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.
Intravitreal injection of anti-VEGF drugs for the treatment of retinopathy of prematurity (ROP) is a hot topic of research, and it can be used to treat the ROP (Ⅰzone). The current anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept and conbercept, etc. However, in recent years, several studies have confirmed that anti-VEGF drugs have an increased recurrence rate and a longer recurrence time than conventional laser photocoagulation therapy. The follow-up period should be extended and repeated injections may be required. Due to the lack of large-scale prospective clinical studies, the recurrence rate, time window of recurrence, risk factors and treatment methods of various anti-VEGF drugs for ROP are still unclear. Anti-VEGF drugs in the treatment of ROP needs to accumulate more evidence-based medical evidence.
ObjectiveTo observe the morphologic characteristics of color Doppler flow imaging (CDFI) and blood stream in patients with retinopathy of prematurity, and provide the new clinical diagnostic gist.MethodsCDFI was performed on 78 patients (156 eyes) with ROP at Ⅳ and Ⅴ stage, who had the diseases history such as prematurity and low birthweight which had been diagnosed by indirect ophthalmoscope, underwent the examination of CDFI. Morphologic characteristics of the results of CDFI and features of blood flow of the pathological changes were observed. ResultsIn the patients with ROP at the Ⅳ stage, a weak zonal echo originated from one side of peripheral wall of eye ball in the vitreous body, and extended to the echo of post pole and wall of eye ball and joined the echo of optic disc. In the patients with ROP at the V stage, lumplike echo connected closely with echo of lens and the circumambience was surrounded; the focus looked like lotus when combined with retinal detachment: the swelled “corona” wrapped and tightly connected with the lens, and the thin “caulis” showed weak zonal echo which attached to the optic disc. The features of blood flow showed the signal of blood stream connected with central retinal artery at the “caulis”, which was analyzed by Doppler spectrum as the bloodflow spectrum of artery and vein in the same direction which was the same as the central retinal artery and vein.ConclusionsIn patients with ROP at the IV and V stage, the results of CDFI mainly shows zonal or lumplike echo, in which the bloodflow signal extended with central retinal artery could be seen. The morphological changes of CDFI and the features of blood flow are useful in diagnosis of ROP. (Chin J Ocul Fundus Dis, 2005,21:282-284)
ObjectiveTo observe the therapeutic effect of segmental scleral buckling and vitrectomy with/without lensectomy on the retinopathy of prematurity (ROP) stage 4a, 4b and 5. MethodsOne hundred and thirty-four ROP infants (181 eyes) diagnosed as stage 4a, 4b and 5, and performed with segmental scleral buckling or vitreous with/without lensectomy were retrospectively analyzed. The operated 4a-, 4b- and 5- stage eyes were 40, 51 and 90 eyes. The operational method depended on the location and severity of fibrovascular membrane. Of 181 eyes, segmental scleral buckling was referred for 37 eyes which include 23 eyes with 4a stage and 14 eyes with 4b stage; vitrectomy was referred for 50 eyes which include 14 eyes with 4a stage, 29 eyes with 4b stage and 7 eyes with 5 stage; vitrectomy with lensectomy was referred for 94 eyes which include 3 eyes with 4a stage, 8 eyes with 4b stage and 83 eyes with 5 stage. The effect was classified as success, improved and failure. Failure includes lost eye. Follow-up for 4a, 4b and 5 stage patients are 34, 31 and 29 months respectively. ResultsSegmental scleral buckling was referred for 37 eyes, success in 23 eyes (62.16%), improved in 11 eyes (29.73%), failure in 3 eyes (8.11%). Vitrectomy was referred for 50 eyes, and success in 20 eyes (40.00%), improved in 22 eyes (44.00%), and failure in 8 eyes (16.00%). In the total of 94 eyes underwent vitrectomy with lensectomy, 20 eyes was success (21.28%), improved in 17 eyes (18.08%), failure in 57 eyes (60.64%). In 40 stage 4a eyes, 33 successes (82.50%), 6 improved (15.00%) and 1 failure (2.50%). In 51 stage 4b eyes, 11 successes (21.57%), 30 improved (58.82%) and 10 failures (19.61%). For 90 stage 5 eyes, 14 successes (17.50%), 19 improved (23.75%) and 57 failures (71.25%). The therapeutic effect of segmental scleral buckling for stage 4a was better than that for stage 5 (χ2=6.707,P=0.035). The difference of therapeutic effect of vitrectomy for different stage was significant (χ2=21.010,P=0.000); stage 4a was the best; stage 4b was the second, stage 5 was the worst. The therapeutic effect of vitrectomy with lensectomy for stage 5 was worse than that for stage 4a and 4b (χ2=16.066,P=0.003). ConclusionThe surgery patterns of ROP was determined based on the disease severity, the surgery effects of stage 4a and 4b were better than stage 5, which had nothing to do with the surgical procedures.
Objective To observe the inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse. Methods 90 one-week-old C57B L/6J mice were divided into four groups at random. 15 mice in the 1st group as normal control group, 15 mice in the 2nd group as oxygen control group, 30 mice in the 3rd group as high-dose Bevacizumab treatment group, 30 mice in the 4th group as low-dose Bevacizumab treatment group. The 2nd, 3rd and 4th groups were exposed to 75% oxygen for 5 days and then to room air. At the 12th day, One eye of each mouse of two control groups were received an intravitreal injection with Be vacizumab at 2 mu;l、1 mu;l respectively, and the same volume of BSS was injected into the other eye of the mice. The adenosine diphosphatase (ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced change s of retinal vessels. The number of the endothelium cell nuclei of proliferative neovascularization was quantified by retinal microtome chromoscopy. Real-time PCR analysis was performed to examine the expression of VEGF mRNA. Results Comparing with oxygen control group, regular distributions, reduced density of retina l vascular and reduced endothelium cell nuclei which extending retinal membrane were observed in the treatment groups(P＜0.001). But the differences between two treatment groups are not statistically significant (P＞0.05). The expression of VEGF mRNA was not significantly different in oxygen control group whatever it whether accepted Bevacizumab treatment or high or low dose (P＞0.05). Conclusion Intravitreal injection with Bevacizumab can effectively inhibits the retinal neova scularization in oxygen-induced retinopathy in the mouse. Intravitreal injection with Bevacizumab might become to the new method to treat retinopathy of premature. （Chin J Ocul Fundus Dis，2008，24：184-188）
Retinopathy of prematurity (ROP) is a retinal angioproliferative disease that occurs in premature and low birth weight infants, and is the most common eye disease that causes blindness and low vision in infants. However, there is no systematic standardized guidance on the overall treatment strategy for ROP. Therefore, in order to standardize the treatment of ROP, the Ophthalmology Group of Pediatrics Society of Chinese Medical Association organized relevant domestic experts to put forward standardized opinions on the treatment of ROP in China after repeated discussion, so as to provide clinicians with reference and application in clinical practice.
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.
Objective To investigate the effect of inducible nitric oxide synth ase (iNOS) or cyclooxygenase－2 (COX－2) on retinal neovascularization and its possible mechanism in oxygen－induced retinopathy （OIR） mouse model. Methods Retinal neovascularization was induced by oxygen with different concentration. The expression of iNOS, COX－2, matrix metalloproteinases 2 (MMP－2) and vascular end othelial growth factor (VEGF) in the retinae of experimental animals were analyzed by immunohistochemistry, realtime polymerase chain reaction and western blotting technologies. Results The inhibition of COX－2 or iNOS obviously attenuated retinal neovascularization and decreased the expression of VEGF and MMP－2. The iNOS inhibition decreased COX－2 expression, and vice versa. Conclusions COX－2 and iNOS may play a role in retinal neovascularization in OIR mouse model, which may act by regulating the expression of VEGF and MMP－2.
Objective To explore the effect of polycythemia on retinopathy of prematurity (ROP). Methods The clinical data of 262 premature cases was analyzed retrospectively in Xi'an Children Hospital from January 2005 to January 2009. Polycythemia was found in 46 cases (17.56%), including 27 males and 19 females. In 216 infants without polycythemia (82.46%), 155 were male and 61 were female. The difference of the birth weight (t=0.730, P=0.466), gestational age (t=1.603,P=0.110), oxygen inhalation numbers (chi;2=0.04,P＞0.90) and times (t=1.225,P=0.223), and concentration (t=1.823,P=0.071) between polycythemia group and no polycythemia group were not significant. In order to diagnose ROP, the ocular fundus of all premature infants was examined with binocular indirect ophthalmoscope,and the stage of ROP was assessed.Results In all the premature infants,ROP was found in 120 cases (45.80%). In 46 cases of polycythemia, ROP was found in 25 cases (54.34%); in 216 infants without polycythemia, ROP was found in 95 cases (43.98%); the difference of ROP incidence between the two groups was not significant (chi;2=1.64, Pgt;0.1).In 120 ROP patients, 104 cases (86.67%) with ROP＜3 stage and 16 cases (13.33%) with ROP ge;3 stage were found. In 25 ROP patients with polycythemia, 18 cases (72.00%) with ROP ＜3 stage and 7 cases (28.00%) with ROP ge;3 stage were found. In 95 ROP patients without polycythemia, 86 cases (90.53%) with ROP ＜3 stage and 9 cases (9.47%) with ROP ge;3 stage were found. The difference of the incidence of ROP ＜and ge;3 stage between the two group was significant (chi;2=4.38, Plt;0.05). In 120 cases of ROP, prethreshold retinopathy was found in 106 cases (88.33%), while threshold and post-threshold retinopathy was in 14 cases (11.67%). In 25 ROP patients with polycythemia, prethreshold retinopathy was found in 19 cases (76.00%), and threshold and post-threshold retinopathy was in 6 cases (24.00%).In 95 ROP infants without polycythemia, pre-threshold retinopathy was found in 87 cases (91.58%),while threshold and post threshold retinopathy was in 8 cases (8.42%).The difference of the incidence of ROP with prethreshold, and threshold and post-threshold retinopathy between the two groups was not significant (chi;2=3.27,P＞0.05).Conclusion Polycythemia may not affect the incidence of ROP,but impact on the severity of ROP.