the damaged bag, but we decided to abandon the AI implantation in the bag or in the ciliary sulcus because of fear to cause further damage. The patient was excluded from the study. In aphakic patients, the IOL-AI complex was carefully and successfully scleral-sutured in the ciliary sulcus in all patients. In pseudophakic patients, the AI was simply placed without suture behind the iris remnants (case 12) or scleral-fixated after removal of the Ophtec lens (cases 1 and 6) as in the aphakic group.

Table 2 lists complications and 3-month postoperative results. Increased IOP was observed in 5 eyes (35.7 %). Three of them had pre-existing controlled glaucoma prior to AI implantation.

Two of these eyes demonstrated significantly elevated IOP and normalization was very difficult necessitating 2 cyclodestructions. One eye (case 6) demonstrated elevated IOP, persisting ocular inflammation and chronic pain. Removing the AI was decided 2 months after initial surgery because no treatment was successful. The symptoms rapidly resolved after removal. As already mentioned, case 13 developed a delayed increased IOP related to the forward migration of the AI. The raised IOP resolved rapidly after repositioning and scleral fixation of the AI. Cases 7 and 11 did not recover a good visual acuity because of corneal scarring and macular degeneration (Berlin's edema) at the time of trauma. Due to pinhole effect and correction of the optical aberrations, best corrected distance visual acuity (CDVA) improved in case 2, 3, 13 and 14. Remarkably, case 2 (aphakic) recovered 20/20 without correction whereas her best-CDVA was 20/32 before surgery, and cases 13 and 14 (congenital aniridia associated with cataract surgery) recovered 20/40 whereas her best-CDVA was 20/100 few years ago before the presence of cataract (best-CDVA was 20/400 just before cataract surgery). Patients were highly satisfied with the cosmetic result. Mean cosmesis score improved by 4.7 points from 3.6 preoperatively to 8.3 after surgery (P = .001). A few representative examples are shown on Figure 1, 2 and 3. One AI was slightly decentered but the patient (case 4) did not think necessary to surgically re-center it. Photophobia has been dramatically reduced. Mean photophobia score improved 5.2 points from 5.9 preoperatively to 0.7 postoperatively (P = .002). Three months postoperatively, mean endothelial density loss was 16 % (P = .001). Case 13 experienced a severe 68 % loss of ECC due to the AI forward migration necessitating a secondary surgical intervention to scleral-fixate it. Table 3 compares the 3-month and 1-year endothelial cell density for the patients who attended, to date, their 1year follow-up visit. There was no statistical difference (P = .320).

III DISCUSSION

Challenging surgical technique. In cases of cataract surgery, in-the-bag placement of the AI is the « gold standard » because it avoids uveal contact, but it is not always easy or possible. A large capsulorhexis, placement of a capsule tension ring before lens implantation, and staining the capsule can be helpful [START_REF] Snyder | Staining the capsule in congenital aniridic eyes[END_REF] . However, zonules and capsular bag are fragile in congenital aniridia 3,[START_REF] Menezo | Implantation of iris devices in congenital and traumatic aniridias: surgery solutions and complications[END_REF][START_REF] Osher | Cataract surgery combined with implantation of an artificial iris[END_REF] . The risk is dislocation or tearing of the capsular bag when inserting the AI and it is sometimes safer to place the AI in the sulcus. We recommend to systematically order the 'with-fiber' and 'fiber-free' versions of AI for aniridia cataract surgery. In cases of sulcus placement, it is paramount to carefully place the AI in the posterior chamber behind the iris remnants to avoid irrecoverable rapid endothelial cell loss and trabecular impairment as frequently described with the devices (that should not be used) destinated at changing iris colors and placed in front of the natural iris [START_REF] George | Bilateral irreversible severe vision loss from cosmetic iris implants[END_REF][START_REF] Thiagalingam | Complications of cosmetic iris implants[END_REF] . It is also important to make sure that the tissue remnants will sufficiently « hold back » the AI and prevent its forward migration. In doubt it is best to scleral-fixate it.

Visual acuity. Visual acuity is usually not very relevant concerning aniridia studies because many patients have comorbidities that can affect the final visual outcome. However, because of pinhole effect and decreased optical aberrations, best-CDVA improvement is often observed as experienced by 4 patients (case 2, 3, 13 and 14) in our study.

Photophobia. The AI is very efficient at reducing photophobia. Photophobia can be very disturbing, and some patients report a profound life enhancement after their operation even without improvement of visual acuity. We consider photophobia in itself a very good indication. Most studies report a great improvement in the reduction of photophobia with the older devices 2-5, 7-9, 16,19 or with this new device [START_REF] Mayer | Pupillary reconstruction and outcomes after artificial iris implantation[END_REF][START_REF] Spitzer | Customized humanoptics silicone prosthesis in eyes with postraumatic iris loss: outcomes and complications[END_REF][START_REF] Srinivasan | Prosthetic iris devices[END_REF][START_REF] Aylife | Small incision insertion of artificial iris[END_REF][START_REF] Gooi | Sutureless intrascleral fixation of a custom-tailored iris prosthesis with an intraocular lens[END_REF] .

Cosmetic appearance. At split lamp some color differences between the rest of the iris and the prosthesis may be detected but overall the match of the iris color between both eyes are excellent and most of the time relatives cannot tell the difference at conversational distance.

All the patients were overwhelmed by the cosmetic result especially young patients who were sometimes psychologically very disturbed by their preoperative cosmetic appearance. All studies [START_REF] Mayer | Pupillary reconstruction and outcomes after artificial iris implantation[END_REF][START_REF] Spitzer | Customized humanoptics silicone prosthesis in eyes with postraumatic iris loss: outcomes and complications[END_REF][START_REF] Srinivasan | Prosthetic iris devices[END_REF][START_REF] Aylife | Small incision insertion of artificial iris[END_REF][START_REF] Gooi | Sutureless intrascleral fixation of a custom-tailored iris prosthesis with an intraocular lens[END_REF][START_REF] Koch | Artificial iris devices: benefits, limitations and management of complications[END_REF][START_REF] Rana | A new customized artificial iris diaphragm for treatment of traumatic aniridia[END_REF][START_REF] Forlini | Simultaneous correction of post traumatic aphakia and aniridia with the use of artificial iris and IOL implantation[END_REF] report an excellent cosmetic result with this new device when compared to older devices. Endothelial density. Patients experienced a mean 16 % cell loss 3 months after the surgery. It is more than for a standard cataract surgery, but it is acceptable given the surgical challenge.

One of our patients (Case 13) had a 68 % endothelial cell loss due to the AI forward migration. This case emphasizes the absolute necessity to perfectly place the AI in the sulcus and to prevent its migration. In our study, there was no significant loss between the 3-month and the 1-year ECC for the patients having attended, to date, their one-year follow -up visit. It seems to corroborate the long-term endothelial innocuity. However, larger and longer followup series are necessary to ascertain it.

Raised postoperative IOP was the main complication. It is a well-known complication with

Morcher and Ophtec aniridia lenses placed in the sulcus [START_REF] Sundmacher | Black-diaphragm intraocular lens for correction of aniridia[END_REF][START_REF] Reinhard | Black diaphragm aniridia intraocular lens for congenital and traumatic aniridia: long term follow-up[END_REF][3][START_REF] Menezo | Implantation of iris devices in congenital and traumatic aniridias: surgery solutions and complications[END_REF][START_REF] Miller | Outcomes of implantation of modified capsule tension rings with multiple black occluder paddles for eyes with congenital and acquired iris defects: report 3[END_REF][START_REF] Mavrikakis | Surgical management of iris defects with prosthetic iris devices[END_REF][START_REF] Miller | Safety and efficacy of black iris diaphragm intraocular lens implantation in eyes with large iris defects: Report 4[END_REF][START_REF] Roman | Artificial iris intraocular lenses in aniridia or iris deficiencies[END_REF] . This new device makes no exception. We observed significantly elevated IOP in 5 eyes (35.7 %) of which 3 had preexisting glaucoma. Sptizer [START_REF] Spitzer | Customized humanoptics silicone prosthesis in eyes with postraumatic iris loss: outcomes and complications[END_REF] reports significantly increased IOP in 18 % of the eyes of which 50% had pre-existing glaucoma. Postoperative elevated IOP can sometimes be explained by a misplacement in the anterior chamber causing trabecular irritation and can be resolved by a better repositioning in the ciliary sulcus. It can also be explained by uveal tissue chafing which can cause elevated intraocular pressure but also chronic inflammation and ocular pain as observed in one of our patients. The only relieving treatment was AI removal. Pre and postoperative UBM could be helpful for a better AI sizing and positioning. We now currently use the smaller vertical WTW and not the longer horizontal WTW to determine the right diameter of the AI when inserted in the sulcus (trephine diameter: vertical WTW -1 mm).

We consider postoperative IOP a major concern and patients with pre-existing glaucoma not good candidates. There were no retinal detachment or vitreous hemorrhage in our series. If necessary, a vitrectomy through the pseudo 3.35 mm pupil is technically possible [START_REF] Toygar | Pars plana vitrectomy through a custom flexible iris prosthesis[END_REF] .

In conclusion, the customized flexible artificial iris prosthesis offers an incomparable cosmetic result. Careful selection of patients and precise surgical technique are necessary. As with older devices, when placed in the sulcus, elevated IOP is the main complication and patients with pre-existing glaucoma may not be good candidates. Patients should also be warned of a possible chronic painful inflammation eventually requiring removal of the AI.

1

  Flexible silicone artificial iris in cases of aniridia and iris deficienciesIrisartificiel en silicone flexible pour aniridies et déficiences iriennes But: Evaluer un nouvel iris artificiel en silicone flexible en cas d'aniridie ou de déficience irienne Lieu: Centre Hospitalier National d'Ophtalmologie, Hôpital des Quinze-Vingts, Paris, France. Type d'étude: Etude retrospective étudiant le résultat cosmétique, la photophobia, la densité endothéliale et la pression intraoculaire.

  : L'implantation du nouvel iris artificiel est une bonne solution du fait de ses résultats esthétiques probants. Cependant, les patients atteints de glaucome pré-existant ne sont pas de bons candidats. Les patients doivent être prévenus de la nécessité d'une possible explantation Mots clés : iris artificiel, aniridie, déficience irienne Purpose: To evaluate a customized silicone flexible artificial iris in cases of aniridia or iris deficiencies. Setting: Centre Hospitalier National d'Ophtalmologie, Hôpital des Quinze-Vingts, Paris, France. Design: Retrospective case series investigating cosmetic result, photophobia, endothelial cell density and intraocular pressure. Methods: Patients with iris deficiencies requiring cataract surgery or correction of aphakia, or pseudophakic patients, complaining of photophobia or cosmetic disturbances were implanted with the new flexible artificial iris.

Figure 1 .Figure 2 .Figure 3 .

 123 Figure 1. Case 2. Post traumatic aphakia and partial aniridia. IOL sewn to the artificial iris

Table 1 . Preoperative data

 1

	Study	Age	Etiology of	Phakic status	Best	Ocular comorbidities	Photo	Cosme	ECC
	Eye	and	Iris defect		CDVA		Phobia	sis	(cells/mm 2 )
	Number	Sex					Score	score
	1	F,37	trauma	pseudophakia	20/200	amblyopia	3	2	660
				(Ophtec311)
	2	F,62	trauma	aphakia	20/32		6	3	2027
	3	M,48	trauma	aphakia	20/32		4	3	2345
	4	M,54	trauma	aphakia	20/70	glaucoma	6	2	600
	5	M,32	trauma	cataract	20/400	subluxated lens	3	1	3412
	6	M,40	trauma	pseudophakia	20/400	amblyopia	3	4	1642
				(Ophtec311)		glaucoma
	7	M,25	trauma	aphakia	20/400	corneal scarring, glaucoma	6	4	unable (corneal
									scar)
	8	M,65	surgical trauma	aphakia	20/40	retinitis pigmentosa,	9	5	2615
						monophthalmos
	9	F,47	surgical trauma	cataract	20/32	high myopia	6	3	2190
	10	M,71	surgical trauma	aphakia	20/2000	corneal decompensation	5	5	unable (corneal
									edema)
	11	M,84	trauma	aphakia	20/200	macular degeneration	9	5	2412
	12	M,69	surgical trauma	pseudophakia	20/32		7	5	1200
	13	F,29	congenital	cataract	20/400	nystagmus	8	4	2645
	14	F,29	congenital	cataract	20/400	nystagmus	8	4	2522
	15	M,30	congenital	cataract	20/2000	nystagmus	8	4	2250
	CDVA : corrected distance visual acuity. Photophobia score from 0 (no photophobia) to 10 (intolerable photophobia). Cosmesis score from 0
	(very unsatisfied) to 10 (very satisfied). ECC : endothelial cell count

Table 2 . Three-month follow-up

 2

	Study	Best-	AI placement	Photo	Cosmesis	ECC	Complications
	Eye	CDVA		Phobia	score	(cells/mm 2 )
	Number			score
	1	20/200	(IOL-AI) sulcus scleral-fixated	1	8	620	elevated IOP
	2	20/20	(IOL-AI) sulcus scleral-fixated	0	9	1812
	3	20/25	(IOL-AI) sulcus scleral-fixated	1	9	2122
	4	20/2000	(IOL-AI) sulcus scleral-fixated	1	7	corneal edema	-elevated IOP
							-slight decentration of the
							AI
							-corneal decompensation
	5	20/25	IOL in the bag	0	10	3213
			AI sulcus scleral-fixated
	6	20/400	(IOL-AI) sulcus scleral-fixated	3	4 (8	1414	-elevated IOP
					before AI		-chronic pain and
					removal)
							-AI removal at 2 months
							postop
	7	20/400	(IOL-AI) sulcus scleral-fixated	2	6	preoperative	elevated IOP
						corneal scar
	8	20/40	(IOL-AI) sulcus scleral-fixated	0	9	2412
	9	20/20	IOL and AI In the bag	0	9	1980
	10	20/200	(IOL-AI) sulcus scleral-fixated	1	6	preoperative
			PKP			corneal edema
	11	20/200	(IOL-AI) sulcus scleral-fixated	1	9	2124
	12	20/32	Sulcus without suture	0	9	1020
	13	20/40	Sulcus without suture	0	9	842	AI migration and elevated
							IOP necessitating secondary
							surgical scleral fixation
	14	20/40	Sulcus sleral-fixated	0	9	2350
	15		AI not inserted			excluded from	Intraoperative Argentinian
			Excluded from the study			study	flag. AI not inserted.

Table 3 . ECC change between 3-month and 1-year follow-up visit

 3

	Study Eye	3-month ECC	1-year ECC
	Number	(cells/mm 2 )	(cells/mm 2 )
	1	620	628
	2	1812	1814
	3	2122	2112
	4	corneal edema	corneal edema
	5	3213	3215
	6	1414	1412
	7	preoperative corneal scar
	8	2412	2405
	9	1980	1975
	ECC: endothelial cell count

Funding Statement : The authors received no financial support for the research, authorship, and /or publication of this article