ObjectiveTo investigate the prognosis and differences of visual function and fundus structure in retinopathy of prematurity (ROP) undergoing anti-vascular endothelial growth factor agents (VEGF) or laser photocoagulation treatment with long-term follow-up. MethodsRetrospective case control series. From January 2010 to December 2021, A total of 35 children (63 eyes) with ROP who were first diagnosed in Department of Ophthalmology, Peking University People's Hospital and followed up for as long as 5 years were included. Among them, 21 males (36 eyes) and 15 females (27 eyes) were enrolled. The average gestational age (GA) of the children at birth was 29.30±1.77 weeks. Among the included 12 aggressive ROP (A-ROP) eyes and 51 pre-threshold type 1 ROP eyes, no retinal detachment occurred. Each eye received only intravitreal injection of anti-VEGF agents or laser monotherapy after diagnosis, and divided into anti-VEGF group or laser group according to the treatment. Thirty-five eyes of 20 infants were included in the anti-VEGF group and 28 eyes of 15 infants were included in the laser group. GA, birth weight (BW) and postmenstrual age receiving first treatment were compared and no significant difference between the two groups was defined (P=0.844, 0.859, 0.694). The number of A-ROP, pre-threshold type 1 ROP eyes were also compared, and statistically significance can be defined (P=0.005). During the follow-up period, best corrected visual acuity (BCVA), refractive status, visual field, optical coherence tomography (OCT) and fluorescein fundus angiography (FFA) were performed. The BCVA examination was carried out using the international standard decimal visual acuity chart, which was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity for statistics. Refractive status was calculated as spherical equivalent (SE). Comparative observation of 5-year outcomes including BW, GA, fundus examination at the initial diagnosis, and BCVA, refractive status, visual field defect, central foveal thickness (CFT), subfoveal choroidal thickness (SFCT) and abnormality of peripheral retina in FFA were performed between the two groups. Differences between groups were compared using t test or nonparametric test for measurement data, and χ2 test was used for comparison between groups in enumeration data. ResultsFive years after treatment, retinal avascular areas were seen around the eyes in the anti-VEGF treatment group, with a size of 2.32±1.84 optic disc diameters, and 1 eye had fluorescein leakage at the junction of the peripheral avascular areas; eyes in the laser treatment group old photocoagulation spots were seen in the peripheral retina, and no fluorescein leakage was seen. The logMAR BCVA of the eyes in the anti-VEGF treatment group and laser treatment group were 0.15 (0.00, 0.20), 0.10 (0.00, 0.16), respectively; SE were 0.50 (－1.25, 1.31), 0.38 (－4.25, 1.75) D, respectively; mean defect (MD) values of visual field were 2.70 (1.20, 4.80), 4.25 (2.83, 6.98) dB; CFT, SFCT were 225.00±29.31, 287.18±68.56 μm and 237.17±32.81, 279.79±43.61 μm. There was no significant difference in logMAR BCVA, CFT and SFCT between the two groups (P=0.363, 0.147, 0.622); the lower quartile of SE and visual field MD value in the laser treatment group were significantly higher than those in the laser treatment group, but there was no significant difference in the median SE (P=0.109), and there was a statistically significant difference in the median MD value of the visual field (P=0.037). ConclusionsAnti-VEGF agents and laser therapy can achieve similar good visual prognosis for early ROP, and the peripheral visual field can be preserved to a greater extent, however, the peripheral visual field defect in the laser group is more significant than that in the anti-VEGF group. For ROP without retinal detachment, the thickness of the retina and choroid in the fovea is generally normal.
ObjectiveTo screen compounds or drugs can affect the hypoxia induced-gene expression of retinal vascular endothelial cell based on gene expression microarrays and connectivity map (CMAP) technology. MethodsTotally 326 up-regulated and down-regulated genes of hypoxic human embryonic retinal microvascular endothelial cells minduced by cobalt chloride in the previous study were converted into query signature format documents. Gene profile of the disease characteristics was then compared with that of control in CMAP website database, positive and negative compounds related to retinopathy of prematurity (ROP) were finally screened out. Results44 and 18 compounds or drugs have positive and negative relationship with ROP respectively by searching CMAP database with differentially expressed genes. Ciclopirox, cobalt chloride, gossypol and withaferin A have positive relationship with ROP. Cyclic adenosine monophosphate, harmalol, naringin and probenecid have a negative effect on ROP. ConclusionsCiclopirox, cobalt chloride, gossypol and withaferin A have a positive effect on ROP. However, cyclic adenosine monophosphate, harmalol, naringin and probenecid have a negative effect.
Retinopathy of prematurity (ROP) is the leading cause of blindness for children, early detection and treatment can prevent ROP progression and improve the visual prognosis. ROP prevention system, including advocacy, screening, diagnosis/treatment and follow-up, is the key to reducing the rate of blindness in children. The proposed tertiary ROP prevention network includes primary health centers in county-level, secondary health centers in municipal-level and tertiary health centers in provincial-level or national-level. The idea is to explore the greatest benefits in the ROP prevention process from the existing allocation of medical resources, but also to avoid wasting at the current stage of social development. We tested this idea in Shaanxi Province recently. The preliminary practice results indicated that ROP tertiary prevention network can increase the ROP screening coverage, promote the prevention and treatment of ROP. However this work is still in its infancy. We need to expand its scope and strength the advocacy efforts to find a way to prevent and treat ROP in China.
ObjectiveTo observe the effect of intravitreal injection of Conbercept with two different doses in the treatment of retinopathy of prematurity (ROP）and explore the clinical feasibility of ROP treatment by lower dose conbercept.MethodsThis was a prospective study. The premature infants were enrolled with pre-threshold type 1, threshold and acute aggressive posterior retinopathy of prematurity (AP-ROP) from March 2018 to June 2019, who received fundus screening in neonatal intensive care unit (NICU) of Henan Provincial People's Hospital, Henan Eye Hospital. They were randomly divided into two groups. The group A (lower dose group) were received intravitreal injection of conbercept with 0.15 mg/0.015 ml, and those in group B (control group) were received intravitreal injection of conbercept with 0.25 mg/0.025 ml. We checked and recorded the lesion area, stage, scope (according to the clock range), additional lesion (plus), etc. Fundus examination should be performed with the pediatric wide-field fundus imaging system within 7 days after treatment. It was used to observe the plus disese, ridge, regression of neovascularization on ridge, and development of retinal vessels to serrated edge or scarring. The follow-up period was at least 24 weeks. The effect evaluation was divided into recovery, improvement, recurrence and aggravation.ResultsThe 43 ROP subjects (84 eyes) were enrolled including 21 cases (40 eyes) in group A and 22 (44 eyes) in group B. There was no significant difference between the two groups in gender (χ2=1.169), birth age (t=0.283), birth weight (t=0.547), hospitalization days in NICU (t=1.187), first examination time (t=1.811), first injection time (t=0.492), follow-up time (t=0.899) and ROP condition (χ2=0.854) (P>0.05). In group A, 21 eyes (52.5%) were cured, 17 eyes (42.5%) were improved, 2 eyes (5.0%) were recurred, and no aggravating cases were found. In group B, 24 eyes (54.5%) were cured, 14 eyes (31.8%) were improved, 6 eyes (13.6%) were recurred, and no aggravating cases were found. There was no significant difference of the cure rate (χ2=2.210, P>0.05) and effective (recovery and improvement) rate (χ2=1.814, P=0.269）between two groups after the first injection.ConclusionIntravitreal injection of conbercept with the two doses should be effective in the treatment of ROP.
Objective To investigate the degree of retinal development in preterm infants.MethodsFlash electroretinography (ERG) was performed on 25 healthy preterm infants and 25 full-term ones, and the response of rod cells and cone cells and maximal mixed responses were recorded. The delitescence and amplitudes of a-and b-waves and the ratio of amplitudes of b-/a-wave of maximal responses were analyzed. ResultsCompared with the full-term infants, The delitescence of responses of rod cells in preterm infants was statistically longer（t=11.007，P=0.000）but without any significant changes of amplitudes （t=1.836，P=0.069）; statistically longer delitescence (t=2.44, P=0.010; t=10.800, P=0.000) and lower amplitude (t=5804，P=0.000; t=5.809,P=0.000) of a-and b-wave of maximal response were found in preterm infants group. In the response of cone cells, there were significant differences of the delitescence （t=4.444，P=0.000）and amplitude （t=3.819，P=0.000）of a-wave and delitescence of b-wave（t=2.850，P=0.005） between the two groups, and no statistical difference of amplitude of b-wave （t=0.486，P=0.628） between the two groups. The ratio of amplitudes of b-/a-wave of the maximal mixed response was not significantly different between the two groups （t=1.142，P=0.256）.ConclusionsThe development of retinal function is slower in preterm infants than that in full-term ones.(Chin J Ocul Fundus Dis, 2005,21:285-287)
ObjectiveTo analyze the clinical characteristics and evaluate the effect and safety of anti-vascular endothelial growth factor (VEGF) therapy in retinopathy of prematurity (ROP) in Sichuan province. MethodsA retrospective study. From January 2013 to January 2022, 156 patients (306 eyes) with ROP who received intravitreal anti-VEGF therapy for the first time in the Department of Ophthalmology, West China Hospital of Sichuan University were selected. According to the type of anti-VEGF drugs, the children were divided into intravitreal injection of ranibizumab (IVR) group and intravitreal injection of conbercept (IVC) group; IVC group was divided into hospital group and referral group according to the different paths of patients. After treatment, the patients were followed up until the disease degenerated (vascular degeneration or complete retinal vascularization) or were hospitalized again for at least 6 months. If the disease recurred or progressed, the patients were re-admitted to the hospital and received anti-VEGF drug treatment, laser treatment or surgical treatment according to the severity of the disease. Clinical data of these children was collected, including general clinical characteristics: gender, gestational age at birth (GA), birth weight (BW), history of oxygen inhalation; pathological condition: ROP stage, zone, whether there were plus lesions; treatment: treatment time, postmenstrual gestational age at the time of the first anti-VEGF drug treatment; prognosis: re-treat or not, time of re-treatment, mode of re-treatment; adverse events: corneal edema, lens opacity, endophthalmitis, retinal injury, and treatment-related systemic adverse reactions. The measurement data between groups were compared by t test, and the count data were compared by χ2 test or rank sum test. ResultsOf the 306 eyes of 156 children with ROP, 74 were male (47.44%, 74/156) and 82 were female (52.56%, 82/156). Each included child had a history of oxygen inhalation at birth. The GA was (28.43±2.19) (23.86-36.57) weeks, BW was (1 129±335) (510-2 600) g, and the postmenstrual gestational age was (39.80±3.04) (31.71-49.71) weeks at the time of the first anti-VEGF drug treatment. All patients were diagnosed as type 1 ROP, including 26 eyes (8.50%, 26/306) of aggressive ROP (A-ROP), 39 eyes (12.74%, 39/306) of zone Ⅰ lesions, and 241 eyes (78.76%, 241/306) of zone Ⅱ lesions. The children were treated with intravitreal injection of anti-VEGF drugs within 72 hours after diagnosis. Among them, 134 eyes (43.79%, 134/306) of 68 patients were treated with IVR, and 172 eyes (56.21%, 172/306) of 88 patients were treated with IVC. In IVC group, 67 eyes of 34 patients (38.95%, 67/172) were in the hospital group and 105 eyes of 54 patients (61.05%, 105/172) were in the referral group. 279 eyes (91.18%, 279/306) were improved after one treatment, 15 eyes (4.90%, 15/306) were improved after two treatments, and 12 eyes (3.92%, 12/306) were improved after three treatments. The one-time cure rate of IVR group was lower than that of IVC group, but the difference was not statistically significant (χ2=1.665, P=0.197). In different ROP categories, IVC showed better therapeutic effect in A-ROP, and its one-time cure rate was higher than that in IVR group, with statistically significant difference (χ2=7.797, P<0.05). In the hospital group of IVC group, the GA, BW and the postmenstrual gestational age at first time of anti-VEGF drug treatment were lower than those in the referral group, and the difference was statistically significant (t=－2.485, －2.940, －3.796; P<0.05). The one-time cure rate of the hospital group and the referral group were 94.94%, 92.38%, respectively. The one-time cure rate of the hospital group was slightly higher than that of the referral group, but the difference was not statistically significant (χ2=0.171, P=0.679). In this study, there were no ocular and systemic adverse reactions related to drug or intravitreal injection in children after treatment. ConclusionsCompared with the characteristics of ROP in developed countries, the GA, BW and postmenstrual gestational age of the children in Sichuan province are higher. Both IVR and IVC can treat ROP safely and effectively. There is no significant difference between the two drugs in the overall one-time cure effect of ROP, but IVC performed better in the treatment of A-ROP in this study.
ObjectiveTo retrospectively analyze incidence and trends of retinopathy of prematurity (ROP) from 2004 to 2013 in Shenzhen. MethodsA total of 9100 preterm children (5401 males, 3699 females) were screened for ROP in Shenzhen from January 2004 to June 2013 using binocular ophthalmoscope or RetCam Ⅱ. First examination was performed from 4-6 weeks after birth. The birth weight was 520-2990 g with an average of (1710±410) g.The gestational age were 24-36 weeks with an average of (31.57±1.99) weeks. The gestational age of 208 children were <28 weeks, 3608 children were 28-32 weeks, 3553 children was 33-34 weeks, 1731 children was >34 weeks. The ocular findings were recorded according to the International Classification of ROP and The Early Treatment for ROP. Only the more aggressive eye of bilateral asymmetrical cases was counted for statistical purpose, and the cases required surgeries were defined as severe cases. The 10 years period was divided into first phase (2004-2008) and second phase (2009-2013). The incidence of ROP and severe ROP of these two phases was compared and statistics was analyzed. ResultsIn the past 10 years, the overall incidence of ROP and sever ROP in Shenzhen was 12.49% and 4.99% in this screen. The children were divided into 4 groups according to the birth weight, the ROP incidences of birth weight <1000 g, 1000-1499 g, 1500-1999 g and ≥2000 g were 62.62%, 28.40%, 11.34% and 3.63% respectively. The severe ROP incidences were 34.95%, 12.21%, 3.73% and 0.49% respectively in these birth weight groups. The children were divided into 4 groups according to gestational weeks, the ROP incidences of gestational age <28 weeks, 28-32 weeks, 33-34 weeks and >34 weeks were 67.31%, 25.27%, 7.22% and 3.87% respectively. Severe ROP incidences were 37.02%, 10.71%, 1.79% and 0.68% in these gestational age groups respectively. ROP and severe ROP incidences were decreased from 14.64% at first phase to 11.47% at second phase, and from 6.52% at first phase to 4.26% second phase respectively, the differences were statistical significant (χ2=26.96, 26.61; P<0.05). ROP and severe ROP incidence in <1000 g birth weight group at second phase were much less than the first phase (χ2=13.676, 5.271; P<0.05). In <28 weeks gestational age group, the ROP incidence was the same in first phase and second phase (χ2=0.843, P>0.05), but the severe ROP incidence at second phase was much less the first phase (χ2=4.757,P<0.05). ConclusionFrom 2004 to 2013, the incidences of ROP and severe ROP have decreased significantly in Shenzhen.
ObjectiveTo detect the effect of adeno-associated-virus induced Kringles5 gene on retinal neovascularization in rats with retinopathy of prematurity (ROP), and to explore the new ways of treatment for ROP.MethodspSNAV-Kringle5-gfp carrier was constructed by subclone and adeno-associated-virus was packed to form rAAV-Kringle5-gfp. ROP model was set up under circumstances of high oxygen in 21 SD rats which were divided into experimental (21 eyes) and control group (21 eyes). Eighteen eyes from each group was used to making the histologic section of retina, and the other 3 eyes in each group was detected by polymerase chain reaction (PCR) and Western blotting. There were 5 rats in the normal control group. AAV-Kringle5-gfp with the dosage of 10 μl and titer of 2.5×1012vg/ml was injected into the eyes in experimental group, while rAAVlacZ with the same dosage and titer of 2.5×1011vg/ml was injected in to the eyes in control group. The expression of target gene in ocular tissues was observed under the fluoroscope. Twelve weeks later, the rats were executed, and the staining of Ⅷ factor related antigens in retinal vascular endothelial cells was performed and number of nucleolus of vascular endothelial cells were counted. ResultsThe plasmid of pSNAV-Kringle5-gfp was correct according to the sequence measurement; the expression of rAAV-Kringle5-gfp was found in vitreous cavity and on retina; the expression of target gene was found on the level of mRNA and protein; the number of nucleolus of vascular endothelial cells on the surface of retina was (19.954 2±3.825 7) in experimental group and (7.335 2±2.731 3) in the control group, which had significant difference between the two groups (P＜0.01）.ConclusionsAdeno-associated-virus induced Kringles5 gene can inhibit the occurrence of retinal neovascularization in patients with ROP.(Chin J Ocul Fundus Dis, 2005,21:288-291)
Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are common and critically important diseases of preterm infants. The common feature of both conditions is altered angiogenesis and pathological changes in the case of incomplete organ development. The interaction of multiple factors leads to abnormal angiogenesis, which not only increases the possibility of comorbidity of BPO and ROP, but also reveals the potential co-pathogenesis between the two. However, the specific mechanism of this angiogenic balance in the occurrence and development of BPD or ROP is still unclear, and there are no animal models to explore the pathogenesis of both diseases. At present, effective prevention measures for BPO and ROP are still lacking, and treatment methods mainly rely on drug therapy and surgery. In the future, more studies should be conducted to find common therapeutic targets for factors affecting angiogenesis, so as to provide better treatment options for BPD and ROP and improve the effectiveness of treatment.
Objective To observe the factors influencing for results of laser treatment of zone one retinopathy of premature（ROP）. Methods The clinical data of 35 patients（69 eyes）with ROP in zone one who diagnosed by examination of indirect ophthalmoscopy were retrospectively analyzed. The eyes were divided into anterior zone one（49 eyes ）and posterior zone one（20 eyes）. The 69 eyes, aggressive posterior ROP（AP-ROP）in 12 eyes, anterior zone one in four eyes and posterior zone one in eight eyes. The laser photocoagulation of diode indirect ophthalmoscopy with +20 D lens and sclera compressor were used to entire avascular retina. Followup ranged from two to 48 months with the mean of (10.85plusmn;11.35 )months. Take the cristae fadeaway and stable condition as cure; retinopathy proceed to the stage 4 and 5 ROP as retinopathy progress. Results Forty-two out of 69 eyes (60.87%) were cured and retinopathy progress in 27 eyes (39.13%). Thirty-four out of 49 eyes (69.38%) with anterior zone one were cured and retinopathy progress in 15 eyes (30.61%); eight out of 20 eyes (40.00%) with posterior zone one were cured and retinopathy progress in 12 eyes (60.00%). The difference of progress rate between anterior and posterior zone one was statistically significant（chi;2=5.15, P＜0.05).Conclusions Laser photocoagulation is effective for treatment of zone one ROP, the prognosis of anterior zone one is better than posterior zone one; retinopathy progress after photocoagulation was associated with extent of fibrovascular organization.