Effectiveness and Safety of Weekly Adalimumab for Non-Infectious Chronic Anterior Uveitis in Children.

PURPOSE: Non-infectious chronic anterior uveitis (CAU) remains a therapeutic challenge. The purpose of this study was to analyze the effectiveness and safety of weekly dosing of adalimumab in children with non-infectious refractory CAU. Methods: Demographic and clinical data of children followed by non-infectious CAU treated with adalimumab were retrospectively reviewed. RESULTS: Of the 42 children with CAU, 27/42 (64.3%) were treated with adalimumab. Escalation to weekly dosing of adalimumab was necessary for 11/27 children (40.7%). After 3 and 6 months, 7/11 children (63.6%) met the composite endpoint of inflammation control improvement. Children requiring weekly adalimumab had initially more severe uveitis: anterior chamber cells (p = 0.02), aqueous flare (p = 0.02), and presence of macular edema (p = 0.007). No children had serious systemic side effects. CONCLUSION: Weekly adalimumab in children with refractory CAU appears to be an effective and safe treatment for inflammation control and corticosteroid sparing, and an alternative before biologic switching. Controlled studies are needed.

An Efficient Technique for the Long-term Preservation of SMILE Lenticules Using Desiccation.

PURPOSE: To evaluate a desiccation protocol for the long-term preservation of human small incision lenticule extraction (SMILE) lenticules and to study their integration in an in vivo rabbit model. METHODS: Lenticules were retrieved after SMILE procedures in patients, then desiccated according to a novel protocol. Histologic and electron microscopic analyses were performed. Six rabbit eyes received grafts with an inlay technique, which consisted of inserting a desiccated lenticule into a stromal pocket. Rabbits were killed at different times between 6 and 24 weeks. Rabbit corneas were analyzed using optical coherence tomography, histology, and DAPI staining. RESULTS: Microscopic analysis of desiccated lenticules showed a preserved stromal architecture after rehydration. A decellularization of the lenticules after desiccation was observed without any chemical treatment. All rabbit corneas remained clear after grafting human lenticules and no rejection occurred. Optical coherence tomography showed regular lenticular implantation and no decrease in lenticule thickness. Histologic analysis showed no inflammatory infiltration around lenticules and no nuclear material inside lenticules after 6 months. CONCLUSIONS: A favorable integration of desiccated human SMILE lenticules in rabbit corneas was observed. The refractive issue of lenticular implantation must be investigated next. Clinical trials are needed to evaluate the use of desiccated SMILE lenticules to treat hyperopia or keratoconus in humans. [J Refract Surg. 2023;39(7):491-498.].

Efficacious switching from subcutaneous to intravenous tocilizumab in patients with non-infectious non-anterior uveitis.

PURPOSE: The efficacy of tocilizumab in refractory chronic noninfectious uveitis has been previously reported, but no data comparing intravenous and subcutaneous tocilizumab in uveitis are available. RESULTS: We report a case series of patients with chronic noninfectious uveitis with incomplete efficacy of subcutaneous tocilizumab, improved after switching to intravenous routes. Improvement of visual acuity was observed with intravenous tocilizumab for all patients. Half of the patients could stop corticosteroids. Rapid efficacy of intravenous tocilizumab was observed, between 2 and 3 months. CONCLUSION: In uveitis, tocilizumab administration could be optimized by a switching from a subcutaneous to an intravenous administration route.

Keratoconus and the Impact of Treatment on Patients' Quality of Life: A Qualitative Study.

INTRODUCTION: Keratoconus has a significant impact on patients' quality of life (QoL), from diagnosis to the advanced stages of the disease. The aim of this research was to identify domains of QoL affected by this disease and its treatment. METHODS: Phone interviews were conducted using a semi-structured interview guide, with patients with keratoconus stratified according to their current treatment. A board of keratoconus experts helped identify the guide's main themes. RESULTS: Thirty-five patients (rigid contact lenses, n = 9; cross-linking, n = 9; corneal ring implants, n = 8; and corneal transplantation, n = 9) were interviewed by qualitative researchers. Phone interviews revealed several QoL domains affected by the disease and its treatments: "psychological", "social life", "professional life", "financial costs" and "student life". All domains were impacted, independently of the treatment history. Few differences were found between treatment regimens and keratoconus stages. Qualitative analysis enabled the development of a conceptual framework based on Wilson and Cleary's model for patient outcomes common to all patients. This conceptual model describes the relationship between patients' characteristics, their symptoms, their environment, their functional visual impairment and the impact on their QoL. CONCLUSIONS: These qualitative findings supported the generation of a questionnaire to evaluate the impact of keratoconus and its treatment on patients' QoL. Cognitive debriefings confirmed its content validity. The questionnaire is applicable for all stages of keratoconus and treatments and may help tracking change over time in regular clinical settings. Psychometric validation is yet to be performed before its use in research and clinical practices.

Ocular sequelae of epidermal necrolysis: French national audit of practices, literature review and proposed management.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious and rare diseases, most often drug-induced, and their incidence has been estimated at 6 cases/million/year in France. SJS and TEN belong to the same spectrum of disease known as epidermal necrolysis (EN). They are characterized by more or less extensive epidermal detachment, associated with mucous membrane involvement, and may be complicated during the acute phase by fatal multiorgan failure. SJS and TEN can lead to severe ophthalmologic sequelae. There are no recommendations for ocular management during the chronic phase. We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. Ophthalmologists and dermatologists from the French reference center for epidermal necrolysis were asked to complete a questionnaire on management practices in the chronic phase of SJS/TEN. The survey focused on the presence of a referent ophthalmologist at the center, the use of local treatments (artificial tears, corticosteroid eye drops, antibiotic-corticosteroids, antiseptics, vitamin A ointment (VA), cyclosporine, tacrolimus), the management of trichiatic eyelashes, meibomian dysfunction, symblepharons, and corneal neovascularization, as well as the contactologic solutions implemented. Eleven ophthalmologists and 9 dermatologists from 9 of the 11 centers responded to the questionnaire. Based on questionnaire results, 10/11 ophthalmologists systematically prescribed preservative-free artificial tears, and 11/11 administered VA. Antiseptic or antibiotic eye drops or antibiotic-corticosteroid eye drops were recommended as needed by 8/11 and 7/11 ophthalmologists, respectively. In case of chronic inflammation, topical cyclosporine was consistently proposed by 11/11 ophthalmologists. The removal of trichiatic eyelashes was mainly performed by 10/11 ophthalmologists. Patients were referred to a reference center for fitting of scleral lenses (10/10,100%). Based on this practice audit and literature review, we propose an evaluation form to facilitate ophthalmic data collection in the chronic phase of EN and we also propose an algorithm for the ophthalmologic management of ocular sequelae.

Long-term follow-up of bilateral ectasia after laser-assisted Small-Incision Lenticule Extraction (SMILE) with known risk factors.

PURPOSE: To report the long-term follow-up of bilateral ectasia after laser-assisted small-incision lenticule extraction (SMILE) with known risk factors. CASE REPORT: We report the case of a 23-year-old woman. Preoperative refraction was - 7.25 -2.00 × 20 in the right eye and -7.25 -1.50 × 155 in the left eye. Maximal keratometry was 47.32 diopters and 48.37 diopters, respectively, which was a contraindication to Laser Assisted In Situ Keratomileusis (LASIK) and a SMILE was proposed in 2015. One year after surgery, ectasia developed in the left eye and crosslinking (CXL) was performed. Two years after surgery, ectasia also developed in the right eye and CXL was also performed, leading to stabilization in both eyes five years after surgery. CONCLUSIONS: Known contraindications for LASIK are also contraindications for the performance of refractive surgery with SMILE. CXL is an efficient treatment of post-SMILE corneal ectasia.

Saprochaete clavata Chorioretinitis in a Post-chemotherapy Immunocompromised 9-Year-Old Child.

PURPOSE: To describe the management of bilateral chorioretinitis with Saprochaete clavata in a post-chemotherapy immunocompromised young patient. METHOD: A retrospective case report. RESULT: A 9-year-old boy treated with chemotherapy for type 2 acute myeloid leukaemia was diagnosed with Saprochaete clavata (formerly called Geotrichum clavatum) fungaemia. Systematic ocular examination revealed chorioretinitis of the left eye becoming bilateral within the next 3 days. Therapy was based on systemic administration of voriconazole, amphotericin B and flucytosine associated with granulocytic stimulation without stabilizing the ophthalmological situation. Bilateral intravitreal injections of amphotericin B were administered. Voriconazole residual blood concentration was monitored to adjust daily dose. Final best corrected visual acuity in the right eye was 20/50 and 20/20 in the left eye. CONCLUSION: This is the first report of chorioretinitis with Saprochaete clavata. Because of its unpredictable pharmacokinetics, especially in pediatric population, therapeutic drug monitoring of voriconazole is essential to control fungal infection.

Anterior chamber fibrin reaction during Descemet membrane endothelial keratoplasty.

PURPOSE: To report a series of five cases of intraoperative spontaneous anterior chamber fibrin reaction during Descemet Membrane Endothelial Keratoplasty (DMEK). METHODS: We retrospectively collected demographic data and data for ocular disease history for each patient. Donor age, preoperative graft endothelial density, surgical complications on surgery and intraoperative OCT videos, intraoperative management and outcome were assessed. The same standardized DMEK technique was used for all patients. RESULTS: We report intraoperative fibrin formation in five eyes subjected to DMEK. Three pseudophakic eyes underwent single DMEK, and the other two underwent combined DMEK and cataract surgery. In one case, a fibrin filament was observed before graft insertion, with multiplication during surgery, whereas, in the other four cases, strands of fibrin from the iris appeared after graft insertion. This complication resulted in graft failure in four cases (80%). No recipient- or donor-related risk factor was identified. CONCLUSIONS AND IMPORTANCE: The anterior chamber fibrin reaction is a very uncommon complication of DMEK. The underlying pathophysiological mechanisms remain unknown, but analyses of surgical videos and intraoperative OCT suggest iris involvement. This phenomenon may be induced by chronic subclinical anterior chamber inflammation, due to a blood-aqueous barrier breakdown associated with acute iris trauma during surgery. Thus, intraoperative microtraumatism of the iris should be avoided.

TREATMENT OF SUBRETINAL PERFLUOROCARBON LIQUID BUBBLES COMPLICATING RETINAL DETACHMENT SURGERY USING AIR FOR DRAINAGE.

PURPOSE: The authors describe an original technique for treating multiple subretinal perfluorocarbon liquid (PFCL) bubbles complicating previous surgery for rhegmatogenous retinal detachment. METHODS: To facilitate the induction of macular redetachment and peripheral displacement of the PFCL bubbles, we performed the subretinal injection of filtered air in addition to balanced salt solution. In this setting, the action of the PFCL in the vitreous cavity, combined with globe manipulation, allowed bubbles' displacement and full aspiration. RESULTS: A 57-year-old man had a history of repeated pars plana vitrectomies for recalcitrant rhegmatogenous retinal detachment, the latter leading to multiple subretinal PFCL bubbles retained at the posterior pole. The described technique was performed 8 weeks after the last pars plana vitrectomy. A complete flattening of the macular region was obtained with visual improvement. CONCLUSION: Direct injection of air into the subretinal space may represent an effective strategy to help the surgical management of multiple retained PFCL bubbles.

Comparison of conventional immunosuppressive drugs versus anti-TNF-α agents in non-infectious non-anterior uveitis.

OBJECTIVE: To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis. METHODS: Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compared between patients treated with DMARDs or anti-TNF-α agents. The primary outcome was treatment failure or occurrence of serious adverse events. Treatment failure was determined by ophthalmologic criteria. RESULTS: Seventy-three patients were included, mostly female (52%). Among them, 39 were treated with DMARDs and 34 with anti-TNF-α agents. The main uveitis causes were idiopathic (30%), birdshot chorio-retinopathy (25%), sarcoidosis (16%) and Behçet's disease (14%). The primary outcome was observed in 56% of patients treated with anti-TNF-α agents versus 59% of patients treated with DMARDs (p = 0.82). Median time to observe the primary outcome was 16 months (anti-TNF-α group) versus 21 months (p = 0.52). There was no significant difference between the two groups in terms of treatment failure, corticosteroid sparing effect, visual acuity improvement or adverse events. Earlier control of ocular inflammation was achieved with anti-TNF-α agents than with DMARDs (p = 0.006). In relapsing patients, anti-TNF-α agents allowed better corticosteroid sparing (p = 0.06). CONCLUSION: DMARDs could still be used as first-line therapy for non-infectious non-anterior uveitis after corticosteroid therapy. However, anti-TNF-α agents could be proposed as an alternative in cases of severe inflammation or initial high level of steroid dependency.

Corneal Pharmacokinetics of Voriconazole and Posaconazole following Intrastromal Injection and Posaconazole Eye Drops Instillation in Rats.

Purpose/Aims: Infectious keratitis is a major cause of visual impairment and blindness worldwide. Common difficulties in treating fungal keratitis prompt new therapeutic possibilities. In this study, intrastromal voriconazole and posaconazole, and topical posaconazole were tested for their potential to obtain therapeutic cornea concentrations. Materials and Methods: Pharmacokinetics of triazole intracorneal/eye drop administration was studied in rats. Sixty-two rats were treated either by voriconazole or posaconazole. Twenty-nine and 33 rats received intrastromal injection of voriconazole solution (1 µl, 10 mg/ml) and posaconazole solution (1 µl, 18 mg/ml), respectively, administered under microscopic examination with a 32 gauge needle in the left cornea. Posaconazole (1.8% solution) eye drops were used. Cornea and plasma concentrations were determined using 2D HPLC separation and tandem MS, at 30 min, 3 h, 6 h, 24 h, 48 h, 72 h, and 144 h (6 days) post-intrastromal injection. The entire rat cornea was used for chromatography analyses. Results: In anesthetized rats, single intracorneal injection resulted, after 30 min, in respectively, >300 ng/mg and >260 ng/mg cornea concentrations, dropping to low levels within hours, while staying low in plasma. The effect of hourly posaconazole eye drops resulted in >10 ng/mg cornea concentration, which was maintained with instillations every 2 and then every 4 h. Conclusion: Our results show that there is little interest of intrastromal triazole administration due to the short duration of high cornea concentrations obtained after intracorneal injection. Posaconazole eye drops maintain therapeutic cornea concentrations in rats and could be used to treat severe infectious keratitis.

Mapping of proteomic profile and effect of the spongy layer in the human amniotic membrane.

The graft of human amniotic membrane (HAM) contributes to the healing of corneal perforating ulcers and so to save a large number of eyes suffering of severe chemical burns. This biological material is used for the treatment of ocular surface diseases because of its capacity to reduce inflammation and promote a quicker wound healing. For clinical use, the HAM is denuded from its spongy layer, but this layer can be an important source of growth factors which promote re-epithelialization. The aim of our study is to provide a general view of protein expression of the HAM and the spongy layer and therefore to determine if the spongy layer and/or a specific part of HAM have a beneficial role in the process of wound healing in patients with corneal ulcers. For this study, human placentas were obtained from healthy women after vaginal delivery or caesarean section after signing the consent form. Mapping of protein expression is done by dividing the placenta in 2 equal parts, one with spongy layer and another without (conventional HAM). Each part is also divided in 3 zones depending on the distance from the umbilical cord. The proteomic analysis was done by ELISA, targeting growth factors (EGF, HGF, KGF, NGF and TGF-beta1) and pro inflammatory cytokine TNF-α in the HAM without spongy layer and in the spongy layer. In this study we observed significant difference in the total amount of protein extract between the different donors. We do not observe a significant difference in the growth factor level between the conventional HAM and the spongy layer. No variation was observed in the expression of HGF, KGF and NGF in different zone of HAM and neither between conventional HAM and spongy layer in each zone. (*p value < 0.05, **p value<0.01,***p value < 0.001). We do detect very low dose of TNF-α and no correlation with the amount of growth factors. In our study we demonstrated that keeping the spongy layer in conventional method of handling HAM can add more GF, and so probably have a positive affect the wound healing process. Variation in some growth factors expression has been observed between the placentas and therefore this may explain the variation in clinical results. No indicator for the selection of placentas with a higher rate of growth factor was found.

Complications of cosmetic iris implants: French series of 87 eyes.

PURPOSE: Iris intraocular implants were developed to manage congenital or traumatic iris defects. However, they are also used to change the color of patient eyes. The aim of this retrospective series was to report complications in patients managed in France after cosmetic implantation. SETTING: Ophthalmological institutions and private ophthalmologists in France. DESIGN: Multicenter retrospective observational study. METHODS: Questionnaires were sent to all ophthalmology departments in university hospitals and to private ophthalmologists. This questionnaire listed demographic and clinical data for each implanted eye with a focus on safety, the description of ocular complications (corneal edema, endothelial cell loss, increased intraocular pressure, and intraocular inflammation), and the therapeutic management implemented. RESULTS: Forty-four questionnaires (87 eyes) were collected, and ultimately, 33 questionnaires (65 eyes) were considered complete and analyzed. Two types of implants were identified. Of the 65 eyes analyzed, only 5 eyes (7.7%) did not experience any complication and 60 eyes (92.3%) had at least 1 complication. The most commonly reported complication was corneal decompensation (78.5%). The diagnosis of glaucoma was made in over half (52.3%) of the cases. Explantation was needed in 81.5% of cases. The mean final visual acuity was 0.45 ± 0.08 logarithm of the minimum angle of resolution (logMAR) (0 to 2 logMAR). CONCLUSIONS: Several ocular complications with a decreased mean visual acuity were described in a young healthy population. In addition, patient information on the safety of this procedure appeared insufficient.

Contact Lenses and Infectious Keratitis: From a Case-Control Study to a Computation of the Risk for Wearers.

PURPOSE: Contact lens (CL)-related microbial keratitis (MK) has major public health implications, with about 300 million wearers worldwide, and certain potentially modifiable risk factors. This study aimed to identify the risk factors of CL-related MK. METHODS: A multicenter case-control study was conducted between 2014 and 2017. Cases presenting with CL-related MK were submitted to an anonymous 52-item questionnaire, which was also completed by healthy controls. Univariate followed by multivariate logistic regression analysis was performed. Risk factors for CL-related MK were given as odds ratio (OR) with 95% confidence interval and P-value. RESULTS: The study included a total of 2267 patients (1198 cases and 1069 controls). The MK risk factors for the daily disposable lenses group were exceeding the lens renewal period (OR = 9.16, P = 0.008) and occasionally wearing CL when sleeping (OR = 15.83, P = 0.035). The most important risk factors in the nondaily disposable lenses group were lens cleaning solution distributed by eye care brands (OR = 3.50, P < 0.001) and failure to renew lens cases (OR = 3.39, P = 0.001). Statistically and clinically significant variables were used to establish the MK risk equation for CL wearers, allowing an individual calculation of the risk of MK under lenses. CONCLUSIONS: The MK risk equation is a valuable tool for educating patients about the risks associated with wearing CL. It allows the patient to be informed about their overall risk of infection while detailing the precipitating elements of the infectious risk with the aim of modifying risk behavior.

Face-to-face phacoemulsification using a slitlamp in patients who are unable to lie flat.

Phacoemulsification can be challenging in patients who are unable to lie flat or sit in a reclined position that exceeds 30 degrees to 45 degrees during surgery. We describe a new technique that we have used on 4 eyes of two patients. Both were operated on while sitting in a strictly upright position, resting their chin in front of a mobile slitlamp in the same manner as during a standard ophthalmologic examination. The surgeon sits on the other side of the slitlamp, facing the patient, and operates via a temporal corneal incision. The described operating conditions were deemed perfectly adequate by the experienced surgeon. Both patients recovered a corrected distance visual acuity of 20/20 in both eyes and said they would recommend this surgery to anyone who cannot lie flat. Surgeons should consider this technique when standard surgical positioning is not possible.

Confirmation and further delineation of the SMG9-deficiency syndrome, a rare and severe developmental disorder.

INTRODUCTION: SMG9 deficiency is an extremely rare autosomal recessive condition originally described in three patients from two families harboring homozygous truncating SMG9 variants in a context of severe syndromic developmental disorder. To our knowledge, no additional patient has been described since this first report. METHODS: We performed exome sequencing in a patient exhibiting a syndromic developmental delay and in her unaffected parents and report the phenotypic features. RESULTS: Our patient presented with a syndromic association of severe global developmental delay and diverse malformations, including cleft lip and palate, facial dysmorphic features, brain abnormalities, heart defect, growth retardation, and severe infections. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous. CONCLUSIONS: We confirm that bi-allelic truncating SMG9 variants cause a severe developmental syndrome including brain and heart malformations associated with facial dysmorphic features, severe growth and developmental delay with or without ophthalmological abnormalities, severe feeding difficulties, and life-threatening infections.