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Deng W, Hoffman E, Stoller J, Rubsam M, Ku M, Barbieri M, Lacci C, Jayaraman A. Environment Enrichment Strategies for Pre- and Post-Term Infants: A Summarized Communication From Pediatric Physical Therapists. Pediatr Phys Ther 2025; 37:265-276. [PMID: 40085791 DOI: 10.1097/pep.0000000000001187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
PURPOSE Environmental enrichment (EE) represents a dynamic approach to enhance infants' cognitive and motor development through augmented environment with stimulating, novel opportunities. Despite the recognized benefits of EE on neuromotor outcomes, its integration into early physical therapy interventions for infants at risk of neuromotor delays and disabilities remains under-defined and inconsistently applied in standard practice. This gap underscores the necessity for comprehensive guidance to systematically incorporate EE into early intervention programs and daily routines. SUMMARY OF KEY POINTS This paper provides a preliminary framework for the integration of EE into the clinical and home environments for infants from birth to 1 year of age. RECOMMENDATIONS FOR PRACTICE With the 7 key components of EE, including sensory system stimulation (auditory, proprioceptive, tactile, vestibular, and visual stimulations), cognitive challenges, and social engagement, this framework aims to maximize cognitive and motor development for infants at both pre and post-term age by leveraging the principles of EE(Supplemental Digital Content,Video, available at: http://links.lww.com/PPT/A624 ).
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Affiliation(s)
- Weiyang Deng
- Max Nader Center for Rehabilitation Technologies & Outcomes Research, Shirley Ryan AbilityLab, Chicago, Illinois (Drs Deng, Hoffman, Stoller, Rubsam, Ku, Barbieri, Lacci, and Jayaraman); Department of Rehabilitation Science, University of Illinois Chicago, Chicago, Illinois (Dr Rubsam); Department of Psychological and Brain Sciences, University of Massachusetts Amherst, Amherst, Massachusetts (Dr Barbieri); Department of Physical Medicine & Rehabilitation, Feinberg School of Medicine, Northwestern Medicine, Chicago, Illinois (Dr Jayaraman); Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Dr Jayaraman); Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Dr Jayaraman)
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Zhou M, Hashimoto K, Liu W, Cai Y, Liang J, Shi X, Zhao M. Efficacy comparison of anti-vascular endothelial growth factor drugs for the treatment of type 1 retinopathy of prematurity: A network meta-analysis of randomised controlled trials. Graefes Arch Clin Exp Ophthalmol 2024; 262:1409-1419. [PMID: 37815595 DOI: 10.1007/s00417-023-06224-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 08/11/2023] [Accepted: 08/26/2023] [Indexed: 10/11/2023] Open
Abstract
PURPOSE To compare the efficacy of different anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) in preterm infants. METHODS Seven databases were searched for eligible literature up to February 22, 2023. Studies were included if they were randomised controlled trials (RCTs) investigating the efficacy of anti-VEGF agents for ROP in infants. A network meta-analysis (NMA) was performed. We also conducted subgroup analyses to determine the efficacy ranking of regimens used in different regions. The odds ratio (OR), standardised mean difference (SMD), and surface under the cumulative ranking curve (SUCRA) were calculated for each outcome. RESULTS Thirteen RCTs of 10 different regimens, involving 1196 infants (2388 eyes), were identified. Bevacizumab (0.625 mg; OR = 0.16, 95% confidence interval [CI] 0.06-0.40, SUCRA = 80.6%) and conbercept (0.15 mg; OR = 0.08, 95% CI 0.02-0.30, SUCRA = 96.0%) were the most effective regimens in reducing the risk of ROP recurrence requiring retreatment in Western countries and China, respectively. Compared with laser therapy, bevacizumab (0.625 mg; SMD = 1.54, 95% CI 0.06-3.02) achieved significantly longer intervals between treatment and recurrence. No significant difference in the risk of retinal detachment was detected between any anti-VEGF agent and laser (p > 0.05). CONCLUSIONS Bevacizumab (0.625 mg) and conbercept (0.15 mg) appeared to be the most effective therapies for ROP in Western countries and China, respectively. More high-quality RCTs are warranted to evaluate the efficacy and long-term safety of anti-VEGF drugs for the management of ROP.
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Affiliation(s)
- Miao Zhou
- Department of Ophthalmology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
- Eye Diseases and Optometry Institute, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Kinji Hashimoto
- Department of Ophthalmology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
- Eye Diseases and Optometry Institute, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Wenbo Liu
- Department of Ophthalmology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
- Eye Diseases and Optometry Institute, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Yi Cai
- Department of Ophthalmology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
- Eye Diseases and Optometry Institute, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Jianhong Liang
- Department of Ophthalmology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
- Eye Diseases and Optometry Institute, Beijing, China.
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
- College of Optometry, Peking University Health Science Center, Beijing, China.
| | - Xuan Shi
- Department of Ophthalmology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
- Eye Diseases and Optometry Institute, Beijing, China.
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
- College of Optometry, Peking University Health Science Center, Beijing, China.
| | - Mingwei Zhao
- Department of Ophthalmology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
- Eye Diseases and Optometry Institute, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
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Curran ALK, Stukin J, Ambrosio L, Mantagos IS, Wu C, Vanderveen DK, Hansen RM, Akula JD, Fulton AB. Electroretinographic Responses in Retinopathy of Prematurity Treated Using Intravitreal Bevacizumab or Laser. Am J Ophthalmol 2023; 252:275-285. [PMID: 37146743 PMCID: PMC10524994 DOI: 10.1016/j.ajo.2023.04.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 04/22/2023] [Accepted: 04/24/2023] [Indexed: 05/07/2023]
Abstract
PURPOSE Intravitreal injection of bevacizumab (IVB) offers advantages over laser photoablation for treatment of type 1 retinopathy of prematurity (ROP). However, retinal function has not, to date, been quantitatively compared following these interventions. Therefore, electroretinography (ERG) was used compare retinal function among eyes treated using IVB or laser, and control eyes. In addition, among the IVB-treated eyes, ERG was used to compare function in individuals in whom subsequent laser was and was not required. DESIGN Prospective clinical cohort study. METHODS ERG was used to record dark- and light-adapted stimulus/response functions in 21 children treated using IVB (12 of whom required subsequent laser in at least 1 eye for persistent avascular retina [PAR]). Sensitivity and amplitude parameters were derived from the a-wave, b-wave, and oscillatory potentials (OPs), representing activity in photoreceptor, postreceptor, and inner retinal cells, respectively. These parameters were then referenced to those of 76 healthy, term-born controls and compared to those of 10 children treated using laser only. RESULTS In children with treated ROP, every ERG parameter was significantly below the mean in controls. However, these significant ERG deficits did not differ between IVB- and laser-treated eyes. Among children treated using IVB, no ERG parameter was significantly associated with dose or need for subsequent laser. CONCLUSION Retinal function was significantly impaired in treated ROP eyes. Function in IVB-treated eyes did not differ from that in laser-treated eyes. Functional differences also did not distinguish those IVB-treated eyes that would subsequently need laser for PAR.
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Affiliation(s)
| | - Justyna Stukin
- Boston Children’s Hospital, Ophthalmology
- Northeastern University, Behavioral Neuroscience
| | - Lucia Ambrosio
- University of Naples Federico II, Department of Neuroscience, Reproductive and Odontostomatological Sciences
- University of Naples Federico II, Department of Public Health
| | - Iason S. Mantagos
- Boston Children’s Hospital, Ophthalmology
- Harvard Medical School, Ophthalmology
| | - Carolyn Wu
- Boston Children’s Hospital, Ophthalmology
- Harvard Medical School, Ophthalmology
| | | | - Ronald M. Hansen
- Boston Children’s Hospital, Ophthalmology
- Harvard Medical School, Ophthalmology
| | - James D. Akula
- Boston Children’s Hospital, Ophthalmology
- Harvard Medical School, Ophthalmology
| | - Anne B. Fulton
- Boston Children’s Hospital, Ophthalmology
- Harvard Medical School, Ophthalmology
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De Bruyn H, Hansen RM, Akula JD, Fulton AB. The Development of Retinal Function and Refractive Error in Children With Retinopathy of Prematurity. Invest Ophthalmol Vis Sci 2023; 64:35. [PMID: 37651111 PMCID: PMC10476440 DOI: 10.1167/iovs.64.11.35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 07/29/2023] [Indexed: 09/01/2023] Open
Abstract
Purpose The purpose of this study was to test the hypothesis that retinopathy of prematurity (ROP) prolongs development of rod-mediated thresholds for detection of stimuli at 10 degrees but not 30 degrees eccentricity. In addition, to evaluate the thresholds at each site for an association with visual acuity (VA) and spherical equivalent (SE). Methods We estimated rod-mediated dark-adapted thresholds (DATs) for the detection of 2 degree diameter, 50 ms, blue (λ < 510 nm) flashes at 10 degrees and 30 degrees eccentric in former preterm subjects (n = 111), stratified by ROP severity: None (n = 32), Mild (n = 66), and Severe (n = 13). We also tested Term-born (n = 28) controls. To determine the age at half-maximal sensitivity (Agehalf) for each group and eccentricity, we fit DATs to logistic growth curves. We obtained VA and SE for Preterm subjects and evaluated the course of threshold development at 10 degrees and 30 degrees for significant association with VA and SE predicted at age 10 years. Results DAT development at 10 degrees was significantly delayed in ROP (Mild and Severe); ROP did not significantly alter DAT development at 30 degrees. At age 10 years, among Preterm subjects, both VA and SE were significantly associated with group (None,Mild, and Severe). SE was predicted by the course of DAT development at 30 degrees. VA was not associated with the course of DAT development at 10 degrees. Conclusions At 10 degrees, ROP-whether mild or severe-is associated with significant delays in DAT development, evidence that the late-maturing central retina is vulnerable to ROP. The association of 30 degree threshold and myopia are evidence that more peripheral retina is important to refractive development.
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Affiliation(s)
- Hanna De Bruyn
- Ophthalmology Department, Boston Children's Hospital, Boston, Massachusetts, United States
| | - Ronald M. Hansen
- Ophthalmology Department, Boston Children's Hospital, Boston, Massachusetts, United States
- Ophthalmology Department, Harvard Medical School, Boston, Massachusetts, United States
| | - James D. Akula
- Ophthalmology Department, Boston Children's Hospital, Boston, Massachusetts, United States
- Ophthalmology Department, Harvard Medical School, Boston, Massachusetts, United States
| | - Anne B. Fulton
- Ophthalmology Department, Boston Children's Hospital, Boston, Massachusetts, United States
- Ophthalmology Department, Harvard Medical School, Boston, Massachusetts, United States
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Systemic Cytokines in Retinopathy of Prematurity. J Pers Med 2023; 13:jpm13020291. [PMID: 36836525 PMCID: PMC9966226 DOI: 10.3390/jpm13020291] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 01/30/2023] [Accepted: 01/30/2023] [Indexed: 02/09/2023] Open
Abstract
Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP.
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Simkin SK, Kersten HM, Misra SL, McGhee CN, Dai S. Long-term visual outcomes of children screened for retinopathy of prematurity with telemedicine in New Zealand. Clin Exp Optom 2022; 106:409-414. [PMID: 35378056 DOI: 10.1080/08164622.2022.2053329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
CLINICAL RELEVANCE Children with a history of regressed retinopathy of prematurity (ROP) are at increased risk of peripheral avascular retina. Wide-field digital retinal imaging and telemedicine is an effective tool for ROP screening. Ophthalmologists and Optometrists should have a high level of clinical suspicion for peripheral retinal changes in children screened for ROP. BACKGROUND Retinopathy of prematurity, a vaso-proliferative disorder of the pre-term retina, is a preventable cause of childhood visual impairment. The Auckland Regional Telemedicine ROP (ART-ROP) network, established in 2006, utilises wide-field digital imaging and telemedicine to screen at-risk infants for ROP. This prospective observational study reports the long-term ocular outcomes of ART-ROP network infants. METHODS A comprehensive paediatric eye examination including cycloplegic autorefraction and wide-field retinal imaging was completed on all participants. Participants had been screened for ROP by the ART-ROP network between May 2008 and October 2011. RESULTS A total of 69 children, with a mean age of 5 to 8 years old were assessed and divided into two groups: those with or without a history of ROP, 44 and 25 children, respectively. Infants with a history of ROP had significantly lower gestational age (26.6 ± 1.9 vs. 29.1 ± 1.6 weeks, p < 0.001) and birth weight (937 ± 237 vs. 1177 ± 311 grams, p = 0.001). No significant differences were detected between the two groups for visual acuity (p = 0.596), stereopsis (p = 0.219), refractive error (p = 0.472), or strabismus. Clinically significant refractive error was noted in 10 participants; none with moderate or high myopia. Retinal imaging exposed asymptomatic, persistent, peripheral avascular retina in four children, all of whom had a history of regressed ROP. CONCLUSION Visual and ocular outcomes did not vary based on history of ROP, with no participant having reduced vision as a result of undetected or untreated ROP. Further research is required into the long-term implication of persistent avascular retina in regressed ROP.
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Affiliation(s)
- Samantha K Simkin
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Hannah M Kersten
- School of Optometry and Vision Sciences, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Stuti L Misra
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Charles Nj McGhee
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Shuan Dai
- Department of Ophthalmology, Queensland Children's Hospital, School of Clinical Medicine, University of Queensland, Brisbane, Queensland, Australia
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Berrocal AM, Fan KC, Al-Khersan H, Negron CI, Murray T. Retinopathy of Prematurity: Advances in the Screening and Treatment of Retinopathy of Prematurity Using a Single Center Approach. Am J Ophthalmol 2022; 233:189-215. [PMID: 34298009 PMCID: PMC8697761 DOI: 10.1016/j.ajo.2021.07.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 06/30/2021] [Accepted: 07/15/2021] [Indexed: 01/03/2023]
Abstract
PURPOSE To focus on the longitudinal evaluation of high-risk infants for the development of retinopathy of prematurity (ROP) at a single tertiary neonatal intensive care unit (NICU), and to evaluate evolving demographics of ROP and the transition of treatment-warranted disease. DESIGN Retrospective cohort study. METHODS A consecutive retrospective review was performed of all infants screened for ROP between 1990 and 2019 at the Jackson Memorial Hospital neonatal intensive care unit. All inborn infants meeting a birth criteria of <32 weeks' gestational age (GA) or a birthweight (BW) of 1500 g were included. Longitudinal demographic, diagnostic, and treatment data were reported. RESULTS Between January 1, 1990, and June 20, 2019, a total of 25,567 examinations were performed and 7436 patients were included. Longitudinal trends over 3 decades demonstrated a decreasing incidence of ROP (P < .05). Although the mean BW and GA increased over 3 decades, patients with ROP demonstrated lower BW and GA over time (P < .05). The prevalence of micro-premature infants (as defined by BW <750 g) continues to rise over time. Micro-preemies demonstrated increasing severity of zone and stage grading, plus disease, and propensity to require treatment (P < .05). The rate of progression of ROP to stage 4 and 5 disease has decreased over time, and there has been an associated increased adoption of intravitreal bevacizumab as primary and salvage therapy. CONCLUSIONS Understanding the evolution of ROP infants and treatment over time is critical in identifying high-risk infants and in reducing the incidence of severe-stage ROP. Micro-prematurity is one of the significant risk factors for treatment-warranted ROP that continues to increase as neonatal care improves. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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Affiliation(s)
- Audina M Berrocal
- Department of Ophthalmology (A.M.B, K.C.F., H.A.-K., C.I.N.), Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA.
| | - Kenneth C Fan
- Department of Ophthalmology (A.M.B, K.C.F., H.A.-K., C.I.N.), Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Hasenin Al-Khersan
- Department of Ophthalmology (A.M.B, K.C.F., H.A.-K., C.I.N.), Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Catherin I Negron
- Department of Ophthalmology (A.M.B, K.C.F., H.A.-K., C.I.N.), Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Timothy Murray
- Murray Oncology and Retina (T.M.), South Miami, Florida, USA
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Tsai AS, Chou HD, Ling XC, Al-Khaled T, Valikodath N, Cole E, Yap VL, Chiang MF, Chan RVP, Wu WC. Assessment and management of retinopathy of prematurity in the era of anti-vascular endothelial growth factor (VEGF). Prog Retin Eye Res 2021; 88:101018. [PMID: 34763060 DOI: 10.1016/j.preteyeres.2021.101018] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/27/2021] [Accepted: 10/29/2021] [Indexed: 02/06/2023]
Abstract
The incidence of retinopathy of prematurity (ROP) continues to rise due to the improved survival of very low birth weight infants in developed countries. This epidemic is also fueled by increased survival of preterm babies with variable use of oxygen and a lack of ROP awareness and screening services in resource-limited regions. Improvements in technology and a basic understanding of the disease pathophysiology have changed the way we screen and manage ROP, educate providers and patients, and improve ROP awareness. Advancements in imaging techniques, expansion of telemedicine services, and the potential for artificial intelligence-assisted ROP screening programs have created opportunities to improve ROP care in areas with a shortage of ophthalmologists trained in ROP. To address the gap in provider knowledge regarding ROP, the Global Education Network for Retinopathy of Prematurity (GEN-ROP) created a web-based tele-education training module that can be used to educate all providers involved in ROP, including non-physician ROP screeners. Over the past 50 years, the treatment of severe ROP has evolved from limited treatment modalities to cryotherapy and laser photocoagulation. More recently, there has been growing evidence to support the use of anti-vascular endothelial growth factor (VEGF) agents for the treatment of severe ROP. However, VEGF is known to be important in organogenesis and microvascular maintenance, and given that intravitreal anti-VEGF treatment can result in systemic VEGF suppression over a period of at least 1-12 weeks, there are concerns regarding adverse effects and long-term ocular and systemic developmental consequences of anti-VEGF therapy. Future research in ophthalmology to address the growing burden of ROP should focus on cost-effective fundus imaging devices, implementation of artificial intelligence platforms, updated treatment algorithms with optimal use of anti-VEGF and careful investigation of its long-term effects, and surgical options in advanced ROP. Addressing these unmet needs will aid the global effort against the ROP epidemic and optimize our understanding and treatment of this blinding disease.
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Affiliation(s)
- Andrew Sh Tsai
- Singapore National Eye Centre, Singapore; DUKE NUS Medical School, Singapore
| | - Hung-Da Chou
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Xiao Chun Ling
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Tala Al-Khaled
- Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Illinois Eye and Ear Infirmary, Chicago, IL, USA
| | - Nita Valikodath
- Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Illinois Eye and Ear Infirmary, Chicago, IL, USA
| | - Emily Cole
- Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Illinois Eye and Ear Infirmary, Chicago, IL, USA
| | - Vivien L Yap
- Division of Newborn Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Michael F Chiang
- National Eye Institute, National Institutes of Health, Bethesda, MD, USA
| | - R V Paul Chan
- Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Illinois Eye and Ear Infirmary, Chicago, IL, USA.
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Narnaware SH, Bawankule PK, Raje D. Aggressive Posterior Retinopathy of Prematurity (APROP): LASER as the Primary Modality of Treatment. J Ophthalmic Vis Res 2021; 16:400-407. [PMID: 34394869 PMCID: PMC8358764 DOI: 10.18502/jovr.v16i3.9437] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 06/15/2019] [Indexed: 11/29/2022] Open
Abstract
Purpose To study the success rate of LASER as a primary modality of treatment in aggressive posterior retinopathy of prematurity (APROP) cases. Methods This is a prospective case series of 56 eyes of 28 preterm babies (males = 21) with APROP who underwent laser therapy. Babies were divided into groups on the basis of gestational age (GA), birth weight (BW), and postmenstrual age (PMA) at which treatment was performed. GA (in weeks): <28 (n = 7), 28–30 (n = 11), >30 (n = 10). BW (in grams): <1000 (n = 8), 1000–1200 (n = 10), >1200 (n = 10). PMA (in weeks): < 32 (n = 6), 32–34 (n = 18), >34 (n = 4). Success was calculated as complete regression of disease without need for any other modality of treatment such as anti-vascular endothelial growth factor (anti-VEGF) or pars plana vitrectomy. Results The overall success rate was 94.64% (53/56). Two babies who needed additional modality of treatment were <28 weeks of GA (one eye) and 28–30 weeks (two eyes). One baby (one eye) was <1000 gm and the other (two eyes) was >1200 gm, while PMA at which additional treatment was needed was 30 weeks in one baby (one eye) and 33 weeks in the other (two eyes). Conclusion In this era of anti-VEGF treatment, even in cases of APROP, LASER should still be considered as a primary modality of treatment, as it is a one-time treatment without the concern of systemic side effects and recurrent/persistent avascular zones.
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Affiliation(s)
- Shilpi H Narnaware
- Consultant Vitreo-retina & ROP Specialist, Sarakshi Netralaya, Rajiv Nagar, Wardha Road, Nagpur 440025, Maharashtra, India
| | - Prashant K Bawankule
- Vitreo-Retinal Surgeon, Rajiv Nagar, Wardha Road, Nagpur 440025 Maharashtra, India
| | - Dhananjay Raje
- Head, Data Analysis Group, MDS Bio-analytics Pvt. Ltd., Shankar Nagar, Nagpur 440010, Maharashtra, India
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Katargina LA, Chesnokova NB, Beznos OV, Osipova NA, Panova AY. [Pathogenetically oriented approach to prevention of retinopathy of prematurity (experimental study)]. Vestn Oftalmol 2021; 137:26-31. [PMID: 34156775 DOI: 10.17116/oftalma202113703126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Intraperitoneal injections of exogenous melatonin during the development of the retinal vascular system in experimental rats has been shown in a number of experimental studies on the model of EROP to prevent the appearance of histological signs of the development of experimental retinopathy of prematurity (EROP), stabilize the blood-retinal barrier and have a pronounced antioxidant effect, but pathogenetic basis for these phenomena hasn't been studied. PURPOSE To study the influence mechanism of melatonin and its analogues on the development of EROP at the preclinical stage of the pathological process to substantiate new approaches to prevention of ROP. MATERIAL AND METHODS The study included 42 Wistar rat pups (84 eyes) divided into 6 groups: control group, experimental group (rat pups with EROP), experimental groups who underwent injections of melatonin and its analogues K-148, AL-3, K-096. The pups were euthanized on day 7 (4-5 pups from each group at each study period), binocular enucleation was performed, and the content of hypoxia-induced factor1α (HIF-1α) and VEGF-A was determined in retinal samples. RESULTS The intraperitoneal injections of melatonin and its analogs led to a significant decrease in the level of HIF-1α and VEGF-A in the retina of the rat pups of the experimental group until the beginning of pathological vasoproliferation. CONCLUSION Melatonin and its analogues are able to prevent the development of EROP by reducing the level of angiogenic factors in the retina of rat pups at the stage of existing avascular zones, which allows for them to be considered as a new promising approach to preventing the development of ROP.
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Affiliation(s)
- L A Katargina
- Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
| | - N B Chesnokova
- Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
| | - O V Beznos
- Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
| | - N A Osipova
- Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
| | - A Yu Panova
- Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
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Ekinci DY, Vural AD, Bayramoglu SE, Onur IU, Hergunsel GO. Assessment of vascular leakage and its development with FFA among patients treated with intravitreal anti-VEGF due to aggressive posterior ROP. Int Ophthalmol 2019; 39:2697-2705. [PMID: 30830544 DOI: 10.1007/s10792-019-01088-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Accepted: 02/23/2019] [Indexed: 10/27/2022]
Abstract
OBJECTIVE Evaluation of vascular leakage and retinal vascular development with fundus fluorescein angiography for infants diagnosed with aggressive posterior retinopathy of prematurity who underwent intravitreal anti-VEGF treatment. METHOD Medical recordings of 30 patients who received RetCam fluorescein angiography during follow-up and had been treated with anti-VEGF on diagnosis of aggressive posterior ROP in the zone I or zone II between the dates of April 2014-January 2017 were evaluated retrospectively. RESULTS Fifty-nine eyes of 30 patients were included in the study. Mean birth weight was 1145 g; gestation week was 28.4. Recurrence occurred in 30.5% of the patients, and 10.1% of them were given a second dose of injection of anti-VEGF. Leakage was detected in 15.3% of the eyes during angiography, and all of these eyes were treated with laser photocoagulation. Evaluation of vascular development revealed that in the temporal, complete retinal vascular development was achieved in only 8% of the eyes. It was detected that complete retinal vascularization was not observed in any of the cases which were given second dose of injection due to recurrence. The patients were distributed into groups according to postmenstrual week taken to angiography as 32 eyes of 16 patients in group 1, 17 eyes of 9 patients in group 2 and 10 eyes of 5 patients in group 3. The vascular leakage rate of group 3 patients was statistically significantly higher (p < 0.05) and vascular development between groups was not statistically significant (p > 0.05). DISCUSSION With the initiation of FFA usage in pediatric cases, especially treated with anti-VEGF due to retinopathy of prematurity (ROP), more findings (vascular arrest, leakage, and abnormalities, etc.) are obtained than those achieved via ophthalmoscopic examination. In the light of these findings, early intervention with laser photocoagulation in early stages becomes possible enabling prevention of possible blindness.
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Leung MP, Thompson B, Black J, Dai S, Alsweiler JM. The effects of preterm birth on visual development. Clin Exp Optom 2017; 101:4-12. [PMID: 28868651 DOI: 10.1111/cxo.12578] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 04/30/2017] [Accepted: 05/07/2017] [Indexed: 12/18/2022] Open
Abstract
Children born very preterm are at a greater risk of abnormal visual and neurological development when compared to children born at full term. Preterm birth is associated with retinopathy of prematurity (a proliferative retinal vascular disease) and can also affect the development of brain structures associated with post-retinal processing of visual information. Visual deficits common in children born preterm, such as reduced visual acuity, strabismus, abnormal stereopsis and refractive error, are likely to be detected through childhood vision screening programs, ophthalmological follow-up or optometric care. However, routine screening may not detect other vision problems, such as reduced visual fields, impaired contrast sensitivity and deficits in cortical visual processing, that may occur in children born preterm. For example, visual functions associated with the dorsal visual processing stream, such as global motion perception and visuomotor integration, may be impaired by preterm birth. These impairments can continue into adolescence and adulthood and may contribute to the difficulties in learning (particularly reading and mathematics), attention, behaviour and cognition that some children born preterm experience. Improvements in understanding the mechanisms by which preterm birth affects vision will inform future screening and interventions for children born preterm.
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Affiliation(s)
- Myra Ps Leung
- School of Optometry and Vision Science, The University of Auckland, Auckland, New Zealand
| | - Benjamin Thompson
- School of Optometry and Vision Science, The University of Auckland, Auckland, New Zealand.,School of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada
| | - Joanna Black
- School of Optometry and Vision Science, The University of Auckland, Auckland, New Zealand
| | - Shuan Dai
- Department of Ophthalmology, The University of Auckland, Auckland, New Zealand
| | - Jane M Alsweiler
- Department of Paediatrics, The University of Auckland, Auckland, New Zealand
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Hansen RM, Moskowitz A, Akula JD, Fulton AB. The neural retina in retinopathy of prematurity. Prog Retin Eye Res 2017; 56:32-57. [PMID: 27671171 PMCID: PMC5237602 DOI: 10.1016/j.preteyeres.2016.09.004] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 09/15/2016] [Accepted: 09/20/2016] [Indexed: 12/26/2022]
Abstract
Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP.
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Affiliation(s)
- Ronald M Hansen
- Department of Ophthalmology, Children's Hospital and Harvard Medical School, 300 Longwood Ave., Boston, MA 02115-5737, USA.
| | - Anne Moskowitz
- Department of Ophthalmology, Children's Hospital and Harvard Medical School, 300 Longwood Ave., Boston, MA 02115-5737, USA.
| | - James D Akula
- Department of Ophthalmology, Children's Hospital and Harvard Medical School, 300 Longwood Ave., Boston, MA 02115-5737, USA.
| | - Anne B Fulton
- Department of Ophthalmology, Children's Hospital and Harvard Medical School, 300 Longwood Ave., Boston, MA 02115-5737, USA.
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Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical Management of Recurrent Retinopathy of Prematurity after Intravitreal Bevacizumab Monotherapy. Ophthalmology 2016; 123:1845-55. [PMID: 27241619 PMCID: PMC4995132 DOI: 10.1016/j.ophtha.2016.04.028] [Citation(s) in RCA: 127] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 04/13/2016] [Accepted: 04/17/2016] [Indexed: 10/21/2022] Open
Abstract
PURPOSE To determine incidence, risk factors, risk period, and characteristics of recurrent retinopathy of prematurity (ROP) treated by intravitreal bevacizumab (IVB) monotherapy. DESIGN Retrospective case series. PARTICIPANTS Premature infants with type 1 ROP (subdivided into stage 3+ ROP and aggressive posterior ROP [APROP]) in zone I or zone II posterior who received IVB monotherapy and were followed up for at least 65 weeks adjusted age (AA). METHODS Retrospective review of infants who demonstrated recurrence of type 1 ROP after IVB monotherapy, including examination of RetCam fundus photographs and fluorescein angiograms. MAIN OUTCOMES MEASURES Incidence, risk factors, risk period, and characteristics of recurrent ROP. RESULTS Intravitreal bevacizumab monotherapy in 241 infants (471 eyes) was reviewed. Recurrence incidence was 8.3% (20/241) for infants and 7.2% (34/471) for eyes. Recurrence risk factors of greatest significance were appearance of neovascularization as APROP (P = 0.006), extended duration of hospitalization (P = 0.01), and lower birth weight (P = 0.024). Recurrence risk period was between approximately 45 and 55 weeks AA (90.0% [18/20] for infants and 94.1% [32/34] for eyes), with mean recurrence of 51.2 weeks AA (±4.6 weeks; range, 45.7-64.9 weeks) and mean interval of 16.2 weeks (±4.4 weeks) between treatments. Recurrence characteristics included plus disease (20/20 infants [100%]) and neovascularization, which appeared at the following sites: stage 3+ ROP with confluent neovascularization recurred both at the advancing edge and at the initial ridge and extraretinal fibrovascular proliferative complex (12/14 infants [85.7%]). However, APROP (6/6 infants [100%]) and stage 3+ ROP with nonconfluent neovascularization (2/14 infants [14.3%]) recurred only at the advancing edge. Also, the anterior extent of retinal vascularization was decreased (mean, 1.76 disc diameters [DD] vs. 4.48 DD), and the rate of retinal vascularization was delayed (mean, 0.11 DD/week vs. 0.23 DD/week) in those with versus without recurrence, respectively. After retreatment with IVB, retinal vascularization proceeded minimally and slowly. CONCLUSIONS Premature children with severe ROP are being treated successfully with IVB monotherapy. However, recurrence is not uncommon, so vigilant follow-up is necessary to ensure timely re-treatment. Knowledge of recurrence incidence, risk factors, risk period, and characteristics allows for tailored clinical management.
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Affiliation(s)
- Helen A Mintz-Hittner
- Ruiz Department of Ophthalmology and Visual Science, The University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, Houston, Texas; W. T. & Louise J. Moran Pediatric Eye Clinic, Robert Cizik Eye Clinic, Houston, Texas.
| | - Megan M Geloneck
- Ruiz Department of Ophthalmology and Visual Science, The University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, Houston, Texas; W. T. & Louise J. Moran Pediatric Eye Clinic, Robert Cizik Eye Clinic, Houston, Texas
| | - Alice Z Chuang
- Ruiz Department of Ophthalmology and Visual Science, The University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, Houston, Texas
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Ngo MH, Borowska-Fielding J, Heathcote G, Nejat S, Kelly ME, McMaster CR, Robitaille JM. Fzd4 Haploinsufficiency Delays Retinal Revascularization in the Mouse Model of Oxygen Induced Retinopathy. PLoS One 2016; 11:e0158320. [PMID: 27489958 PMCID: PMC4973993 DOI: 10.1371/journal.pone.0158320] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Accepted: 06/14/2016] [Indexed: 12/11/2022] Open
Abstract
Mutations in genes that code for components of the Norrin-FZD4 ligand-receptor complex cause the inherited childhood blinding disorder familial exudative vitreoretinopathy (FEVR). Statistical evidence from studies of patients at risk for the acquired disease retinopathy of prematurity (ROP) suggest that rare polymorphisms in these same genes increase the risk of developing severe ROP, implying that decreased Norrin-FZD4 activity predisposes patients to more severe ROP. To test this hypothesis, we measured the development and recovery of retinopathy in wild type and Fzd4 heterozygous mice in the absence or presence of ocular ischemic retinopathy (OIR) treatment. Avascular and total retinal vascular areas and patterning were determined, and vessel number and caliber were quantified. In room air, there was a small delay in retinal vascularization in Fzd4 heterozygous mice that resolved as mice reached maturity suggestive of a slight defect in retinal vascular development. Subsequent to OIR treatment there was no difference between wild type and Fzd4 heterozygous mice in the vaso-obliterated area following exposure to high oxygen. Importantly, after return of Fzd4 heterozygous mice to room air subsequent to OIR treatment, there was a substantial delay in retinal revascularization of the avascular area surrounding the optic nerve, as well as delayed vascularization toward the periphery of the retina. Our study demonstrates that a small decrease in Norrin-Fzd4 dependent retinal vascular development lengthens the period during which complications from OIR could occur.
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Affiliation(s)
- Michael H. Ngo
- Department of Pharmacology, Dalhousie University, Halifax, NS, Canada
| | | | - Godfrey Heathcote
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Department of Ophthalmology and Visual Sciences, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada
| | - Sara Nejat
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Melanie E. Kelly
- Department of Pharmacology, Dalhousie University, Halifax, NS, Canada
- Department of Ophthalmology and Visual Sciences, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada
| | | | - Johane M. Robitaille
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Department of Ophthalmology and Visual Sciences, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada
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16
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Darlow BA. Retinopathy of prematurity: New developments bring concern and hope. J Paediatr Child Health 2015; 51:765-70. [PMID: 25757043 DOI: 10.1111/jpc.12860] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/20/2015] [Indexed: 12/22/2022]
Abstract
Blindness from retinopathy of prematurity (ROP) in Australian and New Zealand is an uncommon event although 3% of <31 weeks gestation infants receive treatment for the disease. New world-wide estimates of the incidence of blindness from ROP are much higher than previously at 20 000 children annually. The impact of severe ROP can be reduced through good evidence-based care of very preterm infants and careful organisation of eye examinations and follow-up services. Recent oxygen saturation targeting trial results might mean the adoption of higher targets than formerly in very preterm infants and will require vigilance to ensure all eligible infants are examined appropriately. A true screening examination for acute ROP might involve non-opthalmologists obtaining photographic retinal images and remote reading of these. Although treatment with laser gives good outcomes, there is interest in intravitreal anti-vascular endothelial factor agents, but issues concerning the systemic safety and retinal results of such treatment are unresolved.
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Affiliation(s)
- Brian A Darlow
- Department of Paediatrics, University of Otago at Christchurch, Christchurch, New Zealand
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17
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Pulido CM, Quiram PA. Current understanding and management of aggressive posterior retinopathy of prematurity. World J Ophthalmol 2015; 5:73-79. [DOI: 10.5318/wjo.v5.i2.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/12/2015] [Accepted: 03/05/2015] [Indexed: 02/06/2023] Open
Abstract
Aggressive posterior retinopathy of prematurity (ROP), previously referred to as “Rush disease”, is a rapidly progressive form of ROP. This form of ROP typically presents in very low birth weight babies of early gestational age. Historically, anatomical and functional outcomes have been poor with standard treatment. This review is designed to discuss current knowledge and treatment regarding this aggressive form of ROP. Recommendations regarding management of these difficult cases are detailed.
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18
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Fielder A, Blencowe H, O'Connor A, Gilbert C. Impact of retinopathy of prematurity on ocular structures and visual functions. Arch Dis Child Fetal Neonatal Ed 2015; 100:F179-84. [PMID: 25336678 DOI: 10.1136/archdischild-2014-306207] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
The preterm baby may develop ophthalmic sequelae which can be due to prematurity per se, due to retinopathy of prematurity (ROP) or due to neurological damage. Focusing on the former two, we discuss how in high-income countries the risk of sight-threatening ROP is largely confined to babies <1000 g birth weight (BW), whereas in low-income or middle-income countries babies exceeding 2500 g BW can be blinded. The effects of prematurity and ROP are presented as regional and global estimates of acute-phase ROP and the consequent mild/moderate and severe visual impairment. We discuss sequelae and how they affect the eye and its shape, strabismus and finally consider their impact on visual functions, including visual acuity, the visual field, colour vision and contrast sensitivity.
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Affiliation(s)
- Alistair Fielder
- Division of Optometry & Visual Science, City University, London, UK
| | - Hannah Blencowe
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Anna O'Connor
- Directorate of Orthoptics and Vision Science, University of Liverpool, Liverpool, UK
| | - Clare Gilbert
- Department of Clinical Research, International Centre for Eye Health, London School of Hygiene & Tropical Medicine, London, UK
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19
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Holm M, Msall ME, Skranes J, Dammann O, Allred E, Leviton A. Antecedents and correlates of visual field deficits in children born extremely preterm. Eur J Paediatr Neurol 2015; 19:56-63. [PMID: 25455711 PMCID: PMC4276499 DOI: 10.1016/j.ejpn.2014.10.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Accepted: 10/05/2014] [Indexed: 11/26/2022]
Abstract
AIM We sought to identify the antecedents and correlates of visual field deficits (VFDs) at age 2 years among infants born before the 28th week of gestation. METHODS The visual fields of 1023 infants were assessed by confrontation at age 2 years. We compared the ante-and postnatal characteristics and exposures of the 65 infants with a VFD to their peers who did not have a VFD. We used time-oriented logistic regression risk models to assess the associations of potential antecedents and correlates with a VFD. RESULTS In the final regression model, VFD was associated with maternal consumption of aspirin during the current pregnancy, recurring/persistent acidemia during the first 3 postnatal days, cerebral ventriculomegaly seen on neonatal ultrasound, prethreshold retinopathy of prematurity (ROP), and supplemental oxygen and ventilator dependence at 36 weeks post-menstrual age. Birth before the 27th week was also associated with increased risk, but its significance was diminished by the addition of postnatal variables. CONCLUSION In this sample of extremely preterm born infants, antenatal as well as early and late postnatal characteristics and exposures are associated with an increased risk of having a VFD. Our study adds to our knowledge about the complex etiology of visual deficits of prematurity, and supports a multifactorial cause of these deficits.
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Affiliation(s)
- Mari Holm
- Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, N-7489 Trondheim, Norway; Department of Public Health and Community Medicine, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA.
| | - Michael E Msall
- Department of Pediatrics, Section of Developmental and Behavioral Pediatrics and JP Kennedy Research Center on Intellectual and Developmental Disabilities, University of Chicago Comer Children's Hospital, 5721 S. Maryland Avenue, Chicago, IL 60637, USA.
| | - Jon Skranes
- Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
| | - Olaf Dammann
- Department of Public Health and Community Medicine, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA; Neuroepidemiology Unit, Hannover School of Medicine, Hannover, Germany.
| | - Elizabeth Allred
- Neurology Departments, Boston Children's Hospital, and Harvard Medical School, Au-414 300 Longwood Avenue, Boston, MA 02115-5724, USA.
| | - Alan Leviton
- Neurology Departments, Boston Children's Hospital, and Harvard Medical School, Au-414 300 Longwood Avenue, Boston, MA 02115-5724, USA.
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20
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Mezu-Ndubuisi OJ, Wanek J, Chau FY, Teng PY, Blair NP, Reddy NM, Raj JU, Reddy SP, Shahidi M. Correspondence of retinal thinning and vasculopathy in mice with oxygen-induced retinopathy. Exp Eye Res 2014; 122:119-22. [PMID: 24703909 DOI: 10.1016/j.exer.2014.03.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/05/2014] [Accepted: 03/25/2014] [Indexed: 11/30/2022]
Abstract
The aberrantly vascularized peripheral retina in retinopathy of prematurity (ROP) may be associated with visual field constriction, retinal dysfunction, and abnormalities in retinal thickness which is commonly assessed by spectral domain optical coherence tomography (SDOCT). However, due to the limitation of SDOCT for peripheral retinal imaging, retinal thickness in avascular peripheral retina in ROP has not been evaluated. Oxygen induced retinopathy (OIR) in mice has features of vasculopathy similar to those in human ROP. These features occur in the posterior retina and thereby are accessible by standard imaging methods. The purpose of the current study was to determine the correspondence between abnormalities in retinal thickness and vasculopathy in neonatal OIR mice by simultaneous SDOCT imaging and fluorescein angiography (FA). Newborn mice (N = 19; C57BL/6J strain) were exposed to 77% oxygen from postnatal day 7 (P7) to P12. Age-matched control mice (N = 12) were raised in room air. FA and SDOCT were performed in mice between P17 and P19 to visualize retinal vasculature and measure retinal thickness, respectively. Retinal thickness measurements in vascular regions of interest (ROIs) of control mice, and in hypovascular and avascular ROIs of OIR mice were compared. In control mice, FA showed uniformly dense retinal capillary networks between major retinal vessels and retinal thickness of vascular ROIs was 260 ± 7 μm (N = 12). In OIR mice, FA displayed hypovascular regions with less dense and fewer capillaries and avascular regions devoid of visible capillaries. Retinal thickness measurements of hypovascular and avascular ROIs were 243 ± 21 μm and 209 ± 11 μm (N = 19), respectively. Retinal thickness in hypovascular and avascular ROIs of OIR mice was significantly lower than in vascular ROIs of control mice (p ≤ 0.01). Likewise, retinal thickness in avascular ROIs was significantly lower than in hypovascular ROIs (p < 0.001). Retinal thinning in hypovascular and avascular regions may be due to arrested retinal development and/or ischemia induced apoptosis.
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Affiliation(s)
- Olachi J Mezu-Ndubuisi
- Departments of Pediatrics and Ophthalmology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA
| | - Justin Wanek
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612, USA
| | - Felix Y Chau
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612, USA
| | - Pang-Yu Teng
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612, USA
| | - Norman P Blair
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612, USA
| | - Narsa M Reddy
- Department of Pediatrics, University of Illinois at Chicago, 840 S. Wood Street Chicago, IL 60612, USA
| | - J Usha Raj
- Department of Pediatrics, University of Illinois at Chicago, 840 S. Wood Street Chicago, IL 60612, USA
| | - Sekhar P Reddy
- Department of Pediatrics, University of Illinois at Chicago, 840 S. Wood Street Chicago, IL 60612, USA
| | - Mahnaz Shahidi
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612, USA.
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21
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Wang J, Ren X, Shen L, Yanni SE, Leffler JN, Birch EE. Development of refractive error in individual children with regressed retinopathy of prematurity. Invest Ophthalmol Vis Sci 2013; 54:6018-24. [PMID: 23920368 DOI: 10.1167/iovs.13-11765] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
PURPOSE We investigated longitudinally the refraction development in children with regressed retinopathy of prematurity (ROP), including those with and those without a history of peripheral retinal laser photocoagulation. METHODS Longitudinal (0-7 years) cycloplegic refraction data were collected prospectively for two groups of preterm children: severe ROP group included those with regressed ROP following bilateral panretinal laser photocoagulation (n = 37; median gestational age [GA] = 25.2; range, 22.7-27.9 weeks) and mild/no ROP group included those with spontaneously regressed ROP or no ROP (n = 27; median GA = 27.1; range, 23.1-32.0 weeks). Analyses were based on spherical equivalent (SEQ), anisometropia, astigmatism, and age (corrected for gestation). RESULTS The prevalence, magnitude, and rate of myopic progression all were significantly higher in the severe ROP group than in the mild/no ROP group. Longitudinal SEQ in the severe ROP group were best fit with a bilinear model. Before 1.3 years old, the rate of myopic shift was -4.7 diopters (D)/y; after 1.3 years, the rate slowed to -0.15 D/y. Longitudinal SEQ in the mild/no ROP group was best fit with a linear model, with a rate of -0.004 D/y. Anisometropia in the severe ROP group increased approximately three times faster than in the mild/no ROP group. In the severe ROP group, with-the-rule astigmatism increased significantly with age. CONCLUSIONS The severe ROP group progressed rapidly toward myopia, particularly during the first 1.3 years; anisometropia and astigmatism also increased with age. The mild/no ROP group showed little change in refraction. Infants treated with laser photocoagulation for severe ROP should be monitored with periodic cycloplegic refractions and provided with early optical correction.
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Affiliation(s)
- Jingyun Wang
- Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
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22
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Abstract
In prematurely born children, various visual and ophthalmologic sequelae occur because of both retinopathy of prematurity (ROP) and preterm birth per se. Several long-term follow-up studies have described the outcome of ROP. Visual impairment and blindness are well-known consequences, but the prevalence varies globally because of differing neonatal and ophthalmologic care. Improving treatment options and criteria for the treatment of ROP are continuously changing the ophthalmologic outcome. The anatomic outcome has improved with treatment, but good anatomic outcome in treated severe ROP does not always reflect the functional outcome. There is no consensus regarding long-term follow-up of prematurely born children.
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Affiliation(s)
- Gerd Holmström
- Department of Neuroscience/Ophthalmology, University Hospital, Uppsala University, Uppsala 75185, Sweden.
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23
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Allen LE, Slater ME, Proffitt RV, Quarton E, Pelah A. A new perimeter using the preferential looking response to assess peripheral visual fields in young and developmentally delayed children. J AAPOS 2012; 16:261-5. [PMID: 22681943 DOI: 10.1016/j.jaapos.2012.01.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2011] [Revised: 12/20/2011] [Accepted: 01/02/2012] [Indexed: 10/28/2022]
Abstract
PURPOSE To compare the sensitivity, specificity, and interpretability of a newly developed semiautomated static perimeter based on the preferential looking response to the results of confrontation visual field testing in a group of young and/or developmentally delayed children with and without visual field deficit. METHODS The preferential looking perimeter (PLP) uses observation of the child's natural eye movement response to an appearing target to determine the peripheral visual field. We compared preferential looking perimetry to confrontation testing in 74 children 3-10 years of age (mean, 6.6 years; median, 7 years), including 32 controls and 42 children with neurological and ocular disorders that could cause significant visual field deficit. RESULTS Using confrontation testing as the gold standard, the PLP was 100% sensitive and 100% specific (95% CI, 90%-100%), with excellent interobserver agreement. An interpretable result could be achieved in 15 (71%) of the 21 children in whom confrontation testing was unhelpful. CONCLUSIONS PLP is a useful new technique for assessing significant visual field loss in young or developmentally delayed children, with many advantages over confrontation testing.
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Affiliation(s)
- Louise E Allen
- University of Cambridge, The Old Schools, Trinity Lane, Cambridge, United Kingdom.
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