Publications by authors named "Deborah K Vanderveen"

77 Publications

Early Experience with Ahmed Clear Path Glaucoma Drainage Device in Childhood Glaucoma.

J Glaucoma 2021 Apr 23. Epub 2021 Apr 23.

Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Purpose: To evaluate the short-term outcomes of Ahmed Clear Path (ACP) valveless glaucoma drainage device in childhood glaucoma.

Methods: Retrospective chart review of all patients ≤16 years with childhood glaucoma who had ACP implantation at Boston Children's Hospital from December 2019 to June 2020 with at least 6 months follow-up period.

Results: The study included 7 eyes of 5 patients implanted by a single surgeon. The median follow-up was 12 months. The mean IOP was reduced from 36±3.5▒mmHg on a mean of 2.7±0.6 glaucoma medications preoperatively to a mean IOP of 12.4±2.8▒mmHg (P<0.001) on a mean of 0.7±0.8 medications postoperatively at final follow-up (P=0.0009). Complete success was achieved in 4 eyes while qualified success was achieved in 3 eyes.

Conclusion: The ACP GDD provided good short term IOP control and technical advantages for implantation for pediatric eyes were observed.
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http://dx.doi.org/10.1097/IJG.0000000000001855DOI Listing
April 2021

Retinopathy of prematurity screening and risk mitigation during the COVID-19 pandemic.

J AAPOS 2021 Apr 18. Epub 2021 Apr 18.

Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.

Background: The coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted the delivery of healthcare. Although most nonurgent ophthalmology visits at Boston Children's Hospital were canceled, premature infants at risk for retinopathy of prematurity (ROP) still required timely, in-person care during the initial 3-month period of the infection surge in Massachusetts. The purpose of the current study was to report our protocols for mitigating risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between infants and eye care providers and to compare examination rates and results with the same 3-month period in 2019.

Methods: During the infection surge, we added new infection control measures and strengthened existing ones. Additional personal protective equipment was used, and the number of ophthalmologists rotating in the three high-capacity NICUs we service was limited.

Results: More infants required ROP examinations during the study period in 2020 than in the same period in 2019, but fewer examinations were performed. There were no cases of missed progression to severe ROP during this time and no known transmission of SARS-CoV-2 between ROP patients and ophthalmology staff.

Conclusions: Overall, effective ROP care was safely provided during the COVID-19 pandemic, and contact with this vulnerable population was minimized.
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http://dx.doi.org/10.1016/j.jaapos.2020.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053364PMC
April 2021

Impact of higher oxygen saturation levels on postnatal weight gain to predict retinopathy of prematurity.

Acta Paediatr 2021 Apr 2. Epub 2021 Apr 2.

Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1111/apa.15868DOI Listing
April 2021

Glaucoma-Related Adverse Events at 10 Years in the Infant Aphakia Treatment Study: A Secondary Analysis of a Randomized Clinical Trial.

JAMA Ophthalmol 2021 02;139(2):165-173

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.

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.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.5664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747044PMC
February 2021

Outcomes of secondary intraocular lens implantation in the Infant Aphakia Treatment Study.

J Cataract Refract Surg 2021 Feb;47(2):172-177

From the Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School (VanderVeen), Boston, Massachusetts, Department of Epidemiology (Drews-Botsch), Department of Biostatistics and Bioinformatics (Nizam), Rollins School of Public Health, Emory University, Atlanta, Georgia, Department of Ophthalmology, Mayo Clinic (Bothun), Rochester, Minnesota, Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University School of Medicine (L.B. Wilson), Portland, Oregon, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina (M.E. Wilson), Charleston, South Carolina, Department of Ophthalmology, Stanford University School of Medicine (Lambert), Stanford, California, USA.

Purpose: To report outcomes of secondary intraocular lens (IOL) implantation in the Infant Aphakia Treatment Study (IATS).

Setting: Multicenter clinical practice.

Design: Secondary analysis of patients enrolled in a randomized clinical trial.

Methods: Details regarding all secondary IOL surgeries conducted in children enrolled in the IATS were compiled. Visual outcomes, refractive outcomes, and adverse events at the age of 10½ years were evaluated. Comparisons were made with eyes that remained aphakic and with eyes randomized to primary IOL placement.

Results: The study included 114 infants, 57 in the aphakic group and 57 in the primary IOL group; 55 of 57 patients randomized to aphakia with contact lens correction were seen for the 10½-year study visit; 24 (44%) of 55 eyes had secondary IOL surgery. Median age at IOL surgery was 5.4 years (range 1.7 to 10.3 years). Mean absolute prediction error was 1.00 ± 0.70 diopters (D). At age 10½ years, the median logarithm of the minimum angle of resolution visual acuity (VA) was 0.9 (range 0.2 to 1.7), similar to VA in the 31 eyes still aphakic (0.8, range 0.1 to 2.9); the number of eyes with stable or improved VA scores between the 4½-year and 10½-year study visits was also similar (78% secondary IOL eyes; 84% aphakic eyes). For eyes undergoing IOL implantation after the 4½-year study visit (n = 22), the mean refraction at age 10½ years was -3.20 ± 2.70 D (range -9.90 to 1.10 D), compared with -5.50 ± 6.60 D (n = 53, range -26.50 to 3.00 D) in eyes with primary IOL (P = .03).

Conclusions: Delayed IOL implantation allows a more predictable refractive outcome at age 10½ years, although the range of refractive error is still large.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936988PMC
February 2021

Outcomes of Bilateral Cataract Surgery in Infants 7 to 24 Months of Age Using the Toddler Aphakia and Pseudophakia Treatment Study Registry.

Ophthalmology 2021 Feb 15;128(2):302-308. Epub 2020 Jul 15.

Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon; Departments of Ophthalmology and Pediatrics, Stanford University Medical Center, Palo Alto, California.

Purpose: 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.

Design: Retrospective clinical study at 10 Infant Aphakia Treatment Study (IATS) sites. Statistical analyses comparing this cohort with previously reported TAPS registry cohorts.

Participants: Children enrolled in the TAPS registry between 2004 and 2010.

Methods: 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.

Main Outcome Measures: Visual acuity (VA), occurrence of strabismus, AEs, and reoperations.

Results: 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).

Conclusions: 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 at < 7 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.
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http://dx.doi.org/10.1016/j.ophtha.2020.07.020DOI Listing
February 2021

Workforce Shortage for Retinopathy of Prematurity Care and Emerging Role of Telehealth and Artificial Intelligence.

Pediatr Clin North Am 2020 08;67(4):725-733

Center for Policy, Outcomes, and Prevention, Stanford University School of Medicine, 117 Encina Commons, Stanford, CA 94305, USA.

Retinopathy of prematurity (ROP) is the leading cause of childhood blindness in very-low-birthweight and very preterm infants in the United States. With improved survival of smaller babies, more infants are at risk for ROP, yet there is an increasing shortage of providers to screen and treat ROP. Through a literature review of new and emerging technologies, screening criteria, and analysis of a national survey of pediatric ophthalmologists and retinal specialists, the authors found the shortage of ophthalmology workforce for ROP a serious and growing concern. When used appropriately, emerging technologies have the potential to mitigate gaps in the ROP workforce.
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http://dx.doi.org/10.1016/j.pcl.2020.04.012DOI Listing
August 2020

Outcomes of Glaucoma Drainage Devices in Childhood Glaucoma.

Semin Ophthalmol 2020 Apr 20;35(3):194-204. Epub 2020 Jun 20.

Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School , Boston, MA, USA.

Purpose: Angle surgery is the gold standard for the management of many types of childhood glaucoma, yet glaucoma drainage devices (GDD) are effective tools for refractory advanced cases or secondary childhood glaucomas. The purpose of this article is to review recently published literature focused on the use of GDDs for pediatric glaucoma, including GDD general principles and surgical outcomes.

Methods: Literature review of various electronic databases was performed.

Results: 71 papers were reviewed for outcomes of GDD in childhood glaucomas. Success rates were usually defined by intraocular pressure (IOP) of 5-22 mmHg, with or without medications. Success rates were typically higher for non-valved GDDs but varied by length of follow-up. Non-valved GDDs afford lower and longer-lasting IOP control in pediatric eyes than valved GDD, however, no randomized controlled trials exist in childhood glaucoma.

Conclusion: Various designs of GDDs are available for management of childhood glaucoma with good short-term success rates; individual patient factors should be taken into consideration when selecting a specific device.
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http://dx.doi.org/10.1080/08820538.2020.1781906DOI Listing
April 2020

Ocular injury via epinephrine auto-injector.

J AAPOS 2020 06 2;24(3):179-181. Epub 2020 Jun 2.

Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Intraocular injury by epinephrine auto-injector has been rarely reported. Toxic risk to the intraocular structures is suspected, but the evidence is inconclusive. We present the case of a 2-year-old girl who sustained an injury to her right eye by inadvertent epinephrine injection. Cataract surgery was performed to treat an increasingly opaque lens, and an intraocular lens was implanted. The visual outcome was good, with no retinal damage.
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http://dx.doi.org/10.1016/j.jaapos.2020.02.008DOI Listing
June 2020

Short-term Outcomes After Very Low-Dose Intravitreous Bevacizumab for Retinopathy of Prematurity.

JAMA Ophthalmol 2020 06;138(6):698-701

Mayo Clinic, Rochester, Minnesota.

Importance: Intravitreous bevacizumab (0.25 mg to 0.625 mg) is commonly used to treat type 1 retinopathy of prematurity (ROP), but there are concerns about systemic toxicity, particularly the risk of neurodevelopmental delay. A much lower dose may be effective for ROP while reducing systemic risk. Previously, after testing doses of 0.25 mg to 0.031 mg, doses as low as 0.031 mg were found to be effective in small cohorts of infants.

Objective: To find the lowest dose of intravitreous bevacizumab effective for severe ROP.

Design, Setting, And Participants: Between April 2017 and May 2019, 59 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, dose de-escalation study. In cohorts of 10 to 14 infants, 1 eye per infant received 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreous bevacizumab. Diluted bevacizumab was prepared by individual research pharmacies and delivered using 300-µL syringes with 5/16-inch, 30-guage fixed needles. Analysis began July 2019.

Interventions: Bevacizumab intravitreous injections at 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg.

Main Outcomes And Measures: Success was defined as improvement by 4 days postinjection and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks.

Results: Fifty-five of 59 enrolled infants had 4-week outcomes completed; the mean (SD) birth weight was 664 (258) g, and the mean (SD) gestational age was 24.8 (1.6) weeks. A successful 4-week outcome was achieved for 13 of 13 eyes (100%) receiving 0.016 mg, 9 of 9 eyes (100%) receiving 0.008 mg, 9 of 10 eyes (90%) receiving 0.004 mg, but only 17 of 23 eyes (74%) receiving 0.002 mg.

Conclusions And Relevance: These data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness of very low-dose intravitreous bevacizumab and its effect on plasma vascular endothelial growth factor levels and peripheral retinal vascularization.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.0334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180729PMC
June 2020

Accuracy of Autorefraction in Children: A Report by the American Academy of Ophthalmology.

Ophthalmology 2020 09 18;127(9):1259-1267. Epub 2020 Apr 18.

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.

Purpose: The purpose of this assessment is to evaluate the accuracy of autorefraction compared with cycloplegic retinoscopy in children.

Methods: Literature searches were last conducted in October 2019 in the PubMed and the Cochrane Library databases for studies published in English. The combined searches yielded 118 citations, of which 53 were reviewed in full text. Of these, 31 articles were deemed appropriate for inclusion in this assessment and subsequently assigned a level of evidence rating by the panel methodologists. Four articles were rated level I, 11 were rated level II, and 16 were rated level III articles. The 16 level III articles were excluded from this review.

Results: Thirteen of the 15 studies comparing cycloplegic autorefraction with cycloplegic retinoscopy found a mean difference in spherical equivalent or sphere of less than 0.5 diopters (D); most were less than 0.25 D. Even lower mean differences were found when evaluating the cylindrical component of cycloplegic autorefraction versus cycloplegic retinoscopy. Despite low mean variability, there was significant individual measurement variability; the 95% limits of agreement were wide and included clinically relevant differences. Comparisons of noncycloplegic with cycloplegic autorefractions found that noncyloplegic refraction tends to over minus by 1 to 2 D.

Conclusions: Cycloplegic autorefraction is appropriate to use in pediatric population-based studies. Cycloplegic retinoscopy can be valuable in individual clinical cases to confirm the accuracy of cycloplegic autorefraction, particularly when corrected visual acuity is worse than expected or the autorefraction results are not consistent with expected findings.
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http://dx.doi.org/10.1016/j.ophtha.2020.03.004DOI Listing
September 2020

An ophthalmologist's view on breaking bad news to patients.

J AAPOS 2020 02 31;24(1):1.e1-1.e2. Epub 2020 Jan 31.

Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.jaapos.2019.05.019DOI Listing
February 2020

Outcomes of Bilateral Cataracts Removed in Infants 1 to 7 Months of Age Using the Toddler Aphakia and Pseudophakia Treatment Study Registry.

Ophthalmology 2020 04 9;127(4):501-510. Epub 2019 Nov 9.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia; Departments of Ophthalmology and Pediatrics, Stanford University School of Medicine, Palo Alto, California.

Purpose: 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.

Design: Retrospective case series review at 10 IATS sites.

Participants: The Toddler Aphakia and Pseudophakia Study (TAPS) is a registry of children treated by surgeons who participated in the IATS.

Methods: Children underwent bilateral cataract surgery with or without intraocular lens (IOL) placement during IATS enrollment years 2004 through 2010.

Main Outcome Measures: Visual acuity (VA), strabismus, adverse events (AEs), and reoperations.

Results: 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%).

Conclusions: 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.
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http://dx.doi.org/10.1016/j.ophtha.2019.10.039DOI Listing
April 2020

Reply.

Ophthalmology 2020 01;127(1):e8-e9

Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, Tennessee.

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http://dx.doi.org/10.1016/j.ophtha.2019.09.040DOI Listing
January 2020

Reply.

Ophthalmology 2020 01 11;127(1):e6-e7. Epub 2019 Oct 11.

Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, Tennessee.

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http://dx.doi.org/10.1016/j.ophtha.2019.09.017DOI Listing
January 2020

Early presentation of pigment dispersion syndrome.

Can J Ophthalmol 2020 02 12;55(1):e47-e48. Epub 2019 Aug 12.

Boston Children Hospital, Harvard Medical School, Boston, MA. Electronic address:

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http://dx.doi.org/10.1016/j.jcjo.2019.06.012DOI Listing
February 2020

Binocular Treatment of Amblyopia: A Report by the American Academy of Ophthalmology.

Ophthalmology 2020 02 13;127(2):261-272. Epub 2019 Oct 13.

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.

Purpose: To review the published literature assessing the efficacy of binocular therapy for the treatment of amblyopia compared with standard treatments.

Methods: Literature searches with no date restrictions and limited to the English language were conducted in January 2018 and updated in April 2019 in the PubMed database and the Cochrane Library database with no restrictions. The search yielded 286 citations, and the full text of 50 articles was reviewed. Twenty articles met the inclusion criteria for this assessment and were assigned a level of evidence rating by the panel methodologist. Six studies were rated level I, 1 study was rated level II, and 13 studies were rated level III because of the impact on the development and popularization of this technology.

Results: Two of the level I and II studies reviewed described a significant improvement in visual acuity in the binocular group versus standard patching standard treatment (the total number of patients in these 2 studies was 147). However, the 5 studies that failed to show a visual improvement from binocular therapy compared with standard treatments were larger and more rigorously designed (the total number of patients in these 5 studies was 813). Level I and II studies also failed to show a significant improvement over baseline in sensory status, including depth of suppression and stereopsis of those treated with binocular therapy. Several smaller level III case series (total number of patients in these 13 studies was 163) revealed more promising results than the binocular treatments studied in the level I and II studies, especially using treatments that are more engaging and are associated with better compliance.

Conclusions: There is no level I evidence to support the use of binocular treatment as a substitute for current therapies for amblyopia (including patching and optical treatment). Furthermore, 2 large randomized controlled trials showed inferior performance compared with standard patching treatment. On the basis of this review of the published literature, binocular therapy cannot be recommended as a replacement for standard amblyopia therapy. However, more research is needed to determine the potential benefits of proposed binocular treatments in the future.
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http://dx.doi.org/10.1016/j.ophtha.2019.08.024DOI Listing
February 2020

Placental CpG Methylation of Inflammation, Angiogenic, and Neurotrophic Genes and Retinopathy of Prematurity.

Invest Ophthalmol Vis Sci 2019 07;60(8):2888-2894

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States.

Purpose: Extremely preterm infants are at increased risk for retinopathy of prematurity (ROP). We previously identified several inflammatory proteins that were expressed early in life and are associated with an increased risk of ROP and several angiogenic and neurotrophic growth factors in the neonatal systemic circulation that are associated with a lower risk of ROP. In this paper, we report the results of a set of analyses designed to test the hypothesis that placental CpG methylation levels of 12 inflammation-, angiogenic-, and neurotrophic-associated genes predict the occurrence of prethreshold ROP in extremely preterm newborns.

Methods: We used placental CpG methylation data from 395 newborns from the Extremely Low Gestational Age Newborns study.

Results: Multivariable regression models revealed that placental DNA methylation of 16 CpG sites representing 8 genes were associated with prethreshold ROP. Specifically, CpG methylation in the serum amyloid A SAA1 and SAA2, brain-derived neurotrophic factor (BDNF), myeloperoxidase (MPO), C-reactive protein (CRP), angiopoietin 1 (ANGPT1), and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) genes was associated with a lower risk of prethreshold ROP. Conversely, CpG methylation at three probes within tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and in two alternative probes within the BDNF and ANGPT1 genes was associated with an increased risk of ROP.

Conclusions: CpG methylation may be a useful marker for improving ROP prediction, opening the opportunity for early intervention to lessen disease severity.
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http://dx.doi.org/10.1167/iovs.18-26466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607927PMC
July 2019

Third-Party Coverage for Aphakic Contact Lenses for Children.

Transl Vis Sci Technol 2019 May 14;8(3):41. Epub 2019 Jun 14.

Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

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http://dx.doi.org/10.1167/tvst.8.3.41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6574195PMC
May 2019

Intraocular Lens Implantation during Early Childhood: A Report by the American Academy of Ophthalmology.

Ophthalmology 2019 10 21;126(10):1454-1461. Epub 2019 Jun 21.

Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Purpose: To compare the visual outcomes and adverse events associated with optical correction using an intraocular lens (IOL), contact lenses, or spectacles after cataract surgery in children 2 years of age or younger.

Methods: Literature searches were conducted in PubMed, the Cochrane Library, and the databases of clinical trials in February 2019, without date or language restrictions. The search resulted in 194 potentially relevant citations, and 34 were selected for full-text review. Fourteen studies were determined to be relevant to the assessment criteria and were selected for inclusion in this assessment. The panel methodologist then assigned a level of evidence rating to these studies.

Results: Intraocular lenses were associated with visual outcomes similar to outcomes for contact lenses or spectacles for children who had both bilateral and unilateral cataracts. Intraocular lenses were also associated with an increased risk of visual axis opacities. All treatments were associated with a similar incidence of glaucoma. Although ocular growth was similar for all treatments, infants younger than 6 months who underwent IOL implantation had large myopic shifts that often resulted in high myopia or severe anisometropia later in childhood. Corneal endothelial cell counts were lower in eyes that underwent IOL implantation. The incidence of strabismus was similar with all treatments.

Conclusions: Intraocular lens implantation is not recommended for children 6 months of age or younger because there is a higher incidence of visual axis opacities with this treatment compared with aphakia. The best available evidence suggests that IOL implantation can be done safely with acceptable side effects in children older than 6 months of age. However, the unpredictability of ocular growth means that these children will often have large refractive errors later in childhood that may necessitate an IOL exchange or wearing spectacles or contact lenses with a large refractive correction. In addition, the training and experience of the surgeon as well as ocular and systemic comorbidities should be taken into consideration when deciding whether IOL implantation would be appropriate.
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http://dx.doi.org/10.1016/j.ophtha.2019.05.009DOI Listing
October 2019

Anti-vascular endothelial growth factor intravitreal therapy for retinopathy of prematurity.

Semin Perinatol 2019 10 10;43(6):375-380. Epub 2019 May 10.

Department of Pediatric Neonatology, Brigham and Women's Hospital, Harvard Medical School; Boston, MA, USA.

Retinopathy of prematurity treatment modalities have expanded over the years, from cryotherapy to laser therapy and now, anti-vascular endothelial factor (VEGF) therapy by intravitreal injection. Use of anti-VEGF treatment varies regionally and depends on multiple factors including severity and progression of ROP, availability of alternative treatments, experience of the local ophthalmologists, medical status of the infant, and expectations for long-term follow-up. While the advantages and disadvantages of anti-VEGF intravitreal treatment on the eye are relatively well-described, few studies provide information about potential long-term systemic effects of this treatment, which is known to transiently reduce systemic VEGF concentrations.
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http://dx.doi.org/10.1053/j.semperi.2019.05.011DOI Listing
October 2019

Intraocular Lens Techniques in Pediatric Eyes with Insufficient Capsular Support: Complications and Outcomes.

Semin Ophthalmol 2019 28;34(4):293-302. Epub 2019 May 28.

a Department of Ophthalmology , Boston Children's Hospital, Harvard Medical School , Boston , MA , USA.

Intraocular lens (IOL) implantation in pediatric eyes with insufficient capsular support is challenging and there are multiple IOL options. These include placement of an IOL within the capsular bag with a capsular tension ring, a scleral-fixated posterior-chamber IOL (PCIOL) with or without capsular tension segment or ring, an intra-scleral fixated IOL, an iris-sutured PCIOL, or an anterior chamber iris-fixated IOL. We reviewed 48 articles and 1 published abstract describing the surgical techniques, complications and visual outcomes of different IOL options in the management of aphakic pediatric eyes with insufficient capsular support. The present review found that the visual acuity outcomes of various IOLs are comparable. Furthermore, each IOL design and surgical technique has different rates of serious complications, including IOL dislocation or decentration, intraocular hemorrhage, glaucoma, endothelial cell loss, and endophthalmitis. An understanding of the risks and benefits of different IOL designs is important for counseling patients and families.
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http://dx.doi.org/10.1080/08820538.2019.1620809DOI Listing
July 2019

Outcomes of Unilateral Cataracts in Infants and Toddlers 7 to 24 Months of Age: Toddler Aphakia and Pseudophakia Study (TAPS).

Ophthalmology 2019 08 14;126(8):1189-1195. Epub 2019 Mar 14.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia; Departments of Ophthalmology and Pediatrics, Stanford University Medical Center, Palo Alto, California.

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.
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http://dx.doi.org/10.1016/j.ophtha.2019.03.011DOI Listing
August 2019

Early Postnatal IGF-1 and IGFBP-1 Blood Levels in Extremely Preterm Infants: Relationships with Indicators of Placental Insufficiency and with Systemic Inflammation.

Am J Perinatol 2019 12 27;36(14):1442-1452. Epub 2019 Jan 27.

Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts.

Objective: To evaluate to what extent indicators of placenta insufficiency are associated with low concentrations of insulin-like growth factor 1 (IGF-1) and IGF-1-binding protein-1 (IGFBP-1) in neonatal blood, and to what extent the concentrations of these growth factors are associated with concentrations of proteins with inflammatory, neurotrophic, or angiogenic properties.

Study Design: Using multiplex immunoassays, we measured the concentrations of IGF-1 and IGFBP-1, as well as 25 other proteins in blood spots collected weekly from ≥ 880 infants born before the 28th week of gestation, and sought correlates of concentrations in the top and bottom quartiles for gestational age and day the specimen was collected.

Results: Medically indicated delivery and severe fetal growth restriction (sFGR) were associated with low concentrations of IGF-1 on the first postnatal day and with high concentrations of IGFBP-1 on almost all days. Elevated concentrations of IGF-1 and IGFBP-1 were accompanied by elevated concentrations of many other proteins with inflammatory, neurotrophic, or angiogenic properties.

Conclusion: Disorders associated with impaired placenta implantation and sFGR appear to account for a relative paucity of IGF-1 on the first postnatal day. Elevated concentrations of IGF-1 and especially IGFBP-1 were associated with same-day elevated concentrations of inflammatory, neurotrophic, and angiogenic proteins.
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http://dx.doi.org/10.1055/s-0038-1677472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252600PMC
December 2019

Use of Orthokeratology for the Prevention of Myopic Progression in Children: A Report by the American Academy of Ophthalmology.

Ophthalmology 2019 04 23;126(4):623-636. Epub 2018 Nov 23.

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.

Purpose: To review the published evidence to evaluate the ability of orthokeratology (Ortho-K) treatment to reduce myopic progression in children and adolescents compared with the use of spectacles or daytime contact lenses for standard refractive correction.

Methods: Literature searches of the PubMed database, the Cochrane Library, and the databases of clinical trials were last conducted on August 21, 2018, with no date restrictions but limited to articles published in English. These searches yielded 162 citations, of which 13 were deemed clinically relevant for full-text review and inclusion in this assessment. The panel methodologist then assigned a level of evidence rating to the selected studies.

Results: The 13 articles selected for inclusion include 3 prospective, randomized clinical trials; 7 nonrandomized, prospective comparative studies; and 3 retrospective case series. One study provided level I evidence, 11 studies provided level II evidence, and 1 study provided level III evidence. Most studies were performed in populations of Asian ethnicity. Change in axial length was the primary outcome for 10 of 13 studies and change in refraction was the primary outcome for 3 of 13 studies. In these studies, Ortho-K typically reduced axial elongation by approximately 50% over a 2-year study period. This corresponds to average axial length change values of approximately 0.3 mm for Ortho-K patients compared with 0.6 mm for control patients, which corresponds to a typical difference in refraction of approximately 0.5 diopters (D). Younger age groups and individuals with larger than average pupil size may have a greater effect with Ortho-K. Rebound can occur after discontinuation or change to alternative refractive treatment.

Conclusions: Orthokeratology may be effective in slowing myopic progression for children and adolescents, with a potentially greater effect when initiated at an early age (6-8 years). Safety remains a concern because of the risk of potentially blinding microbial keratitis from contact lens wear.
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http://dx.doi.org/10.1016/j.ophtha.2018.11.026DOI Listing
April 2019

Bilateral Immediate Sequential Vitrectomy and Lensectomy for Bilateral Lens Dislocation in Severe Neonatal Marfan Syndrome.

Ophthalmic Surg Lasers Imaging Retina 2018 10;49(10):e151-e153

A newborn with severe neonatal Marfan syndrome (NMS), characterized by aortic root dilation, mitral and tricuspid valve regurgitation, diaphragmatic eventration with respiratory distress, intestinal malrotation, and various skeletal abnormalities, developed bilateral pupillary block from luxated crystalline lenses. He underwent bilateral immediate sequential vitrectomy and lensectomy to prevent further episodes of pupillary block. Bilateral surgery was performed due to the extremely high anesthesia risk. NMS is a rare and severe form of the connective tissue disease that can present with numerous systemic and ocular findings. Measures to decrease anesthesia risk are recommended, including the consideration of bilateral surgery. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e151-e153.].
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http://dx.doi.org/10.3928/23258160-20181002-19DOI Listing
October 2018

The Use of β-Blockers for the Treatment of Periocular Hemangiomas in Infants: A Report by the American Academy of Ophthalmology.

Ophthalmology 2019 01 1;126(1):146-155. Epub 2018 Aug 1.

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.

Purpose: To review the published literature assessing the efficacy of β-blockers for the treatment of periocular hemangioma in infants.

Methods: Literature searches were conducted in May 2018 in PubMed with no date restrictions and limited to studies published in English and in the Cochrane Library database without any restrictions. The combined searches yielded 437 citations. Of these,16 articles were deemed appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist.

Results: None of the 16 studies included in this assessment were rated level I, 3 were rated level II, and 13 were rated level III. The most common treatment regimen was 2 mg/kg daily oral propranolol, but intralesional and topical β-blockers were also used. Treatment effect was most often measured in terms of reduction in the size of the lesions, which occurred in the majority of patients. β-Blockers were consistently shown to reduce astigmatism, but this reduction was shown to be statistically significant in only 2 series. The effect of β-blockers on amblyopia was not adequately documented. β-Blockers were generally well tolerated and had mild side effects (fatigue, gastrointestinal upset/diarrhea, restlessness/sleep disturbances, minor wheezing, and cold extremities). Complications severe enough to require cessation of treatment occurred in only 2 patients out of a total of 229 who received β-blockers.

Conclusions: There is limited evidence to support the safety and efficacy of both topical and systemic β-blockers to promote regression of periocular hemangiomas. Additional research may confirm the best dosage and route of administration to maximize efficacy in reducing induced astigmatism and amblyopia associated with periocular hemangiomas while minimizing side effects.
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http://dx.doi.org/10.1016/j.ophtha.2018.07.023DOI Listing
January 2019

Contact Lens Correction of Aphakia in Children: A Report by the American Academy of Ophthalmology.

Ophthalmology 2018 09 7;125(9):1452-1458. Epub 2018 Apr 7.

Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Purpose: To review the published literature to assess the visual outcomes and adverse events associated with the 2 most commonly used contact lenses for treating aphakia in children: silicone elastomer (SE) and rigid gas permeable (RGP).

Methods: Literature searches were last conducted in January 2018 in the PubMed, Cochrane Library, and ClinicalTrials.gov databases with no date or language restrictions. These combined searches yielded 167 citations, 27 of which were reviewed in full text. Of these, 10 articles were deemed appropriate for inclusion in this assessment and subsequently assigned a level of evidence rating by the panel methodologist.

Results: The literature search identified 4 level II studies and 6 level III studies. There were insufficient data to compare visual outcomes for eyes treated using SE lenses versus RGP lenses. Silicone elastomer lenses have the advantage that they can be worn on an extended-wear basis, but they were associated with more adverse events than RGP lenses. These adverse events included microbial keratitis, corneal infiltrates, corneal edema, corneal scars, lenses adhering to the cornea, superficial punctate keratopathy, lid swelling, and conjunctival hyperemia. The lens replacement rate was approximately 50% higher for RGP lenses in the only study that directly compared SE and RGP lenses.

Conclusions: Limited evidence was found in the literature on this topic. Silicone elastomer and RGP contact lenses were found to be effective for treating aphakia in children. Silicone elastomer lenses are easier to fit and may be worn on an extended-wear basis. Rigid gas permeable lenses must be removed every night and require a more customized fit, but they are associated with fewer adverse events. The choice of which lens a practitioner prescribes should be based on the particular needs of each patient.
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http://dx.doi.org/10.1016/j.ophtha.2018.03.014DOI Listing
September 2018

Weighing in on New Screening Models for Retinopathy of Prematurity.

JAMA Ophthalmol 2018 04;136(4):417-418

Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamaophthalmol.2018.0359DOI Listing
April 2018

Global Practice Patterns in the Management of Infantile Cataracts.

Eye Contact Lens 2018 Nov;44 Suppl 2:S292-S296

Department of Ophthalmology (E.B.K., S.R.L.), Stanford University School of Medicine, Stanford, CA; and Pediatric Ophthalmology (D.K.V.), Boston Children's Hospital, Harvard Medical School, Boston, MA.

Objectives: Surveys are an important tool to assess the impact of research on physicians' approach to patient care. This survey was conducted to assess current practice patterns in the management of infantile cataracts in light of the findings of the Infant Aphakia Treatment Study.

Methods: Pediatric ophthalmologists were emailed a link to the survey using newsletters from American Association of Pediatric Ophthalmology and Strabismus, World Society of Pediatric Ophthalmology and Strabismus, and the Pediatric Listserv. The 17-question survey was anonymous and active during July to August 2016.

Results: One hundred twenty-five respondents (North America, 65%; Asia, 12%; Europe, 9%; and other, 14%) reported operating on pediatric cataracts. Most practice in a university setting (55%). There was a strong consensus that unilateral cataract surgery should be performed between ages 4 to 6 weeks and aphakic contact lenses should be used to optically correct their eyes, particularly in children ≤6 months of age. For bilateral cataracts, there was a trend for surgeons to perform cataract surgery at an older age than unilateral cataract surgery. Surgeons who performed less than 5 versus greater than 20 pediatric cataract surgeries/year were more likely to use aphakic contact lenses in children undergoing cataract surgery more than 6 months of age (62% vs. 35%, P=0.04). Most respondents (73%) indicated that the Infant Aphakia Treatment Study had changed how they manage unilateral congenital cataracts.

Conclusion: Most pediatric cataract surgeons perform congenital cataract surgery between ages 4 to 6 weeks and use aphakic contact lenses for initial optical correction in infants less than 6 months. Surgeons have equal preference for intraocular lenses and contact lenses in infants more than 6 months of age.
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http://dx.doi.org/10.1097/ICL.0000000000000461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046272PMC
November 2018