A Novel Autosomal Recessive Variant of the NRL Gene Causing Enhanced S-Cone Syndrome: A Morpho-Functional Analysis of Two Unrelated Pediatric Patients.

Enhanced S-cone syndrome (ESCS) is a rare autosomal recessive retinal degeneration mainly associated with pathogenic variations in the NR2E3 gene. Only a few pathogenic variations in the NRL gene associated with ESCS have been reported to date. Here, we describe the clinical and genetic findings of two unrelated pediatric patients with a novel frameshift homozygous variant in the NRL gene. Fundus examinations showed signs of peripheral degeneration in both patients, more severe in Proband 2, with relative sparing of the macular area. Spectral domain optical coherence tomography (SD-OCT) revealed a significant macular involvement with cysts in Proband 1, and minimal foveal alteration with peripheral retina involvement in Proband 2. Visual acuity was abnormal in both patients, but more severely affected in Proband 1 than Proband 2. The electroretinogram recordings showed reduced scotopic, mixed and single flash cone responses, with a typical supernormal S-cone response, meeting the criteria for a clinical diagnosis of ESCS in both patients. The present report expands the clinical and genetic spectrum of NRL-associated ESCS, and confirms the age-independent variability of phenotypic presentation already described in the NR2E3-associated ESCS.

Dexamethasone Intravitreal Implant (Ozurdex) in Paediatric Patients with Non-infectious Intermediate Uveitis and Related Cystoid Macular Oedema: Evaluation of Macular Morphology and Function with Six-month Follow-up; a Deeper Role of MfERG?

PURPOSE: To evaluate the efficacy of Ozurdex implant by analyzing macular morphology and function in pediatric uveitis and related cystoid macular edema (CMO). METHODS: Main outcomes were visual acuity, mfERG and photopic ERG response, and central macular thickness. Mean values recorded at each time-point were compared to baseline and correlations between functional and anatomical parameters were evaluated. RESULTS: Resolution of intraocular inflammation and CMO was achieved in all eyes 1 month after implant without procedure or drug-related complications. Mean visual acuity and mfERG amplitude improved showing a statistically significant difference to baseline values for the first 4 months. Mean central macular thickness showed a statistically significant reduction for all follow-up time. Photopic ERG did not vary significantly. Statistically significant correlation was found between trends of visual acuity, central macular thickness, and mfERG responses. CONCLUSION: Correlation found between macular morphology and function confirms the efficacy of Ozurdex in pediatric uveitis.

Treatment of Advanced Coats' Disease With Combination Therapy of Laser Photocoagulation, Intravitreal Ranibizumab, and Sub-Tenon Methylprednisolone Acetate.

PURPOSE: To investigate the efficacy of combination therapy with laser photocoagulation, intravitreal ranibizumab, and sub-Tenon methylprednisolone acetate in patients presenting with advanced Coats' disease. METHODS: This was a retrospective analysis of 16 patients who underwent laser photocoagulation combined with intravitreal ranibizumab and sub-Tenon methylprednisolone acetate between 2008 and 2017. The primary outcome was anatomic success and the secondary outcomes were globe preservation and final visual acuity. RESULTS: The average age at surgery was 5.12 ± 2.7 years (range: 3 to 10 years). The mean follow-up time was 45.43 ± 29.01 months (range: 12 to 108 months). Of the 16 patients (16 eyes) reviewed, 6 patients had stage 3A and 10 patients had stage 3B Coats' disease. The mean number of applications was 10 (range: 4 to 18). Globe preservation was achieved in all patients. Final visual acuity outcomes were satisfactory: 20/20 to 20/50 in 2 patients, 20/60 to 20/100 in 1 patient, and 20/200 or worse in 13 patients. CONCLUSIONS: Intravitreal ranibizumab used in combination with laser photocoagulation and sub-Tenon methylprednisolone acetate could be an effective treatment option for patients with advanced Coats' disease. The combined therapy achieved anatomical success, globe preservation, and reasonable visual acuity outcomes. [J Pediatr Ophthalmol Strabismus. 2022;59(3):187-191.].

TUBB3 E410K syndrome: Case report and review of the clinical spectrum of TUBB3 mutations.

The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The ß-tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron-specific expression pattern. A recurrent heterozygous mutation, c.1228G > A; p.E410K, in TUBB3 gene is responsible of a rare disorder clinically characterized by congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual disability and a wide range of neurological and endocrine abnormalities. Other mutations have been described spanning the entire gene and genotype-phenotype correlations have been proposed. We report on a 3-year-old boy in whom clinical exome sequencing allowed to identify a de novo TUBB3 E410K mutation as the molecular cause underlying a complex phenotype characterized by a severe bilateral palpebral ptosis refractory to eye surgery, psychomotor delay, absent speech, hypogonadism, celiac disease, and cyclic vomiting. Brain MRI revealed thinning of the corpus callosum with no evidence of malformation cortical dysplasia. We reviewed available records of patients with TUBB3 E410K mutation and compared their phenotype with the clinical outcome of patients with other mutations in TUBB3 gene. The present study confirms that TUBB3 E410K results in a clinically recognizable phenotype, unassociated to the distinct cortical dysplasia caused by other mutations in the same gene. Early molecular characterization of TUBB3 E410K syndrome is critical for targeted genetic counseling and prompt prospective care in term of neurological, ophthalmological, endocrine, and gastrointestinal follow-up.

Propofol and fentanyl sedation for laser treatment of retinopathy of prematurity to avoid intubation.

BACKGROUND: Despite the optimization of neonatal assistance, severe retinopathy of prematurity (ROP, stage III-IV) remains a common condition among preterm infants. Laser photocoagulation usually requires general anesthesia and intubation, but extubation can be difficult and these infants often affected by chronic lung disease. We retrospectively evaluated the clinical charts of 13 neonates that were sedated with propofol in association with fentanyl for the laser treatment of ROP. This protocol was introduced in our unit to avoid intubation and minimize side effects of anesthesia and ventilation. METHODS: Propofol 5% followed by a bolus of fentanyl was administered as sedation during laser therapy to 13 preterm infants, affected by ROP stage III-IV. Propofol was initially infused as a slow bolus of 2-4 mg/kg and then continuously during the entire procedure, at 4 mg/kg/hour, increasing the dosage to 6 mg/kg/hour if sedation was not achieved. A laryngeal mask was placed and patients were ventilated with a flow-inflating resuscitation bag. RESULTS: Thirteen neonates were treated allowing to perform surgery without intubation. Only 4/13 (30.8%) of infants required minimal respiratory support during and/or after surgery. Heart rate after the intervention was higher than that at the beginning while remaining in the range of normal values. Blood pressures before, during and after surgery were similar. No episodes of bradycardia nor hypotension were recorded. Laser treatment was always successful. CONCLUSION: The good level of anesthesia and analgesia achieved sustains the efficacy of sedation with propofol during laser photocoagulation to avoid intubation and mechanical ventilation during and after the procedure.

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7-19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.

Corrigendum to "Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy".

[This corrects the article DOI: 10.1155/2017/3080245.].

Optical coherence tomography and electrophysiological findings in torpedo maculopathy.

PURPOSE: To describe the morphofunctional findings in a 6-year-old child with a unilateral lesion of the temporal macula called "torpedo maculopathy" throughout a 1-year follow-up. METHODS: Evaluation of retinal morphology and function was assessed by means of spectral-domain OCT scans, best-corrected visual acuity, full-field flash electroretinogram (ERG), multifocal electroretinogram (mfERG) and pattern visual evoked potentials (VEP). Patient was examined every 4 months for a 1-year follow-up time. RESULTS: Torpedo maculopathy consisted in a sharply demarcated hypopigmented oval iuxta-macular lesion (1.5 DD wide × 0.7 DD high). The baseline visual acuity of the affected eye was 20/25. OCT showed a sensorial retinal detachment in correspondence with the torpedo lesion. Pattern VEPs revealed a reduced response in left eye, as compared to contralateral eye. Full-field flash ERGs amplitude was normal in both eyes. Multifocal ERG response was reduced at all sites, more significantly at the site of the lesion in the eye with torpedo maculopathy and normal in fellow eye. Visual acuity, fundoscopic evaluation, OCT scans and electrophysiological tests showed no changes from baseline throughout the follow-up time. CONCLUSIONS: Torpedo maculopathy, although known as benign, may affect visual function if macular involvement is associated with neuroretinal detachment.