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.

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.

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.

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.

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.

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.

Identifying the ophthalmic needs of families living in Toronto shelters.

OBJECTIVE: To assess the ophthalmic needs of families with children residing in Toronto shelters. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-nine families, including 86 children (age 0-16 years) and 55 adult and youth family members (AYFM) (age >16 years), randomly selected from 5 family shelters in Toronto, Ont. METHODS: Ten families with at least 1 child aged 16 years or younger were randomly recruited from each shelter. Data on sociodemographics, medical history, ocular history, and access to eye care were collected through a structured interview. Eye examinations were performed in the shelters for all children and AYFM. RESULTS: The mean age for AYFM was 34.9 ± 9.3 years (range, 17-60 years), and the mean age for children was 6.1 ± 4.3 years (range, 1 month-16 years). Thirty-nine percent of parents reported dissatisfaction with their vision, and 6.7% of children had parents who perceived that their child had eye problems. Overall, fewer parents had accessed care for their own eye problems in the last year than for their children (parents 36.4%, children 81.8%). Examination revealed abnormal ocular findings in 47.3% of AYFM and 24.4% of children. The commonest finding in AYFM was refractive error (30.9%); among children, it was refractive errors (16.3.%) and strabismus (3.5%). CONCLUSIONS: We found that a significant percentage of families living in shelters had eye problems that required treatment. We propose a proactive approach to identify these families and their dependent children in order to expedite access to appropriate eye care in a timely fashion for this vulnerable population.

Transient lens vacuoles in premature infants.

We report 6 cases of bilateral vacuolar lens opacities in premature infants. These uncommon opacities were multiple, located peripherally in the lens, and unrelated to the severity of retinopathy. The vacuoles were transient in nature, did not interfere with ROP examination, and were not adversely affected by antivascular endothelial growth factor treatment. On long-term follow-up, the cataracts had no effect on vision.

Retinal astrocytoma regression in tuberous sclerosis patients treated with everolimus.

Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) that has been approved by the US Food and Drug Administration for the treatment of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC). Retinal hamartomas, which are one of the major diagnostic features of TSC, tend to remain stable or gradually progress in the natural history of the disease. We report 2 patients with TSC treated with everolimus for SEGA in whom fundus photographs and spectral domain optical coherence tomography demonstrated regression of previously documented multiple retinal hamartomas in all 4 eyes.

Macular morphology following unilateral bevacizumab injection for retinopathy of prematurity: an OCT study.

This retrospective case series assessed the influence of unilateral intravitreal bevacizumab (IVB) for unilateral type 1 retinopathy of prematurity (ROP) on macular thickness and foveal development. Seven infants with unilateral type 1 ROP were treated with intravitreal bevacizumab 0.625 mg/0.025 ml in one eye only. To determine whether macular thickness and fovea structural development were affected by treatment, spectral domain optical coherence tomography was performed on both treated and untreated eyes. The mean gestational age of infants was 25.3 ± 0.3 weeks; the mean birth weight, 776 ± 17.6 g. Treatment was given at a mean postmenstrual age of 37.2 ± 0.4 weeks. Foveal development was normal in 3 (43%) treated versus 5 (71%) untreated eyes. The mean central foveal thickness for treated and untreated eyes was 270.1 µm ± 19.6 and 253.0 µm ± 27.2 respectively (P = 0.15). There was small but nonsignificant difference in foveal development and thickness in eyes treated with intravitreal bevacizumab compared to fellow eyes. This study generates important data to test the hypothesis that foveal thickness is greater in unilateral type 1 ROP eyes treated with IVB compared to untreated fellow eyes.

Use of the Delphi process in paediatric cataract management.

PURPOSE: To identify areas of consensus and disagreement in the management of paediatric cataract using a modified Delphi approach among individuals recognised for publishing in this field. DESIGN: A modified Delphi method. PARTICIPANTS: International paediatric cataract experts with a publishing record in paediatric cataract management. METHODS: The process consisted of three rounds of anonymous electronic questionnaires followed by a face-to-face meeting, followed by a fourth anonymous electronic questionnaire. The executive committee created questions to be used for the electronic questionnaires. Questions were designed to have unit-based, multiple choice or true-false answers. The questionnaire included issues related to the preoperative, intraoperative and postoperative management of paediatric cataract. MAIN OUTCOME MEASURE: Consensus based on 85% of panellists being in agreement for electronic questionnaires or 80% for the face-to-face meeting, and near consensus based on 70%. RESULTS: Sixteen of 22 invited paediatric cataract surgeons agreed to participate. We arrived at consensus or near consensus for 85/108 (78.7%) questions and non-consensus for the remaining 23 (21.3%) questions. CONCLUSIONS: Those questions where consensus was not reached highlight areas of either poor evidence or contradicting evidence, and may help investigators identify possible research questions.

Anterior segment imaging in pediatric ophthalmology.

Anterior segment imaging in the pediatric population using commercially available equipment is rewarding but can be challenging. Successful imaging requires familiarity with the imaging modality used, a positive attitude, and the ability to quickly develop rapport with children. In this review, we demonstrate how external and slitlamp photography, Scheimpflug imaging, handheld digital fundus camera, ultrasound biomicroscopy, and anterior segment optical coherence tomography can be valuable in the documentation, diagnosis, and management of pediatric anterior segment disease. Families understand their child's disease process when it is demonstrated photographically and feel more motivated and involved in their care. Compliance with treatment is often enhanced through this process.

Computer-assisted image analysis of temporal retinal vessel width and tortuosity in retinopathy of prematurity for the assessment of disease severity and treatment outcome.

PURPOSE: To quantify the severity of retinopathy of prematurity (ROP) through temporal retinal vessel diameter and tortuosity by the use semiautomated analysis and to evaluate the effects of laser treatment on retinal vessel measurements. METHODS: A total of 176 RetCam digital fundus images from 63 infants diagnosed with ROP between January 2005 and December 2008 were retrospectively analyzed with Retinal Vessel Measurement V5.8 software. Patients were classified into 1 of 3 groups: stage 1 and 2 (Group 1), stage 3 not requiring treatment (Group 2), and stage 3 requiring treatment (Group 3). Diameter and tortuosity of the 4 major temporal retinal arteries and veins close to the optic disk were quantified. Tortuosity was measured as central (within 2 disk diameters from the center of the optic disk) and paracentral (from 2 to 4 disk diameters). For Group 3, measurements of vessels immediately before treatment and all follow-up post-treatment measurements of vessels were analyzed. RESULTS: Differences in central and paracentral arteriolar tortuosity were pronounced. The average central arteriolar tortuosities were 1.12 ± 0.018 for Group 1, 1.13 ± 0.018 for Group 2, and 1.32 ± for Group 3; the paracentral arteriolar tortuosities were 1.11 ± 0.019 for Group 1, 1.12 ± 0.019 for Group 2, and 1.31 ± 0.02 for Group 3. In the post-treatment analysis of Group 3 patients, significant reductions in all vascular measurements were observed compared to pre-treatment, except for central and paracentral vein tortuosity. CONCLUSIONS: Computerized systems can be used to objectively assess differences in vascular parameters between ROP stages.

Pediatric eye injuries in a Canadian emergency department.

OBJECTIVE: This study assesses the descriptive epidemiology of children with eye injuries presenting to the emergency department of a major Canadian pediatric hospital. STUDY DESIGN: A retrospective cohort study. PARTICIPANTS: All pediatric patients (up to 18 years of age) presenting with ocular injuries to a tertiary care pediatric emergency department between January 1 and December 31, 2002. METHODS: Chart review was conducted using Canadian Hospital Injury Reporting and Prevention Program forms. All injuries were classified by Birmingham Eye Trauma Terminology (BETT). RESULTS: There were 149 patients who presented with eye injuries to the emergency department in 2002, and all of them were included in the study. Patient ages ranged from 3 months to 18 years with a median age of 8 years 8 months (interquartile range 4-11 years). Boys accounted for 73.2% of the patient total. Most of the cases (57.7%) needed some treatment and required follow-up. Eleven patients (7.3%) had vision-threatening eye injuries that required surgical management, and 3 of these required multiple surgeries. Seven of the 11 patients suffered open globe lacerations, 3 open globe ruptures, and 1 closed globe injury. CONCLUSIONS: Most eye injuries occurred at home during the summer, and over 7% of children presenting to the emergency department with eye trauma had vision-threatening injuries that required surgical management. Increasing awareness of the serious nature of ocular injuries will help to develop a comprehensive plan for educating both parents and children to minimize preventable pediatric eye injuries.

Morning glory disc anomaly, midline cranial defects and abnormal carotid circulation: an association worth looking for.

We report on a 4-year-old boy who presented to the ophthalmology department for assessment of convergent strabismus. Ophthalmic examination showed a left morning glory optic disc anomaly and retinal detachment. Plain films obtained for investigation of short stature prior to ophthalmic examination revealed delayed bone age. Ophthalmological findings prompted CT and MRI imaging and angiographic investigations. Midline cranial defects and abnormal carotid circulation were identified. These findings may be associated with morning glory optic disc anomaly, and their association is often under-recognized. It is important that clinicians and radiologists be aware of this spectrum of disorders, as the vascular abnormalities may predispose the patient to transient ischemic attacks and strokes. Growth delay may result from hypopituitarism.