Objective To determine the association between the geneti c polymorp hisms of vascular endothelial growth factor (VEGF) gene and the prognosis for retinopathy of prematurity (ROP) in Chinese. Methods Twenty infants with threshold ROP who had undergone retinal photocoagulation were in the treated group and 20 infants with self-regressed ROP without any treatment were in the control grou p . In the two groups, all the infants had oxygen-breathing history and the sex a n d gestational age were all suitable to be compared, except birth weight. Polymer ase chains reaction-restriction fragment length polymorphism was used to determine the frequencies of VEGF genes in the two groups. Results The frequencies of +405C allele were higher in the treated group than those in the control group (P＜0.05). The frequencies of the VEGF-460T/C and +936C/T ploymorphisms were similar in both groups (P＞0.05). Conclusions The +4 05C/G ge netic polymorphisms of VEGF may correlate to the prognosis of ROP. The carriers of +405CC allele are more susceptible to ROP.
Objective To learn the screening results of retinopathy o f prematur ity (ROP) of the preterm infants in three hospitals in Shenzhen. Metho ds From Jan. 2004 to Jan. 2007, 1372 preterm infants (2744 eyes) with birth weight lt;200 0 g or but the ones having severe systemic disease in Shenzhen People's Hospita l, Shenzhen Maternity and Child Healthcare Hospital and Shenzhen Eye Hospital we re screened for ROP with binocular indirect ophthalmoscope and (or) widefield digital pediatric retinal imaging system (RetCamII). Cryotherapy or laser photoco agulation was performed if threshold or pre-threshold type I ROP was found. All preterm infants were followed up until retina is completely vascularized or the disease regressed. Results In all the infants, 218 cases (436 eyes) (15.9％) developed ROP, including 190 eyes (6.9％) suffering from threshold or pre-threshold type 1 ROP, 16 eyes (0.6％) from stage 4 or stage 5, and 230 eyes (8.4％) from stages below threshold or pre-threshold type 1 ROP. There were 435 infants ( 870 eyes) (31.7%) with BW of 1500g or less, in which 236 eyes (27.1％) developed ROP, including 126 eyes (14.5％) suffering from threshold or pre-threshold type 1 ROP, 10 eyes (1.1％) from stage 4 or stage 5, and 100 eyes (11.5％) from stages below threshold or pre-threshold type 1 ROP. There were 137 infants 274 eyes (10%) with BW of 1250g or less, in which 108 eyes (39.4％) developed ROP, including 60 eyes (21.9％) suffering from th reshold or pre-threshold type 1 ROP, 4 eyes (1.4％) from stage 4 or stage 5, and 44 eyes (16％) from stages below threshold or pre-threshold type 1 ROP. Th eincidence of ROP（chi;2=60.43，Plt;0.001）, the incidence of threshold or pre-threshold type 1 ROP（chi;2=46.82，Plt;0.001）and the incidence of below threshold or pre-threshold type 1 ROP （chi;2=10.71，P=0.005）among the total group, BWle;1500g group and BWle;1250g group had statistical differences. Conclusions The incidence of ROP in the three hospitals in Shenzhen was lower. However, the incidence of severe ROP (threshold or pre-threshold type 1 ROP) was higher. Birth weight is an important factor to affect ROP incidence.
Objective To observe the expression of erythropoietin (EPO) and its receptor (EPOR) mRNA and protein levels in retinae of mice with oxygen-induced retinopathy, and to evaluate the effect of EPO and EPOR in retinal vascular develo pment and in the occurrence and development of oxygen-induced retinopathy. Methods One hundred and thirty-two 7-day-old C57BL/6J mice were divided into two g rou ps: normal control group (control group) and oxygen-induced retinopathy group (experimental group). The proliferative neovascular response was estimated by obse rving the vascular pattern in adenosine diphosphatease (ADPase) stained retina flat-mounts by executing 6 mice in each group at the 12th, 15th, and 17th day, respectively. The expression of EPO, EPOR mRNA was determined by reverse transcription-polym erase chain reaction (RT-PCR), and the protein levels of EPO and E PO R were determined by immunohistochemistry. RT-PCR and immunohistochemistry were done every other day from the 7th to the 21st day. Results In the control group, retinal vascularization was found. In the experimental group, the large vesse ls were constricted straight, the branches decreased, and alarge nonperfusion area was observed at the 12th day; the large vessels were dilated and tortuous and neovascularization occurred at the 15th day; a mass of neovascularization was found and the vascular net structure of the deep and shallow layer was destroye d at the 17th day. The expression of EPO mRNA decreased from the 7th day and kee p decreasing in the whole oxygen-breathing duration in the experimental group. A fter the mice were returned to room air, the expression increased obviously from the 15th day and kept the high level until the 21st day. The expression of EPO mRNA increased at the 7th day and reached the peak at the 11th day, and kept the high level until the 21st day. The changes of protein levels of these three fac tors were later than that of their mRNA, but had the same trend. The difference of the expression between the two groups at the different time point was signifi cant except for the 7thday point (Plt;0.05). Conclusion It 's suggested that EPO and EPOR played important roles on the development of normal retina vascularizati on and the pathogenesis of ROP, which may provide new conception and method for the prevention and treatment of the oxygen-induced retinopathy.
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 evaluate the effectiveness and complications associated with the use of ranibizumab in the treatment of ZoneⅠand ZoneⅡretinopathy of prematurity (ROP). MethodsData from patients of ROP who had received intravitreal ranibizumab (IVR) injections in Peking University People's Hospital for the treatment of ROP from July 2012 to December 2013 were collected. In total, 151 eyes from 85 patients (56 male and 29 female) were analyzed. The mean birth weight was (1438.6±334.5) g (range:790-2280 g), mean gestational age was (30.1±2.0) weeks (range:25-37 weeks), mean age at the time of intervention was (37.0±6.2) gestational weeks (range:32-45 weeks), mean follow-up was (4.9±3.3) months (range:1.4-20.8 months). The main outcome measures were the regression of ROP and the complications that were associated with the IVR injections. ResultsAfter receiving IVR injections, 120 eyes (79.5%) exhibited ROP regression after single injection. Twenty-six eyes (17.2%) required additional laser treatment for ROP regression after the absence of a positive response to the IVR injections. Five eyes (3%) progressed to stage 4 ROP and required vitrectomy to reattach the retinas. Fifty of 120 eyes which were regressed after single IVR had recurrence of ROP and need additional laser or additional IVR. All of the eyes (100.0%) had attached retinas after the various treatments that they received. No notable systemic complications related to the IVR injections were observed. ConclusionsIVR injection seems to be an effective and well-tolerated method to treat ZoneⅠand ZoneⅡROP. Recurrence of ROP is common and long-term follow up may be needed.
Objective To observe the effect of assisted reproductive technology (ART) on retinopathy of prematurity (ROP) in preterm infants. MethodsA retrospective clinical study. From January 2016 to January 2020, 639 preterm infants who were hospitalized at Children's Hospital of Zhengzhou University and underwent fundus screening at a gestational age ≤32 weeks were included in the study. There were 366 males and 273 females. Gestational age at birth were (28.3±1.4) weeks; birth weight were (1 153.8±228.8) g. Severe ROP was detected in 60 cases (9.4%, 60/639); 120 were ART recipients, and 519 were naturally conceived, and were divided into the ART group and the control group accordingly. The incidence of gestational diabetes mellitus (χ2=21.675), pulmonary surfactant application (χ2=13.558), and twin births (yes) (χ2=145.568) in mothers of the children examined in both groups were significantly higher than that of the control group, and the difference were statistically significant in all cases (P＜0.001). Comparison of quantitative data between groups was performed by t-test, and comparison of count data was performed by χ2 test; logistic regression was used to analyze the effect of ART on the incidence of ROP. ResultsOf the 60 cases of severe ROP, 18 (15.0%, 18/120) and 42 (8.1%, 42/519) cases were in the ART group and control group, respectively. The incidence of severe ROP was significantly higher in the ART group than in the control group, and the difference was statistically significant (χ2=4.680, P=0.024). Compared with the control group, the incidence of severe ROP was significantly higher in the ART group for gestational age at birth ＜28 weeks and birth weight ＜1 000 g, and the differences were statistically significant (χ2=10.116, 3.785; P=0.002, 0.037). Logistic regression analysis showed that ART was a non-independent risk factor for the occurrence of ROP (P＞0.05). ConclusionAssisted reproductive technology may have a certain influence on the occurrence of ROP, which is not an independent factor.
ObjectiveTo analyze the regulative rule of mRNA of vascular endothelial growth factor (VEGF) in mice with oxygen-induced retinopathy, and to elucidate the possible mechanism of occurrence of neovascularization in retinopathy of prematurity (ROP).MethodsSixty 7-day-old C57BL/6J mice were divided into oxygen-induced retinopathy group and control group. In oxygen-induced retinopathy group, 36 mice were exposed to 75% oxygen for 5 days and then to room air for 5 days; in control group, 24 mice were raised in room air. Vascular perfusion of fluorescein and retinal stretched preparation were used to observe the morphologic changes of retinal vessels. Reversal transcriptionpolymerase chain reaction (RT-PCR) was used to observe changes of VEGF mRNA in each group. ResultsIn oxygen-induced retinopathy group, the morphologic characteristics of retinal vessels were the unperfused area at the center of superficial and deepseated vessels, and the neovascularization appeared at mid-peripheral retina after 2 days in relative hypoxia condition. The results of RT-PCR showed space-time corresponding relation between expression of VEGF and neovascularization, which meant that the transcription of VEGF mRNA decreased in hyperxia conditionand increased in relative hypoxia condition. ConclusionHypoxia is the main reason of occurrence of retinal neovascularization; increased expression of VEGF caused by relative hypoxia after hyperxia might be effective in reducing the occurrence of neovascularization in ROP.(Chin J Ocul Fundus Dis, 2005,21:292-295)
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.
ObjectiveTo investigate the fundus fluorescein angiography (FFA) characteristics of spontaneous regression in retinopathy of prematurity (ROP) and the range of retinal vascularization. MethodsA clinical retrospective study. A total of 82 eyes of 41 infants with ROP, who underwent FFA from January 2019 to December 2021 in Department of Ophthalmology of Xijing Hospital after completion of ROP regression, were included. There were 25 males (50 eyes) and 16 females (32 eyes). ROP was diagnosed in Zone Ⅱ in 44 eyes, with 38 eyes in stage 2 and 6 eyes in stage 3, and in zone Ⅲ in 38 eyes of stage 2. All patients underwent FFA examination under general anesthesia, at postmenstrual age of 70.70±12.25 weeks, after the natural regression of ROP was completed. Focus on the retinal vascular development, as well as choroid circulation and macular abnormalities, and compare and observe the differences between zone Ⅱ and Ⅲ after spontaneous regression. The extent of retinal vascularization was determined by the ratio between the distance of the center of the disc to the border of the vascularized zone (DB) and the center of the disc to the fovea distance (DF). The width of avascular area, recorded as the distance from the ora serrata to the vascular termination, was counted by disc diameters (DD). The measurement data between zone Ⅱ and zone Ⅲ ROP were compared by the independent sample t-test, and the count data were compared by χ2 test or Fisher exact probability test. ResultsThe linear choroidal pattern was present in 9 eyes (21.95%, 9/41), and the tortuous arteries in the posterior retina were detected in 32 eyes (39.02%, 32/82). It was noted that increased branching of vessels presented in 45 eyes (54.88%, 45/82), straight shape of vessels shown in 27 eyes (32.93%, 27/82), circumferential vessels arisen in 45 eyes (54.88%, 45/82), arteriovenous shunt appeared in 18 eyes (21.95%, 18/82), and capillary bed lost in 46 eyes (56.10%, 46/82) in areas from initial ridge to vascular termini. Punctate or linear dye leakage was observed in 23 eyes (28.05%, 23/82) during the late phase of FFA. Macular abnormalities, such as the absence of foveal avascular zone and hypoperfusion, were observed in 28 eyes (34.15%, 28/82), of which the macular ectopia presented in 1 eye. The mean DB/DF ratio of all the 82 eyes on the temporal side was 4.63±0.29 and 3.77±0.23 in the nasal. The mean avascular area on the temporal retina was 1.74±1.00 DD. Compared with ROP in zone Ⅲ, increased branching of vessels and dye leakage were more common (χ2=9.303, 10.774; P=0.002, 0.001), the extent of temporal retinal vascularization was smaller (t=－2.285, P=0.026), and the avascular area of the retina was more significant (t=5.491, P＜0.001) in zone Ⅱ ROP. ConclusionsEven after completion of spontaneous regression in ROP, incomplete retinal vascularization and vascular abnormalities may exist permanently in FFA, including those such as the tortuous arteries in the posterior retina, increased branching and straight shape of vessels, circumferential vessels, capillary bed lost and macular abnormality. Further appropriate follow-up is needed for long-term safety.
ObjectiveTo observe the color Doppler flow imaging (CDFI) features of vitreoretinal lymphoma (VRL). MethodsRetrospective case series. From January 2022 to December 2024, 71 eyes of 42 patients diagnosed with VRL at the Eye Center of Beijing Tongren Hospital were enrolled. Among them, 17 were male and 25 female; 29 had bilateral and 13 unilateral involvement. Age ranged 17-78 years (median 59 years). Eleven cases had histopathologic confirmation and 31 were clinically diagnosed. All patients underwent CDFI and optical coherence tomography (OCT). CDFI findings were analyzed, noting the presence or absence of vitreous opacities (centrifugal distribution), posterior vitreous detachment (PVD), retinal detachment, and retinal elevated lesions. With Doppler overlay, blood flow within retinal lesions was assessed. The χ2 test was used to compare the detection rates of retinal lesions by CDFI and OCT, while Cohen’s Kappa assessed agreement in identifying the depth of lymphoma cell infiltration. ResultsAmong 71 eyes, vitreous opacity occurred in 66 eyes (93.0%, 66/71), of which 40 eyes (60.6%, 40/66) showed centrifugal opacity. 58 eyes (81.7%, 58/71) had posterior vitreous detachment. Retinal detachment occurred in 7 eyes (9.9%, 7/71). Retinal occupying lesions occurred in 23 eyes (32.4%, 23/61), of which 15 eyes (65.2%, 15/23) showed blood flow signals on the surface of the lesions but no blood flow signals inside the lesions by CDFI, and OCT showed that tumor cells gathered under the retinal pigment epithelium. CDFI showed blood flow signals inside the lesions in 8 eyes (34.8%, 8/23), and OCT showed that tumor cells gathered between retinal neuroepithelial layers. The lesion detection rate of OCT (69.6%, 16/23) was significantly lower than that of CDFI (100.0%, 23/23) (χ2= 6.066, P=0.014). OCT and CDFI showed perfect agreement in determining the depth of tumor cell infiltration (Kappa=1.0).ConclusionsThe ultrasonographic manifestations of VRL include vitreous opacity, PVD, and some retinal occupying lesions. Vitreous opacity often presents a characteristic centrifugal distribution. By observing whether there is blood flow signal in retinopathy using Doppler, the level of lymphoma cell infiltration can be suggested.