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Nakagawa Y, Murayama Y, Suzuki Y, Uchiyama A, Suzuki T. Therapeutic outcomes of ranibizumab for zone ii stage 2 retinopathy of prematurity with plus disease. Jpn J Ophthalmol 2025:10.1007/s10384-025-01199-y. [PMID: 40377801 DOI: 10.1007/s10384-025-01199-y] [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: 10/10/2024] [Accepted: 03/09/2025] [Indexed: 05/18/2025]
Abstract
PURPOSE This study aimed to evaluate the efficacy of intravitreal injections of ranibizumab (IVR) in treating zone II stage 2 retinopathy of prematurity with plus disease (ROP II2+) in preterm infants, focusing on two primary outcomes: reactivation and persistent avascular retina (PAR). STUDY DESIGN Retrospective and consecutive case series. METHODS This retrospective study reviewed the medical records of preterm infants treated with IVR at Tokai University hospital between December 2019 and September 2023. Data on reactivation, PAR, and other clinical outcomes were analyzed using generalized estimating equations to account for correlations between eyes. RESULTS Thirty eyes from 16 infants received IVR treatment. Following initial IVR all eyes achieved remission for over one year with IVR alone. Forty percent of these eyes required subsequent treatment due to reactivation, with a median reactivation time of 70 days. One year after initial IVR, PAR was observed in 11 out of the 30 eyes. Lower birth weight was associated with a tendency toward reactivation, and it also showed a significant correlation with the development of PAR. CONCLUSIONS This research supports the effectiveness of IVR for ROP II2+ over a one-year period. The links between lower birth weight and both reactivation and PAR might guide refinements in therapeutic strategies.
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Affiliation(s)
- Yoshihiro Nakagawa
- Department of Ophthalmology, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa, 259-1193, Japan.
| | - Yoshifumi Murayama
- Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan
| | - Yasuyuki Suzuki
- Department of Ophthalmology, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa, 259-1193, Japan
| | - Atsushi Uchiyama
- Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan
| | - Takahiro Suzuki
- Department of Ophthalmology, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa, 259-1193, Japan
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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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Lee CC, Chiang MC, Chu SM, Wu WC, Ho MMC, Lien R. Clinical Risk Factors for Retinopathy of Prematurity Reactivation after Intravitreal Antivascular Endothelial Growth Factor Injection. J Pediatr 2024; 273:113913. [PMID: 38218371 DOI: 10.1016/j.jpeds.2024.113913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 12/15/2023] [Accepted: 01/09/2024] [Indexed: 01/15/2024]
Abstract
OBJECTIVE To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of antivascular endothelial growth factor (VEGF) agents. STUDY DESIGN Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into 2 groups: those with and without ROP reactivation. Information on ROP variables and patient variables were analyzed using multivariable logistic regression. RESULTS A total of 114 infants with 223 eyes were enrolled in the study. The ROP reactivation rate was 11.4% of infants (9.9% of eyes). The mean duration of reactivation was 84 ± 45 days. Among the 223 eyes treated with IVI, reactivation rates were 6% for bevacizumab, 13.9% for aflibercept, and 22.2% for ranibizumab. A multivariable regression model showed that ranibizumab was an independent risk factor (OR 11.4, P = .008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR 13.8, P = .003), patent ductus arteriosus ligation (OR 10.7, P = .032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR 7.0, P = .018). CONCLUSIONS All anti-VEGF agents carry a risk of ROP reactivation, with the risk being greater with ranibizumab 0.25 mg than with bevacizumab 0.625 mg. Reactivation of ROP should be assessed vigilantly, especially in those infants with increased risks. Future research to determine the optimal anti-VEGF selection and dosage in high-risk infants is warranted.
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Affiliation(s)
- Chien-Chung Lee
- Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Ming-Chou Chiang
- Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Shih-Ming Chu
- Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Margaret Ming-Chih Ho
- Department of Ophthalmology, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Reyin Lien
- Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
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Obata S, Matsumoto R, Iwasa M, Kakinoki M, Sawada O, Sawada T, Saishin Y, Ohji M. Visual field after anti-vascular endothelial growth factor therapy and laser treatment for retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2023; 261:3207-3213. [PMID: 37674073 DOI: 10.1007/s00417-023-06227-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 08/08/2023] [Accepted: 08/26/2023] [Indexed: 09/08/2023] Open
Abstract
PURPOSE To evaluate the visual field after anti-vascular endothelial growth factor (VEGF) therapy and laser treatment for retinopathy of prematurity. METHOD Retrospective cohort study. Infants with retinopathy of prematurity treated by anti-VEGF therapy or laser treatment were included in the study. Degrees of visual field in eight directions examined by Goldmann perimeter (intensity, 1000 apostilb; size, V4e = 64 mm2) were compared between the anti-VEGF therapy and laser treatment groups. The visual acuity (VA) and spherical equivalent refraction were also compared between the two groups. RESULTS Nine eyes with anti-VEGF therapy and 12 eyes with laser treatment were enrolled in the analysis. The total, upper, nasal upper, nasal, nasal lower, temporal lower, and temporal upper visual fields were significantly wider in the eyes with anti-VEGF therapy than in those with laser treatment (496 vs 416, P = .002; 53 vs 45, P = .008; 56 vs 43, P = .003; 58 vs 39, P < .001; 55 vs 44, P = .01; 72 vs 65, P = .01; and 62 vs 56, P = .03, respectively). The logarithm of the minimum angle of resolution VA tended to be better in the eyes with anti-VEGF therapy than in those with laser treatment (0.01 vs 0.15, P = .06). Eyes with anti-VEGF therapy had significantly lower myopia than those with laser treatment (spherical equivalent refraction: -0.72 vs -5.7, P = .001). CONCLUSION Anti-VEGF therapy may provide a wider visual field, better VA, and less myopia compared with laser treatment.
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Affiliation(s)
- Shumpei Obata
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan.
| | - Riko Matsumoto
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan
| | - Maki Iwasa
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan
| | - Masashi Kakinoki
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan
| | - Osamu Sawada
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan
| | - Tomoko Sawada
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan
| | - Yoshitsugu Saishin
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan
| | - Masahito Ohji
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan
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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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Huang F, He Y, Zhang M, Luo K, Li J, Li J, Zhang X, Dong X, Tang J. Progress in Research on Stem Cells in Neonatal Refractory Diseases. J Pers Med 2023; 13:1281. [PMID: 37623531 PMCID: PMC10455340 DOI: 10.3390/jpm13081281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/03/2023] [Accepted: 08/16/2023] [Indexed: 08/26/2023] Open
Abstract
With the development and progress of medical technology, the survival rate of premature and low-birth-weight infants has increased, as has the incidence of a variety of neonatal diseases, such as hypoxic-ischemic encephalopathy, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity. These diseases cause severe health conditions with poor prognoses, and existing control methods are ineffective for such diseases. Stem cells are a special type of cells with self-renewal and differentiation potential, and their mechanisms mainly include anti-inflammatory and anti-apoptotic properties, reducing oxidative stress, and boosting regeneration. Their paracrine effects can affect the microenvironment in which they survive, thereby affecting the biological characteristics of other cells. Due to their unique abilities, stem cells have been used in treating various diseases. Therefore, stem cell therapy may open up the possibility of treating such neonatal diseases. This review summarizes the research progress on stem cells and exosomes derived from stem cells in neonatal refractory diseases to provide new insights for most researchers and clinicians regarding future treatments. In addition, the current challenges and perspectives in stem cell therapy are discussed.
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Affiliation(s)
- Fangjun Huang
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
| | - Yang He
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
| | - Meng Zhang
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
| | - Keren Luo
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
| | - Jiawen Li
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
| | - Jiali Li
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
| | - Xinyu Zhang
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
| | - Xiaoyan Dong
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
| | - Jun Tang
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
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Yazdanyar A, Cai CL, Aranda JV, Shrier E, Beharry KD. Comparison of Bevacizumab and Aflibercept for Suppression of Angiogenesis in Human Retinal Microvascular Endothelial Cells. Pharmaceuticals (Basel) 2023; 16:939. [PMID: 37513851 PMCID: PMC10383229 DOI: 10.3390/ph16070939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 05/19/2023] [Indexed: 07/30/2023] Open
Abstract
Bevacizumab (Avastin) is a vascular endothelial growth factor (VEGF) inhibitor that is widely used for aggressive posterior retinopathy of prematurity (APROP). Its use is associated with multiple adverse effects. Aflibercept (Eylea) is a VEGFR-1 analogue that is approved for ocular use, but its efficacy for APROP is less studied. We tested the hypothesis that Eylea is as effective as Avastin for suppression of intermittent hypoxia (IH)-induced angiogenesis. Human retinal microvascular endothelial cells (HRECs) were treated with Avastin and low- or high-dose Eylea and exposed to normoxia, hyperoxia (50% O2), or neonatal IH for 24, 48, or 72 h. Cells were assessed for migration and tube formation capacities, as well as biomarkers of angiogenesis and oxidative stress. Both doses of Eylea suppressed migration and tube formation in all oxygen environments, although the effect was not as robust as Avastin. Furthermore, the lower dose of Eylea appeared to be more effective than the higher dose. Eylea induced soluble VEGFR-1 (sVEGFR-1) coincident with high IGF-I levels and decreased Notch/Jagged-1, demonstrating a functional association. Given the role of VEGFR-1 and Notch as guidance cues for vascular sprouting, these data suggest that Eylea may promote normal vascular patterning in a dose-dependent manner.
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Affiliation(s)
- Amirfarbod Yazdanyar
- Department of Ophthalmology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
- Retina Group of New England, Waterford, CT 06385, USA
| | - Charles L Cai
- Department of Ophthalmology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - Jacob V Aranda
- Department of Ophthalmology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
- Department of Pediatrics/Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - Eric Shrier
- Department of Pediatrics/Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - Kay D Beharry
- Department of Ophthalmology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
- Department of Pediatrics/Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
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Retinopathy of Prematurity in the 21st Century and the Complex Impact of Supplemental Oxygen. J Clin Med 2023; 12:jcm12031228. [PMID: 36769876 PMCID: PMC9918247 DOI: 10.3390/jcm12031228] [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: 01/07/2023] [Revised: 01/19/2023] [Accepted: 01/23/2023] [Indexed: 02/05/2023] Open
Abstract
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Not only do the epidemiologic determinants and distributions of patients with ROP vary worldwide, but clinical differences have also been described. The Third Edition of the International Classification of ROP (ICROP3) acknowledges that aggressive ROP (AROP) can occur in larger preterm infants and involve areas of the more anterior retina, particularly in low-resource settings with unmonitored oxygen supplementation. As sub-specialty training programs are underway to address an epidemic of ROP in sub-Saharan Africa, recognizing characteristic retinal pathology in preterm infants exposed to unmonitored supplemental oxygen is important to proper diagnosis and treatment. This paper describes specific features associated with various ROP presentations: oxygen-induced retinopathy in animal models, traditional ROP seen in high-income countries with modern oxygen management, and ROP related to excessive oxygen supplementation in low- and middle-income countries: oxygen-associated ROP (OA-ROP).
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Verma R, Rathi M, Phogat J, Sodhi A, Lochab S. Reactivation of retinopathy of prematurity after intravitreal bevacizumab monotherapy in aggressive posterior retinopathy of prematurity. JOURNAL OF CLINICAL OPHTHALMOLOGY AND RESEARCH 2023. [DOI: 10.4103/jcor.jcor_77_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
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RNA-Seq Provides Insights into VEGF-Induced Signaling in Human Retinal Microvascular Endothelial Cells: Implications in Retinopathy of Prematurity. Int J Mol Sci 2022; 23:ijms23137354. [PMID: 35806359 PMCID: PMC9266443 DOI: 10.3390/ijms23137354] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/19/2022] [Accepted: 06/28/2022] [Indexed: 02/04/2023] Open
Abstract
The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal neovascularization (IVNV). Although intravitreal agents that reduce the bioactivity of vascular endothelial growth factor (VEGF) are used to treat IVNV, concerns exist regarding their effects on intraretinal vascularization. In an experimental ROP model, VEGF receptor 2 (VEGFR2) knockdown in retinal endothelial cells reduced IVNV and promoted intraretinal vascularization, whereas knockdown of a downstream effector, signal transducer and activator of transcription 3 (STAT3) in retinal endothelial cells only reduced IVNV. In this study, we tested the hypothesis that the different pathways involved in VEGF-triggered VEGFR2 signaling and VEGF-triggered STAT3 signaling in retinal endothelial cells would allow us to delineate signaling pathways involved in IVNV from those involved in intraretinal vascularization in ROP. To address our hypothesis, we used RNA-sequencing and pathway enrichment analysis to determine changes in the transcriptome of cultured human retinal microvascular endothelial cells (HRMECs). Of the enriched pathways, inactivation of oncostatin M signaling was predicted by either KDR or STAT3 knockdown in the presence of VEGF. Activation of kinetochore metaphase signaling was predicted by KDR knockdown, whereas inactivation was predicted by STAT3 knockdown in the presence of VEGF. Inactivation of signaling by the Rho family of GTPases was predicted by KDR knockdown, but activation was predicted by STAT3 knockdown in the presence of VEGF. Taken together, our data identified unique signaling pathway differences between VEGF-triggered VEGFR2 and VEGF-triggered STAT3 in HRMECs that might have implications in ROP.
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Sternfeld A, Rahmani S, Rossen JL, Zhang DL, Li YD, Quan VL, Huang R, Yoon HH. Long-term retinal vasculature abnormalities following intravitreal bevacizumab for retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2022; 260:1915-1921. [PMID: 34851464 DOI: 10.1007/s00417-021-05499-0] [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: 07/16/2021] [Revised: 11/06/2021] [Accepted: 11/14/2021] [Indexed: 01/01/2023] Open
Abstract
PURPOSE To report long-term fluorescein angiography (FA) findings in consecutive patients with type 1 retinopathy of prematurity (ROP) treated with intravitreal bevacizumab (IVB), whose ROP seemed to have resolved clinically. METHODS Data were retrospectively collected for all patients with IVB-treated type 1 ROP who underwent an exam under anesthesia (EUA) and FA at 60 weeks post-gestational age (PGA) or older at a tertiary medical center between 2011 and 2020. FA results were reviewed for pathological vascular findings. RESULTS Twenty-nine eyes of 16 patients were included. Mean gestational age and birth weight were 25.3 ± 1.5 weeks and 762.2 ± 189.8 g, respectively. The mean age at the time of EUA and FA was 23.4 ± 15.8 months. All eyes had a peripheral avascular zone and irregular peripheral branching. Vascular loops were seen in 27 eyes (93.1%) and vascular bulbs and anastomoses in 16 eyes each (55.2%). Additional abnormal findings included leakage (10 eyes, 34.5%), vessels crossing the fovea (5 eyes, 17.2%), tortuous arteries and veins (9 eyes, 31%, and 5 eyes, 17.2%, respectively), and neovascularization (2 eyes, 6.9%). When comparing patients who were less than or greater than 70 weeks PGA at follow-up, FA findings in the group with shorter follow-up were significant for more anastomoses and vascular bulbs (p = 0.002 and p = 0.024, respectively) and trended towards more leakage (45.5% vs. 27.8%, p = 0.331). CONCLUSION The vast majority of IVB-treated type 1 ROP eyes suffered from vascular pathologies long after treatment. There may be long-term progression in the vascularization process of the retina in some cases.
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Affiliation(s)
- Amir Sternfeld
- Ophthalmology Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Safa Rahmani
- Division of Ophthalmology, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago, Box 70, Chicago, IL, 60611, USA
- Department of Ophthalmology, Northwestern Feinberg School of Medicine, Chicago, IL, USA
| | - Jennifer L Rossen
- Division of Ophthalmology, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago, Box 70, Chicago, IL, 60611, USA
- Department of Ophthalmology, Northwestern Feinberg School of Medicine, Chicago, IL, USA
| | - David L Zhang
- Division of Ophthalmology, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago, Box 70, Chicago, IL, 60611, USA
| | - Yuping D Li
- Division of Ophthalmology, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago, Box 70, Chicago, IL, 60611, USA
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Victor L Quan
- Division of Ophthalmology, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago, Box 70, Chicago, IL, 60611, USA
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- Department of Dermatology, Northwestern Feinberg School of Medicine, Chicago, IL, USA
| | - Russell Huang
- Department of Ophthalmology, Northwestern Feinberg School of Medicine, Chicago, IL, USA
| | - Hawke H Yoon
- Division of Ophthalmology, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago, Box 70, Chicago, IL, 60611, USA.
- Department of Ophthalmology, Northwestern Feinberg School of Medicine, Chicago, IL, USA.
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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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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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Schaffer LR, Hubbard GB, Mukkamala K, Rao P. Atypical Late-Onset Exudative Retinal Detachment in a Treatment-Naïve Infant With Retinopathy of Prematurity. Ophthalmic Surg Lasers Imaging Retina 2021; 52:403-406. [PMID: 34309432 DOI: 10.3928/23258160-20210628-09] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
A male infant born at 23 weeks gestation with a birthweight of 660 grams presented with retinopathy of prematurity (ROP) that began progressing at 44 weeks. He subsequently developed Zone III, Stage 3, pre-plus disease in both eyes (OU), as well as scattered exudates in the macula, dragged vessels temporally, and an exudative retinal detachment temporally in the left eye after a period of regressing and stable ROP. After bilateral laser photocoagulation, there was regression of the neovascularization, resolution of the exudative detachment, and eventual stabilization of disease OU by 12 months postmenstrual age. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:403-406.].
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The results of intravitreal bevacizumab monotherapy for treating aggressive posterior retinopathy of prematurity and Type 1 retinopathy of prematurity. Eye (Lond) 2021; 35:3302-3310. [PMID: 33514904 DOI: 10.1038/s41433-021-01413-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 11/23/2020] [Accepted: 01/15/2021] [Indexed: 11/09/2022] Open
Abstract
OBJECTIVES This study evaluated the efficacy of intravitreal bevacizumab (IVB) monotherapy for aggressive posterior retinopathy of prematurity (APROP) and Type 1 retinopathy of prematurity (ROP), along with recurrence rates and treatment outcomes for recurrences. METHODS This retrospective cohort study reviewed the records of infants with ROP (Type 1 and APROP), who received IVB treatment between March 2013 and February 2018. RESULTS A total of 257 eyes from 130 cases (unilateral eyes in three cases) were included. Cases were followed for 121.7 ± 45.7 weeks (range: 70-260 weeks). Recurrence requiring treatment was determined in 14.8% of all eyes at a mean of 9.6 ± 2.7 weeks (range: 6-15 weeks) after initial treatment and a mean of 42.3 ± 2.2 weeks (range: 38-48 weeks) postmenstrual age. Recurrence requiring treatment was observed in 20.8% of APROP and 5.8% of Type 1 ROP eyes at a statistically significant difference (p = 0.001). Persistent avascular areas were found in 54 eyes (25.8%) at the corrected age of 1 year, and prophylactic laser treatment was applied. This was statistically significantly higher in APROP (38.6%) than in Type 1 ROP (10.5%) (p < 0.001). An unfavourable structural outcome (progression to retinal detachment) occurred in one eye (0.4%), which developed insufficient regression and progression. CONCLUSIONS IVB monotherapy is effective for APROP and Type 1 ROP with Zone 1 and posterior Zone 2 localisation. However, because of recurrences requiring treatment and persistent peripheral avascular areas, severe, late complications must be considered, and follow-up examinations must be made. Prophylactic laser treatment for persistent avascular areas seems effective for minimising long-term complications.
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Duggan TJ, Cai CL, Aranda JV, Beharry KD. Acute and chronic effects of intravitreal bevacizumab on lung biomarkers of angiogenesis in the rat exposed to neonatal intermittent hypoxia. Exp Lung Res 2020; 47:121-135. [PMID: 33377400 DOI: 10.1080/01902148.2020.1866712] [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: 10/22/2022]
Abstract
PURPOSE/AIM Intravitreal bevacizumab (Avastin) is an irreversible vascular endothelial growth factor (VEGF) inhibitor used to treat severe retinopathy of prematurity (ROP) in extremely low gestational age neonates (ELGANs). ELGANs who are at the highest risk for developing severe ROP often experience brief intermittent hypoxia (IH) episodes which may cause oxidative damage. We tested the hypothesis that intravitreal Avastin leaks into the systemic circulation during exposure to IH and has adverse effects on biomarkers of pulmonary microvascular maturation, thus leading to pulmonary hemorrhage and long-term pulmonary sequelae. METHODS Neonatal rats at postnatal day (PN) 0 (birth) were exposed to either: 1) hyperoxia (50% O2) or 2) neonatal IH (50% O2 with brief episodes of 12% O2) from PN0 to PN14. Room air (RA) littermates served as controls. At PN14, the time of eye opening in rats, a single dose of Avastin (0.125 mg in 5 µL) was injected into the vitreous cavity of the left eyes. A control group received equivalent volume saline. At PN23 and PN45, blood gases, lung-to-body weight ratios, histology, immunofluorescence, and lung biomarkers of angiogenesis were examined. RESULTS At PN23, Avastin increased lung VEGF, nitric oxide derivatives (NOx), and hypoxia-inducible factor (HIF)1a in the hyperoxia-exposed groups, but decreased soluble VEGFR-1 (sVEGFR-1). At PN45, lungs from animals exposed to neonatal IH and treated with Avastin were severely hemorrhagic with morphologic changes in lung architecture consistent with chronic lung disease. This was associated with higher VEGF and NOx levels, and lower insulin-like growth factor (IGF)-I and sVEGFR-1. CONCLUSIONS These findings prove our hypothesis that intravitreal Avastin penetrates the blood-ocular barrier in IH and alters lung biomarkers of angiogenesis. Avastin targeting of VEGF could affect normal lung development which may be exaggerated under pathologic conditions such as IH, ultimately leading to vascular permeability, vessel rupture, and pulmonary hemorrhage.
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Affiliation(s)
- Thomas J Duggan
- aDepartment of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, New York, USA
| | - Charles L Cai
- aDepartment of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, New York, USA
| | - Jacob V Aranda
- aDepartment of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, New York, USA.,Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, New York, USA.,State University of New York Eye Institute, Brooklyn, New York, USA
| | - Kay D Beharry
- aDepartment of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, New York, USA.,Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, New York, USA.,State University of New York Eye Institute, Brooklyn, New York, USA
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Mori Y, Arima M, Ueda E, Fujiwara K, Seki E, Nakama T, Tsukamoto S, Akiyama M, Sonoda KH. Risk factors for myopia at 1-year corrected age following laser photocoagulation for retinopathy of prematurity. Eye (Lond) 2020; 35:2820-2825. [PMID: 33257802 DOI: 10.1038/s41433-020-01321-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 11/10/2020] [Accepted: 11/12/2020] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND/OBJECTIVES The prevalence of myopia is higher in preterm infants who underwent laser photocoagulation (LPC) for retinopathy of prematurity (ROP). The aim of this study was to investigate factors associated with myopia in preterm infants who undergo LPC for ROP. SUBJECTS/METHODS We retrospectively analysed the medical records of preterm infants born at Kyushu University Hospital (October 2008-March 2018) at ≤32 weeks of gestational age or with birth weight ≤1500 g. We evaluated the associations between nine clinical factors and the spherical equivalent at 1-year corrected age by performing multivariable linear regression in LPC-treated ROP patients. RESULTS Among the 485 infants enroled, 76 developed ROP requiring treatment. Of these, 71 underwent LPC, which was provided to 63 infants as the primary treatment (LPC alone or the combination therapy of LPC and intravitreal injection of bevacizumab [IVB]) and to eight infants as additional LPC after IVB monotherapy. The results of a refractive examination at 1-year corrected age were available for 110 eyes of 56 infants (78.9%). The mean ± standard deviation of the SE value was -0.5 ± 3.0 dioptres (D). Multivariable linear regression analysis revealed a significant association between laser spot count and SE value (ß = -0.081 ± 0.040 D per 100 spots [mean ± standard error], p = 0.045). CONCLUSIONS Our results suggest that an increased laser spot count observed during ROP treatment associates with myopia.
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Affiliation(s)
- Yujiro Mori
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Mitsuru Arima
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| | - Emi Ueda
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kohta Fujiwara
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eiko Seki
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahito Nakama
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shoko Tsukamoto
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masato Akiyama
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Koh-Hei Sonoda
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Zhang DL, Shapiro MJ, Schechet SA, Rabiah PK, Rodriguez SH, Blair MP. Macular Sequelae Following Exudative Retinal Detachment After Laser Photocoagulation for Retinopathy of Prematurity. Ophthalmic Surg Lasers Imaging Retina 2020; 51:698-705. [PMID: 33339051 DOI: 10.3928/23258160-20201202-04] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 11/09/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND OBJECTIVE To report a series of exudative retinal detachments (ERDs) following laser photocoagulation for retinopathy of prematurity (ROP). PATIENTS AND METHODS Retrospective case series. RESULTS Eleven eyes of seven infants were identified who developed ERD following laser. Median gestation age was 25 weeks (interquartile range [IQR]: 24-27 weeks), and median birth weight was 662 grams (IQR: 538-850 grams). Median postmenstrual age at time of laser was 35 weeks (IQR: 33-39 weeks). ERD was diagnosed at a median of 7 days (IQR: 5-7 days) after laser and was managed with steroids. Bevacizumab was also used for certain cases. Time to resolution ranged from 1 to 5 weeks. Macular pigment changes, atrophy, window defect on fluorescein angiography, and photoreceptor loss on optical coherence tomography were noted in some cases following ERD resolution. Excluding one patient who expired at 3 months, median length of follow-up was 10 years (IQR: 9-13.5 years). Overall, only one patient, who presented with less severe ERD, had normal vision. CONCLUSIONS ERD is an uncommonly reported complication following laser for ROP. Macular changes following ERD resolution may have negative visual consequences. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:698-705.].
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Daruich A, Bremond-Gignac D, Behar-Cohen F, Kermorvant E. [Retinopathy of prematurity: from prevention to treatment]. Med Sci (Paris) 2020; 36:900-907. [PMID: 33026333 DOI: 10.1051/medsci/2020163] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Retinopathy of prematurity (ROP) is one of the leading cause of preventable blindness in children. Its incidence increases with increasing survival of extremely preterm babies. ROP results from a multifactorial impairment of retinal development, the retinal vascular network, involving both oxygen-dependent and nutritional factors. The numerous factors involved in ROP development suggest that preventive strategies should be synergistic and complementary, including tight control of oxygen therapy, optimized nutritional intakes and postnatal growth, breastfeeding, adequate ω-3 PUFAs supply and control of hyperglycemic episodes associated with prematurity. ROP requires a multidisciplinary management, which includes systematic screening, appropriate treatment and long-term follow-up. Current screening modalities are based on wide-field digital retinal imaging systems, which also allow screening by telemedicine. The gold-standard treatment for ROP remains laser photocoagulation. It may be combined with intravitreal anti-VEGF administration, which is currently being evaluated, or surgery for advanced stages.
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Affiliation(s)
- Alejandra Daruich
- Service d'ophtalmologie, Hôpital universitaire Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75015 Paris, France - Inserm, UMRS1138, Équipe 17, Université Sorbonne Paris Cité, Centre de recherche des Cordeliers, 15 rue de l'École de Médecine, 75006 Paris, France - Université de Paris, Paris, France
| | - Dominique Bremond-Gignac
- Service d'ophtalmologie, Hôpital universitaire Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75015 Paris, France - Inserm, UMRS1138, Équipe 17, Université Sorbonne Paris Cité, Centre de recherche des Cordeliers, 15 rue de l'École de Médecine, 75006 Paris, France - Université de Paris, Paris, France
| | - Francine Behar-Cohen
- Inserm, UMRS1138, Équipe 17, Université Sorbonne Paris Cité, Centre de recherche des Cordeliers, 15 rue de l'École de Médecine, 75006 Paris, France - Université de Paris, Paris, France - Ophtalmopole, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Elsa Kermorvant
- Inserm, UMRS1138, Équipe 17, Université Sorbonne Paris Cité, Centre de recherche des Cordeliers, 15 rue de l'École de Médecine, 75006 Paris, France - Université de Paris, Paris, France - Service de pédiatrie et réanimation néonatales, AP-HP, Hôpital universitaire Necker-Enfants malades, 149 rue de Sèvres, 75015 Paris, France
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Zhang MH, Blair MP, Ham SA, Rodriguez SH. Two-Year Outcomes Comparing Anti-VEGF Injections to Laser for ROP Using a Commercial Claims Database. Ophthalmic Surg Lasers Imaging Retina 2020; 51:486-493. [DOI: 10.3928/23258160-20200831-02] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 07/08/2020] [Indexed: 01/09/2023]
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Yu Y, Wang J, Chen F, Chen W, Jiang N, Xiang D. Study protocol for prognosis and treatment strategy of peripheral persistent avascular retina after intravitreal anti-VEGF therapy in retinopathy of prematurity. Trials 2020; 21:493. [PMID: 32513245 PMCID: PMC7278113 DOI: 10.1186/s13063-020-04371-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 05/05/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Prophylactic peripheral photocoagulation has been proposed to be applied to persistent, peripheral, avascular retina for retinopathy of prematurity (ROP) patients who have received an intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, there are doubts regarding the necessity of this prophylactic action regardless of fundus fluorescein angiography (FFA) results. The adverse prognosis for persistent avascular retina after anti-VEGF therapy in ROP patients is not well understood. The relationship between vascular leakage and an adverse prognosis is also unknown. Therefore, it would be of value to study the above issues to shape the treatment strategy of persistent avascular retina after intravitreal anti-VEGF therapy in ROP patients. METHODS/DESIGN This is a prospective study of ROP patients with persistent avascular retina who have received anti-VEGF intravitreal therapy and have never received laser therapy. All the eyes being studied will be followed up and examined by FFA after anti-VEGF treatment and categorized into two groups, a leakage group and a non-leakage group according to the extent of vascular leakage from FFA results. The eyes being studied in the leakage group will be further randomized into two groups, a laser group and a non-laser group. A cohort study (observational) will be conducted on the non-leakage group and the non-laser group (with leakage) to investigate the incidence of an adverse prognosis for reactivation, retinal tear and retinal detachment; as well as to investigate the relationship between vascular leakage from FFA results and the abovementioned pathological changes. A randomized controlled study (experimental) will be conducted on the leakage group to compare the prognosis between the laser group and the non-laser group. DISCUSSION The present study aims to investigate the occurrence rates of an adverse prognosis including reactivation, retinal tear and retinal detachment after anti-VEGF therapy in ROP patients with persistent avascular retina; to assess the relationship between vascular leakage from FFA results and the abovementioned pathological changes; to compare the prognosis of persistent avascular retina with or without prophylactic peripheral photocoagulation in these patients; to shape the treatment strategy and provide evidence for the indications of prophylactic photocoagulation. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ID: ChiCTR-ROC-17013253. Registered on 5 November 2017. http://www.chictr.org.cn/showproj.aspx?proj=22703.
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Affiliation(s)
- Ying Yu
- Department of Ophthalmology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510230, China
| | - Jianxun Wang
- Department of Ophthalmology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510230, China
| | - Feng Chen
- Department of Ophthalmology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510230, China
| | - Wensi Chen
- Department of Ophthalmology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510230, China
| | - Nan Jiang
- Department of Ophthalmology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510230, China
| | - Daoman Xiang
- Department of Ophthalmology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510230, China.
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Stahl A. [Review of clinical trials in retinopathy of prematurity : Current state and future perspectives]. Ophthalmologe 2019; 115:456-463. [PMID: 29789899 DOI: 10.1007/s00347-018-0720-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND The treatment of retinopathy of prematurity (ROP) has gained a new dynamic since the introduction of anti-vascular endothelial growth factor (VEGF) therapy. This review summarizes clinical trial data in order to aid informed decision-making. METHODS In this article, pivotal clinical trials are summarized and discussed with regard to their implications for ROP therapy. RESULTS The longest follow-up phase exists for children treated in the CRYO-ROP study, which used retinal cryocoagulation to treat ROP. Based on results of the ETROP study and others, retinal laser therapy has replaced cryotherapy as standard of care. For anti-VEGF treatment, three controlled clinical trials exist to date: BEAT-ROP, CARE-ROP, and the PEDIG study. Combined, these studies demonstrate efficacy of anti-VEGF in treating acute ROP. However, they also emphasize the risk of (late) recurrences and the largely unsolved questions regarding choice of drug and dose as well as long-term safety. CONCLUSION Treatment of ROP remains a highly individual decision in which many variables need to be considered. The data discussed in this article can help in decision-making and emphasize the unique characteristics of the available therapeutic approaches, in particular regarding postoperative follow-up.
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Affiliation(s)
- Andreas Stahl
- Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Killianstraße 5, 79106, Freiburg, Deutschland.
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Abstract
Introduction Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Areas covered Recent methods to identify and manage treatment-warranted vascularly active ROP are recognized and being compared to standard care by laser treatment in prospective large-scale clinical studies. Pharmacologic anti-angiogenic (anti-VEGF) treatment has changed the natural history of vascularly active ROP by reducing stage 3 intravitreal neovascularization and extending physiologic retinal vascularization in many infants. Tractional retinal detachments in stage 4 ROP after treatment with anti-VEGF agents show additional fibrovascular complexity compared to eyes treated with laser only. We review current management and outcomes for vascularly active and fibrovascular retinal detachment in ROP (stages 3, 4, 5 ROP), highlighting the evidence from recent clinical studies. Included are technical details important in surgery for retinal detachment in ROP. Literature searches were employed through PubMed. Expert opinion Methods in pediatric imaging, safer pharmacologic treatments, and surgical techniques continue to advance to improve future ROP outcomes.
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Affiliation(s)
- Eric D Hansen
- John A. Moran Eye Center, University of Utah, Salt Lake City, USA
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Reply. Retina 2019; 39:e2-e4. [DOI: 10.1097/iae.0000000000002391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Theophanous C, Schechet S, Rodriguez SH, Blair M. Bilateral Vitreous Hemorrhage Following Bilateral Intravitreal Injections of Bevacizumab in an Infant With Retinopathy of Prematurity. Ophthalmic Surg Lasers Imaging Retina 2018; 49:893-896. [DOI: 10.3928/23258160-20181101-11] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 10/02/2018] [Indexed: 11/20/2022]
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Functional and Structural Outcomes of Temporal Zone II-Sparing Laser Photocoagulation Combined with Intravitreal Bevacizumab in Retinopathy of Prematurity. J Ophthalmol 2018; 2018:2376240. [PMID: 30363696 PMCID: PMC6180920 DOI: 10.1155/2018/2376240] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 06/29/2018] [Accepted: 07/29/2018] [Indexed: 11/24/2022] Open
Abstract
Background/Aim The aim of the study was to investigate the outcomes of temporal Zone II-sparing laser photocoagulation combined with intravitreal bevacizumab (IVB) in patients with Type 1 retinopathy of prematurity (ROP) in Zone I. Methods Medical records of 74 eyes of 37 infants were analysed. Only infants with Type 1 ROP in Zone I were included. Thirty-two eyes were treated with temporal-sparing laser + IVB. Both Zone I and temporal Zone II were spared to minimise potential visual field loss. Forty-two eyes were treated with laser alone conventionally. Early treatment outcomes, late complications, and refractive errors were analysed. Results The mean gestational age and birth weight of the enrolled patients were 25.7 ± 2.5 weeks and 798.8 ± 440.2 g, respectively. In the combined treatment group, plus sign regression was achieved faster (12.1 ± 6.2 days vs. 25.6 ± 21.3 days, p=0.011) and retreatment was required less (0% vs. 23.8%, p=0.004) than in the laser-alone group. Retinal/preretinal haemorrhages occurred more often in the laser-alone group (42.9% vs. 9.4%, p=0.002). Normal development of temporal retinal vessels was also observed in twelve eyes in the combined treatment group. No differences in late complications or refractive errors were observed between the groups. Conclusion Temporal Zone II-sparing laser treatment combined with IVB showed good early treatment outcome and temporal retinal vessels development.
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Golas L, Shapiro MJ, Blair MP. Late ROP Reactivation and Retinal Detachment in a Teenager. Ophthalmic Surg Lasers Imaging Retina 2018; 49:625-628. [DOI: 10.3928/23258160-20180803-11] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 01/22/2018] [Indexed: 02/04/2023]
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Late-onset tractional fibrovascular proliferation post-intravitreal bevacizumab following treatment of retinopathy of prematurity. Can J Ophthalmol 2018; 53:e99-e103. [PMID: 29784188 DOI: 10.1016/j.jcjo.2017.09.028] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 09/15/2017] [Accepted: 09/25/2017] [Indexed: 11/22/2022]
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Blair M, Gonzalez JMG, Snyder L, Schechet S, Greenwald M, Shapiro M, Rodriguez SH. Bevacizumab or laser for aggressive posterior retinopathy of prematurity. Taiwan J Ophthalmol 2018; 8:243-248. [PMID: 30637196 PMCID: PMC6302568 DOI: 10.4103/tjo.tjo_69_18] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
PURPOSE The purpose of this study was to report the rate of reactivation and structural outcome, after the laser or bevacizumab treatment for aggressive posterior retinopathy of prematurity (APROP). METHODS Retrospective chart review was conducted on consecutive infants with APROP treated with (1) laser or (2) bevacizumab, followed by fluorescein angiography and prophylactic laser to the persistent avascular retina. RESULTS Thirty-six eyes of 19 patients were included in this study. The mean gestational age was 24.5 weeks with a mean birth weight of 632 g in the bevacizumab group and 24.7 weeks and 777 g in the laser group. Unfavorable outcome occurred in 1 of 22 eyes treated with bevacizumab and in 5 of 14 eyes in the laser group (P = 0.002). Reactivation requiring treatment was common in both groups, 9/22 after bevacizumab and 6/14 after laser (ns). CONCLUSION Regardless of the initial treatment reactivation requiring retreatment is common in eyes with APROP. The unfavorable structural outcome was significantly more common after initial laser treatment than after initial bevacizumab treatment.
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Affiliation(s)
- Michael Blair
- Department of Ophthalmology and Visual Science, University of Chicago, 5841 S. Maryland Avenue, MC2114, Chicago, IL, USA.,Retina Consultants, Ltd., Des Plaines, IL 60016, USA
| | | | - Laura Snyder
- Department of Ophthalmology and Visual Science, University of Chicago, 5841 S. Maryland Avenue, MC2114, Chicago, IL, USA
| | - Sidney Schechet
- Department of Ophthalmology and Visual Science, University of Chicago, 5841 S. Maryland Avenue, MC2114, Chicago, IL, USA
| | - Mark Greenwald
- Department of Ophthalmology and Visual Science, University of Chicago, 5841 S. Maryland Avenue, MC2114, Chicago, IL, USA
| | | | - Sarah Hilkert Rodriguez
- Department of Ophthalmology and Visual Science, University of Chicago, 5841 S. Maryland Avenue, MC2114, Chicago, IL, USA
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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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Ocular Adverse Effects of Intravitreal Bevacizumab Are Potentiated by Intermittent Hypoxia in a Rat Model of Oxygen-Induced Retinopathy. J Ophthalmol 2017; 2017:4353129. [PMID: 28770109 PMCID: PMC5523466 DOI: 10.1155/2017/4353129] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 05/09/2017] [Accepted: 05/30/2017] [Indexed: 12/02/2022] Open
Abstract
Intravitreal bevacizumab (Avastin) use in preterm infants with retinopathy of prematurity is associated with severe neurological disabilities, suggesting vascular leakage. We examined the hypothesis that intermittent hypoxia (IH) potentiates intravitreal Avastin leakage. Neonatal rats at birth were exposed to IH from birth (P0)–P14. At P14, the time of eye opening in rats, a single dose of Avastin (0.125 mg) was injected intravitreally into the left eye. Animals were placed in room air (RA) until P23 or P45 for recovery (IHR). Hyperoxia-exposed and RA littermates served as oxygen controls, and equivalent volume saline served as the placebo controls. At P23 and P45 ocular angiogenesis, retinal pathology and ocular and systemic biomarkers of angiogenesis were examined. Retinal flatmounts showed poor peripheral vascularization in Avastin-treated and fellow eyes at P23, with numerous punctate hemorrhages and dilated, tortuous vessels with anastomoses at P45 in the rats exposed to IH. These adverse effects were associated with robust increases in systemic VEGF and in both treated and untreated fellow eyes. Histological analysis showed severe damage in the inner plexiform and inner nuclear layers. Exposure of IH/IHR-induced injured retinal microvasculature to anti-VEGF substances can result in vascular leakage and adverse effects in the developing neonate.
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Hajrasouliha AR, Garcia-Gonzales JM, Shapiro MJ, Yoon H, Blair MP. Reactivation of Retinopathy of Prematurity Three Years After Treatment With Bevacizumab. Ophthalmic Surg Lasers Imaging Retina 2017; 48:255-259. [PMID: 28297039 DOI: 10.3928/23258160-20170301-10] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 01/11/2017] [Indexed: 11/20/2022]
Abstract
Although intravitreal injection of anti-vascular endothelial growth factor agents (IVA) can induce rapid regression of retinopathy of prematurity (ROP), late reactivation of the ROP can occur in the form of tractional retinal detachment (TRD) from contracted recurrent extraretinal fibrovascular proliferation. The authors report a case of bilateral TRD for recurrent ROP in a 3-year-old, which is the latest-reported reactivation to date. The authors propose that persistent avascular retina in eyes that have undergone IVA for ROP receive laser ablation to prevent late recurrences. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:255-259.].
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Mataftsi A, Koulali E, Papageorgiou E, Ziakas N, Brazitikos P. Letter to the Editor: Very Late Reactivation of Retinopathy of Prematurity After Monotherapy With Intravitreal Bevacizumab. Ophthalmic Surg Lasers Imaging Retina 2017; 48:372. [DOI: 10.3928/23258160-20170428-01] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Snyder LL, Garcia-Gonzalez JM, Shapiro MJ, Blair MP. Very Late Reactivation of Retinopathy of Prematurity After Monotherapy With Intravitreal Bevacizumab. Ophthalmic Surg Lasers Imaging Retina 2016; 47:280-3. [PMID: 26985803 DOI: 10.3928/23258160-20160229-12] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 01/25/2016] [Indexed: 11/20/2022]
Abstract
The authors report a case of very late reactivation of retinopathy of prematurity (ROP) after bevacizumab monotherapy. A female born at 630 g and 24 weeks received two bilateral treatment of bevacizumab (Avastin; Genentech, South San Francisco, CA) for aggressive posterior ROP (APROP). At 2.5 years of age, ROP reactivated in the form of tractional retinal detachment in one eye and milder reactivation in the other. Although intravitreal bevacizumab treatment is effective in inducing regression of ROP, late reactivation and retinal detachments can occur after initial extended quiescence. Due to alterations of disease progression after bevacizumab, close follow-up by peripheral fluorescein angiography and laser ablation of persistent avascular retina is recommended to prevent disease reactivation and progression to retinal detachment.
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Karkhaneh R, Khodabande A, Riazi-Eafahani M, Roohipoor R, Ghassemi F, Imani M, Dastjani Farahani A, Ebrahimi Adib N, Torabi H. Efficacy of intravitreal bevacizumab for zone-II retinopathy of prematurity. Acta Ophthalmol 2016; 94:e417-20. [PMID: 27009449 DOI: 10.1111/aos.13008] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 01/09/2016] [Indexed: 11/30/2022]
Abstract
PURPOSE To assess the effect of intravitreal bevacizumab for Type 1 retinopathy of prematurity (ROP) in zone II ROP. METHODS We conducted a randomized clinical trial. Preterm infants with a gestational age less than 34 weeks or birthweight less than 2000 g were examined at 4 weeks chronological age or 31 weeks postmenstrual age (whichever was later). Preterm infants with Zone-II/Stage 2 or 3 and plus disease were included. Eligible infants were randomized to receive either conventional indirect laser therapy or intravitreal bevacizumab injections (0.625 mg/0.025 ml). The primary outcome was defined as treatment failure: ROP persistence or recurrence by 90 weeks postmenstrual age. RESULTS Our study population comprised 79 infants (158 eyes) with Zone-II ROP. Randomly, 43 infants (86 eyes) were assigned to receive intravitreal bevacizumab and 36 infants (72 eyes) to receive conventional indirect laser therapy. All the infants were followed up at least until 90 weeks postmenstrual age. Stage-3 ROP recurred in nine eyes (10.5%) in the bevacizumab group and one eye (1.4%) in the laser group (p value = 0.018). In recurrent cases after the second treatment, ROP in eight of the nine eyes (88.8%) in the bevacizumab group and the eye in the laser group regressed. CONCLUSION Recurrence of neovascularization with bevacizumab monotherapy seems to be higher than that with conventional laser therapy among infants with Type 1 ROP in zone II ROP but reinjection of bevacizumab causes regression in most recurrent cases.
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Affiliation(s)
- Reza Karkhaneh
- Eye Research Center; Farabi Eye Hospital; Tehran University of Medical Science (TUMS); Tehran Iran
| | - Alireza Khodabande
- Eye Research Center; Farabi Eye Hospital; Tehran University of Medical Science (TUMS); Tehran Iran
| | - Mohammad Riazi-Eafahani
- Eye Research Center; Farabi Eye Hospital; Tehran University of Medical Science (TUMS); Tehran Iran
| | - Ramak Roohipoor
- Eye Research Center; Farabi Eye Hospital; Tehran University of Medical Science (TUMS); Tehran Iran
| | - Fariba Ghassemi
- Eye Research Center; Farabi Eye Hospital; Tehran University of Medical Science (TUMS); Tehran Iran
| | - Marjan Imani
- Eye Research Center; Farabi Eye Hospital; Tehran University of Medical Science (TUMS); Tehran Iran
| | - Afsar Dastjani Farahani
- Eye Research Center; Farabi Eye Hospital; Tehran University of Medical Science (TUMS); Tehran Iran
| | - Nazanin Ebrahimi Adib
- Eye Research Center; Farabi Eye Hospital; Tehran University of Medical Science (TUMS); Tehran Iran
| | - Hamidreza Torabi
- Eye Research Center; Farabi Eye Hospital; Tehran University of Medical Science (TUMS); Tehran Iran
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Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical Management of Recurrent Retinopathy of Prematurity after Intravitreal Bevacizumab Monotherapy. Ophthalmology 2016; 123:1845-55. [PMID: 27241619 PMCID: PMC4995132 DOI: 10.1016/j.ophtha.2016.04.028] [Citation(s) in RCA: 127] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 04/13/2016] [Accepted: 04/17/2016] [Indexed: 10/21/2022] Open
Abstract
PURPOSE To determine incidence, risk factors, risk period, and characteristics of recurrent retinopathy of prematurity (ROP) treated by intravitreal bevacizumab (IVB) monotherapy. DESIGN Retrospective case series. PARTICIPANTS Premature infants with type 1 ROP (subdivided into stage 3+ ROP and aggressive posterior ROP [APROP]) in zone I or zone II posterior who received IVB monotherapy and were followed up for at least 65 weeks adjusted age (AA). METHODS Retrospective review of infants who demonstrated recurrence of type 1 ROP after IVB monotherapy, including examination of RetCam fundus photographs and fluorescein angiograms. MAIN OUTCOMES MEASURES Incidence, risk factors, risk period, and characteristics of recurrent ROP. RESULTS Intravitreal bevacizumab monotherapy in 241 infants (471 eyes) was reviewed. Recurrence incidence was 8.3% (20/241) for infants and 7.2% (34/471) for eyes. Recurrence risk factors of greatest significance were appearance of neovascularization as APROP (P = 0.006), extended duration of hospitalization (P = 0.01), and lower birth weight (P = 0.024). Recurrence risk period was between approximately 45 and 55 weeks AA (90.0% [18/20] for infants and 94.1% [32/34] for eyes), with mean recurrence of 51.2 weeks AA (±4.6 weeks; range, 45.7-64.9 weeks) and mean interval of 16.2 weeks (±4.4 weeks) between treatments. Recurrence characteristics included plus disease (20/20 infants [100%]) and neovascularization, which appeared at the following sites: stage 3+ ROP with confluent neovascularization recurred both at the advancing edge and at the initial ridge and extraretinal fibrovascular proliferative complex (12/14 infants [85.7%]). However, APROP (6/6 infants [100%]) and stage 3+ ROP with nonconfluent neovascularization (2/14 infants [14.3%]) recurred only at the advancing edge. Also, the anterior extent of retinal vascularization was decreased (mean, 1.76 disc diameters [DD] vs. 4.48 DD), and the rate of retinal vascularization was delayed (mean, 0.11 DD/week vs. 0.23 DD/week) in those with versus without recurrence, respectively. After retreatment with IVB, retinal vascularization proceeded minimally and slowly. CONCLUSIONS Premature children with severe ROP are being treated successfully with IVB monotherapy. However, recurrence is not uncommon, so vigilant follow-up is necessary to ensure timely re-treatment. Knowledge of recurrence incidence, risk factors, risk period, and characteristics allows for tailored clinical management.
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Affiliation(s)
- Helen A Mintz-Hittner
- Ruiz Department of Ophthalmology and Visual Science, The University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, Houston, Texas; W. T. & Louise J. Moran Pediatric Eye Clinic, Robert Cizik Eye Clinic, Houston, Texas.
| | - Megan M Geloneck
- Ruiz Department of Ophthalmology and Visual Science, The University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, Houston, Texas; W. T. & Louise J. Moran Pediatric Eye Clinic, Robert Cizik Eye Clinic, Houston, Texas
| | - Alice Z Chuang
- Ruiz Department of Ophthalmology and Visual Science, The University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, Houston, Texas
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Ngo MH, Borowska-Fielding J, Heathcote G, Nejat S, Kelly ME, McMaster CR, Robitaille JM. Fzd4 Haploinsufficiency Delays Retinal Revascularization in the Mouse Model of Oxygen Induced Retinopathy. PLoS One 2016; 11:e0158320. [PMID: 27489958 PMCID: PMC4973993 DOI: 10.1371/journal.pone.0158320] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Accepted: 06/14/2016] [Indexed: 12/11/2022] Open
Abstract
Mutations in genes that code for components of the Norrin-FZD4 ligand-receptor complex cause the inherited childhood blinding disorder familial exudative vitreoretinopathy (FEVR). Statistical evidence from studies of patients at risk for the acquired disease retinopathy of prematurity (ROP) suggest that rare polymorphisms in these same genes increase the risk of developing severe ROP, implying that decreased Norrin-FZD4 activity predisposes patients to more severe ROP. To test this hypothesis, we measured the development and recovery of retinopathy in wild type and Fzd4 heterozygous mice in the absence or presence of ocular ischemic retinopathy (OIR) treatment. Avascular and total retinal vascular areas and patterning were determined, and vessel number and caliber were quantified. In room air, there was a small delay in retinal vascularization in Fzd4 heterozygous mice that resolved as mice reached maturity suggestive of a slight defect in retinal vascular development. Subsequent to OIR treatment there was no difference between wild type and Fzd4 heterozygous mice in the vaso-obliterated area following exposure to high oxygen. Importantly, after return of Fzd4 heterozygous mice to room air subsequent to OIR treatment, there was a substantial delay in retinal revascularization of the avascular area surrounding the optic nerve, as well as delayed vascularization toward the periphery of the retina. Our study demonstrates that a small decrease in Norrin-Fzd4 dependent retinal vascular development lengthens the period during which complications from OIR could occur.
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Affiliation(s)
- Michael H. Ngo
- Department of Pharmacology, Dalhousie University, Halifax, NS, Canada
| | | | - Godfrey Heathcote
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Department of Ophthalmology and Visual Sciences, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada
| | - Sara Nejat
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Melanie E. Kelly
- Department of Pharmacology, Dalhousie University, Halifax, NS, Canada
- Department of Ophthalmology and Visual Sciences, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada
| | | | - Johane M. Robitaille
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Department of Ophthalmology and Visual Sciences, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada
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Trinh TLP, Li Calzi S, Shaw LC, Yoder MC, Grant MB. Promoting vascular repair in the retina: can stem/progenitor cells help? Eye Brain 2016; 8:113-122. [PMID: 28539806 PMCID: PMC5398749 DOI: 10.2147/eb.s94451] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Since its first epidemic in the 1940s, retinopathy of prematurity (ROP) has been a challenging illness in neonatology. Higher than physiological oxygen levels impede the development of the immature retinal neuropil and vasculature. Current treatment regimens include cryotherapy, laser photocoagulation, and anti-VEGF agents. Unfortunately, none of these approaches can rescue the normal retinal vasculature, and each has significant safety concerns. The limitations of these approaches have led to new efforts to understand the pathological characteristics in each phase of ROP and to find a safer and more effective therapeutic approach. In the era of stem cell biology and with the need for new treatments for ROP, this review discusses the possible future use of unique populations of proangiogenic cells for therapeutic revascularization of the preterm retina.
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Affiliation(s)
| | | | | | - Mervin C Yoder
- Department of Pediatrics.,Herman B. Wells Center for Pediatric Research.,Department of Biochemistry and Molecular Biology, Indiana University - Purdue University Indianapolis, Indianapolis, IN, USA
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Nicoară SD, Ștefănuţ AC, Nascutzy C, Zaharie GC, Toader LE, Drugan TC. Regression Rates Following the Treatment of Aggressive Posterior Retinopathy of Prematurity with Bevacizumab Versus Laser: 8-Year Retrospective Analysis. Med Sci Monit 2016; 22:1192-209. [PMID: 27062023 PMCID: PMC4918525 DOI: 10.12659/msm.897095] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Retinopathy is a serious complication related to prematurity and a leading cause of childhood blindness. The aggressive posterior form of retinopathy of prematurity (APROP) has a worse anatomical and functional outcome following laser therapy, as compared with the classic form of the disease. The main outcome measures are the APROP regression rate, structural outcomes, and complications associated with intravitreal bevacizumab (IVB) versus laser photocoagulation in APROP. Material/Methods This is a retrospective case series that includes infants with APROP who received either IVB or laser photocoagulation and had a follow-up of at least 60 weeks (for the laser photocoagulation group) and 80 weeks (for the IVB group). In the first group, laser photocoagulation of the retina was carried out and in the second group, 1 bevacizumab injection was administered intravitreally. The following parameters were analyzed in each group: sex, gestational age, birth weight, postnatal age and postmenstrual age at treatment, APROP regression, sequelae, and complications. Statistical analysis was performed using Microsoft Excel and IBM SPSS (version 23.0). Results The laser photocoagulation group consisted of 6 premature infants (12 eyes) and the IVB group consisted of 17 premature infants (34 eyes). Within the laser photocoagulation group, the evolution was favorable in 9 eyes (75%) and unfavorable in 3 eyes (25%). Within the IVB group, APROP regressed in 29 eyes (85.29%) and failed to regress in 5 eyes (14.71%). These differences are statistically significant, as proved by the McNemar test (P<0.001). Conclusions The IVB group had a statistically significant better outcome compared with the laser photocoagulation group, in APROP in our series.
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Affiliation(s)
- Simona D Nicoară
- Department of Ophthalmology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Anne C Ștefănuţ
- Department of Ophthalmology, Emergency County Hospital, Cluj-Napoca, Romania
| | - Constanta Nascutzy
- Department of Ophthalmology, Institute for Mother and Child Care, Bucharest, Romania
| | - Gabriela C Zaharie
- Department of Neonatology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Laura E Toader
- Department of Ophthalmology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Tudor C Drugan
- Department of Medical Informatics and Biostatistics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Beharry KD, Valencia G, Lazzaro D, Aranda J. Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity. Semin Perinatol 2016; 40:189-202. [PMID: 26831641 PMCID: PMC4808450 DOI: 10.1053/j.semperi.2015.12.006] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Retinopathy of prematurity (ROP), a significant morbidity in prematurely born infants, is the most common cause of visual impairment and blindness in children and persists till adulthood. Strict control of oxygen therapy and prevention of intermittent hypoxia are the keys in the prevention of ROP, but pharmacologic interventions have decreased risk of ROP. Various drug classes such as methylxanthines (caffeine), VEGF inhibitors, antioxidants, and others have decreased ROP occurrence. The timing of pharmacologic intervention remains unsettled, but early prevention rather than controlling disease progression may be preferred. These drugs act through different mechanisms, and synergistic approaches should be considered to maximize efficacy and safety.
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Isaac M, Tehrani N, Mireskandari K. Involution patterns of retinopathy of prematurity after treatment with intravitreal bevacizumab: implications for follow-up. Eye (Lond) 2016; 30:333-41. [PMID: 26869159 PMCID: PMC4791711 DOI: 10.1038/eye.2015.289] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 10/27/2015] [Indexed: 11/08/2022] Open
Abstract
PURPOSE To describe involution patterns following monotherapy with intravitreal bevacizumab injection (IVB) for type 1 retinopathy of prematurity (ROP) in zone I or zone II posterior. METHODS A retrospective chart review of infants treated with IVB from January 2010-April 2014. Infants with minimum of 82 weeks postmenstrual age at last follow-up were included. Primary outcome was timing of involution of type 1 ROP for the first 12 weeks post treatment. Secondary outcomes were development of any recurrence and structural outcome at last follow-up. Retinal examination records, fundus, and flourescein angiography images were reviewed. RESULTS Twenty-eight eyes were included. Average follow-up post treatment was 33.9±9.7 months (range 21.4-61.9). Cumulative frequency of regression of plus disease was seen in 73.3, 86.7, and 100% of eyes by days 3, 5, and 8, respectively. Regression of both stage 3 and plus disease was observed in 29, 82, 88, and 100% by weeks 1, 2, 3, and 4, respectively. Within the first 3 months, 17/28 eyes developed recurrence to stage 1 or 2 after regression. None developed recurrence of plus disease. By the end of 3 months 18% of eyes vascularized into zone III. At a mean of 24±17.3 months, 39% of eyes were not vascularized into zone III as seen on flourescein angiography with scleral indentation. CONCLUSION Our experience suggests regression of plus disease and stage 3 are expected within the first 4 weeks after bevacizumab treatment. Recurrence may occur despite initial regression and requires careful follow-up.
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Affiliation(s)
- M Isaac
- Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - N Tehrani
- Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
| | - K Mireskandari
- Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
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Darlow BA. Retinopathy of prematurity: New developments bring concern and hope. J Paediatr Child Health 2015; 51:765-70. [PMID: 25757043 DOI: 10.1111/jpc.12860] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/20/2015] [Indexed: 12/22/2022]
Abstract
Blindness from retinopathy of prematurity (ROP) in Australian and New Zealand is an uncommon event although 3% of <31 weeks gestation infants receive treatment for the disease. New world-wide estimates of the incidence of blindness from ROP are much higher than previously at 20 000 children annually. The impact of severe ROP can be reduced through good evidence-based care of very preterm infants and careful organisation of eye examinations and follow-up services. Recent oxygen saturation targeting trial results might mean the adoption of higher targets than formerly in very preterm infants and will require vigilance to ensure all eligible infants are examined appropriately. A true screening examination for acute ROP might involve non-opthalmologists obtaining photographic retinal images and remote reading of these. Although treatment with laser gives good outcomes, there is interest in intravitreal anti-vascular endothelial factor agents, but issues concerning the systemic safety and retinal results of such treatment are unresolved.
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Affiliation(s)
- Brian A Darlow
- Department of Paediatrics, University of Otago at Christchurch, Christchurch, New Zealand
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Pertl L, Steinwender G, Mayer C, Hausberger S, Pöschl EM, Wackernagel W, Wedrich A, El-Shabrawi Y, Haas A. A Systematic Review and Meta-Analysis on the Safety of Vascular Endothelial Growth Factor (VEGF) Inhibitors for the Treatment of Retinopathy of Prematurity. PLoS One 2015; 10:e0129383. [PMID: 26083024 PMCID: PMC4470662 DOI: 10.1371/journal.pone.0129383] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 05/07/2015] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION Laser photocoagulation is the current gold standard treatment for proliferative retinopathy of prematurity (ROP). However, it permanently reduces the visual field and might induce myopia. Vascular endothelial growth factor (VEGF) inhibitors for the treatment of ROP may enable continuing vascularization of the retina, potentially allowing the preservation of the visual field. However, for their use in infants concern remains. This meta-analysis explores the safety of VEGF inhibitors. METHODS The Ovid Interface was used to perform a systematic review of the literature in the databases PubMed, EMBASE and the Cochrane Library. RESULTS This meta-analysis included 24 original reports (including 1.457 eyes) on VEGF inhibitor treatment for ROP. The trials were solely observational except for one randomized and two case-control studies. We estimated a 6-month risk of retreatment per eye of 2.8%, and a 6-month risk of ocular complication without the need of retreatment of 1.6% per eye. Systemic complications were only reported as isolated incidents. DISCUSSION VEGF inhibitors seem to be associated with low recurrence rates and ocular complication rates. They may have the benefit of potentially allowing the preservation of visual field and lower rates of myopia. Due to the lack of data, the risk of systemic side effects cannot be assessed.
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Affiliation(s)
- Laura Pertl
- Department of Ophthalmology, Medical University Graz, Auenbruggerplatz 4, 8036, Graz, Austria
| | - Gernot Steinwender
- Department of Ophthalmology, Medical University Graz, Auenbruggerplatz 4, 8036, Graz, Austria
| | - Christoph Mayer
- Department of Ophthalmology, Medical University Graz, Auenbruggerplatz 4, 8036, Graz, Austria
| | - Silke Hausberger
- Department of Ophthalmology, Medical University Graz, Auenbruggerplatz 4, 8036, Graz, Austria
| | - Eva-Maria Pöschl
- Department of Ophthalmology, Medical University Graz, Auenbruggerplatz 4, 8036, Graz, Austria
| | - Werner Wackernagel
- Department of Ophthalmology, Medical University Graz, Auenbruggerplatz 4, 8036, Graz, Austria
| | - Andreas Wedrich
- Department of Ophthalmology, Medical University Graz, Auenbruggerplatz 4, 8036, Graz, Austria
| | - Yosuf El-Shabrawi
- Department of Ophthalmology, Klagenfurt Hospital, Feschnigstraße 11, 9020, Klagenfurt am Wörthersee, Austria
| | - Anton Haas
- Department of Ophthalmology, Medical University Graz, Auenbruggerplatz 4, 8036, Graz, Austria
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Pulido CM, Quiram PA. Current understanding and management of aggressive posterior retinopathy of prematurity. World J Ophthalmol 2015; 5:73-79. [DOI: 10.5318/wjo.v5.i2.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/12/2015] [Accepted: 03/05/2015] [Indexed: 02/06/2023] Open
Abstract
Aggressive posterior retinopathy of prematurity (ROP), previously referred to as “Rush disease”, is a rapidly progressive form of ROP. This form of ROP typically presents in very low birth weight babies of early gestational age. Historically, anatomical and functional outcomes have been poor with standard treatment. This review is designed to discuss current knowledge and treatment regarding this aggressive form of ROP. Recommendations regarding management of these difficult cases are detailed.
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Klufas MA, Chan RVP. Intravitreal anti-VEGF therapy as a treatment for retinopathy of prematurity: what we know after 7 years. J Pediatr Ophthalmol Strabismus 2015; 52:77-84. [PMID: 25798707 DOI: 10.3928/01913913-20150216-01] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Accepted: 12/10/2014] [Indexed: 12/21/2022]
Abstract
The authors review published clinical case reports, case series, and clinical trials evaluating the use of anti-vascular endothelial growth factor (VEGF) medications for the primary or adjunctive treatment of retinopathy of prematurity (ROP). A literature search of peer reviewed reports on PubMed was performed. More than 50 pertinent peer-reviewed publications between 2006 and 2014 were selected to be included in this review and are summarized in this report. There is a growing body of literature on the use of anti-VEGF therapy as a treatment for ROP, predominately in the form of case reports and small case series. Adverse effects from anti-VEGF treatment for ROP have been reported, but with limited follow-up time. The use of anti-VEGF as a treatment for ROP remains off-label.
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[Off-label use of intravitreal bevacizumab for severe retinopathy of prematurity]. ACTA ACUST UNITED AC 2014; 90:81-6. [PMID: 25459682 DOI: 10.1016/j.oftal.2014.09.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2011] [Revised: 09/15/2014] [Accepted: 09/30/2014] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To examine the quality of evidence and the variability in the off-label use of intravitreal bevacizumab for retinopathy of prematurity (ROP). METHODS A wide review of the literature was performed using Pubmed, Medline, and Cochrane database, using the words vascular endothelial growth factor (VEGF), retinopathy of prematurity, treatment and bevacizumab. RESULTS Case reports, case series, reviews, one sistematic review and one randomized controlled trial were found on the use of intravitreal bevacizumab in severe ROP, as monotherapy or combined with láser and/or vitrectomy. CONCLUSIONS The results shown on the use of intravitreal bevacizumab in ROP stage 3+ in zone I or in aggressive posterior ROP are promising. However, uncertainty remains regarding its maximum tolerable dose in the neonatal group, its ocular and systemic safety profile, or its efficacy and bioactivity in a developing child. This report found no significant differences in the recurrence rates of ROP stage 3+ in zone II in patients treated with intravitreal bevacizumab monotherapy in comparison to láser, although the latter is the best option due to long-term safety and efficacy. The use of intravitreal bevacizumab is not indicated in stages 1 and 2 of ROP as the risk of severe visual loss is low and VEFG is necessary for normal retinal vessel development. On the other hand, the use of intravitreal bevacizumab would be contraindicated in stages 4 and 5 because the retinal detachment is accelerated.
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Intravitreal injection of bevacizumab for retinopathy of prematurity. Jpn J Ophthalmol 2014; 58:237-43. [DOI: 10.1007/s10384-014-0310-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 01/31/2014] [Indexed: 02/02/2023]
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Jiang Y, Wang H, Culp D, Yang Z, Fotheringham L, Flannery J, Hammond S, Kafri T, Hartnett ME. Targeting Müller cell-derived VEGF164 to reduce intravitreal neovascularization in the rat model of retinopathy of prematurity. Invest Ophthalmol Vis Sci 2014; 55:824-31. [PMID: 24425851 DOI: 10.1167/iovs.13-13755] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To determine whether knockdown of Müller cell-derived VEGFA-splice variant, VEGF164, which is upregulated in the rat retinopathy of prematurity (ROP) model, safely inhibits intravitreal neovascularization (IVNV). METHODS Short hairpin RNAs for VEGF164 (VEGF164.shRNAs) or luciferase.shRNA control were cloned into lentivectors with CD44 promoters that specifically target Müller cells. Knockdown efficiency, off-target effects, and specificity were tested in HEK reporter cell lines that expressed green fluorescent protein (GFP)-tagged VEGF164 or VEGF120 with flow cytometry or in rat Müller cells (rMC-1) by real-time PCR. In the rat oxygen-induced retinopathy (OIR) ROP model, pups received 1 μL subretinal lentivector-driven luciferase.shRNA, VEGFA.shRNA, or VEGF164.shRNA at postnatal day 8 (P8). Analyses at P18 and P25 included: IVNV and avascular retina (AVA); retinal and serum VEGF (ELISA); density of phosphorylated VEGFR2 (p-VEGFR2) in lectin-labeled retinal endothelial cells (ECs; immunohistochemistry); TUNEL staining and thickness of inner nuclear (INL) and outer nuclear layers (ONL) in retinal cryosections; and pup weight gain. RESULTS In HEK reporter and in rMC-1 cells and in comparison to lucifferase.shRNA, VEGFA.shRNA reduced both VEGF120 and VEGF164, but VEGF164.shRNA only reduced VEGF164 and not VEGF120. Compared with luciferase.shRNA, VEGFA.shRNA and VEGF164.shRNA reduced retinal VEGF and IVNV without affecting AVA at P18 and P25. At P25, VEGF164.shRNA more effectively maintained IVNV inhibition than VEGFA.shRNA. VEGFA.shRNA and VEGF164.shRNA reduced pVEGFR2 in retinal ECs at P18, but VEGFA.shRNA increased it at P25. VEGFA.shRNA increased TUNEL+ cells at P18 and decreased ONL thickness at P18 and P25. VEGFA.shRNA and VEGF164.shRNA did not affect pup weight gain and serum VEGF. CONCLUSIONS Short hairpin RNA to Müller cell VEGF164 maintained long-term inhibition of IVNV and limited cell death compared with shRNA to VEGFA.
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Affiliation(s)
- Yanchao Jiang
- Department of Ophthalmology, The John Moran Eye Center, University of Utah, Salt Lake City, Utah
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Diagnostic and Therapeutic Challenges. Retina 2014; 34:414-7. [DOI: 10.1097/iae.0b013e31829f7396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Armada-Maresca F, Peralta-Calvo J, Pastora-Salvador N, Grabowska A, Vallejo-Garcia J. External subretinal drainage, bevacizumab, and scleral buckling for complete exudative retinal detachment after photocoagulation in retinopathy of prematurity. Retin Cases Brief Rep 2014; 8:33-36. [PMID: 25372204 DOI: 10.1097/icb.0b013e3182a48bf1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
BACKGROUND Total serous retinal detachment after laser photocoagulation for retinopathy of prematurity is an infrequent type of retinal detachment in preterm babies. PURPOSE To describe the successful outcome for treatment by scleral drainage, bevacizumab, and scleral buckling for complete serous exudative retinal detachment in a patient with retinopathy of prematurity. METHODS A preterm baby with primary pulmonary hypertension under treatment with sildenafil developed a total (retrolental) serous retinal detachment after photocoagulation for threshold retinopathy. The dense subretinal fluid was externally drained using a bent needle with an infusion placed in the anterior chamber. Additional bevacizumab and scleral buckling helped to control the plus disease and subretinal leakage. RESULTS Retinal apposition was obtained with the described approach. CONCLUSION Total serous retinal detachment is a rare but severe visual complication in retinopathy of prematurity. The described technique may restore the retinae immediately in a visually critical period.
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Affiliation(s)
- Felix Armada-Maresca
- *Department of Ophthalmology, Hospital Universitario La Paz, Madrid, Spain; and †Department of Ophthalmology, Istituto Clinico Humanitas, Rozzano, Milan, Italy
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