Purpose To investigate retinoic acid (RA) induced apoptosis in retinal pigment epithelial (RPE) cells. Methods 10-5、10-6、10-7 mol/L were added to cultured PRE cells.Aridine orange fluorescence and TdT-mediated dUTP nick end labelling(TUNEL) techniques were used to observe apoptotic changes. Resultss 10-5、10-6、10-7 mol/L RA induced apoptosis in RPE cells.Cell shringkage,chromatin condensation and nuclear DNA fragmentation of RPE cells were observed by TUNEL technique.When 10-7、10-6、10-5mol/L RA treated RPE cells for 5 days,apoptotic index(AI)was 36.9%、4409% and 61.4% respectively,and 48.0%、59.9%、74.2% for 6 days.At the same concentration of RA,AI increased when time prolonged．At the same day,AI increased when the concentration of RA rose.There was significant difference in the results(Plt;0.05). Conclusion Our results showed that RA-induced apoptosis in RPE cells was detected with a good dose and time response. (Chin J Ocul Fundus Dis,1998,14:153-155)
ObjectiveTo observe the efficacy and safety of combined photodynamic therapy (PDT) with intravitreal ranibizumab injection in patients with polypoidal choroidal vasculopathy (PCV). MethodsTwenty-four PCV patients (24 eyes) were enrolled in this retrospective case study.All patients were assessed by the examinations of Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart, color fundus photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optic coherence tomography (OCT). The mean visual acuity was (33.41±19.43) letters; the mean macular retinal thickness was (343.63±88.60) μm. Patients received PDT first, and intravitreal injected ranibizumab 0.5 mg (0.05 ml) 72 hours later. Treatments were repeated as a single intravitreal injection of ranibizumab combined with or without PDT if the monthly follow-up indicated that it was necessary. The average follow-up period was 13.1 months. The average treatment times were analyzed for each eye. Systemic and ocular adverse events were observed. Visual acuity, macular retinal thickness and leakage of PCV before and after the treatment were analyzed. ResultsIntravitreal ranibizumab injections was repeated (2.8±1.6) times per eye on average, and intravitreal injection of ranibizumab combined with PDT was repeated (0.4±0.5) times per eye on average. No systemic and ocular adverse effects were found during and after combined therapy. In the last follow-up, the mean visual acuity of ETDRS was (44.21±17.24) letters, improved by 10.8 letters (t=-4.77, P<0.01).Visual acuity was improved in 11 eyes (45.8%) and stable in 13 eyes (54.2%). FFA and ICGA showed complete closed PCV in 17 eyes (70.8%), partial closed PCV in 7 eyes (29.2%). OCT image showed that the retinal edema was disappeared in 19 eyes (79.2%) and alleviated in 5 eyes (20.8%). The mean macular retinal thickness was (171.33±38.06) μm, which was 172.30 μm less than that of pre-treatment values (t=11.96, P<0.05). ConclusionPhotodynamic therapy combined with intravitreal ranibizumab injections for PCV is safe and effective, with visual acuity improvement, reduction of retinal edema and PCV leakage.
ObjectiveTo investigate the efficacy and safety of intravitreal ranibizumab and (or) triamcinolone combined with laser photocoagulation for macular edema secondary to branch retinal vein occlusion (BRVO) during one year period. MethodsThe data of 31 eyes from 31 consecutive patients with macular edema secondary to BRVO during one year follow-up visit were retrospectively analyzed. Mean best corrected visual acuity (BCVA) logMAR was (0.74±0.36) and mean central retinal thickness (CRT) was (484.48±164.81)μm at baseline. All patients received standardized clinical comprehensive examinations including vision, intraocular pressure and optical coherence tomography for diagnosis before treatment. All patients received intravitreal injections of 0.5 mg ranibizumab (0.05 ml) at first visit. The continue PRN treatment were based on the visual acuity changes and the optical coherence tomography findings. Eyes received combined triamcinolone acetonide 0.05 ml (40 mg/ml) and ranibizumab for macular edema recurrence after two injections of ranibizumab and received laser photocoagulation during 10-14 days after third injections of ranibizumab. Mean injection of ranibizumab was 3.52±2.01, 15 eyes with triamcinolone acetonide (0.84±1.21), 21 eyes with laser photocoagulation (0.97±0.95) and 12 eyes with three treatment. Compared the visual acuities and CRTs of the first and the last visits by statistical analysis. ResultsMean visual acuity improved significantly to 0.42±0.33 logMAR (t=6.611, P=0.000). Mean improvement of visual acuity was 2.90±3.07 lines. A gain of three or more logarithmic lines was evaluated in 20/31 eyes (64.52%) at the last visit. Mean CRT was (326.19±117.80)μm (t=4.514, P=0.000).Mean reduction of CRT was (333.58±134.17)μm. A decrease of 100μm of CRT was evaluated in 17/31 eyes (54.84%). No severe ocular and systematic side effect was found. ConclusionThe efficacy and safety of intravitreal ranibizumab and (or) triamcinolone combined with laser photocoagulation for macular edema secondary to BRVO were assured.
Corticosteroids, anti-vascular endothelial growth factor, antibiotics and antiviral were the main 4 classes of drugs for intravitreal injection. Depending on the class and volume of medication, age and gender of patients, ocular axial lengths or vitreous humour reflux, intraocular pressure (IOP) can be elevated transiently or persistently after intravitreal injection. Transient IOP elevation occurred in 2 weeks after intravitreal injection, and can be reduced to normal level for most patients. Only a small portion of such patients have very high IOP and need intervention measures such as anterior chamber puncture or lowering intraocular pressure by drugs. Long term IOP elevation is refers to persistent IOP increase after 2 weeks after intravitreal injection, and cause optic nerve irreversible damage and decline in the visual function of patients. Thus drug or surgical intervention need to be considered for those patients with high and long period of elevated IOP. Large-scale multicenter clinical trials need to be performed to evaluate the roles of the drug and patients factors for IOP of post-intravitreal injection, and to determine if it is necessary and how to use methods reducing IOP before intravitreal injection.
Objective To observe the alterations of macular vascular density and the area of foveal avascular zone (FAZ) in branch retinal vein occlusion (BRVO) eyes. Methods A retrospective case-control study. Forty-five patients with unilateral BRVO and macular edema were enrolled in this study. Optical coherence tomography angiography (OCTA) was performed on the BRVO and fellow eyes. The scanning region in the macular area was 3 mm×3 mm. Macular vascular density and FAZ area in the superficial and deep retinal capillary plexi were measured in all eyes. The values of macular vascular density and FAZ area between BRVO eyes and fellow eyes, affected sector and unaffected sector were compared. Results The mean overall vascular density measured in the entire scan was lower in BRVO eyes compared with fellow eyes in both the superficial and deep capillary plexus (t=14.186, 9.468; P＜0.05). The reduce degree of vascular density in the deep capillary plexus (7.65%) was higher than that in the superficial plexus (7.27%). In the superficial plexus, the vascular density was lower in the affected sector and the unaffected sector of the BRVO eyes compared with the corresponding sector in the fellow eyes (t=15.386, 9.435; P＜0.05). The FAZ area enlarged in the BRVO eyes compared with the fellow eyes in the superficial capillary plexus and in the deep capillary plexus (t=3.216, 5.119; P＜0.05). The degree of enlargement of FAZ area in the deep capillary plexus (0.19 mm2) was higher than that in the superficial plexus (0.11 mm2). Conclusions In eyes with BRVO, quantitative OCTA measurements confirm that vascular density decreased and FAZ area enlarged in the superficial and deep capillary plexi. The reduce degree of vascular density and enlargement degree of FAZ area in the deep capillary plexus are higher than those in the superficial plexus.
Objective To evaluate the efficacy and safety of dexamethasone intravitreal implant (Ozurdex) in the treatment of macular edema (ME) secondary to retinal vein occlusion (RVO). Methods Thirty-nine patients (39 eyes) with ME secondary to RVO were enrolles in this study. Of the patients, 27 were male and 12 were female. The mean age was (41.9±16.3) years. The mean course of disease was (5.0±5.3) months. The best corrected visual acuity (BCVA), intraocular pressure and optical coherence tomography (OCT) were performed. BCVA was measured by Early Treatment Diabetic Retinopathy Study charts. Central macular thickness (CMT) was measured by OCT. The mean BCVA was (13.4±15.3) letters. The mean intraocular pressure (IOP) was (14.1±2.8) mmHg (1 mmHg=0.133 kPa). The mean CMT was (876.1±437.9) μm. Of the 39 eyes, 33 were central RVO, 6 were branch RVO. Patients were categorized into ischemic (18 eyes)/non-ischemic (21 eyes) groups and previous treatment (22 eyes)/treatment naïve (17 eyes) groups. All eyes underwent intravitreal 0.7 mg Ozurdex injections. BCVA, IOP and CMT were assessed at 1, 2, 3, 6, 9, 12 months after injection. Three months after injection, intravitreal injections of Ozurdex, triamcinolone acetonide or ranibizumab could be considered for patients with ME recurrence or poor treatment effects. Change of BCVA, IOP and CMT were evaluated with paired t test. The presence of ocular and systemic adverse events were assessed. Results BCVA, IOP significantly increased and CMT significantly decreased at 1 month after injection compared to baseline in all groups (t=3.70, 3.69, 4.32, 3.08, 4.25, 6.09, 6.25, 4.02, 5.49, 8.18, 6.54, 5.73; P＜0.05). Two months after injection, change of BCVA, IOP and CMT was most significant (t=4.93, 6.80, 6.71, 5.53, 4.97, 5.89, 5.13, 7.68, 7.31, 8.67, 8.31, 5.82; P＜0.05). Twelve months after injection, there was no statistical difference regarding BCVA of ischemic RVO group and previous treatment group, compared to baseline (t=1.86, 0.67; P＞0.05); BCVA of non-ischemic RVO group and treatment naïve group significantly increased compared to baseline (t=2.27, 2.30; P＜0.05); there was no statistical difference regarding IOP in all groups (t=0.30, 0.13, 0.64, 1.53; P＞0.05);however, CMT significantly decreased in all groups (t=4.60, 3.26, 3.00, 4.87; P＜0.05). Twenty-seven eyes (69.2%) experiences ME recurrence (4.5±1.5) months after injection. Most common side-effect was secondary glaucoma. 41.0% eyes had IOP more than 25 mmHg, most of which were lowered to normal range with use of topical IOP lowering drugs. Four eyes (10.3%) presented with significant cataract progression and needed surgical treatment, all were central RVO eyes. No serious ocular or systemic adverse events such as vitreous hemorrhage, retinal detachment or endophthalmitis were noted. Conclusions Intravitreal injection of Ozurdex for patients with ME secondary to RVO is effective in increasing BCVA and lowering CMT in the first few months. Significant treatment effect could be seen at 1 month after injection and was most significant at 2 months after injection. The long-term vision of eyes in non-ischemic RVO group and treatment naïve group are better. 69.2% eyes experience ME recurrence at 4 months after injection. Short term adverse events were mostly secondary glaucoma and long term adverse events are mostly cataract progression.
ObjectiveTo observe the macular capillary morphology in diabetic patients.MethodsA total of 61 patients (104 eyes) with diabetes mellitus (DM group) and 31 healthy controls (41 eyes) were enrolled in the study. According to the degree of diabetic retinopathy (DR), the DM group was divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group. There were 13 patients (23 eyes), 21 patients (34 eyes) and 27 patients (47 eyes) in each group, respectively. According to whether there was diabetic macular edema (DME), the DM patients were divided into DME group and non-DME group, each had 20 patients (28 eyes) and 41 patients (76 eyes), respectively. The age (F=2.045) and sex (χ2=2.589) between the control group, the NDR group, the NPDR group and PDR group were not statistically significant (P=0.908, 0.374). The 3 mm × 3 mm region in macula was scanned by optical coherence tomography angiography (OCTA), and the retinal capillary morphological changes of superficial capillary layer (SCL) and deep capillary layer (DCL) were observed. Chi-square test and t test were used to compare data among different groups.ResultsThere was no abnormal change of retinal capillary morphology in control group. Microaneurysms and foveal avascular zone (FAZ) integrity erosion can be found in NDR group. There were microaneurysms, FAZ integrity erosion, vascular tortuosity bending, capillary non-perfusion and venous beading in NPDR and PDR groups. The microaneurysms of DCL were significantly more than that of the SCL (t=4.759, P＜0.001). The eyes with microaneurysms in NDR group, NPDR group, and PDR group showed significant differences (χ2=44.071, P＜0.001), and the eyes with FAZ integrity erosion among these three groups also showed significant differences (χ2=30.759, P＜0.001). Compared with NPDR group and PDR group, there were significant differences in vascular tortuosity bending and capillary non-perfusion (vascular tortuosity bending: OR=0.213, 95%CI 0.070−0.648, P=0.004; capillary non-perfusion: OR=0.073, 95%CI 0.022−0.251, P＜0.001), and there was no significant difference in venous beading (OR=0.415, 95%CI 0.143−1.208, P=0.102). SCL blood flow density in the 4 groups (control, NDR, NPDR and PDR group) was 49.233±1.694, 48.453±2.581, 45.020±4.685 and 40.667±4.516, respectively. While the difference between the control and NDR group was not significant, the differences between other pairs (control vs NPDR/PDR, NDR vs NPDR/PDR, NPDR vs PDR) were significant. The ratio of FAZ integrity erosion and non-perfusion of DME group was significantly higher than those of non-DME group (vascular tortuosity bending: OR=7.719, 95%CI 1.645−36.228, P=0.004; capillary non-perfusion: OR=14.560, 95%CI 3.134−67.646, P＜0.001).ConclusionsOCTA can distinctively detect the abnormal retinal capillary changes of SCL and DCL in diabetic patients. Even in DM patients without diabetic retinopathy, OCTA can detect abnormal blood vessels.
ObjectiveTo observe the alterations of microvascular structure in patients with macular edema (ME) associated with branch retinal vein occlusion (BRVO) before and after anti-VEGF drug therapy.MethodsA retrospective case study. Thirty-two eyes of 32 patients with unilateral BRVO-ME at Department of Ophthalmology in Beijing Hospital during November 2016 to June 2018 were enrolled in this study. There were 14 males (14 eyes) and 18 females (18 eyes), with the mean age of 57.81±10.58 years, and the mean course of the disease of 12.13±7.13 d. The affected eyes was defined as the eyes with BRVO-ME. All the affected eyes received intravitreal anti-VEGF drug injections (3+PRN). BCVA and OCT angiography (OCTA) were performed on the BRVO and fellow eyes before and after intravitreal anti-VEGF drug injections. The scanning region in the macular area was 3 mm×3 mm. Macular blood flow density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), macular hemodynamics parameters [foveal avascular area (FAZ) area, perimeter (PERIM), acircularity index (AI) and vessel density within a 300um width ring surrounding the FAZ (FD-300)] and central retinal thickness (CRT) were measured in all eyes. Paired samples t-test and Univariate Linear Regression were used in this study.ResultsComparing with fellow eyes, the mean macular blood flow density measured in the entire scan was lower in BRVO-ME eyes in the SCP (t=6.589, P=0.000) and DCP (t=9.753, P=0.000), PERIM (t=4.054, P=0.000) ), AI enlarged in BRVO-ME eyes (t=4.988, P=0.000), FD-300 was lower in BRVO-ME eyes (t=2.963, P=0.006), FAZ area enlarged in BRVO-ME eyes (t=0.928, P=0.361). The blood flow density in the DCP was the parameter most significantly correlated with BCVA and FAZ area (r=0.462, −0.387;P＜ .05). After 3 intravitreal injections of anti-VEGF drug, the CRT and FD-300 decreased, BCVA increased (t=9.865, 3.256, −10.573; P＜0.05), PERIM and AI was not changed significantly (t=0.520, 2.004; P＞0.05). The blood flow density in the SCP decreased (t=2.814, P＜0.05), but the blood flow density in the DCP was not changed significantly (t=0.661, P=0.514). Contrarily, comparing with after 1 anti-VEGF drug injection, the blood flow density in the DCP increased after 2 anti-VEGF drug injections (t=3.132, P＜0.05). FAZ area enlarged in BRVO-ME eyes (t=5.340, P＜0.001). Comparing with last anti-VEGF drug injection, FAZ area enlarged after every anti-VEGF drug injection (t=2.907, 3.742, 2.203; P＜0.05).ConclusionsIn BRVO-ME eyes, the blood flow density in the SCP and DCP are decreased. The blood flow density in the DCP is positively correlated with BCVA and negatively correlated with FAZ area. After anti-VEGF drug therapy, the blood flow density is decreased in the SCP and increased in the DCP, FAZ area enlarged gradually, PERIM and AI are not changed significantly.
ObjectiveTo observe the correlation analysis between the deep-superficial flow-density ratio (DSFR) and treatment response of macular edema secondary to branch retinal vein occlusion (BRVO).MethodsForty-eight patients（48 eyes）with macular edema secondary to BRVO from December 2018 to December 2019 in the Department of Ophthalmology of Beijing Hospital were enrolled in this study. There were 29 males (29 eyes) and 19 females (19 eyes), with the mean age of 58.77±10.88 years. All eyes were treated with intravitreal injection of ranibizuma once a month for 3 months, and then treated as needed. According to the central retinal thickness (CRT) 12 months after treatment, the patients were divided into good response group (CRT≤250 μm) and refractory group (CRT＞250 μm). The flow density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of all subjects was measured by optical coherence tomography angiography. The flow density of DCP and SCP measured at 3 follow-up times was selected and DSFR was calculated. The DSFR was recorded by the Study for the Treatment of Diabetic Retinopathy (ETDRS) -grid and Nine-grid. The flow density of DCP, SCP and DSFR were compared between the two groups by paired t test. At 3 months post-treatment, the efficacy of DSFR in ME treatment response was evaluated according to area under curve (AUC) of receiver operating characteristic. Univariate and multivariate binary logistic regression were used to analyze the factors affecting the response to ME treatment.ResultsAt 12 months after treatment, there were 27 eyes in good response group and 21 eyes in refractory group. There was no statistical significance in the flow density of DCP (t=1.804, 1.064, 0.660) and SCP (t=0.581, 0.641, 0.167) and DSFR (t=0.393、－0.553、0.474) in all area of response group and refractory group using ETDRS-GRID recording method (P＞0.05). The SCP, DCP and DSFR of the most severe non-perfusion area were (27.10±5.70) %, (28.33±8.95) %, 1.35±0.54 and (27.54±6.70) %, (29.11±0.42) %, 1.01±0.40 in the response group and refractory group, respectively. There was no significant difference in the flow density of DCP and SCP between the two groups (t=－0.237, －0.340; P＞0.05). The difference of DSFR between two groups was statistically significant (t=2.288, P=0.024). Univariate and multivariate binary logistic regression analysis showed that DSFR in the most severe non-perfusion area was associated with ME response (odds ratio=0.212, 0.085; P=0.027, 0.024). The AUC was used to evaluate the efficacy of DSFR in ME treatment response, the results showed that the AUC was 0.800, P=0.001, Youden index was 1.348, sensitivity was 67.7%, and specificity was 86.7%.ConclusionsDSFR reduction is more common in BRVO secondary to ME patients. DSFR correlates with ME treatment response.