Interleukin-18 is an inactive precursor which lacks a signal peptide, it has a role in regulating retinal pathological angiogenesis. It also inhibits experimental choroidal neovascularization (CNV) via interferon-γand thrombospondin-1. Currently little is known about its mechanisms of inhibition for CNV, may be speculated to be due to effects of anti-angiogenesis, down-regulates vascular permeability and lower vascular endothelial growth factor (VEGF) levels via directly acting on the vascular endothelial cell and epithelial cells. Exogenous administration of mature recombinant interleukin-18 has no adverse effect on retinal pigment epithelial cell viability. In addition, the anti-VEGF role of interleukin-18 is tested to be safe and effective for humans. Interleukin-18 alone or in combination with anti-VEGF shows to be a good prospect for improving the prognosis of experimental CNV. However, more large clinical studies are required to confirm the exact efficacy of interleukin-18 for CNV.
ObjectiveTo summarize the clinical results and safety of photodynamic therapy (PDT) through 4 years after single and multi-treatments of patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration(AMD). MethodsClinical data of 73 AMD cases (95 eyes) diagnosed through fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optic coherence tomography (OCT), treated with PDT were reviewed and analyzed in this hospital from June 2000 to June 2004. The changes of best corrected visual acuity (BCVA), fundus pictures, FFA, ICGA and OCT were compared before and after PDT. Follow-up time varied from 3 months to 4 years (mean, 2 years). ResultsThe mean age of 73 patients was 67.8 years old. The BCVA was from CF/10 cm to 1.0. At the final follow up, the BCVA was improved (increase≥2 lines) in 39 eyes (41.1%), stabilized (±1 line) in 51 eyes (53.7 %) and decreased 2 lines in 5 eyes (5.3%). Fundus hemorrhage and exudation reduced after PDT. FFA and ICGA showed CNV complete closure in 58 eyes (61.05%), partial closure in 6 eyes (6.32%), CNV incomplete closure in 22 eyes (23.16% ) and recurrence in 9 eyes (9.47%). After once PDT of 12 eyes with early-stage AMD, the BCVA improved (from 0.6 to 1.5), CNV completely closed, and the OCT showed disappearance of macular edema and neursensory retinal deta chment. No CN V recurred in our four years follow-up observation and the BCVA of the patients remained stable. The mean number of PDT treatment was 1.8 per eye in 95 cases. No serious local or systemic complications were encountered. ConclusionsSingle or multiple sessions of PDT can acheive long-term safety and efficacy. For early-stage AMD patients with minimally classic CNV, PDT can completely make CNV closed and reduce the risk of visual loss.(Chin J Ocul Fundus Dis，2004，20：275-279)
Objective To investigate the inhibitory effects of IBI302 on experimental choroidal neovascularization (CNV). Methods Affinity of IBI302 to vascular endothelial growth factor (VEGF) family cytokines (including VEGF-A165, VEGF-A121 and placental growth factor PlGF) and complements (C3b, C4b) was determined by enzyme-linked immunosorbent assay (ELISA). The antagonist effect of IBI302 on VEGF was measured by proliferation, migration and tube formation tests of human umbilical vein endothelial cells (HUVEC). The anti-complement activity of IBI302 was measured by hemolysis test mediated by complement classical pathway and alternative pathway. Rhesus laser-induced CNV model was divided into 5 groups including model control group, bevacizumab group, IBI302 0.25 mg group, IBI302 0.50 mg group and IBI302 1.25 mg group. Fluorescein angiography and optical coherence tomography were performed on these monkeys at 14 and 28 days after drug delivery to observe the fluorescein leakage area and retinal thickness. The aqueous VEGF concentration was measured at 29 days after drug delivery. Results IBI302 showed good affinity to VEGF-A165, VEGF-A121 and PlGF, as well as C3b and C4b. IBI302 significantly inhibited the proliferation, migration and tube formation of HUVEC induced by VEGF-A165. IBI302 inhibited the hemolysis induced by complements obviously. At 14 and 28 days after drug delivery, the area of fluorescein leakage and retinal thickness in IBI302 0.25 mg group, IBI302 0.50 mg group, IBI302 1.25 mg group were reduced. The differences of the area of fluorescein leakage and retinal thickness in three IBI302 groups were not significant (P > 0.05). At 29 days after drug delivery, the VEGF concentration in the aqueous of rhesus monkey in bevacizumab group [(38.644±6.521) pg/ml] was decreased than that in model control group [(94.203±17.360) pg/ml], the difference was significant (P < 0.05). The VEGF concentration in the aqueous of rhesus monkey in three IBI302 groups were less than 31.300 pg/ml. Conclusion IBI302 inhibited experimental CNV through blocking the activity of VEGF and complement.
ObjectiveTo observe and classify the characteristics of optical coherence tomography (OCT) for several common diseases which could lead to submacular choroidal neovascularization (CNV), and to provide the warrant to make the differential diagnosis and treatment of CNV.MethodsThe data of OCT of 165 patients (187 eyes) with CNV due to AMD, CEC, high myopia and ICNV diagnosed by fundus photography and fundus fluorescein angiography (FFA) were retrospectively analyzed, and the images of OCT were classified considering the results of FFA, and the characteristics of different types of the images were sumerized.ResultsWell-defined fusiform thickening of retinal pigment epithelial (RPE) and choriocapillary layer in CNV with well-defined border (60 eyes), dispersed backscattering increase in poorly-defined CNV (101 eyes), optic darkspace beneath RPE layer in serous detachment of RPE layer (19 eyes), quickly decreased high backscattering region under RPE layer in hemorrhagic detachment of RPE layer (11 eyes), slight to moderate backscattering region between RPE layer in fibrovascular detachment of RPE layer (10 eyes), and detachment of neurepithelial layer from RPE layer with the optic darkspace between the layers in detachment of neurepithelial layer (45 eyes) were observed.ConclusionsThe images of OCT for the common diseases which could lead to submacular choroidal neovascularization may be divided into 6 types. Analyzing the characteristics of images of OCT is helpful in differential diagnosis and treatment of CNV. (Chin J Ocul Fundus Dis, 2005,21:69-73)
The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors. Comprehensive thorough analysis of clinical features, imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient, and also can optimize the treatment regime to make a personalized therapy plan. Precise medicine with data from genomics, proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy, to achieve individualized precise diagnosis and treatment, to improve the therapeutic outcome of nAMD.
Objective To summarize the therapeutic effect and clinical characteristics of repetitive photodynamic therapy (PDT) for patients with exudative age-related macular degeneration (AMD). Methods The clinical data from 78 patients (94 eyes) with exudative AMD who had undergone PDT from July, 2002 to March, 2005 were retrospectively analyzed. The average age of the patients was 68.4, and the treated times was 132 (mean 1.4). Thirty eyes underwent PDT 68 times, including twice in 22 eyes (73.3%), 3 times in 7 eyes (23.3%), and 6 times in 1 eye (3.3%). The follow-up period lasted 3-32 months with the average of 16.7 months. Results In the final follow-up examination, the results of fundus fluorescein angiography or combined with indocyanine green angiography showed that the leakage of choroidal neovascularization (CNV) stopped in 14 eyes (46.7%), reduced in 12 (40%), and remained in 4 (13.3%). Compared with the condition before first PDT, the correct visual acuity increased ge;2 lines in 7 eyes (23.3%), changed plusmn;1 line in 14 eyes (43.3%), and decreased ge;2 lines in 9 eyes (30%) in the final examination. After first PDT, the best corrected visual acuity increased ge;2 lines in 13 eyes (43.3%), changed plusmn;1 line in 12 eyes (40%), and decreased ge;2 lines in 5 eyes (16.7%). During the follow-up period, the best corrected visual acuity occurred after first PDT in 24 eyes (80%), after second PDT in 5 eyes (16.7%), and after third PDT in 1 eye (3.3%). Conclusions In patients undergone repetitive PDT, CNV in most of the affected eyes completely or partly closed and the visual acuity improved or remained still in 67.8% of the patients in the final follow-up examination. The best correct visual acuity mainly happened after the first PDT, and as the times of PDT increased, the probability of the best correct visual acuity decreased. (Chin J Ocul Fundus Dis, 2006, 22: 220-223)
ObjectiveTo assess the occurrence of CNV in patients presenting with flat irregular pigment epithelial detachments (FIPED). MethodsForty-five patients (49 eyes) with FIPED on OCT were enrolled in this retrospective study. There were 25 males (28 eyes) and 20 females (21 eyes). The mean age was 61.022±9.292 years. FFA, ICGA, spectral domain OCT and OCT angiography (OCTA) were performed in all patients during the same period. The FIPED was defined as an irregular elevation of the RPE allowing distinct visualization of Bruch’s membrane on OCT B-scan. The abnormal vascular signals from the deep retinal layer to the choroid layer on OCTA was defined as CNV. The CNV was classified into a type 1 CNV and a type 2 CNV according to the OCT characteristics. The CNV was classified into a typical and occult CNV according to the characteristics of the FFA image. Of all 49 eyes, fundus angiography revealed 18 eyes (36.7%) with CNV, and 31 eyes (63.3%) with no characteristic signs of CNV. FFA examination found that CNV in 8 eyes (classic CNV in 1 eyes, occult CNV in 7 eyes), which confirmed by OCT were type 1 CNV; transmitted fluorescence in 41 eyes. ICGA examination showed that CNV-like hyperfluorescence spots in 18 eyes, suspicious hyperfluorescence spots in late stage in 20 eyes, and choroidal high permeability in 11 eyes, respectively; and 18 CNV eyes were confirmed to be type 1 CNV by OCT. To compare the detection of CNV by OCTA and fundus angiography. ResultsOf the 49 eyes with FIPED, OCTA detected 36 eyes (73.5%) of type 1 CNV, and full or partial strong reflex signals were seen in FIPED; 13 eyes (26.5%) were not associated with CNV, and some strong reflection signals were found in FIPED in 9 eyes, 4 eyes with weak reflection signal. The FFA was examined for 1, 7 eyes of the classic and occult CNV, which confirmed to be type 1 CNV by OCTA. Among the 18 eyes with CNV which detected by ICGA, OCTA also found type 1 CNV. Among the 20 eyes with ICGA’s late suspicious strong fluorescent spots, OCTA showed 17 eyes of type 1 CNV; in 11 eyes with high choroidal permeability, OCTA showed type 1 CNV in 1 eye. Among the 36 eyes with CNV which detected by OCT, there were SRD in 32 eyes, no SRD in 2 eyes and retinal interlamellar cavities in 2 eyes. ConclusionOCTA can detect 73.5% of FIPED eyes with CNV. Compared with traditional fundus angiography, OCTA has a higher detection rate of CNV under FIPED. The FIPED of the internal strong reflection signal has a certain diagnostic value for the type 1 CNV.