ObjectiveTo study changes in choroidal thickness(CT) with intravitreal injections of ranibizumab treatment. MethodsThis is a prospective, uncontrolled, open-label study. A total of 31 eyes of 31 patients diagnosed with wet age-related macular degeneration (AMD) and 33 eyes of 33 patients diagnosed with choroidal neovascularization (CNV) secondary to pathological myopia (PM) were included in the study. All affected eyes were treated with intravitreal ranibizumab 0.05 ml (10 mg/ml) and followed up monthly until 6 months. Enhanced depth imaging on Cirrus spectral-domain optical coherence tomography was used to measure the CT. The initial CT was compared with the data at 1, 3 and 6 month after treatment, and the correlation between of the decrease of CT at the 6 month and the number of injection times was analyzed. ResultsIn AMD group, the average CT respectively decreased by (9.68±11.02), (12.58±11.04), (13.84±11.67)μm at 1, 3 and 6 month, and the differences were significant(t=4.89, 6.34, 6.60;P < 0.001). In PM group, the average CT respectively decreased by (2.06±10.92), (3.64±8.78), (3.27±7.20)μm at 1, 3 and 6 month. The difference at 1 month was not significant (t=1.08, P=0.287). While after 3 months and 6 months, the differences were significant(t=2.38, 2.61;P=0.024, 0.014). The injection times were not correlated with the CT decreases at 6 month in both groups(r=0.04, 0.30;P=0.815, 0.099). ConclusionIntravitreal injections of ranibizumab can induce choroidal thickness reduction for wet age-related macular degeneration and choroidal neovascularization secondary to pathologic myopia.
Objective To observe the clinical effects and safety of Bevacizumab on recurrent idiopathic choroidal neoascularization(CNV). Methods To analyze retrospectively the clinical data of 21 eyes of 20 patients with recurrent idiopathic CNV who had intravitreal injection of Bevacizumab(0.05 ml 1.25 mg) after signing the letter of consent. In these patients, 12 cases (13 eyes) had been cured by photodynamic therapy (PDT), and 8 cases (8 eyes) had been cured by transpupillary thermotherapy (TTT). The follow-up periods were 2 weeks, 1 month, 3 months and 6 months after injection. The inspection findings of best-corrected visual acuity(BCVA), fundus fluorescein angiography (FFA) and optical coherence tomogr aphy (OCT) before and after the treatment were observed and analyzed. It could inject once more by the same way if there are recurrences in follow-up period. Results At the end of follow-up period, the BCVA improved obviously (gt;1 lines) in 14 eyes (66.7%)，kept stable (changed within 1 line)in 5 eyes (23.8%) and decreased (gt;1 lines) in 2 eyes(9.5%). The complete closure of CNV in 17 eyes (81.0%) and partial closure in 4 eyes (19.0%) were observed by FFA images. The thickness of retina in macular region decreased 115 micron. 3 eyes (14.3%) has inject again during follow-up period. The intraocular pressure increased in 4 eyes(19.0%) , the average intraocular pressure was 26.7 mm Hg（1 mm Hg=0.133 kPa). They have been returned to normal through the treatment. There was no serious adverse reaction in process of treatment. Conclusion Intravitreal infection of Bevacizumab can reduce the leakage of recurrent CNV and macular edema after PDT or TTT. About 2/ 3 patients can improve their visual acuity obviously. No severe complication or adverse reaction was observed in this study. (Chin J Ocul Fundus Dis,2008,24:168-171)
Age-related macular degeneration (AMD) is the third leading cause of irreversible blindness worldwide. Wet AMD (wAMD) is the primary type of AMD leading to blindness, characterized by rapid vision loss due to neovascularization. Currently, the primary treatment for wAMD relies on anti-vascular endothelial growth factor (VEGF) drugs. However, some patients respond poorly to this therapy, suggesting a complex pathogenesis that necessitates the exploration of multi-target therapeutic strategies. Recent studies have revealed that aberrant activation of the complement system plays a crucial role in the development of wAMD. Specifically, molecules such as C3, C5, C3a, C5a, and the membrane attack complex (MAC) are involved in the formation of choroidal neovascularization (CNV) by modulating VEGF and other inflammatory factors. Genetic studies have confirmed a strong association between mutations in complement-related genes and wAMD, such as CFH and C3. Furthermore, animal experiments support the therapeutic potential of complement inhibitors in treating CNV. Currently, clinical trials targeting complement components like C3, C5, and MAC are underway, with some drugs having advanced to phase Ⅱ/Ⅲ clinical studies. However, their efficacy requires further validation. In the future, complement-targeted therapy, particularly in combination with anti-VEGF treatment, is poised to become a new direction in wAMD management, potentially offering superior therapeutic options for patients.
ObjectiveTo observe the imaging characteristics of optical coherence tomography angiography (OCTA) and the changes of choroidal capillary density (CCD) in the eyes of patients with high myopia choroidal neovascularization (mCNV). MethodsA case-control study. From January 2018 to October 2020, 50 cases of mCNV patients with 50 eyes (mCNV group) were included in the study. There were 18 males and 32 females; their age was 42.11±11.66 years old. Fifty eyes of 50 patients with normal fundus with matching myopia refractive power (≥6.00 D) were selected as the simple high myopia group, and 50 normal volunteers (refractive power －0.25-0.25 D) while 50 eyes were selected as the normal control group. There was no statistically significant difference in age (F=0.028) and gender composition ratio (χ2=0.136) among the three groups of patients (P＞0.05); the difference in best corrected visual acuity was statistically significant (F=14.762, P=0.004). Compared with mCNV group and pure high myopia group, the refractive index (t=－0.273) and axial length (t=0.312) of the examined eyes were not statistically significant (P＞0.05). OCTA instrument was used to measure the CCD in the macular area of the examined eye. Analysis of variance was used for comparison of measurement data among the three groups; χ2 test was used for comparison of categorical variables. The paired t test was performed to compare the CCD of the mCNV patient's eye and the contralateral eye. ResultsAmong the 50 eyes in the mCNV group, Ⅰ, Ⅱ, and mixed choroidal neovascularization (CNV) were 12 (24%, 12/50), 34 (68%, 34/50), and 4 (8%, 4/50) eyes, respectively. Corresponding to the OCTA cross-sectional image of the lesion, there was a clear “flower cluster”-like strong blood flow signal. Among them, the focal shape, the filament shape, and the group net shape were 6 (12%, 6/50), 8 (11%, 8/50), and 36 (72%, 36/50) eyes, respectively. The CCD of the eyes in the mCNV group, the pure high myopia group, and the normal control group were (57.39±3.24)%, (59.33±2.23)%, and (61.87±1.62)%, respectively. The CCD of the eyes in the mCNV group was significantly lower than that of the simple high myopia group (P=0.030) and the normal control group (P＜0.001). The CCD of the affected eye and the contralateral eye in the mCNV group were (57.39±3.24)% and (59.82±3.94)%, respectively; there was no statistically significant difference between the CCD of the affected eye and the contralateral eye (t=－0.496, P=0.100). The CCDs of eyes with Ⅰ, Ⅱ and mixed CNV were (57.38±3.31)%, (57.39±2.83)%, and (57.36±4.21)%, respectively. There were no statistically significant differences in CCD (F=1.476), age (F=0.274), sex ratio (χ2=0.825), and diopter (F=0.348) in different CNV types (P＞0.05). ConclusionThe mCNV is mostly type Ⅱ, and OCTA has a "bloom" appearance of abnormal reticular blood vessels; the CCD is significantly reduced, and it is bilateral.
The severe visual impairment caused by neovascular age-related macular degeneration (nAMD) is associated with macular neovascularization (MNV) invasion and subretinal fibrosis (SF). Excessive SF can lead to subretinal scarring, irreversible damage to photoreceptors, retinal pigment epithelium, and choroid tissue, resulting in permanent visual impairment in nAMD patients. The pathogenesis of SF is complex, involving many pathological processes such as tissue repair after injury, inflammation, and related signaling pathways and cytokine complex. Current experimental treatments for SF only target inhibition of a single cytokine. Timely and effective inhibition of the formation and progression of MNV and early identification of risk factors for SF are crucial to improving the prognosis of nAMD patients.
ObjectiveTo investigate the clinical effects and influence factors of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs in the treatment of idiopathic choroidal neovascularization (ICNV). MethodsThis retrospective study involved 27 patients (27 eyes) with ICNV from July 2012 to July 2015. Patients received intravitreal bevacizumab (1.25 mg), ranibizumab (0.05 mg), additional injection was provided if it was needed. The average follow-up time was 168 weeks. The recovery of best corrected visual acuity (BCVA) and central foveal retinal thickness (CRT) of the affected eye was observed. Follow up once a month after the initial treatment until the lesion was completely absorbed or scarred (the first follow-up period). Follow up every 12 weeks was performed to observe the recurrence of the lesions (the second stage of long-term follow-up). One month after the last injection of the first follow-up period, according to the regression of choroidal neovascularization (CNV), the affected eyes were divided into a significant improvement group (significant improvement group) and an insignificant improvement group (non-significant improvement group)), to analyze the effects of age, course of disease, type of drugs, number of injections, baseline BCVA and CRT on the regression of CNV lesions. According to the results of long-term follow-up, the eyes were divided into recurrence group and non-recurrence group, and the factors affecting the recurrence of CNV lesions were analyzed. Measurement data between groups was compared by using independent sample t test or non-parametric test; count data was compared by using χ2 test. Logistic regression analysis was used to analyze the factors affecting the regression and recurrence of the lesion. ResultsAt baseline and 1 month after the last injection in the first stage, the average BCVA of the eyes were 55.70±15.21 and 73.59±12.08 letters; CRT was 338.3±89.32 and 264.5±47.47 μm, respectively. The BCVA and CRT of the affected eyes were compared at the two time points, and the differences were statistically significant (Z= －3.886, －4.061; P＜0.001). The BCVA of the eyes in the significant improvement group and the insignificant improvement group were 65.38±17.27 and 51.63±12.61 letters, respectively; the difference between the two groups of BCVA was statistically significant (t=－2.316, P=0.029). The results of long-term follow-up showed that of the 27 eyes, 6 eyes had recurrence; the average recurrence time was 90.83±49.02 weeks. After another intravitreal injection of anti-VEGF drugs, the CNV lesions was resolved. The average injection times of the relapsed group and the non-relapsed group were 3.67±0.816 and 2.24±0.768, respectively. The average injection times of the relapsed group was significantly higher than that of the non-relapsed group, and the difference was statistically significant (Z=－3.253, P＜0.001). There was no statistically significant difference between the two groups of eyes at baseline and CRT at the last follow-up (Z=－1.342,－1.313; P=0.195, 0.195). ConclusionIntravitreal injection of anti-VEGF drugs can effectively increase the regression rate of BCVA and CNV lesions in ICNV eyes; high baseline visual acuity indicates better CNV lesion regression after treatment. Relapsed patients can be effectively improved after re-treatment with anti-VEGF drugs, and CNV recurrence has no significant effect on the final prognosis.
ObjectiveTo observe the OCT angiography (OCTA) features of adult-onset foveomacular vitelliform dystrophy (AFVD).MethodsRetrospective clinical observational study. Twelve patients (22 eyes) diagnosed as AFVD by multi-modal imaging in Ophthalmology Department of Yunnan Second People’s Hospital from March 2018 to May 2019 were included in this study. There were 8 males (16 eyes) and 4 females (6 eyes). The patients aged from 33 to 62 years, with the mean age of 48.7±8.9 years. Ten patients were binocular, 2 patients were monocular. The visual acuity was 0.08-0.6. In 22 eyes, the vitelloid-like substance was relatively complete in 8 eyes, the vitelloid-like substance had different degrees of rupture in 14 eyes, secondary choroidal neovascularization (CNV) was observed in 10 eyes. The Heidelberg OCTA instrument was used for OCTA examination. The central wavelength was 840 nm, the acquisition speed was 85,000 times/s. A 3 mm × 3 mm scan was obtained. In the scanning process, eye-tracking technology was adopted to select images with better image quality and position for marking and saving. The image characteristics of vitelloid-like substance, fundus vascular changes and secondary CNV in OCTA were analyzed.ResultsIn 8 eyes with a relatively complete vitelloid-like substance, B-scan images showed dense vitelloid-like substance under the retinal neurocortical layer, which was located between the RPE layer and the ellipsoid zone and had a uniform density. Blood flow signals at the vitelloid-like substance can be seen in the en-face image, which was the artifact of the vitelloid-like substance reflecting the blood vessels above. In the 14 eyes with different degrees of vitellin-like material rupture, the signal of vitellin-like substance between the ellipsoid zone and the RPE layer in the B-scan image was not uniform, and some weak reflected signal lacunae could be seen. In the image of en-face, the relatively intact areas of vitelloid-like substance still showed the artifact of the blood vessels above the reflection, while there was no blood flow signal at the rupture of vitelloid-like substance. In 22 eyes, the morphology of retinal small blood vessels in the superficial and deep capillary arch ring region of retina was abnormal in 10 eyes. Some small blood vessels could be seen to have branch and shape changes, and the anastomosis failed to show a complete arch ring structure.No significant structural changes in retinal capillaries were observed in 12 eyes. Among the 10 eyes with secondary CNV, 8 eyes showed the non-active CNV which was as thick as "wild branches", and 2 eyes showed the active CNV which was composed of dense and small vascular branches.ConclusionAFVD in OCTA can be manifested as abnormal retinal vascular morphology caused by the vitelliform material pushing, vascular artifacts reflected by the vitelliform material itself, and the presence of CNV under the vitelliform material.
ObjectiveTo compared the macular blood flow parameters among myopic choroidal neovascularization (mCNV), high myopia (HM) and normal subjects.MethodsRetrospective study. Forty patients (40 eyes) diagnosed as mCNV (mCNV group) in the Eye Hospital of Wenzhou Medical University at Hangzhou from June 2016 to November 2018, age-matched, sex-matched and diopter-matched 40 HM patients (40 eyes, HM group), age-matched and sex-matched 40 healthy persons (40 eyes, normal group) were enrolled in this study. Retina superficial and deep vessel density, the area of foveal avascular zone (FAZ), a-circularity index (AI) and vessel density around the 300 μm width of the FAZ region (FD) on macular 3 mm×3 mm scan on OCTA of 3 groups were compared.ResultsThere were significant differences in the average retina superficial, deep vessel density, the area of FAZ, AI and FD among 3 groups (F=24.82, 9.18, 3.58, 7.68, 14.15; P＜0.05). The average retina superficial and deep vessel density and FD in mCNV group were lower than those in HM group (P＜0.05). The average retina superficial and deep vessel density and FD in HM group were lower than those in control group (P＜0.05). The average area of FAZ in mCNV group was smaller than that in control group (P＜0.05). The average AI in mCNV group was less than that in the other 2 groups (P＜0.05).ConclusionsThe retina superficial, deep vessel density and FD decreased, the area and the form of FAZ remained unchanged in HM subjects comparing with normal subjects. While retina superficial, deep vessel density and FD decreased more, the area of FAZ reduced, the form of FAZ tend to be irregular in mCNV.
Objective To investigate the possible effects of phosphorylated signal transduction and activator of transcription3 (STAT3) in the formation of choroidal neovascuarization (CNV) induced by photocoagulation in rats. Methods The CNV model in rats induced by photocoagulation was established, and the expression of phosphorylated STAT3 at the early stage in CNV were observed by immunofluorescence. To set up the hypoxia model, the specific inhibitor of Janus kinase 2 (JAK2), AG490 was mixed into cell culture fluid and then cultured for 0,1 hour,3,6,12,and 24 hours.Retinal pigment epithelial (RPE) cells proliferation activity were detected by flow cytometry (FCM).the expression of hypoxiainducible factor (HIF)1α and vascular endothelial grow factor (VEGF) mRNA were detected by reverse transcriptase polymerase chain reaction (RT-PCR); the expression of HIF1α protein was detected by Western blot; the content of VEGF in the supernatant of cell culture fluid was measured by enzyme linked immunosorbent assay (ELISA). Results Phosphorylated STAT3 highly expressed in CNV areas in rats 3 days after the photocoagulation. The proliferation activity of human RPE cells under hypoxia condition significantly decreased after inhibition of JAK2/STAT3 signal transduction pathway (t=1.472, 3.566,2.391,6.420; P=0.054,0.038,0.042,0.016). The expression of HIF-1α and VEGF mRNA increased gradually with increasing time of hypoxia;while the expression of HIF1α and VEGF mRNA and the activation of HIF1α protein in cultured human RPE cells with the JAK/STAT3 signal transduction pathway blocked by AG490 were suppressed obviously under hypoxia condition (t=0.07,0.02,0.01, P<0.05); the content of VEGF in RPE cells supernatant decreased significantly (t=1.330,1.106,2.828,7.742,5.610,6.894; P=0.082,0.063,0.014,0.002,0.016,0.011). Conclusion STAT3 may be involved in CNV formation, which may partly dependent on JAK2/STAT3 signal transduction pathway regulating the expression of HIF-1α and VEGF in RPE cells.
Objective To evaluate the clinical efficacy of intravitreal injections of antivascular endothelial growth factor monoclonal antibody ranibizumab in choroidal neovascularization (CNV) secondary to pathologic myopia (PM). Methods This is a prospective, uncontrolled, open-label study. 34 eyes of 34 patients with CNV secondary to PM were included in the study. All affected eye were treated with intravitreal ranibizumab 0.05 ml (10 mg/ml). Before the injection, bestcorrected visual acuity of early treatment of diabetic retinopathy study (ETDRS), noncontact tonometer, ophthalmoscope, fundus photography, fundus fluorescein angiograph (FFA) and optical coherence tomography (OCT) examination were necessary. The initial average letters of ETDRS acuity were 33.85plusmn;14.67, range from 0 to 69. The initial average central macular thickness (CMT) was（293.41plusmn;79.45） m, range from 210 m to 543 m. The patients were followed up for 3 to 12 months. Best-corrected visual acuity, OCT and ophthalmoscope examination were assessed monthly. If necessary, FFA was used. The letters of ETDRS acuity and CMT were compared before and after treatment. Results All eyes received an average of 1.68 injections, the final vision of follow-up increased （13.50plusmn;9.94） letters than before （t=7.92，P=0.00）, CMT decreased （71.14plusmn;72.26） m (t=4.62，P=0.00). There were no systemic or ocular serious side effects during the follow up. Conclusion Intravitreal ranibizumab for pathologic myopia choroidal neovascularization showed visual acuity improvement, retinal thickness reduction and safety.