A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus.

Coats plus (CP) can be caused by mutations in the CTC1 component of CST, which promotes polymerase α (polα)/primase-dependent fill-in throughout the genome and at telomeres. The cellular pathology relating to CP has not been established. We identified a homozygous POT1 S322L substitution (POT1(CP)) in two siblings with CP. POT1(CP)induced a proliferative arrest that could be bypassed by telomerase. POT1(CP)was expressed at normal levels, bound TPP1 and telomeres, and blocked ATR signaling. POT1(CP)was defective in regulating telomerase, leading to telomere elongation rather than the telomere shortening observed in other telomeropathies. POT1(CP)was also defective in the maintenance of the telomeric C strand, causing extended 3' overhangs and stochastic telomere truncations that could be healed by telomerase. Consistent with shortening of the telomeric C strand, metaphase chromosomes showed loss of telomeres synthesized by leading strand DNA synthesis. We propose that CP is caused by a defect in POT1/CST-dependent telomere fill-in. We further propose that deficiency in the fill-in step generates truncated telomeres that halt proliferation in cells lacking telomerase, whereas, in tissues expressing telomerase (e.g., bone marrow), the truncations are healed. The proposed etiology can explain why CP presents with features distinct from those associated with telomerase defects (e.g., dyskeratosis congenita).

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.

A curious case of growth failure and hypercalcemia: Questions.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown etiology that rarely presents in childhood. Here, we report a case of pediatric sarcoidosis presenting with renal failure and hypercalcemia. CASE DIAGNOSIS/TREATMENT: A previously well 14-year-old Caucasian boy was admitted to the Hospital for Sick Children, Canada, for hypertension and renal failure following work-up by his family physician for initial concerns of growth failure. On admission, his weight was 35 kg (<3rd percentile), his height was 148 cm (≪3rd percentile), and his blood pressure was 154/116 mmHg (>99th percentile for height). Laboratory findings showed elevated creatinine (218 µmol/L), hypercalcemia (3.21 mmol/L), and normocytic anemia (hemoglobin 105 g/L). His further assessment showed a urinary concentrating defect with hypercalciuria (calcium/creatinine 1.76 mmol/mmol) and nephrocalcinosis on ultrasound. His eye examination showed uveitis with conjunctival biopsy remarkable for granulomas, which led to pursuit of a diagnosis of possible sarcoidosis. Angiotensin-converting enzyme was found to be high at 96 U/L, and he had a renal biopsy that was consistent with interstitial nephritis with granulomas. Treatment was started with prednisone leading to resolution of his hypercalcemia but persistence of his mild chronic kidney disease. CONCLUSIONS: This case represents an atypical presentation of a rare pediatric disease and highlights the spectrum of renal manifestations and treatment options in sarcoidosis.

A curious case of growth failure and hypercalcemia: Answers.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown etiology that rarely presents in childhood. Here, we report a case of pediatric sarcoidosis, presenting with renal failure and hypercalcemia. CASE DIAGNOSIS/TREATMENT: A previously well 14-year-old Caucasian boy was admitted to the Hospital for Sick Children, Canada, for hypertension and renal failure following work-up by his family physician for initial concerns of growth failure. On admission, his weight was 35 kg (<3rd percentile), his height was 148 cm (<<3rd percentile), and his blood pressure was 154/116 mmHg (>99th percentile for height). Laboratory findings showed elevated creatinine (218 umol/L), hypercalcemia (3.21 mmol/L), and normocytic anemia (hemoglobin 105 g/L). His further assessment showed a urinary concentrating defect with hypercalciuria (calcium/creatinine 1.76 mmol/mmol) and nephrocalcinosis on ultrasound. His eye examination showed uveitis with conjunctival biopsy remarkable for granulomas, which led to pursuit of a diagnosis of possible sarcoidosis. Angiotensin Angiotensin-converting enzyme was found to be high at 96 U/L, and he had a renal biopsy that was consistent with interstitial nephritis with granulomas. Treatment was started with prednisone leading to resolution of his hypercalcemia but persistence of his mild chronic kidney disease. CONCLUSIONS: This case represents an atypical presentation of a rare pediatric disease and highlights the spectrum of renal manifestations and treatment options in sarcoidosis.

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.

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.

Long-term outcomes of type 1 retinopathy of prematurity following monotherapy with bevacizumab: a Canadian experience.

OBJECTIVE: To report long-term structural, visual, and refractive outcomes after monotherapy with intravitreal bevacizumab injection. DESIGN: Cohort retrospective chart review. PARTICIPANTS: A total of 56 premature infants with type 1 retinopathy of prematurity. METHODS: This is a chart review at 2 Canadian institutions. Inclusion criteria were single injection of 0.625 mg  intravitreal bevacizumab and minimum age at last follow-up of 3 years. Primary outcome was retinal structure. Secondary outcomes were refractive error in spherical equivalent, monocular visual acuity, strabismus, and amblyopia. RESULTS: Fifty-six infants (101 eyes) met inclusion criteria. Mean birth weight was 707 ± 178 g (range, 420-1520 g). Mean gestational age was 25.0 ± 1.3 weeks (range, 22.9-29.7 weeks). Twenty-four eyes were in zone I (24%) and 77 in zone II (76%). Mean postmenstrual age at treatment was 36.9 ± 2.1 weeks (range, 32.8-42.0 weeks). At a mean age of 5.4 ± 1.6 years (range, 3.0-8.0 years), all eyes had a favourable structural outcome with no reactivation requiring treatment. Mean monocular visual acuity was 0.29 ± 0.27 logMAR (range, 0.0-1.3 logMAR; 89 of 101 eyes). Mean spherical equivalent was -1.98 ± 4.91 D (range, -16.63 to +5.38 D; 101 of 101 eyes). Prevalence of emmetropia (>-1.0 to ≤1 D) was 43.6%; low myopia (≥1.0 to <5 D) was 17.8%; high myopia (≥5 to <8 D) was 8.9 %; very high myopia (≥8.0 D) was 12.9%; and hyperopia (>1 D) was 16.8%. Twelve children (23%) had amblyopia, and 17 (32%) developed strabismus. CONCLUSIONS: All patients demonstrated a favourable structural outcome with a single bevacizumab injection without the need for additional laser. We suggest regular monitoring following regression of acute retinopathy of prematurity as an alternative to universal, preplanned delayed prophylactic laser treatment. Future studies to evaluate other aspects of visual function are needed.

A Meta-Analysis of Neurodevelopmental Outcomes following Intravitreal Bevacizumab for the Treatment of Retinopathy of Prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is the most common cause of preventable blindness in preterm infants. First-line treatments include intravitreal bevacizumab (IVB) or laser photocoagulation (LPC). OBJECTIVES: The aim of the study was to evaluate neurodevelopmental safety of IVB compared to LPC for ROP. METHODS: MEDLINE, Embase, and Cochrane library were searched up to September 2022. Studies were included with at least 12-month follow-up of primary outcomes such as severe neurodevelopmental impairment (sNDI), cerebral palsy (CP), and hearing impairment (HI). Secondary outcomes were moderate-to-severe neurodevelopmental impairment (msNDI), Bayley Scores of Infant Development (BSID-III), and visual impairment. RESULTS: 1,231 patients from 11 comparative studies were included. Quality of evidence was rated low for all outcomes. IVB was associated with a higher risk for sNDI (risk ratio [RR] = 1.25, 95% confidence interval [CI]: [1.01, 1.53], p = 0.04); and CP (RR = 1.40, CI: [1.08, 1.81], p = 0.01) compared to LPC. There was no significant difference between IVB and LPC for msNDI (RR = 1.15, CI: [0.98, 1.35], p = 0.08) and HI (RR = 1.43, CI: [0.86, 2.39], p = 0.17). BSID-III percentile scores were similar between IVB and LPC, with weighted mean differences of 1.51 [CI = -1.25, 4.27], 2.43 [CI = -1.36, 6.22], and 1.97 [CI = -1.06, 5.01] for cognitive, language, and motor domains, respectively (p > 0.05). CONCLUSION: To our knowledge, this is the largest meta-analysis on neurodevelopmental outcomes and the first to rigorously examine IVB monotherapy in ROP treatment. Compared to LPC, there was a marginally increased risk for sNDI and CP with IVB but little or no difference in the risk of msNDI and HI. Further randomized studies are needed to strengthen these findings.

Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

OBJECTIVE: To develop Canadian recommendations for the screening, monitoring, and treatment of uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach. A working group of 14 pediatric rheumatologists, 6 ophthalmologists, 2 methodologists, and 3 caregiver/patient representatives reviewed recent American College of Rheumatology (ACR)/Arthritis Foundation (AF) recommendations and worked in pairs to develop evidence-to-decision (EtD) tables. A survey to assess agreement and recommendations requiring group discussion was completed. EtD tables were presented, discussed, and voted upon at a virtual meeting, to produce the final recommendations. A health equity framework was applied to all aspects of the adolopment process including the EtD tables, survey responses, and virtual meeting discussion. RESULTS: The survey identified that 7 of the 19 recommendations required rigorous discussion. Seventy-five percent of working group members attended the virtual meeting to discuss controversial topics as they pertained to the Canadian environment, including timing to first eye exam, frequency of screening, escalation criteria for systemic and biologic therapy, and the role of nonbiologic therapies. Equity issues related to access to care and advanced therapeutics across Canadian provinces and territories were highlighted. Following the virtual meeting, 5 recommendations were adapted, 2 recommendations were removed, and 1 was developed de novo. CONCLUSION: Recommendations for JIA-associated uveitis were adapted to the Canadian context by a working group of pediatric rheumatologists, ophthalmologists with expertise in the management of uveitis, and parent/patient input, taking into consideration cost, equity, and access.

Demographic Risk Factors of Retinopathy of Prematurity: A Systematic Review of Population-Based Studies.

INTRODUCTION: Current national guidelines use gestational age (GA) and birth weight (BW) as their basis for retinopathy of prematurity (ROP) screening. The strength of association of these and other demographic risk factors is inconsistent across studies. This review aims to evaluate the strength of association of documented risk factors for ROP in large sample, population-based studies. METHODS: MEDLINE, EMBASE, and Cochrane Library were searched from January 2010 to May 2020. Original studies reporting the risk of ROP in a region and demographic risk factors were included. RESULTS: Eighteen studies comprising 342,005 infants were included. The overall risk of ROP in preterm infants was 18.8%. For every week decrease in GA, there was a median adjusted odds ratio (aOR) of 1.4 times (range 1.2-1.9) of developing ROP. For every 100-g decrease in BW, the median aOR was 1.8 times (range 1.2-2.7). Higher risk was found in infants with neonatal sepsis and bronchopulmonary dysplasia. The risk of any, severe, and treatment-requiring ROP was highest for 23 weeks GA, which was 66.5, 40.3, and 39.4%, respectively. Regions with higher neonatal mortality rates had the highest mean GA of infants with ROP. CONCLUSION: For every week decrease in GA and every 100-g decrease in BW, there was a median of 1.4 times and 1.8 times the odds of developing ROP, respectively. Further research is required to clarify the role of additional risk factors.

Bitot-like spots in children with normal vitamin A levels.

BACKGROUND/AIMS: A Bitot spot is a conjunctival lesion, classically associated with severe vitamin A deficiency. In this paediatric series, we describe conjunctival lesions indistinguishable from Bitot spots, seen in the presence of normal vitamin A levels. METHODS: This descriptive case series was performed by retrospective review of case notes, including all patients with Bitot-like spots found to have normal serum vitamin A levels, seen at the Hospital for Sick Children, Toronto, between 2006 and 2016. Data collected included age at presentation, ophthalmic and systemic diagnoses, and the presence of recognised genetic mutations. Histopathology was reviewed in one case. RESULTS: Ten patients with Bitot-like spots with laboratory-confirmed normal serum vitamin A levels were identified. The conjunctival lesions were indistinguishable clinically and histopathologically from classic Bitot spots and were noted to occur in a range of anterior segment pathologies, including aniridia, WAGR syndrome, Axenfeld-Rieger syndrome, and blepharokeratoconjunctivitis. CONCLUSIONS: Bitot-like spots are found in children with a number of anterior segment pathologies in the absence of vitamin A deficiency.

Optic disk anatomical features of children with central retinal vein occlusion.

PURPOSE: To report a case series of children with central retinal vein occlusion (CRVO) showing a high prevalence of crowded optic disks with minimal cupping. METHODS: We retrospectively reviewed the medical records of children diagnosed with CRVO from 2008 to 2019 at a single tertiary care pediatric hospital. Clinical records, fundus photographs, and optical coherence tomography (OCT) images were reviewed. Optic disk anatomical parameters of the unaffected fellow eyes, including OCT-measured optic disk area and vertical cup:disk ratio, were collected and analyzed. RESULTS: Six patients with unilateral CRVO were identified. All patients were female. Age at presentation ranged between 9 and 17 years. Five patients were otherwise healthy, with negative systemic investigations (idiopathic group). The remaining patient had a known systemic risk factor of active Takayasu arteritis. Within the idiopathic group, "disk-at-risk" optic nerve configuration, defined as a cup:disk ratio of 0.2 or smaller, was identified in the fellow eye of all 5 patients. In the unaffected eyes, mean OCT-measured optic disk area was 1.67 ± 0.13 mm2 and mean cup:disk ratio was 0.19 ± 0.12. The patient with Takayasu arteritis had normal OCT disk area of 2.1 mm2 and cup:disk ratio of 0.61. CONCLUSIONS: We observed a high prevalence of anatomical features potentially consistent with a constrictive optic disk configuration in pediatric patients with CRVO.

Video interpretation and diagnosis of pediatric amblyopia and eye disease.

AIM: The aim of this study was to assess the potential of using video screening to interpret the results of paediatric eye examinations. DESIGN: Prospective multi-centred, blinded study. METHODS: Children aged 5 months to 11 years referred to a paediatric ophthalmology centre were enrolled in the study. Outcome measures included the degree of agreement between examiners for assessment of various aspects of paediatric eye examination. In Phase 1, children were individually assessed in the clinic by three different examiners to determine the level of agreement. In Phase 2 a video recording was made of the first ophthalmologist examining the children. The other two examiners viewed the video recordings to make their diagnoses. Areas of assessment included lid function, pupillary function, ocular motility, strabismus, nystagmus, torticollis and facial asymmetry. Agreement between examiners was measured using Gwet's agreement coefficient (AC1). RESULTS: A total of 27 patients in Phase 1 (mean age 4.0 years) and 160 children in Phase 2 (mean age 4.8 years) underwent clinical and video-recorded screening. In Phase 1, all but one area of ocular examination (heterotropia) achieved ≥84% agreement between three examiners. In Phase 2, there was greater variation between direct clinical examination and interpretation of video findings, ranging from 55-100% agreement. CONCLUSION: Using experienced clinicians and changing only one variable in Phase 2 (the method of assessment - direct examination versus video interpretation), the results show the possible usefulness of video-recorded screening as a means of assessing children. Further research is indicated to assess the accuracy of ophthalmologists interpreting video recordings of eye examinations performed by trained non-eye-care professionals.

Binocularity outcomes following treatment for retinopathy of prematurity.

OBJECTIVE: Retinopathy of prematurity (ROP) is a leading cause of childhood visual impairment. Treatment options for severe ROP include laser and/or anti-vascular endothelial growth factor (anti-VEGF) injections. Previous studies have compared the 2 treatments for functional outcomes including visual acuity, amblyopia, and strabismus. The purpose of this study was to evaluate the influence of treatment on binocularity. METHODS: In this masked, cross-sectional study, binocularity was measured using Bagolini lenses and the Frisby stereotest in children aged 3-8 years with a history of ROP treatment in 2 Canadian centres. Events associated with disruption of binocularity including amblyopia, anisometropia, and strabismus, were recorded and analyzed as secondary outcomes. RESULTS: A total of 42 children were recruited: 19 were treated with laser and 23 with an anti-VEGF agent. The mean age at the time of assessment in the laser group was 81.2 (6.8 years) ± 16.2 months versus 63 (5.25 years) ± 15.7 months in the anti-VEGF group (p < 0.001). No statistically significant difference in rates of binocularity was detected (68% laser vs 82% anti-VEGF, p = 0.27). Laser-treated participants experienced a greater number of cumulative insults to binocularity (p = 0.01). CONCLUSIONS: Patients with a history of ROP treated with laser or anti-VEGF agents require long-term follow-up to address binocularity-disrupting factors. Although we did not detect a difference in rates and level of binocularity between treatment groups, we did find an increased rate of cumulative binocularity disrupting events in the laser-treated group.

Corneal endothelium in paediatric patients with uveitis: a prospective longitudinal study.

PURPOSE: To study the longitudinal effect of anterior chamber inflammation on the corneal endothelium in children. METHODS: In this prospective longitudinal observational study, children (aged <18 years) with anterior chamber inflammation and those at risk of developing uveitis due to juvenile idiopathic arthritis (JIA) were included. Changes in central endothelial cell density (ECD) and morphological variables were determined by non-contact specular microscopy, and their correlations with uveitis activity and surgical interventions were analysed. RESULTS: Ninety-nine eyes of 99 children (mean age (±SD): 10.0±4.1 years) with a history of anterior chamber inflammation were recruited. Mean follow-up was 12.3±3.5 months. Eleven children, who were under surveillance but had not developed JIA-associated uveitis were included as controls. While there were no significant differences in mean ECD between controls and subjects without prior surgery (group 1) at all time points, those who had prior ophthalmic surgery (group 2) displayed significantly lower ECD than the controls at recruitment (p=0.002) and at follow-up (p=0.004). However, longitudinal ECD assessments did not show significant changes in either group (group 1, p=0.07, group 2, p=0.54). On regression analysis, once the patient's age was adjusted for, only the occurrence of intraocular procedures during the study (r=0.43, adjusted p=0.03) was associated with a significant annual rate of ECD loss. CONCLUSION: During the study period, longitudinal ECD changes among children with uveitis were associated with intraocular surgery for uveitis-related complications but not uveitis activity. By reducing the need for surgical intervention, the corneal endothelium in these children may be preserved.

Intravitreal antivascular endothelial growth factor injection versus laser photocoagulation for retinopathy of prematurity: A meta-analysis of 3,701 eyes.

We investigate the efficacy and safety of intravitreal injection (IVI) of antivascular endothelial growth factor agents and laser photocoagulation (LPC) for retinopathy of prematurity. We performed a systematic search of Ovid MEDLINE, EMBASE, and Cochrane CENTRAL (2005-2019). Comparative studies reporting on ocular efficacy and/or safety outcomes after IVIs and LPC for retinopathy of prematurity were included. The primary outcome was the regression rate, whereas secondary endpoints included the likelihood of requiring additional treatment, visual and refractive outcomes, and complications. Overall, 777 publications were identified. Twenty-four articles were included, with 1,289 eyes receiving IVI and 2,412 eyes undergoing LPC. There was no significant difference in the regression rate between IVI and LPC (P = 0.68); however, eyes that underwent IVI were associated with a significantly higher likelihood of requiring additional treatment (risk ratio = 2.16, 95% confidence interval (CI) = [1.26, 3.73], P = 0.005) and longer time from treatment to retreatment or recurrence (weighted mean difference = 6.43 weeks, 95% CI = [2.36, 10.51], P = 0.002). Eyes receiving IVI required surgical intervention significantly less often (risk ratio = 0.45, 95% CI = [0.23, 0.89], P = 0.02). Astigmatism was significantly lower after IVI relative to LPC (weighted mean difference = -0.25 D, 95% CI = [-0.45, -0.06], P = 0.01), and there was a lower proportion of emmetropic eyes at last follow-up after LPC (risk ratio = 0.51, 95% CI = [0.27, 0.99], P = 0.05). There were no differences in visual and safety outcomes between IVI and LPC. LPC had a lower likelihood of requiring additional treatment, whereas IVIs were associated with a longer interval from treatment to retreatment or recurrence, reduced risk of surgical intervention and superior refractive outcomes. All other outcomes were comparable between IVIs and LPC.

Toward community predictions: Multi-scale modelling of mountain breeding birds' habitat suitability, landscape preferences, and environmental drivers.

Across a large mountain area of the western Swiss Alps, we used occurrence data (presence-only points) of bird species to find suitable modelling solutions and build reliable distribution maps to deal with biodiversity and conservation necessities of bird species at finer scales. We have performed a multi-scale method of modelling, which uses distance, climatic, and focal variables at different scales (neighboring window sizes), to estimate the efficient scale of each environmental predictor and enhance our knowledge on how birds interact with their complex environment. To identify the best radius for each focal variable and the most efficient impact scale of each predictor, we have fitted univariate models per species. In the last step, the final set of variables were subsequently employed to build ensemble of small models (ESMs) at a fine spatial resolution of 100 m and generate species distribution maps as tools of conservation. We could build useful habitat suitability models for the three groups of species in the national red list. Our results indicate that, in general, the most important variables were in the group of bioclimatic variables including "Bio11" (Mean Temperature of Coldest Quarter), and "Bio 4" (Temperature Seasonality), then in the focal variables including "Forest", "Orchard", and "Agriculture area" as potential foraging, feeding and nesting sites. Our distribution maps are useful for identifying the most threatened species and their habitat and also for improving conservation effort to locate bird hotspots. It is a powerful strategy to improve the ecological understanding of the distribution of bird species in a dynamic heterogeneous environment.

Outcomes and complications of immediate versus delayed sequential bilateral cataract surgery in children.

PURPOSE: To present the largest series to date comparing outcomes and complications of immediate versus delayed sequential bilateral cataract surgery (ISBCS vs DSBCS) in children at a single center over a 10-year period. METHODS: The medical records of children <2 years of age who underwent ISBCS and DSBCS were reviewed retrospectively. Data was collected on outcomes and complications (ophthalmological and anesthesia-related) up to 8 weeks postoperatively. RESULTS: A total of 53 children were included: 37 ISBCS and 16 DSBCS. There were no differences between groups with regard to sex, age at surgery, and type of surgery. The ISBCS group had significantly more patients with systemic or ocular comorbidities than the DSBCS group (35% vs 6%; P = 0.029). Mean operating room time was significantly lower for the ISBCS group (3.61 vs 4.09 hours; P = 0.037), whereas total surgical time was similar. No major intraoperative surgical complications or anesthesia-related adverse events occurred in either group. Postoperative complications (most commonly, raised intraocular pressure) occurred in 5 eyes (7%) in the ISBCS group and 8 eyes (25%) in the DSBCS group (P = 0.009). Patients in the ISBCS group required significantly fewer follow-up visits compared to the DSBCS group (4 vs 6; P = 0.0002). CONCLUSIONS: ISBCS avoids multiple anesthesia sessions and reduces follow-up visits, with intra- and postoperative ophthalmological or anesthesia-related complications comparable to DSBCS.