Defects in the Cell Signaling Mediator ß-Catenin Cause the Retinal Vascular Condition FEVR.

Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder characterized by the abnormal development of the retinal vasculature. The majority of mutations identified in FEVR are found within four genes that encode the receptor complex (FZD4, LRP5, and TSPAN12) and ligand (NDP) of a molecular pathway that controls angiogenesis, the Norrin-ß-catenin signaling pathway. However, half of all FEVR-affected case subjects do not harbor mutations in these genes, indicating that further mutated genes remain to be identified. Here we report the identification of mutations in CTNNB1, the gene encoding ß-catenin, as a cause of FEVR. We describe heterozygous mutations (c.2142_2157dup [p.His720∗] and c.2128C>T [p.Arg710Cys]) in two dominant FEVR-affected families and a de novo mutation (c.1434_1435insC [p.Glu479Argfs∗18]) in a simplex case subject. Previous studies have reported heterozygous de novo CTNNB1 mutations as a cause of syndromic intellectual disability (ID) and autism spectrum disorder, and somatic mutations are linked to many cancers. However, in this study we show that Mendelian inherited CTNNB1 mutations can cause non-syndromic FEVR and that FEVR can be a part of the syndromic ID phenotype, further establishing the role that ß-catenin signaling plays in the development of the retinal vasculature.

A simple modification to the 25-gauge trocar and cannula system for retinopathy of prematurity related lens-sparing vitrectomy.

BACKGROUND: Recently, 25-gauge vitrectomy has become more popular. However, most still perform the surgery in pediatric patients without the use of the trocars and cannulas as in adult vitrectomies. METHODS: We described a simple modification using adult 25-gauge cannulas and 270-silicone watzke sleeves, enabling these instruments to be used in pediatric cases. The sleeve is cut into segments of 2 mm in length, and then introduced up the shaft of the 25-gauge trocar. One is introduced first, and a second one is introduced on top of the first one. This secures the two sleeves on the shaft of the trocar, such that they act as a spacer. The effective shaft of the trocar was then reduced to 2 mm in length. RESULTS: This method enabled successful surgery in two cases. CONCLUSIONS: This allows the adaptation of the standard 25-gauge system for pediatric cases with only the slightest modification needed.

Three different ophthalmic presentations of juvenile xanthogranuloma.

Three cases of juvenile xanthogranuloma from two ophthalmology departments were reviewed. Clinical histories, ophthalmic examination, physical examination, investigations, and treatment of these cases are described. A 4-month-old boy presented with spontaneous hyphema and secondary glaucoma. He was treated with intensive topical steroid and anti-glaucomatous eye drops. The hyphema gradually resolved and the intra-ocular pressure reverted to 11 mm Hg without any other medication. Biopsy of his scalp mass confirmed the diagnosis of juvenile xanthogranuloma. A 31-month-old boy presented with a limbal mass. Excisional biopsy of the mass was performed and confirmed it was a juvenile xanthogranuloma. A 20-month-old boy was regularly followed up for epiblepharon and astigmatism. He presented to a paediatrician with a skin nodule over his back. Skin biopsy confirmed juvenile xanthogranuloma. He had no other ocular signs. Presentation of juvenile xanthogranuloma can be very different, about which ophthalmologists should be aware of. Biopsy of the suspected lesion is essential to confirm the diagnosis.

Prediction model to predict type 1 retinopathy of prematurity using gestational age and birth weight (PW-ROP).

PURPOSE: To develop a prediction model for type 1 retinopathy of prematurity (ROP) from an Asian population. METHODS: This retrospective cohort study included 1043 premature infants who had ROP screening in a tertiary hospital in Hong Kong from year 2006 to 2018. The ROP prediction model was developed by multivariate logistic regression analyses on type 1 ROP. The cut-off value and the corresponding sensitivity and specificity were determined by receiver operating characteristic curve analysis. A validation group of 353 infants collected from another tertiary hospital in another region of Hong Kong from year 2014 to 2017 was used for external validation. RESULTS: There were 1043 infants in the study group. The median gestational age (GA) was 30 weeks and 1 day and median birth weight (BW) was 1286 g. The prediction model required only GA and BW as parameters (prematurity-birth weight ROP (PW-ROP)). The area under curve value was 0.902. The sensitivity and specificity were 87.4% and 79.3%, respectively. Type 1 ROP developed in 0.9%, 17.4% and 50% of infants with PW-ROP scores<0, between 0 and <300, and ≥300 respectively (p<0.001). On external validation, our prediction model correctly predicted 95.8% of type 1 ROP (sensitivity=95.8%, specificity=74.8%) in the validation group. CONCLUSION: The PW-ROP model is a simple model which could predict type 1 ROP with high sensitivity and specificity. Incorporating this model to ROP examination would help identify infants at risk for ROP treatment.

Change in vision disorders among Hong Kong preschoolers in 10 years.

BACKGROUND: To determine the change in refractive error and the prevalence of amblyopia and strabismus among preschool children in Hong Kong over a period of 10 years. DESIGN: Two cross-sectional population-based studies conducted in 1996 to 1997 (part A) and 2006 to 2007 (part B) PARTICIPANTS: Children attending randomly selected kindergarten participated in the study. METHODS: Ocular alignment, visual acuity, cover and uncover tests, cycloplegic refraction, slit-lamp and fundi examination were performed under a standardized testing environment. MAIN OUTCOME MEASURES: The prevalence of amblyopia (best-corrected visual acuity ≤6/12 in one or both eyes, or a bilateral difference of ≥2 best-corrected visual acuity lines), strabismus and significant refractive error (hyperopia ≥+2.50 D; myopia ≥-1.00 D; astigmatism ≥2.00 D) among preschool children. RESULTS: Of the 601 children in part A of the study, reduced visual acuity was presented in 3.8%; whereas strabismus was found in 1.8%. The commonest type of refractive error was astigmatism in 6.3% of children, followed by hyperopia (5.8%) and myopia (2.3%). Among 823 children in part B, reduced visual acuity was presented in 2.7% of children, and strabismus was found in 1.7%. The commonest type of refractive error was myopia (6.3%), followed by astigmatism (5.7%) and hyperopia (5.1%). The percentage of children having myopia has significantly increased (P = 0.001). CONCLUSION: A significant increase in myopia has been noted in Hong Kong preschoolers. Visual screening programmes may need to be tailored to correspond to the local population and be adjusted accordingly from time to time.

Deep Learning Algorithm for Automated Diagnosis of Retinopathy of Prematurity Plus Disease.

PURPOSE: This study describes the initial development of a deep learning algorithm, ROP.AI, to automatically diagnose retinopathy of prematurity (ROP) plus disease in fundal images. METHODS: ROP.AI was trained using 6974 fundal images from Australasian image databases. Each image was given a diagnosis as part of real-world routine ROP screening and classified as normal or plus disease. The algorithm was trained using 80% of the images and validated against the remaining 20% within a hold-out test set. Performance in diagnosing plus disease was evaluated against an external set of 90 images. Performance in detecting pre-plus disease was also tested. As a screening tool, the algorithm's operating point was optimized for sensitivity and negative predictive value, and its performance reevaluated. RESULTS: For plus disease diagnosis within the 20% hold-out test set, the algorithm achieved a 96.6% sensitivity, 98.0% specificity, and 97.3% ± 0.7% accuracy. Area under the receiver operating characteristic curve was 0.993. Within the independent test set, the algorithm achieved a 93.9% sensitivity, 80.7% specificity, and 95.8% negative predictive value. For detection of pre-plus and plus disease, the algorithm achieved 81.4% sensitivity, 80.7% specificity, and 80.7% negative predictive value. Following the identification of an optimized operating point, the algorithm diagnosed plus disease with a 97.0% sensitivity and 97.8% negative predictive value. CONCLUSIONS: ROP.AI is a deep learning algorithm able to automatically diagnose ROP plus disease with high sensitivity and negative predictive value. TRANSLATIONAL RELEVANCE: In the context of increasing global disease burden, future development may improve access to ROP diagnosis and care.

An in vitro comparison of ultraviolet versus white light in the detection of adhesive remnants during orthodontic debonding.

OBJECTIVES: To assess the effectiveness and efficiency of ultraviolet (UV) illumination compared to conventional white light in the detection of fluorescent-tagged adhesive remnants during orthodontic debonding. MATERIALS AND METHODS: Orthodontic brackets were bonded to extracted human premolars using one of two bonding resins having fluorescent properties (Pad Lock, Reliance Orthodontics, Itasca, Ill; Opal Bond MV, Opal Orthodontics, South Jordan, Utah; n = 40 each). The brackets were then debonded and, in each adhesive group, half the teeth had the remaining adhesive resin removed under illumination using the operatory light and the other half using a UV (395 nm) light emitting diode (LED) flashlight (n = 20/group). Time for teeth cleanup was recorded. Follow-up images were obtained under a dissecting microscope using UV illumination, and the surface area of adhesive remnants was calculated. Effectiveness of adhesive removal was also assessed using scanning electron microscopy imaging. Analysis of variance and Kruskal-Wallis tests were used to analyze time and adhesive remnants, respectively. RESULTS: Assessment using the dissecting microscope found groups using UV light during adhesive removal had statistically significantly lower amounts of adhesive remnants than groups using white light (P ≤ .01). Time for adhesive removal was significantly lower with Opal Bond MV adhesive using UV light when compared with the white light (P ≤ .01). Assessment by scanning electron microscopy showed that thin remnants of adhesive (<2 µm) remained undetected by UV illumination. CONCLUSIONS: UV light is more effective and tends to be more efficient than white light in the detection of fluorescent adhesive during orthodontic debonding. Although there are limitations, the use of UV LED lighting is a practical tool that aids in adhesive detection.

Effects of orthodontic appliances on the diagnostic capability of magnetic resonance imaging in the head and neck region: A systematic review.

OBJECTIVES: Patients in active fixed orthodontic treatment or fixed retention phase may require magnetic resonance (MR) scans of the head and neck region. Orthodontists are challenged to decide whether to keep or remove orthodontic appliances prior to the scans. The aim of this study was to determine the effect of orthodontic appliances on the diagnostic capability of MR images. METHODS: Four electronic databases were searched, with no language restrictions, from database inception to October 2016: PubMed, EMBASE, CINAHL, EBMR. A search in Google Scholar and ProQuest, as well as a manual search, were also conducted. Two independent reviewers assessed articles for inclusion. Original studies including any orthodontic appliance on human subjects were considered. Outcomes measured were development of artefacts, diagnostic quality, accuracy, and treatment outcomes. Risk of bias was assessed with the Cochrane Risk of Bias Assessment and QUADAS-2 tools. RESULTS: Five of 1052 studies identified were included in the final qualitative synthesis. A total of 90 adult human subjects were included. Orthodontic appliances evaluated were brackets, bands, archwires, and fixed retainers. The outcomes assessed were production of artefacts, diagnostic quality and diagnostic accuracy. Detrimental effects on diagnostic quality, and subsequently diagnostic accuracy, rose with increased stainless steel (SS) and proximity to anatomic area of interest. Orthodontic appliances may render images uninterpretable and non-diagnostic. CONCLUSIONS: There is fair evidence to suggest orthodontic appliances, mainly those with SS, cause MR artefacts. Removal of metal orthodontic appliances prior to MR scans is recommended, especially if the area of interest is near the orthodontic appliance. Additional evidence is needed to provide guidelines to clinicians.

ExPRESS Mini-Shunt as a Treatment Alternative for Medically Uncontrolled Steroid-Induced Glaucoma in a Pediatric Patient.

This case report illustrates the use of ExPRESS mini-shunt in a pediatric glaucoma patient. We describe the management of steroid-induced glaucoma with ExPRESS mini-shunt in a 9-year-old boy with allergic keratoconjunctivitis. The intraocular pressure of both of his eyes was uncontrolled with medical and laser treatment. Both eyes were treated with ExPRESS mini-shunt and mitomycin-C. Transient overfiltration with postoperative hypotony occurred in both eyes and resolved after 2 weeks. One year postoperatively, intraocular pressure was maintained below 21 mm Hg without medication in 1 eye. Bleb needling with mitomycin-C was done to maintain filtration. The fellow eye received cataract extraction but developed bleb failure a few months afterwards. The intraocular pressure was controlled medically. To conclude, ExPRESS mini-shunt is a new surgical option in selected patients. Bleb failure developed after cataract extraction. Postoperative inflammation should be minimized. Patient selection, such as those with stable ocular condition, is important to increase surgical success.

Bilateral exudative retinal detachments as the presenting features of idiopathic orbital inflammation.

Idiopathic orbital inflammation, also known as orbital pseudotumour, is a term describing a spectrum of idiopathic, non-neoplastic, non-infectious, space-occupying orbital lesion without identifiable local or systemic cause. This disease occurs mainly in young adults and typically presents with acute proptosis, chemosis and limited extraocular movement. Herein an unusual case of idiopathic orbital inflammation presenting with bilateral exudative retinal detachment in a 9-year-old girl is described. It demonstrates that prompt diagnosis and corticosteroid treatment can yield good clinical response and significant visual recovery.