Intravitreal triamcinolone with photodynamic therapy for subfoveal choroidal neovascularisation in age related macular degeneration

AIMS: To report the effects of intravitreal triamcinolone acetonide (iTAAC) injections as an adjunctive treatment to photodynamic therapy (PDT) with verteporfin for new subfoveal choroidal neovascularisation (CNV) in age related macular degeneration (AMD). METHODS: We retrospectively reviewed the records of all AMD patients who had iTAAC within 6 weeks of their first PDT and had a follow up of one year or longer. The proportion of eyes after one year follow up that lost or gained >or=15 and >or=30 ETDRS letters, baseline and one year lesion greatest linear dimension (GLD), number of PDTs, and side effects were assessed. RESULTS: Fourteen patients were evaluated. Eleven received one initial combined treatment and three received an additional combined treatment after 6 months. Median follow up was 18 months (range 12 to 25 months). Overall, 7% gained >or=30 letters, 50% maintained stable vision, 14% lost 15-29 letters, and 29% lost >or=30 letters. Overall, mean GLD increased from 2580 (SD 1088) microm to 3946 (SD 1503) micro m (p = 0.01). The mean number of PDTs during the first year was 2.57. Side effects were mild intraocular pressure elevation in 28.5% and cataract progression in 50% of phakic eyes. CONCLUSIONS: iTAAC with PDT in AMD was found to be relatively safe and had reasonable results for lesions with some classic component.     

Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of subfoveal choroidal neovascularisation in age related macular degeneration: a comparative study

AIM: To evaluate the outcomes of combined intravitreal triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) caused by age related macular degeneration (AMD). METHODS: 48 eyes from 48 patients with subfoveal CNV caused by AMD were prospective recruited, with 24 eyes treated with combined PDT with IVTA and compared with a control group of 24 eyes which received PDT monotherapy. In the combined treatment group, IVTA was performed immediately after PDT as an outpatient procedure. The mean number of treatments, mean logMAR best corrected visual acuity (BCVA), mean line of visual acuity changes, and proportion of patients without moderate visual loss at 1 year were compared between the combined and monotherapy groups. RESULTS: At 1 year the logMAR BCVA for the PDT with IVTA group changed from 0.88 to 0.95 (p = 0.32 compared with baseline), whereas the logMAR BCVA for the monotherapy group reduced from 0.74 to 1.09 (p<0.001 compared with baseline). A significantly higher proportion of patients who had PDT with IVTA did not develop moderate visual loss at 1 year compared with the monotherapy group (70.8% and 33.3% respectively, p = 0.009). Eyes which had combined treatment had significantly fewer lines lost compared with monotherapy alone (0.7 and 3.5 lines respectively, p = 0.015). Subgroup analysis showed that PDT with IVTA is effective in preventing visual loss in both predominately classic and occult CNV groups. The mean number of treatments for the combined and monotherapy groups was 1.5 and 1.96 respectively (p = 0.076). CONCLUSIONS: Combined PDT with IVTA appeared more effective statistically at 12 months for stabilisation of vision (<3 logMAR lines change) compared with PDT monotherapy. Further randomised control trials might be justified to conclude the efficacy of PDT with IVTA.     

Verteporfin photodynamic therapy for extrafoveal choroidal neovascularisation secondary to age-related macular degeneration

PURPOSE: To report the results of verteporfin photodynamic therapy (PDT) of extrafoveal predominantly classic choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). METHODS: In this retrospective study 20 consecutive patients (20 eyes) undergoing verteporfin PDT for extrafoveal predominantly classic CNV in AMD were examined. Colour photography of the fundus, fluorescein angiography and complete ophthalmic examination, including visual acuity assessment with ETDRS charts, were performed before treatment and at 3-month intervals thereafter. The primary outcome criterion was the change in visual acuity. The secondary outcome criterion was the extension of the CNV beneath the centre of the fovea during the follow-up period. RESULTS: Mean follow-up time of the patients was 24.2 months (range 12 to 58 months). Visual acuity at baseline varied from 20/200 to 20/20 (mean 20/50+/-2.3 lines). Final visual acuity ranged from 20/1000 to 20/20 (mean 20/200+/-5.1 lines) (P<0.001). In 85% (17/20) of the eyes visual acuity worsened. Visual acuity improved in 15% (3/20) of the eyes. During the course of the follow-up period, subfoveal extension of the CNV was detected in 80% (16/20) of the eyes. CONCLUSION: In 85% of the eyes with extrafoveal predominantly classic CNV secondary to AMD, visual acuity worsened after verteporfin PDT in an average follow-up time of 24 months. Subfoveal CNV was found in 80% of the eyes during follow-up. Even though verteporfin PDT can preserve visual acuity in selected cases, deterioration was seen in the majority of the patients.     

Long term results of radiotherapy for subfoveal choroidal neovascularisation in age related macular degeneration

BACKGROUND/AIMS: Radiotherapy has been proposed as an alternative treatment for patients with subfoveal choroidal neovascularisation (CNV) that is untreatable according to macular photocoagulation study guidelines. This prospective study was designed to evaluate whether radiotherapy may affect the functional and anatomical outcome in a large cohort of patients affected by subfoveal CNV, with a follow up period up to 24 months. METHODS: 212 patients (231 eyes) with newly diagnosed subfoveal CNV not amenable to laser therapy were included in this study. Two radiotherapy methods, the lateral beam technique (6 MV, 20 Gy in five fractions) and lateral arc therapy (25 MV, 16 to 20 Gy, in four or five fractions), were used. Comparisons of best corrected visual acuity (VA), fluorescein (FA) and indocyanine green (ICG) angiography, at inclusion and 6, 12, 18, and 24 months after radiotherapy were performed using univariate analysis. RESULTS: A VA improvement of two or more lines was observed in 34% at 12 months, 31% at 18 months, and 32% of the eyes at 24 months. Paired comparisons of CNV areas in FA and ICG showed no significant change between baseline and each visit. However, 12 and 18 months after treatment, 47% of the eyes showed a decrease of 10% or more in CNV size both in ICG and FA. Radiation side effects included radiation retinopathy (eight eyes), optic neuropathy (four eyes), choroidal vasculopathy (five eyes), and branch retinal vein occlusion (three eyes). CONCLUSION: Compared with the natural course of subfoveal CNV, the results of this prospective study suggest that radiotherapy could stabilise visual and anatomical outcome in selected cases.     

Using optical coherence tomography to monitor photodynamic therapy in age related macular degeneration

PURPOSE: To evaluate the role of optical coherence tomography (OCT) in determining choroidal neovascularization (CNV) activity before and after photodynamic therapy (PDT) in patients with age-related macular degeneration (ARMD). DESIGN: Prospective observational case series. METHODS: SETTING: Institutional study. patient population: Fifty-three patients (62 eyes) with ARMD. OBSERVATION PROCEDURE: Prospective observational case study. MAIN OUTCOME MEASURES: Presence or absence of leakage on fluorescein angiography, presence of intraretinal or sub-retinal fluid on OCT, and macular and choroidal neovascular complex thickness on OCT. RESULTS: The macular thickness decreased significantly after PDT (P = .001). However, no significant changes in CNV thickness were measured after PDT (P = .567). Once the diagnosis of ARMD was established before treatment, OCT had a sensitivity of 96.77% for detecting CNV activity. After treatment, OCT had a good sensitivity (95.65%) and a moderate specificity (59.01%) in determining CNV activity, which resulted in a diagnostic efficiency (proportion of correct results) of 82.95%. CONCLUSIONS: OCT appears to be useful for indicating CNV activity. Therefore, it may serve as a complementary technique for deciding the need for PDT and re-treatment in patients with ARMD.     

Angiographic features after photodynamic therapy for choroidal neovascularisation in age related macular degeneration and pathological myopia

AIM: To describe the angiographic features after photodynamic therapy (PDT) with verteporfin in choroidal neovascularisation (CNV) associated both with age related macular degeneration (AMD) and pathological myopia (PM). METHODS: 36 patients affected by subfoveal CNV in AMD and 25 patients with subfoveal CNV in PM underwent an ophthalmological examination including fluorescein angiography (FA) and indocyanine green angiography (ICGA) using the IMAGEnet System. Post-PDT examinations were performed 7, 30, and 90 days later. RESULTS: The typical angiographic aspect after PDT for AMD related CNV was a round hypofluorescence visible both on FA and on ICGA, which included both CNV and the surrounding tissues and corresponded to the area exposed to laser light. In PM the CNV appeared hypofluorescent during the early phases and gradually became hyperfluorescent during the late phases on FA, whereas on ICGA it was detectable in its whole extension as a hyperfluorescent lesion since the early phases. Differently from AMD, there was no round hypofluorescence surrounding the CNV on FA or on ICGA. Moreover, five patients in the AMD group showed hot spots on ICGA, which spontaneously disappeared during the follow up. Classic and occult components of the AMD related CNV revealed a different angiographic response to PDT, showing with the latter only a partial closure 1 week after PDT followed by a complete reopening at the first month in 100% of cases. CONCLUSION: The post-PDT hypofluorescence typical of AMD related CNV, especially visible on FA, might be secondary to a combination of choriocapillary occlusion and masking effect due to swelling of retinal pigment epithelium cells. Hot spots in the AMD affected patients could be interpreted as the expression of a non-thermal choroidal vasculitis secondary to PDT.     

Radiotherapy for isolated occult subfoveal neovascularisation in age related macular degeneration: a pilot study

BACKGROUND/AIMS: Teletherapy has been proposed as a possible treatment for choroidal neovascular membranes (CNV), secondary to age related macular degeneration (AMD) not amenable to laser photocoagulation. The aim of this prospective study has been to investigate the effect of teletherapy on isolated occult choroidal neovascular membranes of subfoveal location. METHODS: 28 AMD patients presenting with retrofoveal isolated occult CNV demonstrated by fluorescein angiography were treated by external beam radiation. A complete ophthalmological examination, fluorescein angiography, and indocyanine green angiography (ICG) were performed within 15 days before treatment and repeated at follow up. A total dose of 16 Gy was applied in four sessions of 4 Gy using a 4 MeV photon beam. Follow up ranged from 6 to 9 months (mean follow up 6.4 months). RESULTS: Visual acuity was found to be stable in 68% of the cases. The decrease in visual acuity was of 3-6 lines in 18% and of more than 6 lines in 10% of the eyes at last examination. On fluorescein angiography the size of the lesion area was found to be stable in 67%, decreased in 13%, and increased in 20% of the cases. On ICG angiography the size of the CNV was stable in 93% and increased in 7% of the cases. All the eyes experiencing a visual acuity decrease showed either no change or an increase in size of the membrane on fluorescein angiography and/or on ICG. CONCLUSION: According to this study with strict inclusion criteria, external beam radiotherapy seems to have a beneficial effect on the evolution of isolated occult subfoveal CNV.     

Electrophysiological changes after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in age related macular degeneration

AIM: To evaluate electrophysiological changes after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in patients with age related macular degeneration (AMD). METHODS: A consecutive series of 32 patients suffering from subfoveal choroidal neovascularisation secondary to AMD underwent 360 degrees retinotomy and macular translocation. The ERG served as the main parameter of the study and was recorded 1 day before the translocation surgery and no earlier than 4 weeks after the silicone oil removal. RESULTS: The scotopic ERG amplitudes were significantly reduced after translocation surgery. Depending on the applied flash luminance the mean b-wave amplitude reduction of the scotopic ERG varied between 67% (0.2 cd.s/m2) and 74% (0.03 cd.s/m2). The a-waves and b-waves of the saturating light response decreased significantly by 46% and 59%, respectively. The photopic a-wave and b-wave amplitudes were significantly lower after the translocation surgery resulting in a mean reduction of 27% and 43%, respectively. CONCLUSIONS: Although macular translocation may provide the potential of preserving and even restoring vision in patients with subfoveal choroidal neovascular membranes secondary to AMD the present study indicates that a significant electrophysiological decrease is caused by surgical procedures associated with this technique. Further research is necessary to clarify if certain modifications of the surgical procedure are able to substantially reduce the neuroretinal trauma.     

Radiotherapy for recurrent choroidal neovascularisation complicating age related macular degeneration

AIMS: To report the safety and visual outcome data of external beam irradiation for recurrent choroidal neovascularisation complicating age related macular degeneration. METHODS: Eighteen consecutive eyes received external beam irradiation with seven fractions of 2 Gy (total dose 14 Gy). The next 16 consecutive eyes received external beam irradiation with five fractions of 3 Gy (total dose 15 Gy). Main outcome measure was change in visual acuity. Secondary outcome variables were contrast sensitivity and fundus photographic/fluorescein angiographic progression. RESULTS: The 3 Gy fraction group lost fewer lines of distance visual acuity at the three and six month follow up. At one year follow up, this difference was not maintained with 2 Gy fraction and 3 Gy fraction eyes. At one year follow up a decrease in visual acuity of three or more lines (moderate visual loss) occurred in 58% of 2 Gy and 42% of 3 Gy fraction eyes (p<0.36). At one year follow up a decrease in visual acuity of six or more lines (severe visual loss) occurred in 41% of 2 Gy eyes and 17% of 3 Gy eyes (p<0.23). At three months follow up, 3 Gy eyes were less likely (0%) than 2 Gy eyes (47%) to show moderate visual loss (p<0.003). However, Kaplan Meier curves estimate a significantly lower rate of severe visual loss in the 3 Gy group (p = 0.02). There were no significant differences in contrast sensitivity loss or fluorescein angiographic stabilisation rates. No evidence of radiation toxicity was observed. CONCLUSION: Our results are consistent with trends for a palliative benefit with higher fraction sizes and doses. The radiobiologic differences between low and high fraction size groups in this study are modest and correlate with the modest and short term difference in visual outcomes. These trends support further investigation of radiotherapy using fraction sizes of 4 Gy or higher.     

Optical coherence tomography following photodynamic therapy with verteporfin for subfoveal predominantly classic choroidal neovascularization

We characterized the changes in optical coherence tomography following photodynamic therapy (PDT) for subfoveal predominantly classic choroidal neovascularization (CNV) in 26 eyes before, 1 week after, and 3 months after treatment. There appears to be a temporal decrease in central retinal thickness, increase incentral retinal pigment epithelium/CNV complex thickness, and decrease in subretinal fluid following PDT, making it a useful adjunct in the management of CNV due to of age-related macular degneration. The authors have stated that they do not have a significant financial interest or other relationship with any product manufacturer or provider of services discussed in this article. The authors also do not discuss the use of off-label products, which includes unlabeled, unapproved, or investigative products or devices.     

Phase I clinical trial results of verteporfin enhanced feeder vessel therapy in subfoveal choroidal neovascularisation in age related macular degeneration

AIMS: To investigate the safety and effectiveness of extrafoveal photodynamic therapy (PDT) occlusion of feeder vessels (FVs) in patients with subfoveal choroidal neovascularisation (CNV) as a result of age related macular degeneration. METHODS: FVs were identified using dynamic fluorescein and indocyanine green angiography with scanning laser ophthalmoscope. The standard doses of verteporfin and laser wavelength were used. The light dose was escalated by increasing the duration of the light dose so the light regimen was 50 J/cm2 for patients 1 and 2; 100 J/cm2 for patients 3, 4, 5; 125 J/cm2 for patients 6 and 7; and 150 J/cm2 for patients 8 and 9. Patients were examined at weeks 1, 4, and 12. RESULTS: The mean improvement on EDTRS chart 3 months after treatment was an increase of 2.1 lines (p = 0.07). Closure of the FV was achieved angiographically in three eyes at various light doses, in three eyes the FV was hypoperfused, and in three eyes the vessels were were neither closed nor hypoperfused. At the last follow up all FVs were reperfused. There was no evidence of retinal damage. CONCLUSION: Verteporfin enhanced FV therapy does not cause subfoveal retinal damage and may have potential to improve central vision in subfoveal CNV caused by exudative macular degeneration. It is not recommended as a monotherapy for CNV.     

Verteporfin photodynamic therapy in highly myopic subfoveal choroidal neovascularisation

AIMS: To analyse the visual and angiographic results of photodynamic therapy (PDT) with verteporfin in highly myopic patients with subfoveal choroidal neovascularisation (CNV). METHODS: PDT was performed on highly myopic patients with subfoveal CNV. The patient population was divided into two groups according to age at onset of CNV (group 1 aged < or = 55 and group 2 aged >55 years old). Best corrected visual acuity (BCVA) and angiographic findings were considered. RESULTS: At the end of follow up group 2 had worse BCVA than group 1. 76% of patients in both groups showed a complete closure of CNV at the end of follow up. CONCLUSION: Visual prognosis of myopic CNV treated by PDT is influenced by age at onset.     

The cost-effectiveness of photodynamic therapy for fellow eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: Photodynamic therapy (PDT) has recently been demonstrated to be beneficial for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). Herein, we determine the cost-effectiveness of PDT for the treatment of subfoveal choroidal neovascularization (CNV) in patients with disciform degeneration in one eye and whose second and better-seeing eye develops visual loss secondary to predominantly classic subfoveal CNV. The analysis was performed from the perspective of a for-profit third-party insurer. DESIGN: Cost-utility Markov models were created to determine the cost-effectiveness of PDT under two different scenarios, by using efficacy data derived from the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study and patient-based utilities. METHODS: Decision analyses were performed by incorporating data from the TAP Study, expected longevity data, and patient-based utilities. Cost-effective models were then created by incorporating incremental medical costs. Various sensitivity analyses were carried out to determine the robustness of our models. A Monte Carlo simulation was also used to determine whether there was a significant difference in quality-of-life adjusted years (QALYs) gained between PDT therapy and the placebo. RESULTS: For the hypothetical patient whose second and better-seeing eye becomes affected and who has 20/40 vision at baseline in this affected eye (base case 1), PDT was associated with a 10.7% relative increase in their quality-of-life (treatment conferred an additional undiscounted 0.1342 QALYs over a 2-year period). For the hypothetical patient whose second and better-seeing eye becomes affected and who has 20/200 vision at baseline in this affected eye (base case 2), PDT was associated with a 7.8% relative increase in their quality-of-life (treatment conferred an additional undiscounted 0.0669 QALYs over a 2-year period). Sensitivity analysis showed our models were robust and that PDT was usually the dominant treatment choice. Our cost-effective model demonstrated that the cost for a QALY was $86,721 (US dollars discounted at 3%) for base case 1, assuming 5.5 treatments; and $173,984 (USD discounted at 3%) for base case 2. CONCLUSIONS: PDT will cost a third-party insurer $86,721 for an AMD patient with 20/40 vision in the better-seeing eye to obtain one QALY and $173,984 for an AMD patient with 20/200 vision in the better-seeing eye to obtain one QALY. PDT can be considered to be a treatment that is of only minimal cost-effectiveness for AMD patients who have subfoveal CNV in their second and better-seeing eyes and who have good presenting visual acuity at baseline. It is a cost-ineffective treatment for AMD patients who have poor visual acuities in their affected better-seeing eyes.     

光动力学疗法治疗AMD后OCT检查的特征性改变

目的：通过前瞻性观察PDT治疗湿性年龄相关性黄斑变性（aged-related macular degeneration,AMD）前后不同随访时间点光学相干断层成像（optical coherence tomography, OCT）的特征性改变,旨在更好地反馈PDT治疗后黄斑区结构的变化过程。方法：将在本院接受PDT治疗的26例30眼湿性AMD患者纳入本研究。维速达尔用量根据厂家推荐方法计算。治疗前后均行FFA,ICG,OCT及最佳矫正视力等相关临床检查,术后随访日期为术后2wk; 1,2,3mo。傅立叶OCT扫描以标准五线结合六线扫描,覆盖病变的关键部位并保持前后扫描位置的一致性。重点观察黄斑中心凹层间厚度、外层高反射带高度、囊肿（包括视网膜下积液和视网膜内积液）的总面积。分析这些变化与随访时间的依赖关系。统计分析使用SPSS 13.0软件。结果：至治疗后3mo,PDT治疗后22眼（73%）视力提高两行以上,3眼视力无明显改变,3眼视力下降,2例患者因故失访。视力提高的22眼治疗前平均黄斑厚度为 722.5±55.6μm,治疗后2wk,平均黄斑层间厚度为708.3±45.3μm,1mo 为584.4±49.3μm,2mo为430.7±50.2μm,3mo为 180.6±36.3μm。治疗前和治疗后外层高反射带厚度分别为302.3±50.2,277.5±42.3,202.7±40.1,180.6±35.7,100.8±22.9μm,囊肿的总面积为0.34±0.12,0.25±0.07,0.10±0.05,0.08±0.04,0.05±0.01mm2。结论：AMD患者在PDT治疗后1mo黄斑区视网膜下液有显著吸收,视网膜水肿显著吸收,黄斑中心凹层间厚度、外层高反射厚度也有明显变薄倾向。     

经瞳孔温热疗法治疗老年性黄斑变性中心凹下新生血管

目的探讨经瞳孔温热疗法(transpupillarythermotherapy,TTT)治疗老年性黄斑变性中心凹下新生血管的安全性及疗效。方法应用810nm激光对53例(62眼)经FFA或ICG确诊的AMD黄斑中心凹下CNV进行TTT治疗。每个光斑的照射时间为60s,激光能量为120~150mW/mm光斑直径。以矫正视力、眼底及FFA改变评价疗效。末次治疗后随诊3~15月,平均7.5月。结果末诊时,62眼共接受151次TTT治疗,平均治疗2.4次。视网膜出血完全吸收者46眼(74.19%),大部分吸收者5眼(8.06%),部分吸收者5眼(8.06%),复发性出血者6眼(9.68%)。视力提高者16眼(25.81%),不变者42眼(67.74%),下降者4眼(6.45%);其中视力低于0.1者30眼(48.39%),0.1~0.3者27眼(43.55%),>0.3者5眼(8.06%)。结论TTT是一种安全的治疗AMD黄斑中心凹下CNV的方法,能有效地促进视网膜出血吸收和CNV癍痕化,使大部分患者的视力保持稳定,但对视力的提高作用不明显。