[A randomized study of subconjonctival bevacizumab (Avastin®) injection for corneal neovascularization]. / Étude randomisée de l'injection sous-conjonctivale de bévacizumab (Avastin®) dans la néo-vascularisation cornéenne.

PURPOSE: The goal of this phase III, comparative, multicentric, randomized, double-blinded clinical trial was to investigate the superiority of subconjunctival bevacizumab injections versus placebo in the treatment of corneal neovascularization. PATIENTS AND METHODS: We included 38 eyes (38 patients) with corneal neovascularization. Twenty patients received bevacizumab and 18 placebos. Patients received 3 monthly injections of either 5mg (0.2mL) bevacizumab or placebo. The main criteria of success was reduction of the surface area of corneal neovascularization after 3months (M3) versus baseline, as measured using semi-automatic analysis of color photographs. RESULTS: The percentage of neovascularized corneal surface decreased by -8.6%±32.8 with bevacizumab, versus -2.6%±20.8 with placebo (p=0.5284). Four patients were determined to be responders (reduction of more than 30%), 3 in the bevacizumab group and 1 in the placebo group, all with neovascularization of less than 1year duration. When restricting the analysis to neovascularization of less than 1 year duration, the difference approached the threshold for significance (-31.8%±42.4 in the bevacizumab group and -0.9%±23.1 in the placebo group) (p=0.0637), as well as the number of responders (3/6 in the bevacizumab group versus 1/10 in the placebo group) (p=0.1181). No serious adverse event was reported. CONCLUSION: This study shows the efficacy of subconjunctival bevacizumab injection in the reduction of neovascularized corneal surface area versus placebo, but only when the neovascularization has been present less than 1year. Nevertheless, the study did not attain the statistical power to pass the threshold of significance.

[Limitations of outpatient vitreoretinal surgery at the Toulouse University hospital between 2016 and 2020: Causes for traditional hospitalization]. / Les limites de l'ambulatoire en chirurgie vitréo-rétinienne au CHU de Toulouse entre 2016 et 2020 : identification des causes d'hospitalisation traditionnelle.

INTRODUCTION: Currently, the majority of patients undergoing vitreoretinal surgery (VRS) are managed on an outpatient basis; this has been made possible by major surgical and anesthetic advances over the past decades. Nevertheless, the conversion to "all outpatient" surgery still poses some problems that are interesting to identify, and traditional hospitalization remains the solution in many situations. METHODS: All patients undergoing VRS at the Toulouse University Hospital between 2016 and 2020 were included retrospectively. For each patient, we analyzed the entire medical, anesthesia and demographic records. We performed a simple descriptive analysis of all parameters studied, followed by a bi-variate analysis between the "Outpatient/Hospitalization" parameter and all other parameters. RESULTS: Three thousand patients were included over the study period; 79.4% of patients were managed on an outpatient basis compared to 20.6% by traditional hospitalization. Failure of ambulatory care was the cause of 41.9% of the traditional hospitalizations, with the absence of an accompanying person on the evening of the surgery being the main reason (47.8%). DISCUSSION: Social isolation is found to be one of the main causes of failure of ambulatory care; improvements might be made at this level, in order to reduce the burden on the inpatient hospital system.

[Validation of identification criteria for patients having surgery for rhegmatogenous retinal detachment at Toulouse University Hospital]. / Validation des critères d'identification des patients opérés d'un décollement de rétine rhegmatogène au CHU de Toulouse.

INTRODUCTION: Seasonal variations seem to modify the incidence of rhegmatogenous retinal detachment (RRD), with a summer peak, although the meteorological parameters involved have not been studied in France. In order to conduct a national study evaluating the association between the occurrence of RRD and various climatological variables (METEO-POC study), we need to establish a national cohort of patients having undergone surgery for RRD. The data of the National Health Data System (SNDS) allow the realization of epidemiological studies concerning various pathologies. However, as these databases were initially intended for medical administrative use, the identification of the pathologies coded in these databases must be validated before any use for research purposes. In order to carry out a cohort study using SNDS data, the objective of this study is to validate the identification criteria for patients having undergone RRD surgery at Toulouse University Hospital. METHODS: We compared the cohort of RRD surgery patients at Toulouse University Hospital from January to December 2017 assembled from SNDS data with the cohort of patients meeting the same selection criteria assembled from Softalmo software data. RESULTS: With a positive predictive value of 82.0%, a sensitivity of 83.8%, a specificity of 69.9%, and a negative predictive value of 72.5%, we can consider that our eligibility criteria are performing well. CONCLUSION: Since the selection of patients via SNDS data is reliable at Toulouse University Hospital, we can use it at the national level for the METEO-POC study.

Abnormal brain function in photophobic patients with dry eye disease: An fMRI study.

BACKGROUND AND OBJECTIVES: Photophobia, a frequent and disabling symptom observed in various neurological conditions and eye diseases, is thought to involve maladaptive brain functioning. We assessed this hypothesis, using functional magnetic resonance imaging (fMRI) in photophobic patients with minimal-to-severe dry eye disease (DED), as compared to healthy controls. METHODS: This prospective, monocentric, comparative, cohort study included eleven photophobic DED patients compared to eight controls. Photophobic patients had a complete evaluation of DED to exclude any other cause of photophobia. All participants were scanned with fMRI under intermittent light stimulation with a LED lamp (27s. ON, 27 s. OFF), and cerebral activations were studied with univariate contrasts between the ON and OFF conditions, and with functional connectivity methods. RESULTS: Firstly, stimulation activated the occipital cortex more strongly in patients than in controls. Moreover, stimulation deactivated the superior temporal cortex in patients less than in controls. Secondly, functional connectivity analysis showed that light stimulation induced lesser decoupling between the occipital cortex and the salience and visual networks in patients than in controls. DISCUSSION: The current data shows that DED patients with photophobia have maladaptive brain anomalies. There is hyperactivity in the cortical visual system, associated with abnormal functional interactions, both within the visual cortex, and between visual areas and salience control mechanisms. Such anomalies show similarities with other conditions such as tinnitus, hyperacusis, and neuropathic pain. Those findings support novel neurally oriented methods for the care of patients with photophobia.

[Influence of the COVID-19 pandemia on the ophthalmologic emergency department in the Toulouse University Hospital during the first lockdown from March the 17th to May the 10th of 2020]. / Impact de la pandémie de COVID-19 sur les urgences ophtalmologiques du CHU de Toulouse lors du premier confinement du 17 mars au 10 mai 2020.

INTRODUCTION: We conducted this study to assess the impact of the COVID-19 pandemic and the lockdown in France from March 17, 2020 to May 10, 2020, on the ophthalmic emergency department at Toulouse University Hospital, compared to the period from March 2 to March 16, 2020. MATERIALS AND METHODS: This was a retrospective observational study, conducted in the ophthalmic emergency department of Toulouse University Hospital. We included the patients presenting to the emergency department from March 2 to May 10, 2020. We recorded age, sex, day of visit, time until care was received, past ocular history, outpatient or inpatient status, final diagnosis and its severity, outpatient or inpatient disposition, and medical or surgical treatment after the emergency department visit. RESULTS: We found a substantial decrease in the number of patients per day, mostly during the first month of the lockdown: 44 patients per day before the lockdown compared to 23 patients per day during the first month, followed by 38 patients per day for the second month of lockdown; more patients visiting promptly; and elderly patients represented a higher proportion of patients. CONCLUSION: The first lockdown in France due to the COVID-19 pandemic had an impact on the Toulouse ophthalmic emergency department, especially concerning the number of patients per day; this study helps to assess individual behavior in this context of a public health crisis.

[Dupilumab-related blepharoconjunctivitis: Recommendations of the CEDRE group. Atopic dermatitis, conjunctivitis and dupilumab: Which management approach?] / Blépharo-conjonctivites sous dupilumab : recommandations du groupe CEDRE. Dermatite atopique, conjonctivites et dupilumab : quelle prise en charge ?

Dupilumab is a recombinant monoclonal IgG4 type antibody which inhibits IL4 and IL13 signaling. It is indicated in moderate to severe atopic dermatitis (AD) in adults and adolescents over 12 years of age. Its side effects include conjunctivitis and blepharoconjunctivitis, affecting between 4.7% and 28% of patients depending on the study. The incidence of conjunctivitis in patients treated with dupilumab for AD appears to be higher than placebo in clinical studies. This increase was not observed in patients treated with dupilumab for asthma or sinonasal polyposis. The risk factors for conjunctivitis in patients with AD are disease severity, pre-existence of conjunctivitis and low concentrations of dupilumab, but the pathophysiology of this disease is poorly understood. A literature search carried out in April and May 2020 showed an increase in the number of publications on the subject, but there are currently no official joint dermatologist-ophthalmologist recommendations for prevention and management. The objective of this article is to provide an overview of the status of this subject, to address the main questions raised by this type of conjunctivitis and to suggest a course of action for starting and continuing treatment with dupilumab in patients with AD, according to the recommendations of the French Ophthalmologist/Dermatologist group CEDRE.

Incidence and risk factors for dupilumab associated ocular adverse events: a real-life prospective study.

BACKGROUND: Dupilumab is approved for use in moderate-to-severe atopic dermatitis (AD) and as an add-on maintenance treatment in patients suffering from severe asthma with type 2 inflammation. Ocular adverse events (OAEs) have been reported with dupilumab almost exclusively in patients treated for AD. OBJECTIVES: The objectives of this study were to describe the incidence and nature of dupilumab-induced OAEs and to assess the potential predisposing factors. PATIENTS AND METHODS: We conducted a prospective, single-centre, real-life study in adult AD patients treated with dupilumab, who were systematically examined by an ophthalmologist before and during treatment. RESULTS: Forty-six patients were included prospectively with a median age of 41.1 years and a median initial SCOring Atopic Dermatitis of 46.0 (IQR: 34.5-55.5). OAEs concerned 34.8% of patients and were mostly of mild to moderate severity. Two patients had to discontinue treatment due to OAE. The majority of patients developed or aggravated dry eye disease, with superficial punctate keratitis (SPK). Six patients developed conjunctivitis. Dupilumab-induced OAEs were associated with the following pre-existing parameters: dry eye disease with SPK (Odds ratio (OR); 6.3 [95% confidence interval (CI): 1.3-31.6]), eyelid eczema (OR: 8.7 [95%CI: 1.8-40.6]), history of food allergy (OR 3.8 (95% CI: 1.002-14,070) and IgE serum level> 1000 kU/L (OR:10.6 [CI 95%: 1.2-91.3]). CONCLUSION: Atopic dermatitis patients with eyelid eczema or dry eye disease symptoms may be referred to an ophthalmologist before starting dupilumab to consider initiating preventive eye hydration measures. Further multicentric and translational studies are warranted to better explain OAEs pathophysiology.

[Assessment of astigmatism associated with the iris-fixated ARTISAN aphakia implant: Anterior fixation versus posterior fixation, study of postoperative follow-up at one year]. / Évaluation de l'astigmatisme associé à l'implant ARTISAN Aphakia fixé à l'iris en face antérieure versus face postérieure : étude du suivi postopératoire sur un an.

PURPOSE: The goal of our retrospective, single-center study of a case series was to compare the total, corneal, and internal astigmatism, and the visual acuity at one year after combined or stand-alone surgery consisting of iris fixation of an iris-claw intraocular lens (ARTISAN aphakia) in aphakic patients, according to whether the lens was fixated to the anterior (n=21) or posterior (n=51) surface of the iris. RESULTS: We did not find a significant difference between these two types of fixation for any of the studied variables. The surgically induced astigmatism was 1.67 D at 176° in group A versus 1.19 D at 11° in group P. CONCLUSION: Although this surgery creates additional corneal astigmatism, it has not been proven that it differs depending on the type of fixation of the iris-claw. If we adhere to the notion that the posterior fixated iris-claw decreases the risk of endothelial decompensation in case the implant becomes disenclavated, then reverse iris fixation of the iris-claw makes sense.

[Evaluation of the nurse triage at the ophtalmology emergency department of Pierre-Paul-Riquet Hospital]. / Évaluation du questionnaire de tri infirmier aux urgences ophtalmologiques de l'hôpital Pierre-Paul-Riquet au CHU de Toulouse.

INTRODUCTION: The steady increase in the number of visits to the various emergency services combined with the decrease in medical demographics, make it necessary to optimize triage of patients to improve their care. The purpose of this study was to evaluate the pertinence of our triage questionnaire in the classification of ophthalmologic emergencies by severity. METHODS: We used a monocentric cross-sectional study. From September 5 through September 25 2017, 858 patients who had all been seen in the ophthalmology emergency department of Pierre Paul Riquet Hospital of Toulouse university medical center and had responded to the triage nurse questionnaire were included. According to the symptoms presented or not by the patient, a color code was attributed (GREEN, ORANGE or RED) in order of increasing level of emergency. For each patient, we compared the severity of the final diagnosis by Base Score with the level of emergency established by our questionnaire. RESULTS: There were 118 "GREEN" patients, 606 "ORANGE" patients and 134 "RED." We were able to analyze 822 patients. 21.65% of patients were correctly classified, 73.36% were overestimated (of which 87.06% by one level and 12.94% by two levels of severity), and 4.99% were underestimated (of which 90.24% by one level and 9.76% by two levels). CONCLUSION: Our current triage questionnaire is not sufficiently discriminating for effective triage of ophthalmologic emergencies. It often overestimates minor emergencies, causing a delay in treating other emergencies. We propose a new questionnaire modified according to the results obtained during our study.

[Efficacy of corneal cross-linking for the treatment of keratoconus]. / Efficacité du cross-linking du collagène cornéen pour le traitement du kératocône.

Keratoconus (KC) is a complex disease whose pathophysiology is only partially understood. The priority in management is to halt the progression of corneal deformation as soon as possible in the course of KC disease. Corneal cross-linking (CXL) is at present the only dedicated treatment for this purpose. Its biochemical mechanism of action leads to changes in the viscoelastic properties of the cornea induced by matrix bonding and renewal of keratocytes. The effect of CXL is difficult to quantify when measured in in-vivo conditions because of a lack of consistent tools adapted for clinical practice. Nevertheless, a large amount of evidence has been collected so far confirming the positive action of CXL on corneal structural reinforcement, and numerous studies have demonstrated significant efficacy in halting progression of KC with long-term follow-up. Published studies, however, are of relatively low scientific power given the great heterogeneity of the disease and the numerous associated biases in evaluation. The purpose of this paper is to summarize the consistent evidence of efficacy of CXL and to justify its role in our therapeutic armamentarium for management of progressive KC.

[Keratoconus]. / Kératocône.

Keratoconus is a slowly progressive, non-inflammatory disorder of the eye characterized by thinning and protrusion of the cornea. Typically diagnosed in the patient's adolescent years, keratoconus may lead to substantial distortion of vision primarily from irregular astigmatism and myopia, and secondarily from corneal scarring. The classic histopathologic features include breaks in Bowman's layer and thinning of the corneal stroma. The etiology of keratoconus remains unclear. Form fruste keratoconus shows little progression, and has become known due to videotopographic analysis; it is very important to rule out in refractive surgery candidates. Treatment begins first and foremost with contact lenses, progressing to surgery as contact lens intolerance develops, with the goal of stabilization, including: cross-linking, intrastromal corneal ring segments and corneal transplantation.

[Predictive factors for successful Ferrara intracorneal ring segment implantation in keratoconus]. / Facteurs prédictifs de succès des anneaux intracornéens de Ferrara dans le kératocône.

OBJECTIVE: To define predictive factors after manual implantation of intrastromal corneal ring segments (Ferrara ring) for the management of keratoconus. PATIENTS AND METHODS: Twenty-five eyes of 25 patients with keratoconus were implanted with Ferrara intracorneal ring segments using a mechanical procedure. We measured corneal ring implantation depth, best spectacle-corrected visual acuity (BSCVA), as well as refractive and keratometric outcomes. Patients were separated into two groups according to the gain of at least two lines of BSCVA ("good response") or the gain of only one line of BSCVA, no change, or the loss of lines of BSCVA ("poor response"). RESULTS: After a 6-month follow-up, 41% patients experienced a gain of at least two lines of BSCVA, 31.8% a gain of only one line, 13.6% no change, and 13.6% a loss of BSCVA. The sphere reduced from 4.39 to 2.34D (p<0.01), the cylinder from 4.19 to 2.77D (p<0.01), and the mean keratometry from 51.44 to 48.74D (p<0.02). As successful predictive factors, we found the asymmetry of keratoconus (p<0.01) in relation to the steepest meridian and patients implanted with a single ring (p<0.02). CONCLUSION: Defining preoperative successful predictive factors for Ferrara intracorneal ring segments is essential to enhance postoperative outcomes.

Matrix metalloproteinase 14 overexpression reduces corneal scarring.

Once a corneal scar develops, surgical management remains the only option for visual rehabilitation. Corneal transplantation is the definitive treatment for a corneal scar. In addition to the challenges posed by graft rejections and other postoperative complications, the lack of high-quality donor corneas can limit the benefits possible with keratoplasty. The purpose of our study was to evaluate a new therapeutic strategy for treating corneal scarring by targeting collagen deposition. We overexpressed a fibril collagenase (matrix metalloproteinase 14 (MMP14)) to prevent collagen deposition in the scar tissue. We demonstrated that a single and simple direct injection of recombinant adeno-associated virus-based vector expressing murine MMP14 can modulate gene expression of murine stromal keratocytes. This tool opens new possibilities with regard to treatment. In a mouse model of corneal full-thickness incision, we observed that MMP14 overexpression reduced corneal opacity and expression of the major genes involved in corneal scarring, especially type III collagen and α-smooth muscle actin. These results represent proof of concept that gene transfer of MMP14 can reduce scar formation, which could have therapeutic applications after corneal trauma.

[Survey of complications in Descemet stripping automated endothelial keratoplasty in 32 eyes]. / Complications après Descemet stripping automated endothelial keratoplasty : étude monocentrique sur 32 yeux.

OBJECTIVE: To report complications during and after Descemet stripping automated endothelial keratoplasty (DSAEK) in 32 eyes at a single academic center with two techniques for delivering the endothelial corneal graft. PATIENTS AND METHODS: Outcomes from a single center of 32 consecutives cases of DSAEK were analyzed prospectively. In the first 23 patients, the endothelial graft underwent single-fold delivery with forceps, and in the remaining nine patients, the graft was delivered with the Busin glide-based technique. The complications of DSAEK were noted from the intra- and postoperative periods. RESULTS: Graft detachment was the most common type of complication encountered. In seven of 32 eyes (22%), graft detachments were observed. Three of the 32 eyes (9.5%) were considered to have failed DSAEK, meaning that persistent edema was present after DSAEK. One of the 32 eyes had a late corneal decompensation. Three eyes (9.5%) demonstrated graft rejection. Four eyes with detached grafts were successfully rebubbled after surgery. Two of the 32 eyes (6.2%) underwent repeat DSAEK and three eyes (9.5%) underwent penetrating keratoplasty. CONCLUSIONS: DSAEK is becoming the preferred method for treating endothelial dysfunction because it maintains the structural integrity of the eye and provides rapid visual recovery with minimal refractive change. However, we experienced some complications. Graft detachment is the most common complication, but postoperative rebubbling allows for graft reattachment in most cases. Other common complications found in this series were graft failure and graft rejection.

[Corneal allograft rejection after Descemet stripping automated endothelial keratoplasty (DSAEK): report of three cases]. / Rejet d'allogreffe de cornée après Descemet stripping automated endothelial keratoplasty (DSAEK) : à propos de trois cas.

INTRODUCTION: Descemet stripping automated endothelial keratoplasty (DSAEK) is an exciting alternative to standard full-thickness penetrating keratoplasty (PK) for the treatment of patients suffering from endothelial failure of the cornea. Corneal transplant rejection is the leading cause of endothelial failure after PK. While DSAEK may reduce the risk of corneal allograft rejection, endothelial rejection can still occur. CASE REPORTS: We report three cases of endothelial rejection after DSAEK. Subacute endothelial rejection occurred in all three cases after the topical steroid treatment regimen had been stopped. CONCLUSION: A lower rejection rate in comparison with PK cannot be assumed and comparative studies are necessary. Extended topical steroid may be used. Subacute endothelial graft rejection implies that the patient needs to be fully informed of the functional signs and the need to seek medical advice immediately.

[Iris-fixated intraocular lenses: reinforced monitoring]. / Implants de chambre antérieure à fixation irienne : une surveillance renforcée.

In 1986, the concept of the claw lens was applied to correct myopia in phakic patients. Since then, progress has made iris-fixated phakic intraocular lenses (IOL) relatively safe, predictable, and effective for the correction of myopia, hyperopia, and astigmatism. All these models have undergone a series of design improvements to prevent complications. Despite having excellent refractive results, the principal risk is a potential progressive endothelial cell loss. Many authors have presented encouraging results. Phakic iris-fixated IOL surgery is a potentially reversible procedure, but the surgeon cannot rule out the possibility of complications. Therefore, long-term follow-up is mandatory.