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 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 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.
In the expert consensus published by the Pediatrics in 2013, it was first proposed that anti-VEGF drugs can be considered for retinopathy of prematurity (ROP) with stage 3, zone Ⅰ with plus disease. However, there are many problems worth the attention of ophthalmologists, including the advantages and disadvantages of anti-VEGF therapy compared with traditional laser therapy, systemic and ocular complications after anti-VEGF therapy, and what indicators are the end points of anti-VEGF therapy. Combined with this consensus and numerous research findings, we recommend that the first treatment for anti-VEGF or laser therapy should be considered from disease control effects. For the threshold and pre-threshold lesions, the effect of anti-VEGF therapy for zoneⅡ lesions is better than that for zone Ⅰ lesions and the single-time effective rate is high. So, it is suggested that anti-VEGF therapy should be preferred for the first treatment. The choice of repeat treatment should be considered from the final retinal structure and functional prognosis. Laser therapy is advisable for the abnormal vascular regression slower and abnormalities in the posterior pole. It can reduce the number of reexaminations and prolong the interval between re-examinations. However, the premature use of laser has an inevitable effect on peripheral vision field. Excluding the above problems, supplemental therapy can still choose anti-VEGF therapy again. Most of the children with twice anti-VEGF therapy are sufficient to control the disease. Anti-VEGF therapy should be terminated when there are signs such as plus regression, threshold or pre-threshold lesions controlled without recurrence, peripheral vascularization, etc.
ObjectiveTo detect the development of retinal neovascularization (NV) induced by metabolic acidosis in neonatal rats and investigate the relationship between the occurrence of NV and vascular endothelial growth factor (VEGF). MethodsA total of 425 newborn Sprague-Dawley rats in experimental group underwent tubal feeding of NH4Cl (535 mg/kg) with the concentration of (50 mg/ml) (twice per day) from the 2nd day after the birth for 6 days and followed by a period of recovery. Additional 150 neonatal rats were in the control group without the tubal feeding. The rats were executed at the 3rd, 5th, 8th, 10th, 13th, 20th day after birth respectively. The retinal vessels were evaluated through retinal stretched preparation andadenosine diphosphatase (ADPase) staining; VEGF in retina was detected by enzymelinked immunosorbent assay(ELISA).ResultsIn the experimental group, the incidence of retinal NV at the 3rd, 5th, 8th, 10th, 13th, 20th day after birth was 0%，9%，26%，55%，19%, and 0% respectively. At the 3rd day, the expression of VEGF protein was lower in experimental group ［（101.1±14.2 ）pg/mg］ than that in the control group ［（133.2±15.9） pg/mg］（P＝0.004）, while at the 8th day it was higher in experimental group［(98.4±19.2) pg/mg］than that in the control group［（78.1±8.7） pg/mg］（P=0.028). There was no significant difference between the two groups at the 5th, 10th, 13th, and 20th day (Pgt;0.05). ConclusionsMetabolic acidosis may induce NV by injuring the developing retinal vessels. Retinal NV induced by acidosis relates to VEGF. (Chin J Ocul Fundus Dis, 2005,21:296-299)
Retinopathy of prematurity (ROP) is one of the leading causes of visual impairment in children. As understanding on the pathogenesis of ROP accumulated, anti-vascular endothelial growth factor (VEGF) drugs and their application have changed the treatment mode. Anti-VEGF therapy, with convenient operation and clear efficacy, has become an important treatment method for ROP. However, due to the dysfunction of organs in children with ROP, anti-VEGF drugs can enter blood circulation after intravitreal injection and then lead to temporarily reduction of the VEGF level in the blood, which may theoretically cause adverse effects on the development of all organs (especially the brain) in children with ROP. Therefore, it's necessary to pay attention to the effect of anti-VEGF drugs on neurodevelopment in children with ROP, strictly grasp the indications, and standardize its clinical application, so as to continuously improve the overall prognosis of ROP.
Objective To determine the effect of methimazole (MMI) on retinal vascular development in neonatal rats, and to investigate the relationship between the concentration of insulin-like growth factor-I (IGF-I) in serum and the development of normal blood vessels and between the concentration of IGF-I and the formation of abnormal blood vessels. Methods There were 75 neonatal SpragueDawley rats in experimental group whose mothers were raised with water with 0.1% MMI at the first day of parturition. Another 50 neonatal rats were in the control group whose mothers were raised with normal water. The rats in the two groups were sub-divided into 4day and 10day subgroup, respectively. The retinal flatmount of the right eyes were stained with adenosine diphosphatase (ADPase); with the paraffin section of the left eyes, the number of nucleolus breaking through retinal inner limiting membrane was counted and the retinal blood vessels were evaluated. Serum IGF-I levels were detected by radioimmunoassay, and the weight of the neonatal rats in each group were observed and recorded. Results The incidence of retinal neovascularization in 10 day MMI group was 27%, and 0% in 4-day MMI group and control group. The serum IGF-I level in 4-day and 10-day MMI group (73.07 ng/ml, 175.13 ng/ml) was obviously lower than which in the 4-day and 10-day control group (168.73 ng/ml,306.38 ng/ml) （P=0.00）. Obvious slow growth of the neonatal rats was found in MMI group compared with which in the control group. Conculsions MMI may inhibit the normal growth of retinal blood vessels and lead neovascularization, which may relate to the initial decrease of the serum IGF-I level. (Chin J Ocul Fundus Dis, 2007, 23: 198-201)
Objective To investigate the incidence of retinopathy of prematuri ty (ROP) in the area of Shanghai, and to provide the preliminary data for the ev aluation of present criteria for ROP screening. Methods Record s of 289 prematur e infants who had undergone ROP screening from the four NICU in Shanghai between February 2004 and January 2005 were analyzed. Screening criteria included prete rm infants or low birth weight (LBW) infants with BW of 2000g or less. The first examination starts at 4 to 6 weeks chronologic age or 32 weeks post conceptual age. Results In the 289 screened infants, 19 had developed acu te ROP. There we re 3 threshold ROP, 7 prethreshold ROP and 9 developed ROP less than prethreshol d. The incidence of ROP was 6.6%. According to the British recommended guideline s（BWle;1500 g or GAle;31 weeks）, only 119 out of 289 needed screening and one ca se of stage 1 ROP was missed; the incidence of ROP was 15.1% (18/119). When lowered sc reening criteria to the American guidelines（BWle;1500g or GAle;28 weeks）, t here were only 83 infants needed screening, and we missed 2 stage 1 and 1 prethreshold ROP and the incidence of ROP was 19.3% (16/83). Conclusions The i ncidence of ROP i s 6.6% according to our study. It is lower than other reports and it has somethi ng to do with our present screening guideline. Further epidemiological data are needed to modify the guideline accordingly.
Objective To observe the systemic inhalation anesthetic effects of preterm children with different gestational ages under ocular fundus examination, and to assess its safety. Methods Fifty-one preterm children with retinopathy of prematurity (ROP) were included in the study. These kids were divided into 2 groups, group Ⅰ included 24 kids with a corrected gestational age of 33 to ＜44 weeks, and group Ⅱ included 27 kids with a corrected gestational age of 44 to 64 weeks. The preterm months were same (t=-1.3.P＞0.05), but the body weights were different (t=-10.5.P＜0.05) between these two groups. Anesthesia was induced by inhalation of 6% sevoflurane, and the period from the beginning of inhalation to disappearance of body movement was the induction time. 6% sevoflurane was inhaled continuously for another period of the induction time, and then the concentration of sevoflurane was adjusted to a maintenance concentration. The initial maintenance concentration was 3%, and was adjusted by 0.5% each time. Sequential method was used to determine the subsequent maintenance concentration. If the preceding patient had not moved during the maintenance period, the sevoflurane concentration was decreased by 0.5% for the next patient. If the preceding patient had moved during the maintenance period, the sevoflurane concentration was increased by 0.5% for the next patient. Respiratory depression and cough during the induction and maintenance period, duration of anesthesia and recovery time were recorded. Choking and vomiting during drinking or milk-feeding in one hour after the ocular fundus examination were also recorded. Results The effective inhale concentration in 50% patient of sevoflurane was 2.5% in group Ⅰ, 2.9% in group Ⅱ. The average maintenance concentration was (2.5plusmn;0.5)% in group Ⅰ, (3.0plusmn;0.5)% in group Ⅱ. The difference was statistically significant (t=-3.3.P＜0.05). The average duration of anesthesia and the average awake time were the same (t=0.04 and -1.0 respectively.P＞0.05) between these two groups. The average induction time was significantly shorter in group Ⅰ than in group Ⅱ, the difference was statistically significant (t=-4.9.P＜0.05). All patients were successfully completed the ocular examination. No respiratory depression or cough occurred during and after the examination. No choking and vomiting during drinking or milkfeeding in one hour after the ocular fundus examination. Conclusion Anesthesia with inhaled sevoflurane by a face mask is safe for preterm outpatients undergoing fundus examination.