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Bajgai P, Satavisa S, Das T, Jalali S, Samanataray B, Nayak S, Padhi TR. Bedside bilateral sequential intravitreal anti-VEGF injections for retinopathy of prematurity. Indian J Ophthalmol 2025; 73:S112-S118. [PMID: 39257079 PMCID: PMC11834912 DOI: 10.4103/ijo.ijo_558_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 06/04/2024] [Accepted: 06/21/2024] [Indexed: 09/12/2024] Open
Abstract
PURPOSE To evaluate the outcome and ocular adverse events of bedside bilateral sequential intravitreal anti-vascular endothelial growth factor injections for retinopathy of prematurity (ROP) (BBSIR). METHODS This retrospective interventional study included infants who received BBSIR with a follow-up of at least 1 month. Clinical history, intravitreal injection details, indications, intraoperative and postoperative ocular adverse events, and outcomes were analyzed. RESULTS The study cohort included 192 babies (384 eyes) spread over 9 years. The mean gestational age was 30.2 ± 2.6 weeks (28.8-34.1), and the birth weight was 1098.11 ± 271.65 g (650-2000). The indications for BBSIR were as follows: 73.4% (n = 141 infants) were too sick to transfer to an ophthalmic unit, 10.9% (n = 21 infants) due to the parents' inconvenience of traveling to the ophthalmic center, and 15. 6% (n = 30 infants) due to both reasons. The injections were given by an ROP specialist/ROP-trained ophthalmologist after due parental consent, considering each eye as a fresh eye with separate scrubbing and draping. Light from the head-worn indirect ophthalmoscope served as the source of illumination. The retinopathy was regressing/regressed in 92.4% of babies until the last follow-up. The major ocular complication was cataract in 2 eyes (0.5%). There was no incidence of endophthalmitis till last follow-up (median 5.7 months). CONCLUSIONS As per this study, BBSIR was observed to be effective and safe if given by those fully trained in the management of ROP. Though the rate of complications like cataract is small, they can pose management challenges and impact vision in a growing child.
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Affiliation(s)
- Priya Bajgai
- Vitreoretinal Services, Nepal Eye Institute, Kathmandu, Nepal
| | - Susree Satavisa
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, Odisha, India
| | - Taraprasad Das
- Anant Bajaj Retina Institute, Srimati Kannuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute (Kallam Anji Reddy Campus), Hyderabad, Telangana, India
| | - Subhadra Jalali
- Anant Bajaj Retina Institute, Srimati Kannuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute (Kallam Anji Reddy Campus), Hyderabad, Telangana, India
| | - Balakrushna Samanataray
- Department of Ophthalmology, Srirama Chandra Bhanja Medical College and Hospital, Cuttack, Odisha, India
| | - Sameera Nayak
- Vitreoretinal Services, Anant Bajaj Retina Institute, L V Prasad Eye Institute (Kode Venkatadri Chowdary Campus), Vijayawada, Andhra Pradesh, India
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Ünal AC, Akıdan M, Erol MK. A comparation of three different anti-VEGF drugs in development of persistent avascular retina in premature children. Sci Rep 2024; 14:31097. [PMID: 39732747 DOI: 10.1038/s41598-024-82445-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 12/05/2024] [Indexed: 12/30/2024] Open
Abstract
Our current prospective cross-sectional study aimed to investigate the effect of anti-vascular endothelial growth factor (VEGF) drugs used in the treatment of retinopathy of prematurity on retinal maturation and persistent avascular retina (PAR). Retinal imaging was performed with Optos confocal laser ophthalmoscopy for 100 patients aged 4 to 8 years who were screened and treated for retinopathy of prematurity (ROP) during the neonatal period. The ROP examination findings (stage and zone) and treatment history (age in weeks at time of treatment and anti-VEGF drug used) from the neonatal period were reviewed. Retinal vascularization was assessed in fundus images using the green filter on the Optos device and the presence of PAR was evaluated by two investigators. Relationships between the rate of PAR, age in weeks at time of treatment, and type of anti-VEGF drug used were analyzed statistically. The study included 196 eyes of 100 patients. Sixty-four eyes were analyzed in Group 1 (no ROP), 23 eyes in Group 2 (ROP, no treatment), and 108 eyes in Group 3 (treated group; anti-VEGF treatment of ROP with ranibizumab, bevacizumab, or aflibercept). The number of eyes with PAR in these groups was 2 (3.7%), 4 (17.4%), and 45 (41.7%), respectively. PAR was detected in 30 of 44 eyes treated with aflibercept. The rate of PAR was higher after aflibercept treatment (68.2%) with statistical significance (p = 0.000). This study showed that the prevalence of PAR differs between anti-VEGF drugs. Patients treated with aflibercept have a higher risk of late complications and should be followed closely.
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Affiliation(s)
- Ayşe Cengiz Ünal
- Department of Ophthalmology, University of Health Sciences, Antalya Education and Research Hospital, Antalya, 07050, Turkey.
| | - Melih Akıdan
- Department of Ophthalmology, Antalya Akseki State Hospital, Antalya, Turkey
| | - Muhammet Kazım Erol
- Department of Ophthalmology, University of Health Sciences, Antalya Education and Research Hospital, Antalya, 07050, Turkey
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Kvopka M, Chan W, Lake SR, Durkin S, Taranath D. Fundus fluorescein angiography imaging of retinopathy of prematurity in infants: A review. Surv Ophthalmol 2023; 68:849-860. [PMID: 37211096 DOI: 10.1016/j.survophthal.2023.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 05/11/2023] [Accepted: 05/15/2023] [Indexed: 05/23/2023]
Abstract
Fluorescein angiography in retinopathy of prematurity is increasingly utilized over the past decade. The development of ultra-wide-field imaging combined with fluorescein angiography has allowed improved visualization of the peripheral retinal vasculature. Patient cooperation in the pediatric population is particularly challenging, but hand-held digital retinal photography has shown promise and can visualize the infant retina without the need for anesthesia and intravenous access. Many features of retinopathy of prematurity and its response to laser and anti-VEGF treatment can be either exclusively or better visualized on fluorescein angiography compared to indirect ophthalmoscopy or color fundus photography. Disease treatment is gradually shifting from laser photocoagulation to intravitreal anti-VEGF agents, the latter being associated with late-onset vision-threatening sequelae. The role of fluorescein angiography in retinopathy of prematurity monitoring will continue to increase with the longer follow-up required and different clinical behavior seen with anti-VEGF treatment. We highlight the utility, safety, and importance of fluorescein angiography in the diagnosis, treatment, and follow-up of retinopathy of prematurity.
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Affiliation(s)
- Michael Kvopka
- Department of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia.
| | - WengOnn Chan
- Department of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia; Discipline of Ophthalmology and Visual Sciences, University of Adelaide, Australia; Machine Learning Division, Ophthalmic Research Laboratory, University of Adelaide, Australia
| | - Stewart R Lake
- Department of Ophthalmology, Division of Surgery, Flinders Medical Centre, Adelaide. Australia
| | - Shane Durkin
- Department of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia
| | - Deepa Taranath
- Department of Ophthalmology, Division of Surgery, Flinders Medical Centre, Adelaide. Australia
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Chiang MC, Chen YT, Kang EYC, Chen KJ, Wang NK, Liu L, Chen YP, Hwang YS, Lai CC, Wu WC. Neurodevelopmental Outcomes for Retinopathy of Prematurity: A Taiwan Premature Infant Follow-up Network Database Study. Am J Ophthalmol 2023; 247:170-180. [PMID: 36343698 DOI: 10.1016/j.ajo.2022.10.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 10/29/2022] [Accepted: 10/29/2022] [Indexed: 11/06/2022]
Abstract
PURPOSE To evaluate the neurodevelopmental outcomes in premature infants who received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections to treat retinopathy of prematurity (ROP). DESIGN Retrospective cohort study. METHODS This study was conducted using the database from the Taiwan Premature Infant Follow-up Network. Demographic data, systemic risk factors, ROP status, and neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were collected. Patients were divided into 4 groups: prematurity without ROP, ROP without treatment, ROP with laser treatment, and ROP with intravitreal anti-VEGF treatment. A generalized estimating equation was used for analyzing repeated measurements of Bayley-III at the corrected ages of 6, 12, and 24 months. RESULTS A total of 2090 patients with a mean gestational age of 31.2 weeks were included. The Bayley-III composite scores of patients with ROP treated with anti-VEGF were comparable to those of patients with ROP without treatment (cognitive: P = .491; language: P = .201; motor: P = .151) and premature patients without ROP (cognitive: P = .985; language: P = .452; motor: P = .169) after adjusting for confounders. Patients with ROP treated with laser photocoagulation exhibited poorer cognitive composite scores than did those without treatment (P < .001), premature patients without ROP (P < .001), and those treated with anti-VEGF (P < .001), but they had similar language and motor composite scores. CONCLUSIONS Intravitreal anti-VEGF treatment for ROP was not associated with adverse neurodevelopment in premature infants. Further studies are needed to determine whether general anesthesia or sedation used in laser treatment for ROP has significant impacts on neurodevelopmental outcomes.
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Affiliation(s)
- Ming-Chou Chiang
- Division of Neonatology, Department of Pediatrics (M.-C.C), Chang Gung Memorial Hospital, Linkou, Taiwan; Taiwan Premature Infant Follow-up Network (M.-C.C); College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan
| | - Yen-Ting Chen
- College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Taiwan Premature Infant Follow-up Network (Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H.,, C.-C.L., W.-C.W.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Ophthalmology (Y.-T.C., Y.-P.C.), New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan
| | - Eugene Yu-Chuan Kang
- College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Taiwan Premature Infant Follow-up Network (Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H.,, C.-C.L., W.-C.W.), Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Kuan-Jen Chen
- College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Taiwan Premature Infant Follow-up Network (Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H.,, C.-C.L., W.-C.W.), Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Nan-Kai Wang
- College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Taiwan Premature Infant Follow-up Network (Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H.,, C.-C.L., W.-C.W.), Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Laura Liu
- College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Taiwan Premature Infant Follow-up Network (Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H.,, C.-C.L., W.-C.W.), Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Yen-Po Chen
- College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Taiwan Premature Infant Follow-up Network (Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H.,, C.-C.L., W.-C.W.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Ophthalmology (Y.-T.C., Y.-P.C.), New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan
| | - Yih-Shiou Hwang
- College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Taiwan Premature Infant Follow-up Network (Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H.,, C.-C.L., W.-C.W.), Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Chi-Chun Lai
- College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Taiwan Premature Infant Follow-up Network (Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H.,, C.-C.L., W.-C.W.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Ophthalmology (C.-C.L.), Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wei-Chi Wu
- College of Medicine (M.-C.C., Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H., C.-C.L., W.-C.W.), Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Taiwan Premature Infant Follow-up Network (Y.-T.C., E.Y.-K, K.-J.C., N.-K.W, L.L., Y.-P.C., Y.-S.H.,, C.-C.L., W.-C.W.), Chang Gung Memorial Hospital, Linkou, Taiwan.
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Hammer JD, Nguyen H, Palmer J, Furtney S, Agarwal-Sinha S. Computed Analysis of Retinal Vascular Growth After Bevacizumab Treatment of Retinopathy of Prematurity Until Age 3 Years. Clin Ther 2023; 45:4-16. [PMID: 36581528 DOI: 10.1016/j.clinthera.2022.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 10/19/2022] [Accepted: 12/05/2022] [Indexed: 12/29/2022]
Abstract
PURPOSE Premature infants, after anti-vascular endothelial growth factor injections for retinopathy of prematurity, have persistent peripheral avascular retina (PAR). PAR is ablated with laser; however, physiologic growth of the retinal vasculature in the long term has not been measured. The purposes of this study were to measure retinal vessel growth after treatment with intravitreal bevacizumab (IVB) for retinopathy of prematurity, using serial fluorescein angiography (FA), until age 3 years, and to assess the timing for providing laser ablation in PAR. METHODS Data from an observational, longitudinal clinical study were collected. Angiographic images of eyes treated with IVB were included; imaging data from laser photocoagulation were excluded. All eyes underwent initial examination under general anesthesia with FA and photographic imaging. The retinal vessel length was measured from the temporal margin of the optic disc passing through the foveal center, and the lengths at subsequent FA were compared. To compare the changes in retinal vessel length over time in individual eyes, a paired-sample t test was performed. FINDINGS FA images from 70 eyes (35 infants) treated with IVB were available. A total of 150 FA images were available for review; data from 125 images of good quality were used for analysis. The mean postmenstrual ages (PMAs) at first, second, third, and fourth FA were 66.2, 100.9, 135.1, and 180.7 weeks, respectively. The mean retinal vessel length was 14.177 mm at first FA and 13.199 mm at fourth FA (PMA range, 42...234 weeks). Retinal vascular lengths of individual eyes compared over time showed no statistically significant growth from the first FA to age 3 years. The changes in retinal vessel length from first to second FA were -0.117 ± 0.79 mm (p = 0.42; n = 30); from first to third FA, +0.060 ± 0.85 mm (p = 0.79; n = 15); and first to fourth FA, -0.404 ± 1.32 mm (p = 0.45; n = 7). IMPLICATIONS Beyond 65 weeks' PMA, no meaningful retinal vascular growth occurred after IVB up to age 3 years, guiding the timing for physicians if laser photocoagulation is being considered. Future studies are needed to address retinal growth changes in the growing eyes of infants.
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Affiliation(s)
- J D Hammer
- Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida
| | - Henry Nguyen
- Department of Biomedical Sciences, University of Florida, Gainesville, Florida
| | - Jacqueline Palmer
- Department of Biomedical Sciences, University of Florida, Gainesville, Florida
| | - Sarah Furtney
- Department of Biomedical Sciences, University of Florida, Gainesville, Florida
| | - Swati Agarwal-Sinha
- Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida; Deparment of Pediatric Ophthalmology, Seattle Children's Hospital, University of Washington, Seattle, Washington.
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Tawfik GM, Shahein EA, Dabour SA, Hassanein D, Elshewy AM. Comparison of intravitreal injection of ranibizumab versus bevacizumab for treatment of type 1 and aggressive retinopathy of prematurity in rural Egypt. A randomized clinical trial. BMJ Open Ophthalmol 2022. [DOI: 10.1136/bmjophth-2022-001173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
ObjectiveThe objective of this study is to evaluate the efficacy of intravitreal ranibizumab (IVR) monotherapy compared with intravitreal bevacizumab (IVB) monotherapy for treatment of type 1 and aggressive retinopathy of prematurity (ROP) in rural Egypt.Methods36 eyes of 18 infants with bilateral aggressive or type 1 ROP were recruited between September 2020 and September 2022. Mean follow-up duration was 16.53 months. IVB was injected in the right eye and IVR in the left eye, rescue injection of the same initial anti-vascular endothelial growth factor (VEGF) in case of ROP reactivation. Outcome measures included regression achieved either by single injection or multiple injections or additional laser therapy at 55 weeks’ postmenstrual age (PMA), recurrence of ROP, total retinal vascularisation time and complications.ResultsInitial regression of ROP within 1 week occurred in 11/18 eyes (61.1%) in bevacizumab group and 15/18 eyes (83.3%) in ranibizumab group (p=0.137). Primary outcome measure was achieved in 14/18 eyes (77.8%) and 16/18 eyes (88.9%) in bevacizumab and ranibizumab groups, respectively (p=0.658). Late reactivation requiring retreatment with anti-VEGF was encountered in 4/18 eyes (22.2%) and 1/18 eyes (5.6%) in bevacizumab and ranibizumab groups, respectively (p=0.338). Peripheral laser therapy on the avascular retina was done in 3/18 eyes (16.7%) in each group at mean of 55.67 weeks' PMA.ConclusionBevacizumab and ranibizumab proved to be effective regarding regression of acute ROP and continuing peripheral retinal vascularisation. Higher proportion of reactivation with bevacizumab, however, clinically non-significant. Laser therapy can be postponed to reduce its complications.Trial registration numberNCT05033106.
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Wu PL, Ling XC, Kang EYC, Chen KJ, Wang NK, Liu L, Chen YP, Hwang YS, Lai CC, Yang SF, Wu WC. Effects of TIMP-2 Polymorphisms on Retinopathy of Prematurity Risk, Severity, Recurrence, and Treatment Response. Int J Mol Sci 2022; 23:14199. [PMID: 36430677 PMCID: PMC9694036 DOI: 10.3390/ijms232214199] [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: 08/25/2022] [Revised: 10/31/2022] [Accepted: 11/14/2022] [Indexed: 11/18/2022] Open
Abstract
Tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in endogenous angiogenesis besides the regulation of matrix metalloproteinase (MMP) activity. Associations between TIMP-2 gene polymorphisms and the risk of retinopathy of prematurity (ROP) were examined. Premature infants born between 2009 and 2018 were included. Five single-nucleotide polymorphisms (SNPs) of TIMP-2 were analyzed with real-time polymerase chain reaction (PCR). Multivariate logistic regression was applied to model associations between TIMP-2 polymorphisms and ROP susceptibility and severity. The GA+AA genotype in individuals with the TIMP-2 polymorphism of rs12600817 was associated with a higher risk of ROP (odds ratio [OR]: 1.518, 95% confidence interval [CI]: 1.028-2.242) compared with their wild-type genotypes. The AA genotype (OR: 1.962, 95% CI: 1.023-3.762) and the AA+GA genotype (OR: 1.686, 95% CI: 1.030-2.762) in individuals with the rs12600817 polymorphism had higher risks of severe, treatment-requiring ROP relative to their wild-type counterparts. In patients with treatment-requiring ROP, the AG+GG genotypes in the TIMP-2 polymorphism of rs2889529 were correlated with the treatment response (p = 0.035). The TIMP-2 polymorphism of rs12600817 help in predicting ROP risks in preterm infants, while the polymorphism of rs2889529 can serve as a genetic marker in evaluating the ROP treatment response.
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Affiliation(s)
- Pei-Liang Wu
- Department of Medicine, National Taiwan University, Taipei 106, Taiwan
| | - Xiao Chun Ling
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
| | - Eugene Yu-Chuan Kang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Kuan-Jen Chen
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Nan-Kai Wang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Laura Liu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Yen-Po Chen
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Tucheng, New Taipei City 236, Taiwan
| | - Yih-Shiou Hwang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chi-Chun Lai
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
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Huang CY, Lai SH, Tseng HJ, Yao TC, Wu WC. Pulmonary function in school-age children following intravitreal injection of bevacizumab for retinopathy of prematurity. Sci Rep 2022; 12:18788. [PMID: 36335152 PMCID: PMC9637204 DOI: 10.1038/s41598-022-22338-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 10/13/2022] [Indexed: 11/06/2022] Open
Abstract
The effect of anti-vascular endothelial growth factor on neonatal lung development was inconclusive. To evaluate pulmonary function in school-age children who have received intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP), this study included 118 school-aged children who were grouped into three groups: full-term control children (group 1), preterm children who had not received IVB treatment (group 2) and preterm children with ROP who had received IVB treatment (group 3). Pulmonary function was measured by spirometry and impulse oscillometry. Pulmonary function was significantly better in group 1 than in groups 2 and 3 (all p < 0.05 in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow between 25 and 75% of FVC (FEF25-75), and respiratory resistance at 5 Hz and difference between respiratory resistance at 5 and 20 Hz (R5-R20). There were no statistically significant differences between group 2 and group 3 in all pulmonary function parameters, including FVC, FEV1, ratio of FEV1 to FVC, FEF25-75, R5, R20, R5-R20, and respiratory reactance at 5 Hz. In conclusion, our study revealed that preterm infants receiving IVB for ROP had comparable pulmonary function at school age to their preterm peers who had not received IVB treatment.
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Affiliation(s)
- Ching-Yen Huang
- grid.413801.f0000 0001 0711 0593Department of Ophthalmology, Chang Gung Memorial Hospital, 5 Fu-Hsin Street, Kweishan, Taoyuan, 33305 Taiwan
| | - Shen-Hao Lai
- grid.145695.a0000 0004 1798 0922College of Medicine, Chang Gung University, Taoyuan, Taiwan ,grid.413801.f0000 0001 0711 0593Division of Pulmonology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Hsiao-Jung Tseng
- grid.413801.f0000 0001 0711 0593Clinical Trial Center, Biostatistics Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tsung-Chieh Yao
- grid.145695.a0000 0004 1798 0922College of Medicine, Chang Gung University, Taoyuan, Taiwan ,grid.413801.f0000 0001 0711 0593Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, 5 Fu-Hsin Street, Gueishan, Taoyuan, 33305 Taiwan
| | - Wei-Chi Wu
- grid.413801.f0000 0001 0711 0593Department of Ophthalmology, Chang Gung Memorial Hospital, 5 Fu-Hsin Street, Kweishan, Taoyuan, 33305 Taiwan ,grid.145695.a0000 0004 1798 0922College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Liu J, Tsang JKW, Fung FKC, Chung SK, Fu Z, Lo ACY. Retinal microglia protect against vascular damage in a mouse model of retinopathy of prematurity. Front Pharmacol 2022; 13:945130. [PMID: 36059936 PMCID: PMC9431881 DOI: 10.3389/fphar.2022.945130] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/11/2022] [Indexed: 11/25/2022] Open
Abstract
Retinopathy of prematurity (ROP) is a common cause of blindness in preterm babies. As a hypoxia-induced eye disease characterized by neovascularization, its association with retinal microglia has been noted but not well documented. We performed a comprehensive analysis of retinal microglia and retinal vessels in mouse oxygen-induced retinopathy (OIR), an animal model of ROP. In combination with a pharmacological inhibitory strategy, the role of retinal microglia in vascular network maintenance was investigated. Postnatal day (P) 7 C57BL/6J mouse pups with their nursing mother were exposed to 75% oxygen for 5 days to induce OIR. Age-matched room air-treated pups served as controls. On P12, P17, P21, P25, and P30, retinal microglia and vessels were visualized and quantified based on their location and activation status. Their relationship with retinal vessels was also analyzed. On P5 or P12, retinal microglia inhibition was achieved by intravitreal injection of liposomes containing clodronate (CLD); retinal vasculature and microglia were examined in P12 and P17 OIR retinae. The number of retinal microglia was increased in the superficial areas of OIR retinae on P12, P17, P21, P25, and P30, and most of them displayed an amoeboid (activated) morphology. The increased retinal microglia were associated with increased superficial retinal vessels in OIR retinae. The number of retinal microglia in deep retinal areas of OIR retinae also increased from P17 to P30 with a ramified morphology, which was not associated with reduced retinal vessels. Intravitreal injection of liposomes-CLD caused a significant reduction in retinal microglia. Loss of retinal microglia before hyperoxia treatment resulted in increased vessel obliteration on P12 and subsequent neovascularization on P17 in OIR retinae. Meanwhile, loss of retinal microglia immediately after hyperoxia treatment on P12 also led to more neovascularization in P17 OIR retinae. Our data showed that activated microglia were strongly associated with vascular abnormalities upon OIR. Retinal microglial activation continued throughout OIR and lasted until after retinal vessel recovery. Pharmacological inhibition of retinal microglia in either hyperoxic or hypoxic stage of OIR exacerbated retinal vascular consequences. These results suggested that retinal microglia may play a protective role in retinal vasculature maintenance in the OIR process.
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Affiliation(s)
- Jin Liu
- Department of Ophthalmology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Jessica Kwan Wun Tsang
- Department of Ophthalmology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Frederic Khe Cheong Fung
- Department of Ophthalmology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Sookja Kim Chung
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Zhongjie Fu
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- *Correspondence: Zhongjie Fu, ; Amy Cheuk Yin Lo,
| | - Amy Cheuk Yin Lo
- Department of Ophthalmology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- *Correspondence: Zhongjie Fu, ; Amy Cheuk Yin Lo,
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Chow SC, Lam PY, Lam WC, Fung NSK. The role of anti-vascular endothelial growth factor in treatment of retinopathy of prematurity-a current review. Eye (Lond) 2022; 36:1532-1545. [PMID: 35017699 PMCID: PMC9307789 DOI: 10.1038/s41433-021-01922-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 11/27/2021] [Accepted: 12/22/2021] [Indexed: 11/08/2022] Open
Abstract
The review aims to evaluate the uses of conventional laser therapy and intravitreal injection of various anti-VEGF in terms of efficacy and side effects for the treatment of retinopathy of prematurity. A literature search of the publication, concerning conventional laser treatment and intravitreal injection of anti-VEGF for ROP. A total of 40 articles were reviewed after curation by the authors for relevance. Intravitreal anti-VEGF showed better ocular efficacy in zone I ROP while laser therapy had a lower recurrence rate in zone II. Comparing the two mainstay anti-VEGF agents, bevacizumab showed lower ROP recurrence rate than ranibizumab. Anti-VEGF has a higher chance in developing persistent peripheral avascularisation compared to conventional laser therapy, but a lower chance of developing high myopia. Ranibizumab has a lower systemic absorption than bevacizumab, despite having no difference in the incidence of persistent peripheral avascularisation. In conclusion, it is advised that intravitreal anti-VEGF should be used as the first-line treatment for zone I ROP while laser therapy should be the mainstay for zone II ROP owing to the different pathogenetic mechanisms. In patients with recurrence after initial anti-VEGF injection, that given ranibizumab may opt to repeat the injection while that given bevacizumab should consider supplement laser ablative treatment.
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Affiliation(s)
- Shing Chuen Chow
- The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Pun Yuet Lam
- The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Wai Ching Lam
- The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
- Queen Mary Hospital & Grantham Hospital, Pok Fu Lam, Hong Kong
| | - Nicholas Siu Kay Fung
- The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.
- Queen Mary Hospital & Grantham Hospital, Pok Fu Lam, Hong Kong.
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Chen Y, Wang S, Chen S, Chen X, Han L, Zhong Q, Zhang K. Appropriate dose of intravitreal ranibizumab for ROP: a retrospective study. BMC Ophthalmol 2022; 22:271. [PMID: 35729540 PMCID: PMC9210651 DOI: 10.1186/s12886-022-02489-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 06/09/2022] [Indexed: 11/10/2022] Open
Abstract
Objective To compare the recurrence rate of retinopathy of prematurity (ROP) after treatment with 0.3 mg vs. 0.25 mg ranibizumab. Subjects All patients with ROP who underwent intravitreal injection of ranibizumab in Hainan General Hospital between January 2014 and May 2020 were included in this retrospective study. Methods Eighty-two cases (146 eyes) who received intravitreal injection of 0.25 mg ranibizumab were included in the conventional-dose group, and 59 cases (108 eyes) who received intravitreal injection of 0.3 mg ranibizumab were included in the high-dose group. The two groups were further divided into the 25-28-week, 29-31-week, 32-34-week, and 35-36-week GA subgroups. The differences between the conventional-dose group and the high-dose group in gestational age (GA), birth weight (BW), age at initial injection (weeks), incidence of systemic diseases, the recurrence rate of ROP, and age at retinal vascularization completed (weeks) were analyzed. Results GA, BW, age at initial injection, and the incidence of systemic diseases were not significantly different between the conventional-dose group and the high-dose group (p > 0.05). The recurrence rates of ROP were significantly lower in the 25-28-week, 29-31-week, and 32-34-week subgroups of the high-dose group than in the same subgroups of the conventional-dose group (p < 0.05). Within the conventional-dose group, the recurrence rate of ROP was significantly lower in the 32-34-week and 35-36-week subgroups than in the 25-28-week and 29-31-week subgroups (p < 0.05). Within the high-dose group, the recurrence rate of ROP was not significantly different between the four subgroups (p > 0.05). Retinal vascularization was completed at a later age in the 32-34-week subgroup of the high-dose group than in the 32-34-week subgroup of the conventional-dose group (p < 0.05) but was not significantly different between the two groups at any other GA range (p > 0.05). No severe ocular or systemic complications occurred in any patient. Conclusion Treatment with 0.3 mg ranibizumab can reduce the recurrence rate of ROP without prolonging retinal vascularization or causing serious systemic complications. Therefore, this dose may be an appropriate therapeutic dose for ROP.
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Affiliation(s)
- Yingying Chen
- Hainan General Hospital , Hainan Affiliated Hospital Of Hainan Medical University, Xiuhua road, Hainan General Hospital, Hainan, China
| | - Shaoli Wang
- Hainan General Hospital , Hainan Affiliated Hospital Of Hainan Medical University, Xiuhua road, Hainan General Hospital, Hainan, China
| | - Siying Chen
- Hainan General Hospital , Hainan Affiliated Hospital Of Hainan Medical University, Xiuhua road, Hainan General Hospital, Hainan, China
| | - Xingyue Chen
- Hainan General Hospital , Hainan Affiliated Hospital Of Hainan Medical University, Xiuhua road, Hainan General Hospital, Hainan, China
| | - Lizhen Han
- Hainan General Hospital , Hainan Affiliated Hospital Of Hainan Medical University, Xiuhua road, Hainan General Hospital, Hainan, China
| | - Qionglei Zhong
- Hainan General Hospital , Hainan Affiliated Hospital Of Hainan Medical University, Xiuhua road, Hainan General Hospital, Hainan, China.
| | - Kaiyan Zhang
- Hainan General Hospital , Hainan Affiliated Hospital Of Hainan Medical University, Xiuhua road, Hainan General Hospital, Hainan, China.
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Morphological outcome and indication for laser following intravitreal bevacizumab monotherapy for posterior retinopathy of prematurity. Lasers Med Sci 2022; 37:2501-2508. [PMID: 35106690 DOI: 10.1007/s10103-022-03515-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/26/2022] [Indexed: 10/19/2022]
Abstract
The purpose of this study is to determine the natural course of retinal vascular development and recurrence requiring laser in eyes receiving intravitreal bevacizumab (IVB) for posterior retinopathy of prematurity (ROP). Data of babies receiving IVB for posterior ROP was retrospectively analyzed. Birth weight, gestational age (GA) and post-menstrual age (PMA) at injection, need for laser, retinal maturation, and their timing were recorded. The study included 63 eyes of 32 babies, born at a median GA of 31 (IQR 29-32) weeks, and birth weight 1410 (1280-1697.5) g. Aggressive posterior ROP was seen in 36 (57%) eyes and staged ROP in 27 (43%). IVB was injected at a median PMA of 36 (34.5-37) weeks. Complete retinal vascularization was seen in 33 (52.4%) at a median PMA of 52 (47-60) weeks, prophylactic laser was needed in 17 (27%) at 61 (55.5-63) weeks, and only 13 (20.6%) eyes had recurrence needing treatment laser, at 42 (39-57) weeks respectively. Babies requiring laser had a significantly lower birth weight (p = 0.033) and received injection earlier (p = 0.08). Retinal vascular development progresses with IVB monotherapy with 21% of eyes developing recurrence that requires laser in this subset of Indian babies. Following IVB, monotherapy laser can be selectively performed only in cases with recurrence or failure to mature.
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13
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Süren E, Özkaya D, Çetinkaya E, Kalaycı M, Yiğit K, Kücük MF, Erol MK. Comparison of bevacizumab, ranibizumab and aflibercept in retinopathy of prematurity treatment. Int Ophthalmol 2022; 42:1905-1913. [DOI: 10.1007/s10792-021-02188-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 12/18/2021] [Indexed: 11/29/2022]
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14
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Kondo C, Iwahashi C, Utamura S, Kuniyoshi K, Konishi Y, Wada N, Kawasaki R, Kusaka S. Characteristics of Eyes Developing Retinal Detachment After Anti-vascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity. Front Pediatr 2022; 10:785292. [PMID: 35463897 PMCID: PMC9021749 DOI: 10.3389/fped.2022.785292] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 03/15/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND We investigated the incidence and clinical characteristics of eyes showing retinal detachment (RD) after anti-vascular endothelial growth factor (VEGF) for retinopathy of prematurity (ROP). METHODS A retrospective chart review of 76 consecutive eyes of 45 patients (18 girls and 27 boys) with stage 3 ROP who received anti-VEGF therapy between January 2012 and August 2020 with a minimum follow-up of 6 months was conducted. Eyes were divided into two groups: the vitrectomy (V) group that required vitrectomy for RD after anti-VEGF therapy and the non-vitrectomy (non-V) group that did not require vitrectomy. Data were collected from patient charts, including sex, postmenstrual age (PMA) at birth, birth weight, PMA at anti-VEGF therapy, comorbidities, reactivation, examination interval, and subsequent vitrectomies. RESULTS The median PMA at birth was 24.7 (range, 22.1-29.3) weeks. Twenty-seven eyes (35.1%) exhibited ROP reactivation at 6.4 ± 3.1 weeks after anti-VEGF therapy. The V group included six eyes of five patients, all of whom exhibited reactivation and developed RD 10.1 ± 6.5 weeks after anti-VEGF therapy. The types of RD were conventional (classic) in two eyes and circumferential (unique to RD after anti-VEGF) in four eyes. Three eyes required repeated vitrectomy. All eyes, except one eye in the V group, achieved retinal attachment at the last examination. The non-V group included 70 eyes of 40 patients, of which 21 exhibited reactivation and were treated successfully with laser (17 eyes) or second anti-VEGF (4 eyes). The proportion of eyes with plus disease was significantly higher in the V group (50.0%) than in the non-V group (10.0%) (P = 0.035). V group included 3 of 22 eyes (13.6%) in which the interval between the last examination and the diagnosis of reactivation was <1 week and 3 of 5 eyes (60.0%) in which the interval was more than 1 week (P = 0.024). The two groups showed no significant differences in the other factors. CONCLUSION Approximately 8% of eyes developed RD about 10 weeks after anti-VEGF therapy for ROP. Eyes with history of plus disease should be carefully monitored at appropriate intervals after anti-VEGF therapy for ROP.
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Affiliation(s)
- Chiori Kondo
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Chiharu Iwahashi
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Shoko Utamura
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Kazuki Kuniyoshi
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Yuhei Konishi
- Department of Pediatrics, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Norihisa Wada
- Department of Pediatrics, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Ryo Kawasaki
- Department of Vision Informatics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Shunji Kusaka
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
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15
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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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Angiographic findings in cases with a history of severe retinopathy of prematurity treated with anti-VEGFs: Follow-up to age 6 years. Int Ophthalmol 2021; 42:1317-1337. [PMID: 34729633 DOI: 10.1007/s10792-021-02119-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 10/21/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE To report the effects of anti-vascular endothelial growth factor (VEGF) treatment in vascular development for cases of acute retinopathy of prematurity (ROP) using fluorescent angiography (FA) and to present the results of our observational approach to retinal sequelae. METHODS A total of 31 eyes in 19 patients with a history of treatment with anti-VEGF agents for classic type 1 ROP and aggressive posterior ROP who underwent FA between March 2014 to February 2020 were reviewed. Angiograms of retinal developmental features of patients aged 4 months to 6 years were examined. RESULTS The patients mean gestational age were 26.06 ± 1.90 weeks and the mean birth weight were 837.68 ± 236.79 g. All cases showed various abnormalities at the vascular and avascular retina, and the posterior pole. All but one case showed a peripheral avascular area on FA evaluation during the follow-up period. We did not apply prophylactic laser treatment to these avascular retina. On the final examination, except one case, we did not observe any late reactivation in any patients. CONCLUSION FA is an important tool for assessing vascular maturation in infants. Every leakage should not be assumed to be evidence of late activation, as some leaks may be related to vascular immaturity. Retinal vascularization may not be completed in all patients, however this does not mean that all these patients need prophylactic laser application. Our observational approach may be more daring than the reports frequently encountered in the literature, but it should be noted that unnecessary laser treatment will also eliminate all the advantages of anti-VEGF treatment.
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Iwahashi C, Utamura S, Kuniyoshi K, Sugioka K, Konishi Y, Wada N, Kusaka S. FACTORS ASSOCIATED WITH REACTIVATION AFTER INTRAVITREAL BEVACIZUMAB OR RANIBIZUMAB THERAPY IN INFANTS WITH RETINOPATHY OF PREMATURITY. Retina 2021; 41:2261-2268. [PMID: 33958533 DOI: 10.1097/iae.0000000000003196] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To investigate the efficacy and risk factors of intravitreal antivascular endothelial growth factor injection (anti-VEGF therapy) for retinopathy of prematurity (ROP). METHODS We retrospectively reviewed 80 consecutive eyes of 43 patients with Type 1 ROP or worse who received anti-VEGF therapy during January 2012-February 2018. Patients were divided into those who were injected with 0.25 mg of bevacizumab (IVB group, 37 eyes) and 0.25 mg of ranibizumab (IVR group, 43 eyes). Serum VEGF concentrations of 18 patients were measured before and after IVR. RESULTS Antivascular endothelial growth factor injection therapy reduced ROP activity in all eyes; however, 14 eyes (17.5%) exhibited reactivation. The reactivation rates of the IVB and IVR groups were 13.5% and 20.9%, respectively (P = 0.556). Multivariate logistic regression analysis showed that postmenstrual age ≤35 weeks at anti-VEGF therapy (P = 0.014) and aggressive posterior ROP (P = 0.044) was significantly associated with reactivation. Serum VEGF was significantly suppressed at Days 1 (P < 0.001) and 7 (P = 0.012) after IVR and returned to the preinjection level by Day 14 (P = 0.210). CONCLUSION Both IVR and IVB seemed effective in reducing ROP activity. Reactivation after anti-VEGF therapy may be associated with younger postmenstrual age at anti-VEGF therapy and aggressive posterior ROP.
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Affiliation(s)
| | | | | | | | - Yuhei Konishi
- Pediatrics, Kindai University Faculty of Medicine, Osaka, Japan
| | - Norihisa Wada
- Pediatrics, Kindai University Faculty of Medicine, Osaka, Japan
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Xu LT, Levine DA, Hutchinson AK, Rao P, Hubbard GB. CLINICAL FEATURES AND OUTCOMES OF INFANTS WITH RETINOPATHY OF PREMATURITY WHO FAIL ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY. Retina 2021; 41:2269-2277. [PMID: 34190725 PMCID: PMC8542626 DOI: 10.1097/iae.0000000000003249] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE To describe characteristics and outcomes of patients with retinopathy of prematurity who failed intravitreal antivascular endothelial growth factor. METHODS A retrospective case series of 211 eyes (112 patients) treated with antivascular endothelial growth factor as initial therapy for retinopathy of prematurity at a single academic institution between 2011 and 2019 and an additional 6 eyes (3 patients) referred to us for management of failed antivascular endothelial growth factor. RESULTS Among the 211 eyes receiving initial treatment at our institution, 17 eyes (11%) failed. Of the 23 total eyes managed by us for failure, 3 eyes (13%) failed after 50-week postmenstrual age. Failure manifested as recurrent plus in 14 eyes (58%), recurrent Stage 3 in 13 eyes (54%) and retinal detachment in 5 eyes (21%). Treatment failures were managed with laser (13 eyes), repeat injection (4 eyes), vitrectomy (2 eyes), or a combination of modalities (4 eyes). Follow-up of ≥6 months was available for 18 of the 23 eyes. The retina was fully attached in 17 eyes, and fixation behavior was present in 10 eyes. CONCLUSION The most common manifestations of treatment failure were recurrent plus and Stage 3. The failure rate at our institution was 11.0%. A significant proportion of failures occurred after 50-week postmenstrual age. Most failed eyes had favorable anatomical outcomes and over half demonstrated fixation behavior.
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Affiliation(s)
- Lucy T Xu
- Department of Ophthalmology, Emory Eye Center, Atlanta, Georgia
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19
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Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize complications of treatment for retinopathy of prematurity (ROP) and to compare complications of laser and intravitreal antivascular endothelial growth factor (VEGF) injections. RECENT FINDINGS Poor structural outcomes and myopia are more common with laser for severe ROP than with anti-VEGF. Clinical trial data show unfavourable outcomes in 9.1-9.5% of laser treated, and 1.4-3.6% of anti-VEGF treated eyes. Additional randomized trial data show risk for very high myopia (≥-8.00D) to be 3.8 and 51.4% for zone I eyes treated with bevacizumab and laser, respectively. However, anti-VEGF may be complicated by late recurrence and is more likely to require retreatment than laser. Laser often necessitates general anaesthesia with its attendant risks, including worse short-term respiratory outcomes. Neurodevelopmental complications have been reported with anti-VEGF, but existing studies are subject to bias. SUMMARY Treatment complications are substantially different for the two modalities in common use today. In more severe cases, risk of poor structural outcome and myopia favour treatment with anti-VEGF. In less severe ROP, risk of recurrence and the need for additional treatments may favour laser. Additional data are needed to establish comparative risks of neurodevelopmental complications.
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Affiliation(s)
- Joshua M Barnett
- The Emory Eye Center, Emory University School of Medicine, Atlanta, Georgia, USA
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20
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Ozdemir O, Arman A, Tayman C. Intraocular pressure effect of anti-vascular endothelial growth factor injection for aggressive posterior retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2021; 259:3469-3476. [PMID: 34151383 DOI: 10.1007/s00417-021-05278-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 06/03/2021] [Accepted: 06/09/2021] [Indexed: 11/26/2022] Open
Abstract
PURPOSE To compare the effect of 0.0125 mL and 0.025 mL doses of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection on intraocular pressure (IOP) in eyes with aggressive posterior retinopathy of prematurity (ROP). METHODS In this retrospective cohort study, charts of 52 eyes of 26 consecutive infants were reviewed. The patients received 0.0125 mL (Group 1) or 0.025 mL (Group 2) anti-VEGF agents' intravitreally. The IOP was measured before injection, on the first day, during the first week, and in the first month. After each injection, optic nerve head perfusion was evaluated by a binocular indirect ophthalmoscope. IOP values, complications, use of antiglaucomatous drops, and the effects of anti-VEGF drugs were recorded. RESULTS The mean baseline IOP before injection was 16.0 ± 3.7 mmHg for Group 1 and 15.5 ± 4.5 mmHg for Group 2 (p = 0.365). The mean value of IOP on the first day was statistically increased in Group 2 (29.2 ± 6.1 mmHg) compared with Group 1 (24.1 ± 6.8 mmHg) (p = 0.013). Moreover, antiglaucomatous drops were needed in 12 eyes for Group 2 compared with seven eyes for Group 1. Anterior chamber paracentesis was not performed after any of the injections. CONCLUSION This study found that IOP increases after intravitreal injections of anti-VEGF agents for the treatment of ROP. The injection of 0.025 mL anti-VEGF agents increases IOP more than the 0.0125 mL injection in the treatment of infants with aggressive posterior ROP.
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Affiliation(s)
- Ozdemir Ozdemir
- Department of Ophthalmology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey.
| | - Aysegul Arman
- Department of Ophthalmology, Ankara City Hospital, Ankara, Turkey
| | - Cuneyt Tayman
- Division of Neonatology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
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Mohammadi SF, Rahban A, Darabeigi S, Salimi N, Farahani A, Lashay A, Alinia C. Cost-effectiveness analysis of tele-retinopathy of prematurity screening in Iran. Int J Ophthalmol 2021; 14:560-566. [PMID: 33875948 DOI: 10.18240/ijo.2021.04.13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 08/18/2020] [Indexed: 11/23/2022] Open
Abstract
AIM To conduct a cost-utility analysis of the tele-retinopathy of prematurity (ROP) screening program against no screening. METHODS A decision tree model was developed to identify and treat the infants with threshold ROP through the tele-screening system compared with no screening program from the societal perspective. We used the quality adjusted life years (QALY) index to measure the scenarios' effectiveness, which was discounted for the future years by 0.058. One hundred twenty-six randomly selected newborns with ROP required treatment were investigated to extract the treatment information. We considered the direct medical and non-medical costs in cost calculations analysed by the bottom-up approach. The figures of the model's inputs were calculated using the Monte Carlo simulation that generated 1000 random iteration of the data, and a one-way sensitivity analysis was performed on the model to cope with the potential uncertainties. RESULTS The total and per capita needed the budget to establish a tele-ROP screening system were estimated at over 1.5 million and 35.13 USD, respectively. The total cost of identifying and treating an ROP case in tele-screening and no screening strategies were obtained as 108.72 and 63.52 USD, respectively, and their lifetime discounted QALY gained were calculated as 15.39 and 15.11, respectively. Therefore, incremental cost-effectiveness ratio (ICER) of tele-screening strategy against the competitive strategy was achieved as 161.43 USD. CONCLUSION Tele-ROP screening program is one of the most cost-effective interventions in the Iranian health system and has a high priority to receive a budget for implementation.
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Affiliation(s)
- Seyed-Farzad Mohammadi
- Translational Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran 6719851351, Iran
| | - Ameneh Rahban
- Department of Health Management and Economics, School of Public Health, Urmia University of Medical Sciences, Urmia 571478334, Iran
| | - Sahel Darabeigi
- Translational Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran 6719851351, Iran
| | - Nastaran Salimi
- Translational Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran 6719851351, Iran
| | - Afsar Farahani
- Translational Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran 6719851351, Iran
| | - Alireza Lashay
- Translational Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran 6719851351, Iran
| | - Cyrus Alinia
- Department of Health Management and Economics, School of Public Health, Urmia University of Medical Sciences, Urmia 571478334, Iran
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Murakami T, Sugiura Y, Okamoto F, Okamoto Y, Kato A, Hoshi S, Nagafuji M, Miyazono Y, Oshika T. Comparison of 5-year safety and efficacy of laser photocoagulation and intravitreal bevacizumab injection in retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2021; 259:2849-2855. [PMID: 33744981 DOI: 10.1007/s00417-021-05137-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 02/18/2021] [Accepted: 03/02/2021] [Indexed: 11/24/2022] Open
Abstract
PURPOSE To compare laser photocoagulation and intravitreal injection of bevacizumab (IVB) treatment for retinopathy of prematurity (ROP). METHODS The study included 52 eyes of 26 patients after ROP treatment who were observed up to 5 years of age. Twenty-eight eyes received laser photocoagulation as the initial treatment (laser group), and twenty-four eyes underwent IVB (IVB group). We collected data on gestational age, birth weight, 1- and 5-min Apgar scores, zone and stage at the time of treatment, recurrence of ROP and best-corrected visual acuity (BCVA) (logMAR), equivalent spherical value (SE), ocular complications, and developmental delay at the age of 5. RESULTS More zone I low-stage eyes were treated with IVB than laser. There was no difference in BCVA (p = 0.836). Although the mean SE was not different between the groups (p = 0.280), the prevalence of myopia was significantly higher in the laser group (p = 0.020). Developmental delay was observed in 3 of 14 and 3 of 12 cases in the laser and IVB groups, respectively (p = 0.596). Retinal holes were observed in 2 eyes in the IVB group, with 1 developing localized retinal detachment. There were no significant differences between the groups in the other factors. CONCLUSIONS Compared to laser for ROP, IVB was not inferior in neurodevelopment or visual outcome and was superior in refractive error. As cases in the IVB group showed retinal holes, long-term follow-up with fundus examination is recommended after IVB.
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Affiliation(s)
- Tomoya Murakami
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan.
| | - Yoshimi Sugiura
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Fumiki Okamoto
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yoshifumi Okamoto
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Atsuko Kato
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Sujin Hoshi
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Motomichi Nagafuji
- Department of Child Health, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Yayoi Miyazono
- Department of Child Health, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Tetsuro Oshika
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
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Fan YY, Liu CH, Wu AL, Chen HC, Hsueh YJ, Chen KJ, Lai CC, Huang CY, Wu WC. MicroRNA-126 inhibits pathological retinal neovascularization via suppressing vascular endothelial growth factor expression in a rat model of retinopathy of prematurity. Eur J Pharmacol 2021; 900:174035. [PMID: 33727052 DOI: 10.1016/j.ejphar.2021.174035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 03/06/2021] [Accepted: 03/11/2021] [Indexed: 01/11/2023]
Abstract
Vascular endothelial growth factor (VEGF) is the principal growth factor responsible for the retinal neovascularization in the pathogenesis of retinopathy of prematurity (ROP). Current therapies for ROP include laser ablation and intravitreal anti-VEGF injection. However, these treatments either destroy the peripheral retina or associate with problems of persistent peripheral avascular retina or later recurrence of ROP. In the present study we investigated a new therapeutic approach by exploring the potential role of a specific microRNA, miR-126, in regulating VEGFA expression and retinal neovascularization in a rat oxygen-induced retinopathy (OIR) model. We demonstrated that miR-126 mimic and plasmid effectively suppresses VEGFA mRNA expression in both human and rat retinal pigment epithelium cell lines, quantified with qRT-PCR. Animal experiments on rat OIR model revealed that intravitreal injection of miR-126 plasmid efficiently downregulated VEGFA expression in the intraocular fluid and retinal tissues measured by ELISA, and significantly suppressed retinal neovascularization, which was confirmed by calculating sizes of neovascularization areas on fluorescence microscopic images of flat mounted retina stained with Alexa Fluor 594-conjugated isolectin B4 to visualize blood vessels. Together, these results showed that intravitreal injection of miR-126 plasmid could inhibit retinal neovascularization by down-regulating VEGFA expression, suggesting a potential therapeutic effect for ROP.
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Affiliation(s)
- Yuan-Yao Fan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Hsien Liu
- Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan
| | - An-Lun Wu
- Department of Ophthalmology, Mackay Memorial Hospital, Hsinchu, Taiwan
| | - Hung-Chi Chen
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Limbal Stem Cell Laboratory, Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yi-Jen Hsueh
- Limbal Stem Cell Laboratory, Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Kuan-Jen Chen
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Chun Lai
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chung-Ying Huang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Lee YS, Teh WM, Tseng HJ, Hwang YS, Lai CC, Wu WC. Comparison of foveal thickness in preschool children with a history of retinopathy of prematurity and laser photocoagulation or anti-vascular endothelial growth factor treatment: a prospective, longitudinal study. Br J Ophthalmol 2020; 106:106-112. [PMID: 33055087 DOI: 10.1136/bjophthalmol-2020-317284] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/10/2020] [Accepted: 09/23/2020] [Indexed: 11/04/2022]
Abstract
AIMS To determine longitudinal differences in foveal thickness in preschool-aged patients with or without a history of type I retinopathy of prematurity (ROP). METHODS A study of 201 eyes, including 32 laser±intravitreal bevacizumab (IVB)-treated eyes, 37 IVB-treated eyes, 14 spontaneously regressed ROP eyes, and 118 age-matched controls were enrolled in this study. The retinal thicknesses (full, inner and outer) were measured in the foveal area at 6-month intervals four consecutive times by optical coherence tomography. RESULTS The foveal thicknesses among the four groups were similar at all four visits (all p>0.05) after gestational age (GA) adjustment and remained similar with no differences after the full retinal thickness was divided into inner and outer thicknesses (all p>0.05). The full and outer foveal thicknesses of premature children increased over time (0.17 μm/month and 0.17 μm/month; p=0.0001 and 0.0003, respectively), but the inner foveal thickness remained unchanged with time (0.002 μm/month; p=0.09). Moreover, the positive correlation with best-corrected visual acuity was stronger for outer foveal thickness than for inner foveal thickness (γ=0.281, p<0.0001 and γ=0.181, p<0.0001, respectively). CONCLUSION The thickness of fovea in laser±IVB-treated, IVB-treated, regressed ROP and preterm eyes showed no difference after GA adjustment. The whole and outer foveal thicknesses increased with time in preschool-aged children over a 1.5-year follow-up period, but the inner foveal thickness remained unchanged with time.
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Affiliation(s)
- Yung-Sung Lee
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Wee-Min Teh
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Ophthalmology, Hospital Selayang, Selangor, Malaysia
| | - Hsiao-Jung Tseng
- Biostatistics Unit, Clinical Trial Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Yih-Shiou Hwang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Chun Lai
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan .,College of Medicine, Chang Gung University, Taoyuan, Taiwan
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An inhibitor of endothelial ETS transcription factors promotes physiologic and therapeutic vessel regression. Proc Natl Acad Sci U S A 2020; 117:26494-26502. [PMID: 33020273 DOI: 10.1073/pnas.2015980117] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
During the progression of ocular diseases such as retinopathy of prematurity and diabetic retinopathy, overgrowth of retinal blood vessels results in the formation of pathological neovascular tufts that impair vision. Current therapeutic options for treating these diseases include antiangiogenic strategies that can lead to the undesirable inhibition of normal vascular development. Therefore, strategies that eliminate pathological neovascular tufts while sparing normal blood vessels are needed. In this study we exploited the hyaloid vascular network in murine eyes, which naturally undergoes regression after birth, to gain mechanistic insights that could be therapeutically adapted for driving neovessel regression in ocular diseases. We found that endothelial cells of regressing hyaloid vessels underwent down-regulation of two structurally related E-26 transformation-specific (ETS) transcription factors, ETS-related gene (ERG) and Friend leukemia integration 1 (FLI1), prior to apoptosis. Moreover, the small molecule YK-4-279, which inhibits the transcriptional and biological activity of ETS factors, enhanced hyaloid regression in vivo and drove Human Umbilical Vein Endothelial Cells (HUVEC) tube regression and apoptosis in vitro. Importantly, exposure of HUVECs to sheer stress inhibited YK-4-279-induced apoptosis, indicating that low-flow vessels may be uniquely susceptible to YK-4-279-mediated regression. We tested this hypothesis by administering YK-4-279 to mice in an oxygen-induced retinopathy model that generates disorganized and poorly perfused neovascular tufts that mimic human ocular diseases. YK-4-279 treatment significantly reduced neovascular tufts while sparing healthy retinal vessels, thereby demonstrating the therapeutic potential of this inhibitor.
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Frosini S, Franco F, Vicini G, Nicolosi C, Varriale G, Dani C, Virgili G, Giansanti F. Efficacy and safety of intravitreal bevacizumab for the treatment of retinopathy of prematurity: a single-center retrospective review. J Matern Fetal Neonatal Med 2020; 35:3337-3342. [PMID: 32933350 DOI: 10.1080/14767058.2020.1818214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE The aim of this study is to report our experience in the management of type 1 retinopathy of prematurity (ROP) or aggressive posterior retinopathy of prematurity (APROP) in premature infants, who received intravitreal bevacizumab (IVB) injections either as first-line monotherapy or as rescue therapy following laser therapy. METHODS Single-center retrospective study on 37 patients (74 eyes) affected by sight-threatening ROP that underwent treatment either with IVB alone or laser photocoagulation followed by IVB at the Neonatal Intensive Care Unit of Careggi University Hospital of Florence, between 2008 and 2015. RESULTS Seventeen patients were males (45.9%) and 20 were females (54.1%). The mean gestational age was 24 weeks and the mean birth weight was 610 g. Fifty-six eyes (75.7%) of 28 patients were diagnosed as type 1 ROP and 18 eyes (24.3%) of nine patients as APROP. Sixty-six eyes of 33 patients received IVB as first-line monotherapy, eight eyes of four patients were treated with IVB after laser photocoagulation treatment, as rescue therapy. The mean postmenstrual age at treatment was 33.9 weeks. All the patients received bilateral injections. None of the infants required repeat injections. The mean follow-up time was 59.6 months. All the patients achieved a good response to treatment, showing the regression of the proliferative phase and a complete peripheral retinal vascularization within 2 months from the injection of bevacizumab. One patient with a bilateral ROP had only a partial resolution of a vitreous hemorrhage in the left eye. The procedures were well tolerated without local or systemic adverse events during the follow-up. No infants showed recurrences. Ocular motility alterations appeared in four patients (10.8%), with the absence of stereopsis in six cases (16.20%). After treatment, spherical equivalent values in cycloplegic refraction ranged from -4.0 D to +5.0 D, with a mean value of +1.75 D. All the patients showed a normal neuropsychomotor development. CONCLUSION Our study confirms the effectiveness and safety of IVB in the treatment of ROP, both as monotherapy and rescue therapy after laser photocoagulation, according to the published literature.
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Affiliation(s)
- Saverio Frosini
- Eye Clinic, Neuromuscular and Sense Organs Department, Careggi University Hospital, Florence, Italy
| | - Fabrizio Franco
- Eye Clinic, Neuromuscular and Sense Organs Department, Careggi University Hospital, Florence, Italy
| | - Giulio Vicini
- Eye Clinic, Neuromuscular and Sense Organs Department, Careggi University Hospital, Florence, Italy
| | - Cristina Nicolosi
- Eye Clinic, Neuromuscular and Sense Organs Department, Careggi University Hospital, Florence, Italy
| | - Gaia Varriale
- Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy
| | - Carlo Dani
- Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.,Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
| | - Gianni Virgili
- Eye Clinic, Neuromuscular and Sense Organs Department, Careggi University Hospital, Florence, Italy.,Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
| | - Fabrizio Giansanti
- Eye Clinic, Neuromuscular and Sense Organs Department, Careggi University Hospital, Florence, Italy.,Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
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Comparison of foveal optical coherence tomography angiography findings between premature children with ROP and non-premature healthy children. Eye (Lond) 2020; 35:1721-1729. [PMID: 32873943 DOI: 10.1038/s41433-020-01161-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 08/07/2020] [Accepted: 08/20/2020] [Indexed: 11/09/2022] Open
Abstract
PURPOSE Our aim is to compare foveal microvascular structure, foveal retinal thickness, and best-corrected visual acuity (BCVA) in children with a history of premature retinopathy (ROP) and healthy children. It is also evaluated whether microvascular structural changes in the course of ROP had resulted from treatment modalities of ROP or the disease itself. METHODS This is a cross-sectional observational comparative study. Seventy-one children were analyzed in four different groups: children treated with bevacizumab (18), or laser (19) for ROP; or spontaneously regressed disease (18) and non-premature healthy children (16). We analyzed foveal avascular zone (FAZ) and vessel densities (VDs) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at foveal and parafoveal region with optical coherence tomography angiography (OCT-A). Foveal thickness was measured by cross-sectional OCT. Correlations between FAZ area, foveal VD, central foveal thickness (CFT), BCVA, gestational age (GA), and birth weight (BW) were evaluated. RESULTS After comparing of OCT-A parameters between all premature children (groups 1-3) and non-premature children (group 4), significant differences were found in VD-SCP (whole), VD-SCP (foveal), VD-SCP (parafoveal), CFT, and VD-DCP (foveal) (all p < 0.001). Significantly smaller FAZ area was also noted in ROP children. Higher foveal VD of SCP, DCP, and smaller FAZ area were significantly associated with lower GA and BW. CONCLUSION By using OCT-A, significant foveal microvascular anomalies were identified in children with ROP irrespective of the treatment option or spontaneous regression. There has been a correlation between microvascular anomalies, CFT, and a lower BCVA.
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Sen P, Wu WC, Chandra P, Vinekar A, Manchegowda PT, Bhende P. Retinopathy of prematurity treatment: Asian perspectives. Eye (Lond) 2020; 34:632-642. [PMID: 31664193 PMCID: PMC7093470 DOI: 10.1038/s41433-019-0643-4] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 07/05/2019] [Indexed: 01/04/2023] Open
Abstract
Retinopathy of prematurity (ROP) is a vasoproliferative disease of developing retinal vessels that affects premature infants and can lead to severe and irreversible visual loss if left untreated. India and some other Asian countries are in the middle of a 'third ROP epidemic'. Blindness due to ROP is largely preventable if appropriate, adequate and accessible screening programmes are available. Screening of the premature babies is the first step in ROP management. With the increase in use of tele-screening techniques, more premature babies have been brought under the screening network both from urban and rural regions. Laser photocoagulation to the avascular retina using indirect ophthalmoscopy delivery system is the gold standard for ROP treatment and is usually done under topical anaesthesia in the Asian region in contrast to the western world. Use of intravitreal anti-vascular endothelial growth factors (VEGF) although controversial in management of ROP has been found to be effective in various Asian studies as well. ROP surgery in India and other middle-income Asian countries is largely performed only in few tertiary eye care centres. Poor visual prognosis, late presentation with advanced retinal detachments, lack of adequate number of trained paediatric retinal surgeons and paediatric anaesthetists also contribute to this problem. This current paper summarizes the Asian experience of ROP management.
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Affiliation(s)
- Parveen Sen
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, India
| | - Wei-Chi Wu
- Chang Gung Memorial Hospital Taoyuan, Taoyuan, Taiwan
| | - Parijat Chandra
- Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Anand Vinekar
- Paediatric Retina Department, Narayana Nethralaya, Bangalore, India
| | | | - Pramod Bhende
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, India.
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ANATOMICAL AND FUNCTIONAL RESULTS OF INTRAVITREAL AFLIBERCEPT MONOTHERAPY FOR TYPE 1 RETINOPATHY OF PREMATURITY. Retina 2020; 40:2366-2372. [DOI: 10.1097/iae.0000000000002754] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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30
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Etezad Razavi M, Shoeibi N, Hassanzadeh S, Kianmehr S, Bakhtiari E. Refractive outcome of intravitreal bevacizumab injection in comparison to spontaneous regression of retinopathy of prematurity (ROP). Strabismus 2019; 28:49-54. [PMID: 31790628 DOI: 10.1080/09273972.2019.1697302] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Purpose: To assess refractive errors in preterm infants following intravitreal bevacizumab (IVB) injection for retinopathy of prematurity (ROP) and to compare it with premature babies with spontaneous regressed ROP.Materials and Methods: Eighty seven premature infants were included in this study, comprising group1: 38 infants who underwent IVB monotherapy, and group2: 49 infants with spontaneously regressed ROP. Cycloplegic refraction was performed for all infants at 1-year adjusted age and the refractive outcome was compared between the groups.Results: At 1- year adjusted age, the mean SEQ value was not significantly different between group 1 and 2 (p = .646). Four eyes (10.5%) in group1 and 4 eyes (8.2%) in group 2 were myopic. Also, refractive anisometropia was found in 9 infants (23.7%) from group1 and 5 infants (10.2%) in groups 2, which was not significantly different between groups (χ2 (1, n = 87) = 2.87, p = .081). At the time of follow up, none of our cases were strabismic. After making an adjustment for gestational age and birth weight in a logistic regression model, mean SEQ was not significantly different between two groups (p = .61)Conclusion: At adjusted 1 year of age, refractive outcomes were not significantly different between premature infants who underwent IVB injection and the infants with spontaneous regression of ROP. Further studies with longer duration are warranted to elucidate the effects of IVB on the emmetropization process. Biometry assessments would be helpful in this regard.
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Affiliation(s)
| | - Nasser Shoeibi
- Ophthalmology, Eye Research Center, Mashhad University of Medical Sciences
| | - Samira Hassanzadeh
- Optometry, Student Research Committee, Paramedical College, Mashhad University of Medical Sciences
| | - Sedigheh Kianmehr
- Ophthalmology, Eye Research Center, Mashhad University of Medical Sciences
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Tan QQ, Christiansen SP, Wang J. Development of refractive error in children treated for retinopathy of prematurity with anti-vascular endothelial growth factor (anti-VEGF) agents: A meta-analysis and systematic review. PLoS One 2019; 14:e0225643. [PMID: 31790445 PMCID: PMC6886775 DOI: 10.1371/journal.pone.0225643] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 11/09/2019] [Indexed: 01/11/2023] Open
Abstract
Objective To investigate refractive error development in preterm children with severe retinopathy of prematurity (ROP) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and laser photocoagulation. Methods Selection criteria were comparative studies that compared the refractive errors in children, birthweights ≤1500 grams and gestational ages ≤30 weeks, and treatments for Type I ROP with intravitreal bevacizumab (IVB) versus laser photocoagulation. Studies were identified using PubMed, Google Scholar, and published reviews. Meta-analyses were performed on the post-treatment outcomes of spherical equivalent (SEQ), cylindrical power, and prevalence of high myopia. Longitudinal development of refractive error in IVB, or in laser-treated children, or in normal full-term children was visually summarized. Results Two randomized controlled trials and 5 non-randomized studies, including a total of 272 eyes treated by IVB and 247 eyes treated by laser, were included in this study. Compared with laser-treated children, IVB-treated children have less myopic refractive error (P<0.001), lower prevalence of high myopia (P<0.05), and less astigmatism (P = 0.02). Conclusions Treatment with IVB is associated with less myopia and astigmatism than laser treatment for infants with severe ROP. Given the complexity of ROP and the variability of dosing, our review supports close monitoring of refractive error outcomes in children treated with IVB.
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Affiliation(s)
- Qing-Qing Tan
- Department of Ophthalmology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- Department of Ophthalmology and Optometry, North Sichuan Medical College, Nanchong, Sichuan, China
- Salus University Pennsylvania College of Optometry, Elkins Park, Pennsylvania, United States of America
| | - Stephen P. Christiansen
- Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States of America
- Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts, United States of America
- Boston Medical Center, Boston, Massachusetts, United States of America
| | - Jingyun Wang
- Salus University Pennsylvania College of Optometry, Elkins Park, Pennsylvania, United States of America
- * E-mail:
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Ling KP, Liao PJ, Wang NK, Chao AN, Chen KJ, Chen TL, Hwang YS, Lai CC, Wu WC. RATES AND RISK FACTORS FOR RECURRENCE OF RETINOPATHY OF PREMATURITY AFTER LASER OR INTRAVITREAL ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY. Retina 2019; 40:1793-1803. [DOI: 10.1097/iae.0000000000002663] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Kang HG, Kim TY, Han J, Han SH. Refractive Outcomes of 4-Year-old Children after Intravitreal Anti-vascular Endothelial Growth Factor versus Laser Photocoagulation for Retinopathy of Prematurity. KOREAN JOURNAL OF OPHTHALMOLOGY 2019; 33:272-278. [PMID: 31179659 PMCID: PMC6557791 DOI: 10.3341/kjo.2019.0011] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 02/18/2019] [Accepted: 02/27/2019] [Indexed: 01/13/2023] Open
Abstract
Purpose To compare long-term refractive outcomes associated with intravitreal anti-vascular endothelial growth factor (VEGF) versus laser photocoagulation treatment for retinopathy of prematurity (ROP). Methods A total of 52 eyes from 27 ROP patients treated at two tertiary referral-based hospitals from August 2006 to December 2013 were reviewed. The primary outcome was refractive error measured at the age of 4 years, accounting for within-patient inter-eye correlation. Secondary outcomes included the recurrence rate and treatment complications. Results The mean age at refraction was 4.7 ± 0.3 years in the laser group (n = 30) and 4.4 ± 0.3 years in the anti-VEGF group (n = 22). No significant differences were noted in gestational age, birthweight, post-menstrual age at treatment, or ROP stage/zone distribution between groups. Mean spherical equivalent was also not significantly different (−1.0 diopters in the laser group and −0.3 diopters in the injection group, p = 0.603). Clustered regression analysis revealed that only gestational age was significantly correlated with mean spherical equivalent (p < 0.001; 95% confidence interval, −0.007 to −0.002). Recurrence was noted in four eyes (13.3%) in the laser group, but this difference was not significant (p = 0.128). There were no major systemic complications reported in either group. Conclusions Treatment type, whether laser or anti-VEGF injection, does not appear to influence long-term refractive outcomes in ROP. Concern regarding refractive outcomes should not be the most important factor when selecting ROP treatment modality.
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Affiliation(s)
- Hyun Goo Kang
- Department of Ophthalmology, Institute of Vision Research, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Young Kim
- Department of Ophthalmology, Institute of Vision Research, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jinu Han
- Department of Ophthalmology, Institute of Vision Research, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sueng Han Han
- Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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Li W, Zhang W, Zhang C, Zhu C, Yi X, Zhou Y, Lv Y. Soluble Tei2 fusion protein inhibits retinopathy of prematurity occurrence via regulation of the Ang/Tie2 pathway. Exp Ther Med 2019; 18:614-620. [PMID: 31258697 PMCID: PMC6566045 DOI: 10.3892/etm.2019.7608] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 03/23/2019] [Indexed: 12/31/2022] Open
Abstract
The aim of the present study was to investigate the potential mechanism of retinopathy of prematurity (ROP) using an oxygen-induced retinopathy (OIR) mouse model. For experiments, mice were divided into either the OIR group or control group. Fluorescein isothiocyanate-dextran cardiac perfusion and stretched retina preparation were performed. The total retina area, area of instillation, density of microvascular network, area of new blood vessels, vein width and the tortuosity of arteries were measured. Next, mice were randomly assigned into the PBS, soluble TEK receptor tyrosine kinase (sTie2)-fusion protein (Fc), angiopoietin 1 (Ang1), ranibizumab, ranibizumab + sTie2-Fc and ranibizumab + Ang1 treatment groups. Following housing for 5 days, the body weight of each mouse was recorded. Mice in the OIR group presented smaller total retina area and larger area of instillation, larger area of new blood vessels, and higher microvascular network density compared with the control PBS group. Obvious retinal vein dilatation and arterial tortuosity were identified in the OIR group. The amount of endotheliocyte nuclei of new vessels beyond the inner limiting membrane was larger in the OIR group compared with the control group. Furthermore in the next set of experiments, a larger area of instillation, smaller area of new blood vessels and decreased amount of endotheliocyte nuclei of new vessels were observed in the sTie2-Fc group, Ang1 group, ranibizumab group, ranibizumab + sTie2-Fc group and ranibizumab + Ang1 group compared with the PBS group. Specifically, the ranibizumab + sTie2-Fc group and ranibizumab + Ang1 group demonstrated markedly reduced retina instillation area and microvascular network density in the instillation area. Total retina area and body weight following 10 days of the experiment for the ranibizumab group were significantly lower compared with other groups. In conclusion, the combined regulation of the Ang/Tie2 and the vascular endothelial growth factor (VEGF)/VEGF receptor pathways markedly increased the efficacy of treatment with retinal neovascularization (RNV). Regulation of these pathways has a potential for treating RNV, in particular ROP.
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Affiliation(s)
- Weijing Li
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
| | - Weihua Zhang
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
| | - Cuiying Zhang
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
| | - Chunfang Zhu
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
| | - Xiangling Yi
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
| | - Yan Zhou
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
| | - Yan Lv
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
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Fan YY, Huang YS, Huang CY, Hsu JF, Shih CP, Hwang YS, Yao TC, Lai CC, Wu WC. Neurodevelopmental Outcomes after Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity: A Prospective Case-Control Study. Ophthalmology 2019; 126:1567-1577. [PMID: 30954553 DOI: 10.1016/j.ophtha.2019.03.048] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 03/29/2019] [Accepted: 03/29/2019] [Indexed: 02/07/2023] Open
Abstract
PURPOSE To evaluate the neurodevelopmental and ocular developmental outcomes in premature children who have undergone intravitreal bevacizumab injection (IVB) for treatment of type 1 retinopathy of prematurity (ROP). DESIGN Prospective case-control study. PARTICIPANTS We enrolled 3 groups of premature patients: premature children who had no history of ROP (group 0), premature children with history of ROP without treatment (group 1), and premature children with ROP who had received a single IVB (0.625 mg; group 2). METHODS Ocular developmental assessment, including cycloplegic refractometry, axial length, Cardiff acuity, and neurodevelopmental assessment via the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), were performed at 1 to 3 years of age and were compared between groups. MAIN OUTCOME MEASURES Ocular developmental outcomes and Bayley III scores. RESULTS A total of 148 patients (85 boys and 63 girls) were included. The mean age at assessment was 1.49±0.59 years. Group 0 patients demonstrated significantly higher gestational age (GA), birth weight, and Apgar scores compared with group 1 and 2 patients. There were no significant differences between groups 1 and 2 in demographics or systemic risk factors except for lower GA in group 2. The cylindrical power was significantly larger in groups 1 and 2 compared with group 0. The spherical equivalent was significantly more myopic and the Cardiff acuity was significantly poorer in group 2 than in group 0. There were no significant differences between groups 1 and 2 in refractive status, axial length, or Cardiff acuity. Neurodevelopmental assessment using Bayley III showed no significant difference among the 3 groups in any aspect after adjusting for GA and other systemic risk factors. The risks for poor neurodevelopmental outcomes also were not significantly different. CONCLUSIONS At the mean age of 1.5 years, children with prior history of IVB (group 2) showed similar refractive and visual outcomes and similar neurodevelopmental outcomes compared with premature patients with ROP without requirement of treatment (group 1), although there is a possibility that a small but clinically significant difference may not have been detected in the current study.
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Affiliation(s)
- Yuan-Yao Fan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yu-Shu Huang
- Department of Child Psychiatry and Sleep Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chung-Ying Huang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jen-Fu Hsu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chia-Pang Shih
- Department of Nursing, Yuanpei University of Medical Technology, Hsinchu, Taiwan
| | - Yih-Shiou Hwang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tsung-Chieh Yao
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chi-Chun Lai
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Bai Y, Nie H, Wei S, Lu X, Ke X, Ouyang X, Feng S. Efficacy of intravitreal conbercept injection in the treatment of retinopathy of prematurity. Br J Ophthalmol 2019; 103:494-498. [PMID: 30030391 DOI: 10.1136/bjophthalmol-2017-311662] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 05/03/2018] [Accepted: 05/30/2018] [Indexed: 01/18/2023]
Abstract
BACKGROUND To evaluate the safety and efficacy of intravitreal conbercept (IVC) injection in the treatment of retinopathy of prematurity (ROP). METHODS Patients with ROP who underwent IVC injection in Zhujiang Hospital from June 2015 to July 2016 were studied retrospectively. The primary outcome was defined as the regression of plus disease. The secondary outcomes were defined as the presence of recurrence, number of injections and the final regression of disease. RESULTS A total of 48 eyes of 24 patients with ROP were included. Among them, 9 eyes of 5 patients had zone I ROP, 35 eyes of 18 patients had zone II ROP and 4 eyes of 2 patients had aggressive posterior ROP. The mean gestational age was 28.5±1.6 weeks, the mean birth weight was 1209.6±228.6 g, the mean postmenstrual age of first injection was 34.2±1.9 weeks and the mean follow-up period was 31.0±4.7 weeks. Forty of 48 eyes (83.3%) received IVC only once, and the regression of plus disease occurred at an average of 3.5±1.5 weeks after the first injection of conbercept. For eight recurrent eyes (16.7%), four eyes received a second IVC and the remaining four eyes received laser photocoagulation, and the regression of plus disease occurred in 3 weeks. No lens opacity, vitreous haemorrhage, entophthalmia or retinal detachment was observed during follow-up. CONCLUSION IVC injection is an effective treatment for ROP.
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Affiliation(s)
- Yichen Bai
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Huanjie Nie
- Department of Gynecology, Liwan Chinese Traditional Medicine Hospital, Guangzhou, China
| | - Shiyu Wei
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaohe Lu
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaoyun Ke
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xuejun Ouyang
- Department of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Songfu Feng
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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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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Wu L. The omnipresence of vascular endothelial growth factor in retinal diseases. Taiwan J Ophthalmol 2019; 9:213-215. [PMID: 31942425 PMCID: PMC6947743 DOI: 10.4103/tjo.tjo_73_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Kang HG, Choi EY, Byeon SH, Kim SS, Koh HJ, Lee SC, Kim M. Intravitreal ranibizumab versus laser photocoagulation for retinopathy of prematurity: efficacy, anatomical outcomes and safety. Br J Ophthalmol 2018; 103:1332-1336. [DOI: 10.1136/bjophthalmol-2018-312272] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 10/29/2018] [Accepted: 10/30/2018] [Indexed: 11/04/2022]
Abstract
Background/AimsTo compare the efficacy, anatomical outcomes and complications of intravitreal ranibizumab with those of laser photocoagulation for retinopathy of prematurity (ROP).MethodsThis is a retrospective case series of 314 eyes from 165 infants diagnosed with type I ROP and treated with either laser photocoagulation (161 eyes) or intravitreal ranibizumab (0.25 mg/0.025 mL) injection (153 eyes) between January 2006 and December 2016 in a tertiary referral-based hospital. The main outcome was the rate of recurrence requiring additional treatment. Secondary outcomes included the incidence of major complications and final refractive error.ResultsThe mean follow-up was 36.3±31.9 months. Recurrences requiring further intervention were noted in 22 (13.7%) laser-treated and 15 (9.8%) ranibizumab-treated eyes (p=0.196). Retinal detachment (8 vs 1, p=0.037) and macular dragging (7 vs 1, p=0.039) were observed in the laser-treated and injection-treated groups, respectively, but no systemic or neurodevelopmental adverse events were reported. In the ranibizumab group, 95.6% showed fully vascularised retinas. Multivariate analyses revealed that birth weight (OR 0.993, p=0.023) and higher ROP stage (OR 11.222, p=0.008) influenced the incidence of major complications.ConclusionIntravitreal ranibizumab for ROP appears to achieve similar therapeutic effects than did laser photocoagulation, but with fewer surgical complications such as retinal detachment or macular dragging.
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Kang HG, Choi EY, Byeon SH, Kim SS, Koh HJ, Lee SC, Kim M. Anti-vascular Endothelial Growth Factor Treatment of Retinopathy of Prematurity: Efficacy, Safety, and Anatomical Outcomes. KOREAN JOURNAL OF OPHTHALMOLOGY 2018; 32:451-458. [PMID: 30549468 PMCID: PMC6288015 DOI: 10.3341/kjo.2018.0011] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 03/19/2018] [Indexed: 12/22/2022] Open
Abstract
PURPOSE To investigate the efficacy, safety, and anatomical outcomes associated with intravitreal anti-vascular endothelial growth factor (VEGF) treatment of retinopathy of prematurity (ROP). METHODS We performed a retrospective review of intravitreal anti-VEGF (bevacizumab or ranibizumab) treatment of 153 eyes (83 infants) diagnosed with ROP at two tertiary hospitals from June 2011 to January 2017. The primary outcome was the rate of recurrence requiring additional treatment; secondary outcomes included incidence of major complications and final refractive error. RESULTS A total of 101 eyes were treated with bevacizumab, and 52 with ranibizumab. The bevacizumab and ranibizumab groups were characterized by mean birthweights of 941.8 ± 296.1 and 1,257.7 ± 514.5 g, gestational ages at birth of 26.9 ± 1.9 and 28.1 ± 3.2 weeks, and postmenstrual ages at treatment of 40.4 ± 2.4 and 39.2 ± 2.3 weeks, respectively. The two groups differed significantly in birthweights and gestational ages at birth, but not in postmenstrual ages at treatment. The mean follow-up duration was 30.9 ± 18.4 months for the bevacizumab group, and 13.9 ± 12.5 months for ranibizumab. More cases were classified as zone 1 ROP in the ranibizumab group (44.2% vs. 11.9%, p < 0.001). Major surgical interventions included scleral encircling and vitrectomy (one and two eyes, respectively, both in the bevacizumab group). Retinal detachment was noted in one eye treated with bevacizumab. There was no significant difference in the most recent spherical equivalence for the two groups (+0.10 ± 3.66 and +0.22 ± 3.00 diopters for bevacizumab and ranibizumab, respectively). Univariable analysis revealed that only ROP stage influenced the occurrence of major complications (odds ratio, 9.046; p = 0.012). CONCLUSIONS Intravitreal anti-VEGF treatment of ROP with both bevacizumab and ranibizumab achieved stable retinal vascularization with a low rate of complications and recurrence. Ranibizumab achieved similar anatomical outcomes as bevacizumab, without additional risk for major complications.
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Affiliation(s)
- Hyun Goo Kang
- Department of Ophthalmology, Institute of Vision Research, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Young Choi
- Department of Ophthalmology, Institute of Vision Research, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Suk Ho Byeon
- Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Soo Kim
- Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyoung Jun Koh
- Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Chul Lee
- Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Min Kim
- Department of Ophthalmology, Institute of Vision Research, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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Roohipoor R, Torabi H, Karkhaneh R, Riazi-Eafahani M. Comparison of intravitreal bevacizumab injection and laser photocoagulation for type 1 zone II retinopathy of prematurity. J Curr Ophthalmol 2018; 31:61-65. [PMID: 30899848 PMCID: PMC6407151 DOI: 10.1016/j.joco.2018.10.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2018] [Revised: 10/15/2018] [Accepted: 10/22/2018] [Indexed: 11/25/2022] Open
Abstract
Purpose To compare the efficacy of intravitreal bevacizumab (IVB) injection with conventional laser photocoagulation in eyes with type 1 zone II retinopathy of prematurity (ROP). Methods Preterm infants with type 1 ROP in zone II (stage 2 or 3 ROP with plus disease) were randomly assigned to intravitreal injection of 0.625 mg/0.025 ml bevacizumab (Group 1) or laser photocoagulation (Group 2). Patients were followed weekly for 4 weeks and then biweekly till 90 weeks gestational age. Also, spherical and cylindrical refractive errors were compared at 90 weeks postmenstrual age (PMA). Results A total of 116 preterm infants (232 eyes) were treated and completed the follow-up period. IVB injection was done in 154 eyes (77 cases), and laser photocoagulation was done in 78 eyes (39 cases). ROP regressed after single IVB injection in 149 eyes (96.8%) and in 5 eyes (3.2%) after the second injection. Cataract developed in one eye (0.63%) after IVB injection. ROP regressed in 94.7% of treated eyes (76 eyes) in the laser photocoagulation group; however, retinal fold and traction developed in 2 eyes. Spherical and also cylindrical refractive errors had no significant difference. Conclusions Both IVB injection and laser photocoagulation are effective methods for the treatment of type 1 zone II ROP. However, re-treatment requirement may be higher in the IVB injection group. IVB re-injection is an effective option for re-treatment in persistent cases.
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Affiliation(s)
- Ramak Roohipoor
- Eye Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Torabi
- Eye Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Health Management Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Reza Karkhaneh
- Eye Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Lee YS, See LC, Chang SH, Wang NK, Hwang YS, Lai CC, Chen KJ, Wu WC. Macular Structures, Optical Components, and Visual Acuity in Preschool Children after Intravitreal Bevacizumab or Laser Treatment. Am J Ophthalmol 2018; 192:20-30. [PMID: 29753851 DOI: 10.1016/j.ajo.2018.05.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Revised: 04/28/2018] [Accepted: 05/03/2018] [Indexed: 01/19/2023]
Abstract
PURPOSE To investigate the macular structures, optical components, and visual acuity in preschool-aged children with a history of type I retinopathy of prematurity who underwent either intravitreal bevacizumab (IVB), laser, or a combination of treatments. DESIGN Comparative interventional case series. METHODS Setting: A referred medical center in Taiwan. STUDY POPULATION Eighty eyes from 42 patients (33 IVB-treated eyes from 17 children, 24 laser-treated eyes from 13 children, and 23 laser + IVB-treated eyes from 12 children). OBSERVATION PROCEDURE Spectral-domain optical coherence tomography. MAIN OUTCOME MEASURES The retinal thickness in the foveal area and the associated morphologic changes in foveal depression. RESULTS Compared with the laser-treated and laser + IVB-treated eyes, the IVB-treated eyes had less myopia and deeper anterior chamber depths but presented similar axial lengths and corneal curvatures (P = .001, P = .002, P = .95, and P = .16, respectively). The IVB-treated eyes had significantly thinner foveal, parafoveal, and perifoveal retinal thicknesses (P < .01 for all) and a higher incidence of foveal depression than the laser- or laser + IVB-treated eyes. The macular and subfoveal choroidal thicknesses did not differ among the groups (P = .21 and P = .63, respectively). Moreover, compared with the eyes treated with laser or laser + IVB, the IVB-treated eyes had better uncorrected visual acuity, although a significant difference was not observed in best-corrected visual acuity (P = .008 and P = .29, respectively). CONCLUSIONS Compared with laser therapy, IVB-treated eyes were associated with deeper anterior chamber depths and thinner foveal, parafoveal, and perifoveal thicknesses. Moreover, these IVB-treated eyes had fewer refractive errors and better uncorrected visual acuity.
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Affiliation(s)
- Yung-Sung Lee
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Lai-Chu See
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Biostatistics Core Laboratory, Molecular Medicine Research Centre, Chang Gung University, Taoyuan, Taiwan
| | - Shu-Hao Chang
- Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Nan-Kai Wang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yih-Shiou Hwang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Chun Lai
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kuan-Jen Chen
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Jiang C, Ruan L, Zhang J, Huang X. Inhibitory Effects On Retinal Neovascularization by Ranibizumab and sTie2-Fc in An Oxygen-Induced Retinopathy Mouse Model. Curr Eye Res 2018; 43:1190-1198. [PMID: 29857790 DOI: 10.1080/02713683.2018.1484144] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
PURPOSE To study retinal neovascularization (RNV) inhibition by intravitreal injections (IVs) of ranibizumab, sTie2 fusion protein (sTie2-Fc), and a combined therapy in an oxygen-induced retinopathy (OIR) model. MATERIALS AND METHODS An OIR mouse model was used to simulate RNV in retinopathy of prematurity (ROP); and the effect of blocking the angiopoietin (Ang) and its receptor (Tie2) and the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling pathways was compared using an IV of sTie2-Fc (Ang inhibitor) and/or ranibizumab (aVEGF antagonist). The effects were assessed using fluorescein isothiocyanate (FITC)-dextran cardiac perfusion, isolectin B4 (IB4) staining with whole retinal mounting, and hematoxylin and eosin (HE) staining to count the endothelial cells (ECs) that broke through the internal limiting membrane (ILM). The mRNA and protein levels of VEGF-A, VEGFR-2, Ang1, Ang2, and Tie2 were also determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analysis. RESULTS Compared with the control group injected with phosphate-buffered saline (PBS), all three experimental groups, ranibizumab, sTie2-Fc, and ranibizumab + sTie2-Fc, had a significant decrease in micro-vessel densities and neovascular clusters, and fewer ECs broke through the ILM (all p < 0.05). The non-perfusion areas decreased in both mono-treated groups, although the combined therapy had larger non-perfusion areas. All three treatments decreased the mRNA and protein levels of VEGFA, Ang1, and Tie2. CONCLUSION In this study, it was confirmed that blocking the Ang/Tie2 and/or VEGF/VEGFR pathways could inhibit RNV and decrease abnormal micro-vessel density; and the mono-blockage of Ang/Tie2 might cause a smaller non-perfusion area.
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Affiliation(s)
- Chen Jiang
- a Eye and ENT Hospital , Shanghai Medical College, Fudan University , Shanghai , People's Republic of China.,b Shanghai Key Laboratory of Visual Impairment and Restoration , Fudan University , Shanghai , People's Republic of China
| | - Lu Ruan
- a Eye and ENT Hospital , Shanghai Medical College, Fudan University , Shanghai , People's Republic of China
| | - Juan Zhang
- a Eye and ENT Hospital , Shanghai Medical College, Fudan University , Shanghai , People's Republic of China.,b Shanghai Key Laboratory of Visual Impairment and Restoration , Fudan University , Shanghai , People's Republic of China
| | - Xin Huang
- a Eye and ENT Hospital , Shanghai Medical College, Fudan University , Shanghai , People's Republic of China
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Fouzdar Jain S, Song HH, Al-Holou SN, Morgan LA, Suh DW. Retinopathy of prematurity: preferred practice patterns among pediatric ophthalmologists. Clin Ophthalmol 2018; 12:1003-1009. [PMID: 29881255 PMCID: PMC5978463 DOI: 10.2147/opth.s161504] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Purpose The treatment of retinopathy of prematurity (ROP) is not standardized and can vary significantly between providers. This study aims to determine preferred practices in treating ROP by globally surveying pediatric ophthalmologists. Methods Between January and February 2017, an international pediatric ophthalmology interest group was invited to complete an anonymous survey of 18 questions. The main objectives were to determine the preferred first line of treatment for ROP, the preferred dosage of intravitreal bevacizumab (IVB) used, and the outcome and possible complications following bevacizumab injection. Results Out of 101 pediatric ophthalmologists, 72 (71.8%) stated that they had direct involvement in the treatment of ROP. When presented with type 1 ROP which requires treatment, 69 ophthalmologists (68.3%) stated that they prefer laser treatment over bevacizumab, and 33 ophthalmologists (32.7%) stated they would recommend bevacizumab as a first choice. Ninety-three ophthalmologists (92.1%) reported the success of 1 laser treatment between 75% and 100%, and 35 ophthalmologists (34.7%) perceive bevacizumab to be 75%–100% successful. Half dose of adult-prescribed bevacizumab at 0.625 mg/0.05 mL was preferred by 47 of the ophthalmologists (46.5%). No cases of endophthalmitis were reported with intravitreal injection. Conclusion Laser photoablation remains the preferred mode of treatment for ROP among surveyed ophthalmologists across the world. Though bevacizumab is currently being used, this form of treatment is not as common, primarily due to the unknown safety profile and potential long-term ramifications of the drug.
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Affiliation(s)
| | - Helen H Song
- Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA
| | - Shaza N Al-Holou
- Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA
| | - Linda A Morgan
- Ophthalmology Department, Children's Hospital and Medical Center, Omaha, NE, USA
| | - Donny W Suh
- Ophthalmology Department, Children's Hospital and Medical Center, Omaha, NE, USA.,Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA
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Refractive and Biometric Outcomes in Patients with Retinopathy of Prematurity Treated with Intravitreal Injection of Ranibizumab as Compared with Bevacizumab: A Clinical Study of Correction at Three Years of Age. J Ophthalmol 2018; 2018:4565216. [PMID: 29713524 PMCID: PMC5866885 DOI: 10.1155/2018/4565216] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 01/14/2018] [Indexed: 11/17/2022] Open
Abstract
Purpose To compare refractive and biometric outcomes in patients with type 1 retinopathy of prematurity (ROP) treated with intravitreal injection of ranibizumab (IVR) versus bevacizumab (IVB), at a corrected age of 3 years. Methods A retrospective case series compared cycloplegic refractive statuses and biometric statuses in patients who received either IVR or IVB for type 1 ROP, from April 2011 to April 2014. Results A total of 62 eyes (33 patients) with type 1 ROP were evaluated (26 eyes in 13 IVR patients and 36 eyes in 20 IVB patients). There were no differences in birth statuses including gestational age and birth body weight between the two groups. The prevalence of refractive error greater than 1 D was higher in the IVB group (p = 0.03), and there was a higher prevalence of high myopia (<-5.0 D, p = 0.03) in the IVB group. Comparisons in biometric finding showed that IVB patients had shallower anterior chamber depth (p = 0.01). Conclusion Both IVR and IVB showed low refractive errors, even followed at the corrected age of 3 years. No difference was noted between the two groups in refractive statuses. However, IVB was associated with shallower anterior chamber and higher prevalence of refractive error at the corrected age of 3 years. This trial is registered with NCT03334513.
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Roohipoor R, Karkhaneh R, Riazi-Esfahani M, Dastjani Farahani A, Khodabandeh A, Ebrahimi Adib N, Imani M, Khojasteh Jafari H, Riazi-Esfahani H, Hosseinpour J, Zarei M, Ghasemi H, Mirghorbani M, Yaseri M, Davoudi S, Modjtahedi BS. Comparison of Intravitreal Bevacizumab and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity. Ophthalmol Retina 2018; 2:942-948. [PMID: 31047228 DOI: 10.1016/j.oret.2018.01.017] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Revised: 01/25/2018] [Accepted: 01/25/2018] [Indexed: 10/17/2022]
Abstract
PURPOSE To compare the outcomes of patients with type I retinopathy of prematurity (ROP) treated with either intravitreal bevacizumab (IVB) or retinal laser photocoagulation (RLP). DESIGN Retrospective case series. PARTICIPANTS Infants treated for type I ROP with IVB or RLP. METHODS Patients who were born between January 2011 and December 2014 and were treated in Farabi Eye Hospital were included. The outcomes were stratified and analyzed, based on the treatment type and ROP zone. MAIN OUTCOME MEASURES Need for retreatment, time to regression, refractive errors, retinal adverse anatomic outcomes, and rate of complications. RESULTS Five hundred twenty-three patients were treated for type 1 ROP, of whom 493 (986 eyes) met inclusion criteria. Seven hundred twenty-four eyes (73.4%) received IVB, and 262 eyes (26.5%) received RLP. Re-treatment (because of recurrent or persistent retinopathy) occurred in 14.4% (106/724) of eyes initially treated with IVB and in 8.8% (23/262) eyes initially treated with RLP (P = 0.065). Re-treatment was not significantly different between the 2 groups for patients with zone I disease (P = 0.978). Re-treatment rate was considerably higher in patients with zone II disease treated with IVB (69/558 [12.3%]) compared with those treated with RLP (20/251 [7.9%]; P = 0.017). In the IVB group, 82.8% and 53.4% of eyes showed an avascular area in zone III (despite ROP regression) at 1 and 2 years after treatment, respectively. The spherical power and the spherical equivalent were significantly higher in eyes treated with RLP (-1.31±2.83 diopters [D] and -2.84±2.77 D, respectively) than eyes treated with IVB (0.19±3.21 D and -1.26±3.19 D, respectively; P = 0.016 and P = 0.007, respectively). Differences in astigmatic power were not significant. CONCLUSIONS Both IVB and RLP are effective treatments for type 1 ROP. Longer follow-up time is necessary for infants treated with IVB. More patients with zone II disease treated with RLP achieved disease regression after a single treatment than those who received IVB, although outcomes after re-treatment were comparable except for a greater refractive error in patients treated with RLP.
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Affiliation(s)
- Ramak Roohipoor
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Karkhaneh
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Riazi-Esfahani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, California
| | - Afsar Dastjani Farahani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Khodabandeh
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Nazanin Ebrahimi Adib
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Marjan Imani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hassan Khojasteh Jafari
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Riazi-Esfahani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Jamaleddin Hosseinpour
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Zarei
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamed Ghasemi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Mirghorbani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Yaseri
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Samaneh Davoudi
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
| | - Bobeck S Modjtahedi
- Department of Ophthalmology, Southern California Permanente Medical Group, Baldwin Park, California; Eye Monitoring Center, Kaiser Permanente Southern California, Baldwin Park, California
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Sankar MJ, Sankar J, Chandra P, Cochrane Neonatal Group. Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity. Cochrane Database Syst Rev 2018; 1:CD009734. [PMID: 29308602 PMCID: PMC6491066 DOI: 10.1002/14651858.cd009734.pub3] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis in foetal life. Researchers have recently attempted to use anti-VEGF agents for the treatment of retinopathy of prematurity (ROP), a vasoproliferative disorder. The safety and efficacy of these agents in preterm infants with ROP is currently uncertain. OBJECTIVES To evaluate the efficacy and safety of anti-VEGF drugs when used either as monotherapy, that is without concomitant cryotherapy or laser therapy, or in combination with planned cryo/laser therapy in preterm infants with type 1 ROP (defined as zone I any stage with plus disease, zone I stage 3 with or without plus disease, or zone II stage 2 or 3 with plus disease). SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11), MEDLINE (1966 to 11 December 2016), Embase (1980 to 11 December 2016), CINAHL (1982 to 11 December 2016), and conference proceedings. SELECTION CRITERIA Randomised or quasi-randomised controlled trials that evaluated the efficacy or safety of administration, or both, of anti-VEGF agents compared with conventional therapy in preterm infants with ROP. DATA COLLECTION AND ANALYSIS We used standard Cochrane and Cochrane Neonatal methods for data collection and analysis. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS Six trials involving a total of 383 infants fulfilled the inclusion criteria. Five trials compared intravitreal bevacizumab (n = 4) or ranibizumab (n = 1) with conventional laser therapy (monotherapy), while the sixth study compared intravitreal pegaptanib plus conventional laser therapy with laser/cryotherapy (combination therapy).When used as monotherapy, bevacizumab/ranibizumab did not reduce the risk of complete or partial retinal detachment (3 studies; 272 infants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.21 to 5.13; risk difference (RD) 0.00, 95% CI -0.04 to 0.04; very low-quality evidence), mortality before discharge (2 studies; 229 infants; RR 1.50, 95% CI 0.26 to 8.75), corneal opacity requiring corneal transplant (1 study; 286 eyes; RR 0.34, 95% CI 0.01 to 8.26), or lens opacity requiring cataract removal (3 studies; 544 eyes; RR 0.15, 95% CI 0.01 to 2.79). The risk of recurrence of ROP requiring retreatment also did not differ between groups (2 studies; 193 infants; RR 0.88, 95% CI 0.47 to 1.63; RD -0.02, 95% CI -0.12 to 0.07; very low-quality evidence). Subgroup analysis showed a significant reduction in the risk of recurrence in infants with zone I ROP (RR 0.15, 95% CI 0.04 to 0.62), but an increased risk of recurrence in infants with zone II ROP (RR 2.53, 95% CI 1.01 to 6.32). Pooled analysis of studies that reported eye-level outcomes also revealed significant increase in the risk of recurrence of ROP in the eyes that received bevacizumab (RR 5.36, 95% CI 1.22 to 23.50; RD 0.10, 95% CI 0.03 to 0.17). Infants who received intravitreal bevacizumab had a significantly lower risk of refractive errors (very high myopia) at 30 months of age (1 study; 211 eyes; RR 0.06, 95% CI 0.02 to 0.20; RD -0.40, 95% CI -0.50 to -0.30; low-quality evidence).When used in combination with laser therapy, intravitreal pegaptanib was found to reduce the risk of retinal detachment when compared to laser/cryotherapy alone (152 eyes; RR 0.26, 95% CI 0.12 to 0.55; RD -0.29, 95% CI -0.42 to -0.16; low-quality evidence). The incidence of recurrence of ROP by 55 weeks' postmenstrual age was also lower in the pegaptanib + laser therapy group (76 infants; RR 0.29, 95% CI 0.12 to 0.7; RD -0.35, 95% CI -0.55 to -0.16; low-quality evidence). There was no difference in the risk of perioperative retinal haemorrhages between the two groups (152 eyes; RR 0.62, 95% CI 0.24 to 1.56; RD -0.05, 95% CI -0.16 to 0.05; very low-quality evidence). However, the risk of delayed systemic adverse effects with any of the three anti-VEGF drugs is not known. AUTHORS' CONCLUSIONS Implications for practice: Intravitreal bevacizumab/ranibizumab, when used as monotherapy, reduces the risk of refractive errors during childhood but does not reduce the risk of retinal detachment or recurrence of ROP in infants with type 1 ROP. While the intervention might reduce the risk of recurrence of ROP in infants with zone I ROP, it can potentially result in higher risk of recurrence requiring retreatment in those with zone II ROP. Intravitreal pegaptanib, when used in conjunction with laser therapy, reduces the risk of retinal detachment as well as the recurrence of ROP in infants with type 1 ROP. However, the quality of the evidence was very low to low for most outcomes due to risk of detection bias and other biases. The effects on other critical outcomes and, more importantly, the long-term systemic adverse effects of the drugs are not known. Insufficient data precludes strong conclusions favouring routine use of intravitreal anti-VEGF agents - either as monotherapy or in conjunction with laser therapy - in preterm infants with type 1 ROP. IMPLICATIONS FOR RESEARCH Further studies are needed to evaluate the effect of anti-VEGF agents on structural and functional outcomes in childhood and delayed systemic effects including adverse neurodevelopmental outcomes.
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Affiliation(s)
- Mari Jeeva Sankar
- All India Institute of Medical SciencesNewborn Health Knowledge Centre, WHO Collaborating Centre for Training and Research in Newborn Care, Department of PediatricsDelhiIndia
| | - Jhuma Sankar
- All India Institute of Medical SciencesDepartment of PediatricsNew DelhiNew DelhiIndia
| | - Parijat Chandra
- Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences (AIIMS)New DelhiDelhiIndia110029
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Karkhaneh R, Torabi H, Khodabande A, Roohipoor R, Riazi-Esfahani M. Efficacy of Intravitreal Bevacizumab for the Treatment of Zone I Type 1 Retinopathy of Prematurity. J Ophthalmic Vis Res 2018; 13:29-33. [PMID: 29403586 PMCID: PMC5782452 DOI: 10.4103/jovr.jovr_198_16] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Purpose To describe the efficacy of intravitreal bevacizumab for the treatment of type 1 retinopathy of prematurity (ROP) in zone I. Methods Preterm infants with type 1 ROP in zone I (zone I ROP, any stage with plus disease or zone I ROP, stage 3 without plus disease) were enrolled in this prospective study. Intravitreal bevacizumab (0.625 mg/0.025 ml) was injected under topical anesthesia. Patients were followed weekly for 4 weeks and then biweekly till 90 weeks gestational age. Results Seventy eyes of 35 patients with type 1 ROP in zone I were enrolled. At a gestational age of 90 weeks, ROP regressed with complete or near-complete peripheral retinal vascularization, in 82.9% of eyes after a single injection and in 92.9% of eyes after up to two injections. In five eyes (7.1%), ROP progressed to stage 4B or 5, so surgical management was required. There were no major complications such as endophthalmitis, cataract, or vitreous hemorrhage after injection. Conclusion Intravitreal bevacizumab injection is an effective method for the management of patients with Zone I ROP requiring treatment; however, some cases may progress to more advanced stages and require surgical management. Close monitoring for recurrence or progression is necessary. Eyes with persistent zone I ROP may progress to advanced stages when treated with intravitreal bevacizumab injection and re-treatment may be needed.
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Affiliation(s)
- Reza Karkhaneh
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Department of Ophthalmology, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Torabi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Department of Ophthalmology, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Alireza Khodabande
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Department of Ophthalmology, Tehran University of Medical Sciences, Tehran, Iran
| | - Ramak Roohipoor
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Department of Ophthalmology, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Riazi-Esfahani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Department of Ophthalmology, Tehran University of Medical Sciences, Tehran, Iran
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Tran KD, Cernichiaro-Espinosa LA, Berrocal AM. Management of Retinopathy of Prematurity--Use of Anti-VEGF Therapy. Asia Pac J Ophthalmol (Phila) 2018; 7:56-62. [PMID: 29376233 DOI: 10.22608/apo.2017436] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Although laser photocoagulation re-mains the gold standard for treating threshold and prethreshold disease (type 1 ROP), the off-label use of anti‒vascular endothelial growth factor (anti-VEGF) therapy to treat ROP is increasing. Benefits include acute regression of ROP, growth of retinal vasculature beyond the demarcation line, lesser degree of myopia and peripheral visual field loss, and avoidance of sedation and intubation required for laser. However, controversies regarding anti-VEGF in this vulnerable population persist including choice of anti-VEGF agent, dosing, systemic absorption, safety, and late recurrence. This review updates recent evidence regarding the use of anti-VEGF therapy in the management of ROP.
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Affiliation(s)
- Kimberly D Tran
- Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida
| | | | - Audina M Berrocal
- Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
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Changes in systemic vascular endothelial growth factor levels after intravitreal injection of aflibercept in infants with retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2017; 256:479-487. [PMID: 29290015 DOI: 10.1007/s00417-017-3878-4] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Revised: 12/07/2017] [Accepted: 12/14/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND To investigate the levels of VEGF in the systemic circulation of patients with type 1 ROP who received intravitreal injections of 1 mg (0.025 mL) aflibercept (IVA) or 0.625 mg (0.025 mL) bevacizumab (IVB). METHODS Patients who had type 1 ROP and received either IVA or IVB were enrolled in this prospective study. Serum and plasma samples were collected prior to and up to 12 weeks after IVB or IVA treatment. The serum and plasma VEGF levels were measured using enzyme-linked immunosorbent assays (ELISAs), and the platelet levels in the blood were also quantified. The serum and plasma levels of VEGF, as well as the ratio of VEGF to platelet count (VEGF/PLT) were measured prior to and up to 12 weeks after anti-VEGF treatment. RESULTS In total, 14 patients with type 1 ROP were enrolled in this study; five patients received IVA, and nine patients received IVB. Following either IVA or IVB treatment, all the eyes (100%) showed complete resolution of ROP-induced abnormal neovascularization and presented continued vascularization toward the peripheral retina. Compared to baseline, the serum VEGF levels were significantly reduced in the ROP patients up to 12 weeks after either IVA or IVB treatments (all P < 0.05). At 2, 4, and 8 weeks after intravitreal injection, the serum VEGF levels were more suppressed in the IVB group than in the IVA group (P = 0.039, P = 0.004, and P = 0.003, respectively). The serum VEGF/PLT ratio after IVA or IVB showed similar reductions and trends as the serum VEGF data. Changes in the plasma VEGF levels could not be properly assessed because some of the samples had VEGF levels below the detection limit of the ELISA. CONCLUSIONS Serum VEGF levels and the VEGF/PLT ratio in patients with type 1 ROP were suppressed for 3 months after treatment with either IVA or IVB, but the suppression of systemic VEGF was more pronounced in patients treated with IVB than those treated with IVA.
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