Recurrence of polypoidal choroidal vasculopathy after photodynamic therapy

Purpose  To evaluate the recurrence of polypoidal lesions after photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV). Methods  This is a retrospective review of data on 28 patients with PCV treated with PDT. The recurrent polypoidal lesions were observed with fluorescein and indocyanine green angiography. Results  In 26 of the 28 eyes the PCV remained inactive for more than 12 months after one to three treatments with PDT. Recurrence of the polypoidal lesions after more than a 12-month inactive period was reported in eight eyes: three at 15 months, two at 18 months, and three at 21 months. Kaplan-Meier estimates of recurrence were 11.5% at 15 months, 20.4% at 18 months, and 38.8% at 21 months, with no subsequent recurrence until passage of 36 months of inactivity after the last PDT. Additional PDT after recurrence improved or preserved visual acuity in 80% of those treated compared to the visual acuity before the first PDT. Conclusions  Recurrence of PCV occurs in about 40% of eyes treated for PCV even after a long period of inactivity, so careful follow-up is needed.     

Extensive submacular haemorrhage in polypoidal choroidal vasculopathy managed by sequential gas displacement and photodynamic therapy: a pilot study of one-year follow up

BACKGROUND: Polypoidal choroidal vasculopathy (PCV) with peculiar vascular lesions presents frequently as recurrent submacular haemorrhage. The best treatment is still not certain. It is the authors' objective to evaluate the 1-year safety and efficacy of photodynamic therapy (PDT) using verteporfin for persistent macular PCV after pneumatic displacement of the massive submacular haemorrhage with intravitreal perfluoropropane (C(3)F(8)). METHODS: A prospective, non-comparative, interventional case series on patients with extensive and thick submacular haemorrhage secondary to PCV, which was displaced pneumatically with intravitreal pure 0.4 ml C(3)F(8). Fluorescein angiography and indocyanine green angiography were repeated 1-2 weeks later to delineate any persistent active leaking polypoidal lesions, which were then treated with PDT. Retreatment might be considered in each follow up at every 3 months. RESULTS: Six eyes of six patients with the mean age of 53.6 years had been recruited and completed 1-year follow up. The mean baseline Snellen equivalent best-corrected visual acuity (BCVA) was 6/92 and the mean final BCVA at 1 year was 6/17. The mean improvement in logMAR BCVA after the sequential treatments was seven lines (range +3 to +19 lines) (Wilcoxon signed-ranks test, P = 0.03). All patients had at least moderate visual gains. No patient suffered serious complications from PDT. CONCLUSIONS: This first report on combined treatment with intravitreal gas injection and sequential PDT on PCV seems to be a well-tolerated option. Further comparative studies with larger sample size and longer follow up are warranted.     

Use of fluorescein and indocyanine green angiography in polypoidal choroidal vasculopathy patients following photodynamic therapy

Background: Exudative age-related macular degeneration (AMD) is a sight-threatening event in many elderly people. Some patients have a much better outcome in visual acuity (VA) than others after treatment with photodynamic therapy (PDT) with verteporfin. The combination of fluorescein angiography (FA) and indocyanine green (ICG) angiography using the Heidelberg Retina Angiograph II (HRA 2) should make a delineation of distinct pattern(s) possible in order to better select and assess therapy.Methods: This is a retrospective, case-control, single-centre study. We identified a total of 168 eyes of 168 patients from July 2003 to June 2006, including 30 eyes of 30 patients with better visual outcome, defined in this study as VA ≤0.48 logMAR (≥20/60 Snellen chart) at the end of the study. Best-corrected VA, maximal central retinal thickness as measured by optical coherence tomography, and results of the FA/ICG angiography using the HRA 2 were analyzed. In this article, we discuss patients with polypoidal choroidal vasculopathy (PCV) and their characteristics.Results: The average follow-up time was 15.3 months (range 4–28 months). Seventeen (57%) of the 30 patients with better visual outcome had PCV. All patients in the group with better visual outcome needed fewer PDT treatments compared with our control group of patients with an exudative AMD.Interpretation: Simultaneous FA/ICG angiography using the HRA 2 allowed delineation of a subgroup of patients with PCV who showed a better visual outcome compared with those with other types of exudative AMD, after treatment with PDT.     

息肉样脉络膜血管病变的临床特征与手术治疗进展

息肉样脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)是一组以脉络膜异常分支血管网及末端息肉样血管扩张病灶为特征的眼底疾病,临床治疗较为棘手。大面积视网膜黄斑下出血(submacular hemorrhage,SMH)甚至玻璃体腔出血是PCV的严重并发症,往往需要手术干预。其手术治疗包括气体填充和/或组织型纤溶酶原激活物(tPA)注射、玻璃体切割联合视网膜切开或外路引流等。本文就目前国内外关于PCV的临床特征、并发症及手术治疗新进展等内容进行综述。     

Comparison of intravitreal bevacizumab to photodynamic therapy for polypoidal choroidal vasculopathy: Short-term results

Aims:

To compare the short-term therapeutic effects of intravitreal bevacizumab (IVB) to those of photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV).

Materials and Methods:

Retrospective interventional case study. Eighty-nine eyes of 89 patients with symptomatic PCV were treated by IVB or PDT. Eighteen eyes were treated with a single injection of IVB (s-IVB group), 22 eyes with three consecutive monthly IVB injections (m-IVB group), and 49 eyes with PDT alone (PDT group). The best-corrected visual acuity (BCVA) and OCT-determined central foveal thickness (CFT) were evaluated before, and one and three months after the treatment. For statistical analyses, one-factor ANOVA and Chi-square test were used.

Results:

The differences in the BCVA and CFT among the three groups at the baseline were not significant (P=0.992, P=0.981, respectively). Three months after the treatment, the BCVA improved by >0.2 logMAR units in two out of 18 eyes (11%) in the s-IVB group, three out of 22 eyes (14%) in the m-IVB group, and 15 out of 49 eyes (31%) in the PDT group (P=0.124). A decrease in the CFT by >20% was achieved in six out of 18 eyes in the s-IVB group, ten eyes (46%) in the m-IVB group, and 35 eyes (71%) in the PDT group (P=0.009). The resolution of polyps was achieved in three out of 18 eyes in the s-IVB group, one eye (5%) in the m-IVB group and 35 eyes (71%) in the PDT group (P<0.001).

Conclusion:

The better short-term therapeutic outcomes in the PDT group than in the s-IVB and m-IVB groups indicate that PDT may be more effective than IVB in short term after treatment for PCV.     

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 24-48h 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 24-48h 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 logMAR, respectively. The cumulative hazard rate for recurrence at 1 and 2y follow-up was 15.4% and 30.3% respectively. The percentage of eyes with polyps regression at 3, 12 and 24mo 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 before PDT 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 24-48h 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.     

息肉状脉络膜血管病变的研究进展

息肉状脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)与渗出型年龄相关性黄斑变性(age-related macular degeneration,AMD)的临床表现十分相似,但PCV的流行病学特点、自然病程、影像学特征、预后均与渗出型AMD不同.临床上主要通过特异性眼底表现和吲哚青绿血管造影进行诊断及鉴别.目前PCV的病因、发病机制仍不清,治疗方法主要有激光光凝、光动力治疗、抗血管内皮生长因子药物治疗及联合治疗.     

息肉样脉络膜血管病变的诊断及治疗

息肉样脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)特征是后极部视网膜下桔红色息肉样病变,伴有出血性和浆液性视网膜色素上皮及神经上皮脱离.荧光素眼底血管造影无特征性表现,吲哚青绿血管造影能显示分支血管组成的脉络膜血管网和血管末端息肉样或动脉瘤样扩张.OCT表现为视网膜色素上皮及脉络膜毛细血管高反射层呈陡峭的穹窿状隆起,其下见中等反射或结节状改变.本病应与湿性年龄相关性黄斑变性和某些长期不愈的中心性浆液性脉络膜视网膜病变进行鉴别.尽管PCV的治疗仍缺乏通用的方案,光动力疗法结合玻璃体内注射血管内皮生长因子抑制剂可改善或稳定患者视力.     

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

AIM: To 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).METHODS: A 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.RESULTS: Three 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≤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<0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P<0.01) after removal of a heterogeneous study.CONCLUSION: IVR 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.     

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.     

Pathological features of surgically excised polypoidal choroidal vasculopathy membranes

The histopathological features are reported of surgically excised specimens from five patients with polypoidal choroidal vasculopathy, which had been diagnosed by indocyanine green angiography. On stereomicroscopy, four of the five cases demonstrated large choroidal arterioles with an inner elastic layer. Disruption of the inner elastic layer and arteriosclerotic changes of the vessels were identified by light microscopy. Transmission electron microscopy demonstrated increased deposition of basement membrane-like material, together with collagen fibres, in the arteriolar walls. This study indicates that large choroidal arterioles and venules can be found in excised specimens from patients with polypoidal choroidal vasculopathy and arteriosclerosis is an important pathological feature.     

Polypoidal choroidal vasculopathy and photodynamic therapy with verteporfin

Background We evaluated, in a nonrandomised, institutional, prospective study, the efficacy of photodynamic therapy (PDT) with verteporfin in age-related macular degeneration (AMD) eyes with polypoidal choroidal vasculopathy (PCV) and subfoveal exudation. Methods A prospective clinical and angiographic study was done in 40 consecutive eyes with PCV treated with PDT using masked best-corrected visual acuity (VA) and fluorescein and indocyanine green angiographic features at baseline and over 2 years. Results Twenty-one eyes completed 1-year follow-up and showed, after a mean 2.9 PDT sessions, VA improvement in 12 eyes, no change in five eyes, and VA decrease in four eyes. Leakage was absent at the retinal and choroidal level in 14 eyes at 1 year. Recurrence occurred in one eye during the first year. Six eyes completed 2 years of follow-up and showed, after a mean 4 PDT sessions, VA improvement in five eyes and VA decrease in one eye. Leakage was absent at the retinal and choroidal level in five eyes. Recurrence occurred in four of these six eyes during the second year of follow-up. No serious adverse events were observed during the 2 years of follow-up. Conclusions PDT with verteporfin was shown to be safe and effective for treating AMD eyes with PCV with subfoveal involvement. VA improvement and absence of leakage were achieved, respectively, in 57.1% and 66.6% of the eyes at 1 year. Recurrences were more frequent during the second year of follow-up.     

息肉状脉络膜血管病变的现状和进展

息肉状脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)是一种发病原因和发病机制不明的疾病,一些研究表明其可能与某些基因有关。PCV眼底镜下表现常与渗出型年龄相关性黄斑变性(age-related macular degeneration,AMD)相似,通过吲哚青绿血管造影(indocyanine green angiography,ICGA)及光学相干断层扫描(optic coherence tomography,OCT)等影像学检查可予以鉴别。目前主要通过眼底镜下特征性的橘红色息肉状损害和ICGA下见血管网边缘息肉状血管损害对PCV进行诊断。主要的治疗方法包括光动力疗法(photodynamic therapy,PDT)、抗血管生成药物及联合疗法等。我们从历史、流行病学、病理学、发病机制、基因、临床表现、影像学、诊断及治疗等方面对其进行综述,并提出了对PCV的研究方向的讨论和展望。     

Characteristics of fine vascular network pattern associated with recurrence of polypoidal choroidal vasculopathy

Objective

To characterize an irregular capillary-like structure in the vascular network of eyes with polypoidal choroidal vasculopathy (PCV), and to determine whether its presence after photodynamic therapy (PDT) can be used to predict the clinical course of PCV.

Methods

We reviewed the clinical records of 29 eyes of 29 patients with PCV, who underwent PDT and confocal retinal angiographic examinations every 3 months. The images obtained before the PDT were compared with those after the PDT. The correlations between angiography findings and recurrences were evaluated.

Results

An area of fine, densely packed capillary-like vessels, named the fine vascular network, was identified within the polypoidal vascular network in 25 of 29 cases at the initial examination. The fine vascular network regressed in 23 cases (92%) after the first PDT. Thereafter, the fine vascular network remained or enlarged in 19 eyes, and 17 (84.5%) of these eyes had a recurrence of the polypoidal lesions or had exudative changes. In contrast, recurrences were found in only 2 of 10 (20%) eyes, whose fine network had regressed without a subsequent enlargement (P<0.001 compared with the former group).

Conclusions

A fine irregular vascular network is present in the majority of eyes with PCV before PDT. Its presence or expansion after PDT was significantly associated with a recurrence of PCV. Thus, we recommend that this network be monitored after treatment to determine whether a polypoidal vascular network will recur.     

Photodynamic therapy for polypoidal choroidal vasculopathy: Vaso-occlusive effect on the branching vascular network and origin of recurrence

Purpose To determine whether photodynamic therapy (PDT) has a vaso-occlusive effect on the branching vascular network in polypoidal choroidal vasculopathy (PCV) and whether PDT can prevent future recurrence. Methods We analyzed pre-and post-PDT indocyanine green angiography (ICGA) results of 27 patients (27 eyes) who were diagnosed with PCV and who had shown clinical improvement accompanied by occlusion of polypoidal lesions after PDT. We also investigated the recurrent events in these patients and the origin of the recurrences. Results The branching vascular network persisted, at least in part, in 20 (87%) of 23 eyes undergoing one PDT session and in two (50%) of four eyes undergoing two PDT sessions. In the remaining five eyes, we could not determine definitively whether the branching vessels were occluded completely. Recurrent serous changes occurred in nine eyes (33%) 14–48 months after the last PDT. ICGA revealed that these changes were caused by new polypoidal lesions that originated from further-grown branches of the persistent branching vascular network. Diffuse leakage from undetermined sources seemed to coexist in two eyes. Conclusions PDT cannot induce complete occlusion of the branching vascular network. PDT does not prevent future recurrence, because new active polypoidal lesions may develop from the persistent branching vessels in the network.     

Clinical features, management and visual outcome of polypoidal choroidal vasculopathy in Indian patients

Aims:

To present the clinical, indocyanine green angiography (ICGA) features and results of treatment for polypoidal choroidal vasculopathy (PCV) in Indian patients by a retrospective chart review.

Materials and Methods:

Forty five patients with PCV underwent complete ocular examination, fluorescein angiography (FFA) and ICGA. Treatment was advised for patients with macular involvement and progressive loss of visual acuity. Demographic data, clinical features and results of treatment were analyzed.

Results:

Mean age at presentation was 61.06 years. Mean follow up was 18 months. The disease was more prevalent in males. Forty three patients had unilateral disease. The most common location of polyps in ICGA was subfoveal (42.5%). Exudative form was seen in 34 of the 47 eyes and the remaining 13 eyes had a hemorrhagic presentation. Thirty four eyes underwent treatment which included thermal laser (n = 11), photodynamic therapy (PDT) (n = 11) and transpupillary thermo therapy (TTT) (n = 12). Statistical analysis was done using the Chi-square test. Subgroup analysis of visual outcome following various modalities of treatment showed that the results of PDT (P < 0.001) and thermal laser (P < 0.001) were statistically significant.

Conclusions:

PCV is an important differential diagnosis in patients presenting with serosanginous maculopathy and submacular hemorrhage. The disease was more prevalent in males and was unilateral in the Indian population. Timely intervention in cases with symptomatic polyps could achieve stabilization of visual acuity. Thermal laser and PDT were safe and effective.     

Intravitreal bevacizumab and ranibizumab injections for patients with polypoidal choroidal vasculopathy

Purpose

To compare the effectiveness of intravitreal injection of bevacizumab and ranibizumab in patients with treatment-naïve polypoidal choroidal vasculopathy (PCV).

Methods

A total of 66 and 60 eyes of 121 consecutive patients who received intravitreal bevacizumab (1.25 mg) or ranibizumab (0.5 mg) injection for treatment of PCV were retrospectively reviewed. After initial three loading injections by month, injection was performed as needed. Main outcome measures included best corrected visual acuity (BCVA), foveal center thickness (FCT) as assessed by spectral domain optical coherence tomography (SD-OCT), and change in polypoidal lesion on indocyanine green angiography (ICGA).

Results

At 12 months, average number of injections was 4.72±1.84 in the bevacizumab group and 5.52±1.54 in the ranibizumab group. Mean logarithm of the minimum angle of resolution of BCVA from baseline at 12 months after injection improved by 0.11 in the bevacizumab group (P=0.02) and by 0.14 in the ranibizumab group (P=0.01). Average FCT decreased from 368±62.48 to 298±40.77 μm in the bevacizumab group (P=0.01) and from 371±50.79 to 286±36.93 μm in the ranibizumab group (P=0.01). Polyp regression rate was 24.2% (16 eyes out of 66 eyes) in the bevacizumab group and 23.3% (14 eyes out of 60 eyes) in the ranibizumab group. There was no statistically significant difference in BCVA improvement achieved, FCT improvement achieved, and polyp regression rate between groups.

Conclusion

Intravitreal injections of bevacizumab and ranibizumab have similar effects in stabilization of visual acuity, macular edema, and regression of polypoidal complex with PCV eyes.     

Chorioretinal anastomosis after photodynamic therapy for polypoidal choroidal vasculopathy

An 80-year-old woman was treated with photodynamic therapy (PDT) to the left eye for polypoidal choroidal vasculopathy (PCV). About 3 months after PDT, her left eye developed a chorioretinal anastomosis with severe atrophy of the retinal pigment epithelium in the macula; visual acuity in this eye was 20/1000. She received a second session of PDT, plus an intravitreal injection of triamcinolone acetonide. About 3 months after the second treatment, the chorioretinal anastomosis was enlarged and the retinal vessels involved in the anastomosis were more dilated. About 1 year after the first PDT, visual acuity in the left eye had stabilized at 20/400. Development of a chorioretinal anastomosis is a distinct possibility following PDT in eyes with PCV, and can lead to poor visual recovery.