Search

Purpose To review the scientific literature that evaluates the effectiveness of adjustable sutures in the management of strabismus for adult and pediatric patients. Methods Literature searches were performed in the PubMed database through April 2021 with no date limitations and were restricted to publications in English. The searches identified 551 relevant citations, of which 55 were reviewed in full text. Of these, 17 articles met the inclusion criteria and were assigned a level of evidence rating by the panel methodologist. The search included all randomized controlled studies regardless of study size and cohort studies of 100 or more patients comparing the adjustable versus nonadjustable suture technique, with a focus on motor alignment outcomes or reoperation rates. Results The literature search yielded no level I studies. Of the 17 articles that met the inclusion criteria, 11 were rated level II and 6 were rated level III. Among the 12 studies that focused on motor alignment outcomes, 4 small randomized clinical trials (RCTs) did not find a statistically significant difference between groups, although they were powered to detect only very large differences. Seven of 8 nonrandomized studies found a statistically significant difference in motor alignment success in favor of the adjustable suture technique, both overall and in certain subgroups of patients. Successful motor alignment was seen in both exotropia (in 3 studies that were not limited to children) and esotropia (in 1 study of adults and 2 of children). The majority of included studies that reported on reoperation rates found the rates to be lower in patients who underwent strabismus surgery with adjustable sutures, but this finding was not uniformly demonstrated. Conclusions Although there are no level I studies evaluating the effectiveness of adjustable sutures for strabismus surgery, the majority of nonrandomized studies that met the inclusion criteria for this assessment reported an advantage of the adjustable suture technique over the nonadjustable technique with respect to motor alignment outcomes. This finding was not uniformly demonstrated among all studies reviewed and warrants further investigation in the development and analysis of adjustable suture techniques.

Purpose To review home- and office-based vergence and accommodative therapies for treatment of convergence insufficiency (CI) in children and young adults up to 35 years of age. Methods Literature searches were conducted through October 2020 in the PubMed database for English-language studies. The combined searches yielded 359 abstracts, of which 37 were reviewed in full text. Twelve of these were considered appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist. Results Of the 12 studies included in this assessment, 8 were graded as level I evidence, 2 were graded as level II evidence, and 2 were graded as level III evidence. Two of the level I studies included older teenagers and young adults; the remainder of the studies exclusively evaluated children. Two randomized controlled trials found that office-based vergence and accommodative therapies were effective in improving motor outcomes in children with symptomatic CI. However, the studies reported conflicting results on the efficacy of office-based therapy for treating symptoms of CI. Data were inconclusive regarding the effectiveness of home-based therapies (including pencil push-ups and home computer therapy) compared with home placebo. In young adults, office-based vergence and accommodative therapies were not superior to placebo in relieving symptoms of CI. Conclusions Level I evidence suggests that office-based vergence and accommodative therapies improve motor outcomes in children with symptomatic CI, although data are inconsistent regarding symptomatic relief. Evidence is insufficient to determine whether home-based therapies are effective.

Purpose To review the available evidence comparing the effectiveness of extraocular muscle botulinum toxin type A (BTXA) injection with eye muscle surgery for restoring ocular alignment in children and adults with nonparalytic, nonrestrictive horizontal strabismus. Methods Literature searches in the PubMed Cochrane Library, and clinical trial databases with no date restrictions, but limited to articles published in English, were conducted last on January 10, 2021. The searches yielded 515 citations, 40 of which were reviewed in full text by the first author. Fourteen articles met the criteria for inclusion (randomized or nonrandomized comparative studies, or case series with a minimum 50 patients; evaluating extraocular muscle BTXA injection for initial or repeat treatment of horizontal, nonparalytic, nonrestrictive strabismus; with at least 6 months of follow-up) and were graded by a methodologist. Results The 14 included studies consisted of 2 randomized clinical trials, 3 nonrandomized comparative studies, and 9 case series. All 5 comparative studies were graded level II evidence, and the 9 case series were graded level III evidence. Successful motor outcomes after BTXA injection were relatively consistent across 4 of the 5 comparative studies at 60%, when adjustment was made for differential selection bias in 1 of the studies. In the 4 studies, successful motor outcomes after surgery ranged from 66% to 77% with a mean follow-up of 23 to 75 months, and the outcomes were not significantly different from those after BTXA injection. In the fifth level II study, success was significantly higher with BTXA injection than with surgery (94% vs. 72%). The level III BTXA case series demonstrated higher motor success rates of 87% to 89% when children were treated in 2 muscles at a time; rates were lower in adults treated with single-muscle BTXA injection. Conclusions Extraocular muscle injection of BTXA achieves a high rate of successful motor alignment, comparable with that achieved after eye muscle surgery for nonparalytic, nonrestrictive horizontal strabismus. Good alignment may require multiple BTXA injections, and it is not yet clear whether sensory outcomes are equivalent for BTXA injections versus eye muscle surgery in young children.

Purpose To review the published literature assessing the efficacy and safety of in-office probing compared with facility-based probing to treat congenital nasolacrimal duct obstruction (NLDO). Methods Literature searches were conducted in March 2020 in the PubMed database with no date restrictions and limited to studies published in English and in the Cochrane Library database with no restrictions. The combined searches yielded 281 citations. Of these, 21 articles were deemed appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist. Four articles were rated level I, 2 articles were rated level II, and 15 articles were rated level III. Results Treatments consisted of observation, in-office nasolacrimal probing, or facility-based nasolacrimal probing. Success rates and complications or recurrences were recorded from 1 week to 6 months after surgery. Complete resolution of symptoms after surgery ranged from 66% to 95.6% for office-based procedures versus 50% to 97.7% for facility-based procedures. Level I evidence indicated that 66% of cases spontaneously resolved after 6 months of observation in infants between 6 and 10 months of age. Success rates for in-office probing were lower for bilateral than for unilateral NLDO (67% vs. 82%), whereas success rates were high in both unilateral (83%) and bilateral (82%) patients who underwent facility-based probing after 6 months of observation. Cost data did not indicate a definitive cost savings of either treatment method ($562 for in-office vs. $701 for facility-based, depending on cost models predicting spontaneous resolution rates at different ages). No serious adverse events with treatment or anesthesia were reported for either treatment method. Conclusions Evidence supports the efficacy and safety of both in-office and facility-based surgery for congenital NLDO. However, treating bilateral NLDO in a facility setting may be better. Because a significant percentage of children achieved resolution spontaneously before 12 months of age, deferring treatment until 12 to 18 months of age is a reasonable option. Additional research may address symptom burden on families and the impact of anesthesia and emotional trauma of nonsedated office probings on patients and may explore further the cost of treatment for each treatment method.

To evaluate outcomes of bilateral cataract surgery in children aged 7 to 24 months and compare rates of adverse events (AEs) with other Toddler Aphakia and Pseudophakia Study (TAPS) registry outcomes.Retrospective clinical study at 10 Infant Aphakia Treatment Study (IATS) sites. Statistical analyses comparing this cohort with previously reported TAPS registry cohorts.Children enrolled in the TAPS registry between 2004 and 2010.Children underwent bilateral cataract surgery with or without intraocular lens (IOL) placement at age 7 to 24 months with 5 years of postsurgical follow-up.Visual acuity (VA), occurrence of strabismus, AEs, and reoperations.A total of 40 children (76 eyes) who underwent bilateral cataract surgery with primary posterior capsulectomy were identified with a median age at cataract surgery of 11 months (7-23); 68% received a primary IOL. Recurrent visual axis opacification (VAO) occurred in 7.5% and was associated only with the use of an IOL (odds ratio, 6.10; P = 0.005). Glaucoma suspect (GS) was diagnosed in 2.5%, but no child developed glaucoma. In this bilateral cohort, AEs (8/40, 20%), including glaucoma or GS and VAO, and reoperations occurred in a similar proportion to that of the published unilateral TAPS cohort. When analyzed with children aged 1 to 7 months at bilateral surgery, the incidence of AEs and glaucoma or GS correlated strongly with age at surgery (P = 0.011/0.004) and glaucoma correlated with microcornea (P = 0.040) but not with IOL insertion (P = 0.15).Follow-up to age 5 years after bilateral cataract surgery in children aged 7 to 24 months reveals a low rate of VAO and very rare glaucoma or GS diagnosis compared with infants with cataracts operated at7 months of age despite primary IOL implantation in most children in the group aged 7 to 24 months. The use of an IOL increases the risk of VAO irrespective of age at surgery.

Purpose To review the published literature on the accuracy of ophthalmic imaging methods to differentiate between papilledema and pseudopapilledema in children. Methods Literature searches were conducted in January 2020 in the PubMed database for English-language studies with no date restrictions and in the Cochrane Library database without any restrictions. The combined searches yielded 354 abstracts, of which 17 were reviewed in full text. Six of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. All 6 included studies were rated as level III evidence. Results Fluorescein angiography, a combination of 2 OCT protocols, and multicolor confocal scanning laser ophthalmoscopy (Spectralis SD-OCT; Heidelberg Engineering, Heidelberg, Germany) demonstrated the highest positive percent agreement (92%–100%; 95% confidence interval [CI], 69%–100%) and negative percent agreement (92%–100%; 95% CI, 70%–100%) with a clinical diagnosis of papilledema in children. However, results must be interpreted with caution owing to methodologic limitations, including a small sample size leading to wide CIs and an overall lack of data (there was only 1 study each for the above methods and protocols). Ultrasonographic measures showed either a high positive percent agreement (up to 95%) with low negative percent agreement (as low as 58%) or vice versa. Autofluorescence and fundus photography showed a lower positive (40%–60%) and negative (57%) percent agreement. Conclusions Although several imaging methods demonstrated high positive and negative percent agreement with clinical diagnosis, no ophthalmic imaging method conclusively differentiated papilledema from pseudopapilledema in children because of the lack of high-quality evidence. Clinicians must continue to conduct thorough history-taking and examination and make judicious use of ancillary testing to determine which children warrant further workup for papilledema.

To evaluate outcomes of bilateral cataract surgery in infants 1 to 7 months of age performed by Infant Aphakia Treatment Study (IATS) investigators during IATS recruitment and to compare them with IATS unilateral outcomes.Retrospective case series review at 10 IATS sites.The Toddler Aphakia and Pseudophakia Study (TAPS) is a registry of children treated by surgeons who participated in the IATS.Children underwent bilateral cataract surgery with or without intraocular lens (IOL) placement during IATS enrollment years 2004 through 2010.Visual acuity (VA), strabismus, adverse events (AEs), and reoperations.One hundred seventy-eight eyes (96 children) were identified with a median age of 2.5 months (range, 1-7 months) at the time of cataract surgery. Forty-two eyes (24%) received primary IOL implantation. Median VA of the better-seeing eye at final study visit closest to 5 years of age with optotype VA testing was 0.35 logarithm of the minimum angle of resolution (logMAR; optotype equivalent, 20/45; range, 0.00-1.18 logMAR) in both aphakic and pseudophakic children. Corrected VA was excellent (20/40) in 29% of better-seeing eyes, 15% of worse-seeing eyes. One percent showed poor acuity (≥20/200) in the better-seeing eye, 12% in the worse-seeing eye. Younger age at surgery and smaller (9.5 mm) corneal diameter at surgery conferred an increased risk for glaucoma or glaucoma suspect designation (younger age: odds ratio [OR], 1.44; P = 0.037; and smaller cornea: OR, 3.95; P = 0.045). Adverse events also were associated with these 2 variables on multivariate analysis (younger age: OR, 1.36; P = 0.023; and smaller cornea: OR, 4.78; P = 0.057). Visual axis opacification was more common in pseudophakic (32%) than aphakic (8%) eyes (P = 0.009). Unplanned intraocular reoperation occurred in 28% of first enrolled eyes (including glaucoma surgery in 10%).Visual acuity after bilateral cataract surgery in infants younger than 7 months is good, despite frequent systemic and ocular comorbidities. Although aphakia management did not affect VA outcome or AE incidence, IOL placement increased the risk of visual axis opacification. Adverse events and glaucoma correlated with a younger age at surgery and glaucoma correlated with the presence of microcornea.

Purpose To evaluate long-term outcomes of surgical treatment for abnormal head positioning (AHP) associated with infantile nystagmus syndrome (INS). Design Retrospective observational case series. Methods Review of 150 patients who underwent surgery for AHP associated with nystagmus. Outcomes included head positioning, duction limitations, and strabismus, and were evaluated several times postoperatively. Successful collapse of AHP was defined as being ≤10°. Results Thirty-one patients had surgery for AHP in the pitch (chin up/down) position, whereas 119 had surgery for a horizontal AHP. In addition, 54 underwent 50%-60% augmentation, 19 underwent 40% augmentation, 5 underwent less than 40% augmentation. Thirty-eight had surgical dose modified to correct strabismus, and 3 underwent surgery different from standard Kestenbaum procedures. Collapse of AHP: At the 1-3-week follow-up (n = 131), 125 patients (95%) had collapse of AHP. The percentage trended down at the 2-5-month (91%, n = 106) and 2-year follow-ups (83%, n = 57). However, at 5 and 10 years, it was 93% (n = 42) and 93% (n = 14), respectively, due to reoperation in a small minority. Over- and undercorrection: At 1-3 weeks, 5% of patients were overcorrected whereas 0% were undercorrected. Over- and undercorrection rates peaked at 2 years postoperatively. Ten years out, there were no overcorrections and 7% undercorrections. Four percent of patients required reoperation for overcorrection (mean 2.7 years) and 5% did for undercorrection (mean 3.9 years). Conclusion Surgery for the head positioning associated with INS produces excellent outcomes throughout 10 years postoperatively. Overcorrection presents early and resolves either over time or with additional surgery. Undercorrection develops later and can persist despite reoperation.

Purpose To evaluate outcomes of unilateral cataract surgery in children 7 to 24 months of age. Design Retrospective case series at 10 Infant Aphakia Treatment Study (IATS) sites. Participants The Toddler Aphakia and Pseudophakia Study is a registry of children treated by surgeons who participated in the IATS. Methods Children underwent unilateral cataract surgery with or without intraocular lens (IOL) placement during the IATS enrollment years of 2004 and 2010. Main Outcome Measures Intraoperative complications, adverse events (AEs), visual acuity, and strabismus. Results Fifty-six children were included with a mean postoperative follow-up of 47.6 months. Median age at cataract surgery was 13.9 months (range, 7.2–22.9). Ninety-two percent received a primary IOL. Intraoperative complications occurred in 4 patients (7%). At 5 years of age, visual acuity of treated eyes was very good (≥20/40) in 11% and poor (≤20/200) in 44%. Adverse events were identified in 24%, with a 4% incidence of glaucoma suspect. An additional unplanned intraocular surgery occurred in 14% of children. Neither AEs nor intraocular reoperations were more common for children with surgery at 7 to 12 months of age than for those who underwent surgery at 13 to 24 months of age (AE rate, 21% vs. 25% [P = 0.60]; reoperation rate, 13% vs. 16% [P = 1.00]). Conclusions Although most children underwent IOL implantation concurrent with unilateral cataract removal, the incidence of complications, reoperations, and glaucoma was low when surgery was performed between 7 and 24 months of age and compared favorably with same-site IATS data for infants undergoing surgery before 7 months of age. Our study showed that IOL implantation is relatively safe in children older than 6 months and younger than 2 years.

A test of suppression was developed to provide a standardized approach to detecting and grading density of suppression in children with intermittent exotropia when manifestly exotropic. This new Office Suppression Test is a three-step procedure to grade suppression on a 4-point scale (from 0 for "negligible suppression" to 3 for "dense suppression"). The test was performed in 57 children 3-13 years of age with intermittent exotropia (distance angle of 16Δ-35Δ, with spontaneous tropia) during enrollment in a randomized trial. Of the 57 children, 51 could complete testing: 28 (55%) had dense suppression, 12 (24%) had moderate suppression, 5 (10%) had mild suppression, and 6 (12%) had negligible suppression. In a subgroup of 20 untreated children, suppression was evaluated again at 8 weeks. There was moderate agreement between suppression scores at baseline and at 8 weeks (weighted κ = 0.65 [95% CI, 0.45-0.84]).

Context Early integrated palliative care improves quality of life, but palliative care programs are underutilized. Psychoeducational interventions explaining palliative care may increase patients' readiness for palliative care. Objectives To 1) collaborate with stakeholders to develop the EMPOWER 2 intervention explaining palliative care, 2) examine acceptability, 3) evaluate feasibility and preliminary efficacy. Methods The research was conducted at a North American cancer center and involved 21 stakeholders and 10 patient-participants. Investigators and stakeholders iteratively developed the intervention. Stakeholders rated acceptability of the final intervention. Investigators implemented a pre-post trial to examine the feasibility of recruiting 10 patients with metastatic cancer within one month and with a ≥50% consent rate. Preliminary efficacy outcomes were changes in palliative care knowledge and attitudes. Results Using feedback from four stakeholder meetings, we developed a multimedia intervention tailored to three levels of health-literacy. The intervention provides knowledge and reassurance about the purpose and nature of palliative care, addressing cognitive and emotional barriers to utilization. Stakeholders rated the intervention and design process highly acceptable (3.78/4.00). The pilot met a priori feasibility criteria (10 patients enrolled in 14 days; 83.3% consent rate). The intervention increased palliative care knowledge by 83.1% and improved attitudes by 18.9 points on a 0 to 51 scale (Ps Conclusions This formative research outlines the development of a psychoeducational intervention about palliative care. The intervention is acceptable, feasible, and demonstrated promising pilot test results. This study will guide clinical teams in improving patients’ readiness for palliative care and inform the forthcoming EMPOWER 3 randomized clinical trial.

Importance Glaucoma-related adverse events constitute serious complications of cataract removal in infancy, yet long-term data on incidence and visual outcome remain lacking. Objective To identify and characterize incident cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of 10.5 years and to determine whether these diagnoses are associated with optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) assessment. Design, Setting, and Participants Analysis of a multicenter randomized clinical trial of 114 infants with unilateral congenital cataract who were aged 1 to 6 months at surgery. Data on long-term glaucoma-related status and outcomes were collected when children were 10.5 years old (July 14, 2015, to July 12, 2019) and analyzed from March 30, 2019, to August 6, 2019. Interventions Participants were randomized at cataract surgery to either primary intraocular lens (IOL), or aphakia (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis. Main Outcomes and Measures Development of glaucoma and glaucoma + glaucoma suspect in operated-on eyes up to age 10.5 years, plus intraocular pressure, axial length, RNFL (by optical coherence tomography), and ONH photographs. Results In Kaplan-Meier analysis, for all study eyes combined (n = 114), risk of glaucoma after cataract removal rose from 9% (95% CI, 5%-16%) at 1 year, to 17% (95% CI, 11%-25%) at 5 years, to 22% (95% CI, 16%-31%) at 10 years. The risk of glaucoma plus glaucoma suspect diagnosis after cataract removal rose from 12% (95% CI, 7%-20%) at 1 year, to 31% (95% CI, 24%-41%) at 5 years, to 40% (95% CI, 32%-50%) at 10 years. Risk of glaucoma and glaucoma plus glaucoma suspect diagnosis at 10 years was not significantly different between treatment groups. Eyes with glaucoma (compared with eyes with glaucoma suspect or neither) had longer axial length but relatively preserved RNFL and similar ONH appearance and visual acuity at age 10 years. Conclusions and Relevance Risk of glaucoma-related adverse events continues to increase with longer follow-up of children following unilateral cataract removal in infancy and is not associated with primary IOL implantation. Development of glaucoma (or glaucoma suspect) after removal of unilateral congenital cataract was not associated with worse visual acuity outcomes at 10 years. Trial Registration ClinicalTrials.gov Identifier:NCT00212134

Cataract is the most common cause of treatable visual disability in children worldwide and affects approximately 500 children annually in the United States. The prevalence has been reported to range between 1 and 15 per 10,000 children (Foster et al. J Cataract Refract Surg 23(Suppl 1):601–4, 1997). Pediatric cataracts can be classified as congenital or acquired depending on their etiology and age of onset. Congenital cataracts are those that are present at birth, though may be undetected until later in life. Acquired (infantile or juvenile) cataracts are defined as those that develop between 6 months and 2 years or after 2 years, respectively. Acquired cataracts can be classified based on their etiology, morphology, and the presence or absence of associated anterior segment abnormalities. This chapter will focus on evaluation and initial management of secondary and acquired cataracts.

Purpose We evaluated the relative effectiveness of combined recession-resection of vertical rectus muscles versus superior rectus recession with inferior oblique weakening for patients who underwent surgical correction of chin-down abnormal head position (AHP) associated with infantile nystagmus syndrome (INS). Design Retrospective interventional case series. Methods This is a review of 22 patients who underwent surgical correction of chin-down vertical AHP associated with INS at an academic institution. The primary outcome was collapse of AHP. Unfavorable outcomes included repeat surgery and induced strabismus, in addition to failure of collapse of AHP. Results Twenty-two patients had chin-down AHP. Recession-resection (bilateral superior rectus recession 6-9 mm; bilateral inferior rectus resection 5-9 mm) was performed in 11 cases; weakening of both elevators (bilateral superior rectus recession 5-8 mm, bilateral inferior oblique recession or myectomy) occurred in 11 cases. Unfavorable outcome rates were 64% (7/11) compared with 18% (2/11), respectively (P = .03). Reoperation was performed for 6 of 22 patients. Five patients were from the recession-resection group, namely 3 for induced V-pattern esotropia, 1 for alternating esotropia, and 1 to correct recurrent AHP. The last of the 6 who required reoperation was in the elevator weakening group, and required correction of a recurrent AHP (P = .06). Conclusions While recession-resection of the vertical recti and weakening of both elevators each produce acceptable collapse of chin-down AHP, the former frequently induces a V-pattern esotropia requiring reoperation.

Objective: To review a single center experience with the diagnosis of visual impairment in patients with sensorineural hearing loss (SNHL) and propose a diagnostic algorithm. Study Design: Retrospective study of patients with SNHL who were diagnosed with ophthalmologic abnormalities in the course of evaluation. Setting: University children's hospital and university-associated eye institute. Subjects and Methods: Children with the diagnosis of sensorineural hearing loss aged 0-18 who received a formal ophthalmology examination between the dates of December 2000-December 2016 were included for analysis. Children were identified using ICD-9 and ICD-10 billing codes. Primary measures included diagnosis of SNHL, ophthalmologic diagnoses, and referral source. Results: Two hundred and sixty-nine patients with SNHL met inclusion criteria. One hundred and thirty-one (48.5%) of these patients had an ophthalmic abnormality. When evaluating referral source, patients referred by a pediatrician following failed vision screen or visual complaint were more likely to have an ophthalmologic finding (61%, n = 147) when compared to referral by an otolaryngologist following diagnosis of SNHL (9.6%, n = 73). Seventeen of the 131 (13%) patients with at least one ophthalmic abnormality had an abnormality that was deemed unlikely to be detected by routine screening. Conclusion: Our study agreed with previously published works that there is a high rate of ophthalmic abnormalities in patients with SNHL. Evaluation of referral source for ophthalmology evaluation suggests that routine referral by otolaryngologists in patients with SNHL may not be an efficient means of identifying patients with treatable ophthalmic disease. Reliance on school and office screenings to detect ophthalmic abnormalities, prior to referral, is likely a more efficient model, even among patients with SNHL.

Importance Cataract is an important cause of visual impairment in children. Outcomes reported from a large clinical disease-specific registry can provide real-world estimates of visual outcomes and rates of adverse events in clinical practice. Objective To describe visual acuity and refractive error outcomes, as well as rates of amblyopia, glaucoma, and additional eye surgery, during the first year after lensectomy in children. Design, Setting, and Participants A prospective observational study was conducted from June 18, 2012, to July 8, 2015, at 61 pediatric eye care practices among 880 children younger than 13 years at the time of lensectomy in at least 1 eye with follow-up within 15 months after surgery. Statistical analysis was performed from December 12, 2016, to December 14, 2018. Exposures Lensectomy with or without implantation of an intraocular lens. Main Outcomes and Measures Visual acuity as well as rates of amblyopia, glaucoma, suspected glaucoma, and other intraocular surgery. Results Among the 880 children (432 girls and 448 boys; mean [SD] age at annual follow-up, 4.9 [3.8] years) in the study, lens surgery was bilateral in 362 (41.1%; 95% CI, 37.9%-44.4%) children and unilateral in 518 (58.9%; 95% CI, 55.6%-62.1%). An intraocular lens was implanted in 654 of 1132 eyes (60.2%; 95% CI, 57.0%-63.4% [proportions reported for eye-level outcomes account for the potential correlation induced by enrolling both eyes of some individuals; for participants who received bilateral surgery, these numbers will differ from the quotient of the number of cases divided by the total sample size]). Amblyopia was identified in 449 children (51.0%; 95% CI, 47.7%-54.3%). In children age 3 years or older, mean visual acuity was 0.30 logMAR (about 20/40) in 153 bilateral pseudophakic eyes, 0.49 logMAR (about 20/63) in 141 unilateral pseudophakic eyes, 0.47 logMAR (about 20/63) in 21 bilateral aphakic eyes, and 0.61 logMAR (about 20/80) in 17 unilateral aphakic eyes. Mean visual acuity improved with older age at surgery in eyes with bilateral pseudophakia by 0.2 logMAR line (99% CI, 0.02-0.4;P = .005) and by 0.3 logMAR line (99% CI, 0.04-0.60;P = .004) in eyes with unilateral pseudophakia. A new diagnosis of glaucoma or suspected glaucoma was made in 67 of 1064 eyes that did not have glaucoma prior to lensectomy (5.9%; 95% CI, 4.6%-7.7%); 36 of 273 eyes with bilateral aphakia (13.2%; 95% CI, 9.0%-19.0%), 5 of 308 eyes with bilateral pseudophakia (1.5%; 95% CI, 0.6%-4.2%), 14 of 178 eyes with unilateral aphakia (7.9%; 95% CI, 4.7%-12.8%), and 12 of 305 eyes with unilateral pseudophakia (3.9%; 95% CI, 2.2%-6.8%). Additional intraocular surgery, most commonly vitrectomy or membranectomy to clear the visual axis, was performed in 189 of 1132 eyes (17.0%; 95% CI, 14.8%-19.6%). Conclusions and Relevance Amblyopia was frequently observed during the first year after lensectomy in this cohort of children younger than 13 years. For children age 2 years or older at surgery visual acuity was typically less than normal for age and was worse with unilateral cataract. Management of visual axis obscuration was the most common complication requiring surgical intervention during the first year after surgery.

There is no consensus on the surgical management of head position associated with infantile nystagmus syndrome (INS) when strabismus coexists, and few outcome data have been published. We propose classifying strabismus into concordant or discordant based on the relationship between head positioning and strabismus and then modifying surgery accordingly. Our objective is to describe this system and to review surgical outcomes.Retrospective observational case series.Twenty-eight patients with INS and coexisting horizontal strabismus underwent surgery for horizontal head positioning and had ≥2 months of follow-up from 1995-2018 at the Vanderbilt Eye Institute. Outcome variables included head positioning (minimal, ≤10°; mild, 11-30°; moderate 31-44°; and severe ≥45°), strabismus (range 0-70 prism diopters [PDs]; minimal ≤10 PD), and reoperation rates. Nonparametric Wilcoxon signed rank, Fisher exact, and Mann-Whitney U tests were used for statistical analysis.Twenty-one cases were concordant and 7 were discordant; the mean follow-up was 4.1 years. Ninety-six percent of patients had moderate to severe head positioning at baseline. Correction rates (to minimal) were 100% at 2-5 months postoperatively and 86% at last follow-up (P .0001 at both time points compared with preoperatively). The magnitude of strabismus decreased compared with preoperative strabismus (30.8 ± 10.8 PDs; n = 28), strabismus at 2-5 months (9.1 ± 11.9 PDs; P = .0001; n = 26), and last follow-up (12.0 ± 14.1 PDs; P = .0003; n = 28). The overall reoperation rate was 32%.Our classification system in patients with INS allows a systematic way to surgically improve head positioning and strabismus in cases of moderate to severe baseline head positioning.

Importance The Pediatric Eye Disease Investigator Group Cataract Registry provides a multicenter assessment of visual outcomes and complications after lensectomy for traumatic pediatric cataract. Objective To report visual acuity (VA) and the cumulative proportion with strabismus, glaucoma, and other ocular complications by 15 months after lensectomy for traumatic cataract among children younger than 13 years at the time of surgery. Design, Setting, and Participants From June 18, 2012, to July 8, 2015, 1266 eyes of 994 children from 33 pediatric eye care practices seen within 45 days after lensectomy were enrolled in a multicenter, prospective observational registry. Of these, 74 eyes of 72 participants undergoing lensectomy for traumatic cataract were included in a cohort study. Follow-up was completed by November 2, 2015, and data were analyzed from March 20, 2018, to July 7, 2020. Exposures Lensectomy after ocular trauma. Main Outcomes and Measures Best-corrected VA from 9 to 15 months after lensectomy for traumatic cataract (for those 3 years or older) and the cumulative proportion with strabismus, glaucoma, and other ocular complications by 15 months. Results Of 994 participants in the registry, 84 (8%) had traumatic cataract. The median age at lensectomy for 72 participants examined within 15 months after surgery was 7.3 (range, 0.1-12.6) years; 46 (64%) were boys. An intraocular lens was placed in 57 of 74 eyes (77%). In children 3 years or older at outcome, the median best-corrected VA was 20/250 (range, 20/20 to worse than 20/800) in 6 eyes with aphakia and 20/63 (range, 20/20 to 20/200) in 26 eyes with pseudophakia. Postoperative visual axis opacification was reported in 18 of 27 eyes with pseudophakia without primary posterior capsulotomy (15-month cumulative proportion, 77%; 95% CI, 58%-92%). The cumulative proportion with strabismus was 43% (95% CI, 31%-58%) in 64 participants with ocular alignment data; exotropia was present in 14 of 23 participants (61%). The cumulative proportion with glaucoma was 6% (95% CI, 2%-16%). Conclusions and Relevance Trauma was not a common cause of pediatric cataract requiring surgery. For children with traumatic cataract, substantial ocular morbidity including permanent vision loss was found, and long-term eye and vision monitoring are needed for glaucoma, strabismus, and capsular opacification.

Telemedicine for the detection of retinopathy of prematurity (ROP) is becoming increasingly common; however, obtaining the required multiple retinal images from an infant can be challenging. This secondary analysis from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study evaluated the detection of referral-warranted ROP (RW-ROP) by trained readers when a full set of 5 retinal images could not be obtained.A total of 7,905 image sets from 1,257 infants in the study were evaluated. Retinal location of images and image quality were recorded. Sensitivity and specificity of RW-ROP detection by trained readers were calculated by comparing findings in incomplete image sets to the findings on standard eye examination.The majority of image sets contained all 5 retinal images (92.8%). The disk center view was the image most likely to be present and to be of acceptable image quality (96.8%). The nasal retina was the most difficult to obtain with acceptable image quality (83.4%). Sensitivity of detection of RW-ROP was 82.1% when 5 retinal images of acceptable quality were submitted for grading, 67.2% when 4 acceptable images were submitted, and 66.7% for 3 or fewer acceptable images (P = 0.02), with corresponding specificity of 82.2%, 89.0%, and 81.7% respectively (P0.0001). When images of any quality were evaluated, sensitivity was not increased (P = 0.74).The likelihood of detecting RW-ROP by telemedicine screening is decreased when a full set of retinal images is not obtained.

Importance The current guidelines for retinopathy of prematurity (ROP) detection programs in the United States include a range of birth weights (BWs) and gestational ages and likely require examinations of many premature infants who are at low risk for developing serious retinopathy. Objective To determine the incidence, onset, and early course of ROP in what to our knowledge is the largest cohort to date that is representative of infants who are undergoing ROP screening. Design, Setting, and Participants This secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) retrospective cohort study was conducted in 29 hospitals in the United States and Canada between January 2006 and December 2011 and included 7483 infants who underwent serial ROP examinations. Main Outcomes and Measures Most severe ROP in either eye, classified as no ROP, mild ROP, type 2 ROP, or type 1 ROP (per Early Treatment for ROP Study criteria). Onset at postmenstrual age for zone I disease and stage of ROP, plus disease, and treatment. Results This study included 7483 infants with a mean (SD) BW of 1099 (259) g and a mean (SD) gestational age of 28 (3) weeks who underwent ROP examinations. Of these, 3224 infants (43.1%) developed ROP, 459 (6.1%) developed type 1 and 472 (6.3%) type 2 ROP, 514 (6.9%) underwent treatment in 1 or both eyes, and 147 (2%) had zone I disease. Additionally, 98.1% of type 1 or 2 ROP cases occurred in infants with a BW of less than 1251 g. Only about half of the eyes (49.4%) were vascularized into zone III by 37 weeks postmenstrual age. Conclusions and Relevance These findings add to our knowledge of ROP screening as they include all eligible infants, not just high-risk infants as in previous studies. More than 40% of at-risk premature infants develop some stage of ROP, and most retinopathy regresses without treatment. However, approximately 12.5% develop severe ROP, which occurs almost exclusively among infants with a BW of less than 1251 g.

Importance The first Postnatal Growth and Retinopathy of Prematurity Study (G-ROP-1) developed new screening criteria with 100% sensitivity for type 1 retinopathy of prematurity (ROP) and 30% reduction of infants requiring examinations in a retrospective development cohort of 7483 infants from 29 North American hospitals in 2006-2012. Infants meeting 1 or more of the following criteria undergo examinations: gestational age less than 28 weeks or birth weight less than 1051 g; weight gain less than 120 g during age 10 to 19 days, weight gain less than 180 g during age 20 to 29 days, or weight gain less than 170 g during age 30 to 39 days; or hydrocephalus. Objective To evaluate the generalizability of the G-ROP screening criteria in a new cohort of at-risk infants. Design, Setting, and Participants This prospective validation cohort study (G-ROP-2) was conducted at 41 hospitals in the United States and Canada (25 G-ROP-1 hospitals and 16 new hospitals) from September 8, 2015, to June 13, 2017, among 3981 premature infants at risk for ROP and with known ROP outcomes. Main Outcomes and Measures Sensitivity for Early Treatment for Retinopathy of Prematurity Study type 1 ROP and potential reduction in infants receiving examinations. Results Among the 3981 infants in the study (1878 girls and 2103 boys; median gestational age, 28 weeks [range, 22-35 weeks]; median birth weight, 1072 g [range, 350-4080 g]; 1966 white; 942 black; 321 Latino; 120 Asian; 22 Native Hawaian or Pacific Islander; and 25 American Indian or Alaskan Native), the G-ROP criteria correctly predicted 219 of 219 cases of type 1 ROP (sensitivity, 100%; 95% CI, 98.3%-100%), while reducing the number of infants undergoing examinations by 35.6% (n = 1418). In a combined G-ROP-1 and G-ROP-2 cohort of 11 463 infants, the G-ROP criteria predicted 677 of 677 cases of type 1 ROP (sensitivity, 100%; 95% CI, 99.4%-100%), reducing the number of infants receiving examinations by 32.5% (n = 3730), while current criteria (birth weight Conclusions and Relevance This study found that the G-ROP screening criteria were generalizable on validation and, if used clinically in the United States and Canada, could reduce the number of infants receiving examinations. The large G-ROP cohorts provide evidence-based screening criteria that have higher sensitivity and higher specificity (fewer infants receiving examinations) for type 1 ROP than currently recommended guidelines.

The purpose of this study was to investigate the hypoxia-induced Vegf120, Vegf164 and Vegf188 mRNA expression profiles in rat Müller cells (MC), astrocytes, retinal pigmented epithelial cells (RPE) and retinal microvascular endothelial cells (RMEC) and correlate these findings to VEGF secreted protein. Cultured cells were exposed to normoxia or hypoxia. Total RNA was isolated from cell lysates and Vegf splice variant mRNA copy numbers were assayed by a validated qRT-PCR external calibration curve method. mRNA copy numbers were normalized to input total RNA. Conditioned medium was collected from cells and assayed for total VEGF protein by ELISA. Hypoxia increased total Vegf mRNA and secreted protein in all the retinal cell types, with the highest levels observed in MC and astrocytes ranking second. Total Vegf mRNA levels in hypoxic RPE and RMEC were comparable; however, the greatest hypoxic induction of each Vegf splice variant mRNA was observed in RMEC. RPE and RMEC ranked 3rd and 4th respectively, in terms of secreted total VEGF protein in hypoxia. The Vegf120, Vegf164 and Vegf188 mRNA splice variants were all increased in hypoxic cells compared to normoxic controls. In normoxia, the relative Vegf splice variant mRNA levels ranked from highest to lowest for each cell type were Vegf164>Vegf120>Vegf188. Hypoxic induction did not alter this ranking, although it did favor an increased stoichiometry of Vegf164 mRNA over the other two splice variants. MC and astrocytes are likely to be the major sources of total Vegf, and Vegf164 splice variant mRNAs, and VEGF protein in retinal hypoxia.

Objective To describe the prevalence of admissions to New Zealand public hospitals for dental care and associated time trends for people of all ages during the 20-year period 1990–2009. Methods The New Zealand Ministry of Health National Minimum Data Set (NMDS), a collection that covers all publicly funded hospital discharges, was the primary data source for this study. Data over a 20-year period from 1 January 1990 to 31 December 2009 were included, and a subset of ICD 10 codes (K02–K09 and K12 and K13) were selected to identify potentially preventable or ambulatory care sensitive conditions (ACSC) leading to admission to hospital. Volumes, proportions and rates of admission are presented to describe the patterns of admission to hospital. Results There were 120 046 admissions to public hospitals in New Zealand between 1990 and 2009 for which the provision of dental care was the primary reason for admission. The rate of admission to hospital for dental care increased from 0.92 per 1000 population in the period 1990–1994 to 2.15 per 1000 population in 2005–2009. Dental admission rates were greatest in the 3- to 4-year-old age group, for Maori and Pacific people and for people in the most deprived quintile of the NZDep 2006 index. Almost one-third of people aged 18–34 years who were admitted to hospital primarily for dental care were acute admissions. Conclusion Both the volume and the rate of admission to New Zealand public hospitals for dental care have increased over the period of this study. A continued focus on strategies to reduce the impact of dental disease, particularly in the early childhood population and on ensuring accessible primary dental care for the adult population, is required.

Invasive breast cancer is a major cause of death due to cancer for American women. Progress against this disease has only been achieved through a better understanding of the cellular and molecular aspects of breast cancer. To begin with cancer of the breast is not just a loco-regional control issue. In fact, metastatic disease from invasive breast cancer is not a one-way street in that metastases metastasize and send clusters of tumor cells that migrate to other sites of the disease including back to the primary tumor. Since invasive breast cancer at diagnosis is a systemic disease, adjuvant therapy has been initially started with relatively nonselective cytotoxic agents and latter with the use of endocrine therapy. The response rate to endocrine therapy improved once we knew which cancers expressed the actionable target. Endocrine therapy was the first targeted therapy but resistance to it is common in the adjuvant setting and essentially universal in the metastatic setting. Use of everolimus and palbociclib to interdict additional signaling pathways are proof positive that new-targeted agents can overcome resistance to endocrine therapy. In the adjuvant setting the risk of a patient’s having metastatic disease can be approximated by knowing the histological type of breast cancer, size of invasive component of the primary, presence or absence of lymph node or lymphovascular space involvement, the degree of histological atypia, the presence or absence or estrogen, progesterone or Her-2 neu and the patient’s menopausal status. Her-2 neu positive breast cancers have been converted from the most aggressive tumors to very curable cancers in the adjuvant setting by the use of Her-2 neu specific antibodies, such as trastuzumab, to the cell surface portion of the molecule. The use of adjuvant chemotherapy has been further refined on 2 fronts. First, smaller estrogen positive node negative breast cancers benefit from tamoxifen and some benefit more or less from additional therapy with chemotherapy based on the use of predictive models. For larger node positive breast cancers, adjusting the schedule of mostly S-phase cytotoxic chemotherapy to account for tumor cell growth kinetics has improved overall survival. Unfortunately, triple negative breast cancers lack a defined actionable target. Thus, the poorer survival in this group is not understood despite the initial good response to cytotoxic chemotherapy. Refinements in the pharmacokinetics of paclitaxel by using an albumin carrier have also proved beneficial to patients with metatstatic breast cancer. Additional refinements in drug carriers or other delivery systems should help in the care of those with metastatic disease. Only by accounting for the tumor’s cellular biology, growth kinetics, and the targeted drug’s pharmacokinetics as well as pharmacodynamics will blocking or overcoming resistance to targeted therapy be accomplished.

Diagnosis and management of congenital cataracts can be aided by an understanding of cataract morphology and presentation. Smaller opacities may be visually insignificant, and require only serial monitoring, while total opacities may require urgent surgical removal. The appearance and location of the cataract within the lens may provide a clue to the presence of systemic disease or metabolic disorder. A primary decision-making point involves the laterality of lens pathology. In general, unilateral cataracts are idiopathic and will not require systemic work-up. Bilateral cataracts are generally thought to be caused by genetic, metabolic or infectious etiologies; however, idiopathic cases are quite common [1]. Bilateral cataracts without a known pedigree of genetic inheritance require systemic evaluation.

Background Many cases of unilateral congenital cataract have an associated posterior capsular plaque. Observations such as this have led to the hypothesis that posterior capsular plaque is caused by persistent fetal vasculature, generally a unilateral condition, even if no obvious hyaloid remnant is visible. We investigated the incidence of posterior capsular plaque associated with bilateral congenital cataracts. Methods Children with bilateral congenital cataracts were identified from three surgical practices. Children were included if lensectomies were performed prior to age 7 months. Surgical videos were evaluated for cataract morphology. Results Fourteen children with bilateral cataracts were identified. Surgical videos were available for 24 eyes. Five eyes (21%) had evidence of persistent hyaloid remnants. Of the remaining 19 eyes, cataracts were categorized as nuclear in 10 cases, nuclear with cortical extension in 6 cases, and posterior cortical in 3 cases. Evidence of posterior capsular plaque was seen in seven cases (37%) on video review. Conclusions Video review revealed a much lower incidence of posterior capsular plaque in eyes with bilateral congenital cataracts compared to unilateral congenital cataracts, lending presumptive evidence to the hypothesis that most unilateral lens opacities arise from persistent fetal vasculature.

To describe a video-documented assessment of cataract type in the eyes of patients with monocular infantile cataract who were enrolled in the Infant Aphakia Treatment Study.The Infant Aphakia Treatment Study is a randomized clinical trial in which the investigators compared intraocular lens (IOL) versus contact lens correction in 114 infants, aged 28 days to7 months. A total of 83 videos were available for morphological analysis of cataract. Three examiners reviewed all surgical recordings and agreed on the cataract characteristics by using a score sheet to record the lens layer or configuration of the opacity.Nuclear cataract was present in 45 of 83 eyes (54%). Posterior capsule plaque was observed in 73 eyes (88%). All eyes with fetal nuclear cataract had associated posterior capsule plaque. Cortical cataract without nuclear involvement was seen in 21 eyes (25%). Posterior bowing of the posterior capsule was noted in 4 eyes (5%). Evidence of persistent fetal vasculature (PFV) was present in 18 eyes (22%). PFV was the only finding in 5 eyes but was also seen in combination with nuclear (7 eyes) and cortical cataracts (6 eyes). The entire lens was white in 3 eyes (4%), whereas the lens was partially resorbed in 7 (8%) eyes. Anterior capsule fibrosis was noted in 5 eyes with advanced cataract (1 with total cataract, 4 with partially resorbed lens).Nuclear opacities were common, but many different cataract types presented in infancy. PFV occurred in isolation or in association with cataract. Posterior capsule plaque was frequently noted, especially when a nuclear cataract was present.

Purpose To report the outcome of nasolacrimal duct intubation as the primary treatment of congenital nasolacrimal duct obstruction (NLDO) in children less than 4 years of age.

Anisometropia is an important cause of amblyopia. The relationship between anisometropia depth and amblyopia magnitude is not well characterized, as previous studies have been limited to patients identified because of their amblyopia. We analyzed results from anisometropic patients identified with photoscreening to eliminate this selection bias.We performed a retrospective observational study of preschool children with anisometropia1.0 D identified during a statewide photoscreening program. Nine hundred seventy-four children with anisometropia were detected over a 9-year period. Visual acuity, cycloplegic refraction data, and patient age from a formal follow-up examination were analyzed. Effect of anisometropia magnitude on amblyopia was measured by ordinal logistic regression, taking age into account.Six hundred forty (65.7%) children had amblyopiaor =2 lines. Three hundred sixty-four (37.4%) hador =4 lines amblyopia. There was a statistically significant increase in risk of amblyopia with increasing magnitude of anisometropia. Calculated odds ratios for amblyopia with maximal meridional anisometropia ofor =2 to4 D compared with1 to2 D was 2.13 (95% CI [1.63, 2.78], p1 x 10(-7)), and 2.34 (95% CI [1.67, 3.28], p1 x 10(-6)) when comparingor =4 D toor =2 to4 D. Odds ratios for spherical equivalent anisometropia were also highly statistically significant.Children with higher magnitudes of anisometropia had higher prevalence and greater depth of amblyopia. Older children had an increased risk of amblyopia compared with younger children for moderate levels of anisometropia. Low magnitude anisometropia in young children may not predispose to amblyopia; these findings have implications for vision screening criteria at various ages.

We report endothelial cell (EC) characteristics and central corneal thickness (CCT) from the Infant Aphakia Treatment Study (IATS) patients at the 5-year examination.Randomized, controlled trial of the treatment of unilateral cataract with aphakic contact lens (CL) versus primary intraocular lens (IOL) implant.A total of 114 infants with unilateral cataract.The EC density, coefficient of variation (CV), and percent hexagonal cells were measured by noncontact specular microscopy. The CCT was measured using contact pachymetry. Fellow eyes served as controls.Mean differences between treated and fellow eyes of CL and IOL groups were compared with a paired t test. A 1-way analysis of variance model and the Tukey-Kramer multiple comparison procedure were used to assess the effect of a diagnosis of glaucoma or glaucoma suspect.A total of 105 subjects (52 with CLs, 53 with IOLs) had specular microscopy or corneal thickness data recorded. Mean EC densities were higher in aphakic eyes compared with fellow eyes (3921 vs. 3495 cells/mm2, P0.0001). Mean CV was higher (27 vs. 24, P=0.0002) and mean percent hexagonal cells was lower (72% vs. 76%, P=0.002) in aphakic eyes compared with fellow eyes. Mean CCT of aphakic eyes was higher than in controls (637 vs. 563 μm, P0.0001). There was no difference in EC density in eyes treated with IOLs compared with fellow eyes (3445 and 3487 cells/mm2, P=0.68). Means for CV (25 vs. 24, P=0.07) and percent hexagonal cells (74 vs. 76%, P=0.27) were also not significantly different. Mean CCT was higher in eyes with IOLs (605 vs. 571 μm, P0.0001) compared with fellow eyes. Compared with treated eyes without glaucoma or glaucoma suspect, treated eyes with glaucoma had lower EC density (3289 vs. 3783 cells/mm2, P=0.03) and treated eyes with glaucoma suspect had greater mean corneal thickness (660 vs. 612 μm, P=0.0036).Cataract extraction during infancy with IOL implantation was not associated with a reduced EC count in treated compared with fellow eyes, although CCT was increased. Extended-wear aphakic CLs may cause corneal polymegathism with increased EC density and CCT. Glaucoma diagnosis was associated with reduced EC counts and increased CCT.

Purpose The Colorado retinopathy of prematurity (ROP) prediction model (CO-ROP), developed using a cohort of infants from Colorado, calls for ROP examination of infants meeting all of the following criteria: gestational age of ≤30 weeks, birth weight of ≤1500 g, and a net weight gain of ≤650 g between birth and 4 weeks of age. The purpose of this study was to perform an external validation to assess the sensitivity and specificity of the CO-ROP model in a larger cohort of babies screened for ROP from four academic institutions in the United States. Methods The medical records of neonates screened for ROP according current national guidelines was conducted at 4 US academic centers were retrospectively reviewed. Sensitivity, specificity, and respective 95% confidence intervals in detecting ROP using CO-ROP were calculated for type 1, type 2, and any grade of ROP. Results A total of 858 cases were included. The CO-ROP algorithm had a sensitivity of 98.1% (95% CI, 93.3%-99.8%) for type 1 ROP, 95.6% (95% CI 78.0-99.9%) for type 2 ROP, and 95.0% (95% CI, 93.1-97.4%) for all grades of ROP. The CO-ROP model would have reduced the total number of infants screened by 23.9% compared to current 2013 screening guidelines. Conclusions CO-ROP demonstrated high sensitivity in predicting ROP and would have greatly reduced the number of infants needing examination.

Importance Measurable competence derived from comprehensive and advanced training in grading digital images is critical in studies using a reading center to evaluate retinal fundus images from infants at risk for retinopathy of prematurity (ROP). Details of certification for nonphysician trained readers (TRs) have not yet been described. Objective To describe a centralized system for grading ROP digital images by TRs in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study. Design, Setting, and Participants Multicenter observational cohort study conducted from July 1, 2010, to June 30, 2014. The TRs were trained by experienced ROP specialists and certified to detect ROP morphology in digital retinal images under supervision of an ophthalmologist reading center director. An ROP reading center was developed with standard hardware, secure Internet access, and customized image viewing software with an electronic grading form. A detailed protocol for grading was developed. Based on results of TR gradings, a computerized algorithm determined whether referral-warranted ROP (RW-ROP; defined as presence of plus disease, zone I ROP, and stage 3 or worse ROP) was present in digital images from infants with birth weight less than 1251 g enrolled from May 25, 2011, through October 31, 2013. Independent double grading was done by the TRs with adjudication of discrepant fields performed by the reading center director. Exposure Digital retinal images. Main Outcomes and Measures Intragrader and intergrader variability and monitoring for temporal drift. Results Four TRs underwent rigorous training and certification. A total of 5520 image sets were double graded, with 24.5% requiring adjudication for at least 1 component of RW-ROP. For individual RW-ROP components, the adjudication rate was 3.9% for plus disease, 12.4% for zone I ROP, and 16.9% for stage 3 or worse ROP. The weighted κ for intergrader agreement (n = 80 image sets) was 0.72 (95% CI, 0.52-0.93) for RW-ROP, 0.57 (95% CI, 0.37-0.77) for plus disease, 0.43 (95% CI, 0.24-0.63) for zone I ROP, and 0.67 (95% CI, 0.47-0.88) for stage 3 or worse ROP. The weighted κ for grade-regrade agreement was 0.77 (95% CI, 0.57-0.97) for RW-ROP, 0.87 (95% CI, 0.67-1.00) for plus disease, 0.70 (95% CI, 0.51-0.90) for zone I ROP, and 0.77 (95% CI, 0.57-0.97) for stage 3 or worse ROP. Conclusions and Relevance These data suggest that the e-ROP system for training and certifying nonphysicians to grade ROP images under the supervision of a reading center director reliably detects potentially serious ROP with good intragrader and intergrader consistency and minimal temporal drift.

Introduction To evaluate the efficacy of superior oblique Z-tenotomy in the treatment of overdepression in adduction (superior oblique overaction) with respect to collapse of A-pattern strabismus and normalization of versions. Methods The medical records of patients who underwent bilateral superior oblique Z-tenotomy for mild to moderate overdepression in adduction and A-pattern strabismus between June 2004 and August 2010 were retrospectively reviewed. Surgical indications included mild to moderate overdepression in adduction (+2 to 3) and an A pattern of 10 Δ to 40 Δ between upgaze and downgaze. A monopolar electrode microdissection needle was used to make two tenotomies, 60% to 80% in width and 8 mm apart, perpendicular to the axes of the tendon in opposite directions. Surgical success included a postoperative A pattern of ≤10 Δ and overdepression in adduction of ≤1. Results A total of 20 patients (mean age, 9.8 years; age range, 3-34) underwent bilateral superior oblique Z-tenotomy during the study period: 2 patients (10%) with esotropia and 18 with exotropia (90%). Average decrease in pattern was 16 Δ (range, 0 Δ -32.5 Δ ). Success rate for pattern collapse was 78%, with resolution of overdepression in adduction of 90%. Conclusions Z-tenotomy of the superior oblique tendon collapsed A-pattern strabismus and normalized versions.

Acute lymphoblastic leukemia is the most common malignancy in children. We report 3 patients who presented to their general pediatricians and pediatric oncologists with ocular complaints as the only evidence of their leukemic relapses. All patients presented with persistent conjunctival injection and were referred to an ophthalmologist for further management. Two patients were diagnosed with recurrent anterior uveitis, which after extensive workup and treatment with topical glucocorticoids was found to be a result of leukemic ocular disease. One patient had a conjunctival tumor, which was biopsied and confirmed to be leukemic infiltration. All children eventually succumbed to their recurrent disease. These cases demonstrate the need for a high index of suspicion when evaluating ocular symptoms in patients with a prior history of acute lymphoblastic leukemia. Anterior chamber paracentesis and biopsy of suspicious lesions should be considered as possible diagnostic procedures in addition to standard hematologic studies. Collaboration between a primary care physician, pediatric oncologist, and ophthalmologist is essential for optimal diagnosis and treatment.

The purpose of this study was to determine the quality of peripheral blood progenitor cells (PBPC) collected after an initial autologous PBPC transplant. Tandem autologous transplants have been used in the treatment of several malignancies. Routinely, PBPC have been collected prior to the first transplant and used for both transplants. In the current study, PBPC harvested prior to the first high-dose therapy (HDT) were used as a source of progenitors for transplant 1, and a combination of bone marrow harvested prior to the first course of HDT and PBPC collected approximately 85 days after the first transplant were used to support the second HDT. We analyzed the quality of the PBPC collected 85-120 days after HDT and autologous PBPC transplant. CD34 and colony-forming units granulocyte-macrophage (CFU-GM) contents of those collections were poor, and hematopoietic recovery was more consistent with recovery from a bone marrow transplant than a PBPC transplant. Thirteen of 15 patients received both transplants. Days to absolute granulocyte count of 500 was 10 +/- 1.5 for the first transplant and 13.3 +/- 3.7 for the second (p < 0.01). The number of days to platelet count of 20,000 was 14.3 +/- 10.7 for the first transplant and 18 +/- 7 for the second transplant (p = 0.066). The number of days of total parenteral nutrition (TPN) and intravenous morphine used by patients for the first and second transplants was similar, whereas the length of hospitalization was 21.8 +/- 3.6 for the first transplant and 27.6 +/- 7.8 for the second transplant (NS). In conclusion, it appears that the quality of PBPC collected following a previous PBPC transplant may be compromised.

Summary Dissociated vertical deviation (DVD) is a slow, disconjugate hypertropic deviation of a nonfixating eye. It is usually bilateral, asymmetrical, and often associated with congenital esotropia. The deviating eye elevates, abducts, and excyclotorts. This type of strabismus is often variable, making measurement and clinical quantification difficult. Specific knowledge of the mechanisms and characteristics of the dissociated deviation are required for proper assessment and effective treatment. There is currently no consensus on the mechanisms and pathophysiology of DVD. In this workshop, participants discuss the characteristics and most current methods for assessing and quantifying the deviation and explore the potential etiologies, clinical characteristics, and indications for surgical intervention and nonsurgical management of DVD.

Background and purpose Amblyopia is commonly treated with part-time occlusion (PTO) therapy. We have made two anecdotal observations regarding this therapy. First, children undergoing full-time occlusion seem to have better success and compliance rates. Secondly, a subset of children exists that fail PTO but can improve with more aggressive therapy. Methods A retrospective review where treatment, visual outcome, and compliance scores were recorded. Compliance was graded on percent adherence reported by family. Patients scored “1” (for no compliance), “2” (for 1–25% of prescribed treatment performed), “3” (for 26–50%), “4” (for 51–75%), or “5” (for 76–100%). Results Seventy-six children were enrolled in the study: forty-five were treated with part-time occlusion, twenty-two were treated with full time occlusion (FTO), and nine had a history of failed PTO and were subsequently treated with FTO. Visual outcomes for FTO versus PTO were not statistically significant (P = 0.82). However, compliance rates in FTO were significantly better (P = 0.02). Of the nine patients that failed PTO, four improved an average of three lines with full-time occlusion, and five had no change with more aggressive patching. Conclusions This study confirms previous reports of similar visual outcomes between PTO and FTO. However, compliance rates for FTO seem to be higher and some children who have failed PTO may improve with FTO.

Galanin gene expression is markedly increased in the anterior pituitary glands of estrogen-treated rats (lactotroph hyperplasia) as well as human growth hormone-releasing hormone transgenic mice (somatotroph hyperplasia). The objective of this study was to examine galanin in a mouse model of thyrotroph adenoma formation. Male mice were radiothyroidectomized by use of iodine-131 (131I), and galanin peptide levels were assessed in the hypothalamic-pituitary axis. Immunoreactive galanin concentrations in the anterior pituitaries of 131I-treated mice were decreased 80% at 3, 6, 9, and 12 mo after radiothyroidectomy. Galanin peptide levels in the hypothalamus were decreased 20-25% at these times. Treatment with either estradiol or 3,3',5-triiodo-L-thyronine increased galanin peptide concentrations in the anterior pituitaries of 131I-treated mice, but neither treatment restored galanin concentrations. Galanin mRNA levels were decreased > 80% 1 yr after radiothyroidectomy. We conclude that, unlike animal models of lactotroph and somatotroph hyperplasia, galanin gene expression is suppressed throughout the development of thyrotroph adenomas, suggesting that galanin does not have a stimulatory role in the proliferation of thyrotrophs. Moreover, these data show that thyroid hormones are important positive regulators of galanin gene expression in the mouse and that estrogen may stimulate galanin gene expression in the absence of thyroid hormones.

Purpose To report a case of acute myeloid leukemia with bilateral proptosis as the sole presenting sign. Design Observational case report. Methods A patient with bilateral proptosis was seen in consultation by pediatric ophthalmology. Results Complete blood count, computerized tomography, and bone marrow biopsy confirmed the diagnosis of acute myeloid leukemia, with the proptosis due to diffuse infiltration of all extraocular muscles. Conclusion In a child with the sudden onset of proptosis without any other systemic findings, the diagnosis of acute leukemia must be considered.

To examine the feasibility of a retinopathy of prematurity (ROP) telemedicine evaluation system of providing timely feedback to a neonatal intensive care unit (NICU) with at-risk premature infants.This was a prospective observational study of premature infants with birth weights of1251 g in five NICUs in the United States. Infants scheduled for clinically indicated ROP evaluations underwent indirect ophthalmoscopic examinations and digital imaging on the same day. Imaging was performed by nonphysician retinal imagers. Times required were determined from obtaining digital images of both eyes to submission via web-based system to a secure server for grading by trained readers at a central reading center to sending back grading results to the clinical center.A total of 1,642 image sets of eyes of 292 infants were obtained, from 823 imaging sessions. The mean turnaround time from submission of image sets of both eyes to return of the grading results to the clinical center was 10.1 ± 11.3 hours (standard deviation), with a median of 12.0 hours (1st quartile, 0.9 hours; 3rd quartile, 16 hours). Overall, 95.5% of gradings (95% CI, 93.9%-96.7%) were returned within 24 hours. Subgroup analyses found, for image sets submitted to the reading center before 2 p.m. Eastern Standard Time, median time to report was 1.7 hours (1st quartile, 0.7 hours; 3rd quartile, 15.5 hours) compared with those submitted after 2pm (median, 14.1 hours; 1st quartile, 11.2, hours; 3rd quartile, 16.3 hours).An ROP telemedicine approach can provide timely feedback to the NICU regarding the detection of potentially serious ROP and thus referral to an ophthalmologist for examination and consideration of treatment.