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Fukushima M, Iwahashi C, Kurihara T, Kuniyoshi K, Mano F, Endo T, Hayashi A, Kusaka S. Risk factors for reoperation in vitrectomy for stage 4A retinopathy of prematurity. Ophthalmol Retina 2025:S2468-6530(25)00215-5. [PMID: 40349979 DOI: 10.1016/j.oret.2025.05.008] [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: 01/24/2025] [Revised: 04/05/2025] [Accepted: 05/05/2025] [Indexed: 05/14/2025]
Abstract
PURPOSE To determine risk factors for reoperation after vitrectomy for stage 4A retinopathy of prematurity (ROP). DESIGN Retrospective, comparative case series. PARTICIPANTS The selected patients had undergone vitrectomy for stage 4A ROP with a minimum follow-up period of 6 months between 2010 and 2023. METHODS Data collected from patients' charts included gender, gestational age at birth (GA), birth weight (BW), stage of ROP, postmenstrual age (PMA) at vitrectomy, extent of fibrovascular membrane (FVM), preoperative fluorescein angiography, surgical procedure, and subsequent reoperation during the follow-up period. MAIN OUTCOME MEASURES Anatomical success rate, incidence of postoperative vitreous hemorrhage (VH) and redetachment caused by reproliferation, and risk factors for reoperation to treat these postoperative complications. RESULTS We included 132 consecutive eyes (42 bilateral and 48 unilateral) of 90 patients (48 female and 42 male). The mean GA, BW, and PMA at surgery were 24.6 ± 1.6 weeks, 623.3 ± 180.3 g, and 41.6 ± 4.1 weeks, respectively. Final anatomic success was achieved in 128 eyes (97%). Reoperations were necessary due to postoperative VH in 31 eyes (23%), redetachment caused by reproliferation in 8 eyes (6%), and both VH and redetachment caused by reproliferation in 4 eyes (3%). Multivariable logistic regression analysis showed that plus disease (P = 0.007; odds ratio [OR], 3.681; 95% confidence interval [CI], 1.43-9.46) was a risk factor for reoperation due to postoperative VH, and greater extent of fibrovascular membrane (FVM) (P = 0.047: OR, 1.335; 95% CI, 1.004-1.776) and higher grade of fluorescein leakage (P = 0.033; OR, 5.675; 95% CI, 1.149-28.040) were risk factors for reoperation due to redetachment caused by reproliferation. In eyes with plus disease, anti-VEGF therapy as a preoperative adjunct significantly reduced the rate of reoperation for postoperative VH (20.0% vs. 60.7%, P=0.002). CONCLUSION High anatomical success rates could be achieved by vitrectomy for stage 4A ROP. However, eyes with plus disease, greater extent of FVM, or higher grade of fluorescein leakage may have an increased risk of reoperation. In addition, preoperative anti-VEGF therapy may reduce reoperations due to postoperative VH in patients with plus disease.
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Affiliation(s)
- Masaki Fukushima
- Department of Ophthalmology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan; Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Chiharu Iwahashi
- Department of Ophthalmology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Tomoki Kurihara
- Department of Ophthalmology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan; Department of Ophthalmology, Keio University School of Medicine, 35 Shinanochou, Shinjyukuku, Tokyo 160-0016, Japan
| | - Kazuki Kuniyoshi
- Department of Ophthalmology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Fukutaro Mano
- Department of Ophthalmology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Takao Endo
- Department of Ophthalmology, Osaka Women's and Children's Hospital, 840 murodouchou, izumi, Osaka, 594-1101, Japan
| | - Atsushi Hayashi
- Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Shunji Kusaka
- Department of Ophthalmology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
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Basaran Emengen E, Pirhan D, Yazir Y, Duruksu G, Rencber SF, Ozturk A, Kılıc KC. Nintedanib and ranibizumab attenuates pathological neovascularization in a rat model of oxygen induced retinopathy. Exp Eye Res 2025; 253:110285. [PMID: 39952427 DOI: 10.1016/j.exer.2025.110285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 01/14/2025] [Accepted: 02/11/2025] [Indexed: 02/17/2025]
Affiliation(s)
| | - Dilara Pirhan
- Kocaeli University Faculty of Medicine, Department of Ophthalmology, Kocaeli, Turkey
| | - Yusufhan Yazir
- Kocaeli University Faculty of Medicine, Department of Histology and Embryology, Kocaeli, Turkey; Kocaeli University Institute of Health Sciences, Department of Stem Cell, Kocaeli, Turkey; Kocaeli University, Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli, Turkey
| | - Gokhan Duruksu
- Kocaeli University Institute of Health Sciences, Department of Stem Cell, Kocaeli, Turkey; Kocaeli University, Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli, Turkey
| | - Selenay Furat Rencber
- Kocaeli University Faculty of Medicine, Department of Histology and Embryology, Kocaeli, Turkey; Kocaeli University Institute of Health Sciences, Department of Stem Cell, Kocaeli, Turkey; Kocaeli University, Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli, Turkey
| | - Ahmet Ozturk
- Kocaeli University Faculty of Medicine, Department of Histology and Embryology, Kocaeli, Turkey; Kocaeli University Institute of Health Sciences, Department of Stem Cell, Kocaeli, Turkey; Kocaeli University, Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli, Turkey
| | - Kamil Can Kılıc
- Kocaeli University Faculty of Medicine, Department of Histology and Embryology, Kocaeli, Turkey; Kocaeli University Institute of Health Sciences, Department of Stem Cell, Kocaeli, Turkey; Kocaeli University, Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli, Turkey
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Maitra P, Jaju S, Agrawal KU, Das A, Subramaniam P, Venkatapathy N, Shah PK. Comparing safety and efficacy of Bevacizumab, Ranibizumab and Ranibizumab biosimilar in Retinopathy of prematurity. Eye (Lond) 2025:10.1038/s41433-025-03735-z. [PMID: 40016518 DOI: 10.1038/s41433-025-03735-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 02/12/2025] [Accepted: 02/19/2025] [Indexed: 03/01/2025] Open
Abstract
PURPOSE To compare the safety and efficacy of Bevacizumab, Ranibizumab and Ranibizumab biosimilar in treatment of Retinopathy of prematurity (ROP) METHODS: Retrospective study that included newborns with type 1 ROP who received intravitreal Bevacizumab (Avastin) or Ranibizumab (Accentrix) or Ranibizumab biosimilar (Razumab). Babies were followed up as per protocol and retreatment with laser or repeat anti vascular endothelial growth factor (VEGF) was done in case of reactivation and surgery in case of progression to traction. Outcome measures include need for retreatment, proportion of eyes achieving vascularization up to ora and adverse events RESULTS: 148 eyes of 75 babies, received intravitreal injection of which 139 eyes of 70 babies were included in our analysis. 68 eyes received bevacizumab (IVB), 31 eyes received Accentrix (IVA), 40 eyes received Razumab(IVR). The rate of retreatment was 17.6%, 32.2% and 25% for IVB, IVA and IVR respectively (p = 0.1). IVB group showed a significantly delayed reactivation (p < 0.001), while Ranibizumab and its biosimilar Razumab were comparable (p = 0.17). Vascularization up to ora was observed in 60%, 61% and 50% eyes (p = 0.76) at a median of 27, 28 and 24 weeks post-treatment (p = 0.09) in IVB, IVA and IVR groups respectively. No eyes developed intraocular inflammation or cataract. CONCLUSION All three drugs were similar in their efficacy and safety profile with bevacizumab showing a later reactivation.
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Affiliation(s)
- Puja Maitra
- Department of Vitreoretina Services, Aravind, Eye Hospital, Chennai, Tamil Nadu, India
| | - Sujay Jaju
- Ophthalmology Resident, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
| | - Kushal U Agrawal
- Department of Paediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
| | - Abhishek Das
- Department of Paediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
| | - Prema Subramaniam
- Department of Paediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
| | - Narendran Venkatapathy
- Department of Paediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
| | - Parag K Shah
- Department of Paediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India.
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Bayramoglu SE, Sayin N, Erdogan G. Quantitative evaluation of the wide-field fundus photographs in eyes with severe stage 3 and stage 4A retinopathy of prematurity. BMC Ophthalmol 2025; 25:47. [PMID: 39871208 PMCID: PMC11770912 DOI: 10.1186/s12886-025-03869-4] [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: 08/20/2024] [Accepted: 01/14/2025] [Indexed: 01/29/2025] Open
Abstract
BACKGROUND The aim of the study was to investigate the quantitative differences between severe stage 3 and stage 4A retinopathy of prematurity (ROP) by evaluating the pre-treatment fundus photographs. METHODS Thirty-three eyes with clinical diagnosed as severe stage 3 were classified as severe stage 3 group. Twenty-two eyes with retinal detachment without foveal involvement were classified as stage 4A group. Quantitative measurements were performed on pre-treatment 130 degree fundus photographs. RESULTS In the severe Stage 3 group, dense fibrous membranes, vertical tractional bands, and dragging were detected in 18 eyes (55%), in 5 eyes (15%), and in none of the eyes, respectively. In the stage 4A group, dense fibrous membranes, vertical tractional bands, and dragging were detected in 21 eyes (96%), in 22(100%) eyes, and in 17 eyes (77%), respectively. Dragging and vertical tractional bands were higher in the Stage 4A group than in the severe stage 3 group (p = 0.000). Disc-to-fovea distance, the width of the fibrous membranes, the total area of the fibrous membranes, total retinoschisis, and detachment areas were significantly higher in the stage 4A group than in the severe stage 3 group (respectively, p = 0.000,p = 0.006, p = 0.024,p = 0.000). CONCLUSIONS Fibrous membranes and tractional bands can be detected in severe stage 3 ROP, but the width and the total area of the fibrous membranes and total retinoschisis-detachment area were found to be higher in stage 4A eyes. The dragging of the posterior pole can be an important diagnostic indicator for the diagnosis of stage 4A. Therefore this finding may be a simple auxiliary finding for diagnosis and prognosis of stage 4A ROP.
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Affiliation(s)
- Sadik Etka Bayramoglu
- University of Health Sciences, Kanuni Sultan Suleyman Training and Research Hospital, Turgut Ozal Street, Istanbul, Türkiye.
| | - Nihat Sayin
- University of Health Sciences, Kanuni Sultan Suleyman Training and Research Hospital, Turgut Ozal Street, Istanbul, Türkiye
| | - Gurkan Erdogan
- Faculty of Medicine, Ophthalmology Department, Istanbul University, Istanbul, Türkiye
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Padmakumar V, K M H, Jalali S, Panchal B. Management of bleb-like retinal detachment in aggressive retinopathy of prematurity. BMJ Case Rep 2025; 18:e261444. [PMID: 39842895 DOI: 10.1136/bcr-2024-261444] [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] [Indexed: 01/24/2025] Open
Abstract
Bleb-like retinal detachment (BLRD) in posterior zone 1 retinopathy of prematurity (ROP) presents a significant therapeutic challenge and is associated with a guarded visual prognosis. We present a case of a female infant born preterm with a birth weight of 1100 g. Examination revealed bilateral stage 4 aggressive ROP in posterior zone 1 with BLRD. Given the extent of retinal detachment, a combination of bilateral intravitreal bevacizumab injection, followed by lens-sparing vitrectomy surgery was performed. The baby tolerated the procedures well. The initial postoperative course was uneventful, and the child showed good anatomical and visual success. Through this case, we aim to discuss the risk factors associated with BLRD in ROP, the specific treatment challenges encountered and the potential treatment outcomes.
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Affiliation(s)
- Vishakh Padmakumar
- ABRI, LV Prasad Eye Institute, GMRV Campus, Visakhapatnam, Andhra Pradesh, India
| | - Harshitha K M
- ABRI, LV Prasad Eye Institute, GMRV Campus, Visakhapatnam, Andhra Pradesh, India
| | - Subhadra Jalali
- ABRI, KAR Campus, LV Prasad Eye Institute, Hyderabad, Telangana, India
| | - Bhavik Panchal
- ABRI, LV Prasad Eye Institute, GMRV Campus, Visakhapatnam, Andhra Pradesh, India
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Wu KY, Wang XC, Anderson M, Tran SD. Innovative Use of Nanomaterials in Treating Retinopathy of Prematurity. Pharmaceuticals (Basel) 2024; 17:1377. [PMID: 39459018 PMCID: PMC11509985 DOI: 10.3390/ph17101377] [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: 08/06/2024] [Revised: 09/22/2024] [Accepted: 10/12/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Retinopathy of prematurity (ROP) is a severe condition primarily affecting premature infants with a gestational age (GA) of 30 weeks or less and a birth weight (BW) of 1500 g or less. The objective of this review is to examine the risk factors, pathogenesis, and current treatments for ROP, such as cryotherapy, laser photocoagulation, and anti-VEGF therapy, while exploring the limitations of these approaches. Additionally, this review evaluates emerging nanotherapeutic strategies to address these challenges, aiming to improve ROP management. METHODS A comprehensive literature review was conducted to gather data on the pathogenesis, traditional treatment methods, and novel nanotherapeutic approaches for ROP. This included assessing the efficacy and safety profiles of cryotherapy, laser treatment, anti-VEGF therapy, and nanotherapies currently under investigation. RESULTS Traditional treatments, while effective in reducing disease progression, exhibit limitations, including long-term complications, tissue damage, and systemic side effects. Nanotherapeutic approaches, on the other hand, have shown potential in offering targeted drug delivery with reduced systemic toxicity, improved ocular drug penetration, and sustained release, which could decrease the frequency of treatments and enhance therapeutic outcomes. CONCLUSIONS Nanotherapies represent a promising advancement in ROP treatment, offering safer and more effective management strategies. These innovations could address the limitations of traditional therapies, reducing complications and improving outcomes for premature infants affected by ROP. Further research is needed to confirm their efficacy and safety in clinical practice.
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Affiliation(s)
- Kevin Y. Wu
- Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC J1G 2E8, Canada; (K.Y.W.)
| | - Xingao C. Wang
- Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3T 1J4, Canada
| | - Maude Anderson
- Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC J1G 2E8, Canada; (K.Y.W.)
| | - Simon D. Tran
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3A 1G1, Canada
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Lin JB, Narayanan R, Philippakis E, Yonekawa Y, Apte RS. Retinal detachment. Nat Rev Dis Primers 2024; 10:18. [PMID: 38485969 DOI: 10.1038/s41572-024-00501-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/08/2024] [Indexed: 03/19/2024]
Abstract
Retinal detachment (RD) occurs when the neurosensory retina, the neurovascular tissue responsible for phototransduction, is separated from the underlying retinal pigment epithelium (RPE). Given the importance of the RPE for optimal retinal function, RD invariably leads to decreased vision. There are three main types of RD: rhegmatogenous, tractional and exudative (also termed serous) RD. In rhegmatogenous RD, one or more retinal breaks enable vitreous fluid to enter the subretinal space and separate the neurosensory retina from the RPE. In tractional RD, preretinal, intraretinal or subretinal membranes contract and exert tangential forces and elevate the retina from the underlying RPE. Finally, in exudative RD, an underlying inflammatory condition, vascular abnormality or the presence of a tumour causes exudative fluid to accumulate in the subretinal space, exceeding the osmotic pump function of the RPE. The surgical management of RD usually involves pars plana vitrectomy, scleral buckling or pneumatic retinopexy. The approach taken often depends on patient characteristics as well as on practitioner experience and clinical judgement. Advances in surgical technology and continued innovation have improved outcomes for many patients. However, even if retinal re-attachment is achieved, some patients still experience decreased vision or other visual symptoms, such as metamorphopsia, that diminish their quality of life. Continued research in the areas of neuroprotection and retinal biology as well as continued surgical innovation are necessary to enhance therapeutic options and outcomes for these patients.
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Affiliation(s)
- Jonathan B Lin
- Massachusetts Eye and Ear and Harvard Medical School, Boston, MA, USA
| | - Raja Narayanan
- Anant Bajaj Retina Institute, LV Prasad Eye Institute, Hyderabad, India
| | - Elise Philippakis
- Université de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, Paris, France
| | - Yoshihiro Yonekawa
- Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, PA, USA
| | - Rajendra S Apte
- John F. Hardesty, MD, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
- Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
- Department of Developmental, Regenerative, and Stem Cell Biology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
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Murakami T, Okamoto F, Kinoshita T, Shinomiya K, Nishi T, Obata S, Ogura S, Nishihara Y, Tsukitome H, Jujo T, Ueda K, Ishii R, Oshika T. Comparison of long-term treatment outcomes of laser and anti-VEGF therapy in retinopathy of prematurity: a multicentre study from J-CREST group. Eye (Lond) 2023; 37:3589-3595. [PMID: 37149685 PMCID: PMC10686384 DOI: 10.1038/s41433-023-02559-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 04/16/2023] [Accepted: 04/24/2023] [Indexed: 05/08/2023] Open
Abstract
OBJECTIVES To compare real-world, long-term outcomes of laser and anti-vascular endothelial growth factor (VEGF) therapies in patients with retinopathy of prematurity (ROP). METHODS This was a multicentre retrospective study. We included 264 eyes of 139 patients treated for type 1 ROP or aggressive ROP (AROP) who were followed for at least 4 years. Laser treatment was initially performed in 187 eyes (the laser group), and anti-VEGF therapy was initially performed in 77 eyes (the anti-VEGF group). We collected data on sex, birth characteristics, zone, stage, and the presence of plus disease at the time of treatment and best-corrected visual acuity (BCVA), spherical equivalent (SE), and ocular complications (amblyopia and strabismus) in patients aged 4-6 years. We investigated the associations between treatment outcomes (BCVA, SE and the presence of amblyopia and strabismus) and influencing factors, including treatment procedure (anti-VEGF or laser therapy), sex, birth characteristics, zone, stage, and the presence of plus disease, using multivariable analysis and logistic regression analyses. RESULTS The initial treatment procedure was not associated with any specific treatment outcome. Subgroup analysis of patients with zone I ROP revealed that the anti-VEGF-treated eyes had significantly better BCVA and higher SE than laser-treated eyes (p = 0.004, p = 0.009, respectively). Female patients presented significantly better BCVA, less amblyopia and less strabismus than male patients (p < 0.001, p = 0.029, p = 0.008, respectively). CONCLUSIONS In zone I ROP, anti-VEGF therapy led to better visual acuity and less myopic refractive error than laser treatment.
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Affiliation(s)
- Tomoya Murakami
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan.
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
| | - Fumiki Okamoto
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Takamasa Kinoshita
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology, Sapporo City General Hospital, Sapporo, Japan
| | - Kayo Shinomiya
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Tomo Nishi
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology, Nara Medical University, Nara, Japan
| | - Shumpei Obata
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan
| | - Shuntaro Ogura
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yuka Nishihara
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology, Graduate School of Medicine, Kurume University, Kurume, Japan
| | - Hideyuki Tsukitome
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Tatsuya Jujo
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Kaori Ueda
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Division of Ophthalmology, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Japan
| | - Ryota Ishii
- Department of Biostatistics, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Tetsuro Oshika
- Japan-Clinical Retina Study Group (J-CREST), Kagoshima, Japan
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
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Sanghi G, Gupta R, Narula S. Posterior to the ridge laser in zone 2 stage 3 retinopathy of prematurity with plus disease: Efficacy and safety. Indian J Ophthalmol 2023; 71:3501-3505. [PMID: 37870014 PMCID: PMC10752337 DOI: 10.4103/ijo.ijo_1361_23] [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: 05/24/2023] [Revised: 08/07/2023] [Accepted: 08/09/2023] [Indexed: 10/24/2023] Open
Abstract
Purpose This study aimed to ascertain the efficacy and safety of an additional posterior to the ridge laser for treatable zone 2 stage 3 retinopathy of prematurity (ROP). Methods This study was a retrospective chart review of infants undergoing laser treatment for ROP at a single center from March 2014 to March 2022. The chart review specifically searched for infants treated for zone 2 stage 3 ROP with plus disease, where additional posterior to the ridge laser was performed. Results Seventy-eight eyes of 45 infants met the inclusion criterion. The mean birth weight and gestational age were 1166.09 ± 329.66 gm and 29 ± 2 weeks, respectively. Group 1 comprised 52 eyes treated for high-risk prethreshold stage 3 ROP, while group 2 comprised 26 eyes treated for threshold ROP. 532-nm frequency-doubled Nd:YAG laser (Nidek, Japan) was used in all eyes. Apart from the standard laser to the avascular retina, an additional three rows of laser were applied posterior to the ridge in all eyes during the primary laser sitting (except in two eyes where it was performed as a rescue treatment 2 weeks after the first sitting). No complications were observed during or immediately after the laser procedure. A favorable outcome was achieved in 98.07% of eyes with prethreshold ROP and 76.92% of eyes with threshold ROP. Overall, a favorable outcome was achieved in 71 (91.02%) of the 78 eyes. Conclusion Posterior to the ridge laser performed in the primary sitting along with the standard laser for treatable stage 3 ROP in zone 2 is safe and effective. Further prospective studies are needed to study this underutilized approach.
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Affiliation(s)
- Gaurav Sanghi
- Department of Vitreo Retina, Sangam Netralaya, Mohali, Punjab, India
| | - Rajeev Gupta
- Department of Vitreo Retina, Sangam Netralaya, Mohali, Punjab, India
| | - Sunny Narula
- Division of Neonatology, Motherhood Hospital, Mohali, Punjab, India
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Maitra P, Prema S, Narendran V, Shah PK. Safety and efficacy of intravitreal anti vascular endothelial growth factor for severe posterior retinopathy of prematurity with flat fibrovascular proliferation. World J Clin Pediatr 2023; 12:220-229. [PMID: 37753496 PMCID: PMC10518743 DOI: 10.5409/wjcp.v12.i4.220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 06/26/2023] [Accepted: 07/07/2023] [Indexed: 09/06/2023] Open
Abstract
BACKGROUND Intravitreal anti-vascular endothelial growth factor (IVA) injection is known to cause contraction of fibrovascular proliferation (FVP), when present in severe retinopathy of prematurity (ROP). AIM To assess the structural outcomes of IVA injection in the treatment of severe posterior ROP with significant FVP. METHODS It was a retrospective study in which 36 eyes of 18 preterm babies who developed > 4 clock hours of FVP in zone I or posterior zone II, were treated with either intravitreal 0.625 mg bevacizumab or intravitreal 0.2 mg of ranibizumab. Favorable structural outcome included resolution of plus disease and FVP without the development of tractional retinal detachment. Secondary outcome measure included either full retinal maturation at follow-up or development of recurrent disease requiring additional treatment. Adverse outcomes included progression to retinal detachment. RESULTS The mean gestational age of the 18 preterm babies was 30 wk (range 27-36), and mean birth weight was 1319 g (range 650-1980 g). Mean post-menstrual age (PMA) at the time of primary treatment was 35.5 wk (range 31-41 wk). All eyes showed regression of plus disease and FVP. 5 eyes of 3 babies showed reactivation of disease and were treated with repeat IVA (n = 2 eyes) or peripheral laser photocoagulation (n = 3 eyes) respectively. 16 out of 36 (44%) reached retinal vascular maturation at final follow up at 5 years. CONCLUSION There was good resolution of severe posterior ROP with FVP with IVA, with retinal maturity of 44% at 5 year follow-up and a reactivation rate of 13.8%. When the IVA injection is given prior to 37 wk PMA, while disease is in phase 2, it is less likely to cause contracture of pre-existing FVP.
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Affiliation(s)
- Puja Maitra
- Pediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore 641014, Tamil Nadu, India
| | - Subramaniam Prema
- Pediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore 641014, Tamil Nadu, India
| | - Venkatapathy Narendran
- Pediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore 641014, Tamil Nadu, India
| | - Parag K Shah
- Pediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Coimbatore 641014, Tamil Nadu, India
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11
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Modrzejewska M, Nazwalska M. The Long-Term Observation of the Beneficial Effects of Treatment: 0.12 mg Anti-VEGF Monotherapy or Anti-VEGF Combined Therapy and Diode-Laser in Various Stages of Retinopathy of Prematurity-Series of Cases. J Clin Med 2023; 12:5644. [PMID: 37685711 PMCID: PMC10488330 DOI: 10.3390/jcm12175644] [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: 05/21/2023] [Revised: 06/20/2023] [Accepted: 07/11/2023] [Indexed: 09/10/2023] Open
Abstract
Background 2-year observations of ranibizumab monotherapy and combined therapy with diode laser for severe ROP in extremely prematures. Materials and methods: In a group of 18 prematures (n = 36 eyes; 5 study groups); 25.8 ± 1.5 Hbd, birth weight 796.5 ± 166.1 g. Apgar 4.62 ± 1.88) with A-ROP (n = 22; 61%) and 3 ROP (plus) (n = 14; 39%), ranibizumab monotherapy (n = 4 eyes) in dose 0.12 mg/0.12 mL or with diode laser (n = 32 eyes) were applied. The first intervention was carried out in PMA of 33 (gr. 4 and 5) and 34 in (gr. 1, 2, 3), mean follow-up time 21.44 ± 8.7 months. One-way analysis of variance (ANOVA) with Welch's correction, non-parametric Kruskal-Wallis test, Chi square test of independence were used. A retrospective observational study based on a case series. Results Retinal attachment was achieved in 92.3% of the studied eyes. Bilateral retinal detachment was noted in 1 infant (2 eyes). Myopization (-0.75 to -7.5 D) was observed in 5 infants (45%); mild hyperopia (+0.5 to +4.5 D) was observed in the rest infants (55%). Conclusions Individualization strategies in severe ROP with lower dose 0.12 mg Ranibizumab or combined laser-therapy resulted in effective outcomes. Myopia has not been reported in patients where Ranibizumab was the first drug administered in the ROP treatment strategy.
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Affiliation(s)
- Monika Modrzejewska
- Second Department of Ophthalmology, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
| | - Martyna Nazwalska
- Department of Ophthalmology, Independent Public Health Care Center of the Ministry of the Interior and Administration (SP ZOZ MSWiA), ul. Jagiellońska 44, 70-382 Szczecin, Poland;
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12
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Yasin A, Sinha S, Smith R, Jain SF, Hejkal T, Rychwalski P. Reactivation of retinopathy of prematurity six years after intravitreal injection of bevacizumab. J AAPOS 2023; 27:236-239. [PMID: 37451499 DOI: 10.1016/j.jaapos.2023.05.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 05/07/2023] [Accepted: 05/19/2023] [Indexed: 07/18/2023]
Abstract
Although intravitreal anti-vascular endothelial growth factor (VEGF) therapy is effective in the management of retinopathy of prematurity (ROP), reactivations following treatment are known to occur. We present the case of an asymptomatic child who developed a very late reactivation of ROP 6 years after its successful treatment with intravitreal bevacizumab. This case reemphasizes the importance of long-term follow-up after anti-VEGF therapy for ROP until retinal vascularization is complete. It also supports investigating the utility of laser photocoagulation for peripheral avascular retina after successful treatment with anti-VEGF injection for type I ROP.
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Affiliation(s)
- Anas Yasin
- Childrens Hospital and Medical Center, Department of Ophthalmology, Omaha, Nebraska
| | - Shruti Sinha
- Childrens Hospital and Medical Center, Department of Ophthalmology, Omaha, Nebraska
| | - Rachel Smith
- Childrens Hospital and Medical Center, Department of Ophthalmology, Omaha, Nebraska
| | | | - Thomas Hejkal
- Eye Consultants P.C., 8141 W Center Rd, Omaha, Nebraska
| | - Paul Rychwalski
- Childrens Hospital and Medical Center, Department of Ophthalmology, Omaha, Nebraska.
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13
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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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14
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Iwahashi C, Kurihara T, Kuniyoshi K, Kusaka S. Long-Term Visual Prognosis of Patients Following Lens-Sparing Vitrectomy for Stage 4A Retinopathy of Prematurity. Int J Mol Sci 2023; 24:ijms24032416. [PMID: 36768776 PMCID: PMC9916407 DOI: 10.3390/ijms24032416] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/18/2023] [Accepted: 01/21/2023] [Indexed: 01/28/2023] Open
Abstract
This study evaluated the long-term visual outcomes of patients in whom at least one eye underwent successful lens-sparing vitrectomy (LSV) for stage 4A retinopathy of prematurity (ROP). A retrospective chart review was conducted using the data of 61 eyes of 42 patients with a minimum 4-year follow-up after successful LSV, with or without anti-vascular endothelial growth factor (VEGF) therapy, and whose best-corrected visual acuity (BCVA) was measurable using Landolt rings at the final visit. The mean age at the final follow-up was 10.1 ± 3.3 years. Before LSV, all eyes underwent laser ablation therapy. Twenty eyes (32.8%) with high vascular activity received anti-VEGF therapy before LSV. The mean decimal BCVA at the final follow-up was 0.23 ± 0.26 (range: hand motion to 1.2). Twenty-three eyes (54.1%) had a decimal BCVA of ≥0.4. Among 49 phakic eyes at the final examination, the mean refractive error was -10.1 ± 5.0 D, with 37 eyes (75.5%) having high myopia (>-6.0 D). No significant differences were observed in terms of decimal BCVA and refractive errors between eyes with and without anti-VEGF therapy. Approximately half of the patients had a decimal BCVA of ≥0.4, despite myopic refraction after successful LSV for stage 4A ROP. LSV for stage 4A ROP seemed to be associated with good visual function, despite myopic refraction.
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15
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Use of an Iris Speculum for Retrolental Membrane Dissection for Stage 5 Prematurity of Retinopathy Complicated With Pupillary Adhesion. Retina 2023; 43:138-143. [PMID: 31929414 PMCID: PMC9750090 DOI: 10.1097/iae.0000000000002748] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE To report a novel use of an iris speculum to assist with membrane dissection and trough separation for stage 5 retinopathy of prematurity-related funnel-shaped tractional retinal detachment complicated with pupillary adhesion. METHODS Limbus-based closed vitrectomy and membrane dissection were performed in 10 eyes (9 patients) with stage 5 retinopathy of prematurity-related tractional retinal detachment and pupillary adhesion. After synechiolysis, an iris speculum was positioned to enlarge the pupil for surgical visualization and maintain a neutral iris plane. The retrolental membrane was dissected bimanually and circumferentially along the peripheral trough and then toward the central retina with vertical scissors and end-gripping forceps. RESULTS In all 10 eyes, retrolental membranes were entirely removed and troughs were circumferentially unraveled. Follow-up examinations performed 6 to 18 months postoperatively showed reattachment of the retina in 3 eyes with an open-narrow funnel and 6 of 7 eyes with a narrow-narrow funnel. A near-circular pupil without recurrent pupillary adhesion was preserved in all nine eyes showing retinal reattachment. CONCLUSION This use of the iris speculum effectively exposes the surgical field for the entire removal of retrolental tissue and interruption of the peripheral trough in stage 5 retinopathy of prematurity-related tractional retinal detachment complicated with pupillary adhesion. The pupil's configuration is well preserved postoperatively.
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16
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Huang CY, Lai SH, Tseng HJ, Yao TC, Wu WC. Pulmonary function in school-age children following intravitreal injection of bevacizumab for retinopathy of prematurity. Sci Rep 2022; 12:18788. [PMID: 36335152 PMCID: PMC9637204 DOI: 10.1038/s41598-022-22338-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 10/13/2022] [Indexed: 11/06/2022] Open
Abstract
The effect of anti-vascular endothelial growth factor on neonatal lung development was inconclusive. To evaluate pulmonary function in school-age children who have received intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP), this study included 118 school-aged children who were grouped into three groups: full-term control children (group 1), preterm children who had not received IVB treatment (group 2) and preterm children with ROP who had received IVB treatment (group 3). Pulmonary function was measured by spirometry and impulse oscillometry. Pulmonary function was significantly better in group 1 than in groups 2 and 3 (all p < 0.05 in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow between 25 and 75% of FVC (FEF25-75), and respiratory resistance at 5 Hz and difference between respiratory resistance at 5 and 20 Hz (R5-R20). There were no statistically significant differences between group 2 and group 3 in all pulmonary function parameters, including FVC, FEV1, ratio of FEV1 to FVC, FEF25-75, R5, R20, R5-R20, and respiratory reactance at 5 Hz. In conclusion, our study revealed that preterm infants receiving IVB for ROP had comparable pulmonary function at school age to their preterm peers who had not received IVB treatment.
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Affiliation(s)
- Ching-Yen Huang
- grid.413801.f0000 0001 0711 0593Department of Ophthalmology, Chang Gung Memorial Hospital, 5 Fu-Hsin Street, Kweishan, Taoyuan, 33305 Taiwan
| | - Shen-Hao Lai
- grid.145695.a0000 0004 1798 0922College of Medicine, Chang Gung University, Taoyuan, Taiwan ,grid.413801.f0000 0001 0711 0593Division of Pulmonology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Hsiao-Jung Tseng
- grid.413801.f0000 0001 0711 0593Clinical Trial Center, Biostatistics Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tsung-Chieh Yao
- grid.145695.a0000 0004 1798 0922College of Medicine, Chang Gung University, Taoyuan, Taiwan ,grid.413801.f0000 0001 0711 0593Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, 5 Fu-Hsin Street, Gueishan, Taoyuan, 33305 Taiwan
| | - Wei-Chi Wu
- grid.413801.f0000 0001 0711 0593Department of Ophthalmology, Chang Gung Memorial Hospital, 5 Fu-Hsin Street, Kweishan, Taoyuan, 33305 Taiwan ,grid.145695.a0000 0004 1798 0922College of Medicine, Chang Gung University, Taoyuan, Taiwan
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17
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Al-Khaled T, Cole E, Valikodath NG, Khanifar AA, Johnson D, Scripsema NK, Chau FY, Capone A, Chan RVP. POSTERIOR TRACTIONAL MEMBRANES FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINOPATHY OF PREMATURITY. Retin Cases Brief Rep 2022; 16:576-580. [PMID: 32694275 DOI: 10.1097/icb.0000000000001036] [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: 06/11/2023]
Abstract
PURPOSE To report two cases of tractional membrane formation following treatment with anti-vascular endothelial growth factor therapy in infants with Stage-3 retinopathy of prematurity. METHODS Retrospective review of electronic medical record for historical information, clinical examination documentation, and imaging from fundus photography, retinal ultrasonography, and fluorescein angiography. RESULTS Two patients with Stage-3 retinopathy of prematurity, previously treated with laser therapy and intravitreal bevacizumab, were referred to our institution for tractional membranes. The first case is of a male infant with Zone-II disease that progressed to Stage 4A with evidence of inferotemporal tractional retinal detachment only in the left eye. The second case is of a male infant with stable Zone-I disease with an epiretinal membrane in the left eye.Pars plicata vitrectomy and membranectomy were required for both cases because of the concern for subsequent tractional retinal detachment. CONCLUSION Formation of tractional retinal membranes has been associated with anti-vascular endothelial growth factor therapy. These cases describe the formation of posterior tractional membranes after anti-vascular endothelial growth factor therapy. This potential ocular outcome should be considered when determining treatment plans for retinopathy of prematurity.
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Affiliation(s)
- Tala Al-Khaled
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois
| | - Emily Cole
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois
| | - Nita G Valikodath
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois
| | - Aziz A Khanifar
- The Retina Group of Washington, Silver Spring, Maryland; and
| | - Dina Johnson
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois
| | - Nicole K Scripsema
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois
| | - Felix Y Chau
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois
| | | | - Robison Vernon Paul Chan
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois
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18
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Structural outcome following surgery for stage 5 retinopathy of prematurity based on the new international classification: ICROP 3. Retina 2022; 42:1950-1957. [PMID: 35963009 DOI: 10.1097/iae.0000000000003541] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE This study investigated the outcomes of vitrectomy for stage 5 retinopathy of prematurity (ROP) based on the International Classification of Retinopathy of Prematurity 3rd edition (ICROP 3), in which stage 5 ROP is divided into three subgroups. METHODS Fifty-four eyes of 34 patients with stage 5 ROP who underwent vitrectomy between 2004 and 2020 were retrospectively analyzed. Data including sex, gestational age and weight at birth, ICROP 3 subcategories, perioperative use of intravitreal bevacizumab injection (IVB) and laser photocoagulation, surgical procedure and complications, final retinal reattachment, and follow-up period were collected. RESULTS Complete retinal reattachment was achieved in 16 eyes (88.9%) with stage 5A and 13 eyes (39.4%) with stage 5B (P = 0.0003, Wilcoxon rank-sum test). Three patients with stage 5C were considered inoperable. Postoperative anatomical failure was significantly associated with stage (stage 5B vs. 5A; odds ratio, 17.986; 95% confidence interval, 3.712-148.502; P = 0.0001, multivariate logistic regression analysis). Intraoperative IVB was significantly associated with lower postoperative incidence of vitreous hemorrhage and glaucoma (P = 0.041, chi-square test). CONCLUSIONS Staging of preoperative anatomical features based on ICROP 3 is a useful predictor for final anatomical success. Intraoperative IVB might reduce postoperative complication risks.
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19
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Lee IT, Corona ST, Wong TP, Flynn HW, Wykoff CC. Favorable Anti-VEGF Crunch Syndrome: Nonsurgical Relief of Vitreoretinal Traction in Eyes With Proliferative Diabetic Retinopathy and Tractional Retinal Detachment. Ophthalmic Surg Lasers Imaging Retina 2022; 53:455-459. [PMID: 35951712 DOI: 10.3928/23258160-20220628-01] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Herein are reported four eyes among three patients with favorable anti-vascular endothelial growth factor crunch syndrome by which contraction of fibrovascular tissue led to relief of vitreoretinal traction without surgical intervention. This phenomenon led to complete or partial retinal reattachment in two patients with diabetic tractional retinal detachments. These cases represent favorable anatomic outcomes of crunch syndrome secondary to anti-vascular endothelial growth factor pharmacotherapy and are unique compared with most cases, which have been associated with negative outcomes. [Ophthalmic Surg Lasers Imaging Retina 2022;53:455-459.].
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20
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Nakamura S, Nishinaka A, Hidaka Y, Shimazawa M, Thomas L, Bakker RA, Hara H. Efficacy of an Anti-Semaphorin 3A Neutralizing Antibody in a Male Experimental Retinal Vein Occlusion Mouse Model. Invest Ophthalmol Vis Sci 2022; 63:14. [PMID: 35822950 PMCID: PMC9288153 DOI: 10.1167/iovs.63.8.14] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Purpose Semaphorin 3A (Sema3A) is a promising therapeutic target for macular edema in age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion (RVO). Anti-vascular endothelial growth factors (anti-VEGFs) are the current standard of care for many retinal diseases. This study investigated the Sema3A neutralizing antibody BI-X and/or anti-VEGF therapy (aflibercept) in an RVO mouse model. Treatment efficacy was examined and grouped by timing subsequent to the RVO mouse model induction: efficacy against the onset of intraretinal edema 1 day postinduction and protective effects at 7 days postinduction. Methods We examined the changes in expression of Sema3A in the retina of an RVO mouse model. In addition, changes in expression of tumor necrosis factor (TNF)-α and semaphorin-related proteins (neuropilin-1 and plexin A1) in the retina upon treatment were analyzed by Western blotting. The effects of BI-X and/or aflibercept were evaluated using measures of retinal edema, blood flow, and thinning of the inner nuclear layer. Results Induction of vein occlusion in the RVO mouse model significantly increased Sema3A expression in the retina, particularly in the inner nuclear layer. BI-X was effective as a monotherapy and in combination with anti-VEGF therapy, demonstrating a beneficial effect on intraretinal edema and retinal blood flow. Moreover, in the RVO mouse model, BI-X monotherapy normalized the changes in expression of TNF-α and semaphorin-related proteins. Conclusions These findings support targeting Sema3A to treat intraretinal edema and retinal ischemia.
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Affiliation(s)
- Shinsuke Nakamura
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Anri Nishinaka
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Yae Hidaka
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Masamitsu Shimazawa
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Leo Thomas
- Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach and der Riß, Germany
| | - Remko A Bakker
- Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach and der Riß, Germany
| | - Hideaki Hara
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
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21
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Surgical Complications in Retinopathy of Prematurity: Literature Review and Management Strategies. Int Ophthalmol Clin 2022; 62:3-14. [PMID: 35752882 DOI: 10.1097/iio.0000000000000421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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22
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Tang X, Cui K, Lu X, Wu P, Yu S, Yang B, Xu Y, Liang X. A Novel Hypoxia-inducible Factor 1α Inhibitor KC7F2 Attenuates Oxygen-induced Retinal Neovascularization. Invest Ophthalmol Vis Sci 2022; 63:13. [PMID: 35695808 PMCID: PMC9202333 DOI: 10.1167/iovs.63.6.13] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Purpose KC7F2 is a novel molecule compound that can inhibit the translation of hypoxia-inducible factor 1α (HIF1α). It has been reported to exhibit potential antiangiogenic effect. We hypothesized that KC7F2 could inhibit oxygen-induced retinal neovascularization (RNV). The purpose of this study was to investigate this assumption. Methods Oxygen-induced retinopathy (OIR) models in C57BL/6J mice and Sprague-Dawley rats were used for in vivo study. After intraperitoneal injections of KC7F2, RNV was detected by immunofluorescence and hematoxylin and eosin staining. Retinal inflammation was explored by immunofluorescence. EdU incorporation assay, cell counting kit-8 assay, scratch test, transwell assay, and Matrigel assay were used to evaluate the effect of KC7F2 on the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVEC) induced by vascular endothelial growth factor (VEGF) in vitro. Protein expression was examined by Western blot. Results KC7F2 treatment (10 mg/kg/d) in OIR mice significantly attenuated pathological neovascularization and decreased the number of preretinal neovascular cell nuclei, without changing the avascular area, which showed the same trends in OIR rats. Consistently, after the KC7F2 intervention (10 µM), cell proliferation was inhibited in VEGF-induced HUVEC, which was in agreement with the trend observed in the retinas of OIR mice. Meanwhile, KC7F2 suppressed VEGF-induced HUVEC migration and tube formation, and decreased the density of leukocytes and microglia colocalizing neovascular areas in the retinas. Moreover, the HIF1α–VEGF pathway activated in retinas of OIR mice and hypoxia-induced HUVEC, was suppressed by KC7F2 treatment. Conclusions The current study revealed that KC7F2 was able to inhibit RNV effectively via HIF1α–VEGF pathway, suggesting that it might be an effective drug for RNV treatment.
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Affiliation(s)
- Xiaoyu Tang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Kaixuan Cui
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Xi Lu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Peiqi Wu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Shanshan Yu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Boyu Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Yue Xu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Xiaoling Liang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
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23
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Morphological outcome and indication for laser following intravitreal bevacizumab monotherapy for posterior retinopathy of prematurity. Lasers Med Sci 2022; 37:2501-2508. [PMID: 35106690 DOI: 10.1007/s10103-022-03515-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/26/2022] [Indexed: 10/19/2022]
Abstract
The purpose of this study is to determine the natural course of retinal vascular development and recurrence requiring laser in eyes receiving intravitreal bevacizumab (IVB) for posterior retinopathy of prematurity (ROP). Data of babies receiving IVB for posterior ROP was retrospectively analyzed. Birth weight, gestational age (GA) and post-menstrual age (PMA) at injection, need for laser, retinal maturation, and their timing were recorded. The study included 63 eyes of 32 babies, born at a median GA of 31 (IQR 29-32) weeks, and birth weight 1410 (1280-1697.5) g. Aggressive posterior ROP was seen in 36 (57%) eyes and staged ROP in 27 (43%). IVB was injected at a median PMA of 36 (34.5-37) weeks. Complete retinal vascularization was seen in 33 (52.4%) at a median PMA of 52 (47-60) weeks, prophylactic laser was needed in 17 (27%) at 61 (55.5-63) weeks, and only 13 (20.6%) eyes had recurrence needing treatment laser, at 42 (39-57) weeks respectively. Babies requiring laser had a significantly lower birth weight (p = 0.033) and received injection earlier (p = 0.08). Retinal vascular development progresses with IVB monotherapy with 21% of eyes developing recurrence that requires laser in this subset of Indian babies. Following IVB, monotherapy laser can be selectively performed only in cases with recurrence or failure to mature.
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Kondo C, Iwahashi C, Utamura S, Kuniyoshi K, Konishi Y, Wada N, Kawasaki R, Kusaka S. Characteristics of Eyes Developing Retinal Detachment After Anti-vascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity. Front Pediatr 2022; 10:785292. [PMID: 35463897 PMCID: PMC9021749 DOI: 10.3389/fped.2022.785292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 03/15/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND We investigated the incidence and clinical characteristics of eyes showing retinal detachment (RD) after anti-vascular endothelial growth factor (VEGF) for retinopathy of prematurity (ROP). METHODS A retrospective chart review of 76 consecutive eyes of 45 patients (18 girls and 27 boys) with stage 3 ROP who received anti-VEGF therapy between January 2012 and August 2020 with a minimum follow-up of 6 months was conducted. Eyes were divided into two groups: the vitrectomy (V) group that required vitrectomy for RD after anti-VEGF therapy and the non-vitrectomy (non-V) group that did not require vitrectomy. Data were collected from patient charts, including sex, postmenstrual age (PMA) at birth, birth weight, PMA at anti-VEGF therapy, comorbidities, reactivation, examination interval, and subsequent vitrectomies. RESULTS The median PMA at birth was 24.7 (range, 22.1-29.3) weeks. Twenty-seven eyes (35.1%) exhibited ROP reactivation at 6.4 ± 3.1 weeks after anti-VEGF therapy. The V group included six eyes of five patients, all of whom exhibited reactivation and developed RD 10.1 ± 6.5 weeks after anti-VEGF therapy. The types of RD were conventional (classic) in two eyes and circumferential (unique to RD after anti-VEGF) in four eyes. Three eyes required repeated vitrectomy. All eyes, except one eye in the V group, achieved retinal attachment at the last examination. The non-V group included 70 eyes of 40 patients, of which 21 exhibited reactivation and were treated successfully with laser (17 eyes) or second anti-VEGF (4 eyes). The proportion of eyes with plus disease was significantly higher in the V group (50.0%) than in the non-V group (10.0%) (P = 0.035). V group included 3 of 22 eyes (13.6%) in which the interval between the last examination and the diagnosis of reactivation was <1 week and 3 of 5 eyes (60.0%) in which the interval was more than 1 week (P = 0.024). The two groups showed no significant differences in the other factors. CONCLUSION Approximately 8% of eyes developed RD about 10 weeks after anti-VEGF therapy for ROP. Eyes with history of plus disease should be carefully monitored at appropriate intervals after anti-VEGF therapy for ROP.
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Affiliation(s)
- Chiori Kondo
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Chiharu Iwahashi
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Shoko Utamura
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Kazuki Kuniyoshi
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Yuhei Konishi
- Department of Pediatrics, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Norihisa Wada
- Department of Pediatrics, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Ryo Kawasaki
- Department of Vision Informatics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Shunji Kusaka
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan
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Chen PYJ, Rossin EJ, Vavvas DG. Aflibercept for Retinopathy of Prematurity: A Systematic Review and Meta-Analysis. Ophthalmic Surg Lasers Imaging Retina 2021; 52:673-681. [PMID: 34908485 DOI: 10.3928/23258160-20211124-01] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND OBJECTIVE To determine the effectiveness of aflibercept in retinopathy of prematurity (ROP). PATIENTS AND METHODS We performed a systematic review and meta-analysis of proportions from the literature in PubMed and Cochrane Library using search terms related to the use of aflibercept in ROP. Studies in non-preterm infants or that did not use aflibercept as the initial treatment were excluded. Risk of bias was assessed by the ROBINS-I (Risk Of Bias in Non-randomized Studies of Interventions) tool. RESULTS We identified six case series. Collectively, 218 eyes were treated with aflibercept for ROP. We found an average 97% (95% confidence interval [CI], 93% to 99%) regression rate with aflibercept and an average 16% (95% CI, 5% to 41%) recurrence rate. With the exception of one outlier study, these numbers are similar to previous reports using anti-vascular endothelial growth factor (VEGF) agents in ROP. CONCLUSIONS Aflibercept holds promise for use in ROP and has been demonstrated to be efficacious in six case series. Randomized, controlled clinical trials appear warranted to compare aflibercept with other anti-VEGF agents. [Ophthalmic Surg Lasers Imaging. 2021;52:673-681.].
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26
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Huang YH, Kuo CH, Peng IC, Chang YS, Tseng SH, Conway EM, Wu HL. Recombinant thrombomodulin domain 1 rescues pathological angiogenesis by inhibition of HIF-1α-VEGF pathway. Cell Mol Life Sci 2021; 78:7681-7692. [PMID: 34705054 PMCID: PMC11072095 DOI: 10.1007/s00018-021-03950-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 08/12/2021] [Accepted: 09/21/2021] [Indexed: 12/24/2022]
Abstract
Pathological angiogenesis (PA) contributes to various ocular diseases, including age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, which are major causes of blindness over the world. Current treatments focus on anti-vascular endothelial growth factor (VEGF) therapy, but persistent avascular retina, recurrent intravitreal neovascularization, and general adverse effects are reported. We have previously found that recombinant thrombomodulin domain 1 (rTMD1) can suppress vascular inflammation. However, the function of rTMD1 in VEGF-induced PA remains unknown. In this study, we found that rTMD1 inhibited VEGF-induced angiogenesis in vitro. In an oxygen induced retinopathy (OIR) animal model, rTMD1 treatment significantly decreased retinal neovascularization but spared normal physiological vessel growth. Furthermore, loss of TMD1 significantly promoted PA in OIR. Meanwhile, hypoxia-inducible factor-1α, the transcription factor that upregulates VEGF, was suppressed after rTMD1 treatment. The levels of interleukin-6, and intercellular adhesion molecule-1 were also significantly suppressed. In conclusion, our results indicate that rTMD1 not only has dual effects to suppress PA and inflammation in OIR, but also can be a potential HIF-1α inhibitor for clinical use. These data bring forth the possibility of rTMD1 as a novel therapeutic agent for PA.
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MESH Headings
- Animals
- Apoptosis
- Cell Movement
- Cell Proliferation
- Cells, Cultured
- Female
- Gene Expression Regulation
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors
- Hypoxia-Inducible Factor 1, alpha Subunit/genetics
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Male
- Mice, Inbred C57BL
- Mice, Knockout
- Neovascularization, Pathologic/genetics
- Neovascularization, Pathologic/metabolism
- Neovascularization, Pathologic/pathology
- Neovascularization, Pathologic/prevention & control
- Retinal Neovascularization/genetics
- Retinal Neovascularization/metabolism
- Retinal Neovascularization/pathology
- Retinal Neovascularization/prevention & control
- Thrombomodulin/genetics
- Thrombomodulin/metabolism
- Vascular Endothelial Growth Factor A/antagonists & inhibitors
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Mice
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Affiliation(s)
- Yi-Hsun Huang
- Department of Ophthalmology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
| | - Cheng-Hsiang Kuo
- International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan
| | - I-Chen Peng
- Department of Ophthalmology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Yi-Sheng Chang
- Department of Ophthalmology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Sung-Huei Tseng
- Department of Ophthalmology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Edward M Conway
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
| | - Hua-Lin Wu
- International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan.
- Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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27
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Tsai AS, Chou HD, Ling XC, Al-Khaled T, Valikodath N, Cole E, Yap VL, Chiang MF, Chan RVP, Wu WC. Assessment and management of retinopathy of prematurity in the era of anti-vascular endothelial growth factor (VEGF). Prog Retin Eye Res 2021; 88:101018. [PMID: 34763060 DOI: 10.1016/j.preteyeres.2021.101018] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/27/2021] [Accepted: 10/29/2021] [Indexed: 02/06/2023]
Abstract
The incidence of retinopathy of prematurity (ROP) continues to rise due to the improved survival of very low birth weight infants in developed countries. This epidemic is also fueled by increased survival of preterm babies with variable use of oxygen and a lack of ROP awareness and screening services in resource-limited regions. Improvements in technology and a basic understanding of the disease pathophysiology have changed the way we screen and manage ROP, educate providers and patients, and improve ROP awareness. Advancements in imaging techniques, expansion of telemedicine services, and the potential for artificial intelligence-assisted ROP screening programs have created opportunities to improve ROP care in areas with a shortage of ophthalmologists trained in ROP. To address the gap in provider knowledge regarding ROP, the Global Education Network for Retinopathy of Prematurity (GEN-ROP) created a web-based tele-education training module that can be used to educate all providers involved in ROP, including non-physician ROP screeners. Over the past 50 years, the treatment of severe ROP has evolved from limited treatment modalities to cryotherapy and laser photocoagulation. More recently, there has been growing evidence to support the use of anti-vascular endothelial growth factor (VEGF) agents for the treatment of severe ROP. However, VEGF is known to be important in organogenesis and microvascular maintenance, and given that intravitreal anti-VEGF treatment can result in systemic VEGF suppression over a period of at least 1-12 weeks, there are concerns regarding adverse effects and long-term ocular and systemic developmental consequences of anti-VEGF therapy. Future research in ophthalmology to address the growing burden of ROP should focus on cost-effective fundus imaging devices, implementation of artificial intelligence platforms, updated treatment algorithms with optimal use of anti-VEGF and careful investigation of its long-term effects, and surgical options in advanced ROP. Addressing these unmet needs will aid the global effort against the ROP epidemic and optimize our understanding and treatment of this blinding disease.
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Affiliation(s)
- Andrew Sh Tsai
- Singapore National Eye Centre, Singapore; DUKE NUS Medical School, Singapore
| | - Hung-Da Chou
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Xiao Chun Ling
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Tala Al-Khaled
- Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Illinois Eye and Ear Infirmary, Chicago, IL, USA
| | - Nita Valikodath
- Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Illinois Eye and Ear Infirmary, Chicago, IL, USA
| | - Emily Cole
- Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Illinois Eye and Ear Infirmary, Chicago, IL, USA
| | - Vivien L Yap
- Division of Newborn Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Michael F Chiang
- National Eye Institute, National Institutes of Health, Bethesda, MD, USA
| | - R V Paul Chan
- Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Illinois Eye and Ear Infirmary, Chicago, IL, USA.
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Iwahashi C, Utamura S, Kuniyoshi K, Sugioka K, Konishi Y, Wada N, Kusaka S. FACTORS ASSOCIATED WITH REACTIVATION AFTER INTRAVITREAL BEVACIZUMAB OR RANIBIZUMAB THERAPY IN INFANTS WITH RETINOPATHY OF PREMATURITY. Retina 2021; 41:2261-2268. [PMID: 33958533 DOI: 10.1097/iae.0000000000003196] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To investigate the efficacy and risk factors of intravitreal antivascular endothelial growth factor injection (anti-VEGF therapy) for retinopathy of prematurity (ROP). METHODS We retrospectively reviewed 80 consecutive eyes of 43 patients with Type 1 ROP or worse who received anti-VEGF therapy during January 2012-February 2018. Patients were divided into those who were injected with 0.25 mg of bevacizumab (IVB group, 37 eyes) and 0.25 mg of ranibizumab (IVR group, 43 eyes). Serum VEGF concentrations of 18 patients were measured before and after IVR. RESULTS Antivascular endothelial growth factor injection therapy reduced ROP activity in all eyes; however, 14 eyes (17.5%) exhibited reactivation. The reactivation rates of the IVB and IVR groups were 13.5% and 20.9%, respectively (P = 0.556). Multivariate logistic regression analysis showed that postmenstrual age ≤35 weeks at anti-VEGF therapy (P = 0.014) and aggressive posterior ROP (P = 0.044) was significantly associated with reactivation. Serum VEGF was significantly suppressed at Days 1 (P < 0.001) and 7 (P = 0.012) after IVR and returned to the preinjection level by Day 14 (P = 0.210). CONCLUSION Both IVR and IVB seemed effective in reducing ROP activity. Reactivation after anti-VEGF therapy may be associated with younger postmenstrual age at anti-VEGF therapy and aggressive posterior ROP.
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Affiliation(s)
| | | | | | | | - Yuhei Konishi
- Pediatrics, Kindai University Faculty of Medicine, Osaka, Japan
| | - Norihisa Wada
- Pediatrics, Kindai University Faculty of Medicine, Osaka, Japan
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29
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Scleral buckling surgery for stage 4A and 4B retinopathy of prematurity in critically ill neonates. Int Ophthalmol 2021; 42:1093-1100. [PMID: 34724137 DOI: 10.1007/s10792-021-02095-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 10/21/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE To determine the efficacy of scleral buckling in eyes with stage 4A and 4B retinopathy of prematurity (ROP). METHODS Seven eyes of five premature infants underwent scleral buckling for stage 4 ROP in zone II. Five eyes had stage 4A ROP, and two eyes had stage 4B ROP. Six eyes had previous diode laser photocoagulation, and one eye had received an intravitreal ranibizumab injection. Scleral buckling was the procedure of choice due to lack of access to specialized pediatric vitrectomy instrumentation. Average age at surgery was 3.4 months. Postoperative anatomic retinal status, visual acuity outcome and refractive error were assessed. RESULTS The scleral buckle was removed on average 8 months after surgery. Retinal reattachment was achieved in all seven eyes. At final follow-up one eye had macular ectopia and disc dragging, one eye had a macular traction fold and two eyes had optic disc pallor. Average myopic error after buckle removal was -7.5 D. CONCLUSION Scleral buckling can be performed safely and effectively in 4A and 4B stage ROP in critically ill infants, when access to specialized pediatric vitrectomy instrumentation is limited. This surgical technique may provide adequate relief of vitreoretinal traction with improved visual potential.
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30
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Tanaka S, Yokoi T, Katagiri S, Yoshida T, Nishina S, Azuma N. SEVERE RECURRENT FIBROVASCULAR PROLIFERATION AFTER COMBINED INTRAVITREAL BEVACIZUMAB INJECTION AND LASER PHOTOCOAGULATION FOR AGGRESSIVE POSTERIOR RETINOPATHY OF PREMATURITY. Retin Cases Brief Rep 2021; 15:772-777. [PMID: 31339872 DOI: 10.1097/icb.0000000000000887] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE To describe the clinical features of severe recurrent fibrovascular proliferation after intravitreal bevacizumab injections and laser photocoagulation for aggressive posterior retinopathy of prematurity. METHODS This retrospective, nonrandomized case series reviewed the medical and ophthalmic records in the referral hospital and our hospital. PATIENTS Four patients (seven eyes) with aggressive posterior retinopathy of prematurity. RESULTS The patients were referred for vitrectomy with/without lensectomy for recurrent fibrovascular proliferation with a tractional retinal detachment after combined intravitreal bevacizumab injections and laser photocoagulation. Three patients were born at 22 weeks or 23 weeks' gestational age and one patient at 29 weeks' gestational age. Preoperatively, fluorescein angiography images showed all eyes had tractional retinal detachment from regrowth of fibrovascular proliferation 3 months to 5 months after the intravitreal bevacizumab injection and abnormal retinal vasculature; four eyes had a broad ischemic retina. Postoperatively, four eyes had retinal attachment and three eyes a total retinal detachment. Neovascular glaucoma developed in five of the seven eyes during the clinical course. CONCLUSION Severe fibrovascular proliferation may recur due to widespread retinal ischemia with capillary dropout and abnormal vasculature after failed combined intravitreal bevacizumab and laser photocoagulation therapy as the initial treatment for aggressive posterior retinopathy of prematurity. Careful follow-up is important especially after anti-vascular endothelial growth factor treatment, with recognition that severe reactivation is possible.
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Affiliation(s)
- Shin Tanaka
- Department of Ophthalmology and Laboratory for Visual Science, National Center for Child Health and Development, Tokyo, Japan
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31
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Xu LT, Levine DA, Hutchinson AK, Rao P, Hubbard GB. CLINICAL FEATURES AND OUTCOMES OF INFANTS WITH RETINOPATHY OF PREMATURITY WHO FAIL ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY. Retina 2021; 41:2269-2277. [PMID: 34190725 PMCID: PMC8542626 DOI: 10.1097/iae.0000000000003249] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE To describe characteristics and outcomes of patients with retinopathy of prematurity who failed intravitreal antivascular endothelial growth factor. METHODS A retrospective case series of 211 eyes (112 patients) treated with antivascular endothelial growth factor as initial therapy for retinopathy of prematurity at a single academic institution between 2011 and 2019 and an additional 6 eyes (3 patients) referred to us for management of failed antivascular endothelial growth factor. RESULTS Among the 211 eyes receiving initial treatment at our institution, 17 eyes (11%) failed. Of the 23 total eyes managed by us for failure, 3 eyes (13%) failed after 50-week postmenstrual age. Failure manifested as recurrent plus in 14 eyes (58%), recurrent Stage 3 in 13 eyes (54%) and retinal detachment in 5 eyes (21%). Treatment failures were managed with laser (13 eyes), repeat injection (4 eyes), vitrectomy (2 eyes), or a combination of modalities (4 eyes). Follow-up of ≥6 months was available for 18 of the 23 eyes. The retina was fully attached in 17 eyes, and fixation behavior was present in 10 eyes. CONCLUSION The most common manifestations of treatment failure were recurrent plus and Stage 3. The failure rate at our institution was 11.0%. A significant proportion of failures occurred after 50-week postmenstrual age. Most failed eyes had favorable anatomical outcomes and over half demonstrated fixation behavior.
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Affiliation(s)
- Lucy T Xu
- Department of Ophthalmology, Emory Eye Center, Atlanta, Georgia
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32
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Narnaware SH, Bawankule PK, Raje D. Aggressive Posterior Retinopathy of Prematurity (APROP): LASER as the Primary Modality of Treatment. J Ophthalmic Vis Res 2021; 16:400-407. [PMID: 34394869 PMCID: PMC8358764 DOI: 10.18502/jovr.v16i3.9437] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 06/15/2019] [Indexed: 11/29/2022] Open
Abstract
Purpose To study the success rate of LASER as a primary modality of treatment in aggressive posterior retinopathy of prematurity (APROP) cases. Methods This is a prospective case series of 56 eyes of 28 preterm babies (males = 21) with APROP who underwent laser therapy. Babies were divided into groups on the basis of gestational age (GA), birth weight (BW), and postmenstrual age (PMA) at which treatment was performed. GA (in weeks): <28 (n = 7), 28–30 (n = 11), >30 (n = 10). BW (in grams): <1000 (n = 8), 1000–1200 (n = 10), >1200 (n = 10). PMA (in weeks): < 32 (n = 6), 32–34 (n = 18), >34 (n = 4). Success was calculated as complete regression of disease without need for any other modality of treatment such as anti-vascular endothelial growth factor (anti-VEGF) or pars plana vitrectomy. Results The overall success rate was 94.64% (53/56). Two babies who needed additional modality of treatment were <28 weeks of GA (one eye) and 28–30 weeks (two eyes). One baby (one eye) was <1000 gm and the other (two eyes) was >1200 gm, while PMA at which additional treatment was needed was 30 weeks in one baby (one eye) and 33 weeks in the other (two eyes). Conclusion In this era of anti-VEGF treatment, even in cases of APROP, LASER should still be considered as a primary modality of treatment, as it is a one-time treatment without the concern of systemic side effects and recurrent/persistent avascular zones.
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Affiliation(s)
- Shilpi H Narnaware
- Consultant Vitreo-retina & ROP Specialist, Sarakshi Netralaya, Rajiv Nagar, Wardha Road, Nagpur 440025, Maharashtra, India
| | - Prashant K Bawankule
- Vitreo-Retinal Surgeon, Rajiv Nagar, Wardha Road, Nagpur 440025 Maharashtra, India
| | - Dhananjay Raje
- Head, Data Analysis Group, MDS Bio-analytics Pvt. Ltd., Shankar Nagar, Nagpur 440010, Maharashtra, India
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33
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Patel CK, Carreras E, Henderson RH, Wong SC, Berg S. Evolving outcomes of surgery for retinal detachment in retinopathy of prematurity: the need for a national service in the United Kingdom : An audit of surgery for acute tractional retinal detachment complicating ROP in the UK. Eye (Lond) 2021; 36:1590-1596. [PMID: 34290441 PMCID: PMC9307852 DOI: 10.1038/s41433-021-01679-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 06/21/2021] [Accepted: 06/29/2021] [Indexed: 11/09/2022] Open
Abstract
OBJECTIVES To audit the structural and functional outcomes of surgery for acute tractional retinal detachment due to retinopathy or prematurity between 2004 and 2014 in Oxford UK. METHODS Consecutive operations were identified from a surgical log. Clinical data including demography, perioperative data, and retinal outcomes were extracted into a spreadsheet and compared against two international data sets referenced in the method section. Nonparametric tests (Fisher's exact, and the Mann-Whitney U-tests) were used for statistical analysis with a p-value < 0.05 considered significant. RESULTS Twenty-nine eyes of 19 babies underwent surgery. The mean age (SD) at final follow-up was 6.4 (3.7) years of age and comparable to the reference data sets. The mean birth weight and gestational age of babies matched the ETROP data set referenced in the method section. Anatomical success was obtained in 16/29 (55.2%) of eyes and more likely with stage 4 ROP than stage 5 disease (p < 0.05). Thirteen of 29 eyes (44.8%) obtained form vision post-operatively. All instances of macular retinal reattachment during follow up were verified with post-operative OCT. CONCLUSIONS Surgery for stage 5 ROP is not worthwhile. For stage 4 ROP it yielded better visual outcomes than ETROP but registration for visual impairment was not prevented. Innovation such as endoscopic vitrectomy could yield better outcomes. Earlier detection of vitreoretinal fibrosis could result in timelier referral. A formally funded national service is needed to ring-fence resource to avoid delays in access to surgery, which has a narrow surgical window.
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Affiliation(s)
- Chetan Kantibhai Patel
- Oxford Eye Hospital, John Radcliffe Hospital, Oxford, UK. .,Great Ormond Street Hospital for Children, London, UK.
| | - Elisa Carreras
- Oxford Eye Hospital, John Radcliffe Hospital, Oxford, UK.,SJD Barcelona Children's Hospital, Passeig de Sant Joan de Deu,, Barcelona, Spain
| | - Robert H Henderson
- Great Ormond Street Hospital for Children, London, UK.,Moorfields Eye Hospital, London, UK
| | - Sui Chien Wong
- Great Ormond Street Hospital for Children, London, UK.,Moorfields Eye Hospital, London, UK.,Royal Free Hospital, Hampstead, London, UK
| | - Simon Berg
- Oxford Eye Hospital, John Radcliffe Hospital, Oxford, UK
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Wood EH, Chang EY, Beck K, Hadfield BR, Quinn AR, Harper CA. 80 Years of vision: preventing blindness from retinopathy of prematurity. J Perinatol 2021; 41:1216-1224. [PMID: 33674712 PMCID: PMC8225510 DOI: 10.1038/s41372-021-01015-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 02/10/2021] [Accepted: 02/17/2021] [Indexed: 01/31/2023]
Abstract
Retinopathy of prematurity (ROP) is one of the leading yet preventable causes of childhood blindness worldwide. The purpose of this review is to provide a practical template for observational and treatment methods in order to reduce the overall incidence of any ROP and to improve both short-term and long-term outcomes once Type 1 ROP (treatable ROP) develops.
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Affiliation(s)
- Edward H Wood
- Byers Eye Institute, Horngren Family Vitreoretinal Center, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA, USA
| | | | - Kinley Beck
- Eyesight Ophthalmic Services, Portsmouth, NH, USA
| | - Brandon R Hadfield
- University of Texas Health Science Center San Antonio, Department of Pediatrics, Division of Neonatology, San Antonio, TX, USA
| | - Amy R Quinn
- University of Texas Health Science Center San Antonio, Department of Pediatrics, Division of Neonatology, San Antonio, TX, USA
| | - Clio Armitage Harper
- Austin Retina Associates, Austin, TX, USA.
- University of Texas Health Science Center San Antonio, Department of Ophthalmology, San Antonio, TX, USA.
- University of Texas at Austin, Department of Ophthalmology, Austin, TX, USA.
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35
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Tan Y, Fukutomi A, Sun MT, Durkin S, Gilhotra J, Chan WO. Anti-VEGF crunch syndrome in proliferative diabetic retinopathy: A review. Surv Ophthalmol 2021; 66:926-932. [PMID: 33705807 DOI: 10.1016/j.survophthal.2021.03.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 02/23/2021] [Accepted: 03/01/2021] [Indexed: 10/22/2022]
Abstract
Anti-vascular endothelial growth factor (anti-VEGF) crunch syndrome describes the progression to tractional retinal detachment following intravitreal anti-VEGF therapy in an eye with proliferative diabetic retinopathy . We reviewed the literature on the anti-VEGF crunch using the PubMed and Cochrane databases. Anti-VEGF crunch typically manifests as sudden vision loss in the affected eye between 1 and 6 weeks following intravitreal anti-VEGF injection, with a mean onset of 13 days. Risk factors for crunch development include the use of a higher anti-VEGF dose and increased severity of diabetic retinopathy with fibrosis. Our review found that intravitreal anti-VEGF, in particular bevacizumab, should be used with caution when treating patients with severe proliferative diabetic retinopathy and pre-existing intraocular fibrosis. In patients where anti-VEGF is used before a planned vitrectomy, we recommend close monitoring for crunch symptoms and proceeding promptly with surgery if there is new or progression of tractional retinal detachment. For eyes with minimal preexisting traction that develop crunch after anti-VEGF treatment, surgeons should proceed to vitrectomy within 7 days. The existing literature on the anti-VEGF crunch is limited by heterogeneity in the way crunch is documented and characterized and the presence of panretinal photocoagulation as a confounding factor. Because of these methodological flaws, the relative frequency of the anti-VEGF crunch cannot be accurately estimated.
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Affiliation(s)
- Yiran Tan
- South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia.
| | - Akira Fukutomi
- Department of Ophthalmology, Aichi Medical University, Nagakute, Japan
| | - Michelle T Sun
- South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia
| | - Shane Durkin
- South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia
| | - Jagjit Gilhotra
- South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia
| | - Weng Onn Chan
- South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia
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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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Iwahashi C, Tachibana K, Oga T, Kondo C, Kuniyoshi K, Kusaka S. Incidence and Factors of Postoperative Lens Opacity after Lens-Sparing Vitrectomy for Retinopathy of Prematurity. Ophthalmol Retina 2021; 5:1139-1145. [PMID: 33484893 DOI: 10.1016/j.oret.2021.01.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 01/06/2021] [Accepted: 01/12/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE To determine the incidence and factors associated with lens opacity after lens-sparing vitrectomy (LSV) for retinopathy of prematurity (ROP). DESIGN Retrospective, comparative case series. PARTICIPANTS Among the 141 eyes of 94 patients who underwent LSV for ROP between 2006 and 2019, 108 eyes of 71 patients with a minimum follow-up of 12 months after LSV were investigated. METHODS Data were collected from patients' charts, including gender, gestational age at birth, birth weight, stage of ROP, postmenstrual age (PMA) at LSV, surgical procedure, preoperative injection of anti-vascular endothelial growth factor (VEGF) agents, subsequent retinal surgeries, and lensectomy during follow-up. MAIN OUTCOME MEASURES Lens status at last visit, incidence and timing of lensectomy, and risk factors for lens opacity requiring lensectomy. RESULTS Stages of ROP at LSV were 4A, 4B, and 5 in 92 eyes, 13 eyes, and 3 eyes, respectively. The median PMA at LSV was 40.6 weeks. Thirty-two eyes received anti-VEGF therapy before LSV. Lens opacity was found in 17 eyes (15.7%), of which 10 eyes (9.3%) underwent lensectomy. The period between LSV and lensectomy ranged from 21 days to 131.9 months (median, 21.1 months). Eleven other eyes (10.2%) underwent lensectomy as part of a reoperation for worsening of ROP. A total of 80 eyes (74.1%) preserved clear lenses at the latest follow-up examination after surgery (median, 6.8 years; range, 1-14 years). The Kaplan-Meier estimate showed that the proportion of patients with phakia at 5 and 10 years was 92.4% and 89.0%, respectively. Multivariate Cox regression analysis revealed that eyes with the use of tamponade at LSV (P = 0.005; odds ratio [OR], 25.68; 95% confidence interval [CI], 4.187-157.5) and young PMA at LSV (P = 0.033; OR, 1.047; 95% CI, 1.012-1.099) were associated significantly with lens opacity requiring lensectomy. However, anti-VEGF therapy was not associated with lens opacity requiring lensectomy. CONCLUSIONS Nearly 10% of eyes required lensectomy because of lens opacity after LSV for ROP. The development of lens opacity requiring lensectomy seems to be associated with the use of tamponade and young PMA at LSV.
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Affiliation(s)
- Chiharu Iwahashi
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kuniko Tachibana
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Tomoyuki Oga
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Chiori Kondo
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kazuki Kuniyoshi
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Shunji Kusaka
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osaka, Japan.
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Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:6415671. [PMID: 33274003 PMCID: PMC7700023 DOI: 10.1155/2020/6415671] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 06/26/2020] [Accepted: 07/10/2020] [Indexed: 01/01/2023]
Abstract
Control of neovascularization with small molecules is a promising tactics. Here, we tested the roles of sodium butyrate (NaBu) on the neovascularization and primary explained its underlining molecular links. We used models including cell and ex vivo culture of choroid and mouse, as well as the biochemical and cellular techniques, to confirm our hypothesis. We found that treating HUVEC cells with NaBu (both 2.5 mM and 5 mM) significantly inhibited its ability in tube formation and proliferation. This inhibitory effect was also observed in choroid sprouting experiments, compared to the control. Interestingly, the choroid sprouting suppressed by NaBu can proliferate again after removing it, indicating that the cell cycle progression might be arrested. The laser-induced choroid neovascularization (CNV) was significantly alleviated by assessing the CNV size (decreased to 0.73 fold) in contrast with the vehicle control group after 2.5 mM NaBu injection for 7 days. Mechanistically, we found an enhanced TXNIP expression in response to NaBu treatment in all the three models. Overexpressing TXNIP in HUVEC cells blocked its tube formation and inhibited its proliferation; on the other hand, knocking down its expression with shRNA reversed those phenotypes in context of NaBu treatment. Further investigation showed the expression of VEGF receptor 2 (VEGFR2) in HUVEC cells was regulated by TXNIP undergoing NaBu treatment. We therefore argued that NaBu inhibited neovascularization partially through TXNIP-regulated VEGFR2 signal pathway.
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Seery CW, Betesh S, Guo S, Zarbin MA, Bhagat N, Wagner RS. Update on the Use of Anti-VEGF Drugs in the Treatment of Retinopathy of Prematurity. J Pediatr Ophthalmol Strabismus 2020; 57:351-362. [PMID: 33211892 DOI: 10.3928/01913913-20200824-02] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Accepted: 04/30/2020] [Indexed: 11/20/2022]
Abstract
Retinopathy of prematurity (ROP) is one of the many significant consequences of premature birth and remains one of the leading causes of visual impairment in infants. Originally, cryotherapy was used to prevent the complications of vitreous hemorrhage and retinal detachment. Subsequently, laser photocoagulation, which is at least as effective and possibly safer than cryoretinopexy, was adopted as the primary treatment for type 1 ROP (stage 2 or 3 disease in zone II with plus disease or any stage disease in zone I with plus disease or stage 3 disease in zone I without plus disease). Laser therapy has been proven effective, and has a degree of permanence that is yet to be matched by alternative treatments, but can be associated with significant ocular side effects such as myopia. Treatment of type 1 ROP with anti-vascular endothelial growth factor (VEGF) agents seems to have fewer ocular side effects than laser ablation of the retina, particularly if used to treat type 1 ROP in zone I. However, ROP recurrence is a real threat after anti-VEGF therapy and long-term systemic side effects of this therapy remain under evaluation. This review focuses on the ophthalmic and systemic benefits and risks of anti-VEGF therapies for ROP as compared to retinal photocoagulation. Anti-VEGF therapies have dramatically altered the management of ROP and have also been shown to be beneficial with regard to the visual prognosis of patients with ROP, but patients so treated require frequent short- and long-term follow-up to detect and manage potential complications associated with this form of treatment. Such information also will allow clinicians to characterize the efficacy, side effect profile, and utility of intravitreal anti-VEGF agents for this condition. Prospective studies are needed to identify the optimum anti-VEGF drug and dose. [J Pediatr Ophthalmol Strabismus. 2020;57(6):351-362.].
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Patel A, Padhy SK, Saoji K, Saldna M, Multani PK, Khalsa A, Kelgaonkar A, Bhusal U, Nayak S, Das T, Jalali S, Padhi TR. Bleb-like posterior combined retinal detachment in severe retinopathy of prematurity: clinical characteristics, management challenges and outcome. Eye (Lond) 2020; 35:3152-3155. [PMID: 33070158 PMCID: PMC8526577 DOI: 10.1038/s41433-020-01223-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 09/30/2020] [Accepted: 10/05/2020] [Indexed: 11/09/2022] Open
Affiliation(s)
- Anamika Patel
- Department of Retina and Vitreous, MithuTulasiChanrai Campus, LV Prasad Eye Institute, Bhubaneswar, India
| | - Srikanta Kumar Padhy
- Department of Retina and Vitreous, MithuTulasiChanrai Campus, LV Prasad Eye Institute, Bhubaneswar, India
| | - Ketan Saoji
- Department of Retina and Vitreous, GMR Varalakshmi Campus, LV Prasad Eye Institute, Visakhapatnam, India
| | - Merlin Saldna
- Department of Retina and Vitreous, GMR Varalakshmi Campus, LV Prasad Eye Institute, Visakhapatnam, India
| | - Prabhjot Kaur Multani
- Department of Retina and Vitreous, MithuTulasiChanrai Campus, LV Prasad Eye Institute, Bhubaneswar, India
| | - Ashish Khalsa
- Department of Retina and Vitreous, MithuTulasiChanrai Campus, LV Prasad Eye Institute, Bhubaneswar, India
| | - Anup Kelgaonkar
- Department of Retina and Vitreous, MithuTulasiChanrai Campus, LV Prasad Eye Institute, Bhubaneswar, India
| | - Utpal Bhusal
- Department of Retina and Vitreous, MithuTulasiChanrai Campus, LV Prasad Eye Institute, Bhubaneswar, India
| | - Sameer Nayak
- Department of Retina and Vitreous, MithuTulasiChanrai Campus, LV Prasad Eye Institute, Bhubaneswar, India
| | - Taraprasad Das
- Srimati Kanuri Santhamma center for Vitreoretinal Diseases, KallamAnji Reddy Campus, LV Prasad Eye Institute, Hyderabad, Telangana, India
| | - Subhadra Jalali
- Srimati Kanuri Santhamma center for Vitreoretinal Diseases, KallamAnji Reddy Campus, LV Prasad Eye Institute, Hyderabad, Telangana, India
| | - Tapas Ranjan Padhi
- Department of Retina and Vitreous, MithuTulasiChanrai Campus, LV Prasad Eye Institute, Bhubaneswar, India.
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Harper CA, Beck KD, Chang E, Young R, Moshfeghi DM. Playing With Fire. Ophthalmic Surg Lasers Imaging Retina 2020; 51:542-544. [PMID: 33104220 DOI: 10.3928/23258160-20201005-01] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 08/20/2020] [Indexed: 11/20/2022]
Abstract
The authors present their concerns surrounding data presented in studies from 2018 and 2020 regarding very low dose bevacizumab for the treatment of retinopathy of prematurity. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:542-544.].
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Beck KD, Rahman EZ, Ells A, Mireskandari K, Berrocal AM, Harper CA. SAFER-ROP: Updated Protocol for Anti-VEGF Injections for Retinopathy of Prematurity. Ophthalmic Surg Lasers Imaging Retina 2020; 51:402-406. [DOI: 10.3928/23258160-20200702-05] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 05/27/2020] [Indexed: 11/20/2022]
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Sen P, Wu WC, Chandra P, Vinekar A, Manchegowda PT, Bhende P. Retinopathy of prematurity treatment: Asian perspectives. Eye (Lond) 2020; 34:632-642. [PMID: 31664193 PMCID: PMC7093470 DOI: 10.1038/s41433-019-0643-4] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 07/05/2019] [Indexed: 01/04/2023] Open
Abstract
Retinopathy of prematurity (ROP) is a vasoproliferative disease of developing retinal vessels that affects premature infants and can lead to severe and irreversible visual loss if left untreated. India and some other Asian countries are in the middle of a 'third ROP epidemic'. Blindness due to ROP is largely preventable if appropriate, adequate and accessible screening programmes are available. Screening of the premature babies is the first step in ROP management. With the increase in use of tele-screening techniques, more premature babies have been brought under the screening network both from urban and rural regions. Laser photocoagulation to the avascular retina using indirect ophthalmoscopy delivery system is the gold standard for ROP treatment and is usually done under topical anaesthesia in the Asian region in contrast to the western world. Use of intravitreal anti-vascular endothelial growth factors (VEGF) although controversial in management of ROP has been found to be effective in various Asian studies as well. ROP surgery in India and other middle-income Asian countries is largely performed only in few tertiary eye care centres. Poor visual prognosis, late presentation with advanced retinal detachments, lack of adequate number of trained paediatric retinal surgeons and paediatric anaesthetists also contribute to this problem. This current paper summarizes the Asian experience of ROP management.
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Affiliation(s)
- Parveen Sen
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, India
| | - Wei-Chi Wu
- Chang Gung Memorial Hospital Taoyuan, Taoyuan, Taiwan
| | - Parijat Chandra
- Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Anand Vinekar
- Paediatric Retina Department, Narayana Nethralaya, Bangalore, India
| | | | - Pramod Bhende
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, India.
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Sun M, Wadehra M, Casero D, Lin MC, Aguirre B, Parikh S, Matynia A, Gordon L, Chu A. Epithelial Membrane Protein 2 (EMP2) Promotes VEGF-Induced Pathological Neovascularization in Murine Oxygen-Induced Retinopathy. Invest Ophthalmol Vis Sci 2020; 61:3. [PMID: 32031575 PMCID: PMC7325623 DOI: 10.1167/iovs.61.2.3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 11/07/2019] [Indexed: 02/07/2023] Open
Abstract
Purpose Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. ROP occurs as a consequence of postnatal hyperoxia exposure in premature infants, resulting in vasoproliferation in the retina. The tetraspan protein epithelial membrane protein-2 (EMP2) is highly expressed in the retinal pigment epithelium (RPE) in adults, and it controls vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line. We, therefore, hypothesized that Emp2 knockout (Emp2 KO) protects against neovascularization in murine oxygen-induced retinopathy (OIR). Methods Eyes were obtained from wildtype (WT) and Emp2 KO mouse pups at P7, P12, P17, and P21 after normoxia or hyperoxia (P7-P12) exposure. Following hyperoxia exposure, RNA sequencing was performed using the retina/choroid layers obtained from WT and Emp2 KO at P17. Retinal sections from P7, P12, P17, and P21 were evaluated for Emp2, hypoxia-inducible factor 1α (Hif1α), and VEGF expression. Whole mount images were generated to assess vaso-obliteration at P12 and neovascularization at P17. Results Emp2 KO OIR mice demonstrated a decrease in pathologic neovascularization at P17 compared with WT OIR mice through evaluation of retinal vascular whole mount images. This protection was accompanied by a decrease in Hif1α at P12 and VEGFA expression at P17 in Emp2 KO animals compared with the WT animals in OIR conditions. Collectively, our results suggest that EMP2 enhances the effects of neovascularization through modulation of angiogenic signaling. Conclusions The protection of Emp2 KO mice against pathologic neovascularization through attenuation of HIF and VEGF upregulation in OIR suggests that hypoxia-induced upregulation of EMP2 expression in the neuroretina modulates HIF-mediated neuroretinal VEGF expression.
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Affiliation(s)
- Michel Sun
- Department of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States
| | - Madhuri Wadehra
- Department of Pathology Lab Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States
- Jonsson Comprehensive Cancer, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States
| | - David Casero
- Department of Pathology Lab Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States
| | - Meng-Chin Lin
- Division of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States
| | - Brian Aguirre
- Department of Pathology Lab Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States
| | - Sachin Parikh
- Laboratory of Ocular and Molecular Biology and Genetics, Jules Stein Institute, University of California-Los Angeles, Los Angeles, California, United States
| | - Anna Matynia
- Laboratory of Ocular and Molecular Biology and Genetics, Jules Stein Institute, University of California-Los Angeles, Los Angeles, California, United States
| | - Lynn Gordon
- Department of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States
| | - Alison Chu
- Division of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States
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Xu W, Cheng W, Cui X, Xu G. Therapeutic effect against retinal neovascularization in a mouse model of oxygen-induced retinopathy: bone marrow-derived mesenchymal stem cells versus Conbercept. BMC Ophthalmol 2020; 20:7. [PMID: 31906900 PMCID: PMC6945477 DOI: 10.1186/s12886-019-1292-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 12/27/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND To study the therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSC) against retinal neovascularization and to compare with anti-vascular endothelial growth factor (VEGF) therapy. METHODS Neonatal C57BL/6 mice were exposed in hyperoxygen and returned to room air to develop oxygen-induced retinopathy (OIR). Red fluorescent protein-labeled BMSC and Conbercept were intravitreally injected into OIR mice, respectively. Inhibition of neovascularization and apoptosis in OIR mice were assessed through retinal angiography, histopathology and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS BMSC were able to migrate and integrate into the host retina, significantly inhibit retinal neovascular tufts and remodel the capillary network after injecton. Treatment with BMSC increased the retinal vascular density, decreased the number of acellular capillaries and inhibited retinal cell death. This effect was not inferior to current anti-VEGF therapy by using Conbercept. CONCLUSIONS Intravitreal injection of BMSC exerts a protective effect against retinal neovascularization and offers a therapeutic strategy for oxygen-induced retinopathy.
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Affiliation(s)
- Wei Xu
- Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou City, 350005 China
| | - Weijing Cheng
- Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou City, 350005 China
- Fujian Institute of Ophthalmology, Fuzhou, China
| | - Xiaoyuan Cui
- Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou City, 350005 China
| | - Guoxing Xu
- Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou City, 350005 China
- Fujian Institute of Ophthalmology, Fuzhou, China
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Chandra P, Kumawat D, Agarwal D, Chawla R. Combined Vitrectomy and Anti-VEGF Treatment for Stage 4 Retinopathy of Prematurity With Extensive Neovascular Proliferation. J Pediatr Ophthalmol Strabismus 2020; 57:61-66. [PMID: 31972043 DOI: 10.3928/01913913-20191030-01] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/03/2019] [Indexed: 11/20/2022]
Abstract
PURPOSE To study the role of combined vitrectomy and intravitreal anti-vascular endothelial growth factor (VEGF) injection for stage 4 retinopathy of prematurity (ROP) with extensive neovascular proliferation. METHODS In a retrospective interventional study at a tertiary eye care center, 15 eyes (9 infants) with advanced stage 4 ROP underwent 25-gauge vitrectomy combined with intravitreal 0.625 mg of bevacizumab (n = 12) or 0.25 mg of ranibizumab (n = 3) injection and were followed up until 65 weeks' postconceptional age (PCA). The perinatal history, tractional retinal detachment (TRD) characteristics (zone, stage, and presence of "plus" disease), treatment details, and anatomical outcomes were reviewed. The main outcome measures were fibrovascular tissue and TRD regression and final macular status. RESULTS Mean gestational age and birth weight were 28.5 ± 1.2 weeks and 1,167 ± 185 g, respectively. Thirteen eyes had zone I disease and 2 eyes had zone II disease. Thirteen eyes were stage 4A and 2 eyes were stage 4B ROP. The morphology was aggressive posterior ROP in 10 eyes. The mean PCA at surgery was 37.8 ± 2.3 weeks. Lensectomy was also performed in 2 eyes. Rapid fibrovascular tissue regression was seen in 14 eyes within 2 weeks, followed by TRD regression and macular vascularization, although 2 eyes had macular pucker formation. Persistent vitreous bleeding was present in 1 eye, which needed lavage, and eventually the TRD regressed. Disease reactivation was noted in 1 eye at 5 weeks and was managed with repeat intravitreal anti-VEGF injection. CONCLUSIONS Anti-VEGF treatment combined with vitrectomy leads to rapid disease regression in advanced stage 4 ROP with extensive neovascular proliferation. [J Pediatr Ophthalmol Strabismus. 2020;57(1):61-66.].
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Ling KP, Liao PJ, Wang NK, Chao AN, Chen KJ, Chen TL, Hwang YS, Lai CC, Wu WC. RATES AND RISK FACTORS FOR RECURRENCE OF RETINOPATHY OF PREMATURITY AFTER LASER OR INTRAVITREAL ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY. Retina 2019; 40:1793-1803. [DOI: 10.1097/iae.0000000000002663] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Bowe T, Ung C, Campbell JP, Yonekawa Y. Telemedicine for Retinopathy of Prematurity in 2020. JOURNAL OF VITREORETINAL DISEASES 2019; 3:452-458. [PMID: 34278186 PMCID: PMC8281828 DOI: 10.1177/2474126419867634] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Purpose: Retinopathy of prematurity (ROP) is the leading cause of visual impairment in premature infants, and middle-income nations are currently experiencing the “third epidemic” of ROP. Screening programs are essential to prevent negative visual outcomes, but screening efforts require a great amount of resources from healthcare systems and are difficult to marshal, particularly in geographically isolated or resource-limited settings. Telemedical screening programs using remote digital fundus imaging (RDFI) systems hold the promise of alleviating many of the burdens that currently make screening for ROP logistically challenging. Methods: Literature review of the current evidence for RDFI telescreening for ROP, with editorial discussion and recommendations. Results: In this review, we summarize the robust body of literature regarding the efficacy of RDFI, the feasibility of telescreening programs, and experiences from current live telescreening programs. We discuss the strengths and limitations of the current evidence and of the screening programs and consider the best practices in developing de novo telemedical screening programs for ROP. The review concludes with a discussion of promising future areas of research and development. Conclusions: RDFI ROP screening programs can be accurate and reliable. They show promise in improving many current challenges in screening infants for ROP, may be able to improve some aspects of care, and have been demonstrated to be cost-effective.
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Affiliation(s)
- Theodore Bowe
- Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
- Pediatric Retina Service, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Cindy Ung
- Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
| | - J. Peter Campbell
- Department of Ophthalmology, Casey Eye Institute, Oregon Health & Sciences University, Portland, OR
| | - Yoshihiro Yonekawa
- Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
- Pediatric Retina Service, Boston Children’s Hospital, Harvard Medical School, Boston, MA
- Mid Atlantic Retina, Wills Eye Hospital, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA
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A Surgical Technique for the Management of Tractional Retinal Detachment in Aggressive Posterior Retinopathy of Prematurity Treated With Intravitreal Bevacizumab. Retina 2019; 39 Suppl 1:S156-S159. [DOI: 10.1097/iae.0000000000002304] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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50
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Patel SN, Klufas MA. Evidence to date: ranibizumab and its potential in the treatment of retinopathy of prematurity. Eye Brain 2019; 11:25-35. [PMID: 31693715 PMCID: PMC6711562 DOI: 10.2147/eb.s189684] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 07/25/2019] [Indexed: 12/21/2022] Open
Abstract
Retinopathy of prematurity (ROP) is a leading and preventable cause of childhood blindness worldwide. Although laser photocoagulation remains the gold standard for treatment, the off-label use of anti-vascular endothelial growth factor (anti-VEGF) therapy to treat ROP, particularly posterior zone I disease, is increasing. Although initial studies on anti-VEGF therapy for ROP have focused on bevacizumab, recent studies have proposed that ranibizumab may be a safer and more effective alternative for use in this population. This review updates recent evidence regarding the use of ranibizumab in the management of ROP.
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Affiliation(s)
- Samir N Patel
- The Retina Service of Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, PA, USA
| | - Michael A Klufas
- The Retina Service of Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, PA, USA
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