Optic Disc Hypoplasia Assessment in PAX6 -Related Aniridia.

BACKGROUND: This study aims to characterize optic disc hypoplasia in congenital aniridia using ultra-wide-field imaging (UWFI) and nonmydriatic retinal photography (NMRP). We also investigated the relation between optic disc hypoplasia and foveal hypoplasia. METHODS: This is a retrospective case series of patients diagnosed with PAX6 -related aniridia in a National Referral Center, who underwent UWFI, NMRP, and spectral-domain optical coherence tomography (SD-OCT) . The disc diameter (DD) and the disc-to-fovea distance (DF) were measured. The DD:DF ratio was used to assess the relative size of the optic disc. The analyses were carried with respect to paired age- and sex-matched healthy controls. SD-OCT was used for foveal hypoplasia grading (from 1 to 4) and retinal nerve fiber layer (RNFL) analysis. RESULTS: Mean manual DD:DF ratio was 0.33 (95% CI: 0.31-0.35) in aniridia patients versus 0.37 (95% CI: 0.36-0.39) in control patients (n = 20, P = 0.005) measured on NMRP and 0.32 (95% CI: 0.30-0.35) in aniridia patients versus 0.37 (95% CI: 0.37-0.39) in control patients (n = 26, P < 0.0001) when assessed on UWFI. Mean semiautomated DD:DF ratio measured on UWFI in aniridia patients was 0.31 (95% CI: 0.29-0.33) versus 0.37 (95% CI: 0.36-0.38) in control patients ( P < 0.0001). Also, a negative correlation was found significant between the grade of foveal hypoplasia and the mean semiautomated DD:DF ratio (r = -0.52, 95% CI: -0.76 to -0.15, P = 0.0067). Finally, a significant negative correlation was found between the peripapillary temporal RNFL thickness and the grade of foveal hypoplasia ( P = 0.0034). CONCLUSIONS: The DD:DF ratio is significantly reduced in PAX6 -related aniridia patients and correlates with the severity of foveal hypoplasia. This ratio is a valuable tool for optic disc hypoplasia assessment in congenital aniridia, especially when provided semiautomatically by UWFI.

Uveal effusion in Waldenstrom's macroglobulinemia.

PURPOSE: To reastport a case of Waldenstrom macroglobulinemia-related choroidal detachments. METHOD: Case report. RESULTS: A 80-year-old woman was referred for bilateral visual loss for few months. She was hospitalized for a Waldenstrom's disease. Both anterior chambers were deep and quiet. Fundus revealed bilateral choroidal detachment without serous retinal detachments. No vitritis, retinal tear or pigmented lesion were observed. After eliminating all other causes of uveal effusion, the patient was treated for her hemopathy with chemotherapy associated with corticosteroids and plasmapheresis. One month later, fundus showed a complete disappearance of choroidal detachments and vision improved. CONCLUSION: Uveal effusion is an extremely rare ocular damage of Waldenström disease. As choroidal vessels are porous, they may allow immunoglobulins, over produced, to leak toward supra-choroidal space triggering choroidal detachments.

Commercial Versus Compounded Preparations in Pediatric Ophthalmology.

Many conditions managed by pediatric ophthalmologists are rare diseases, and even if pharmacological treatments are available, these have often not been evaluated in children. Off-label prescribing is a common practice in pediatric ophthalmology. In addition, there is often no commercial case for the production of a medicine that may only be used for a small number of patients worldwide. Compounded preparations prepared locally are therefore still in frequent use, although it is known that production may not meet stringent quality assurance standards. For several indications, commercial preparations, evaluated in rigorous clinical trials with children, are now available. Myopia management is joining the list of these indications, with low-concentration atropine formulations derived from recent clinical trials in Australia, USA, and Europe now entering the market. This short article gives an overview of the background and recent developments of compounded and commercial preparations for use in pediatric ophthalmology.

Duloxetine enhances PAX6 expression and suppresses innate immune responses in murine LPS-induced corneal inflammation.

BACKGROUND-AIM: PAX6 is a key regulator of eye development and epithelial homeostasis in the cornea. When deficient, chronic corneal inflammation, neovascularization and limbal stem cell deficiency can occur. Here we investigated the potential of duloxetine, a generic serotonin reuptake inhibitor that can upregulate PAX6 in vitro, for its in vivo activity in the context of corneal inflammation. METHODS: Duloxetine tolerance was tested in a human limbal stem cell line and isogenic CRISPR-knockout PAX6+/- cells. C57BL/6-Wildtype mice were administered duloxetine eye drops at concentrations of 1 µM - 2 mM and tested for toxicity and corneal PAX6 expression. In LPS-induced corneal inflammation in mice, duloxetine's effect on PAX6 expression, corneal opacification and inflammatory responses were evaluated by in vivo corneal imaging, immunostaining, and whole-transcriptome microarray analysis. RESULTS: No toxicity was observed in vitro for duloxetine concentrations up to 10µΜ. In vivo, duloxetine drops were well-tolerated up to 50 µM. Duloxetine drops at 10µΜ significantly upregulated PAX6 protein levels in the cornea by 30 % within 2 days. In the LPS model, duloxetine resulted in a sustained 33 % PAX6 protein upregulation in the cornea at 7 days, and in reduced opacity within 2 days, accompanied by a significant dampening of IL-17A signaling, neutrophil degranulation, microglial activation, macrophage markers, and MMP expression, despite non-significant changes in total inflammatory cell infiltration. CONCLUSION: Short-term administration of a repurposed generic drug, duloxetine, upregulates PAX6 protein levels in the cornea of mice and exerts an anti-inflammatory activity by dampening innate immune responses.

Optic disc drusen and scleral canal size - protocol for a systematic review and meta-analysis.

Background: Around one in forty patients are diagnosed with optic disc drusen (ODD) during their lifetime. Complications of these acellular deposits range from asymptomatic visual field deficits to artery occlusion and subsequent cecity. Still, the pathogenesis of their emergence remains controversial. In particular, it was suggested 50 years ago that a narrow disc and scleral canal is one factor leading to axoplasmic flow disturbance, which induces ODD formation. However, this hypothesis is still debated today. To evaluate the basis of this theory, we will conduct a systematic review and meta-analysis of studies evaluating the scleral canal size in patients with ODD and in healthy subjects. Methods: We will search MEDLINE via PubMed, Cochrane, and EMBASE electronic databases to identify articles published before November 29, 2022 that measure the scleral canal size in patients with ODD and in healthy subjects. In addition, grey literature will be searched. The meta-analysis will include studies that include patients with a clinical or imaging diagnosis of ODD and healthy subjects. Additionally, we will perform a subgroup analysis to compare patients with buried ODD and patients with visible ODD. Extracted data from included studies will be presented descriptively, and effect sizes will be computed based on the recommendations from the Cochrane Collaboration handbook. Discussion: The hypothesis that a narrow scleral canal is a risk factor of ODD has long been debated and this systematic review and meta-analysis should disentangle the different views. Understanding the underlying factors driving the development of ODD should help us focus on patients at risk and develop strategies to prevent advanced stages of the disease in these patients. Besides, focusing on patients with small scleral canals should help us derive associated factors and provide a better understanding of the pathology. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375110.

Gene therapies in pediatric ophthalmology.

Genetic pediatric eye disease frequently leads to severe vision impairment or blindness. Voretigene neparvovec is the first approved gene therapy for an inherited retinal dystrophy (IRD). Voretigene neparvovec has been shown to be well tolerated and safe, with encouraging results in terms of efficacy, mainly when administered early in childhood. While we assisted at the first gene therapy available in clinical practice for an IRD, some questions remain unanswered, especially when gene therapy is delivered in young children. We review here the most recent reports and promising ongoing studies concerning various approaches on gene therapy in pediatric ophthalmology.