Evaluation of IOL power calculation with the Kane formula for pediatric cataract surgery.

PURPOSE: To assess the accuracy of the Kane formula for intraocular lens (IOL) power calculation in the pediatric population. METHODS: The charts of pediatric patients who underwent cataract surgery with in-the-bag IOL implantation with one of two IOL models (SA60AT or MA60AC) between 2012 and 2018 in The Hospital for Sick Children, Toronto, Ontario, CanFada, were retrospectively reviewed. The accuracy of IOL power calculation with the Kane formula was evaluated in comparison with the Barrett Universal II (BUII), Haigis, Hoffer Q, Holladay 1, and Sanders-Retzlaff-Kraff Theoretical (SRK/T) formulas. RESULTS: Sixty-two eyes of 62 patients aged 6.2 (IQR 3.2-9.2) years were included. The SD values of the prediction error obtained by Kane (1.38) were comparable with those by BUII (1.34), Hoffer Q (1.37), SRK/T (1.40), Holaday 1 (1.41), and Haigis (1.50), all p > 0.05. A significant difference was observed between the Hoffer Q and Haigis formulas (p = 0.039). No differences in the median and mean absolute errors were found between the Kane formula (0.54 D and 0.91 ± 1.04 D) and BUII (0.50 D and 0.88 ± 1.00 D), Hoffer Q (0.48 D and 0.88 ± 1.05 D), SRK/T (0.72 D and 0.97 ± 1.00 D), Holladay 1 (0.63 D and 0.94 ± 1.05 D), and Haigis (0.57 D and 0.98 ± 1.13 D), p = 0.099. CONCLUSION: This is the first study to investigate the Kane formula in pediatric cataract surgery. Our results place the Kane among the noteworthy IOL power calculation formulas in this age group, offering an additional means for improving IOL calculation in pediatric cataract surgery. The heteroscedastic statistical method was first implemented to evaluate formulas' predictability in children.

Genome sequencing for detection of pathogenic deep intronic variation: A clinical case report illustrating opportunities and challenges.

Variants in JAM3 have been reported in four families manifesting a severe autosomal recessive disorder characterized by hemorrhagic destruction of the brain, subependymal calcification, and cataracts. We describe a 7-year-old male with a similar presentation found by research-based quad genome sequencing to have two novel splicing variants in trans in JAM3, including one deep intronic variant (NM_032801.4: c.256+1260G>C) not detectable by standard exome sequencing. Targeted sequencing of RNA isolated from transformed lymphoblastoid cell lines confirmed that each of the two variants has a deleterious effect on JAM3 mRNA splicing. The role for genome sequencing as a clinical diagnostic test extends to those patients with phenotypes strongly suggestive of a specific Mendelian disorder, especially when the causal genetic variant(s) are not found by a more targeted approach. Barriers to diagnosis via identification of pathogenic deep intronic variation include lack of laboratory consensus regarding in silico splicing prediction tools and limited access to clinically validated confirmatory RNA experiments.

Natural history and outcomes of stage 3 retinopathy of prematurity persisting beyond 40 weeks of post-menstrual age: Dilemma for treatment and follow up.

IMPORTANCE: To evaluate the natural history and outcomes of infants with stage-3 retinopathy of prematurity (ROP) persisting beyond 40-weeks of post-menstrual age (PMA). BACKGROUND: There are no specific screening guidelines for stage-3 ROP persisting beyond 40 weeks of PMA. Persistent stage-3 disease in zone II without plus disease or in zone III with or without plus disease poses a dilemma for treatment. DESIGN: Retrospective chart review. PARTICIPANT: Neonates with stage-3 ROP persisting beyond 40-weeks of PMA. METHODS: Demographic data and ROP parameters were collected. Univariate/multivariate analyses were utilized to assess risk factors associated with requiring treatment. MAIN OUTCOME MEASURES: Evaluating the structural outcomes for infants with stage-3 ROP persisting beyond 40 weeks of PMA. RESULTS: Out of 2356 screened infants, 115 infants (4.9%, 172 eyes) met inclusion criteria. In 95 infants (139 eyes, 80.8%), ROP resolved spontaneously. Twenty-one infants (33 eyes, 19.2%) were treated with laser-photocoagulation; 16 eyes had reached type 1 ROP and 17 eyes had non-type 1 ROP. No eye had unfavourable structural outcome. On multiple regression, non-type 1 ROP with ≥2 continuous clock hours of persistent stage-3 temporally crossing the horizontal midline was a significant risk factor associated with receiving treatment (OR = 27.29, 95% CI = [1.61, 462.92], P = .0221). CONCLUSION AND RELEVANCE: The majority of stage-3 ROP persisting beyond 40-weeks of PMA resolve spontaneously. In eyes that do not reach type 1 ROP, ≥2 continuous clock hours of persistent stage-3 crossing the temporal horizontal midline and history of pre-plus were considered important risk factors for macular drag and treatment can be considered.

Newborn with bilateral congenital cataracts: Never forget congenital rubella syndrome.

A term, growth-restricted newborn presented with a sepsis-like picture, persistent pulmonary hypertension and bilateral cataracts. Initial review of prenatal and family history, as well as microbiological investigations were noncontributory. Following lenticular extraction, viral examination of the lenses confirmed the presence of rubella. Congenital rubella syndrome (CRS) presents with a constellation of signs and symptoms that overlap with many other conditions. The presence of bilateral cataracts in a newborn is a rare finding and this case is used to review the broad etiology of congenital cataracts. We propose a structured diagnostic approach for clinicians, remembering that CRS is a rare but possible etiology. The early diagnosis of CRS in this case, allowed us to initiate appropriate management and preventive measurements.

Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy.

Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family. We gathered five additional families with eight affected individuals through the Matchmaker Exchange initiative by matching autosomal-recessive mutations in AP3B2. Reverse phenotyping of 12 affected individuals from eight families revealed a homogeneous EOEE phenotype characterized by severe developmental delay, poor visual contact with optic atrophy, and postnatal microcephaly. No spasticity, albinism, or hematological symptoms were reported. AP3B2 encodes the neuron-specific subunit of the AP-3 complex. Autosomal-recessive variations of AP3B1, the ubiquitous isoform, cause Hermansky-Pudlak syndrome type 2. The only isoform for the δ subunit of the AP-3 complex is encoded by AP3D1. Autosomal-recessive mutations in AP3D1 cause a severe disorder cumulating the symptoms of the AP3B1 and AP3B2 defects.

The effect of a single anti-Vascular Endothelial Growth Factor injection on neonatal growth and organ development: In-vivo study.

Retinopathy of prematurity (ROP) is one of the leading causes of blindness in preterm Infants. Anti-vascular endothelial growth factor (VEGF) is emerging as a promising treatment, but there is insufficient evidence on their safety. We investigate the effect of systemic anti-VEGF in rat pups with equivalent maturity to a 32 week neonate. A single dose of either anti-VEGF antibody (n = 7) or saline (control group; n = 6) was administered to newborn rats intra-peritoneally on the first day of life. 14 days' post treatment, the serum concentration of anti-VEGF was measured and the brain, lung, heart, kidney and liver were harvested and weighed. The heart was processed to measure the Fulton index (a surrogate for pulmonary hypertension). All other organs were processed for mRNA expression of VEGF and VEGF-receptors (R1&R2). No group differences in body and organ weights were noted. The anti-VEGF was still detected in serum 14 days post Injection and resulted in increase in lung (p < 0.002) and kidney (p < 0.01) VEGF mRNA expressions and the lung (p < 0.02) VEGF-R1 and kidney (P < 0.001) VEGF-R2 mRNA expressions. The treated pups exhibited increased total heart weight (p < 0.01) and Fulton Index (p < 0.05). No changes were seen in the liver and brain. Anti-VEGF antibody did not affect mortality, total body and organ weights, but was associated with pulmonary hypertension. Expression of lung and kidney VEGF and its receptors was increased, whilst the brain and liver did not show changes. Dosing experiments can now be targeted to assess safety threshold and at anti-VEGF dose used in human ROP treatment.

Expanding the clinical spectrum of ocular anomalies in Noonan syndrome: Axenfeld-anomaly in a child with PTPN11 mutation.

Ocular anomalies have been frequently reported in Noonan syndrome. Anterior segment anomalies have been described in 57% of PTPN11 positive patients, with the most common findings being corneal changes and in particular, prominent corneal nerves and cataracts. We report on a neonate with a confirmed PTPN11 mutation and ocular findings consistent with Axenfeld anomaly. The patient initially presented with non-immune hydrops and subsequently developed hypertrophic cardiomyopathy and dysmorphic features typical of Noonan syndrome. While a pathogenic mutation in PTPN11 was confirmed, prior testing for the two common genes associated with Axenfeld-Rieger syndrome, PITX2, and FOXC1 was negative. This finding expands the spectrum of anterior chamber anomalies seen in Noonan syndrome and perhaps suggests a common neural crest related mechanism that plays a critical role in the development of the eye and other organs.

Nonsurgical Consecutive Exotropia Following Childhood Esotropia: A Multicentered Study.

PURPOSE: Nonsurgical consecutive exotropia (NCX) occurs when an esotropia (ET) spontaneously converts to exotropia (XT) without surgical intervention. Although NCX is considered to occur in early-onset accommodative ET with high hyperopia, consensus on causation is lacking. We report the clinical characteristics of NCX and assess the response to conservative management. DESIGN: Retrospective, multicenter, observational case series. METHODS: Patients aged 6 months and older with an initial diagnosis of ET who converted to XT without surgical intervention. Sensory strabismus was excluded. Age, visual acuity, cycloplegic refraction, glasses prescriptions, deviation, and binocular vision were collected. RESULTS: Forty-nine children were included with a mean age of 3.5 ± 1.6 years and 8.4 ± 3.6 years at the time of ET and NCX, respectively. Mean refractive error was +4.40 ± 2.13 diopters (D) and +4.05 ± 2.74 D at the time of ET and NCX, respectively. Accommodative ET occurred in 60% of cases, and only 35.7% were high hyperopes. All but 1 patient presented with XT at distance. In response to the XT, a mean decrease in hyperopic prescription of 1.55 ± 0.48 D was given (N = 17); only 1 case reverted to ET. Eventually, 43% underwent XT surgery, with similar rates between those who had refractive management and those who did not. CONCLUSIONS: NCX occurs in both accommodative and nonaccommodative ET; high hyperopia is present in only one-third of cases. On average, drift to XT occurs within 5 years. Refractive management has a modest result. No predictive risk factors were identified. Our findings challenge hyperopia-linked theories of causation. Nonrefractive explanations, such as the role of the vergence system, deserve further study.

Efficacy of the Subtenon Block in Children Undergoing Strabismus Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: To investigate the efficacy of the subtenon block in preventing postoperative complications in children undergoing strabismus surgery. DESIGN: Systematic review and meta-analysis. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Scopus, Web of Science, and clinicaltrials.gov. All randomized controlled trials investigating the efficacy of the subtenon block in children undergoing strabismus surgery were included. Outcomes included severity of pain after surgery, number of children requiring postoperative opioid and nonopioid analgesia, and the incidences of postoperative nausea and vomiting, oculocardiac events, and block-related complications. We pooled continuous outcomes using a random-effects model to calculate the mean difference (MD) and/or standardized MD and corresponding 95% confidence intervals (CI). Dichotomous outcomes were pooled using a random-effect model to calculate the relative risk (RR) and corresponding 95% CI. Risk of bias was assessed using the Cochrane Risk of Bias instrument and quality of evidence was assessed using a Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Nine randomized controlled trials (607 participants) were included. We found evidence for an effect of the subtenon block in reducing pain at 20 to 40 minutes after surgery (MD -1.9, 95% CI -2.2 to -1.5; high-quality evidence) and on admission to PACU (MD -1.8, 95% CI -2.2 to -1.4; moderate-quality evidence); however, there was no difference in pain scores at 6 hours after surgery. In addition, evidence was found that the subtenon block decreased the number of children requiring postoperative opioid (RR 0.59, 95% CI 0.37-0.92; high-quality evidence) and nonopioid (RR 0.52, 95% CI 0.27-0.98; moderate-quality evidence) analgesia, and the incidences of postoperative vomiting (RR 0.31, 95% CI 0.12-0.7; high-quality evidence) and intraoperative oculocardiac events (RR 0.40, 95% CI 0.26-0.60; high-quality evidence). Other secondary outcomes had low or moderate-quality evidence. Risk of bias was low in six trials and high in three. There were no reports of block-related complications. CONCLUSIONS: Our findings suggest that the subtenon block reduces the severity of early postoperative pain and the incidences of postoperative vomiting and intraoperative oculocardiac events compared with controls in children undergoing strabismus surgery. REVIEW REGISTRATION: PROSPERO (CRD42015025443).

Pre-term Familial Exudative Vitreoretinopathy: A Novel Nonsense LRP5 Mutation.

PURPOSE: This case report details the diagnosis and management of a pre-term infant with aggressive bilateral retinal pathology. METHODS: A 4-week-old preterm baby girl, born at 28 weeks and 6 days to consanguineous parents, was referred for suspected aggressive posterior retinopathy of prematurity (ROP). She had a family history of bilateral retinal detachments and intellectual disability in an older sister. Clinical assessment included retinal examination, fluorescein angiography, optical coherence tomography, dual-energy X-ray absorptiometry (DEXA), and genetic testing. The genetic testing involved sequence analysis and copy number variation analysis of 25 genes related to vitreoretinopathy. RESULTS: Retinal examination and fluorescein angiography revealed extensive non-perfusion and telangiectatic vessels in both eyes, and a macula-involving tractional retinal detachment in the left eye. Despite treatment with intravitreal bevacizumab and laser photocoagulation, they progressed to total retinal detachment and no light perception in both eyes. Genetic testing revealed a pathogenic homozygous nonsense mutation in the LRP5 gene (c.3259C>T, p.(Gln1087*)), a mutation not previously reported in association with familial exudative vitreoretinopathy (FEVR). At 10 months of age, DEXA demonstrated normal bone density, diverging from the typical presentation of osteoporosis pseudoglioma syndrome associated with LRP5 mutations. CONCLUSION: This case describes a novel mutation in a complex retinal disease and underscores the necessity of considering pre-term FEVR in the differential diagnosis of atypical or aggressive ROP in preterm infants. The overlap in clinical features between ROP and FEVR highlights the complexity of diagnosis and management and the importance of genetic testing in preterm infants with retinal vascular abnormalities.

A Comprehensive Evaluation of 16 Old and New Intraocular Lens Power Calculation Formulas in Pediatric Eyes.

Purpose: To compare the accuracy of 16 intraocular lens (IOL) power calculation formulas in pediatric cataract eyes. Patients and Methods: The data records of pediatric patients who had been implanted with three IOL models (SA60AT, MA60AC, and enVista-MX60) between 2012 and 2018 were analyzed. The accuracy of 16 IOL power calculation methods was evaluated: Barrett Universal II (BUII), Castrop, EVO 2.0, Haigis, Hill-RBF 3.0, Hoffer Q, Hoffer QST, Holladay 1, Kane, LSF AI, Naeser 2, Pearl-DGS, SRK/T, T2, VRF, and VRF-G. The non-optimized (ULIB/IOLcon) and optimized constants were used for IOL power calculation. The mean prediction error (PE), Performance Index (FPI), and all descriptive statistics were calculated. Results: Ninety-seven eyes of 97 pediatric patients aged 13.2 (IQR 11.2-17.1) were included. No statistically significant difference (HS-test) was observed (p > 0.818) except for the Hoffer Q, and Naeser 2 (P = 0.014). With optimized lens constants, the best FPI indices were obtained by Hoffer Q (0.256) and VRF-G (0.251) formulas, followed by Hill-RBF 3.0 and BUII, with an index of 0.248. The highest FPI indices with non-optimized constants showed SRK/T and T2 formulas (0.246 and 0.245, respectively), followed by VRF-G and Holladay 1, with an index of 0.244. The best median absolute error values (MedAE) were achieved by Hoffer Q (0.50 D), VRF-G (0.53 D), and Hill-RBF 3.0 (0.54 D), all P ≥ 0.074. Conclusion: Our results place the Hoffer Q, VRF-G, Hill-RBF 3.0, and BUII formulas as more accurate predictors of postoperative refraction in pediatric cataract surgery.

Controversies in ocular trauma classification and management: review.

Ocular trauma is a topic of unresolved controversies and there are continuous controversial and debatable management strategies for open-globe injuries (OGIs). International classification of ocular trauma proposed almost 15 years ago needs to be reviewed and to be more robust in predicting the outcome in the setting of OGIs. Anterior segment trauma involves controversies related to patching for corneal abrasion, corneal laceration repair, and medical management of hyphema. Timing of cataract surgery and intraocular lens implantation in the setting of trauma is still debated worldwide. There are unresolved issues regarding the management of OGIs involving the posterior segment. Timing of vitrectomy has been and will continue to be debated by proponents of early versus delayed intervention. The use of prophylactic cryotherapy and scleral buckle is still practiced differently throughout the world. The role of intravitreal antibiotics in posterior segment trauma in the absence of infection is still debated. Similarly, the use of vitrectomy versus vitreous tap in the setting of traumatic endophthalmitis is not fully resolved. In optic neuropathy, the role of intravenous methylprednisolone versus conservative management is always debated and still there are no evidence-based guidelines about the beneficial role of pulse steroid therapy. The role of optic canal decompression in the setting of acute traumatic optic neuropathy is also not conclusive. Orbital and adnexal trauma has been shown to adversely affect the outcome of OGI patients but both lids and orbital injury are not taken as preoperative variables in international ocular trauma classification. The timing of intervention in blow-out fracture is still debated. The pediatric age group, owing to the high risk of amblyopia and intraocular inflammation as well as strong vitreoretinal adhesions, has to be managed by different principles. Although the risk of sympathetic ophthalmia is very rare, it is always one of the key debated issues while managing traumatized eyes with no light perception vision. Prospective, controlled clinical studies are not possible in the OGI setting and this article reviews pertinent data regarding these management issues and controversies, and provides recommendations for treatment based on the available published data and the authors' personal experience.

Subdural hemorrhages and severe retinal hemorrhages in a short fall with a rotational component.

We present the case of a 5-month-old referred for child abuse investigation with subdural hemorrhages and extensive retinal hemorrhages following a short fall from a swivel chair seen on video footage. Subdural hemorrhages with extensive retinal hemorrhages are not typically seen as the result of short household falls. Reviewing the footage, contributing factors may have included increased rotational and deceleration forces.

Outcomes of cataract surgery in children who present with cataract at uveitis diagnosis.

PURPOSE: To describe the clinical and demographic characteristics of patients presenting with cataract at uveitis diagnosis treated at a single institution between 2005 and 2019 and to analyze postoperative outcomes following cataract surgery. METHODS: We retrospectively reviewed the medical records of children (<18 years of age) diagnosed with cataract at their initial uveitis presentation who subsequently underwent cataract extraction. Outcome measures were best-corrected visual acuity, number of uveitis flare-ups (cells ≥1+), and postoperative complications. RESULTS: A total of 14 children (17 eyes) were included. Mean patient age was 7.2 ± 3.9 years. Methotrexate was initiated preoperatively in 11 patients; adalimumab, in 3. Primary intraocular lens was implanted in 4 eyes. Best-corrected visual acuity improved from a mean of 0.90 ± 0.40 logMAR preoperatively to 0.50 ± 0.35 logMAR at 1 year and 0.57 ± 0.40 logMAR at mean of 6.3 ± 3.4 years postoperatively. Four eyes (24%) had a single episode of uveitis flare-up during the first postoperative year. Macular and/or disk edema was discovered in 6 eyes following cataract removal. Only 3 eyes (18%) had ocular hypertension in the first year, but glaucoma developed in subsequent years in 7 eyes (41%), 5 of which required surgery. CONCLUSIONS: In our study cohort, surgery for preexisting cataract at uveitis diagnosis resulted in improved visual acuity. Postoperative uveitis flare-ups were relatively uncommon, occurring in 4 of 17 eyes. Glaucoma was the main long-term complication.

Rise in the incidence of severe pediatric blepharokeratoconjunctivitis during the COVID-19 pandemic.

Severe blepharokeratoconjunctivitis (BKC) is associated with vision loss and ocular morbidity; hence, early diagnosis and treatment are crucial. Retrospective data collection using electronic patient and billing database records of all patients <18 years of age with severe BKC between March 2010 and March 2022 was performed at the Eye Clinic at the Hospital for Sick Children in Toronto, Canada. Severe BKC was defined as including corneal inflammation, new vessel formation, scarring, thinning and lipid deposits. We excluded patients with mild or no corneal involvement, and those with other corneal pathologies. Over the study period, 257 patients were diagnosed with severe BKC (161 females), with an average age of 8 years. There was a statistically significant threefold increase in the diagnosis of severe BKC since the beginning of the COVID-19 pandemic in 2020 compared to the previous years. We speculate that the increased use of facial masks during the pandemic contributed to this significant increase.

Bilateral keratouveitis associated with COVID-19 multisystem inflammatory syndrome in children.

We report the case of a 16-year-old girl admitted to hospital with multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19. Conjunctivitis-like symptoms prompted ocular examination, which demonstrated peripheral confluent corneal opacities and anterior uveitis. Uveitis laboratory investigations were negative, and with topical steroid treatment her signs and symptoms resolved completely. These features may be overlooked in the setting of MIS-C, where patients are systemically unwell and are typically examined at the bedside.

Children with high astigmatism: tomographic and refractive characteristics and the ability of current indices to rule out keratoconus.

PURPOSE: To assess corneal tomographic, topographic, and refractive changes in children with high astigmatism and their ability to exclude keratoconus. METHODS: In this longitudinal observational study, the medical records of children with high regular cylindrical refraction of ≥3.50 D referred to the Hospital for Sick Children, Toronto, to exclude keratoconus between January 2009 and June 2020 were reviewed retrospectively. Corneal tomography records (Scheimpflug imaging) were reviewed for subjects with total astigmatism of ≥ +3.50 D by retinoscopy. Children with abnormal anterior segment examination and/or other risk factors for corneal disease or ectasia and those with unreliable corneal tomography were excluded. Baseline demographic, longitudinal tomographic, topographic, and refractive data were analyzed. RESULTS: A total of 67 eyes of 37 children (mean age, 9.1 ± 3.5 years) were included. Mean cylindrical refraction at presentation was 5.10 ± 1.30 D. Mean follow-up was 2.3 ± 1.8 years. Twenty-nine eyes had Kmax ≥47.20 D at baseline, with no change at last follow-up. Ksteep, Kmax, and thinnest pachymetry were 46.44 ± 2.33 D, 47.06 ± 2.57 D, and 525.86 ± 35.45 µm, respectively, at baseline compared with 46.40 ± 2.28 D, 46.98 ± 2.40 D, and 527.61 ± 37.67 µm at last follow-up (P > 0.05). All eyes were predicted as not having keratoconus using inferior-superior dioptric asymmetry ratio (I-S ratio), and the keratometry, inferior-superior, and astigmatism index (KISA%), which also incorporates skew percentage. The other tomographic indices predicted keratoconus or subclinical keratoconus in at least 22.4% of eyes. All parameters did not significantly change during follow-up. CONCLUSIONS: In the absence of other risk factors for keratoconus, children with high regular astigmatism demonstrated clinical and tomographic stability over time. Based on our results, we recommend that I-S ratio and KISA% be primarily used when monitoring normal children with high astigmatism to rule out keratoconus-related changes.