Objective To explore the effect of oxygen inhalation on the retinae of newborn rats and its mechanism.Methods We mimicked the retinopathy of prematurity(ROP) by putting the newborn rats in high concentrated oxygen. One-day old rats were put into the oxygen box with the oxygen concentration of 80% for continuous 7 days; then in air condition for 7 days. The arterial blood oxygen pressure, retinal superoxide dismutase (SOD), and malondialdehyde (MDA) of the rats (1,2,4,7,8,9,11,14 days old) were examined. The diameter of retinal vessels′main branch and the coverage rate of peripheral vessels were measured in 7- and 14-day-old rats by ink perfusion. The retinal neovascularization of rats (8,9,11, 14 days old) were observed by HE staining. The rats of the same age fed in air condition were in the control group.Results The differential pressures of blood oxygen of rats (1,2,4,7 days old) in study group were significantly higher than those in the control group (P＜0.01), while the differential pressures of blood oxygen of rats (8,9,11,14 days old) in study group were lower than those in the control group (P＞0.05). The contents of SOD of the retinae in the rats ( 1,2,4,7,8 days old) were significantly lower than those in the control group(P＜0.01, P＜0.05 ), while the contents of MDA were significantly higher than those in the control group (P＜0.01,P＜0.05). The diameter of retinal vessels′main branch in 7-day rats was 75% of the control group, and the coverage rate of peripheral vessels was 22% of the control group; and was 61% and 73% respectively in 14-day-old rats. The neovascularization could be seen in 16.7% of the rats in the study group and nought in the control group.Conclusion The damage of free radical of the retina in high concentrated oxygen and hypoxia situation after oxygen supply may be one of the most important mechanism of ROP. (Chin J Ocul Fundus Dis，2003，19：269-332)
ObjectiveTo investigate the clinical risk factors of preterm infants and its severity in premature infants with bronchopulmonary dysplasia (BPD) with retinopathy of prematurity (ROP).MethodsRetrospective clinical study was performed. A total of 126 preterm infants with BPD in the Neonatal Department of the Affiliated Hospital of Qingdao University from January 2016 to December 2018 were enrolled in the study. Among them, 69 were males and 57 were females, whose gestational age＜32 weeks and birth weight＜1500 g. BPD grades Ⅰ, Ⅱ, and Ⅲ were 63, 40, and 23 cases respectively. According to the presence or absence of ROP, children were divided into ROP group and non-ROP group, with 48 (38.1%) and 78 (61.9%) cases respectively. The differences of clinical data between the two groups were compared and analyzed. Quantitative data comparison between groups was performed by t test, and count data comparison was performed by χ2 test. The risk factors of ROP in BPD premature infants were analyzed by multi-factor logistics regression. The correlation between BPD severity and ROP severity was tested by Spearman rank correlation test.ResultsCompared with the non-ROP group, the ROP group had a smaller gestational age (t=5.988), lower birth weight (t=7.371), higher the application rate of oxygen concentration＞30% (duration of service＞24 h), high rate (χ2=17.244) and longer noninvasive ventilation time (t=－7.139), the differences were statistically significant (P＜0.05). In the logistic regression model, the noninvasive ventilation time was the risk factor for ROP in preterm infants with BPD (OR≈1.054, P＜0.05), while gestational age and birth weight were importantly protective factors for ROP in preterm infants with BPD (OR≈0.938, 0.996; P＜0.05). The results of the correlation analysis found that the severity of BPD was significantly positively correlated with the severity of ROP. As the severity of BPD increased, the severity of ROP increased, and the difference was statistically significant (rs=0.306, P＜0.035).ConclusionsFetal gestational age, low birth weight, hyperoxia, and long-term non-invasive mechanical ventilation are the main risk factors for ROP in preterm infants with BPD. The severity of BPD is positively correlated with the incidence and severity of ROP.
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 efficacy of laser photocoagulation and intravitreal ranibizumab treatment of retinopathy of premature(ROP). MethodsThis study included 49 ROP infants (96 eyes), including type 1 pre-threshold ROP (7 infants, 14 eyes), threshold ROP (38 infants, 44 eyes) and aggressive posterior ROP (AP-ROP, 4 infants, 8 eyes). According to the treatments received, all patients were divided into laser photocoagulation (LP) group (40 infants, 78 eyes) and intravitreal ranibizumab (IVR) treatment group (9 infants, 18 eyes). Generally, zoneⅡand stage 3 ROP with clear refractive media received laser photocoagulation, zoneⅠROP and AP-ROP, or eyes with unclear refractive media or infants with poor general condition received IVR. The infant gestational age, birth weight, corrected gestational age at first treatment and the cure rate of the first treatment were analyzed between the two groups, and between three disease types (type 1 pre-threshold, threshold and AP-ROP). ResultsThe gestational age and birth weight was no difference between the LP group and IVR group (t=0.827, 1.911; P > 0.05). The corrected gestational age at first treatment of LP group was significantly smaller than that in the IVR group (t=3.041, P < 0.05). In the LP group, 75 of 78 eyes (96.15%) was cured by the first treatment, 3 of 78 eyes (3.85%) progressed to stage 4A after the first treatment and was controlled by vitrectomy. In the IVR group, 8 of 18 eyes (44.44%) was cured by the first treatment, 10 of 18 eyes (55.56%) progressed to next stage after the first treatment and was controlled by additional laser photocoagulation or repeated IVR. The gestational age and birth weight was no difference between type 1 pre-threshold, threshold and AP-ROP infants (t=2.071, 0.664; P > 0.05). The corrected gestational age at first treatment of type 1 pre-threshold infants was the same of the threshold lesion infants (t=2.054, P > 0.05). The corrected gestational age at first treatment of AP-ROP infants was significantly smaller than that of type 1 pre-threshold and threshold lesion infants (t=3.250, P < 0.05). The cure rate was statistically significant (χ2=24.787, P < 0.05) between there three ROP lesions. ConclusionIVR treatment is suitable for zoneⅠlesions, AP-ROP and Plus lesions, while laser photocoagulation is appropriate for zoneⅡlesions with fibrosis and less vascular proliferation.
ObjectiveTo analysis the fundus characteristics of fundus fluorescein angiography (FFA) of retinopathy of prematurity (ROP). MethodsEighty-four cases (168 eyes) who were diagnosed with ROP by a binocular indirect ophthalmoscope were included in the study. Among the 84 cases, there were 2 cases (4 eyes) of stage 1 ROP, 26 cases (52 eyes) of stage 2 ROP, 40 cases (80 eyes) of stage 3 ROP, 4 cases (8 eyes) of stage 4 ROP, and 4 cases (8 eyes) of stage 5 ROP, 9 cases (18 eyes) of plus disease, 8 cases (16 eyes) of aggressive posterior ROP (APROP). All infants received FFA with RetCam Ⅱ under general anesthesia and mydriasis. The retinal vein morphology, capillary filling state, neovascularization morphology and fluorescein leakage were observed. ResultsFFA revealed increased branching, expansion and tortuous peripheral retinal capillaries, increased capillary permeability with a small amount of fluorescein leakage in stage 1 ROP. There was a clear dividing line between the vascular area and the remote avascular area. In stage 2, the peripheral branches of temporal retinal blood vessels increased, and parallel distributed like a broom. The capillary end anastomosed with each other to form a loop. The fibrous tissues at the lesion edge proliferated as a ridge, with popcorn phenomenon. In stage 3, the ridge continued broadening, and the neovascular fibrous membrane formed breakthrough internal limiting membrane, stretched into the vitreous with a lot of fluorescein leakage. The ridge and remote avascular zone demarcated clearly. In stage 4 and 5, the vessel changes had similar phenomenon with the stage 2 and 3 in undetached retina, but the vessels in the detached retina expanded with fluorescein leakage. As for plus disease, the retinal arterioles in the posterior pole were tortuous, there were a large number of non-perfusion area in the peripheral retina with hemorrhage and obscured fluorescence. The retinal vessels in posterior pole in AP-ROP were also tortuous, and the capillaries were extreme expanded, while there were very few tortuous vessels and no capillary formation in the other part of retina.At the avascular zone boundaries, there were a large group of neovascularization with fluorescein leakage. ConclusionsThe demarcation line separating the avascular from the vascularized retinal regions is formed in stage 1, 2 and 3, and the amount of fluorescein leakage gradually increase from stage 1 to stage 3 ROP. The detached retina of stage 4 and stage 5 has an unclear focal length in the FFA. The plus disease mainly has arteriolar tortuosity in the posterior pole retina. In the AP-ROP cases, both of the arterioles and venules in posterior pole of retina are tortuous and expanding with neovascularization leakage of fluorescein.
ObjectiveTo evaluate the safety and efficacy of 27G micro-incision vitrectomy surgery (MIVS) combined with intravitreal injection of ranibizumab (IVR) in the treatment of retinopathy of prematurity (ROP) with early intervention failure.MethodsRetrospective case series was performed. Fourteen eyes (11 infants) with ROP who underwent 27G MIVS combined with IVR were included from March 2016 to January 2018 in Shenzhen Eye Hospital. Among them, there were 5 males with 7 eyes, 6 females with 7 eyes. The average gestational age of the infants was 28.12±0.90 weeks; the average birth weight was 1 023.64±200.96 g. Before the early clinical intervention, 1 infant (2 eyes) had ROP in zone Ⅰstage 3 with plus disease, 8 infants (10 eyes) had ROP in zone Ⅱ stage 3 with plus disease, and 2 infants had ROP in aggressive posterior ROP. Six eyes underwent laser photocoagulation, while 8 eyes received laser therapy combined with IVR. Six eyes of stage 4A ROP and 8 eyes in stage 4B. Retinal detachment was detected with a mean of 10.44±9.21 weeks. At the time of surgery, the average post-conceptional age was 48.02±8.09 weeks. All the affected eyes were treated with standard sclera with three incisions 27G MIVS. During the operation, only local vitrectomy was performed to release and clear fibroascular proliferation in the optic disc, anterior macular area and pericristal area. After surgery, 10 mg/ml of ranibizumab 0.03 ml was injected into the vitreous cavity. The average follow-up time was 23.36±8.34 months. The primary objectives were the condition of retinal reset, ROP progression control and complications.ResultsAll patients had uneventful surgeries with an average duration of 32.86±9.35 mins. Of the 14 eyes, 12 eyes (85.71%) were controlled, 8 eyes (57.14%) had a good rearrangement of macular structure, while 4 eyes with macular traction. Two eyes had ROP progression, recurrence of retinal detachment, posterior synechia. Complicated cataract was in 1 eye. Proliferative vitreoretinopathy and retinal detachment was in 1 eye after 7 months the operation.Conclusion27G MIVS combined with IVR is a safe and effective treatment for ROP with early clinical intervention failure.
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.
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 observe the efficacy and safety of combination of intravitreal injection of ranibizumab and laser photocoagulation for the treatment of aggressive posterior retinopathy of prematurity (AP-ROP). MethodsMedical records of 70 eyes of 35 premature infants with a primary diagnosis of AP-ROP in our clinic were reviewed and analyzed retrospectively. All the lesions were located in posterior zone, with 42 eyes in zone 1 and 28 eyes in zone 2. Forty-six eyes had iris neovascularization, while 19 eyes combined with vitreous hemorrhage. All participants underwent intravitreal injection of ranibizumab as the primary treatment within 12 hours after diagnosis of AP-ROP. The systemic and ocular adverse effects were observed. The change of retinal vascular tortuosity and dilatation before and after the intravitreal injection of ranibizumab was observed one week after injection. Laser photocoagulation was used as adjuvant therapy if the plus disease persisted more than two weeks or new-onset ridge occurred after injection. The mean time interval between injection and laser therapy was (5.1±2.6) weeks (range, 1-10 weeks). Follow-up ranged from 6 to 18 months, with a mean of (10.3±3.9) months. The anatomical results and complications were evaluated after treatment. The eyes that progressed to stage 4 or 5 during the follow-ups were underwent lens-sparing vitrectomy or lensectomy combined with vitrectomy. ResultsNo major systemic or ocular complications were observed. Preretinal hemorrhages were found in 12 eyes of 8 patients (17.1%), but they were absorbed spontaneously during the follow-ups. All lens remained transparent and no iatrogenic retinal hole was occurred during the follow-ups. After the injection, the regression of iris neovascularization was observed in 46 eyes within one week, vitreous hemorrhage absorbed significantly in 16 eyes (84.2%), and plus disease disappeared completely within one week in 61 eyes (87.1%). 59 eyes (84.3%) demonstrated vascularization toward the peripheral retina after treatment. 32 out of 42 eyes (76.2%) with zone 1 demonstrated vascularization toward to zone 2, while 24 out of 28 eyes (85.7%) with zone 2 demonstrated vascularization toward to the junction of zone 2 and 3. After intravitreal injection of ranibizumab combined with laser photocoagulation, 62 of 70 eyes (88.6%) had retinal vascular ridge and plus disease regression. However, 8 eyes of 6 patients (11.4%) showed significant fibrovascular proliferation and progressed to retinal detachment after the combination treatment of intravitreal ranibizumab injection and laser photocoagulation. Four eyes underwent lens-sparing vitrectomy, while the other 4 eyes underwent vitrectomy combined with lensectomy. Five eyes achieved totally retinal reattachment after surgery, while 3 eyes achieved partially retinal reattachment. ConclusionThe combination of intravitreal injection of ranibizumab and laser photocoagulation is safe and effective in the treatment of AP-ROP.
Objective To observe the characteristics of images of ocular fundus obtained by computer-assisted imaging system of binocular indirect ophthalmosco p y (CABIO) in the healthy premature infants and the ones with retinopathy of prem aturity(ROP), and evaluate the value of the clinical practice of CABIO in ROP s creening. Methods From January, 2006 to December, 2006, we exa mined 150 prematur e infants in ROP screening procedure by using the computerassisted imaging sys t em of binocular indirect ophthalmoscope, beginning at the infantsprime;age of postn a tal 4-6 weeks or the corrected age above 32 weeks. The follow-up duration was co nfirmed according to the first examination results. The procedure of the operati on was recorded and the typical pictures were shot to obtain the images of the o cular fundus of the healthy premature infants and the ones with ROP. The charact eristics of the images were retrospectively analyzed and compared. Resu lts The typical images of normal ocular fundus and that with ROP in the 150 premature i nfants were successfully obtained by indirect ophthalmoscope. In normal fundus o f infants, the color of optic disc was pale, peripheral retina was not completel y vascularized and presented gray-tone in color;while all stages of ROP present ed dif ferent appearances under the indirect ophthalmoscope. Conclusions Computer-ass isted imaging system of the binocular indirect ophthalmoscopy can clearly observ e the characteristics of normal ocular fundus of premature infants and the ocula r fundus with ROP, and can save the objective examination results, which may pro vide significant references in screening and treating ROP.