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.

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.

The Scholarly Impact of Student Authorship in Ophthalmology.

Purpose The H-index (H i ), an author-level metric of scholarly impact, is predictive of future scientific achievement. We sought to analyze the scholarly impact of student authorship on the H i of corresponding authors (CAs) within a major academic journal in the specialty of ophthalmology. Materials and Methods We compared the H i of all unique CAs for manuscripts published in Ophthalmology (Journal of the American Academy of Ophthalmology) in 2008, 2012, and 2016. Data abstraction was completed twice: in October 2018 and March 2021. We further grouped published articles for CAs into those with student authors (StA) and those without (nStA). Primary analysis involved a linear regression analysis with change in H i from October 2018 to March 2021 as the outcome variable, CA groups as the predictor variable, adjusting for the covariates of baseline H i , the year when the CA published his or her article, number of research items published in October 2018, and the academic appointment of the CAs. Secondary analysis involved a linear regression analysis with change in H i from October 2018 to March 2021 as the outcome variable, total number of student authors per CA as the predictor variable, adjusting for the covariates of baseline H i , the year CA published his or her article, number of research items published in October 2018, and the academic appointment of the CAs. Results The number of student authors increased from 168 in 2008 to 192 in 2016. Of the 902 articles, 316 articles were co-authored by one or more student authors. The average change in H i of CAs publishing with student authors (StA, 11.0 ± 14.7) was significantly greater ( p < 0.0001) than the change in H i of CAs publishing without student authors (nStA, 6.2 ± 6.2). As the total number of student authors increased, the change in H i of CAs increased linearly for all years combined (regression coefficient = 1.70, p -value < 0.0001). Conclusion CAs publishing with students in the field of ophthalmology have a higher scholarly impact than those publishing without students. The development of programs to integrate students into ophthalmology research early on may encourage their pursuit of a career in ophthalmology, while advancing the careers of their mentors.

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.

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.

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.

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.

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.

Myogenic growth factors can decrease extraocular muscle force generation: a potential biological approach to the treatment of strabismus.

PURPOSE: Future pharmacologic treatment of strabismus may be optimized if drugs that are less potentially toxic to patients can be developed. Prior studies have shown that direct injection of extraocular muscles (EOMs) with insulin growth factor or fibroblast growth factor results in significant increases in the generation of EOM force. The purpose of this study was to examine the morphometric and physiological effects of direct EOM injection with the growth factors BMP4, TGFbeta1, Shh, and Wnt3A. METHODS: One superior rectus muscle of normal adult rabbits was injected with BMP4, TGFbeta1, Shh, or Wnt3A. The contralateral muscle was injected with an equal volume of saline to serve as a control. After 1 week, the animals were euthanatized, and both superior rectus muscles were removed and assayed physiologically. The muscles were stimulated at increasing frequencies to determine force generation. A separate group of treated and control superior rectus muscles were examined histologically for alterations in total muscle cross-sectional area and myosin heavy chain isoform (MyHC) composition. RESULTS: One week after a single injection of BMP4, TGFbeta1, Shh, or Wnt3A, all treated muscles showed significant decreases in generation of force compared with control muscles. BMP4, TGFbeta1, Shh, and Wnt3A significantly decreased the mean myofiber cross-sectional area of fast MyHC-positive myofibers. BMP4 resulted in a conversion of fast-to-slow myofibers and a significant decrease in the percentage of developmental and neonatal MyHC-positive myofibers. Alterations in mean cross-sectional area and proportion of MyHCs were seen after injection with TGFbeta1, Shh, and Wnt3A. TGFbeta1 and BMP4 injections resulted in increased Pax7-positive satellite cells, whereas BMP4, TGFbeta1, and Wnt3A resulted in a decrease in MyoD-positive satellite cells. CONCLUSIONS: These results suggest that, rather than using toxins or immunotoxins, a more biological approach to decrease muscle strength is possible and demonstrate the potential utility of myogenic signaling factors for decreasing EOM strength. Ongoing drug-delivery studies will elucidate means of extending treatment effect to make such agents clinically useful.

Instability of ocular alignment in childhood esotropia.

OBJECTIVE: Instability of ocular alignment may cause surgeons to delay surgical correction of childhood esotropia. The authors investigated the stability of ocular alignment over 18 weeks in children with infantile esotropia (IET), acquired nonaccommodative esotropia (ANAET), or acquired partially accommodative esotropia (APAET). DESIGN: Prospective, observational study. PARTICIPANTS: Two hundred thirty-three children aged 2 months to less than 5 years with IET, ANAET, or APAET of less than 6 months' duration. METHODS: Ocular alignment was measured at baseline and at 6-week intervals for 18 weeks. MAIN OUTCOME MEASURES: Using definitions derived from a nested test-retest study and computer simulation modeling, ocular alignment was classified as unstable if there was a change of 15 prism diopters (PD) or more between any 2 of the 4 measurements, as stable if all 4 measurements were within 5 PD or less of one another, or as uncertain if neither criteria was met. RESULTS: Of those who completed all 3 follow-up visits within time windows for analysis, 27 (46%) of 59 subjects with IET had ocular alignment classified as unstable (95% confidence interval [CI], 33%-59%), 20% as stable (95% CI, 11%-33%), and 34% as uncertain (95% CI, 22%-47%). Thirteen (22%) of 60 subjects with ANAET had ocular alignment classified as unstable (95% CI, 12%-34%), 37% as stable (95% CI, 25%-50%), and 42% as uncertain (95% CI, 29%-55%). Six (15%) of 41 subjects with APAET had ocular alignment classified as unstable (95% CI, 6%-29%), 39% as stable (95% CI, 24%-56%), and 46% as uncertain (95% CI, 31%-63%). For IET, subjects who were older at presentation were less likely to have unstable angles than subjects who were younger at presentation (risk ratio for unstable vs stable per additional month of age, 0.85; 99% CI, 0.74-0.99). CONCLUSIONS: Ocular alignment instability is common in children with IET, ANAET, and APAET. The impact of this finding on the optimal timing for strabismus surgery in childhood esotropia awaits further study. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The effect of resection on satellite cell activity in rabbit extraocular muscle.

PURPOSE: A common treatment for motility disorders of the extraocular muscles (EOMs) is a resection procedure in which there is surgical shortening of the muscle. This procedure results in rotation of the globe toward the resected muscle, increased resting tension across the agonist-antagonist pair, and stretching of the elastic components of the muscles. In the rabbit, due to orbital constraints and limited rotation, resection results in more significant stretch of the surgically treated muscle than the antagonist. This surgical preparation allows for the examination of the effects of surgical shortening of one rectus muscle and passive stretch of its ipsilateral antagonist. METHODS: The insertional 6 mm of the superior rectus muscles of adult rabbits were resected and reattached to the original insertion site. After 7 and 14 days, the animals were injected intraperitoneally with bromodeoxyuridine (BrdU) every 2 hours for 12 hours, followed by a 24-hour BrdU-free period. All superior and inferior rectus muscles from both globes were examined for BrdU incorporation, MyoD expression, neonatal and developmental myosin heavy chain (MyHC) isoform expression, and myofiber cross-sectional area alterations. RESULTS: In the resected muscle and in the passively stretched antagonist muscle, there was a dramatic increase in the number of myofibers positive for neonatal MyHC and in the number of BrdU- and MyoD-positive satellite cells. The addition of BrdU-positive myonuclei increased from 1 per 1000 myofibers in cross sections of control muscles to 2 to 3 per 100 myofibers in the resected muscles. Single myofiber reconstructions showed that multiple BrdU-positive myonuclei were added to individual myofibers. Addition of new myonuclei occurred in random locations along the myofiber length of single fibers. There was no correlation between myofibers with BrdU-positive myonuclei and neonatal MyHC isoform expression. CONCLUSIONS: Both active and passive stretch of the rectus muscles produced by strabismus surgery dramatically upregulated the processes of satellite cell activation, integration of new myonuclei into existing myofibers, and concomitant upregulation of immature myosin heavy chain isoforms. Understanding the effects of strabismus surgery on muscle cell biological reactions and myofiber remodeling may suggest new approaches for improving surgical outcomes.

Increased extraocular muscle strength with direct injection of insulin-like growth factor-I.

PURPOSE: Previous work has demonstrated the effectiveness of insulin-like growth factor (IGF)-II in increasing force generation in extraocular muscle (EOM). Studies in the literature have suggested that IGF-I would be even more effective than IGF-II. This study was performed to assess the effects on muscle mass and force generation of IGF-I injection in adult rabbit superior rectus muscle. METHODS: Adult rabbits received a single injection of IGF-I at one of several doses into one superior rectus muscle. One week after treatment, the rabbits were euthanatized, and the superior rectus muscle from each orbit was removed. Force generation was measured using an in vitro apparatus, and injected muscles were compared with the contralateral control. A second group of animals were injected similarly, and the muscles were examined at 1 week for changes in cross-sectional area of individual myofibers. RESULTS: EOMs demonstrate significant numbers of cells expressing the IGF receptor. After the EOMs were injected with IGF-I, there were significant increases both in muscle force generation and cross-sectional area at all doses tested in this study. Doses of 10 and 25 microg IGF-I were most effective. CONCLUSIONS: Direct muscular injection of IGF-I effectively increases EOM force generation without the potential biomechanical hazards of surgery such as permanently altered muscle length or insertional position on the globe.

Increasing muscle strength as a treatment for strabismus: sustained release of insulin-like growth factor-1 in rabbit extraocular muscle.

PURPOSE: Currently, no drug treatment is available for strengthening underacting extraocular muscles (EOM) in strabismus. We showed previously that single injections of insulin-like growth factor (IGF-1) result in significant but short-term increases in muscle force generation. This study examined the effects of sustained release of IGF-1 on force generation in rabbit superior rectus muscles. METHODS: In adult rabbits, slow-release pellets containing IGF-1 were implanted on the global side of one superior rectus muscle. After 1 week, or 1, 2, 3, or 6 months, treated and control muscles were examined for force generation using an in vitro physiology apparatus. All muscles were prepared for histology and mean myofiber cross-sectional areas were determined. RESULTS: One and 3 months after pellet implantation, treated muscles generated significantly greater force than contralateral control muscles, whereas at 2 months, no significant difference was found. Force per cross-sectional area (mN/cm(2)) at 3 months also increased significantly in the treated muscles. Mean muscle cross-sectional area increased significantly after 1, 2, and 3 months of sustained exposure to IGF-1 compared with controls. After an additional 3 months without IGF-1 exposure, mean cross-sectional areas were significantly greater than controls but significantly reduced compared with areas at 1, 2, and 3 months. CONCLUSIONS: IGF-1 appears to be highly effective in increasing muscle force generation. Because slow release of IGF-1 results in sustained increases in EOM force generation, it may be a potentially useful alternative to surgical resection procedures because it avoids many of the potential long-term biomechanical hazards of resection surgery.

Strabismus and amblyopia in bilateral Peters anomaly.

BACKGROUND: Peters anomaly is a rare form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs at the end of the third week of gestation. We examined the prevalence of strabismus and amblyopia and analyzed predictive factors for their development, as well as the visual outcome and associated anomalies in patients with bilateral Peters anomaly. METHODS: Using a retrospective review, we identified 25 consecutive patients with bilateral Peters anomaly who were observed between August 1995 and February 2005. Ocular structural and systemic anomalies, amblyopia therapy, visual acuity, and binocular alignment at last visit were recorded. Fisher's exact test was used to identify any association between defined predictive factors and the development of strabismus. RESULTS: Mean follow-up time was 5.1 year (range, 0.5-21 years). Median age at presentation was 2.5 months (range, 1 day to 13 years). Penetrating keratoplasties were performed on 34 eyes in 20 patients. Final best-corrected visual acuity ranged from 20/25 to no light perception. Thirteen of 18 patients with recorded motility (72%) developed strabismus: esotropia (n = 7), exotropia (n = 5), and variable (n = 1); one also had dissociated vertical deviation. Patients with equal vision were either orthophoric (n = 4) or had intermittent esotropia (n = 1), whereas strabismus occurred in 100% of patients whose vision was asymmetric by more than 1.5 octaves. Asymmetric vision was the only statistically significant predictive factor for the development of strabismus (P = 0.002). Amblyopia treatment resulted in improved vision in 3 of 5 patients. CONCLUSION: Strabismus occurs frequently in bilateral Peters anomaly. Asymmetric vision, (because of ocular structural anomalies) postoperative complications, and amblyopia may predispose to strabismus. Despite ocular structural limitations, amblyopia therapy is recommended in the aggressive rehabilitation of these eyes.

The natural history of glaucoma and ocular hypertension after pediatric cataract surgery.

INTRODUCTION: We sought to define the prevalence and natural history of ocular hypertension and glaucoma for at least a 10-year period after pediatric cataract surgery. METHODS: We conducted a prospective observational study of patients who received pediatric cataract surgery. Inclusion criteria included 2 directed ophthalmologic examinations performed at a minimum of 5 and 10 years after surgery. RESULTS: A total of 63 patients (22 with bilateral cataracts and 41 with unilateral cataracts) were examined at a median of 15.1 year (range, 10.3-21.3 years) after surgery. A majority of the subjects had glaucoma or ocular hypertension (ie, 59%; 37/63). Nineteen percent (12/63) had glaucoma (5/22 with bilateral cataracts and 7/41 with unilateral cataracts). Approximately half (7/12) had developed glaucoma during the first 5-year observational period and the remainder (5/12) developed it during the following observational period. Forty percent (25/63) of the patients had ocular hypertension in at least one aphakic eye (9/23 with bilateral cataracts and 16/40 with unilateral cataracts). The rate of progression from ocular hypertension to glaucoma over a mean observational period of 7.2 years (range, 6.2-8.1 years) was 23% (5/22). DISCUSSION: Patients who receive surgery for pediatric cataracts are at very high risk of developing ocular hypertension and glaucoma. Patients can develop late-onset glaucoma and ocular hypertension more than 10 years after surgery. Years of ocular hypertension may precede the diagnosis of late-onset glaucoma.