To investigate treat and extend versus pro re nata regimen in neovascular age-related macular degeneration: results from the IDEM study.

PURPOSE: The purpose of this study is to report the 24-month outcomes of a pro re nata (PRN) compared with a treat and extend (T&E) regimen in patients previously treated for neovascular age-related macular degeneration (nAMD). METHODS: This was a 2-year prospective, single-center study. Previously treated patients for nAMD were randomized into two regimen groups: T&E and PRN groups. Main outcome measured was change in best corrected visual acuity (BCVA) from baseline to month 24. Secondary outcomes encompassed anatomical features such as central retinal thickness (CRT), number of intravitreal injections (IVI), and visits required. RESULTS: A total of 124 eyes received the T&E (n = 61) or PRN (n = 63) regimen. At month 24, the mean BCVA change was -4.4 early treatment diabetic retinopathy study (ETDRS) letters (T&E) and -3.4 ETDRS letters (PRN), with a difference of +1.1 ETDRS letters (95% CI [-2.25]; p = 0.006). The mean change in CRT was -10.6 µm (T&E) and -7.9 µm (PRN), with a difference of +2.6 µm (95% CI [+19.2]; p = 0.004). The T&E group had received a mean of +4.6 more injections (95% CI [-7.06; -2.12]; p < 0.001) at month 24. CONCLUSION: There was statistically proven non-inferiority between the PRN and T&E regimens in terms of visual and anatomical outcomes at 24 months, with significantly more IVI administered in the T&E regimen.

Repeat corneal transplantation: indication, surgical technique, and early graft failures trends in France from 2004 to 2019.

PURPOSE: To investigate the repeat corneal transplantation trend in France from 2004 to 2019. METHODS: Review of the prospectively compiled French Biomedicine Agency electronic database containing all corneal transplantation records from 2004 to 2019. The surgical technique, demographic characteristics, diagnosis, and previous graft data were retrieved and analyzed using the Cochran-Armitage trend test. RESULTS: A total of 66,584 corneal transplantations were performed, 51,260 of which were first grafts and 15,324 (23%) were regrafts. For regrafts, 77% were penetrating keratoplasties (PK) and 19.6% were lamellar keratoplasties (LK). Age, hypertonia, glaucoma, trauma, lens surgery, immune disorders, diameter > 8.5 mm, and neovessels in > 2 quadrants were associated with a higher rate of repeat keratoplasty. Keratoconus, secondary endothelial dystrophy, and Fuchs' dystrophy were the principal indications for regrafting. When a previous graft failed, it occurred earlier for patients with LK (4.6 years, median = 2, SD = 7.54) than PK (8.48 years, median = 5, SD = 9.51). Failure within a year was the reason why 28.3% of the LK regrafts and 12.5% of PK regrafts were performed, while for failure within two years these values were 49.9% and 27.8%, respectively. Graft survival decreased with the number of repeat keratoplasty, being more pronounced after a second LK regraft and after a first PK regraft. CONCLUSION: The number of LK regrafts increased continuously, and 1/3 were performed for failure within the year. This rate increased until 2015, after which it stabilized until 2019, probably due to the better mastery of the technique.

Regional trends in corneal transplantation from 2004 to 2015 in France: a 12-year review on indications, technique and waiting period.

The aim of this study was to report the 12-year longitudinal trends in regional disparity in terms of indications, techniques and waiting period for corneal transplantation in France from 2004 to 2015. The records of all corneal transplantations performed from 2004 to 2015 in France were retrospectively reviewed by analasing the registry and the territorial organization [divided France into 7 interregional areas of collection and distribution of grafts (IACD)] of the French Biomedicine Agency. A total of 46,658 corneal transplantations were performed between 2004 and 2015. In 2014, there was 65.8 keratoplasties per million inhabitants (10-6 per capita in France, but there were some regional disparities, from 44.9 × 10-6 per capita in IACD 2 to 87.2 × 10-6 per capita in IACD 5. In 2014, IACD 7 performed the highest number of transplantations for keratoconus with 15.7 × 10 - 6 per capita; IACD 5 ranked first for Fuchs endothelial disease and secondary endothelial failure with, respectively, 20.5 × 10-6 per capita and 21.2 × 10-6 per capita, and IACD 4 ranked first for graft failure with 17.4 × 10-6 per capita. All regions over the years began to perform more lamellar keratoplasties (4.3% in 2004 vs 45.2% in 2015) and fewer penetrating keratoplasties (85.8% in 2004 vs 48.2% in 2015). The mean waiting time was 3.4 ± 5.2 months in France over 12 years, with minimal disparities between regions: all of them under 4 months waiting time in 2015, from 1.4 months for IACD 1-3.8 months for IACD 5. Regional disparities have changed over the years, with a modification of indications, and upgrading surgical techniques for some indications. Some disparities remain, mainly because of the variability in the number and activity of transplantation centres and eye banks. Measures could be taken to minimize these disparities, such as increasing communication between eye banks. The waiting time for keratoplasty decreasing below the 4-month mark is a good indicator of the progress made. Regional disparities have decreased over the years, but some regions remain disadvantaged in terms of needs and access to transplants. Tomorrow's challenge is to identify solutions and adapt the offer to the needs.

Innovative corneal active storage machine for long-term eye banking.

Optimal ex vivo corneal storage in eye banks is crucial to increase both the number of corneas suitable for graft and their intrinsic quality, mainly the number of viable endothelial cells, which dictates graft survival in recipients. With both passive storage methods used worldwide (short-term cold storage in the United States, long-term organ culture in Europe), significant endothelial cell loss is inevitable. Here we show that, with an active storage machine, also called a bioreactor, which restores 2 fundamental physiological parameters, intraocular pressure and medium renewal, endothelial cell survival is improved by 23% compared with organ culture after 4 weeks' storage. Also observed in the bioreactor is a 4-fold higher expression of Na+ /K+ ATPase, which supports one of the major endothelial cell pumping functions. In addition, corneas remain thin and transparent, so they are suitable for surgery at any time. This new active eye banking method may help to reduce the severe global scarcity of donor corneas.

Long-term adverse event: inflammatory orbitopathy induced by pembrolizumab in a patient with metastatic melanoma.

The recent advent of immune checkpoint inhibitors (ICI), including anti-programmed cell death 1 protein (anti-PD-1) agents has revolutionized the therapeutic approach of metastatic malignancies. Yet, ICI can disrupt immune tolerance resulting in enhanced immune activation in normal tissues with significant toxicity. A dysregulated activation of T-cells directed to normal tissues stands as the main mechanism of immune-related adverse events (irAE). To date, only two cases of immune-related inflammatory orbitopathy related to anti-PD-1 agents have been reported. This rare immune adverse event usually occurred early after ICI initiation. Here, we report the first case of late inflammatory orbitopathy occurring in a melanoma patient treated with pembrolizumab. Consequently, the occurrence of irAE under ICI should be monitored, even late after treatment instauration.

Impact of Metamorphopsia on Quality of Life after Successful Retinal Detachment Surgery.

PURPOSE: To determine the impact of metamorphopsia on quality of life after successful retinal detachment (RD) surgery and to determine which retinal changes are related to the most severe distortions. DESIGN: This was a prospective, observational, consecutive study. METHODS: The study included 58 eyes of 58 consecutive patients who underwent successful RD surgery. At 6 months postoperatively, the incidence and severity of metamorphopsia were assessed by a quality-of-life questionnaire. Microstructure retinal changes were studied with spectral domain optical coherence tomography (OCT). The questionnaire score was compared with pre- and postoperative OCT findings. RESULTS: Overall, 20 patients (34.5%) had metamorphopsia. Outer retinal folds (ORFs) and the macular status before surgery, together with postoperative ORFs and decrease in ellipsoid and/or interdigitation photoreceptor zone reflectivity, were identified as risk factors of developing metamorphopsia (relative risk, 1.7-4.8). The most severe visual distortions were associated with ORFs. CONCLUSION: Metamorphopsia is a frequent occurrence after RD surgery and its impact on patients' quality of life appears to be limited. While it may be difficult to prevent photoreceptor loss occurring after surgery, limiting postoperative ORFs may be helpful in reducing their incidence.

Quantitative analysis of photoreceptor layer reflectivity on en-face optical coherence tomography as an estimator of cone density.

BACKGROUND: To investigate whether outer retinal reflectivity on en-face Optical coherence tomography (OCT) can be considered as an estimator of cone density measured in the same area. METHODS: Forty-one points of comparisons were studied in 9 eyes (n = 6 patients) presenting maculopathies with various degrees of impairment of the photoreceptor layer. The inner segment ellipsoid zone (EZ), interdigitation zone (IZ), and retinal pigment epithelium (RPE) reflectivity were measured on coronal reconstruction of the photoreceptor layer using homemade dedicated software (Matlab, MathWorks Inc., Natick, USA). The cone metrics were measured in the same perifoveal region of interest using a high-resolution flood illumination adaptive optics camera. A semi-automatic cone counting method was adopted and all photoreceptor densities provided by the manufacturer's software were recounted manually by two experienced readers. RESULTS: Mean manual cone count was 21,522 ± 6700 (range, 5908-31,233 cells/mm2). Both EZ and IZ reflectivity values were closely correlated with cone density in the area studied (r2: 0.80 and 0.62, respectively; p < 0.0001). CONCLUSION: Outer retinal reflectivity on en-face optical coherence tomography correlates well with photoreceptor density. This cone density estimation method based on retinal reflectivity could have interesting applications in the exploration and management of maculopathies.

A Giant Tumefactive Virchow-Robin Space: A Rare Cause of a Homonymous Quadrantanopia.

A 53-year-old woman was found to have a left inferior homonymous quadrantanopia. Brain MRI disclosed a giant Virchow-Robin space compressing the right optic tract. After fenestration of this cystic lesion, most of the visual field loss resolved. Giant Virchow-Robin spaces may cause homonymous field defects which, with appropriate management, may improve.

Corneal transplantation: study of the data of a regional eye bank for the year 2013 and analysis of the evolution of the adverse events reported in France since 2010.

To analyze the data of the adverse events collected in a single major eye bank (EFS Bourgogne Franche Comté, Besançon, France) for the year 2013 and to report the French data of biovigilance provided by the French National Agency for Medicines and Health Products Safety (ANSM) between 2010 and 2013. we have set up a study of adverse events in 2013, in collaboration with a single eye bank (EFS Bourgogne Franche Comté, Besançon, France). A survey was sent to the surgeon for each delivered corneal button by the eye bank in 2013. They were asked for each grafted patient performed in their center, the type of graft (penetrating keratoplasty, anterior keratoplasty or endothelial keratoplasty), the occurrence of adverse events (primary failure, infectious keratis, endophthalmitis, immune rejection, and other events) and the time interval between surgery and events (Less than 1 postoperative month, between 1 month and 1 year postoperatively, >1 year postoperatively). In 2013, 407 corneal buttons were delivered by the eye bank of Besançon in 21 medical centers which performed corneal grafts and we sent 407 surveys. We received 243 completed questionnaires (59.75%) from 11 centers (52.38%). The global reported rate of adverse events was 27.54% of the graft (n = 65/236 corneal grafts performed in 11 centers in 2013; 20% of Primary graft failure, 11% of infectious keratitis, 1% of endophthalmitis, 34% of rejection, 34% of other incidents). 30.16% of complications were noticed before the first month after surgery versus 52.38% of complications noticed between the first month and the first year after surgery and 17.46% of complications noticed after the post-operative first year The most common causes of adverse events after PK were Immune rejection (13.17%), surgical causes (5.98%) and infection (4.79%) and after EK were Primary graft failure (8.2%) and surgical causes (19.67%). In 2013, in France 0.83% of adverse events were notified in ANSM. For the 236 performed graft issued from a major eye bank (EFS Besançon) in 2013 the global reported rate of post-graft adverse events was 27.54% of the grafts (20% of Primary graft failure, 11% of infectious keratitis, 1% of endophthalmitis, 34% of rejection and 34% of other incidents). Compared to the ANSM data (0.83% of adverse events reported in 2013) this rate is high. This difference can be explained by the low rate of annual notification to the ANSM and shows that biovigilance in France must be more developed. Since biovigilance needs constant improvement for the safety of the graft system, training, information for practitioners, simplifications of procedures and international standardization of the definition are the main points that could be improved.

Considering 3D topography of endothelial folds to improve cell count of organ cultured corneas.

The posterior side of the cornea is covered by the endothelial monolayer, which governs corneal transparency but cannot proliferate. Determination of endothelial cell density (ECD) is therefore the minimal and mandatory quality control in all eye banks. It avoids primary graft failures caused by endothelial insufficiency, and allows allocation of corneas to surgical techniques requiring different numbers of endothelial cells (ECs). Corneas stored in organ culture (17% of grafts worldwide), are characterized by heavy stromal swelling and numerous deep endothelial folds, up to 200 µm high. During microscopic en face observation, flat surfaces are thus exceptional and EC counting is biased by parallax errors, resulting in overestimated eye bank ECD (ebECD). We used a motorized transmitted light microscope to acquire Z-stacks of images every 10 µm, and processed them to reconstruct the 3D surface of the folded endothelium. This method (3D-ECD) takes into account the local point-by-point slope in order to correct ECD. On a set of 30 corneas, we compared 3D-ECD and ebECD determined on five identical zones at the center of the cornea. 3D reconstruction allowed us to visualize twice as many cells, and ebECD was 8.1 ± 4.5% (95%CI 6.4-9.7) higher than 3D-ECD, with 1744 ± 488 versus 1606 ± 473 cells/mm2. 3D counting makes it possible to increase cell sampling and to correct overestimation by the conventional en face counting still routinely performed in eye banks.

Corneal perforation: another side effect of nicorandil.

CONTEXT: Nicorandil is an antianginal drug used for 20 years in Japan and introduced in France in 1994. Since 1997, side effects such as mucocutaneous ulcerations have regularly been reported. OBJECTIVE: To describe the first case of a patient with a spontaneous corneal perforation associated with mucocutaneous ulcerations while taking Nicorandil. MATERIALS AND METHODS: A 81-year-old patient, with no past history of ocular disease but a long past history of cardiovascular disease, presented with a spontaneous paracentral corneal perforation. This was consecutive to 5 months of recurrent keratoconjunctivitis and mucocutaneous ulcerations resistant to conventional therapy. (He was taking nicorandil for 5 years.) A penetrating keratoplasty was performed in emergency. RESULTS: Inflammatory and infectious causes of spontaneous corneal perforation were ruled out. After initial uneventful post-operative wound healing, an epithelial ulcer appeared on the graft. Dermatologists suggested the iatrogenic role of nicorandil and the drug was discontinued. Both mucocutaneous and corneal ulcerations resolved rapidly. DISCUSSION: Although mucocutaneous ulcerations have been attributed several times to nicorandil, this is, to our knowledge, the first major corneal damage due to this antianginal drug. Timing, pattern of illness, absence of other aetiology, recurrence of epithelial ulceration on the corneal graft and its spontaneous healing after nicorandil discontinuation make it highly apparent probable that nicorandil was directly involved in this corneal perforation. CONCLUSION: Ophthalmologists and dermatologists should be aware of the risk of severe but reversible corneal ulcerations in patients treated with nicorandil. A pharmacovigilance warning statement should be compulsory.

P02-A121†Precut DSAEK stored in an active storage machine: feasibility study.

PURPOSE: The number of endothelial grafts precut by eye banks increases. Their shelf life is limited to a few days. We previously demonstrated the superiority of an active storage machine (ASM) over organ culture (passive) for whole corneas. AIMS: to measure endothelial viability of precut DSAEK after 3 or 10 days of storage in our ASM in a preclinical study. METHODS: Human pairs of corneas were included. The endothelial cell density (ECD in cells/mm2), and central corneal thickness (CCT in µm) were measured to ensure their initial intra pair comparability. After deswelling (CorneaJet, Eurobio) grafts preparation was performed by cutting the anterior stroma with a Moria linear microkeratome and keeping the anterior lamellae attached during storage. After randomization, one cornea was kept in the corneajet bottle (CJ) and the other was inserted into the ASM allowing a renewal or storage medium (CorneaMax, Eurobio) at 2.6 µL/min with 21 mmHg of pressure in the endothelial chamber. Both group of corneas were stored for 3 or 10 days at 31°C. The final viable ECD (vECD) was determined using the triple staining with Hoechst-Ethidium-Calcein-AM by an independent experimenter in a masked fashion. RESULTS: Initial ECDs were comparable: 2595±878 in ASM versus 2654±954 cells/mm2 in CJ for the 3-days period (n=5 pairs) and 2416±712 in ASM versus 2492±764 cells/mm2 in CJ for the 10-period (n=5 pairs). CCTs were also comparable. The anterior lamellae stayed attached in either the ASM or CJ. vECD was significantly higher in ASM than in CJ with respectively 2062±695 cells/mm2 versus 1632±633 cells/mm2 after 3 days either a cell loss of 20.5% and 38.5% respectively (p=0.0062) and 1082±649 versus 935±691 cells/mm2 for the 10-day period either a cell loss of 132% and 164% respectively (p=0.005). Grafts thickness did not differ after 3 days 219±25 µm in ASM versus 182±39 µm (p=0.063) or 10 days respectively 221±58 µm versus 189±48 µm (p=0.06). CONCLUSION: The storage of precut DSAEKs into the ASM allows a better preservation of grafts without use on deswelling storage medium. Nevertheless, the cell loss remains high after 10 days, suggesting a significant cell stress.

P01-A120†Pre-dissected dmek stored in an active storage machine: feasibility study.

PURPOSE: The number of endothelial grafts precut by eye banks increases. Their shelf life is limited to a few days. We previously demonstrated the superiority of an active storage machine (ASM) over organ culture (passive) for whole corneas. AIMS: To measure the endothelial viability of pre-dissected DMEK after 3 and 10 days of storage in our ASM in a preclinical study. METHODS: Pairs of human corneas were included. The endothelial cell density (ECD in cells/mm2), thickness and transparency of corneas were measured before graft preparation. Descemet's membrane (DM) was peeled using the no-touch technique leaving the graft attached to the center of the cornea (on approx. 1mm2). After randomization, one cornea was kept in organ culture (OC) and the other in the ASM (21 mmHg, 2.6 µL/min) in the same medium (CorneaMax, Eurobio). The final viable ECD was determined using the triple staining with Hoechst-Ethidium-Calcein-AM. In addition, the expression of CD166 and NCAM (lateral membranes), ZO-1 (apical junctions), Na+/K+ ATPase (endothelial pump function) and COX-IV (mitochondrial content) was studied by immunostaining to characterize endothelial cells after the storage. RESULTS: Initial ECDs were comparable: 2185±232 cells/mm2 in the ASM versus 2276±328 in OC for the 3-day period and 2680±416 cells/mm2 in the ASM versus 2644±420 in OC for the 10-day period. The DMs did not fold back in either BR or OC. The viable ECD did not differ significantly between the ASM and OC for either storage period: 2378±501 (ASM) versus 2342±503 (OC) for the 3-day period (n=8 pairs and p=0.624) and 2482±288 (ASM) versus 2579±315 (OC) for the 10-day period (n=5 pairs and p=0.176). Corneas were more transparent and thinner in the ASM than in OC after 3 days (916±86 versus 1193±136µm, p=0.0001) and 10 days (957±128 versus 1220±105µm, p=0.0625). The functional and structural markers studied were expressed in both groups after 3 and 10 days, some better preserved in the ASM. CONCLUSION: The storage of precut DMEKs is possible in ASM and OC for at least 10 days. Interestingly, a pre-dissected endothelium continues to partially exert its pump function into the ASM. In practice, this could allow the stroma to be used for DALK without further deswelling. In addition to improving the storage of whole grafts, the ASM allows the storage of precut DMEKs for up to 10 days with excellent endothelial survival.

P38-A108†Optimization of the triple HEC staining for laboratory assessment of DMEK graft quality.

INTRODUCTION: The quality of the endothelial graft is critical to the success of DMEK and to the survival time of the graft. The peeling technique, preservation method, and skill level of graft preparers need to be evaluated and validated. The most reliable method of evaluation is the viability test based on a triple staining of Hoechst- Ethidium-Calcein AM (H-E-C) which allows the determination of the total number of viable cells on the graft. However, this test has some shortcomings for DMEK grafts: 1) The undesirable fluorescence of the Calcein AM stain prevents accurate viability analysis, especially in cases where the graft is attached to the cornea for preservation; 2) Incompatibility with immunofluorescence (IF) that could provide additional information. The objective of this study is to develop technical tricks to overcome these drawbacks. METHODS: Two strategies were employed to improve Calcein AM staining: 1. Increase the specific fluorescence intensity by changing the diluent and the concentration of Calcein AM; 2. Decrease undesired fluorescence from keratocytes by adding Trypan Blue (BT). In order to combine the IF after the HEC test, an extension wash in PBS was performed. RESULTS: Calcein AM at 4µM diluted in OptiMEM increased fluorescence intensity 3-fold (p=0.0017, n=5) compared with conventional staining at 2µM in PBS. BT decreased the undesired fluorescence of Calcein and thus optimized count variability between different operators by 42% (p=0.0027, n=10) and saved 40% (p=0.0002, n=10) of count time. To perform IF after HEC, prolonged washing in PBS is an effective method to remove residual Calcein fluorescence and allows release of the FITC/Alexa 488 filter. CONCLUSION: This study provides effective technical tips for optimizing the endothelial viability assay using Calcein AM and for performing IF after the viability assay.

Characterization of Femtosecond Laser and Porcine Crystalline Lens Interactions by Optical Microscopy.

The use of ultrafast laser pulses for eye anterior segment surgery has seen a tremendous growth of interest as the technique has revolutionized the field, from the treatment of myopia, hyperopia, and presbyopia in the cornea to laser-assisted cataract surgery of the crystalline lens. For the latter, a comprehensive understanding of the laser-tissue interaction has yet to be achieved, mainly because of the challenge of observing the interaction zone in situ with sufficient spatial and temporal resolution in the complex and multi-layered tissue of the crystalline lens. We report here on the dedicated characterization results of the laser-tissue interaction zone in the ex vivo porcine lens using three different methods: in situ and real-time microscopy, wide-field optical imaging, and phase-contrast microscopy of the histological cross sections. These complementary approaches together revealed new physical and biological consequences of laser irradiation: a low-energy interaction regime (pulse energy below ~1 µJ) with very limited cavitation effects and a stronger photo-disruption regime (pulse energy above 1 µJ) with a long cavitation duration from seconds to minutes, resulting in elongated spots. These advances in the understanding of the ultrafast laser's interactions with the lens are of the utmost importance for the preparation of the next-generation treatments that will be applied to the lens.

Objective measurement of adherence to topical steroid medication after penetrating keratoplasty using an electronic monitoring aid: A pilot study.

Objectives: Corneal transplantation is the most common transplant worldwide and its success critically depends on the management of corneal graft rejection through topical steroid therapy during the first 12 months after surgery. There is currently no published data on adherence after keratoplasty. This pilot study aims to explore the adherence to topical steroid after penetrating keratoplasty using a smart electronic device. Methods: Thirty patients undergoing penetrating keratoplasty were included to evaluate the adherence to topical dexamethasone medication for 12 months after surgery. Patients received the usual post-transplantation treatment (topical dexamethasone) and follow-up after surgery (day 15, months 1, 2, 3, 4, 5, 6, 9, and 12). Adherence to treatment was monitored using the KaliJAR device (Kali Care, Santa Clara, CA, USA), which recorded the number of single-dose units (SDU) discarded. At control visits, data recorded by the device were compared to the manually count of SDU. Adherence ratio and individual adherence curve were explored for all patients. Results: Data from 27 patients showed a high agreement between adherence ratio calculated based on the device data and obtained from manual counting of the discarded SDU (intraclass coefficient correlation of 0.87 [95% CI: 0.738-0.938]). Mean adherence to the treatment over the 12-month study period was 95.2 ± 4%. Conclusions: Adherence to topical dexamethasone for 12 months after corneal transplantation was high. The connected device was able to record accurately the discarded SDU. This approach would be a particular interest in the early identification and personalized follow-up of poorly adherent patients.

Predictive factors for exudation of quiescent choroidal neovessels detected by OCT angiography in the fellow eyes of eyes treated for a neovascular age-related macular degeneration.

BACKGROUND: To identify predictive factors for exudation for quiescent choroidal neovessels (qCNV) in the fellow eyes of eyes treated for a neovascular age-related macular degeneration (AMD). METHODS: Prospective observational study. One hundred and forty-four contralateral eyes of 144 patients treated for wet AMD were analysed. At a baseline visit, multimodal imaging including dye angiographies and optical coherence tomography angiography (OCT-A) was performed in order to detect qCNV. Patients were followed up for 12 months with a monthly assessment. The manifestation of any type of exudation (either intra- or subretinal fluid or hyperreflective subretinal material) was monitored. RESULTS: The prevalence of qCNV in the treatment-naive eyes was 15.9% with an incidence over a 12-month period of 2.8%. In total, 40.7% of the overall neovessels remained stable with no sign of exudation, while 59.3% presented some fluid during the follow-up. A statistically significant relationship was established for the following variables preceding the exudation: increase in central macular thickness (OR = 116; 95% CI [4.74; 50530] p = 0.038), increase in pigment epithelial detachment height (OR = 1.76; 95% CI [1.17; 3.18] p = 0.021) and width (OR = 1.53; 95% CI [1.12; 2.62] p = 0.042), increase in neovessels' surface on OCT-A (OR = 6.32; 95% CI [1.62; 51.0] p = 0.033), emergence of a branching pattern (OR = 7.50; 95% CI[1.37; 61.5] p = 0.032) and appearance of a hypointense halo surrounding the lesion (OR = 10.00; 95% CI [1.41; 206] p = 0.048). CONCLUSIONS: The risk of exudation in the treatment-naive fellow eyes of eyes treated for neovascular AMD was notably increased in the presence of qCNV. The biomarkers identified will help to detect their activation in order to ensure prompt antiangiogenic therapy.

Changes of Contamination Rate and Microorganism Evaluation in Organ-Cultured Human Corneas: A 14-Year Review From a French Regional Eye Bank.

PURPOSE: This study aimed to assess how the contamination rate of organ-cultured corneas has evolved and to analyze the evolution of microorganisms involved. METHODS: Data from the Besançon eye bank were reviewed over 14 years (2005-2018). The changes in the contamination rate and the contaminant species found during the organ culture storage were analyzed. Microbiological tests were performed twice on the storage media-at day 5 and before the deswelling phase. RESULTS: Among the 17,979 donor corneas collected, 1240 corneas were microbiological-test positive. The average annual contamination rate was 6.8% (range: 5.2%-8.9%). Seventy-five percent of contaminations were bacterial. The most frequently found bacterium was Staphylococcus spp. (31.3%), followed by non-Enterobacteriaceae Gram-negative Bacilli (GNB) (27.3%), with most Sphingomonas spp. and Pseudomonas spp. Fungal contamination (21.9%) was dominated by Candida (82.7%). Seventy-seven types of microorganisms were identified. The Staphylococcus rate tended to decrease, whereas non-Enterobacteriaceae GNB rate has increased in the past few years to reach 46% of bacteria. Most of the contaminations were detected in the early phase of organ culture at day 5 (89.2%). The second microbiological test found 44.8% of fungal contaminations (predominantly Candida spp.). CONCLUSIONS: The annual contamination rate was stable and remains low, but the types of contaminating microorganisms varied from year to year. Staphylococcus spp. and non-Enterobacteriaceae GNB accounted for a significant proportion of the contaminations. We found a significant proportion of contamination, especially fungal, at the late phase of storage. Reassessing the antibiotics and antifungals in the storage medium may be useful to limit corneal disposal.

Epithelial Regeneration in Human Corneas Preserved in an Active Storage Machine.

Purpose: To characterize the corneal epithelium (CE) and limbal epithelium (LE) of human corneas stored in an innovative active storage machine (ASM) after a period of organ culture (OC). Methods: Corneas unsuitable for graft and stored in a standard commercial OC medium for 2 to 5 weeks were transferred into our ASM for 14 days. The ASM actively maintained an overpressure on the endothelial side (20 mm Hg) while ensuring medium renewal. We compared three modalities of storage in the ASM's epithelial chamber: (1) alternating exposure to a supplemental hormonal epithelial medium (SHEM) and air (air-lifting), (2) continuous immersion in SHEM, and (3) continuous immersion in OC medium. Passive immersion of the whole cornea in OC medium or of the CE in SHEM with or without airlifting served as controls. Paired corneas were used for better comparability. Histology, differentiation (by immunolabeling), and ultrastructure were analyzed at the end. Results: The ASM with air-lifting was most effective in regenerating a pluristratified and differentiated CE (apical ZO-1 and MUC16 staining and regeneration of the glycocalyx). In addition, the LE was stratified with preserved expression of ABCB5. The ASM with immersion in SHEM or OC medium gave a less stratified and differentiated CE. In the three control groups, the epithelia, when present, were paucistratified and less differentiated. Conclusions: In human corneas previously stored in OC, the ASM regenerates a CE with differentiation characteristics close to normal. Translational Relevance: Regeneration of the epithelium of human corneas discarded by eye banks will increase tissue availability for research.

Surgical Application of Human Amniotic Membrane and Amnion-Chorion Membrane in the Oral Cavity and Efficacy Evaluation: Corollary With Ophthalmological and Wound Healing Experiences.

Due to its intrinsic properties, there has been growing interest in human amniotic membrane (hAM) in recent years particularly for the treatment of ocular surface disorders and for wound healing. Herein, we investigate the potential use of hAM and amnion-chorion membrane (ACM) in oral surgery. Based on our analysis of the literature, it appears that their applications are very poorly defined. There are two options: implantation or use as a cover material graft. The oral cavity is submitted to various mechanical and biological stimulations that impair membrane stability and maintenance. Thus, some devices have been combined with the graft to secure its positioning and protect it in this location. This current opinion paper addresses in detail suitable procedures for hAM and ACM utilization in soft and hard tissue reconstruction in the oral cavity. We address their implantation and/or use as a covering, storage format, application side, size and number, multilayer use or folding, suture or use of additional protective covers, re-application and resorption/fate. We gathered evidence on pre- and post-surgical care and evaluation tools. Finally, we integrated ophthalmological and wound healing practices into the collected information. This review aims to help practitioners and researchers better understand the application of hAM and ACM in the oral cavity, a place less easily accessible than ocular or cutaneous surfaces. Additionally, it could be a useful reference in the generation of new ideas for the development of innovative protective covering, suturing or handling devices in this specific indication. Finally, this overview could be considered as a position paper to guide investigators to fulfill all the identified criteria in the future.