Intense versus standard regimens of intermittent occlusion therapy for unilateral moderate amblyopia in children: study protocol for a randomized controlled trial.

BACKGROUND: We reported that in our previous study that wearing intermittent occlusion therapy glasses (IO-therapy) for 4 hours (h) was non-inferior to patching for 2 h in 3 to 8-year-old children with amblyopia. We hypothesize that an intense regimen of 12-h IO-therapy per day for 4 weeks could be as effective as the standard regimen of 4-h IO-therapy per day for 12 weeks in treating moderate amblyopia in 3 to 8-year-old children. METHODS/DESIGN: A total of 56 children between 3 and 8 years of age with amblyopia in association with anisometropia and/or strabismus will be enrolled. All participants will be prescribed IO-therapy glasses (Amblyz™), set at 30-s opaque/transparent intervals (i.e., occluded 50% of wear time). They will be randomized to receive the standard regimen for 12 weeks or the intense regimen for 4 weeks. Adherence to using the IO-therapy glasses will be objectively monitored in each participant by means of a microsensor dose monitor. The primary study objective is to compare the effectiveness of an intense regimen to a standard regimen of IO-therapy in 3 to 8-year-old children with moderate amblyopia. The secondary study objectives are to determine whether adherence differs between an intense regimen and a standard regimen of IO-therapy, and to determine the dose-response relationship of IO-therapy. DISCUSSION: In addition to testing the effectiveness, this study will test for the first time the association between treatment adherence and the visual outcome of IO-therapy, which will enhance our understanding of the dose-response relationship of IO-therapy. If an intense regimen is shown to be effective, it would alter amblyopia treatment strategies and improve visual outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02767856. Registered on 10 May 2016.

Challenging Surgical Approach to a Lost Inferior Rectus Muscle Following Penetrating Orbital Trauma.

A 37-year-old man suffered a penetrating left orbital injury with rupture of the inferior rectus muscle and avulsion of the optic nerve. The orbit was explored and the inferior rectus muscle stump was identified 25 mm from the limbus. Despite this, the muscle was successfully reattached and the patient achieved satisfactory postoperative alignment. [J Pediatr Ophthalmol Strabismus. 2019;56:e49-e52.].

Feasibility of monitoring compliance with intermittent occlusion therapy glasses for amblyopia treatment.

BACKGROUND: Liquid crystal glasses use an intermittent occlusion technique and may improve compliance compared to adhesive patches. Previous studies support the effectiveness of intermittent occlusion therapy (IO therapy) glasses for amblyopia treatment. However, objective compliance for these glasses has not been measured. The purpose of this study was to investigate the feasibility of using a microsensor to monitor objective compliance with IO therapy glasses. METHODS: Children 3 to ≤8 years of age with unilateral amblyopia were enrolled. All subjects had optimal refractive correction (if needed) for at least 5 weeks without improvement. Subjects were prescribed IO therapy glasses, set at 30-second opaque/transparent intervals (ie, occluded 50% of wear time). Wear time was prescribed according to amblyopia severity. For each patient, objective compliance with the IO therapy glasses was monitored by means of a microsensor. RESULTS: A total of 13 subjects returned with microsensor data. Compliance varied among and within individuals. General compliance averaged 51.6% (range, 10%-97%). Mean daily compliance decreased slightly over time. On average, patients' visual acuity improved 0.14 ± 0.15 logMAR (range, -0.1 to 0.5 logMAR). No parents reported that their child had social concerns related to the attached microsensor. CONCLUSIONS: Objective compliance with IO therapy glasses can be monitored by a simple microsensor reliably. In our study cohort, objective compliance with IO therapy glasses varied among individuals, but on average it declined slightly over time.

Immediate Postoperative Alignment Measurements as a Predictor of Alignment Stability in Fixed Suture Strabismus Surgery.

PURPOSE: To evaluate the use of immediate postoperative alignment measurements as a predictor of future alignment stability in fixed suture strabismus surgery. METHODS: Forty-seven patients were prospectively evaluated after undergoing horizontal or vertical rectus muscle surgery using a fixed suture technique. Alignment measurements were taken approximately 1 hour, 1 to 3 weeks, and 2 to 3 months postoperatively. A Spearman correlation coefficient was used to compare measurements from the immediate postoperative period to the 2- to 3-month postoperative period. Patients with dissociated strabismus, only oblique muscle surgery, or poor vision in one or both eyes precluding precise alternate cover test were excluded. RESULTS: Mean age of all patients was 46.7 years (range: 12 to 86 years). Twenty-two patients underwent surgery for exotropia: 19 for esotropia and 6 for hypertropia. Mean alignment for all surgeries was 2 prism diopters (PD) undercorrection in the immediate postoperative period, which was similar to the mean of 4.6 PD undercorrection at 2 to 3 months postoperatively. However, the Spearman correlation between the immediate postoperative and 2- to 3-month postoperative measurements was 0.18 for all surgeries, 0.03 for exotropia, 0.56 for esotropia, and 0.40 for hypertropia. The overall success rate, defined as 8 PD or less of horizontal deviation and 4 PD or less of vertical deviation, was 77% at 2 to 3 months postoperatively. CONCLUSIONS: The relationship between immediate postoperative alignment and future alignment stability in fixed suture strabismus surgery has not been previously defined. The current study demonstrated that although the surgical success rate was reasonably good, poor correlation occurred between the alignment immediately postoperatively and 2 to 3 months postoperatively. [J Pediatr Ophthalmol Strabismus. 2018;55(4):240-244.].

Long-term efficacy of endoscopic cyclophotocoagulation in the management of glaucoma following cataract surgery in children.

PURPOSE: To report the long-term efficacy of endoscopic cyclophotocoagulation (ECP) in pediatric glaucoma following cataract surgery (GFCS). METHODS: ECP was performed on 35 eyes of 25 patients <16 years of age with GFCS. Patients were followed for a minimum of 2 years. Treatment failure was defined as consecutive postoperative intraocular pressure (IOP) of >24 mm Hg, alternative glaucoma procedure following ECP, or occurrence of visually significant complications. Analysis was performed to estimate risk factors for failure. RESULTS: A total of 27 aphakic and 8 pseudophakic eyes were included. Pretreatment IOP averaged 33.9 ± 7.9 mm Hg. Final IOP after a mean follow-up period of 7.2 years was 18.9 ± 8.8 mm Hg (P < 0.001). The success rate was 54% (19/35 eyes). The failure rate was not increased in pseudophakic patients relative to aphakic patients. Patients with single ECP demonstrated preserved visual acuity from baseline to final follow-up. CONCLUSIONS: In this patient cohort, with average follow-up period of 7.2 years, ECP was useful in the treatment of pediatric GFCS.

Ocular Pathology of Oculocerebrorenal Syndrome of Lowe: Novel Mutations and Genotype-Phenotype Analysis.

Mutations in the OCRL1 gene result in the oculocerebrorenal syndrome of Lowe, with symptoms including congenital bilateral cataracts, glaucoma, renal failure, and neurological impairments. OCRL1 encodes an inositol polyphosphate 5-phosphatase which preferentially dephosphorylates phosphatidylinositide 4,5 bisphosphate (PI(4,5)P2). We have identified two novel mutations in two unrelated Lowe syndrome patients with congenital glaucoma. Novel deletion mutations are detected at c.739-742delAAAG in Lowe patient 1 and c.1595-1631del in Lowe patient 2. End stage glaucoma in patient 2 resulted in the enucleation of the eye, which on histology demonstrated corneal keloid, fibrous infiltration of the angle, ectropion uvea, retinal gliosis, and retinal ganglion cell loss. We measured OCRL protein levels in patient keratinocytes and found that Lowe 1 patient cells had significantly reduced OCRL protein as compared to the control keratinocytes. Genotype-phenotype correlation of OCRL1 mutations associated with congenital glaucoma revealed clustering of missense and deletion mutations in the 5-phosphatase domain and the RhoGAP-like domain. In conclusion, we report novel OCRL1 mutations in Lowe syndrome patients and the corresponding histopathologic analysis of one patient's ocular pathology.

A pilot randomized clinical trial of intermittent occlusion therapy liquid crystal glasses versus traditional patching for treatment of moderate unilateral amblyopia.

PURPOSE: To compare the effectiveness of intermittent occlusion therapy (IO therapy) using liquid crystal glasses and continuous occlusion therapy using traditional adhesive patches for treating amblyopia. METHODS: Children 3-8 years of age with previously untreated, moderate, unilateral amblyopia (visual acuity of 20/40 to 20/100 in the amblyopic eye) were enrolled in this randomized controlled trial. Amblyopia was associated with strabismus, anisometropia, or both. All subjects had worn any optimal refractive correction for at least 12 weeks without improvement. Subjects were randomized into two treatment groups: a 4-hour IO therapy group with liquid crystal glasses (Amblyz), set at 30-second opaque/transparent intervals (occluded 50% of wear time), and a 2-hour continuous patching group (occluded 100% of wear time). For each patient, visual acuity was measured using ATS-HOTV before and after 12 weeks of treatment. RESULTS: Data from 34 patients were available for analysis. Amblyopic eye visual acuity improvement from baseline was 0.15 ± 0.12 logMAR (95% CI, 0.09-0.15) in the IO therapy group (n = 19) and 0.15 ± 0.11 logMAR (95% CI, 0.1-0.15) in the patching group (n = 15). In both groups improvement was significant, but the difference between groups was not (P = 0.73). No adverse effects were reported. CONCLUSIONS: In this pilot study, IO therapy with liquid crystal glasses is not inferior to adhesive patching and is a promising alternative treatment for children 3-8 years of age with moderate amblyopia.

Macular structural characteristics in children with Down syndrome.

PURPOSE: This prospective study aimed to investigate macular structural characteristics in children with Down syndrome compared to those in healthy children. METHODS: Two groups of children (aged 6-16 years) were enrolled: children with Down syndrome (Down syndrome group, N = 17) and age-matched healthy children who were full-term at birth (control group, N = 18). Eligible patients had visual acuity of 20/100 or better and gestational age at birth of ≥ 36 weeks. Fourier domain optical coherence tomography was used for imaging of the macular retinal structure, and retinal volume scans centered on the macula were obtained. Central subfield thickness (CST) and the thickness of the inner and outer retinal layer regions were analyzed using the instrument's segmentation software. The analysis of data is provided for the right eye only, since there was no significant difference between right and left eyes for either the Down syndrome or control groups. RESULTS: Children in the Down syndrome group generally had identifiable retinal structure. The CST for the full retina and inner and outer retinal layers were all significantly greater in the Down syndrome group than the control group (independent t test, all p < 0.05). Despite the significantly thicker macula, only about 29 % (5 of 17) of the right eyes of patients with Down syndrome had macular thickness outside the normal range. Visual acuity in the Down syndrome group was not directly correlated with increased CST (t = 1.288, r = 0.326, p = 0.202). CONCLUSIONS: On average, CST in the Down syndrome group was greater than that in the control group, suggesting abnormal macular development in children with Down syndrome.

Comparison of 360-degree versus traditional trabeculotomy in pediatric glaucoma.

PURPOSE: To compare intraocular pressure (IOP) control of pediatric glaucoma patients undergoing traditional trabeculotomy (<360 degrees or partial) with those receiving 360-degree circumferential trabeculotomy. METHODS: The medical records of pediatric glaucoma patients receiving trabeculotomy at a single institution from 2000 to 2012 were retrospectively reviewed. Patients were divided into two groups: a traditional trabeculotomy group and 360-degree trabeculotomy group. IOP at baseline and at 1, 3, 6, and 12 months' follow-up were compared within and each groups. RESULTS: A total of 77 eyes of 56 patients (age at surgery, 1.52 ± 2.68 years) in the traditional group and 14 eyes of 10 patients in the 360-degree group (age at surgery, 0.61 ± 0.42 years) were included. Mean baseline IOP was similar in both groups (traditional, 28.75 ± 8.80 mm Hg; 360-degree, 30.35 ± 6.04 mm Hg; t test; P = 0.43). Mean 1-year IOP was 17.05 ± 5.92 mm Hg in the traditional group and 11.0 ± 2.31 mm Hg in the 360-degree group. At 1-year, the surgical success rate was 58.44% in the traditional group and 85.71% in the 360-degree group; 32 eyes in the former and 2 eyes in the latter required another glaucoma procedure within 1 year for IOP control. For both groups, compared to baseline values, IOP decreased significantly with all postoperative measurements (paired t test, all P < 0.01). The 360-degree group had significantly lower IOP compared to the traditional group at 1-year (t test, P < 0.01). CONCLUSIONS: Both 360-degree and traditional trabeculotomy significantly reduced IOP in children through 1 year's follow-up, although the former procedure shows better 1-year postoperative IOP control, with higher rate of surgical success.

Macular structural characteristics in children with congenital and developmental cataracts.

PURPOSE: To investigate macular structural characteristics in children with congenital or developmental cataracts. METHODS: Children 5-16 years of age with a history of surgery for congenital or acquired cataract were enrolled. Eligible patients had visual acuity of 20/400 or better and ≥37 weeks gestational age at birth. Patients were divided into two groups: unilateral (n = 22) and bilateral (n = 19). Fourier domain optical coherence tomography (FD-OCT) was used to image the retinal structure. Retinal volume scans centered on the fovea were obtained. Using the instrument's segmentation software, central subfield thickness (CST) and the thickness of the inner and outer retinal layer regions were measured. RESULTS: In the unilateral group, 1 child with persistent fetal vasculature had unidentifiable retinal structure and was excluded. Most unilateral eyes (20/21) had a CST within the normal range. However, the CST, superior, nasal, inferior, and temporal sectors were all significantly thicker in the cataractous eye compared to the noncataractous eye (all P < 0.01 [paired t test]). The interocular difference for CST was not associated with age at surgery or interocular difference for visual acuity. In the bilateral group, although 34 of 38 eyes were within the normal range, the average CST of this group was significantly thicker than the noncataractous eye in the unilateral group. CONCLUSIONS: Following cataract extraction during infancy or childhood, most cataractous eyes had normal macular structure. Cataractous eyes of both unilaterally and bilaterally affected children have thicker CST values compared to the noncataractous eye.

Hemangiomas treated with propranolol: do the rewards outweigh the risks?

Recent reports of propranolol for the treatment of hemangiomas have led many physicians to question the best treatment strategy for children with vision-threatening hemangiomas. Although propranolol has potential side effects, including hypoglycemia and hypotension, early studies suggest it is more efficacious than systemic cortico steroids with a lower incidence of adverse side effects.

Guidelines for automated preschool vision screening: a 10-year, evidence-based update.

In 2003 the American Association for Pediatric Ophthalmology and Strabismus Vision Screening Committee proposed criteria for automated preschool vision screening. Recent literature from epidemiologic and natural history studies, randomized controlled trials of amblyopia treatment, and field studies of screening technologies have been reviewed for the purpose of updating these criteria. The prevalence of amblyopia risk factors (ARF) is greater than previously suspected; many young children with low-magnitude ARFs do not develop amblyopia, and those who do often respond to spectacles alone. High-magnitude ARFs increase the likelihood of amblyopia. Although depth increases with age, amblyopia remains treatable until 60 months, with decline in treatment effectiveness after age 5. US Preventive Services Task Force Preventative Services Task Force guidelines allow photoscreening for children older than 36 months of age. Some technologies directly detect amblyopia rather than ARFs. Age-based criteria for ARF detection using photoscreening is prudent: referral criteria for such instruments should produce high specificity for ARF detection in young children and high sensitivity to detect amblyopia in older children. Refractive screening for ARFs for children aged 12-30 months should detect astigmatism >2.0 D, hyperopia >4.5 D, and anisometropia >2.5 D; for children aged 31-48 months, astigmatism >2.0 D, hyperopia > 4.0 D, and anisometropia >2.0 D. For children >49 months of age original criteria should be used: astigmatism >1.5 D, anisometropia>1.5 D, and hyperopia >3.5 D. Visually significant media opacities and manifest (not intermittent) strabismus should be detected at all ages. Instruments that detect amblyopia should report results using amblyopia presence as the gold standard. These new American Association for Pediatric Ophthalmology and Strabismus Vision Screening Committee guidelines will improve reporting of results and comparison of technologies.

Outcomes of Harada-Ito surgery for acquired torsional diplopia.

PURPOSE: To evaluate the outcomes of Harada-Ito surgery in correcting various types of torsional diplopia. METHODS: The medical records of patients who underwent Harada-Ito surgery at two academic institutions were retrospectively reviewed. Data collected included etiology of torsional diplopia, strabismus and torsion measurements, reoperation rate, patient symptoms, and use of prism. Postoperative success was defined as a lack of diplopia in the primary position at distance and downgaze at near with or without prism. Failure was defined as persistent torsional diplopia; partial success was defined as surgical success but with restrictive strabismus in the secondary gaze positions. RESULTS: A total of 26 patients (mean age, 46 years; range, 13-89 years) were included. Of these, 17 had superior oblique palsy. The mean follow-up duration was 2 years (range, 2-60 months). The surgical outcome was success in 73% of patients, partial success in 7%, and failure in 19%. All patients with ≤10° of torsion preoperatively obtained surgical success. Patients in the failure group had higher amounts of preoperative torsion compared to the success group (P = 0.009). The reoperation rate was 23%, including four patients with additional surgery for downgaze esotropia or torsion. One-third of the patients wore a prism immediately after surgery. CONCLUSIONS: Harada-Ito surgery successfully treated torsional diplopia. Patients with ≤10° of preoperative torsion had a better outcome. Downgaze diplopia was a common reason for additional surgery.

Glaucoma-related adverse events in the Infant Aphakia Treatment Study: 1-year results.

OBJECTIVES: To report the incidence of glaucoma and glaucoma suspects in the IATS, and to evaluate risk factors for the development of a glaucoma-related adverse event in patients in the IATS in the first year of follow-up. METHODS: A total of 114 infants between 1 and 6 months of age with a unilateral congenital cataract were assigned to undergo cataract surgery either with or without an intraocular lens implant. Standardized definitions of glaucoma and glaucoma suspect were created and used in the IATS. RESULTS: Of these 114 patients, 10 (9%) developed glaucoma and 4 (4%) had glaucoma suspect, for a total of 14 patients (12%) with a glaucoma-related adverse event in the treated eye through the first year of follow-up. Of the 57 patients who underwent lensectomy and anterior vitrectomy, 5 (9%) developed a glaucoma-related adverse event; of the 57 patients who underwent an intraocular lens implant, 9 (16%) developed a glaucoma-related adverse event. The odds of developing a glaucoma-related adverse event were 3.1 times higher for a child with persistent fetal vasculature and 1.6 times higher for each month of age younger at cataract surgery. CONCLUSIONS: Modern surgical techniques do not eliminate the early development of glaucoma following congenital cataract surgery with or without an intraocular lens implant. Younger patients with or without persistent fetal vasculature seem more likely to develop a glaucoma-related adverse event in the first year of follow-up. Vigilance for the early development of glaucoma is needed following congenital cataract surgery, especially when surgery is performed during early infancy or for a child with persistent fetal vasculature. Five-year follow-up data for the IATS will likely reveal more glaucoma-related adverse events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00212134.

Prevalence and course of strabismus through age 6 years in participants of the Early Treatment for Retinopathy of Prematurity randomized trial.

PURPOSE: To present strabismus data for children who participated in the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial. METHODS: The prevalence of strabismus, categorized as present or absent, was tabulated for all children with history of high-risk prethreshold retinopathy of prematurity (ROP) who participated in the ETROP randomized trial and were examined at 9 months to 6 years of age. Relationships among strabismus and demographic measures, eye characteristics, and neurodevelopmental factors were analyzed. RESULTS: Among the 342 children evaluated at 6 years, the prevalence of strabismus was 42.2%. Even with favorable acuity scores in both eyes, the prevalence of strabismus was 25.4%, and with favorable structural outcomes in both eyes the prevalence of strabismus was 34.2%. Of children categorized as visually impaired as the result of either ocular or cerebral causes, 80% were strabismic at the 6-year examination. Of 103 study participants who were strabismic at 9 months, 77 (74.8%) remained so at 6 years. Most strabismus was constant at both the 9-month (62.7%) and the 6-year examination (72.3%). After multiple logistic regression analysis, risk factors for strabismus were abnormal fixation behavior in one or both eyes (P < 0.001), history of amblyopia (P < 0.003), unfavorable structural outcome in one or both eyes (P = 0.025), and history of anisometropia (P = 0.04). Strabismus surgery was performed for 53 children. By 6 years, the cumulative prevalence of strabismus was 59.4%. CONCLUSIONS: Most children with a history of high-risk prethreshold ROP develop strabismus at some time during the first 6 years of life.

Outpatient treatment of periocular infantile hemangiomas with oral propranolol.

BACKGROUND: Propranolol has recently been reported to be useful in the treatment of infantile hemangiomas. However, there are still many questions regarding the dosage, duration, and method of delivery. METHODS: In this retrospective, observational case series, all patients had complete eye examinations and were found to have vision-threatening hemangiomas. All patients had a baseline electrocardiogram. Outpatient, oral propranolol therapy was initiated between 3 weeks and 12 months of age. The dosage was slowly increased to 2 mg/kg daily over the course of 1-2 weeks. Response to therapy was deemed "excellent" (>50% reduction in size), "good" (decreased size but <50%), "fair" (no further growth), or "poor" (continued growth or intolerable adverse effects). RESULTS: A total of 17 patients were treated with oral therapy. Of these, 10 had excellent results, 6 had a good response, 1 fair, and none poor. Mild adverse effects were noted in 6 of the 17 patients and included the following: increased gastric reflux lasting 1 week, intermittent fatigue during the first 2 weeks, gastrointestinal upset, and slight "shakiness" with a missed dose. No symptoms were severe enough to discontinue treatment. All families were satisfied with the treatment. CONCLUSIONS: Outpatient propranolol treatment reduced the size or stopped the growth of all hemangiomas treated, with excellent response in more than half of all patients treated and only minor side effects. Although this is a small initial series, we are encouraged with the efficacy of this treatment modality in comparison with other currently available treatment options.

Refractive outcomes with secondary intraocular lens implantation in children.

PURPOSE: To determine the accuracy of postoperative predicted refractive outcomes in surgically aphakic pediatric patients undergoing secondary intraocular lens (IOL) implantation. Comparisons were also made with other variables historically considered important in cataract surgery. METHODS: Retrospective review of 50 eyes from 35 consecutive pediatric patients (< or =18 years of age) undergoing secondary IOL implantation within the ciliary sulcus or posterior capsular bag. All cases were performed by 1 of 2 surgeons and all refractions were performed manually using the retinoscope by an experienced pediatric ophthalmologist. RESULTS: The mean patient age at the time of the secondary implantation was 6.5 years of age (range, 0.58-15.04). The mean patient age at the time of the primary cataract extraction was 0.78 years (range, 0.08-5.77). For all patients, mean absolute value of prediction error was 1.64 D (SD 1.58 D). There were no significant associations between mean absolute value of prediction error and any of the variables measured including axial length, corneal mean curvature, bag or sulcus implantation, formula used, or age at primary and secondary surgery (p > 0.05). CONCLUSIONS: The mean absolute value of prediction error observed in this study is consistent with previous pediatric primary and secondary IOL data in that it shows a considerable difference from that expected in adult populations. Our findings support the argument that methods currently employed to calculate IOL power may fail to accurately account for all the variations in the eyes of pediatric patients.

Longitudinal assessment of plus disease in retinopathy of prematurity using color Doppler imaging.

Retinal vascular changes and the development of plus disease are the hallmarks of retinopathy of prematurity (ROP). The purpose of this study was to evaluate whether or not serial examinations of retrobulbar blood flow characteristics, as measured by color Doppler imaging (CDI) performed repeatedly over a period of several weeks, would be useful for predicting those infants at risk for developing plus disease and to determine whether this technique may be used as an objective tool for confirming the presence of plus disease. Of the 73 infants followed in this study, 14 (19%) developed plus disease confirmed by a panel of experts. When comparing the group of infants developing plus disease with those infants who did not develop plus disease, we did not find any significant differences in the retrobulbar blood flow characteristics of either the central retinal or ophthalmic arteries. Color Doppler imaging did not appear to be a clinically useful tool in the longitudinal management of ROP, nor did it appear to be useful as an objective determinant of plus disease in these premature infants.