Epstein-Barr virus-positive iris diffuse large B-cell lymphoma detected by metagenomic next-generation sequencing.

PURPOSE: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a relatively rare subtype of DLBCL. Herein, we report a case of a patient with EBV-positive iris DLBCL after undergoing penetrating keratoplasty and discuss its possible pathogenesis. METHODS: A 72-year-old male patient presented to our hospital with progressive blurring of vision in the left eye for the past 4 months. Small white nodular lesions were observed on the iris and retinal surface of the left eye, with a white cloud-like opacity in the vitreous cavity. RESULTS: The patient was eventually diagnosed with EBV-positive iris DLBCL after undergoing pathological and metagenomic tests. After injecting methotrexate in the left vitreous cavity and administering systemic and local antiviral treatments, the ocular lesions disappeared. CONCLUSION: EBV infection, drug immunosuppression, and aging-related immune deterioration may play significant roles in the pathogenesis of EBV-positive iris DLBCL. SYNOPSIS: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a new subtype of DLBCL, which rarely occurs. Herein, we report a case of a patient with EBV-positive iris DLBCL after undergoing penetrating keratoplasty and discuss its possible pathogenesis.

Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration.

PURPOSE: To determine whether supplementation with lutein and zeaxanthin improves macular pigment and visual function in patients with early age-related macular degeneration (AMD). DESIGN: Randomized, double-masked, placebo-controlled trial. PARTICIPANTS: Participants with probable AMD who were 50 to 79 years of age were screened for study eligibility from the local communities. One hundred eight subjects with early AMD were recruited. INTERVENTION: Early AMD patients were assigned randomly to receive 10 mg/day lutein (n = 27), 20 mg/day lutein (n = 27), 10 mg/day lutein plus 10 mg/day zeaxanthin (n = 27); or placebo (n = 27) for 48 weeks. Macular pigment optical density (MPOD) and visual function variables were assessed at baseline, 24 weeks, and 48 weeks. MAIN OUTCOME MEASURES: The primary outcome was MPOD. Secondary outcomes were visual function variables including best-corrected visual acuity (BCVA), contrast sensitivity (CS), photorecovery time, and Amsler grid testing results. RESULTS: Macular pigment optical density increased significantly by a mean ± standard error of 0.076 ± 0.022 density unit in the 20-mg lutein group and 0.058 ± 0.027 density unit in the lutein and zeaxanthin group during 48 weeks. There was a significant dose-response effect for lutein supplementation, and the changes in MPOD from baseline to 48 weeks were correlated negatively with baseline MPOD in all active treatment groups (r = -0.56; P<0.001). At 48 weeks, a trend toward improvement was seen in BCVA, and there was a significant between-group difference in CS at 3 and 6 cycles/degree between the 20-mg lutein group and the placebo group. The increase in MPOD related positively to the reduction in the logarithm of the minimum angle of resolution BCVA (r = -0.31; P<0.01) and the increases in CS at 4 spatial frequencies (r ranging from 0.26 to 0.38; all P<0.05). CONCLUSIONS: Among patients with early AMD, supplementation with lutein and zeaxanthin improved macular pigment, which played a causative role in boosting visual function and might prevent the progression of AMD. Future studies are required to evaluate the effect of these carotenoids on the incidence of late AMD.

Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis.

Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.

Peripheral Monocyte Count and Age-Related Macular Degeneration. The Tongren Health Care Study.

PURPOSE: To assess potential associations between the prevalence of age-related macular degeneration (AMD) and systemic parameters in a Chinese population. DESIGN: Cross-sectional study. METHODS: The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital from 2017 to 2019. Detailed medical examinations and ophthalmic examinations were applied, including fundus photography. AMD was evaluated according to the Beckman Initiative guidelines. RESULTS: The study included 7,719 participants (mean age: 60.5 ± 8.1 years; range: 50-97 years). The prevalence of any, early, intermediate, and late AMD was 1,607 of 7,719 (20.8%; 95% confidence interval [CI]: 20.1%, 21.9%), 832 of 7,719 (10.8%; 95% CI: 10.1%, 11.5%), 733 of 7,719 (9.5%; 95% CI: 8.9%, 10.2%), and 42 of 7,719 (0.50%; 95% CI: 0.40%, 0.70%), respectively. In multivariate analysis, the prevalence of any AMD increased with higher blood monocyte count (odds ratio [OR]:3.49; 95% CI: 2.26, 5.38; P < .001), after adjusting for older age (OR: 1.06; 95% CI: 1.05, 1.07; P < .001), higher serum concentration of calcium (OR: 2.52; 95% CI: 1.32, 4.84; P = .005), high-density lipoproteins (OR: 1.39; 95% CI: 1.19, 1.61; P < .001), and lower lipoprotein a (OR: 0.99; 95% CI: 0.98, 0.99; P = .02). Similar findings were obtained for the prevalence of intermediate and late AMD combined. The association between higher monocyte count and higher AMD prevalence showed the highest odds ratio for the age group of 50-59 years (any AMD: OR: 4.35, P < .001; intermediate and late AMD: OR: 6.14, P < .001). Individuals with a monocyte count of ≥0.5 × 109/L as compared to participants with a monocyte of 0.1-0.4 × 109/L had a 1.45-fold increased risk for any AMD (OR: 1.45; 95% CI: 1.27, 1.64; P < .001) and 1.58 fold increase risk for intermediate/late AMD (OR: 1.58; 95% CI: 1.33, 1.87; P < .001). CONCLUSION: A higher prevalence of early AMD, intermediate AMD, late AMD, and any AMD was associated with a higher peripheral monocyte count. In agreement with previous studies, the observation suggests monocytes playing a role in the pathogenesis of AMD.

Effect of intravitreal ranibizumab pretreatment on vitrectomy in young patients with proliferative diabetic retinopathy.

BACKGROUND: Younger patients who underwent vitrectomy for proliferative diabetic retinopathy (PDR) display more aggressive nature distinguished from the older patients. Preoperative anti-VEGF therapy has been widely used as an adjunct for PDR surgery. However, the effect of anti-VEGF administration in young diabetics has rarely been evaluated in previous studies. The purpose of this study was to evaluate the effects of ranibizumab pretreatment on vitrectomy surgery in young patients with PDR. METHODS: This was a prospective nonrandomized comparative study. Young patients (<40 years old) undergoing diabetic vitrectomy with or without ranibizumab pretreatment (25 eyes in each group) were analyzed in this study. The use of the drug was determined by the patients' own preference. The two surgical groups were matched according to a complexity score. Intravitreal injection of ranibizumab (IVR) was performed 3-5 days prior to the vitrectomy surgery in the IVR group. Intraoperative records including total surgical time, intraoperative bleeding, the use of endodiathermy, the frequency of relaxing retinotomies, the incidence of iatrogenic retinal breaks, and the use of perfluorocarbon liquid (PFCL) and silicone oil tamponade, and postoperative indices regarding recurrent vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, and visual outcome were evaluated between the two groups. All patients were followed up for one year after surgery. RESULTS: In young PDR patients, the severity of intraoperative bleeding was significantly lower in the IVR group than in the control group (P=0.04). The total surgical time was shorter in the IVR group than in the control group. However, the rate of relaxing retinotomy, the incidence of iatrogenic retinal breaks and the use of PFCL and silicone oil tamponade were not affected by IVR pretreatment but affected by the complexity score of the case. Early postvitrectomy hemorrhage occurred less frequently in the IVR group than in the control group (P<0.001), Early visual recovery was better in the IVR group than in the control group (P=0.03). However, there were no significant differences in the development of late recurrent VH, NVG, recurrent retinal detachment, and final visual outcome. CONCLUSIONS: IVR pretreatment is a safe and effective adjunct to vitrectomy in reducing intraoperative and early postvitrectomy bleeding and should be suggested in young PDR patients. However, IVR does not reduce the incidence of intraoperative and late postoperative complications in these patients. The risk of iatrogenic retinal breaks and silicone oil use are closely correlated with the complexity score of the surgical cases.

[Effect of temperature on the secondary structure of fish scale collagen].

Pepsin-soluble collagen (PSC) was extracted from fish scale of grass carp and was analyzed by SDS-PAGE, which confirmed that PSC are typical type I collagen and reach electrophoretic purity. Effect of temperature on the secondary structure of collagen was studied by FTIR, Raman and CD. FTIR indicated that the fish scale PSC had typically characteristic absorptions of collagen, and 1659, 1552 and 1238 cm(-1) were assigned to be amide I, II and III respectively. When the temperature increased, amide A and amide B shifted to low frequency, the absorption of 1658 cm(-1) split into several absorption peaks, the absorption at 1552 cm(-1) had a slight red-shift followed by a distinct blue-shift, and the frequency of 1238 cm(-1) declined. Raman spectra showed that the absorptions of amide I, amide II and amide III appeared at 1669, 1557 and 1245 cm(-1) respectively, which were higher than those in FTIR spectra. Furthermore, the characteristic absorptions of proline at 921 and 855 cm(-1) only appeared in Raman spectra. CD spectra demonstrated a rotatory maximum at 221.6 nm and a negative peak at 204.4 nm of PSC solution, which were typical spectral characteristics of the collagen triple helix structure. The structure changes of the lyophilized PSC appeared mainly between 35 and 60 degrees C in FTIR and Raman spectra, yet CD spectra demonstrated that the configurational changes of PSC in acidic solution appeared in the range of 20 to 35 degrees C, indicating that the lyophilized PSC was more stable than the acidic solution of PSC.

[Prognosis of traumatic eyes with no light perception undergone vitrectomy and analysis of risk factors].

OBJECTIVE: To evaluate the prognosis of traumatic eyes with no light perception post vitrectomy, and to analyze the risk factors influencing the final results. METHODS: Five hundred and ninety nine mechanically injured eyes in 577 patients undergone vitrectomy were registered from 1999 - 2004. Thirty-eight eyes in this group showed no light perception in initial visual examination. Thirty-two eyes (84.2%) had open-globe injury, the other 6 eyes (15.8%) had closed-globe injury. Excluded the enucleated eyes, the others were followed up for at least 6 months, averaged 7.2 months. All registered data were filled in predesigned forms. Each parameter was evaluated strictly according to the standards of the protocol. The risk factors of poor prognosis and traumatic no light perception were analyzed by logistic regression. RESULTS: Fourteen eyes (36.8%) achieved anatomic and functional success. Three eyes (7.9%) attained anatomic success. Nine eyes (23.7%) were enucleated. Hypotony occurred in 4 eyes. Seven eyes were maintained by silicone oil. Atrophy of eyeball occurred in 1 eye. Twenty-one eyes (55.3%) achieved a final visual acuity of light perception or better, including: 0.2 in 3 eyes, 0.02 in 2 eyes, count finger in 3 eyes, hand move in 3 eyes, light perception in 10 eyes. Eight eyes (21.1%) remained no light perception. The logistic regression analysis identified the significant risk factors predictive of poor prognosis, including traumatic no light perception, presence of a relative afferent pupillary defect (RAPD), massive suprachoroid hemorrhage (MSCH), panretinal detachment with closed-funnel, ciliary body injury, preoperative atrophy of eyeball, prolapse of iris and aniridia, extrusion of crystalline lens, length of scleral wound greater than 10 mm and ruptured injury. These factors were also the risk factors of traumatic no light perception, excluded traumatic no light perception, prolapse of iris and aniridia. More than one risk factor usually co-exists in each eye. CONCLUSIONS: The eyes with traumatic no light perception have poor prognosis. However, 45% of them can achieve functional and anatomic success undergone vitrectomy. Eyes with no light perception are related to the combination of various risk factors. MSCH, severe retinal injury and extensive ciliary body injury are the main risk factors for poor prognosis.

Changes following supplementation with lutein and zeaxanthin in retinal function in eyes with early age-related macular degeneration: a randomised, double-blind, placebo-controlled trial.

AIMS: To investigate functional and macular pigment (MP) changes in patients with early age-related macular degeneration (AMD) after multiple supplementation with lutein and zeaxanthin. METHODS: 112 patients with early AMD were randomly (1:1:1:1) assigned to receive 10 mg lutein, 20 mg lutein, lutein (10 mg)+zeaxanthin (10 mg), or placebo daily for 2 years. MP optical density (MPOD) was recorded at baseline, 48 weeks and 2 years. Retinal sensitivities were measured by multifocal electroretinogram for peak-to-trough amplitude (N1P1) at baseline and at 48 weeks, and in terms of microperimeter-determined mean retinal sensitivity (MRS) at 48 weeks and 2 years. RESULTS: Supplementation with lutein and zeaxanthin augmented MPOD significantly in active treatment groups (all p<0.05). N1P1 response densities showed significant increases in ring 1 and ring 2 after 48 weeks of supplementation, while no significant changes were seen in rings 3-6. Significant increases in MRS were detected after supplementation with either 10 or 20 mg lutein, whereas no such increases were seen in the placebo arm. CONCLUSIONS: Supplementation with lutein and/or zeaxanthin increases MPOD, and supplemental lutein enhances retinal sensitivity, in patients with early AMD. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT10528605.

Effect of supplemental lutein and zeaxanthin on serum, macular pigmentation, and visual performance in patients with early age-related macular degeneration.

PURPOSE: To compare the 2-year effect of multiple doses of lutein/zeaxanthin on serum, macular pigmentation, and visual performance on patients with early age-related macular degeneration (AMD). METHODS: In this randomized, double-blinded, and placebo-controlled trial, 112 early AMD patients randomly received either 10 mg lutein, 20 mg lutein, a combination of lutein (10 mg) and zeaxanthin (10 mg), or placebo daily for 2 years. Serum concentration of lutein/zeaxanthin, macular pigment optical density (MPOD), visual functions including best-spectacle corrected visual acuity (BCVA), contrast sensitivity (CS), flash recovery time (FRT), and vision-related quality of life (VFQ25) was quantified. RESULTS: Serum lutein concentration and MPOD significantly increased in all the active treatment groups. Supplementation with 20 mg lutein was the most effective in increasing MPOD and CS at 3 cycles/degree for the first 48 weeks. However, they both significantly increased to the same peak value following supplementation with either 10 mg or 20 mg lutein during the intervention. No statistical changes of BCVA or FRT were observed during the trial. CONCLUSIONS: Long-term lutein supplementation could increase serum lutein concentration, MPOD, and visual sensitivities of early AMD patients. 10 mg lutein daily might be an advisable long-term dosage for early AMD treatment.

Anatomical outcome of vitreoretinal surgery using temporary keratoprosthesis and replacement of the trephined corneal button for severe open globe injuries: one-year result.

In this case series of 74 patients with coexisting vitreoretinal injury and severe corneal opacification, after temporary keratoprosthesis (TKP) assisted pars plana vitrectomy (PPV), an allograft corneal transplant was not performed at the same time; instead, the patient's trephined corneal button was sutured back. One year after the surgery, if intraocular pressure of the injured eyes was above 8 mmHg, removing silicone oil was attempted, and penetrating keratoplasty could be performed. Finally, 10 eyes (13.5%) were enucleated due to atrophia bulbi; 46 eyes (62.2%) were silicone-oil sustained; 15 eyes (20.3%) were anatomically restored; and 3 eyes (4.0%) experienced recurrent retinal detachment. These figures only demonstrate a small percentage of the injured eyes in our series, which have PKP indications. It is a practical option to suture back the patient's trephined cornea following a TKP assisted PPV; keratoplasty was reserved for selected cases.

Serum and macular responses to multiple xanthophyll supplements in patients with early age-related macular degeneration.

OBJECTIVE: This randomized controlled trial examined serum and macular (in vivo measured macular pigment optical density [MPOD]) responses to supplemental lutein and zeaxanthin in Chinese subjects with early age-related macular degeneration. METHODS: One hundred and eight patients with early age-related macular degeneration older than 50 y were randomized to low lutein (LL; 10 mg/d), high lutein (HL; 20 mg/d), lutein plus zeaxanthin (LZ; each 10 mg/d), or placebo during a 48-wk intervention. Serum concentrations were quantified by C(30) high-performance liquid chromatography (at baseline and 4, 12, 24, and 48 wk), and MPOD was measured by analysis of autofluorescence images (at baseline and 24 and 48 wk). RESULTS: Serum lutein levels in the LL, LZ, and HL groups increased significantly in the first 4 wk and then increased 4.24-, 4.66-, and 6.23-fold during the trial, respectively (all P < 0.001). The serum lutein level in the HL group was significantly higher than that in the LL or LZ group at 48 wk (P < 0.05). Similarly, the serum zeaxanthin concentration in the LZ group increased 3.11-fold at 48 wk. MPOD increased smoothly in all treated groups, and the increase from baseline was greatest in the HL group at 24 and 48 wk (both P < 0.05). MPOD and serum lutein levels increased linearly with the dosage and their increasing rates were statistically correlated (all P < 0.05). No notable changes were detected in the placebo group for MPOD and serum concentrations. CONCLUSION: Xanthophyll supplementation significantly increased serum concentrations and MPOD in patients with early age-related macular degeneration, and a higher lutein supplementation (20 mg/d) might be more effective in increasing these two biochemical markers in Chinese patients without significant side effects.

Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial.

PURPOSE: To examine the effects of lutein and zeaxanthin supplementation on retinal function using multifocal electroretinograms (mfERG) in patients with early age-related macular degeneration (AMD). DESIGN: Randomized, double-masked, placebo-controlled trial. METHODS: One hundred eight subjects with early AMD were randomly assigned to receive 10 mg/d lutein (n = 27), 20 mg/d lutein (n = 27), 10 mg/d lutein plus 10 mg/d zeaxanthin (n = 27), or placebo (n = 27) for 48 weeks. Thirty-six age-matched controls without AMD were also enrolled to compare baseline data with early AMD patients. MfERG responses and macular pigment optical densities (MPODs) were recorded and analyzed at baseline and at 24 and 48 weeks. RESULTS: There were significant reductions in N1P1 response densities in ring 1 to ring 3 in early AMD patients compared with the controls (P < .05), whereas neither N1P1 response densities in ring 4 to ring 6 nor P1 peak latencies significantly changed. After 48-week supplementation, the N1P1 response densities showed significant increases in ring 1 for the 20 mg lutein group and for the lutein and zeaxanthin group, and in ring 2 for the 20 mg lutein group. The increases in MPOD related positively to the increases in N1P1 response density in ring 1 and ring 2 for nearly all active treatment groups. N1P1 response densities in ring 3 to ring 6 or P1 peak latencies in all rings did not change significantly in any group. CONCLUSION: Early functional abnormalities of the central retina in the early AMD patients could be improved by lutein and zeaxanthin supplementation. These improvements may be potentially attributed to the elevations in MPOD.

Serum inflammatory factors in patients with idiopathic choroidal neovascularization.

OBJECTIVE: To investigate serum inflammatory factors in patients with idiopathic choroidal vascularization (CNV), including vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNFα), Interleukin1-beta (IL1-ß), IgG, IgA, IgM, IgE, 50% hemolytic unit of complement (CH50), complement C3, complement C4 and C reactive protein (CRP). METHODS: 21 patients and 20 normal individuals were recruited. They received comprehensive ophthalmic examinations. Serous concentrations of VEGF, TNFα, IL1-ß were assayed by ELISA, and the concentrations of other serum factor were assayed by immunonephelometry. RESULTS: The mean serum VEGF level in the CNV group was significantly greater than that in the control group (p=0.025). The median level of IgE in the CNV group was significantly lower than that in the control group (p=0.006). Statistical analysis revealed no significant difference in the levels of TNFα, IL1-ß, IgG, IgA, IgM, CH50, C3, C4 or CRP between the two groups. CONCLUSION: The possible roles of these factors and mechanisms of idiopathic CNV formation were analyzed. Serum VEGF and IgE levels may play an important role in the formation of idiopathic CNV.

Baicalein reduces inflammatory process in a rodent model of diabetic retinopathy.

PURPOSE: This study was designed to elucidate the role of inflammatory process in diabetic retinopathy and to investigate the effect of baicalein treatment on diabetic rat. METHODS: Retinal microglial cells were identified with CD11b antibody, and retinal Müller cells were identified with glial fibrillary acidic protein (GFAP). The gene expression of interleukin (IL)-18, tumor necrosis factor (TNF)-alpha, and IL-1beta was examined by quantitative real-time PCR. The expression of GFAP and vascular endothelial growth factor (VEGF) was examined by quantitative real-time PCR, immunohistochemistry, and Western blot analysis. Vascular permeability was measured in vivo by bovine serum albumin conjugated with FITC. Baicalein was given by oral administration (150 mg/kg/d) with an animal feeding needle beginning 5 days after streptozotocin (STZ) injection. RESULTS: By 24 weeks after onset of diabetes, microglial cells were activated and proliferated, and Müller cells upregulated their GFAP and VEGF expression. Pro-inflammatory factors, including IL-18, TNF-alpha, and IL-1beta, were significantly upregulated. Obvious vascular leakage and abnormality were demonstrated, and ganglion cell loss was significant. Baicalein treatment ameliorated diabetes-induced microglial activation and pro-inflammatory expression, reduced the GFAP and VEGF expression from Müller cells, and significantly reduced vascular abnormality and ganglion cell loss within the retina. CONCLUSIONS: Inflammatory process, characterized by microglial activation and Müller cells dysfunction, was implicated in STZ-induced diabetic retinopathy. Baicalein treatment ameliorated inflammatory process, and therefore inhibited vascular abnormality and neuron loss in diabetic retinas.

Targeted treatment of choroidal neovascularization using integrin-mediated sterically stabilized liposomes loaded with combretastatin A4.

PURPOSE: The objective of this study was to develop an efficient vasculature-targeted liposomal combretastatin A4 (CA4), by the modification of the sterically stabilized liposomes (SSL) with a ligand of integrins and to explore the possibility of such system for the treatment of choroidal neovascularization (CNV). METHODS: CA4-loaded liposomes were prepared by thin-film dispersion method. The linear arginine-glycine-aspartic acid tripeptide (RGD) with affinity for integrins such as alphavbeta3 expressed on rapidly proliferative vascular endothelial cells was coupled to the distal end of polyethylene glycol (PEG) connected on the surface of SSL. The liposome delivery system was characterized in terms of size and size distribution profiles by dynamic light scattering method, entrapment efficiency, and leakage properties by high-performance liquid chromatography (HPLC). The uptake efficiency by human umbilical vein endothelial cells (HUVECs) was evaluated by confocal microscopy. The therapeutic efficacy was quantitatively assessed by choroidal flat mounts. RESULTS: CA4-loaded RGD-SSL (RGD-SSL-CA4) was obtained with an entrapment efficiency over 70% and an average diameter of approximately 120 nm. The leakage property of RGD-SSL-CA4 was similar with SSL-CA4, both were slower than CA4 ethanol solution. Confocal microscopy studies revealed that RGD-SSL could facilitate the liposomes' uptake into HUVECs. Rats treated with two intravenous injections of 7 mg/kg RGD-SSL-CA4 resulted in a significant reduction in the area of CNV compared with control group (P < 0.05). CONCLUSIONS: RGD-modified SSL loaded with CA4 can be successfully prepared, and the vasculature-targeted liposome system would increase the uptake of HUVECs and improve the therapeutic efficacy of CA4 on CNV compared with the control formulations.