The Royal College of Paediatrics and Child Health Retinopathy of Prematurity Screening Guidelines (2022): a series of treated infants falling outside the updated criteria.

BACKGROUND/OBJECTIVES: Screening for retinopathy of prematurity (ROP) is a core healthcare intervention in premature babies to avoid preventable sight loss. A variety of screening criteria are in place globally for this purpose. The Royal College of Paediatrics and Child Health recently updated the United Kingdom ROP screening guidelines (March 2022). A key change was the reduction in the gestational age (GA) to warrant retinal screening (from 32 to 31 weeks). SUBJECTS/METHODS: In the course of informal national surveillance during guideline development (2017-2022) and soon after, babies under our care falling outside the updated screening criteria who underwent treatment for ROP were identified. A retrospective case review was carried out. RESULTS: Six babies were identified as having undergone screening and treatment, prior to implementation of the new guidance. Screening and treatment would have been forfeited as per the March 2022 guidelines. All six had numerous systemic risk factors for developing ROP. Specifically, all had documented poor postnatal weight gain. CONCLUSIONS: We present this case series to bring forth an urgent discussion amongst key stakeholders as to whether the new guidance, as it stands, is safe and fit for purpose.

A nationwide evaluation of bevacizumab-based treatments in pediatric low-grade glioma in the UK: Safety, efficacy, visual morbidity, and outcomes.

BACKGROUND: Bevacizumab is increasingly used in children with pediatric low-grade glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger cohort "real life" safety and efficacy data including functional visual outcomes. METHODS: Children receiving bevacizumab-based treatments (BBT) for PLGG (2009-2020) from 11 centers were included. Standardized neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical-radiological correlation, survival outcomes and multivariate prognostic analysis. RESULTS: Eighty-eight children with PLGG received BBT either as 3rd line with irinotecan (85%) or alongside 1st/2nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3 yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (P = .03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilization (49%) of visual acuity was achieved, more often in patients' best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients' worst eyes. A superior visual outcome (P = .023) was seen in neurofibromatosis type 1-associated optic pathway glioma (OPG). Concordance between visual and radiological responses was 36%; optimized to 48% using only best eye responses. CONCLUSIONS: BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best > worst eye) than radiological response. Further research could optimize the role of BBT toward a potentially sight-saving strategy in OPG.

A Case of Morning Glory Disc Associated With Unilateral Retinopathy of Prematurity.

Morning glory disc anomaly is associated with serous retinal detachments, high refractive errors, amblyopia, and strabismus. There have been limited reports of an association between morning glory disc and peripheral retinal non-perfusion. The authors report a case of unilateral morning glory disc anomaly associated with markedly asymmetric retinopathy of prematurity. [J Pediatr Ophthalmol Strabismus. 2022;59(5):e55-e57.].

Contralateral effect of systemic absorption of low dose bevacizumab (Avastin) after unilateral intravitreal injection in severe retinopathy of prematurity (ROP).

An extremely premature baby boy born at 23 weeks' gestational age was treated with unilateral low dose of 0.16 mg/0.025 mL intravitreal bevacizumab in the left eye for aggressive retinopathy of prematurity (ROP). He developed photographically documented changes in his contralateral right eye on imaging 5 days later. Second eye treatment was at 12 days. He has development assessment and ophthalmic review beyond age 2, which is normal. Systemic absorption of the drug caused an end organ effect to slow down and reverse ROP in his untreated right eye. Both eyes vascularised fully. His normal Bayley III developmental score at age 2 is uncommon for a 23-week gestation baby. Even at a low dose, bevacizumab has the potential for end organ effect on the second eye, and therefore other organs. In this case, there are no medium-term measurable neurodevelopmental side-effects. We suggest longer term follow-up is required before excluding unwanted side-effects.

Ultra-low-dose intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case series.

BACKGROUND: Intravitreal bevacizumab (IVB) has emerged as an effective treatment modality for the management of retinopathy of prematurity (ROP) where the disease is severe and posterior. Despite evidence of systemic vascular endothelial growth factor suppression and concerns about how this might affect the developing neonate, the optimal dose is unknown to date. We report our experience of using ultra-low-dose (0.16 mg) IVB, one-quarter of the 'standard' dose that has widely been reported in the treatment of ROP. METHODS: A retrospective observational case series of consecutive infants who underwent ultra-low-dose IVB injection for the management of ROP at a regional neonatal intensive care unit in the North East of England, between November 2013 and August 2016. RESULTS: 29 eyes of 15 infants underwent IVB injection. We defined 'treatment success' as complete regression of retinopathy and vascularisation into (or laser ablation of) zone 3. Primary success (in response to IVB 0.16 mg alone) was observed in 23/29 eyes (79.3%). Secondary success (where additional treatment was required) was observed in 27/29 eyes (93.1%). One infant died of respiratory disease during follow-up. Retreatment occurred in 6/29 eyes (20.6%). Retreatments occurred at a mean of 9.8 weeks after initial IVB (range 6-15) and at a mean of 44 weeks postmenstrual age (range 40-50). CONCLUSION: 0.16 mg IVB is effective in the treatment of severe and posterior ROP, with no adverse ocular outcomes occurring in our series.

Ultra-low dose of intravitreal bevacizumab in the treatment of retinopathy of prematurity.

Intravitreal bevacizumab is an increasingly common treatment choice for posterior retinopathy of prematurity. Despite concern about its systemic effects, there have been few studies on the lowest effective dose. The authors describe a case that was successfully treated with 0.16 mg of bevacizumab, the first time this dose has been reported.

Interventions for infantile esotropia.

BACKGROUND: Infantile esotropia (IE) is the inward deviation of the eye. Various aspects of the clinical management of IE are unclear; mainly, the most effective type of intervention and the age at intervention. OBJECTIVES: The objective of this review was to assess the effectiveness of various surgical and non-surgical interventions for IE and to determine the significance of age at treatment with respect to outcome. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to June 2013), EMBASE (January 1980 to June 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 June 2013. We manually searched the conference proceedings of the European Strabismological Association (ESA) (1975 to 1997, 1999 to 2002), International Strabismological Association (ISA) (1994) and American Academy of Paediatric Ophthalmology and Strabismus meeting (AAPOS) (1995 to 2003). Efforts were made to contact researchers who are active in the field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised trials comparing any surgical or non-surgical intervention for infantile esotropia. DATA COLLECTION AND ANALYSIS: Each review author independently assessed study abstracts identified from the electronic and manual searches. MAIN RESULTS: No studies were found that met our selection criteria and therefore none were included for analysis. AUTHORS' CONCLUSIONS: The main body of literature on interventions for IE are either retrospective studies or prospective cohort studies. It has not been possible through this review to resolve the controversies regarding type of surgery, non-surgical intervention and age of intervention. There is clearly a need for good quality trials to be conducted in these areas to improve the evidence base for the management of IE.

Corneal endothelial dysfunction in Pearson syndrome.

Mitochondrial disorders are associated with well recognized ocular manifestations. Pearson syndrome is an often fatal, multisystem, mitochondrial disorder that causes variable bone marrow, hepatic, renal and pancreatic exocrine dysfunction. Phenotypic progression of ocular disease in a 12-year-old male with Pearson syndrome is described. This case illustrates phenotypic drift from Pearson syndrome to Kearns-Sayre syndrome given the patient's longevity. Persistent corneal endothelial failure was noted in addition to ptosis, chronic external ophthalmoplegia and mid-peripheral pigmentary retinopathy. We propose that corneal edema resulting from corneal endothelial metabolic pump failure occurs within a spectrum of mitochondrial disorders.

Monozygotic twins discordant for phacomatosis pigmentovascularis: evidence for the concept of twin spotting.

The term phacomatosis pigmentovascularis (PPV) refers to the occurrence of vascular nevi with melanocytic or epidermal nevi. We report on monozygotic twins (MZTs) discordant for phacomatosis cesioflammea (PPV type II) providing evidence for the mechanism of twin spotting in the development of PPV. The affected twin had a nevus flammeus on the right arm and the right maxilla, and a pigmented area on the trunk in keeping with a persistent, aberrant Mongolian spot. The affected twin had bilateral ocular melanocytosis with abnormal scleral pigmentation, iris mamillations, increased pigmentation of the trabecular meshwork, and increased fundal pigmentation and secondary glaucoma. DNA testing confirmed monozygosity. This case of MZTs discordant for PPV supports the hypothesis that PPV results from mosaicism due to a post-zygotic mutational event and the concept of twin spotting.

Postmortem orbital findings in shaken baby syndrome.

PURPOSE: To compare postmortem orbital findings in pediatric accidental head injury to Shaken Baby Syndrome (SBS). DESIGN: Retrospective study. SETTING: Institutional. STUDY POPULATION: Thirty-six patients underwent postmortem modified exenteration with sectioning of the orbital contents; 18 victims of SBS and 18 cases of fatal accidental head trauma. OBSERVATION PROCEDURE: In all cases of children who died from accidental head trauma, the orbital tissues were separated to expose the optic nerve sheath. Patients with gross evidence of hemorrhage within the sheath were included. All cases of SBS were included. After accidental head injury, exenteration was performed only if optic nerve sheath hemorrhage was suspected on gross examination. All children younger than 18 years old with head injury as primary cause of death were included. SBS is defined as having at least two of the following: (1) typical abnormal findings on neuroimaging, (2) typical skeletal injury, (3) retinal hemorrhages, (4) history of abusive shaking with or without blunt head trauma, or (5) an inadequate history to explain the observed injuries. MAIN OUTCOME MEASURE: Presence or absence of orbital hemorrhage. RESULTS: Orbital tissue injury is more common in SBS than accidental head trauma without orbital fracture. In addition, optic nerve sheath and optic nerve intradural hemorrhage are also significantly more common in SBS (P < .0001). CONCLUSIONS: Our study reports new evidence of injury to orbital tissues in SBS and supports the concept that these finding are due to unique acceleration-deceleration forces of this type of abusive head injury.

CRYBB1 mutation associated with congenital cataract and microcornea.

PURPOSE: The molecular characterization of a UK family with an autosomal dominant congenital cataract associated with microcornea is reported. METHODS: Family history and clinical data were recorded. This phenotype was linked to a 7.6 cM region of chromosome 22q11.2-q12.2, spanning the beta-crystallin gene cluster (ZMax of 3.91 for marker D22S1114 at theta=0). Candidate genes were PCR amplified and screened for mutations on both strands using direct sequencing. RESULTS: Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of CRYBB1. SSCP analysis confirmed that this sequence change segregated with the disease phenotype in all available family members and was not found in 109 ethnically matched controls. CONCLUSIONS: X253R is predicted to elongate the COOH-terminal extension of the protein and would be expected to disrupt beta-crystallin interactions. This is the first documented involvement of CRYBB1 in ocular development beyond cataractogenesis.

Surgical outcome for removal of subfoveal choroidal neovascular membranes in children.

OBJECTIVE: To asses the surgical outcome of subfoveal choroidal neovascular membranes in children. METHODS: Two eyes with Best disease and one with idiopathic subfoveal choroidal neovascular membrane underwent vitrectomy and extraction of the subfoveal neovascular membrane. RESULTS: All the three eyes had significant improvement in their visual acuity and there was no recurrence of choroidal neovascular membrane. CONCLUSION: Surgical removal of subfoveal choroidal neovascular membrane in children carries good visual prognosis in selected cases.