Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022)

Background In China's Mainland,patients with neovascular age-related macular degeneration(nAMD)have approximately an 40%prevalence of polypoidal choroidal vasculopathy(PCV).This disease leads to recurrent retinal pigment epithelium detachment(PED),extensive subretinal or vitreous hemorrhages,and severe vision loss.China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes,regarding opinions on inactive PCV,choices of anti-vascular endothelial growth factor(anti-VEGF)monotherapy,photodynamic therapy(PDT)monotherapy or combined therapy,patients with persistent subretinal fluid(SRF)or intraretinal fluid(IRF)after loading dose anti-VEGF,and patients with massive subretinal hemorrhage.An evidence synthesis team conducted systematic reviews,which informed the recommendations that address these questions.This guideline used the GRADE(Grading of Recommendations,Assessment,Development,and Evaluation)approach to assess the certainty of evidence and grade the strengths of recommendations.Results The panel proposed the following six conditional recommendations regarding treatment choices.(1)For patients with inactive PCV,we suggest observation over treatment.(2)For treatment-na?ve PCV patients,we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy.(3)For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment,we suggest later/rescue PDT over initiate PDT.(4)For PCV patients who plan to initiate anti-VEGF monotherapy,we suggest the treat and extend(TE)regimen rather than the pro re nata(PRN)regimen following three monthly loading doses.(5)For patients with persistent SRF or IRF on optical coherence tomography(OCT)after three monthly anti-VEGF treatments,we suggest proceeding with anti-VEGF treatment rather than observation.(6)For PCV patients with massive subretinal hemorrhage(equal to or more than four optic disc areas)involving the central macula,we suggest surgery(vitrectomy in combination with tissue-plasminogen activator(tPA)intraocular injection and gas tamponade)rather than anti-VEGF monotherapy.Conclusions Six evidence-based recommendations support optimal care for PCV patients'management.

One-year outcomes of intravitreal conbercept combined rescue therapy for polypoidal choroidal vasculopathy in a Chinese population: a real-life clinical data

AIM: To evaluate the real-life clinical outcomes of intravitreal injection of conbercept combined rescue therapy for polypoidal choroidal vasculopathy(PCV). METHODS: This was an open label, single center, and interventional study. All enrolled patients were treated initially with three consecutive monthly intravitreal conbercept injections(0.5 mg). Additional conbercept injections were administered upon substantial polyp regression with improved visual acuity(VA). Eyes with partial or no polyp regression and poor VA were rescue treated with photodynamic therapy(PDT) for subfoveal polyps or thermal laser photocoagulation for extrafoveal polyps. Best-corrected visual acuity(BCVA), central foveal thickness(CFT) and polyp regression were observed as primary outcomes. Side effects were also collected during the follow-up period. RESULTS: A total of 56 eyes(56 patients) with PCV were included. BCVA increased significantly from the baseline of 43.52±24.21 letters to 55.88±21.94 letters(P<0.001) at 12 mo, while CFT decreased significantly from 457.41±207.86 μm to 247.98±127.08 μm(P<0.001). All patients showed polyp regression. Twenty-three eyes achieved complete polyp regression after the three initial injections, which increased to 44 eyes at 12 mo. Seventeen eyes underwent rescue therapy, among which 2 eyes treated with PDT and 15 eyes treated with laser photocoagulation. A mean of 4.30±1.43 injections were given per eye. No intraocular inflammation, retinal or vitreous hemorrhage, or systemic complication occurred. CONCLUSION: Conbercept is an effective and safe option for the treatment of PCV in Chinese population. The treatment regimen of three initial conbercept injections followed by additional injections or rescue therapies is efficacious for treating PCV.

Splenic vasculopathy in portal hypertension patients

AIM： To investigate the interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy by observing splenic arterial and venous pathological changes and the role of extracellular matrix in the pathogenesis of portal hypertensive vasculopathy by measuring the expression of type Ⅰ and type Ⅲ procollagen mRNA in splenic venous walls of portal hypertensive patients. METHODS： Morphological changes of splenic arteries and veins taken from portal hypertensive patients （n = 20） and normal controls （n = 10） were observed under optical and electron microscope. Total RNA was extracted and the expression of type Ⅰ and type Ⅲ procollagen mRNA in splenic venous walls of portal hypertensive patients （n= 20） was semi-quantitatively detected using reverse transcription-polymerase chain reaction （RT-PCR）. RESULTS： Under optical microscope, splenic arterial intima was destroyed and internal elastic membrane and medial elastic fibers of the splenic arterial walls were degenerated and broken. Splenic venous intima became remarkably thick. Endothelial cells were not intact with formation of mural thrombus. The tunica media became thickened significantly due to hypertrophy of smooth muscles. Fibers and connective tissues were increased obviously. Under electron microscope, smooth muscle cells of the splenic arteries were degenerated and necrotized. Phenotypes of smooth muscle cells changed from constrictive into synthetic type. Red blood cells and platelets accumulated around the damaged endothelial cells. Synthetic smooth muscle cells were predominant in splenic veins and their cytoplasma had plentiful rough endoplasmic reticulum ribosomes and Golgi bodies. Along the vascular wall, a lot of collagen fibers were deposited, the intima was damaged and blood components accumulated. There was no significant difference in the expression of type Ⅰ procollagen mRNA in splenic venous wall between the patients with portal hypertension and those without portal hypertension （P〉0.05）, but the expression of type Ⅲ procoagen mRNA was significantly stronger in the patients with portal hypertension than in those without portal hypertension （P〈 0.01）. CONCLUSION： Type Ⅲ procollagen and collagen might be important extra-cellular matrix resulting in neointimal formation and vascular remodeling in the pathogenesis of portal hypertensive vasculopathy. The pathological changes in splenic arteries and veins exist in portal hypertension patients. There might be an interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy.

Long-term observation of vitrectomy without subretinal hemorrhage management for massive vitreous hemorrhage secondary to polypoidal choroidal vasculopathy

AIM: To describe the long-term observation of vitrectomy without subretinal hemorrhage(SRH) management for massive vitreous hemorrhage(VH) secondary to polypoidal choroidal vasculopathy(PCV). METHODS: This is a retrospective, consecutive case series. A total of 86 eyes of 86 patients with >14d of massive VH associated with PCV were included. All patients underwent vitrectomy without SRH management, followed by intravitreal ranibizumab injections and/or photodynamic therapy(PDT) as needed. The main outcome measures were best-corrected visual acuity(BCVA), postoperative adverse events and the recurrence of VH. RESULTS: The average follow-up period was 25.5±9.2 mo(range 12-35 mo). Mean BCVA at baseline(2.16±0.39 logM AR)had improved significantly, both 3 mo after surgery(1.42±0.66 log MAR, P<0.001) and by the last visit(1.23±0.74 logM AR, P<0.001). The common postoperative complications included macular subretinal fibrosis in 14 eyes(16.3%) and ciliary body detachment in 4 eyes(4.7%).Nineteen eyes(22.1%) received following treatment with ranibizumab injections without/with PDT, and 15(17.4%)were resolved. Four eyes(4.7%) had recurrent hemorrhage during the follow-up period. In multiple regression analysis,thicker SRH(beta=0.33, P=0.025) in the preoperative B-scan and the presence of foveal subretinal fibrosis(beta=0.28, P=0.018) in the follow up were associated with poor postoperative BCVA. CONCLUSION: Vitrectomy without SRH management for massive VH secondary to PCV improved/stabilized visual function in the long-term observation. Eyes presenting with thicker SRH preoperatively and forming foveal subretinal fibrosis in the follow-up period tended to have worse BCVA.

Analysis of choroidal morphology and comparison of imaging findings of subtypes of polypoidal choroidal vasculopathy:a new classification system

AIM:To classify polypoidal choroidal vasculopathy(PCV)into 2 subtypes based on the subfoveal choroidal thickness(SFCT)and to further evaluate their multimodal image features.METHODS:A retrospective observational case series study.Sixty-four eyes of 64 patients with PCV were enrolled and classified into 2 groups based on SFCT(thick-choroid group/thin-choroid group).Then further analyze the spectrum domain optical coherence tomography(SD-OCT)and indocyanine green angiography(ICGA)differences of the two subtypes.Imaging analysis included measurement of SFCT,maximum vascular diameter ratio(MVDR),choroidal vascularity index(CVI),central macular thickness(CMT),and the presence of pigment epithelial detachment(PED)on SD-OCT.Polypoidal lesions(polyps)number,branching vascular network(BVN)area,greatest linear dimension(GLD),and the choroidal vascular hyperpermeability(CVH)were analyzed by ICGA.RESULTS:The distribution of SFCT was bimodal with two peaks at 195 and 285μm,and a trough at 225μm.The 225μm was taken as the cutoff point for the following classification of thick/thin choroid groups.The PCV eyes in the thick-choroid group presented with greater MVDR,CVI within 3 and 6 mm of the fovea,but lower CMT,less PED,small PED diameters on SD-OCT scans,and fewer polyps,smaller BVN and GLD,but more frequency of CVH on ICGA.CONCLUSION:The SFCT at 225μm can be used as a readily available indicator for the classification of PCV subtypes.The thick-choroid group presents much apparent enlargement of the choroidal layer and vasculature expansion,which indicates different pathogenesis of the two subtypes.

Research progress of vasculopathy in portal hypertension

Portal hypertension, one of the vascular diseases, not only has lesions in liver, but also changes in vascular structures and functions of extrahepatic portal system, systemic system and pulmonary drculation. The pabhological changes of vasculopathy in portal hypertension include remodeling of arterialized visceral veins, intimal injury of visceral veins and destruction of contractile structure in visceral arterial wall. The mechanisms of vasculopathy in portal hypertension may be attributed to the changes of hemodynamics in portal system, immune response, gene modulation, vasoactive substances, and intrahepatic blood flow resistance. Portal hypertension can cause visceral hyperdynamic circulation, and the development and progression of visceral vasculopathy, while visceral vasculopathy can promote the development and progression of portal hypertension and visceral hyperdynamic circulation in turn. The aforementioned three factors interact in the pathogenesis of hepatic cirrhosisinduced portal hypertension and are involved in hemorrhage due to varicose vein rupture.

Ranibizumab alone or in combination with photodynamic therapy vs photodynamic therapy for polypoidal choroidal vasculopathy: a systematic review and Meta-analysis

AIMTo compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODSA systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis.RESULTSThree RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P&#x02264;0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P&#x0003c;0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P&#x0003c;0.01) after removal of a heterogeneous study.CONCLUSIONIVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.

Peripheral Neuropathy and Vasculopathy;Frequency and Associated Risk Factors in Newly Diagnosed Treatment Naive Type 2 Diabetes

Background: The prevalence of diabetes in Pakistan is 11.45%. The reported prevalence of diabetic foot ulceration in Pakistan is between 4% and 10%, with the amputation rate of 8% - 21%. Peripheral neuropathy and vasculopathy are main underlying cause of diabetic foot ulcers. Methodology: It was a cross-sectional non-interventional cohort study where all newly diagnosed treatment na&#239;ve type 2 diabetic patients were enrolled. Peripheral neuropathy and vasculopathy were detected by Michigan neuropathy screening instrument (MNSI) and ankle brachial index (ABI) respectively. Risk factors for peripheral neuropathy and vasculopathy were determined by univariate and multivariate logistic regression analysis. Statistical significance was considered with P value of Result: Fifty seven patients (37.7%) had early neuropathy with MNSI score of 3.3 ± 0.4. Thirty seven patients (20.6%) had vasculopathy with ABI score of 0.76 ± 0.11. Age (Odd ratio 1.07 (1.02 - 1.11), p 0.003), duration of symptoms (Odd ratio 1.11 95% CI: 1.05 - 1.17, p ≤ 0.001), high HbA1C % (Odd ratio 1.94 95% CI: 1.54 - 2.45, P ≤ 0.001), albumin creatinine ratio (Odd ratio 1.01, 95% CI: 1.00 - 1.01, P ≤ 0.001 ) and cholesterol level (Odd ratio 1.01 95% CI: 1.01 - 1.02, p = 0.001) were found as risk factors for early neuropathy and vasculopathy. Conclusion: Peripheral neuropathy and vasculopathy are frequently reported complications among newly diagnosed treatment na&#239;ve patients of type 2 DM. Age, duration of symptoms prior to diagnosis, metabolic parameters like raised HbA1C, hyperlipidemia and spot random albumin creatinine ratio are found to be risk factors for both peripheral neuropathy and vasculopathy.

One-year real-world outcomes of ranibizumab 0.5 mg treatment in Taiwan Residents patients with polypoidal choroidal vasculopathy： a subgroup analysis of the REAL study

AIM： To assess the effectiveness and safety of ranibizumab 0.5 mg in Taiwan Residents patients with polypoidal choroidal vasculopathy（PCV） by performing a retrospective exploratory subgroup analysis of the REAL study.METHODS： REAL was a 12-month, observational, prospective, non-interventional phase IV post-marketing surveillance study conducted at 9 centers in Taiwan. The study collected data as part of the routine patient visits from the medical records of patients with neovascular agerelated macular degeneration treated with ranibizumab 0.5 mg according to local standard medical practice and local label and/or reimbursement guidelines. The presence of PCV at baseline was determined using indocy received prior tanine green angiography. RESULTS： At baseline, PCV was diagnosed in 64 of the 303 enrolled patients（21.1%）. Of these, 41 patients（64.1%） hadreatment; 15（23.4%） patients had received ranibizumab. The intent-to-treat population included 58 patients; 47（80%） who received ranibizumab and 11（20%） who received ranibizumab plus photodynamic therapy（PDT; 9 patients received once, 2 patients received twice）. Bevacizumab was used as a concomitant medication in a similar percentage of patients who received ranibizumab（43%, n=20） or ranibizumab plus PDT（45%, n=5）. In patients who received ranibizumab, visual acuity（VA） at baseline was 50.1±12.9 Early Treatment Diabetic Retinopathy Study letters, and the gain at month 12 was 1.1±17.8 letters. In patients who received ranibizumab plus PDT, VA at baseline was 51.4±15.9 letters, and there was a marked gain in VA at month 12（14.0±9.2 letters, P=0.0009）. In the intent-totreat population, the reduction in central retinal subfield thickness from baseline at month 12 was 69.6±122.6 μm（baseline： 310.8±109.8 μm, P=0.0004）. The safety results were consistent with the well-characterized safety profile of ranibizumab.CONCLUSION： In real-world settings, ranibizumab 0.5 mg treatment for 12 mo results in maintenance of VA and reduction in central retinal subfield thickness in Taiwan Residents patients with PCV. Improvements in VA are observed in patients who received ranibizumab plus PDT. There are no new safety findings.

Coronary microvasculopathy in heart transplantation: Consequences and therapeutic implications

Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy(CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries(50-20 μm), arterioles(20-10 μm), and capillaries(< 10 μm). The etiology of CAV remains unclear; both immunologic and non-immunologic mechanisms contribute to endothelial damage with a sustained inflammatory response. The immunological factors involved are Human Leukocyte Antigen compatibility between donor and recipient, alloreactive T cells and the humoral immune system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcircula-tory resistance during maximal hyperemia, which is calculated by dividing pressure by flow(distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.

Effects of three consecutive monthly intravitreal injection of ranibizumab for polypoidal choroidal vasculopathy in Korea

AIM: To evaluate the efficacy and safety of three consecutive monthly injections of intravitreal ranibizumab for the treatment of polypoidal choroidal vasculopathy(PCV) in Korea.METHODS: A retrospective chart review of 25 patients(27 eyes) with PCV was conducted. Patients received three initial monthly intravitreal injections(0.5 mg) of ranibizumab and were monitored monthly for 12 mo from January 2010 to October 2011. Reinjection of ranibizumab after three initial monthly loading was administered on an as-needed basis, guided by the optical coherence tomography(OCT), fluorescein angiography(FA) and indocyanine green angiography(ICGA). The main outcomes were the changes of the mean best corrected Snellen visual acuity(VA), central macular thickness(CMT) by OCT, the changes of polyps and branching vascular network by FA and ICGA, and total number of injections received by patients during the 12 mo.RESULTS: The mean best corrected Snellen visual acuities at baseline, 1, 3, 6 and 12 mo after primary injection were 0.77 ±0.59, 0.76 ±0.53, 0.70 ±0.47, 0.63 ±0.43,0.61 ±0.43, 0.62 ±0.42 log MAR, respectively, and showed significant improvement at 3, 6, 12mo(P =0.003, P =0.002,P =0.018, Wilcoxon signed-rank test). The mean CMT at baseline, 1, 2, 3, 6, and 12 mo was 312.41 ±66.38 μm,244.59 ±71.47 μm, 232.32 ±69.41 μm, 226.69 ±69.03 μm,228.62 ±37.07 μm, 227.59 ±51.01 μm respectively, and showed significant reduction(all P 【0.001, Wilcoxon signed-rank test). Polypoidal lesions resolved on ICGA in 3 eyes(11.1%) and a branching vascular network remained in all 24 eyes(88.9%). A total of 106 injections were given in the 12-month period, which equaled to a mean of 3.92(range, 3-6) times. Sixteen of the 27 treatedeyes had additional 1.56 ±0.91 injections. The others(11eyes) had just 3 consecutive injections.CONCLUSION: An initial loading dose of three monthly ranibizumab injections is a safe and effective method in treating PCV, with visual and anatomical improvement over one year follow-up.

Combined therapy versus anti-vascular endothelial growth factor monotherapy for polypoidal choroidal vasculopathy： a Meta-analysis

AIM： To evaluate the efficacy and safety of anti-vascular endothelial growth factor （VEGF） combined with photodynamic therapy （PDT） versus anti-VEGF monotherapy for polypoidal choroidal vasculopathy （PCV）. METHODS： We conducted a Meta-analysis of 9 studies to compare the efficacy and safety between combined therapy and anti-VEGF monotherapy for PCV. The programs of RevMan 5.3 and Stata 12.0 were used to analyze data. RESULTS： The best corrected visual acuity （BCVA） in combined therapy group were significantly better than those of anti-VEGF monotherapy group at 6, 24 and 36mo, with pooled weighted means differences （WMDs） of 0.12 （0.06, 0.18）, 0.25 （0.12, 0.38） and 0.28 （0.13, 0.43）, respectively. The central retinal thickness （CRT） reductions in combined therapy group were higher than that in anti- VEGF monotherapy group at 1, 3, 6 and 9mo, with pooled WMDs of 63.90 （20.41, 107.38）, 33.47 （4.69, 62.24）, 30.57 （0.12, 60.01） and 28.00 （2.51, 53.49）, respectively. The regression rate of polyps in combined therapy group was much higher than that in anti-VEGF monotherapy group [RD： 0.47 （0.26, 0.68）; P〈0.0001]. The adverse event retinal hemorrhage did not differ significantly between the two groups. CONCLUSION： Our findings clearly document that anti- VEGF combined with PDT is a more effective therapy for PCV compared with anti-VEGF monotherapy. Furthermore, combined therapy does not increase the incidence of retinal hemorrhage.

Long-term outcomes of focal laser photocoagulation for the treatment of polypoidal choroidal vasculopathy

AIM:To evaluate the long-term effect and safety of focal laser photocoagulation treatment in eyes with polypoidal choroidal vasculopathy(PCV).METHODS:Medical records of 13 eyes of 13 patients with PCV were followed-up for more than 2 y after focal laser photocoagulation treatment.The patients were diagnosed with PCV using indocyanine green angiography,and eyes with other comorbid ocular diseases were excluded.The measurement outcomes of the study were the post-treatment regression and recurrence of polyps,complications,and changes in visual acuities.Paired t-test was performed to compare visual outcome before and after the treatment.RESULTS:The mean age of the 13 patients was 70.2±5.5 y,and the follow-up period was 72.3±31.0(range,25-118)mo.Three eyes had juxtafoveal polyps and 10 eyes had extrafoveal polyps.Of the 13 eyes,9 eyes(69.2%)had regression of polyps 1.7±1.2(range,0.9-4)mo after focal laser photocoagulation.Five eyes(55.6%)showed recurrence of polyps during the follow-up periods,and the recurrence period was 12.8±18.9(range,1.9-48)mo.Mild subretinal hemorrhage occurred in two eyes(15.4%)27 and 72 d after laser treatment,respectively.There were no statistically significant differences in visual acuities at baseline;1,2,3 y post-treatment(all P>0.05);and last follow-up(0.63±0.5,0.73±0.70,0.67±0.57,0.75±0.7,and 0.95±0.8 log MAR,respectively).CONCLUSION:Focal laser photocoagulation is beneficial for early regression of polyps in eyes with PCV and does not result in significant submacular hemorrhage during the long-term follow-up.Furthermore,it can be primarily considered in eyes with PCV with extrafoveal or juxtafoveal polyps to regress risky polyps as well as to maintain visual acuity without serious hemorrhagic complications.

Bilateral choroidal osteoma with unilateral polypoidal choroidal vasculopathy treated with conbercept

Dear Editor,Chorodial osteoma(CO) is a rare choroidal tumor characterized by the presence of mature bone tissue predominantly in the juxtapapillary or macularregion.CO mostly affects young healthy females in the second or third decades of life.It is unilateral in approximately 80%of cases[1],as patients have no obvious visual symptoms during the early stage of CO,and the growth of CO is slow.CO patients usually visit the eye clinic during the later stages of CO and have poor vision.Gradual decline in vision in CO patients is related to changes in retinal pigment epithelium(RPE)and photoreceptor atrophy.Choroidal neovascularization(CNV)and the resultant subretinal fluid and hemorrhage are the most frequent causes of sudden vision loss in CO[2].We report a rare case of bilateral CO with unilateral polypoidal choroidal vasculopathy(PCV)in a middle-aged male.

Combined photodynamic therapy and ranibizumab for polypoidal choroidal vasculopathy：a 2-year result and systematic review

AIM：To report a cohort of patients with polypoidal choroidal vasculopathy（PCV）treated with photodynamic therapy（PDT）followed by intravitreal ranibizumab injection 24-48 h later,and to compare the results between eyes with PCV treated by PDT followed by intravitreal anti-vascular endothelial growth factor（VEGF）injection and intravitreal anti-VEGF injection followed by PDT by Meta-analysis.METHODS：Retrospective study and systematic literature review. Medical records of patients with PCV who were initially treated using PDT followed by intravitreal ranibizumab injection 24-48 h after PDT and had completed at least 2y follow-up were reviewed and analyzed. Clinical data,including age,sex,best-corrected visual acuity（BCVA）,fundus photograph,fluorescein angiography,indocyanine green angiography and optical coherence tomography were investigated. A systematic literature review was also conducted,and a visual outcome of studies over 1y was compared using Meta-analysis. RESULTS：A total of 52 patients were included in the study. Mean BCVA at baseline and follow-up at 1 or 2y were 0.71± 0.61,0.51±0.36 and 0.68±0.51 log MAR,respectively. The cumulative hazard rate for recurrence at 1 and 2y followup was 15.4% and 30.3% respectively. The percentage of eyes with polyps regression at 3,12 and 24 mo follow-up was 88.5%,84.6% and 67.3% respectively. A Meta-analysis based on 22 independent studies showed the overall vision improvements at 1,2 and 3y follow-up were 0.13±0.04（P〈0.001）,0.12±0.03（P〈0.001）,0.16±0.06（P〈0.001）,respectively. The proportion of polyps regression at 1y follow-up was 64.6%（95%CI：51.5%,77.7%,P〈0.001）in 434 eyes treated by intravitreal anti-VEGF agents beforePDT and 76.0%（95%CI：64.8%,87.3%,P=0.001）in 199 eyes treated by intravitreal anti-VEGF agents after PDT. CONCLUSION：Intravitreal ranibizumab injection 24-48 h following PDT effectively stabilizes visual acuity in the eye with PCV. PDT followed by intravitreal anti-VEGF agents may contribute to a relatively higher proportion of polyps＇ regression as compared to that of intravitreal anti-VEGF before PDT.

Potency of Urena lobataleaves extract on the inhibition of vasculopathy on diabetic rats

OBJECTIVE To know the potency of Urena lobataleaves extract on the vasculopathy inhibition of diabetic rats.METHODS This study used control group post test only with male Sprague dawley rats.Diabetic rats were induced by high fructose diet(HFD)and single dose streptozotocin 25mg·kg-1 bw intra peritoneal.The rat was administrated orally with water extract of U.lobataleaves in dose of 250,500and1000mg·kg-1 bw for 4 weeks.After scarifying,blood sample were collected and then superoxyde dismutase(SOD)serum level,malondialdehyda(MDA),tumor necrosis factor-alpha(TNF-α)and circulating endothelial cells(CECs)were examined.The data was analyzed using ANOVA test continued with LSD test(P<0.05).RESULTS The oral administration of U.lobataleaves extract 250,500 and 1000mg·kg-1 bw were able to increase SOD serum level about 40%,70% and 100%respectively compared to diabetic group(P<0.05),while the MDA serum level was decreased by 20%,40%and 50%(P<0.05)respectively.The supplementation of water extract from U.lobatain dose of 250,500 and 1000mg·kg-1 bw also decrease TNF-αserum level approximately 40%,60% and 80% compared to control group(P<0.05),whereas the CECs level was decreased by 30%,50% and 70%(P<0.05)respectively.In diabetic groups,SOD serum level was decreased compared to normal group(P<0.05)while the MDA,TNF-αand CECs were increased(P<0.05).CONCLUSION U.lobata leaves extract could inhibit vasculopathy on diabetic rats by increasing of SOD serum level,decreasing of MDA serum level,TNF-αand CECs.This potency may be related to active substances which act as an anti-inflammatory and antioxidant in U.lobata extract.

Mitochondrial vasculopathy

Mitochondrial disorders(MIDs)are usually multisystem disorders(mitochondrial multiorgan disorder syndrome)either on from onset or starting at a point during the disease course.Most frequently affected tissues are those with a high oxygen demand such as the central nervous system,the muscle,endocrine glands,or the myocardium.Recently,it has been shown that rarely alsothe arteries may be affected(mitochondrial arteriopathy).This review focuses on the type,diagnosis,and treat-ment of mitochondrial vasculopathy in MID patients.A literature search using appropriate search terms was carried out.Mitochondrial vasculopathy manifests as either microangiopathy or macroangiopathy.Clinical manifestations of mitochondrial microangiopathy include leukoencephalopathy,migraine-like headache,stroke-like episodes,or peripheral retinopathy.Mitochondrial macroangiopathy manifests as atherosclerosis,ectasia of arteries,aneurysm formation,dissection,or spontan-eous rupture of arteries.The diagnosis relies on the documentation and confirmation of the mitochondrial metabolic defect or the genetic cause after exclusion of non-MID causes.Treatment is not at variance compared to treatment of vasculopathy due to non-MID causes.Mitochondrial vasculopathy exists and manifests as micro-or macroangiopathy.Diagnosing mitochondrial vasculopathy is crucial since appropriate treatment may prevent from severe complications.

Giant non-pulsatile polypoidal choroidal vasculopathy

Polypoidal choroidal vasculopathy （PCV） was first described by Yannuzzi et al in the 1980s as a distinct choroidal abnormality. Clinically, PCV is seen as orange-red subretinal nodules frequently presenting with submacular haemorrhage or serosanguinous pigment epithelial detachments （PED） .

Diagnosis and management of coronary allograft vasculopathy in children and adolescents

Coronary allograft vasculopathy remains one of the leading causes of death beyond the first year post transplant. As a result of denervation following transplantation, patients lack ischaemic symptoms and presentation is often late when the graft is already compromised. Current diagnostic tools are rather invasive, or in case of angiography, significantly lack sensitivity. Therefore a non-invasive tool that could al ow early diagnosis would be invaluable.This paper review the disease form its different diagnosis techniques,including new and less invasive diagnostic tools to its pharmacological management and possible treatments.

Role of Oxidative Stress in Cardiac Allograft Vasculopathy

Cardiac Allograft Vasculopathy, an accelerated form of arterial occlusive disease, is the major cause of death in the long-term after heart transplantation. Multiple factors influence the initiation and progression of CAV. These include ischemia-reperfusion, dyslipidemia, insulin resistance, and hypertension due to the use of immunosuppressive agents, the direct effects of immunosuppressive agents on endothelial function, and viruses (CMV). Impaired endothelial function reflects abnormalities in the production or activity of several vasoactive substances. Disruption of the nitric oxide synthase (NOS) pathway leads to changes in vascular reactivity, structure, and interaction with circulating blood components. Since endothelium-derived nitric oxide (NO) suppresses vascular cell proliferation and vascular inflammation, a deficit in vascular NO facilitates development of CAV. The link between oxidative stress and CAV largely exists in the balance between free radical superoxide generation and NO production. This review focuses on identifying the oxidative stress factors affecting CAV.