Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial

CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 (NCT03140969), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit–risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development

Vitreous Hemorrhage as Presenting Sign of Retinal Arteriovenous Malformation

Objective. To describe a patient with vitreous hemorrhage and peripheral retinal ischemia, eventually diagnosed with an underlying retinal arteriovenous malformation. Methods. A 15-year-old girl presented with sudden-onset, painless visual loss in the right eye. She underwent a full ophthalmological work-up. Results. BCVA was less than 20/400 in the right eye and 20/20 in the left eye. Intraocular pressure and anterior segment examination were unremarkable. Fundoscopy was impossible due to an opaque vitreous hemorrhage in the right eye. The left eye was completely unremarkable. Examination during a 23-gauge pars plana vitrectomy showed dilated, tortuous arteriovenous vessels extending from the optic disc and silver wiring of the enlarged vessels. A clinical diagnosis of retinal arteriovenous malformation was made. During surgery, a peripheral retinal photocoagulation was executed to avoid rebleeding. Postoperatively, fluorescein angiography demonstrated additional macular microangiopathy and diffuse retinal nonperfusion in the periphery. The MRI brain revealed neither cerebral nor orbital vascular anomaly, confirming a group 2 retinal arteriovenous malformation. Conclusion. Retinal arteriovenous malformations are generally considered stable over time. However, complications due to retinal ischemia can occur. Hence, regular observation is warranted. In so doing, timely treatment can be offered to avoid complications

Paediatric cataract surgery with 27G vitrectomy instrumentation : the Ghent University Hospital experience

ObjectiveTo describe a cohort of paediatric patients who underwent unilateral or bilateral lens extractions at Ghent University hospital using the Dutch Ophthalmic Research Center (D.O.R.C.) ultra-short 27G vitrectomy system. MethodsRetrospective analysis of the medical and surgical records of all children that underwent lens extraction between September 2016 and September 2020 using the D.O.R.C. ultra-short 27G vitrectomy system. ResultsSeventy-two eyes of 52 patients were included. The most important aetiologies in this study were of secondary (25.5%), developmental (13.7%), or genetic (13.7%) nature. No definitive cause could be established in more than a quarter of cases (27.5%) despite extensive work-up, them being deemed idiopathic. The remainder of cases (19.6%) was not assigned a final aetiologic designation at the time of the study due to contradicting or missing diagnostic data. This study could not identify any cataract cases related to infection or trauma. Surgical complications rate was 61.1% of which posterior capsule opacification was the most frequent with a rate of 25%. A significant short-term postoperative best-corrected visual acuity gain (& LE; -0.2 LogMAR) was observed in 60.5% of eyes for which usable acuity data were available (n = 38). ConclusionMany different instruments and techniques have been described and used in the context of paediatric lens extractions, each with its advantages and disadvantages. This study illustrates that an ultra-short 27G vitrectomy system can be used to perform paediatric lens extractions with good surgical outcomes. Further studies and comparative trials are needed to ascertain this further

Spiroplasma infection as a cause of severe congenital keratouveitis, cataract and glaucoma

Background Only seven cases of ocular Spiroplasma infection have been reported to date, all presenting as congenital cataracts with concomitant intraocular inflammation. We describe the first case of Spiroplasma infection initially presenting as a corneal infiltrate. Case presentation A 1-month-old girl was referred for a corneal infiltrate in the left eye. She presented in our hospital with unilateral keratouveitis. Examination showed a stromal corneal infiltrate and dense white keratic precipitates in the left eye. Herpetic keratouveitis was suspected and intravenous acyclovir therapy was initiated. Two weeks later, the inflammation in the left eye persisted and was also noticed in the right eye. Acute angle-closure glaucoma and a cataract with dilated iris vessels extending onto the anterior lens capsule developed in the left eye. The inflammation resolved after treatment with azithromycin. Iridectomy, synechiolysis and lensectomy were performed. Bacterial metagenomic sequencing (16 S rRNA) and transmission electron microscopy revealed Spiroplasma ixodetis species in lens aspirates and biopsy. Consequently, a diagnosis of bilateral Spiroplasma uveitis was made. Conclusions In cases of congenital cataract with concomitant intraocular inflammation, Spiroplasma infection should be considered. The purpose of this case report is to raise awareness of congenital Spiroplasma infection as a cause of severe keratouveitis, cataract and angle-closure glaucoma in newborns. Performing molecular testing on lens aspirates is essential to confirm diagnosis. Systemic macrolides are suggested as the mainstay of treatment

Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect

Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969) with intravitreal injections of an antisense oligonucleotide to restore correct splicing. There were no serious adverse events, and vision improved at 3 months. The visual acuity of one exceptional responder improved from light perception to 20/400