Diverse Research Teams and Underrepresented Groups in Clinical Studies.

Importance: Several ophthalmic diseases disproportionately affect racial and ethnic minority patients, yet most clinical trials struggle to enroll cohorts that are demographically representative of disease burden; some barriers to recruitment include time and transportation, language and cultural differences, and fear and mistrust of research due to historical abuses. Incorporating diversity within the research team has been proposed as a method to increase trust and improve engagement among potential study participants. Objective: To examine how demographic factors of potential research participants and personnel may be associated with patient consent rates to participate in prospective ophthalmic clinical studies. Design, Setting, and Participants: This retrospective cohort study included patients from an urban, academic hospital who were approached for consent to participate in prospective ophthalmic clinical studies conducted between January 2015 and December 2021. Main Outcomes and Measures: Multivariable logistic regression assessing associations between patient and research personnel demographics and rates of affirmative consent to participate was used. Results: In total, 1380 patients (mean [SD] age, 58.6 [14.9] years; 50.3% male) who were approached for consent to participate in 10 prospective ophthalmic clinical studies were included. Of prospective patients, 566 (43.5%) were Black; 327 (25.1%), Hispanic or Latino; 373 (28.6%), White; 36 (2.8%), other race and ethnicity; and 78 (5.8%) declined to answer. Black patients (odds ratio [OR], 0.32; 95% CI, 0.24-0.44; P < .001) and Hispanic or Latino patients (OR, 0.31; 95% CI, 0.20-0.47; P < .001) were less likely to consent compared with White patients. Patients with lower socioeconomic status were less likely to consent than patients with higher socioeconomic status (OR, 0.43; 95% CI, 0.33-0.53; P < .001). Concordance between patient and research staff race and ethnicity was associated with increased odds of affirmative consent (OR, 2.72; 95% CI, 1.99-3.73; P < .001). Conclusions and Relevance: In this cohort study, patients from underrepresented racial and ethnic groups and those with lower socioeconomic status were less likely to participate in ophthalmic clinical studies. Concordance of race and ethnicity between patients and research staff was associated with improved participant enrollment. These findings underscore the importance of increasing diversity in clinical research teams to improve racial and ethnic representation in clinical studies.

Modifiable Risk Factors and Preventative Strategies for Severe Retinopathy of Prematurity.

Severe ROP is characterized by the development of retinal fibrovascular proliferation that may progress to retinal detachment. The purpose of this report is to review five of the most common and well-studied perinatal and neonatal modifiable risk factors for the development of severe ROP. Hyperoxemia, hypoxia, and associated prolonged respiratory support are linked to the development of severe ROP. While there is a well-established association between clinical maternal chorioamnionitis and severe ROP, there is greater variability between histologic chorioamnionitis and severe ROP. Neonatal sepsis, including both bacterial and fungal subtypes, are independent predictors of severe ROP in preterm infants. Although there is limited evidence related to platelet transfusions, the risk of severe ROP increases with the number and volume of red blood cell transfusions. Poor postnatal weight gain within the first six weeks of life is also strongly tied to the development of severe ROP. We also discuss preventative strategies that may reduce the risk of severe ROP. Limited evidence-based studies exist regarding the protective effects of caffeine, human milk, and vitamins A and E.

Long-term strabismus outcomes after unilateral infantile cataract surgery in the Infant Aphakia Treatment Study.

PURPOSE: To characterize long-term strabismus outcomes in children in the Infant Aphakia Treatment Study (IATS). METHODS: This study was a secondary data analysis of long-term ocular alignment characteristics of children aged 10.5 years who had previously been enrolled in a randomized clinical trial evaluating aphakic management after unilateral cataract surgery between 1 and 6 months of age. RESULTS: In the IATS study, 96 of 109 children (88%) developed strabismus through age 10.5 years. Half of the 20 children who were orthophoric at distance through age 5 years maintained orthophoria at distance fixation at 10.5 years. Esotropia was the most common type of strabismus prior to age 5 years (56/109 [51%]), whereas exotropia (49/109 [45%]) was the most common type of strabismus at 10.5 years (esotropia, 21%; isolated hypertropia, 17%). Strabismus surgery had been performed on 52 children (48%), with 18 of these (35%) achieving microtropia <10Δ. Strabismus was equally prevalent in children randomized to contact lens care compared with those randomized to primary intraocular lens implantation (45/54 [83%] vs 45/55 [82%]; P = 0.8). Median visual acuity in the study eye was 0.56 logMAR (20/72) for children with orthotropia or microtropia <10Δ versus 1.30 logMAR (20/400) for strabismus ≥10Δ (P = 0.0003). CONCLUSIONS: Strabismus-in particular, exotropia-is common irrespective of aphakia management 10 years following infant monocular cataract surgery. The delayed emergence of exotropia with longer follow-up indicates a need for caution in managing early esotropia in these children. Children with better visual acuity at 10 years of age are more likely to have better ocular alignment.

Unilateral Familial Exudative Vitreoretinopathy: Clinical Profile and Pathology.

We report a case of a newborn with unilateral retinal detachment that could not be repaired. At examination under anesthesia, the retina was markedly abnormal and a presumptive diagnosis of retinal dysplasia was made. Several years later, the eye was enucleated because it was blind and painful. Final pathology was consistent with familial exudative vitreoretinopathy (FEVR). The literature describing unilateral retinal dysplasia is sparse. This case adds to the clinical spectrum of pathologic findings in FEVR.

Rate of ocular trauma in children operated on for unilateral cataract in infancy-data from the Infant Aphakia Treatment Study.

To determine whether the fellow eye of children who have undergone unilateral cataract extraction in the first year of life are at increased risk of injury and vision loss, the 10.5-year data on 109 of 114 children enrolled in the Infant Aphakia Treatment Study were examined. Based on this limited data, it was estimated that the fellow eye is at greater risk of injury than the operated eye. Our data do not support the risk being higher in children with the worst vision in the treated eye.

Development of refractive error in children treated for retinopathy of prematurity with anti-vascular endothelial growth factor (anti-VEGF) agents: A meta-analysis and systematic review.

OBJECTIVE: To investigate refractive error development in preterm children with severe retinopathy of prematurity (ROP) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and laser photocoagulation. METHODS: Selection criteria were comparative studies that compared the refractive errors in children, birthweights ≤1500 grams and gestational ages ≤30 weeks, and treatments for Type I ROP with intravitreal bevacizumab (IVB) versus laser photocoagulation. Studies were identified using PubMed, Google Scholar, and published reviews. Meta-analyses were performed on the post-treatment outcomes of spherical equivalent (SEQ), cylindrical power, and prevalence of high myopia. Longitudinal development of refractive error in IVB, or in laser-treated children, or in normal full-term children was visually summarized. RESULTS: Two randomized controlled trials and 5 non-randomized studies, including a total of 272 eyes treated by IVB and 247 eyes treated by laser, were included in this study. Compared with laser-treated children, IVB-treated children have less myopic refractive error (P<0.001), lower prevalence of high myopia (P<0.05), and less astigmatism (P = 0.02). CONCLUSIONS: Treatment with IVB is associated with less myopia and astigmatism than laser treatment for infants with severe ROP. Given the complexity of ROP and the variability of dosing, our review supports close monitoring of refractive error outcomes in children treated with IVB.

Don't Miss This! Red Flags in the Pediatric Eye Exam: Pupils.

The pupillary exam in the pediatric population is a vital part of any clinician's workup. In the right clinical setting, pupillary abnormalities such as anisocoria, light-near dissociation, an afferent pupillary defect, and paradoxic pupillary constriction in the dark can be red flags that trigger further examination and workup. Through both careful physical examination and detailed history-taking and observation, potentially vision- and life-threatening conditions can be detected.

Don't Miss This! Red Flags in the Pediatric Eye Examination: Introduction and Essential Concepts.

Although the pediatric eye examination can be made more challenging by inattention, poor cooperation, sleep, or just the wiggles, these should never be justification for an inadequate assessment of the child. In fact, a challenging patient should make the examiner ever more careful to get a good history and to look carefully for potential red flags that should be examined in greater detail. Missing a history of diplopia, or not noticing an abnormal pupil, or blurred disc margins, to name a few, may delay the diagnosis and treatment of potentially life-threatening entities. In this symposium, red flags in the pediatric eye examination will be reviewed in depth with emphasis on diagnosis, testing, and referral.

Strabismus surgery outcomes in the Infant Aphakia Treatment Study (IATS) at age 5 years.

PURPOSE: To report strabismus surgery frequency and outcomes after monocular infantile cataract surgery with or without IOL implantation. METHODS: The Infant Aphakia Treatment Study (IATS) is a randomized, multicenter clinical trial comparing treatment of aphakia with a primary IOL or contact lens in 114 infants with a unilateral congenital cataract. This report is a secondary outcome analysis of ocular motor data from IATS patients who underwent strabismus surgery prior to age 5 years. RESULTS: Strabismus surgery was performed in 45 (39%) patients (contact lens group [CL], 37%; IOL group, 42% [P = 0.70]). The indications for strabismus surgery were esotropia (62%), exotropia (33%), and hypertropia (4%). Infants who underwent cataract surgery at a younger age were less likely to undergo strabismus surgery (28-48 days, 12/50 [24%]; 49-210 days, 33/64 [52%]; P = 0.0037). Of the 42 patients who underwent strabismus surgery, 14 (33%) had a postoperative distance alignment within 8Δ of orthotropia at age 5 years. The 5-year visual acuity of children with strabismus was the same whether or not strabismus surgery had been performed (1.10 logMAR with surgery vs 1.00 without [P = 0.71]). CONCLUSIONS: In this study cohort, cataract surgery performed in the first 6 weeks of life was associated with a reduced frequency of strabismus surgery. Strabismus surgery outcomes in this population are guarded. Surgical improvement of strabismus does not appear to influence long-term visual acuity.

Improvement of Eye Alignment in Adult Strabismic Monkeys by Sustained IGF-1 Treatment.

PURPOSE: The goal of this study was to determine if continuous application of insulin-like growth factor-1 (IGF-1) could improve eye alignment of adult strabismic nonhuman primates and to assess possible mechanisms of effect. METHODS: A continuous release pellet of IGF-1 was placed on one medial rectus muscle in two adult nonhuman primates (M1, M2) rendered exotropic by the alternating monocular occlusion method during the first months of life. Eye alignment and eye movements were recorded for 3 months, after which M1 was euthanized, and the lateral and medial rectus muscles were removed for morphometric analysis of fiber size, nerve, and neuromuscular density. RESULTS: Monkey 1 showed a 40% reduction in strabismus angle, a reduction of exotropia of approximately 11° to 14° after 3 months. Monkey 2 showed a 15% improvement, with a reduction of its exotropia by approximately 3°. The treated medial rectus muscle of M1 showed increased mean myofiber cross-sectional areas. Increases in myofiber size also were seen in the contralateral medial rectus and lateral rectus muscles. Similarly, nerve density increased in the contralateral medial rectus and yoked lateral rectus. CONCLUSIONS: This study demonstrates that in adult nonhuman primates with a sensory-induced exotropia in infancy, continuous IGF-1 treatment improves eye alignment, resulting in muscle fiber enlargement and altered innervational density that includes the untreated muscles. This supports the view that there is sufficient plasticity in the adult ocular motor system to allow continuous IGF-1 treatment over months to produce improvement in eye alignment in early-onset strabismus.

Sensorimotor outcomes by age 5 years after monocular cataract surgery in the Infant Aphakia Treatment Study (IATS).

PURPOSE: To evaluate sensorimotor outcomes among children in the Infant Aphakia Treatment Study (IATS). METHODS: Secondary outcome analysis was performed in this randomized, multicenter, clinical trial comparing treatment of unilateral aphakia with a primary intraocular lens (IOL) or contact lens (CL) correction. The alignment characteristics and sensory status of children through age 5 years were evaluated. RESULTS: In the IATS study, 91 of 112 children (81%) developed strabismus through age 5 years. Of 34 infants who were orthotropic at near 12 months after cataract surgery, at age 5 years 14 (41%) were orthotropic at distance, and 15 (44%) were orthotropic at near at age 5 years without strabismus surgery. Eight of 56 children (14%) in the CL group and 13 of 56 (23%) in the IOL group were orthotropic at distance (P = 0.33) at 5 years of age and had no history of strabismus surgery. Thirteen of 48 (27%) who underwent cataract surgery prior to 49 days of age compared to 8 of 64 (13%) who had surgery after 49 days were orthotropic (P = 0.085). Median visual acuity in the operative eye was 0.4 logMAR (20/50) for children with orthotropia or microtropia (<10(Δ)) versus 1.10 logMAR (20/252) for strabismus ≥10(Δ) (P = 0.0001). Stereopsis was detected in 12 of 21 children (57%) with orthotropia versus 16 of 89 (18%) children with strabismus (P = 0.0006). CONCLUSIONS: IOL placement does not reduce the development of strabismus after monocular congenital cataract surgery. Improved ocular alignment by age 5 years correlated strongly with improved visual acuity and stereopsis.

Tonic pupil after botulinum toxin-A injection for treatment of esotropia in children.

A total of 27 children with esotropia (mean age, 3.9 years; range, 9 months to 13.8 years) were enrolled in a 9-month observational study following botulinum toxin A (BTX-A) injection of one (n = 7) or both (n = 20) medial rectus muscles. BTX-A dosage ranged from 3.0 to 6.0 units per muscle. Three participants developed tonic pupil, noted at the first follow-up visit, occurring 12-19 days after injection. All 3 cases occurred in the left eye of participants who underwent bilateral BTX-A injection by the same surgeon. Anisocoria diminished from a maximum of 4 mm at the 2-week visit to 1-2 mm in all patients over the 9-month postinjection data collection period. No adverse visual outcomes were noted. Tonic pupil is an infrequently reported complication of BTX-A injection for strabismus. The experience of our investigator group suggests the need for careful injection technique and thorough preinjection counseling.

One-year strabismus outcomes in the Infant Aphakia Treatment Study.

OBJECTIVE: To evaluate the characteristics of strabismus in infants who underwent cataract surgery with and without intraocular lens (IOL) implantation. DESIGN: Secondary outcome analysis in a prospective, randomized clinical trial. PARTICIPANTS: The Infant Aphakia Treatment Study is a randomized, multicenter (n = 12), clinical trial comparing treatment of aphakia with a primary IOL or contact lens in 114 infants with a unilateral congenital cataract. INTERVENTION: Infants underwent cataract surgery with or without placement of an IOL. MAIN OUTCOME MEASURES: The proportion of patients in whom strabismus developed during the first 12 months of follow-up was calculated using the life-table method and was compared across treatment groups and age strata using a log-rank test. RESULTS: Strabismus developed within the first 12 months of follow-up in 38 pseudophakic infants (life-table estimate, 66.7%) and 42 infants (life-table estimate, 74.5%) treated with contact lenses (P = 0.59). The younger cohort (<49 days) at the time of surgery demonstrated less strabismus (29 of 50; life-table estimate, 58.0%) than the older cohort (≥ 49 days; 51 of 64; life-table estimate, 80.0%; P<0.01). CONCLUSIONS: Intraocular lens placement does not prevent the early development of strabismus after congenital cataract surgery. However, strabismus was less likely to develop in infants whose cataract was removed at an earlier age. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Incidence of cataract development by 6 months' corrected age in the Early Treatment for Retinopathy of Prematurity study.

PURPOSE: To report the incidence of cataract development by 6 months' corrected age in preterm children who participated in the Early Treatment for Retinopathy of Prematurity study. METHODS: Infants who developed prethreshold retinopathy of prematurity (ROP) in one or both eyes and were determined by the RM-ROP2 model to have a high risk of poor structural outcome without treatment were randomized to receive early treatment (ET), defined as laser photocoagulation at high-risk prethreshold ROP, or to be conventionally managed (CM), receiving treatment only if threshold ROP developed. Data on eyes developing a cataract by 6 months' corrected age were analyzed. RESULTS: Of 401 randomized infants, 366 survived patients were followed, and 8 eyes of 7 patients (1.9%) developed cataracts by 6 months' corrected age. Among these patients, mean birth weight was 754 g, and mean gestational age was 25.7 weeks. Mean gestational age at treatment was 36.3 weeks for ET patients and 39.5 weeks for CM patients. Three ET eyes and 5 CM eyes developed a cataract. Of the CM eyes, 3 with and 2 without laser treatment developed a cataract. All 6 treated eyes had plus disease when treated. Three eyes had ROP in zone 1, whereas the other 3 had ROP in zone 2. All eyes were treated using a diode laser. CONCLUSIONS: By 6 months' corrected age, a small number of both ET and CM eyes developed cataracts following diode laser treatment for retinopathy of prematurity. Absence of obvious intraoperative complications does not preclude subsequent cataract development, which can occur without laser treatment.

Diplopia after glaucoma surgery.

The occurrence of strabismus and symptomatic diplopia following glaucoma surgery is becoming more common as the use of implanted setons increases. Understanding the factors contributing to the diplopia is critical to the development of treatment strategies to alleviate the patient's symptoms.