Non-surgical treatment of stage 4A retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants, often requiring surgical interventions in advanced stages. This retrospective case series study investigates non-surgical management for Stage 4A ROP, specifically the use of combined laser therapy and intravitreal anti-vascular endothelial growth factor (VEGF) injections. METHODS: Ten eyes from five infants with Stage 4A ROP were treated with a combined laser and anti-VEGF approach. Comprehensive follow-up examinations were conducted to evaluate the treatment outcomes. RESULTS: The study demonstrated successful retinal attachment without complications, showcasing the efficacy and safety of this non-surgical method. A comparison with surgical interventions highlighted the potential benefits in terms of reduced adverse effects. DISCUSSION: This combined treatment emerges as a promising first-choice option for Stage 4A ROP, offering rapid regression without surgical intervention, particularly in early stages. However, larger randomized clinical trials are necessary to validate these findings and establish definitive guidelines for managing this complex condition. CONCLUSION: Combined laser and anti-VEGF therapy proved to be an effective and safe non-surgical approach for Stage 4A ROP, with the potential to reduce the need for surgery, especially in its early presentation. Further research is required to confirm these findings and provide comprehensive recommendations for clinical practice.

4D label-free proteomics analysis of oxygen-induced retinopathy with or without anti-VEGF treatment.

Oxygen-induced retinopathy (OIR) animal model is widely used for retinopathy of prematurity (ROP) researches. The purpose of this study was to identify proteins and related pathways of OIR with or without anti-vascular endothelial growth factor (VEGF) treatment, for use as biomarkers in diagnosing and treating ROP. Nine samples were subjected to proteomic analysis. Retina specimens were collected from 3 OIR mice, 3 OIR mice with anti-VEGF treatment and 3 normal mice (control group). Liquid chromatography-tandem mass spectrometry analysis was performed using the 4D label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, InterPro (IPR) and protein interactions were analyzed. In total, 4585 unique proteins were identified as differentially expressed proteins (DEPs). Enrichment analysis of the GO and KEGG indicated functional clusters related to peptide biosynthetic and metabolic process, cellular macromolecule biosynthetic process and nucleic acid binding in OIR group. For anti-VEGF treatment group, DEPs were clustered in DNA replication, PI3K/Akt signaling pathway and Jak/STAT signaling pathway. Proteomic profiling is useful for the exploration of molecular mechanisms of OIR and mechanisms of anti-VEGF treatment. These findings may be useful for identification of novel biomarkers for ROP pathogenesis and treatment.

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity: Two-Year Efficacy and Safety Outcomes in the Nonrandomized Controlled Trial FIREFLEYE next.

Importance: Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. Objective: To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). Design, Setting, and Participants: This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Interventions: Complications of ROP treated at investigator discretion (no study treatment). Main Outcomes and Measures: Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Results: Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. Conclusions and Relevance: In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. Trial Registration: ClinicalTrials.gov Identifier: NCT04015180.

Melatonin and its bioisosteres as potential therapeutic agents for the treatment of retinopathy of prematurity.

We conducted a study on the impact of intraperitoneal injections of melatonin and its three bioisosteres (compounds 1-3) on the development of oxygen-induced retinopathy in newborn rats during a 21-day experiment. It was demonstrated that melatonin and its analogues 1-3 effectively reduce the total protein concentration in the vitreous body of rat pups, decrease concentration of VEGF-A, and lower the level of oxidative stress (as indicated by normalization of antioxidant activity in the vitreous body). Melatonin and its analogues 1-3 equally normalize the level of VEGF-A. Analogues 1 and 2 even exceed melatonin in their ability to reduce protein influx into the vitreous body. However, analogue 2 had no effect on antioxidant activity, while analogues 1 and 3 caused a significant increase in this parameter, with analogue 3 even slightly exceeding melatonin. Thus, it can be concluded that analogues 1-3 are comparable to melatonin and can be utilized as potential therapeutic agents for the treatment of retinopathy of prematurity.

Unilateral Retinopathy in a Preterm Infant With 4q Duplication: Description and Management.

A 33-5/7, 1570 g dichorionic diamniotic twin presented with cryptorchidism, failed hearing examination (both ears), poor feeding, profound hypoglycemia, coagulopathy, conjugated hyper-bilirubinemia, hydronephrosis, and hypotension. Microarray sent with results of whole genome SNP microgray analysis detected an interstitial duplication of the chromosomal segment 4q35 1q35.2. On this basis, telemedicine screening was performed to evaluate for ocular abnormalities in association with abnormal gene testing. Unilateral advanced retinopathy was noted affecting the right eye, with mature vascularization in the left eye. This infant was managed in concordance with retinopathy of prematurity guidelines, despite not making screening criteria. Off-label intravitreal bevacizumab injection (0.625 mg in 0.025 mL) resulted in full vascular maturation assessed by fluorescein angiography 6 months later. This represents the first description and management of retinopathy in 4q duplication syndrome. [Ophthalmic Surg Lasers Imaging Retina 2024;55:228-230.].

Management of Icteric Vitreous, Retinal Opacification, and Atypical Retinopathy of Prematurity.

A dichorionic, diamniotic twin born at 24-0/7 weeks and 740 g developed hyperbilirubinemia, necrotizing enterocolitis, and sepsis. Photographic imaging documented vitreous opacification, which was absent in the fellow twin. Retinal opacification was presumed secondary to embolic sepsis and responded to systemic antibiotics. Subsequent dropout of vascularized retina corresponded to areas of retinal opacification. Type 1 retinopathy of prematurity (ROP)-Zone I, Stage 3 ROP bilateral-demonstrated a rapid and durable response to off-label intravitreal bevacizumab 0.625 mg. Retinal opacification resolved between 39 and 40 weeks postmenstrual age. Systemic comorbidities may alter the appearance, course, and management of ROP. [Ophthalmic Surg Lasers Imaging Retina 2024;55:164-167.].

Intra-Anterior Chamber Injection of Ranibizumab in Advanced Pediatric Vitreoretinal Diseases.

Importance: Anti-vascular endothelial growth factor (VEGF) treatment through intravitreal or subretinal administrations has been proven effective for VEGF-driven pediatric vitreoretinal diseases but are not feasible for advanced cases, such as shallow traction retinal detachments or peripheral circumferential retinal detachments which adhere to the lens. Intra-anterior chamber injection (IAcI) of anti-VEGF may be a viable alternative in such cases but needs evaluation. Objective: To investigate the effects and safety of IAcI of anti-VEGF to treat VEGF-driven pediatric vitreoretinal diseases. Design, Setting, and Participants: This was a retrospective observational case series study conducted at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine in China. The study included 14 eyes of 13 children diagnosed with vitreoretinal disease exhibiting elevated vascular activity between January and August 2023. Intervention: IAcI with ranibizumab. Main Outcomes and Measures: Retinal vascular abnormalities, vitreous hemorrhage resolution, and complications 1 month and 3 months after injection. Results: Of 13 patients included in this study, 12 were male. The mean age was 4.6 years (range, 1 month to 9 years). Six patients were diagnosed with familial exudative vitreoretinopathy, 4 with morning glory syndrome, 1 with retinopathy of prematurity, and 2 with chronic retinal detachments of unknown causes. At 1-month postoperative follow-up, vascular activity had decreased in 14 of 14 eyes. At 3-month follow-up, vascular activity had resolved in 7 of 14 eyes, persisted in 6 of 14 eyes, and reactivated in 1 of 14 eyes. On final observation, no complications were reported. Conclusions and Relevance: These findings support the possibility of treatment using IAcI with ranibizumab to decrease retinal vascular abnormalities in familial exudative vitreoretinopathy or retinopathy of prematurity or related conditions, but further studies are needed to understand more precise benefits and risks. This approach might be considered in cases where intravitreal or subretinal injection are not feasible, recognizing the limitations of these findings and that longer-term outcomes still need to be monitored.

Role of mammalian target of rapamycin in the formation and progression of retinopathy of prematurity-like vascular abnormalities in neonatal rats.

Retinopathy of prematurity (ROP), a retinal disease that can occur in premature infants, can lead to severe visual impairment. In this study, we examined the preventive and therapeutic effects of mammalian target of rapamycin complex 1 (mTORC1) inhibition on abnormal retinal blood vessels in a rat model of ROP. To induce ROP-like vascular abnormalities, rats were subcutaneously treated with KRN633, an inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinase, on postnatal day 7 (P7) and P8. KRN633-treated (ROP) rats were treated subcutaneously with the mTORC1 inhibitor rapamycin according to preventive and therapeutic protocols, i.e., from P11 to P13 (P11-P13) and from P14 to P20 (P14-P20), respectively. To compare with the effects of VEGF inhibition, KRN633 was administered according to similar protocols. Changes in retinal vasculature, phosphorylated ribosomal protein S6 (pS6), a downstream indicator of mTORC1 activity, and the proliferative status of vascular cells were evaluated at P14 and P21 using immunohistochemistry. Rapamycin treatment from P11 to P13 prevented increases in arteriolar tortuosity, capillary density, and the number of proliferating vascular cells, and eliminated pS6 immunoreactivity in ROP rats. KRN633 treatment at P11 and P12 (P11/P12) also prevented the appearance of ROP-like retinal blood vessels. Rapamycin treatment from P14 to P20 failed to attenuate arteriolar tortuosity but prevented increases in capillary density and proliferating vascular cell number at the vascular front, but not at the central zone. KRN633 treatment from P14 to P20 significantly reduced abnormalities in the retinal vasculature; however, the effects were inferior to those of KRN633 treatment on P11/P12. These results suggest that activation of the mTORC1 pathway in proliferating endothelial cells contributes to the appearance and progression of ROP-like retinal blood vessels. Therefore, inhibition of mTORC1 may be a promising approach for selectively targeting abnormal retinal blood vessels in ROP.

Retinal blood flow velocities in infants with retinopathy of prematurity after intravitreal administration of bevacizumab.

BACKGROUND/OBJECTIVES: Progression of retinopathy of prematurity (ROP) is associated with increased retinal blood flow velocities. We investigated changes of central retinal arterial and venous blood flow after intravitreal administration of bevacizumab. SUBJECTS/METHODS: Prospective observational study using serial ultrasound Doppler imaging in preterm infants with bevacizumab-treated ROP. Eyes were examined 1 [0-2] days before injection (median [interquartile range]), and at three time points after injection (1 [1-2] days, 6 [3-8] days, and 17 [9-28] days). Preterm infants with ROP stage 2 displaying spontaneous regression served as controls. RESULTS: In 21 eyes of 12 infants with bevacizumab-treated ROP, peak arterial systolic velocity declined from 13.6 [11.0-16.3] cm/s prior to intravitreal bevacizumab to 11.2 [9.4-13.9] cm/s, 10.6 [9.2-13.3] cm/s and 9.3 [8.2-11.0] cm/s at discharge (p = .002). There was also a decline of the arterial velocity time integral (from 3.1 [2.3-3.9] cm to 2.9 [2.4-3.5], 2.7 [2.3-3.2] cm and 2.2 [2.0-2.7], p = .021) and mean velocity in the central retinal vein (from 4.5 [3.6-5.8] cm/s to 3.7 [2.6-4.1] cm/s, 3.5 [3.0-4.3] cm/s, and 3.2 [2.8-4.6] cm/s, p = .012). Arterial end-diastolic velocity and resistance index remained unchanged. Blood flow velocities in bevacizumab-treated eyes examined before injection were significantly higher than those measured in untreated eyes that ultimately showed spontaneous regression of ROP. Sequential examinations in these controls did not reveal any declines of retinal blood flow velocities. CONCLUSION: Increased retinal arterial and venous blood flow velocities in infants with threshold ROP decline following intravitreal bevacizumab injection.

Evaluation of optical coherence tomography biomarkers to differentiate favourable and unfavourable responders to intravitreal anti-vascular endothelial growth factor treatment in retinopathy of prematurity.

OBJECTIVE: Evaluation of optical coherence tomography biomarkers in predicting treatment response to intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) Bevacizumab, in aggressive retinopathy of prematurity (A-ROP). METHODS: Non-contact ultra-widefield (NC-UWF) fundus imaging with integrated UWF guided swept source Optical coherence tomography (SS-OCT) was performed prospectively in preterm babies before and after intravitreal anti-VEGF (Bevacizumab) monotherapy. OCT biomarkers were analysed in eyes that reached complete vascularization versus others. RESULTS: Eyes with retinal vessels reaching near ora serrata were labelled as regressed ROP and vascularised retina (Group1). Eyes with reactivation of ROP needing laser or vitreoretinal surgery or eyes with peripheral avascular retina (PAR) at 16th week post-injection were considered as Group 2. Pre-injection baseline OCT showed a hyperreflectivity of inner retinal layers in 12 out of 46 eyes in Group 1 versus 30 out of 34 eyes in Group 2 (p value 0.002). None of the eyes in Group 1 showed choroidal thinning at posterior pole as compared to 14 out of 34 eyes in Group 2 (p value 0.001). Intraretinal hypo reflective Cystic changes at fovea were seen in 16 out of 46 eyes in Group 1 and 2 out of 34 eyes in Group 2 (p value 0.012). CONCLUSION: Pre-injection swept source OCT biomarkers could predict the treatment outcomes of anti-VEGF (Bevacizumab) monotherapy in A-ROP eyes. Hyperreflectivity of inner retinal layers and choroidal thinning had poorer and unpredictable response to anti-VEGF injection whereas, cystic changes at fovea predicted favourable response.

Effectiveness of Propranolol in Preventing Severe Retinopathy of Prematurity: A Comprehensive Systematic Review and Meta-Analysis.

PURPOSE: To learn more about the effectiveness of oral propranolol as a therapeutic alternative for preterm newborns with pre-existing retinopathy of prematurity (ROP) as well as an early prevention method for ROP, one of the most common but avoidable causes of juvenile blindness. STUDY DESIGN: Meta-analysis of relevant literature. METHODS: A total of 3464 papers were identified, with 2873 from PubMed, 39 from Scopus, 67 from Medline, and 16 from Embase. After screening, finally, a total of 8 studies were deemed suitable for review. Following the PRISMA guidelines, published literature was systematically assessed up to May 10, 2023. Trials and observational studies were included in which beta blockage was used to prevent severe ROP (defined as stage ≥3 or requiring treatment). A total of 3646 papers were identified, with 2873 from PubMed, 39 from Scopus, 67 from Medline, and 16 from Embase. After screening, a total of 8 studies were deemed suitable for review. RESULTS: The use of propranolol is linked to a lower risk of disease development in ROP compared to other therapies or control groups, according to the overall risk ratio of 0.59 (95% CI = 0.42, 0.82; P = .002, I2 = 41%). Additionally, the overall risk ratio for plus disease is 0.42 (95% CI = 0.23, 0.78; P = .006, I2 = 0%), for laser photocoagulation is 0.48 (95% CI = 0.31, 0.74; P = .001; I2 = 2%), and for intravitreal injection of VEGF is 0.43 (95% CI = 0.24, 0.74; P = 0.003, I2 = 0%), suggesting that use of propranolol may reduce the likelihood of developing a disease such as plus disease, requiring laser photocoagulation or necessitating intravitreal injection of vascular endothelial growth factor for ROP, respectively. No statistically significant heterogeneity was found in this study (P > .10, I2 = 50%). It can be concluded from this that the results of the chosen studies were sufficiently comparable and consistent. CONCLUSION: This study showed that oral propranolol given as a preventive treatment in premature newborns successfully prevented severe ROP. Propranolol dosage and timing must now be carefully considered in the context of the study population, as these factors may have a major impact on the observed outcomes and treatment success.

Extending Peripheral Retinal Vascularization in Retinopathy of Prematurity Through Regulation of VEGF Signaling.

PURPOSE: Experimental studies provide evidence that regulation of VEGF receptor-2 signaling in endothelial cells orders cell divisions and extends developmental angiogenesis while inhibiting pathologic intravitreal angiogenesis and has relevance to retinopathy of prematurity (ROP). We tested the hypothesis that intravitreal anti-VEGF would extend vascularization into peripheral avascular retina in human type 1 ROP compared with controls. DESIGN: Retrospective, nonrandomized treatment comparison. METHODS: The study was conducted at an academic institution, with the study population comprising all premature infants screened for ROP from January 2019 through December 2022. The experimental group included type 1 ROP treated with bilateral bevacizumab (0.25 mg) and had adequate fundus imaging by a certified ophthalmic photographer at 2 examinations: within 2 weeks of treatment and 1-3 weeks later. A control group included gestational age- and birthweight-matched infants with ROP less severe than type 1 ROP. The main outcome measure was extent of temporal retinal vasculature measured by a masked analyst between treated and control eyes. Paired and nonpaired t tests were used. RESULTS: Of 382 screened infants, 34 developed type 1 ROP; 11 comprised the experimental group and 11 the control group. At baseline, there was a trend toward shorter temporal vascular extent in treatment compared with control groups (3667±547 vs 4262±937 pixels, 95% CI -1277, 88; P = .084) but no difference between groups at follow-up (P = .945). Vascular extension was significantly greater in the treatment than control (872±521 vs 253±151 pixels, 95% CI 262, 977; P = .003), showing catch-up growth. CONCLUSIONS: This clinical evidence supports laboratory-based studies that regulation of VEGF using an intravitreal anti-VEGF agent increases developmental angiogenesis into the peripheral avascular retina while inhibiting pathologic intravitreal angiogenesis in ROP.

FLUORESCEIN ANGIOGRAPHY EVALUATION OF CHILDREN PREVIOUSLY TREATED WITH ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY FOR RETINOPATHY OF PREMATURITY.

PURPOSE: To determine the level of vascularization and peripheral vascular findings by fluorescence angiography in patients with aggressive retinopathy of prematurity or Type 1 retinopathy of prematurity treated with a single dose of anti-vascular endothelial growth factor. METHODS: Data of patients referred to the authors' clinic for fluorescence angiography examination between June 2016 and September 2021 were retrospectively analyzed. Patients who had their first fluorescence angiography examination at the age of 1 year or older were included in the study. RESULTS: A total of 486 eyes of 250 patients were included. Of these, 83 eyes (17.1%) had vascular termination in Zone II and 403 eyes (82.9%) in Zone III. In 62.7% of eyes, the distance from the vascular terminals to the temporal ora serrata was less than two disk diameters, and in 20.2%, it was more than two disk diameters. Abnormal vascular findings were noted, including circumferential vessels (41.2%), finger-like projection anomaly (36.2%), hyperfluorescence (16.9%), fine branching and blunt termination (15%), and arteriovenous shunt (9.9%). CONCLUSION: Fluorescence angiography performed late in the course of treatment can clearly define the vascular termini and detect abnormalities that cannot be detected by indirect ophthalmoscopy. Follow-up with fluorescence angiography can help prevent complications that can lead to vision loss.

Evaluation of retinal vascularization in retinopathy of prematurity regressed after intravitreal ranibizumab monotherapy or without treatment based on fluorescein angiography.

To investigate the fluorescein angiography (FA) findings and compare the extent of retinal vascularization in retinopathy of prematurity (ROP), recovered after intravitreal ranibizumab (IVR) monotherapy and those regressed spontaneously. Infants with a history of ROP who underwent FA between April 2018 and November 2021 were retrospectively included. The patients were divided into two groups based on whether they had received IVR (IVR group) or had ROP that regressed spontaneously without treatment (untreated group). The differences between the two groups in zone II ROP were also compared, to equalize the subgroups as much as possible in terms of disease severity. FA findings were recorded. The extent of vascularization was measured by the ratio of the distance from the center of the disk to the border of the vascularized zone (DB) and the distance from the center of the disk to the center of the fovea (DF). The width of the persistent avascular retina (PAR) was counted by disc diameters (DD). One hundred and ten eyes of 55 infants were included in the IVR group and 76 eyes of 38 babies in the untreated group. The ratio of abnormal shape of vessels was significantly higher in the IVR group than in the untreated group (50.9% vs. 35.5%; P = 0.038), while the linear choroidal filling pattern, tortuosity of vessels over the posterior pole, dye leakage, anomalous branching of vessels, circumferential vessels, arteriovenous shunt, abnormal capillary bed, and macular abnormalities were similarly. There was a smaller temporal DB/DF ratio (4.48 vs. 4.63; P = 0.003) and greater PAR (2.63 vs. 1.76; P < 0.001) in the IVR group compared to the untreated group. In zone II ROP, the progression of retinal vascularization was significantly larger in the IVR group than that in the untreated group (P = 0.003), while no statistical differences were observed in FA features, the DB/DF ratio, and PAR between the two subgroups. The residual vascular abnormalities and PAR may be common results of ROP regression. The DB/DF ratio of 4.0 temporally and 3.3 nasally could be used as the preliminary indicators for safe retinal vascularization in the completion of ROP regression.

An Artificial Intelligence System for Screening and Recommending the Treatment Modalities for Retinopathy of Prematurity.

PURPOSE: The purpose of this study was to develop an artificial intelligence (AI) system for the identification of disease status and recommending treatment modalities for retinopathy of prematurity (ROP). METHODS: This retrospective cohort study included a total of 24,495 RetCam images from 1075 eyes of 651 preterm infants who received RetCam examination at the Shenzhen Eye Hospital in Shenzhen, China, from January 2003 to August 2021. Three tasks included ROP identification, severe ROP identification, and treatment modalities identification (retinal laser photocoagulation or intravitreal injections). The AI system was developed to identify the 3 tasks, especially the treatment modalities of ROP. The performance between the AI system and ophthalmologists was compared using extra 200 RetCam images. RESULTS: The AI system exhibited favorable performance in the 3 tasks, including ROP identification [area under the receiver operating characteristic curve (AUC), 0.9531], severe ROP identification (AUC, 0.9132), and treatment modalities identification with laser photocoagulation or intravitreal injections (AUC, 0.9360). The AI system achieved an accuracy of 0.8627, a sensitivity of 0.7059, and a specificity of 0.9412 for identifying the treatment modalities of ROP. External validation results confirmed the good performance of the AI system with an accuracy of 92.0% in all 3 tasks, which was better than 4 experienced ophthalmologists who scored 56%, 65%, 71%, and 76%, respectively. CONCLUSIONS: The described AI system achieved promising outcomes in the automated identification of ROP severity and treatment modalities. Using such algorithmic approaches as accessory tools in the clinic may improve ROP screening in the future.

1†Retreatment for reactivation of ROP following initial anti-VEGF injections. A 5-year retrospective study.

To present the retreatment rates and the characteristics of ROP reactivation, as well as the differences between bevacizumab and ranibizumab injections in premature babies treated in our department over the past 5 years.A retrospective analysis of babies with treated ROP was performed. 89 babies who required treatment from 2017 to 2022 were examined. We studied the severity of their disease with regards to their gestational age, treatment time and type and the need of further treatment. We also focused on the comparison of anti-VEGF agents for ROP.22 out of 89 babies (14 boys and 8 girls) with aggressive posterior retinopathy of prematurity (APROP) and mean gestational age of 25+3w received initially anti-VEGF injections. 16 of those (11 boys and 5 girls) required retreatment with diode laser. 9 out of these 16 babies were treated with ranibizumab (Lucentis) and 7 with bevacizumab (Avastin). It is also of note that only 2 out of 67 babies who initially received laser treatment needed a complementary laser session.The majority of babies with aggressive ROP who receive anti-VEGF agents will most probably require further laser treatment. At an equal level of retinal damage, it seems that their response to ranibizumab and bevacizumab is similar.

Respiratory outcomes in preterm infants following intravitreal bevacizumab for retinopathy of prematurity-a 10-year matched case study.

OBJECTIVES: To evaluate respiratory outcomes in preterm infants with retinopathy of prematurity (ROP) following intravitreal bevacizumab injection (IVB). METHODS: This single-centre study enroled preterm infants with a gestational age (GA) < 34 weeks or a birth weight (BW) < 1500 g with bilateral type 1 ROP who received a single IVB, and a treatment-free control group matched by GA, postmenstrual age, and respiratory status at the time of the IVB. The primary outcome was serial respiratory changes in mean airway pressure (MAP), fraction of inspired oxygen (FiO2), and respiratory severity score (RSS, MAP x FiO2) during the 28-day post-IVB/matching period and overall respiratory improvement at day 28 and at discharge. The duration of supplemental oxygen therapy following IVB/matching was documented. RESULTS: A total of 5578 infants were included. Seventy-eight infants were enroled in the IVB group, and another 78 infants were matched as the control group. Both groups had downward trends in the MAP, FiO2, and RSS over the study period (all P < 0.001), but there were no between-group differences in these measures. The percentage of overall respiratory improvement was similar between the IVB and control groups, so was the duration of invasive and in-hospital oxygen ventilation. A lower percentage of oxygen dependence at discharge in the IVB group (P = 0.03) remained significant after adjusting for GA and BW. CONCLUSIONS: This is a matched case study to evaluate respiratory outcomes in preterm infants following IVB for ROP. We found that the IVBs did not compromise respiratory outcomes in preterm infants during the 28-day post-IVB period and at discharge.

A Meta-Analysis of Neurodevelopmental Outcomes following Intravitreal Bevacizumab for the Treatment of Retinopathy of Prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is the most common cause of preventable blindness in preterm infants. First-line treatments include intravitreal bevacizumab (IVB) or laser photocoagulation (LPC). OBJECTIVES: The aim of the study was to evaluate neurodevelopmental safety of IVB compared to LPC for ROP. METHODS: MEDLINE, Embase, and Cochrane library were searched up to September 2022. Studies were included with at least 12-month follow-up of primary outcomes such as severe neurodevelopmental impairment (sNDI), cerebral palsy (CP), and hearing impairment (HI). Secondary outcomes were moderate-to-severe neurodevelopmental impairment (msNDI), Bayley Scores of Infant Development (BSID-III), and visual impairment. RESULTS: 1,231 patients from 11 comparative studies were included. Quality of evidence was rated low for all outcomes. IVB was associated with a higher risk for sNDI (risk ratio [RR] = 1.25, 95% confidence interval [CI]: [1.01, 1.53], p = 0.04); and CP (RR = 1.40, CI: [1.08, 1.81], p = 0.01) compared to LPC. There was no significant difference between IVB and LPC for msNDI (RR = 1.15, CI: [0.98, 1.35], p = 0.08) and HI (RR = 1.43, CI: [0.86, 2.39], p = 0.17). BSID-III percentile scores were similar between IVB and LPC, with weighted mean differences of 1.51 [CI = -1.25, 4.27], 2.43 [CI = -1.36, 6.22], and 1.97 [CI = -1.06, 5.01] for cognitive, language, and motor domains, respectively (p > 0.05). CONCLUSION: To our knowledge, this is the largest meta-analysis on neurodevelopmental outcomes and the first to rigorously examine IVB monotherapy in ROP treatment. Compared to LPC, there was a marginally increased risk for sNDI and CP with IVB but little or no difference in the risk of msNDI and HI. Further randomized studies are needed to strengthen these findings.