Positive cooperativity in synergistic activation of Wnt proteins.

BACKGROUND: Wnt proteins are crucial for embryonic development, stem cell growth, and tissue regeneration. Wnt signaling pathway is activated when Wnt proteins bind to cell membrane receptors. METHODS AND RESULTS: We employed a luciferase reporter assay in HEK293STF cells to measure Wnt protein-induced signaling. We observed that Wnt3a uniquely promotes the Wnt/ß-catenin pathway through positive cooperativity. Additionally, MFH-ND, a molecular mimic of Wnt ligands, markedly increased Wnt3a-induced signaling in a dose-responsive manner. This suggests that various Wnt ligands can synergistically enhance Wnt pathway activation. CONCLUSIONS: The study suggests the likelihood of various Wnt ligands coexisting in a single signalosome on the cell membrane, providing new insights into the complexities of Wnt signaling mechanisms.

Comparison of Automated and Manual Measurement of Corneal Epithelial Thickness in Eyes With Limbal Stem Cell Deficiency.

PURPOSE: The purpose of this study was to compare the outcomes of manual and automated corneal epithelial thickness (CET) assessments using anterior segment optical coherence tomography in eyes with limbal stem cell deficiency (LSCD). METHODS: Eighty-seven eyes from 64 patients with LSCD and 65 eyes from 39 healthy subjects were included in this cross-sectional study. OCT images of corneas were acquired using a Fourier-domain anterior segment optical coherence tomography. The automated measurement of CET was obtained using the manufacturer's program and the manual measurements were obtained by 2 masked observers. The average CET was obtained from 3 consecutive epithelial profile maps. The average CET of manual measurement was obtained from 3 consecutive cross-line scans using 3-point measurement as previously described. RESULTS: The central CET was thinner in patients with LSCD compared with healthy individuals by both manual and automated measurements. Automated CET measurements were similar to the manually obtained CET in the healthy controls (r = 0.911). However, there is a lower correlation between the automated and manually obtained CET in the LSCD group (r = 0.497). Manual measurements of CET (39.8 ± 11 µm) in eyes with LSCD were significantly lower than the automated measurements (48.8 ± 7.2 µm, P = 0.001, 95% CI -11.0 to -6.9). The correlations between the automated and manually obtained measurements in the mild, moderate, and severe stages of LSCD were 0.623, 0.632, and 0.378, respectively. CONCLUSIONS: There is a large discrepancy between the manual and automated measurements in eyes with LSCD but not in normal eyes. Automated measurements in LSCD exhibited a higher rate of errors and nonuniform measurements due to the presence of subepithelial scars. Automated CET measurements appear to be unreliable in eyes with corneal scars in LSCD.

Aftereffects of visuomanual prism adaptation in auditory modality: Review and perspectives.

Visuomanual prism adaptation (PA), which consists of pointing to visual targets while wearing prisms that shift the visual field, is one of the oldest experimental paradigms used to investigate sensorimotor plasticity. Since the 2000's, a growing scientific interest emerged for the expansion of PA to cognitive functions in several sensory modalities. The present work focused on the aftereffects of PA within the auditory modality. Recent studies showed changes in mental representation of auditory frequencies and a shift of divided auditory attention following PA. Moreover, one study demonstrated benefits of PA in a patient suffering from tinnitus. According to these results, we tried to shed light on the following question: How could this be possible to modulate audition by inducing sensorimotor plasticity with glasses? Based on the literature, we suggest a bottom-up attentional mechanism involving cerebellar, parietal, and temporal structures to explain crossmodal aftereffects of PA. This review opens promising new avenues of research about aftereffects of PA in audition and its implication in the therapeutic field of auditory troubles.

Three-Dimensional Reconstruction of Subbasal Nerve Density in Eyes With Limbal Stem Cell Deficiency: A Pilot Study.

PURPOSE: Corneal subbasal nerve parameters have been previously reported using 2-dimensional scans of in vivo laser scanning confocal microscopy (IVCM) in eyes with limbal stem cell deficiency (LSCD). This study aims to develop and validate a method to better quantify corneal subbasal nerve parameters and changes from reconstructed 3-dimensional (3D) images. METHODS: IVCM volume scans from 73 eyes with various degrees of LSCD (mild/moderate/severe) confirmed by multimodal anterior segment imaging including IVCM and 20 control subjects were included. Using ImageJ, the scans were manually aligned and compiled to generate a 3D reconstruction. Using filament-tracing semiautomated software (Imaris), subbasal nerve density (SND), corneal nerve fiber length, long nerves (>200 µm), and branch points were quantified and correlated with other biomarkers of LSCD. RESULTS: 3D SND decreased in eyes with LSCD when compared with control subjects. The decrease was significant for moderate and severe LSCD ( P < 0.01). 3D SND was reduced by 3.7% in mild LSCD, 32.4% in moderate LSCD, and 96.5% in severe LSCD. The number of long nerves and points of branching correlated with the severity of LSCD ( P < 0.0001) and with declining SND (R 2 = 0.66 and 0.67, respectively). When compared with 2-dimensional scans, 3D reconstructions yielded significant increases of SND and branch points in all conditions except severe LSCD. 3D analysis showed a 46% increase in long nerves only in mild LSCD ( P < 0.01). CONCLUSIONS: This proof-of-concept study validates the use of 3D reconstruction to better characterize the corneal subbasal nerve in eyes with LSCD. In the future, this concept could be used with machine learning to automate the measurements.

Vertical prism adaptation, but not sound presentation, modulates the visuospatial representation: A manual line-bisection study.

The present study aimed at testing whether vertical prism adaptation (PA) can modulate vertical visuospatial representation, assessed with a vertical manual line-bisection (MLB) task (Experiment 1). In a second time, we wanted to investigate the potential influence of sound presentation during such a task. Sound is a spatially valued element that has previously been reported to modify horizontal visuospatial representation. In Experiment 2, we presented either a high pitch, a low pitch, or no sound during the same MLB as in Experiment 1. With this experiment, we also searched for an eventual interaction between the effect of sound presentation and the potential cognitive aftereffects of vertical PA on visual representation. Both Experiments 1 and 2 were constructed with the same design and conducted with two distinct groups of young healthy right-handed participants. First, we assessed the initial sensorimotor state with an open-loop pointing task, and the initial representational state through a vertical MLB (with addition of sound for Experiment 2). Then participants were submitted to a 16-minute PA procedure and were tested again on the open-loop pointing task and the MLB to assess the aftereffects following prism removal. Our results showed sensorimotor aftereffects following both upward and downward PA, in a direction opposed to the optical deviation used. The early aftereffects measured following PA were symmetrical, but at the end of the experiment the residual aftereffects were smaller following downward PA than upward PA. We also provide a new insight on the aftereffects of vertical PA on visuospatial representation, showing that downward PA (but not upward PA) can produce an upward bias on the manual line-bisection task. This is the first proof of such cognitive aftereffects following vertical PA. However, we found no effect of sound presentation on the vertical visual space representation and no interaction between PA and sound presentation.

Co-existence of Neurotrophic Keratopathy in Eyes With Limbal Stem Cell Deficiency.

PURPOSE: To investigate whether neurotrophic keratopathy is present in limbal stem cell deficiency (LSCD), by measuring corneal sensation and characterizing corneal subbasal nerve plexus. DESIGN: Prospective, cross-sectional, case-control comparative study. METHODS: A total of 46 eyes with LSCD and 14 normal eyes were recruited from 2019 to 2022. Corneal sensation was measured using a Cochet-Bonnet esthesiometer, and subbasal nerve plexus was imaged using in vivo confocal microscopy (IVCM) at the central cornea and 4 limbal regions. Subbasal nerve density (SND, number of nerves/mm2), subbasal nerve length (SNL, total length of nerves/mm2) and subbasal nerve branch density (SNBD, number of branches/mm2) were quantified. LSCD was graded to stage 1, 2, and 3 using a previously established staging method consisting of clinical scores, basal cell density, central corneal epithelial thickness, and SNL. RESULTS: The mean (±SD) cornea sensation in the central cornea and limbus were 29.2 ± 21.5 and 33.6 ± 15.1 mm in the LSCD group and 57.6 ± 5.8 and 54.3 ± 4.7 mm in the control group, respectively (all P < .001). In sectoral LSCD, the corneal sensation in the affected regions (29.1 ± 17.6 mm) decreased significantly compared to the unaffected regions (41.4 ± 18.2 mm, P < .001). Central corneal SND, SNL, and SNBD were reduced by 84.6%, 82.6%, and 89.2%, respectively, in LSCD compared to controls (all P < 0.05). The central corneal sensation negatively correlated with the severity of LSCD (rho = -0.64, P < .0001) and positively correlated with SND, SNL, and SNBD (rho = 0.63, 0.66, and 0.56, respectively; all P < .001). CONCLUSIONS: Corneal sensation was reduced in eyes with LSCD. The degree of corneal sensation reduction positively correlated with the severity of LSCD. This finding demonstrated the coexistence of neurotropic keratopathy in LSCD.

Descemet Stripping Endothelial Keratoplasty in Patients With a Custom Foldable Silicone Artificial Iris: Safety and Efficacy Outcomes.

PURPOSE: To assess outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with custom artificial iris (CAI) implantation. METHODS: This is a retrospective, interventional, consecutive, surgical case series of patients who underwent DSEK after CAI implantation between 2010 and 2021 at 2 referral centers. Primary safety measures were loss of corrected distance visual acuity (CDVA), increase in intraocular pressure (IOP), development or progression of glaucoma, and intraoperative and postoperative complications. Efficacy measures were graft survival at year 1 and improvement in cosmesis at postoperative month 3. In general, measures were compared between baseline and postoperative year 1 while any complication was reported for the full follow-up period. RESULTS: Thirty-nine eyes of 39 patients were identified. 64.1% of eyes had acquired aniridia from trauma. The mean follow-up interval was 27.7 months (range 12.2-117.4). Median CDVA improved from logMAR 1.0 to 0.7 at year 1 (P = 0.0047). At the final follow-up, permanent loss of CDVA occurred in 25.6% of eyes, of which 90% was due to glaucoma. The most common postoperative complication was IOP elevation (66.7% of eyes). Graft survival at postoperative year 1 was 82.0% (95% confidence interval, 66.3-91.4). Secondary graft failure occurred in 28.2% of eyes at a mean duration of 39.7 months (SD 27.9 months) after DSEK. Cosmesis improved among 87.2% of eyes at postoperative month 3. CONCLUSIONS: DSEK is an effective procedure for addressing corneal edema in eyes with a CAI, but a majority develop elevated IOP and graft survival is shorter than in eyes without a CAI.

Limbal stem cell therapy.

PURPOSE OF REVIEW: To highlight the progress and future direction of limbal stem cell (LSC) therapies for the treatment of limbal stem cell deficiency (LSCD). RECENT FINDINGS: Direct LSC transplantation have demonstrated good long-term outcomes. Cultivated limbal epithelial transplantation (CLET) has been an alternative to treat severe to total LSCD aiming to improve the safety and efficacy of the LSC transplant. A prospective early-stage uncontrolled clinical trial shows the feasibility and safety of CLET manufactured under xenobiotic free conditions. Other cell sources for repopulating of the corneal epithelium such as mesenchymal stem cells (MSCs) and induced pluripotent stem cells are being investigated. The first clinical trials of using MSCs showed short-term results, but long-term efficacy seems to be disappointing. A better understanding of the niche function and regulation of LSC survival and proliferation will lead to the development of medical therapies to rejuvenate the residual LSCs found in a majority of eyes with LSCD in vivo. Prior efforts have been largely focused on improving LSC transplantation. Additional effort should be placed on improving the accuracy of diagnosis and staging of LSCD, and implementing standardized outcome measures which enable comparison of efficacy of different LSCD treatments for different severity of LSCD. The choice of LSCD treatment will be customized based on the severity of LSCD in the future. SUMMARY: New approaches for managing different stages of LSCD are being developed. This concise review summarizes the progresses in LSC therapies for LSCD, underlying mechanisms, limitations, and future areas of development.

Latent diffusion augmentation enhances deep learning analysis of neuro-morphology in limbal stem cell deficiency.

Introduction: Limbal Stem Cell Deficiency (LSCD) is a blinding corneal disease characterized by the loss of function or deficiency in adult stem cells located at the junction between the cornea and the sclera (i.e., the limbus), namely the limbal stem cells (LSCs). Recent advances in in vivo imaging technology have improved disease diagnosis and staging to quantify several biomarkers of in vivo LSC function including epithelial thickness measured by anterior segment optical coherence tomography, and basal epithelial cell density and subbasal nerve plexus by in vivo confocal microscopy. A decrease in central corneal sub-basal nerve density and nerve fiber and branching number has been shown to correlate with the severity of the disease in parallel with increased nerve tortuosity. Yet, image acquisition and manual quantification require a high level of expertise and are time-consuming. Manual quantification presents inevitable interobserver variability. Methods: The current study employs a novel deep learning approach to classify neuron morphology in various LSCD stages and healthy controls, by integrating images created through latent diffusion augmentation. The proposed model, a residual U-Net, is based in part on the InceptionResNetV2 transfer learning model. Results: Deep learning was able to determine fiber number, branching, and fiber length with high accuracy (R2 of 0.63, 0.63, and 0.80, respectively). The model trained on images generated through latent diffusion on average outperformed the same model when trained on solely original images. The model was also able to detect LSCD with an AUC of 0.867, which showed slightly higher performance compared to classification using manually assessed metrics. Discussion: The results suggest that utilizing latent diffusion to supplement training data may be effective in bolstering model performance. The results of the model emphasize the ability as well as the shortcomings of this novel deep learning approach to predict various nerve morphology metrics as well as LSCD disease severity.

Ocular Surface Regeneration by Limbal Stem Cells Therapies: State of the Art, Challenges, and Perspectives.

Limbal stem cells (LSCs) are adult stem cells located at the limbus ensuring the continuous renewal of the corneal epithelium, critical to maintain an optimal visual function. Damages to the LSCs or their niche microenvironment lead to limbal stem cell deficiency (LSCD), a potentially blinding disease. Transplantation of LSCs as a treatment for severe to total LSCD has gained popularity since 1980s, owing to the clinical success of the first direct limbal autograft transplantation. Recent advances in the understanding of the LSCs' molecular identity and regulation have enabled preclinical and clinical advancements of promising LSCs therapies. However, lack of standardization of the diagnostic methods, staging of the disease severity, manufacturing process, and clinical outcome measures have hindered the advancement of the therapy. To move these therapies to the clinic, optimization and standardization of the diagnostic strategy, cell product manufacturing, and assessment of clinical efficacy with potency assays are key points to the development of customized therapies. Recent findings suggest that residual LSCs exist in eyes presenting with clinical signs of total LSCD, which opens new therapeutic strategies for eyes with partial LSCD. Prospective, randomized, multicentric controlled clinical trials are necessary to determine the efficacy of different LSCs therapies for different stages of LSCD using a set of standardized outcome measures.

Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency.

Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their niche involving numerous signaling pathways, such as Wnt. Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration, and remodeling in adults. It has been shown that a small molecule Wnt mimic could improve LSCs expansion ex vivo. Damage to the LSCs and/or their niche can lead to limbal stem cell deficiency (LSCD), a condition that can cause corneal blindness and is difficult to treat. This study explored if repopulating residual LSCs in partial LSCD through Wnt activation could be a novel therapeutic approach. To mimic LSCD due to a chemical injury, single cultured LSCs were exposed to various concentrations of sodium hydroxide. A progressive loss of the LSCs phenotype was observed: the percentage of p63bright cells and cytokeratin (K)14+ cells decreased while the percentage of K12+ increased. Wnt activation was attained by treating the LSCs with lithium chloride (LiCl) and a small-molecule Wnt mimic, respectively. After 18 h of treatment, LSCs proliferation was increased, and the LSCs phenotype was recovered, while the untreated cells did not proliferate and lost their phenotype. The percentage of p63bright cells was significantly higher in the Wnt mimic-treated cells compared with untreated cells, while the percentage of K12+ cells was significantly lower. These findings suggest that local Wnt activation may rescue LSCs upon alkaline injury.

Descemet membrane endothelial keratoplasty in eyes with glaucoma.

Endothelial keratoplasty has become the standard for the treatment of endothelial dysfunction. In Descemet membrane endothelial keratoplasty (DMEK), only the endothelium and Descemet membrane are transplanted, providing superior outcomes compared to Descemet stripping endothelial keratoplasty (DSEK). A substantial subset of patients who require DMEK have comorbid glaucoma. Even in eyes with complex anterior segment such as eyes with previous trabeculectomy or tube shunts, DMEK can restore meaningful vision and outperforms DSEK in terms of visual recovery, decreased rejection rate, and the need for high dose of topical steroids. However, accelerated endothelial cell loss and secondary graft failure have been described in eyes with previous glaucoma surgery, namely trabeculectomy and drainage device. During DMEK and DSEK procedures, raised intraocular pressure is required to attach the graft, which could worsen preexisting glaucoma or cause de novo glaucoma. Mechanisms of postoperative ocular hypertension include delayed air clearance, pupillary block, steroid response, and damage to angle structures. Medically treated glaucoma has increased risk for postoperative ocular hypertension. By understanding these additional complications and making appropriate modifications in surgical techniques and postoperative management, DMEK can be performed successfully and achieve very good visual outcome in eyes with glaucoma. Such modifications include precisely controlled unfolding technique, iridectomies that can help avoid pupillary block, tube shunts that can be trimmed to facilitate graft unfolding, air fill tension that can be adjusted, and postoperative steroid regimens that can be modified to decrease the risk for steroid response. Long-term survival of the DMEK graft, however, is shorter in eyes with previous glaucoma surgery than those without, as observed after other types of keratoplasty.

Fungal Infection After Descemet Membrane Endothelial Keratoplasty: Incidence and Outcomes.

PURPOSE: The aim of the study was to describe the incidence, presentation, management, and outcomes of fungal infection after Descemet membrane endothelial keratoplasty (DMEK). METHODS: Retrospective case series of culture-proven fungal infections after DMEK reported in the literature, directly by surgeons, and to the Eye Bank Association of America from January 1, 2011, to December 31, 2020. RESULTS: The domestic incidence of fungal infections, fungal keratitis, and fungal endophthalmitis after DMEK from 2011 to 2020 was 3.5, 1.3, and 2.2 per 10,000 cases, respectively, with no significant increasing trend. Thirty-four cases were identified, 14 (41.2%) published and 20 (58.8%) unpublished. Donor tissue fungal cultures were performed in 20 of the 34 (58.8%) cases and were positive in 19 of the 20 (95.0%), all but one Candida species. Recipient fungal cultures were performed in 29 of the 34 (85.3%) cases and were positive in 26 of the 29 (89.7%), all but one Candida species. Infection presented a mean of 33 ± 38 days (median 23, range 2-200, outlier 949) after transplantation: 25 (73.5%) with endophthalmitis and 9 (26.5%) with keratitis. Topical, intrastromal, intracameral, intravitreal, or systemic antifungal therapy was used in all 27 eyes with treatment data. Surgical intervention (DMEK explantation or partial removal, repeat endothelial keratoplasty, penetrating keratoplasty, and/or pars plana vitrectomy) was required in 21 of the 27 (77.8%) eyes. The corrected distance visual acuity at the last follow-up was ≥20/40 in 13 of the 27 (48.1%) eyes and counting fingers or worse in 6 of the 27 (22.2%) eyes. CONCLUSIONS: Fungal infection is a rare but serious complication of DMEK that results in counting fingers or worse corrected distance visual acuity in nearly a quarter of eyes.

Single mRNA detection of Wnt signaling pathway in the human limbus.

Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their close microenvironment. It has been shown that Wnt signaling pathway is crucial for LSCs regulation. Previous differential gene profiling studies confirmed the preferential expression of specific Wnt ligands (WNT2, WNT6, WNT11, WNT16) and Wnt inhibitors (DKK1, SFRP5, WIF1, FRZB) in the limbal region compared to the cornea. Among all frizzled receptors, frizzled7 (Fzd7) was found to be preferentially expressed in the basal limbal epithelium. However, the exact localization of Wnt signaling molecules-producing cells in the limbus remains unknown. The current study aims to evaluate the in situ spatial expression of these 4 Wnt ligands, 4 Wnt inhibitors, and Fzd7. Wnt ligands, DKK1, and Fzd7 expression were scattered within the limbal epithelium, at a higher abundance in the basal layer than the superficial layer. SFRP5 expression was diffuse among the limbal epithelium, whereas WIF1 and FRZB expression was clustered at the basal limbal epithelial layer corresponding to the areas of high levels of Fzd7 expression. Quantitation of the fluorescence intensity showed that all 4 Wnt ligands, 3 Wnt inhibitors (WIF1, DKK1, FRZB), and Fzd7 were highly expressed at the basal layer of the limbus, then in a decreasing gradient toward the superficial layer (P < 0.05). The expression levels of all 4 Wnt ligands, FRZB, and Fzd7 in the basal epithelial layer were higher in the limbus than the central cornea (P < 0.05). All 4 Wnt ligands, 4 Wnt inhibitors, and Fzd7 were also highly expressed in the limbal stroma immediately below the epithelium but not in the corneal stroma (P < 0.05). In addition, Fzd7 had a preferential expression in the superior limbus compared to other limbal quadrants (P < 0.05). Taken together, the unique expression patterns of the Wnt molecules in the limbus suggests the involvement of both paracrine and autocrine effects in LSCs regulation, and a fine balance between Wnt activators and inhibitors to govern LSC fate.

Clinical outcomes and complications of fluid-filled scleral lens devices for the management of limbal stem cell deficiency.

AIMS: To evaluate the clinical and visual outcomes of fluid-filled scleral lens devices (SL) wear in patients with limbal stem cell deficiency (LSCD). DESIGN: Retrospective consecutive case series. METHODS: 27 eyes with LSCD confirmed by in vivo confocal microscopy at the Stein Eye Institute and fitted with SL were included. Correlations between corrected distance visual acuity (CDVA) and LSCD stage determined by clinical grading were performed between baseline (after the SL fit) and the last follow-up (the time of discontinuation of SL wear or the last visit in eyes in which SL were continued). In a subset of patients that had worsened LSCD while using SL, anterior segment optical coherence tomography (AS-OCT) and anterior segment fluorescein angiogram (AS-FA) were performed. RESULTS: Baseline LSCD grading was stage I in 12 eyes (44.4%), stage 2 in 12 eyes (44.4%), and stage III in 3 eyes (11.1%). At the last follow-up, CDVA was improved in 7 eyes (25.9%), remained stable in 13 eyes (48.1%) and decreased in 7 eyes (25.9%, P = 0.16). The LSCD stage was improved in 7 eyes (25.9%), remained stable in 8 eyes (29.6%) and worsened in 12 eyes (44.4%, P = 0.10). AS-OCT and AS-FA, performed in 5 eyes, showed limbal compression and delayed fluorescein filling. CONCLUSION: SL can improve visual acuity and maintain the ocular surface in the majority of eyes. Worsening of the ocular surface might be a result of limbal hypoxia. Close monitoring of SL fit is necessary in these compromised eyes.

Autologous Serum Eye Drops in the Management of Limbal Stem Cell Deficiency Associated With Glaucoma Surgery.

PURPOSE: To evaluate safety and efficacy of autologous serum eye drops (AS) in the treatment of limbal stem cell deficiency (LSCD) associated with glaucoma surgery. METHODS: Retrospective case series of eyes with glaucoma surgery-induced LSCD treated with AS. Diagnosis of LSCD was confirmed by anterior segment optical coherence tomography, in vivo confocal microscopy, and/or impression cytology. Limbal stem cell deficiency severity was staged using a clinical scoring system (2-10 points). Outcome measures were changes (≥2 points) of the LSCD score and best-corrected visual acuity (BCVA) from the baseline to the last follow-up. RESULTS: Thirteen eyes of 12 consecutive patients treated with 50% AS for at least 3 months were included. The mean age was 78.9±7.5 years and the mean duration of AS use was 20.9±16.8 months. Indications of AS included LSCD progression in eight eyes (61.5%) and visual axis threatening in five eyes (38.5%). The mean LSCD score at baseline (6.7±1.6) was similar to that at last follow-up (6.5±2.2, P =0.625). Two eyes (15.4%) showed improvement, nine eyes (69.2%) were stable, and two eyes (15.4%) worsened. The mean baseline BCVA (0.89±0.64 logMAR) was similar to the mean final BCVA (1.05±0.63 logMAR, P =0.173). There were no serious adverse complications related to AS. CONCLUSION: AS appears to be well tolerated and may stabilize the progression of LSCD with limited effects. A larger study is necessary to confirm the findings.

Infectious Crystalline Keratopathy Secondary to Mycobacterium chelonae.

PURPOSE: The aim of this study was to describe the clinical presentation and multimodal imaging of a patient diagnosed with infectious crystalline keratitis (ICK) secondary to Mycobacterium chelonae . METHODS: This is a case report of a patient with a crystalline corneal infiltrate imaged with anterior segment optical coherence tomography and in vivo scanning laser confocal microscopy. Bacterial, fungal, acanthamoeba, and acid-fast cultures were performed to identify the causal pathogen. RESULTS: Examination revealed a white stellate opacity in the midstroma underlying the scalloped border of an area of central corneal stromal thinning, consistent with a diagnosis of ICK. Anterior segment optical coherence tomography demonstrated a hyperreflective diamond-shaped opacity located at a depth of 334 µm, which demonstrated multiple stellate projections on in vivo scanning laser confocal microscopy. The acid-fast culture was positive for Mycobacterium chelonae . CONCLUSIONS: Although ICK is most commonly associated with Streptococcus species, it may be secondary to atypical bacteria including Mycobacterium species, underscoring the importance of diagnostic imaging and collecting corneal cultures to identify the pathogenic organism.

Using prism adaptation to alleviate perception of unilateral tinnitus: A case study.

Tinnitus is described as an uncomfortable sound or noise heard by an individual in the absence of an external sound source. Treating this phantom perception remains difficult even if drug and nondrug therapies are used to alleviate symptoms. The present case study aimed to investigate whether prism adaptation could induce beneficial aftereffects in a tinnitus sufferer. A 75-year-old man, R. B., with chronic unilateral tinnitus in the left ear reported a self-estimation of parameters of his tinnitus-discomfort, pitch and loudness-and performed a manual line-bisection task to study the consequences of lateralized auditory disorder on spatial representation. Aftereffects of prism adaptation were assessed using a sensorimotor open-loop pointing task. In parallel, a control group completed the line-bisection task and the open-loop pointing task before and after lens exposure, under the same experimental condition as those of R. B. Throughout the pretests, the patient assessed his tinnitus at a constant medium pitch (around 3000 Hz), and he was biased toward the affected ear in both the sensorimotor task and the estimation of the subjective center in the manual line-bisection task. Although both optical deviations were effective, an exposure to prism adaptation to a rightward optical deviation (i.e., toward the unaffected ear) produced stronger aftereffects. In posttests, the tinnitus pitch decreased to 50 Hz and the subjective center was shifted toward the right side (i.e., unaffected ear side). Furthermore, the line-bisection task seemed to reflect the changes in the tinnitus perception, and spatial representation could be a new tool to assess tinnitus indirectly. Our findings suggest that prism adaptation may have benefits on unilateral tinnitus and open a new avenue for its treatment.

The StarvAnx Study-Comparison Between the Effects of Non-fasting Vs. Fasting Strategy on Surgical Outcomes, Anxiety and Pain in Patients Undergoing Cataract Surgery Under Topical Anesthesia: A Randomized, Crossover, Controlled Trial.

Background: Fasting is usually recommended in patients undergoing cataract surgery under topical anesthesia. However, starving before surgery may increase preoperative anxiety and affect surgical outcomes. It is not known which fasting or non-fasting strategy is best for cataract surgery. The aim of this study was to compare non-fasting and fasting strategy in patients undergoing cataract surgery under topical anesthesia with regard to surgical outcomes, anxiety and pain. Methods: This randomized, crossover, controlled trial enrolled patients undergoing surgery for bilateral cataract under topical anesthesia at Cochin Hospital (Paris, France), from February to May 2021. Patients were randomly assigned to the non-fasting or fasting group for the first eye surgery and were switched to the other group for the second eye surgery. The primary endpoint was to compare the rate of anesthetist's interventions during surgery. The secondary endpoints included intra-operative complications, duration of surgery, surgeon perception of surgical difficulty, anesthesia-related complications and anxiety and pain level. Results: one hundred and nine consecutive patients were included, with 60 of them being fasted first and non-fasted for the second eye surgery, while the other 59 were non-fasted first and fasted for the next surgery. The number of patients requiring sedation was significantly lower in the non-fasting group compared with the fasting group [1%; 95%IC (0-3.2) vs. 6%; 95%IC (2.9-8.9), P = 0.04]. No anesthesia-related complications were observed. There was no difference in the number of intra-operative complications between the non-fasting and the fasting groups (,respectively, 0 and 1; P = 1). Anxiety level and surgical pain were significantly lower in the non-fasting group compared to the fasting group (,respectively, 2.3 ± 2.0 vs. 4.1 ± 2.4, P = 0.01 and 0.6 ± 0.6 vs. 2.6 ± 3.4, P = 0.003). The mean duration of surgery was significantly shorter in the non-fasting group compared with the fasting group (,respectively, 16.0 ± 5.9 vs. 22.3 ± 6.1 min; P = 0.03). Conclusion: In conclusion pre-operatory non-fasting strategy provides a better patient experience with regards to preoperative anxiety and surgical pain. It allows to reduce operating times and is safe and well-tolerated as regards the anesthetic intervention.