Intravitreal bevacizumab (Avastin®) for neovascular age‐related macular degeneration in treatment‐naive patients

Purpose: To report the effects of intravitreal bevacizumab (Avastin^®) in treatment‐naive patients with exudative age‐related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity. Methods: A prospective, uncontrolled, pilot study of 26 eyes of 26 patients, all previously treatment‐naive to photodynamic therapy, argon laser or anti‐vascular endothelial growth factor (VEGF), were treated with one or more intravitreal injections of 1.25 mg bevacizumab. Of the 26 patients, 15 (57.7%) had occult choroidal neovascularization (CNV), 6 (23.1%) had predominantly classic CNV and 5 (19.2%) had minimally classic CNV. Ophthalmic outcome measures included changes in standardized Early Treatment Diabetic Research Study (ETDRS) VA, contrast sensitivity and OCT. The patients were examined at baseline and 1 week, 6 weeks, 3 months and 6 months after the first injection. Re‐treatment was given on an ‘as needed’ basis. Results: Twenty‐four eyes of 24 patients completed 6 months of follow‐up. Two patients chose to discontinue the study. Mean ETDRS VA score improved from 55 letters at baseline to 60 letters at 1 week (P < 0.01) and to 61 letters at 6 weeks (P < 0.01). No significant improvement in VA from baseline was found after 3 and 6 months. Patients with pigment epithelial detachment (PED) had a significantly worse outcome in VA at 6 months. Contrast sensitivity improved from baseline to 3 or 6 months, but this improvement was not statistically significant. Mean macular thickness decreased significantly from baseline to all follow‐up examinations (P < 0.01). Conclusion: Mean ETDRS VA improved significantly after 1 and 6 weeks; thereafter, it remained stable throughout the study period. Macular thickness improved significantly at all time points. The results indicate that 1.25 mg intravitreal bevacizumab is associated with functional as well as morphological improvement among treatment‐naive ARMD patients.     

抗血管内皮生长因子单克隆抗体Ranibizumab治疗渗出型老年性黄斑变性临床观察

目的 观察抗血管内皮生长因子单克隆抗体Ranibizumab(Lucentis)玻璃体腔注射治疗渗出型老年性黄斑变性（AMD）的临床疗效和安全性。 方法 回顾分析以糖尿病早期治疗研究(ETDRS)视力表、彩色眼底像、荧光素眼底血管造影（FFA）和（或）吲哚青绿血管造影（ICGA ）、光相干断层扫描（OCT）等检查确诊的渗出型AMD 56只眼，采用玻璃体腔注射Ranibizum ab 0.5 mg的方法进行治疗的临床随访资料。治疗前56只患眼ETDRS视力表字母数为25.1个 ，FFA和（或）ICGA检查均有脉络膜新生血管（CNV）渗漏，OCT检查视网膜厚度平均为303.45 μm。Ranibizumab注射治疗次数2～8次，平均治疗次数为3.1次。治疗后随诊时间6～12个月，平均随诊时间8.7个月。回顾分析时，对比分析患者治疗前以及治疗后1、3、6、9、12个月的视力 （ETDRS字母数）、视网膜厚度、CNV病灶渗漏情况以及手术并发症。 结果 56只眼治疗后末次随诊检查时，ETDRS视力表字母数平均为38.5个，字母数较治疗前提高13.4个（t=-3.193，P＜0.01）。其中，视力提高≥15个字母数者22只眼，占39.3%；视力下降>15个字母数者2只眼，占3.6% 。 视网膜厚度平均为191.35 μm，较治疗前下降112.1 μm （t=5.193，P＜0.01）。 CNV渗漏停止者12只眼，占21.4%；渗漏减少者33只眼，占58.9%；无明显改变者9只眼，占16.1%；新发生病灶1只眼，占1.8%。治疗后5只眼有短暂视物模糊，3只眼有轻度眼压升高等不良反应 ，均在1周内消失。 结论 Ranibizumab玻璃体腔注射治疗渗出型AMD可使视力提高，视网膜水肿明显减轻，CNV病灶渗漏停止或减少，安全性高。  (中华眼底病杂志，2008，24：160-163)     

Transpupillary thermotherapy of occult CNV with no or minimally classic CNV in age-related macular degeneration

Transpupillary thermotherapy (TTT) has been suggested as a putative treatment for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). This prospective study comprised 66 consecutive patients referred for exudative AMD with predominantly occult subfoveal CNV. Based on fluorescein angiography, there were 38 cases with occult CNV only, and 28 eyes with minimally classic CNV as well. Visual acuity was determined using the logarithmic ETDRS chart. For TTT a diode laser (810 nm) with a power of 800 mW or 500–600 mW for a 3.0 mm spot was used (duration 60 sec.). Follow-up included clinical examination with biomicroscopy and fluorescein angiography at 2–3 months and 6 months in all cases. In the entire case material (n = 66), the mean visual acuity was preoperatively 20/125 (47.4 letters) and postoperatively 20/160 (41.8 letters) yielding a decay of 5.6 letters (“one line”). Visual acuity improved in 8 cases (12.1%), deteriorated in 17 (25.8%), and remained stable in 74.2%. In purely occult CNV visual acuity remained stable in 81.6% as compared to 64.3% in occult & minimally classic CNV; the former subgroup lost on the average 3.6 letters, the latter 8.3 letters (close to “two lines”) over 6 months. The proportion of eyes losing at least 15 letters was 13.2% in purely occult CNV versus 35.7% in the occult & minimally classic subgroup. In 39 of 66 cases (59.1%) fluorescein leakage regressed to staining only concomitant with absorption of subretinal fluid. Complications associated with deterioration of visual acuity (17 cases) included postoperative hemorrhage, increase of exudation on angiography, and progressive fibrosis. The results indicate that TTT stabilizes visual acuity concomitant with regression of exudation and resorption of subretinal fluid in the majority of cases with predominantly occult CNV. Cases with occult CNV only seem to do better than those with minimally classic CNV as well. The safety and complication rate appear to be acceptable. A randomized controlled trial is in progress.     

Intravitreal triamcinolone for choroidal neovascularization in ocular histoplasmosis syndrome

PURPOSE: To report the effects of intravitreal triamcinolone acetonide injections for subfoveal and juxtafoveal choroidal neovascularization (CNV) in ocular histoplasmosis syndrome. METHODS: In a retrospective analysis, the proportion of eyes that gained >or=5 or lost >or=5 and >or=15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, best-corrected visual acuity using ETDRS letter score (VA), greatest linear dimension (GLD), and treatment side effects were assessed. RESULTS: Ten patients (five subfoveal, five juxtafoveal CNV; median follow-up: 17 months; range, 6-41 months) were evaluated. Thirty percent gained >or=5 letters, 20% lost 5 to 14 letters, and 50% maintained stable VA. Overall, mean VA and GLD remained stable. Side effects were transient intraocular pressure elevation and mild cataract development. CONCLUSIONS: Intravitreal triamcinolone acetonide for CNV resulting from OHS was found to be relatively safe and showed good visual outcome for both subfoveal and juxtafoveal CNV. Further studies are warranted to evaluate this treatment.     

Efficacy and safety of recombinant tissue plasminogen activator and gas versus bevacizumab and gas for subretinal haemorrhage

Purpose: To report the 12 months efficacy of initial intravitreal bevacizumab or intravitreal recombinant tissue plasminogen activator (rtPA) combined with expansile gas in patients with subretinal haemorrhage caused by neovascular age‐related macular degeneration (AMD). Methods: Forty‐five eyes of 45 patients with subretinal haemorrhage (1–5 disc diameters) involving the fovea secondary to neovascular AMD were evaluated retrospectively consecutively. Thirty‐two eyes underwent treatment with rtPA (50 μg/0.05 ml) combined with intravitreal sulphur hexafluoride (SF6). The other 13 eyes were treated with bevacizumab (1.25 mg/0.05 ml) and SF6. Thereafter, all patients received Vascular Endothelial Growth Factor (anti‐VEGF) treatment according to modified PrONTO criteria. Main outcome was change of best‐corrected visual acuity (VA) at 12 months as determined by Early Treatment Diabetic Retinopathy (ETDRS). Results: There was more improvement in patients initially treated with rtPA and gas (14 letters; bevacizumab and gas eight letters) and not suffering from adverse events. The incidence of vitreous haemorrhages was significantly higher in the rtPA group (nine of 32 versus one of 13, p < 0.01). In both groups, an average of 3.5 anti‐VEGF injections were performed per patient during 12 months (no difference between both groups). Conclusion: Both initial treatment regimen lead to improved functional results after 1 year. However, patients, not suffering from adverse events, who underwent initial treatment with rtPA and gas showed better results. To maintain VA, controlling neovascular AMD by anti‐VEGF treatment regime after initial treatment with rtPA+gas is important for all cases.     

Intravitreal triamcinolone,bevacizumab and pegaptanib for occult choroidal neovascularization

Acta Ophthalmol. 2010: 88: e305–e310

Abstract.

Purpose: To evaluate best‐corrected visual acuity (BCVA) and foveal thickness (FT) changes in occult subfoveal choroidal neovascularization (CNV) from age‐related macular degeneration (AMD) after intravitreal bevacizumab (IVB, 1.25 mg/0.05 ml), pegaptanib (IVP, 0.3 mg/0.09 ml) and triamcinolone acetonide (IVTA, 4 mg/0.1 ml) injected on an as needed basis. Methods: Retrospective, interventional, comparative study. BCVA (Early Treatment Diabetic Retinopathy Study LogMAR) and FT by optical coherence tomography (OCT) were evaluated during 12 months from first treatment. Patients were retreated if signs of neovascular activity were still present on angiography or OCT. Results: Forty‐eight eyes received IVB, 43 eyes received IVP, 52 eyes received IVTA. BCVA and FT at baseline were 1.22 ± 0.49 LogMAR and 410.2 ± 41.83 μm in the IVB group, 1.25 ± 0.43 LogMAR and 452.3 ± 44.83 μm in the IVP group and 1.31 ± 0.4 LogMAR and 456.6 ± 48.27 μm in the IVTA group. BCVA and FT improved in the three groups during follow‐up. A significantly greater improvement of BCVA was present at month‐3, month‐6 and at month‐12 in the IVB and IVP groups (p = 0.01). Improvement of FT was greater in the IVTA group at month‐3 (p = 0.02), while it was greater in the anti‐Vascular Endothelial Growth Factor (VEGF) groups at month‐6 and month‐12 (p = 0.01). A postoperative increase of intraocular pressure was detected in 9/52 (17.3%) eyes treated with IVTA, and in two cases it was resistant to topical therapy. Conclusion: Intravitreal injection of anti‐VEGF drugs administered on an as needed basis for AMD‐related occult CNVs provided functional and anatomic improvement during 12 months of follow‐up.     

抗血管内皮生长因子单克隆抗体ranibizumab治疗渗出型老年性黄斑变性方案的探讨

目的 观察抗血管内皮生长因子（VEGF）单克隆抗体ranibizumab（商品名Lucentis）玻璃体腔注射治疗渗出型老年性黄斑变性（AMD）的临床疗效。方法 回顾分析临床确诊为渗出型AMD并接受玻璃体腔注射ranibizumab治疗的46例患者52只眼的临床资料。患者均进行了糖尿病早期治疗研究（ETDRS）视力表、检眼镜、荧光素眼底血管造影（FFA）和（或）吲哚青绿血管造影（ICGA）以及光相干断层扫描（OCT）检查。确诊渗出型AMD后,采用10 mg/ml的 ranibizumab 0.05 ml玻璃体腔注射治疗。每一个月注射1次,连续注射3次,随后根据每一个月的检查情况决定是否进行再次注射。52只眼共注射214次,每一只眼注射2~6次,平均注射4.12次。随访观察12个月。对比分析治疗前后视力、视网膜厚度及脉络膜新生血管（CNV）病灶渗漏变化情况。结果 治疗后12个月,52只眼ETDRS视力表的平均字母数是37.8个,较治疗前提高11.4个（t=-3.475,P＜0.01）。CNV病灶渗漏完全停止11只眼,占21.2%;渗漏范围明显减少34只眼,占65.4%;渗漏无明显变化者4只眼,占7.7%;病灶增大2只眼,占3.8%;新病灶出现1只眼,占1.9%。OCT检查显示,视网膜厚度平均值为187.50 μm ,较治疗前下降122.80 μm（t=4.593,P＜0.01）。结论 按治疗方案进行的ranibizumab玻璃体腔注射治疗渗出型AMD可使视力提高、视网膜水肿明显减轻、CNV病灶渗漏停止或减少。      

Optical coherence tomography analysis of bilateral end-stage choroidal neovascularization where one eye is treated with photodynamic therapy

BACKGROUND: To compare retinal thickness and subretinal hyper-reflectivity using Stratus optical coherence tomography (OCT3) between the eyes of patients with bilateral end-stage exudative age-related macular degeneration (AMD), where one eye has been treated with photodynamic therapy (PDT). METHODS: Patients with PDT-treated stable choroidal neovascularization (CNV), defined as a fibrotic lesion not requiring treatment for 6 months, in one eye and an untreated end-stage CNV (disciform) scar in their fellow eye, underwent refraction protocol logMAR visual acuity (VA) in letters, slit-lamp biomicroscopy, fluorescein angiography and OCT3 scan. Subretinal scar thickness was measured as Outer High Reflectivity Band Thickness (OHRBT) and retinal thickness as neuroretinal foveal thickness (NFT) on OCT3. RESULTS: Thirty-two eyes of 16 patients were studied. Mean OHRBT was 255.62 microm in treated eyes and 350.8 microm in untreated eyes (P = 0.001). Mean NFT was 130.3 microm in the treated eye and 79.9 microm in the untreated eye (P = 0.017). Mean VA was 42 letters in treated eyes and 15 letters in untreated eyes (P < 0.005). CONCLUSION: Based on OCT3 findings, eyes with AMD treated with PDT have a thinner fibrous scar and better preserved retinal thickness when compared with untreated fellow eyes with end-stage fibrotic scarring.     

Transpupillary thermotherapy of occult CNV with no or minimally classic CNV in age-related macular degeneration

Transpupillary thermotherapy (TTT) has been suggested as a putative treatment for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). This prospective study comprised 66 consecutive patients referred for exudative AMD with predominantly occult subfoveal CNV. Based on fluorescein angiography, there were 38 cases with occult CNV only, and 28 eyes with minimally classic CNV as well. Visual acuity was determined using the logarithmic ETDRS chart. For TTT a diode laser (810nm) with a power of 800 mW or 500-600 mW for a 3.0 mm spot was used (duration 60 sec.). Follow-up included clinical examination with biomicroscopy and fluorescein angiography at 2-3 months and 6 months in all cases. In the entire case material (n = 66), the mean visual acuity was preoperatively 20/125 (47.4 letters) and postoperatively 20/160 (41.8 letters) yielding a decay of 5.6 letters ("one line"). Visual acuity improved in 8 cases (12.1%), deteriorated in 17 (25.8%), and remained stable in 74.2%. In purely occult CNV visual acuity remained stable in 81.6% as compared to 64.3% in occult & minimally classic CNV; the former subgroup lost on the average 3.6 letters, the latter 8.3 letters (close to "two lines") over 6 months. The proportion of eyes losing at least 15 letters was 13.2% in purely occult CNV versus 35.7% in the occult & minimally classic subgroup. In 39 of 66 cases (59.1%) fluorescein leakage regressed to staining only concomitant with absorption of subretinal fluid. Complications associated with deterioration of visual acuity (17 cases) included postoperative hemorrhage, increase of exudation on angiography, and progressive fibrosis. The results indicate that TTT stabilizes visual acuity concomitant with regression of exudation and resorption of subretinal fluid in the majority of cases with predominantly occult CNV Cases with occult CNV only seem to do better than those with minimally classic CNV as well. The safety and complication rate appear to be acceptable. A randomized controlled trial is in progress.     

玻璃体内注射康柏西普治疗湿性年龄相关性黄斑变性的临床观察

目的 观察玻璃体内注射康柏西普治疗湿性年龄相关性黄斑变性(age-related macular degeneration,AMD)的临床疗效及安全性.方法 回顾性临床研究.选择2014年3月至2016年3月在我院确诊为湿性AMD患者60例(60眼),给予玻璃体内注射康柏西普0.5 mg,随访6～12(8.5±2.4)个月.对比分析患者注射前和注射后1、2、3、6个月及末次随访的ETDRS视力、黄斑中心凹视网膜厚度(central macular thickness,CMT)及脉络膜新生血管(choroidal neovascularization,CNV)病灶渗漏变化情况.结果 康柏西普注射次数为1 ～5(2.80±0.89)次.首次注射后1、2、3、6个月及末次随访时,ETDRS视力较治疗前分别提高(14.76±5.89)、(19.88±7.13)、(24.75±6.74)、(23.94±6.15)、(22.89±8.53)个字母,差异均有统计学意义(均为P＜0.05);CMT较治疗前分别降低(70.19±60.56) μm、(82.07±57.97) μm、(95.40±87.92)μm、(97.57±46.68) μm、(107.46±56.82) μm,差异均有统计学意义(均为P＜0.05).首次注射前CNV渗漏面积为(12.32±5.67) mm2,与首次注射后3、6个月的CNV渗漏面积比较,差异有统计学意义(均为P＜0.05).注射后仅有4例出现球结膜下点片状出血,3例患者出现轻度眼压升高,均在治疗后1周复查恢复正常.随访期间未见眼部及全身严重不良反应发生.结论 玻璃体内注射康柏西普治疗湿性AMD可提高患眼视力,降低CMT,封闭CNV渗漏,无与治疗相关的严重副反应发生.     

Transpupillary thermotherapy of predominantly occult choroidal neovascularization in age-related macular degeneration with 12 months follow-up

PURPOSE: To perform a phase I/II safety and efficacy study in order to assess the outcome following transpupillary thermotherapy (TTT) for occult choroidal neovascularization (CNV) with no or minimally classic CNV in age-related macular degeneration. METHODS: The study comprised 113 referred patients (79 females, 34 males) aged 59-89 years (mean 77.7 years) with predominantly occult CNV. There were 49 cases of occult with no classic CNV and 64 of occult with minimally classic CNV. According to their greatest linear dimension, lesions were classified as being < 3.0 mm or > 3.0 mm. Transpupillary thermotherapy was delivered with a diode laser, emission at 810 nm, duration 60 seconds, laser power 500-800 mW. Clinical examination, ETDRS logMAR visual acuity and fluorescein angiography were carried out at baseline, and at 3, 6 and 12 months in all cases. RESULTS: The average baseline visual acuity was 0.20 (50.6 letters). Following TTT, it was 0.12 (42.0 letters) at 6 months and 0.12 (38.0 letters) at 12 months. Visual acuity improved in 9/113 eyes (8.0%), remained unchanged in 46 (40.7%) eyes, and deteriorated in 58 (51.3%) eyes. There was no significant difference in the proportion of eyes that had lost at least 15 letters at 12 months in the subgroup of occult with no classic CNV (18/49; 36.7%) versus those with minimally classic lesions < 3.0 mm (15/39; 38.5%). However, 13/25 (52.0%) of cases with minimally classic lesions > 3.0 mm had lost at least 15 letters at 12 months (p = 0.31). The most common complications in the 46 eyes that suffered visual loss comprised subretinal progressive fibrosis (18 eyes) and atrophy of the retinal pigment epithelium (13 eyes). CONCLUSIONS: This study shows that TTT generally prevents moderate and severe visual loss at 12 months follow-up in occult CNV with no classic CNV. Eyes with minimally classic lesions with a greatest linear dimension of < 3.0 mm also show the same positive outcome. These results compare favourably with published data on the natural course of the disease. However, minimally classic lesions of > 3.0 mm responded poorly in this treatment setting.     

Predictors of 1‐year visual outcome in neovascular age‐related macular degeneration following intravitreal ranibizumab treatment

Purpose: To describe predictors of visual outcome in patients treated with intravitreal ranibizumab for choroidal neovascularisation (CNV) in age‐related macular degeneration (AMD). Methods: Retrospective review of 279 patients with CNV in AMD who fulfilled MARINA/ANCHOR study eligibility criteria and were treated with repeated intravitreal injections of ranibizumab 0.5 mg in routine clinical practice, beginning with three initial injections at 4‐week intervals followed by individualized retreatment for the subsequent 9 months. Study parameters included best‐corrected visual acuity (BCVA) and morphological characteristics. Results: Mean BCVA relative to baseline was +4.7 (p < 0.0001), +4.2 (p < 0.0001)and ?0.4 (p > 0.667) Early Treatment Diabetic Retinopathy Study letters after 3, 6 and 12 months, respectively, after a mean of 5.1 injections when the proportion of patients with BCVA ≥70 letters had doubled compared with baseline. Predictive factors for BCVA ≤35 letters after 12 months were BCVA ≤35 letters at baseline and month 3 (p < 0.0001) while BCVA ≥70 letters at month 12 was associated with BCVA ≥70 letters at baseline and month 3 (p < 0.001) and with total lesion size <4 DA (p = 0.0147). Conclusion: Under a ranibizumab regimen with substantially fewer injections than with fixed four‐weekly injection regimens, BCVA was improved compared with the natural history of neovascular AMD, but did not achieve the visual gain observed in randomized clinical trials using fixed 4‐week retreatment. Visual acuity at month 3, after the initial fixed‐interval injections, was the strongest predictor of BCVA at month 12.     

Photodynamic therapy combined with systemic corticosteroids for choroidal neovascularisation secondary to punctate inner choroidopathy

AIM: To report on visual acuity (VA) and angiographic outcomes in patients presenting with subfoveal choroidal neovascular membranes (CNV) secondary to punctate inner choroidopathy (PIC), treated with photodynamic therapy (PDT) with verteporfin combined with systemic corticosteroids. METHODS: A prospective case series of patients with subfoveal CNV secondary to PIC was analysed. All patients were treated with PDT combined with oral prednisolone (1 mg/kg body weight/day) which was started 5 days before PDT. Fluorescein angiography was performed at baseline and every 3 months post-treatment to establish the size, position, and activity of the CNV. Visual acuity was measured using the ETDRS scale. Further PDT treatment was carried out at follow-up visits if there was angiographic evidence of ongoing CNV activity. RESULTS: Five female patients with a mean age of 30.4 years (range 25-43 years) were treated over a 12-month period. The mean greatest linear diameter (GLD) of the CNV was 1.66 mm (range 0.46-3.28 mm). A mean improvement in vision of nine ETDRS letters (range -15-20 letters) after treatment was found, which was maintained at final follow-up. The mean follow-up time was 12 months (range 10-14 months). The mean number of PDT treatments was two (range 1-3). CONCLUSIONS: The vaso-occlusive effect of PDT combined with the vasostatic and anti-inflammatory effect of systemic oral prednisolone appears to be a safe and effective option in the primary treatment of subfoveal CNV in patients with PIC.     

Chorioretinal anastomosis as unfavourable prognostic factor during photodynamic therapy

BACKGROUND: The aim of this study was the documentation of chorioretinal anastomosis in neovascular age-related macular degeneration (AMD) and correlation with functional and angiographic results following photodynamic therapy (PDT). METHOD: A total of 100 patients presenting with neovascular AMD and indication for PDT based on the presence of predominantly classic choroidal neovascularization (CNV), underwent ophthalmoscopic and angiographic screening for chorioretinal anastomosis. Conventional PDT using verteporfin was performed according to the recommended standard procedure.The pre- and post-treatment status at 3 and 6 months post-PDT in all patients and at 1 week in selected patients was documented with respect to the central visual acuity test (ETDRS), ophthalmoscopy as well as fluorescein (FA) and indocyanine green angiography (ICGA). RESULTS: A primary chorioretinal anastomosis was found in 6% ( n=12) of all eyes with CNV and classic PDT indication. Mean visual loss within the first 6 months after therapy was 3 lines indicating lack of visual stabilization according to the PDT study criteria.Furthermore, an increase in visual acuity could not be documented in any case.Angiography demonstrated continuous progression of CNV size although PDT had been uneventful. The characteristic initial occlusion of the CNV with homogeneous hypofluorescence was absent angiographically at 1 week post-PDT.The anastomosis was detected by ICGA in all eyes and by ophthalmoscopy or optical coherence tomography (OCT) in most eyes. DISCUSSION: Chorioretinal anastomosis is not a rare finding associated with predominantly classic CNV.The presence of anastomosis appears to be an unfavourable prognostic factor during PDT. If a chorioretinal shunt is suspected evaluation by ICGA and/or OCT should be performed and the indication for PDT should be rediscussed.     

Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results

PURPOSE: Subgroup data from a pivotal phase 3 study comparing ranibizumab (LUCENTIS) with verteporfin (VISUDYNE) photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) were retrospectively analyzed to identify patient and disease characteristics that may predict visual acuity (VA) treatment outcomes. DESIGN: Retrospective subgroup analysis of 12-month data from the ANCHOR study. METHODS: Univariate analyses were performed to assess VA outcomes across subgroups based on patients' gender and baseline age, VA score, CNV lesion size, CNV lesion type, and duration of neovascular AMD, followed by multivariate analyses to identify predictors of the VA score change from baseline at 12 months. main outcome measures: Proportion of patients losing <15 letters and proportion gaining > or =15 letters from baseline VA; mean change from baseline VA. RESULTS: On average, all subgroups of ranibizumab-treated patients did better than PDT patients for all three VA outcome measures. In the multivariate analysis, lower baseline VA score, smaller baseline CNV lesion size, and younger baseline age were associated with greater gain of letters with ranibizumab treatment and less loss of letters with PDT. CONCLUSIONS: Subgroup analysis of 12-month data from the ANCHOR study showed ranibizumab to be superior to PDT in all subgroups evaluated, and was consistent with the subgroup analysis of 24-month data from the other pivotal phase 3 study of ranibizumab (MARINA) in showing that the most important predictors of VA outcomes were, in decreasing order of impact, the patient's baseline VA score, CNV lesion size, and age.     

Visual acuity and contrast sensitivity in patients with neovascular age-related macular degeneration

Background Patients with advanced age-related macular degeneration (AMD) suffer not only from impairment in central visual acuity (VA), but also from reduction in contrast sensitivity (CS). We examined VA and CS changes over time in patients with subfoveal choroidal neovascularizations (CNV) as well as the correlation between the two parameters.Methods VA was determined according to a standardized protocol with the Early Treatment Diabetic Retinopathy (ETDRS) chart. CS was measured with Pelli–Robson charts. The angiographic characteristics of CNV and the presence of CNV in the fellow eye as well as gender and age were evaluated as possible prognostic factors of VA and CS progression. Two hundred and five patients with neovascular AMD were recruited within the Radiation Therapy for Age-Related Macular Degeneration (RAD) Study and were reviewed over 2 years. The treatment and control groups showed no significant difference for VA or for CS (P>0.05), and both groups were considered together.Results At baseline, mean VA was 55.6±14.5 SD letters (EDTRS chart), and mean CS was 22.8±6.9 letters (Pelli–Robson chart). Spearman Correlation Coefficient (r_s) between VA and CS was r_s=0.60, P=0.0001. Over 2 years the mean VA loss was 23.6±21.4 letters and mean CS reduction was 9.0±9.7 letters. Agreement between change of VA and change of CS was moderate (r_s=0.65, P=0.0001; kappa coefficient (grouped into VA loss 15, >15, >30 letters; CS loss 6, >6, >15 letters) =0.43, 95% CI [0.32;0.54]). Proportional hazard models did not show any apparent influence of type of CNV, or CNV in the fellow eye, on change in VA and CS.Conclusion The results indicate that VA and CS do not always show the same progression in visual function loss although they show a moderate correlation in eyes with neovascular AMD. Both parameters provide important information about visual disability and should be evaluated as outcome in interventional studies.Caren Bellmann is at present Marie Curie Individual Fellow at the Institute of Ophthalmology (Marie Curie Individual Fellowship, European Commission # QLK6-CT2000-51262)The work was presented in part at the 100th meeting of the German Ophthalmology Society (DOG), 2002, Berlin, Germany     

Ranibizumab for treatment of exudative age-related macular degeneration--own experience

It is commonly agreed nowadays that one of the key elements of neovascular age-related macular degeneration (AMO) pathogenesis is deregulation of the angiogenesis factors. Treatment of subfoveal choroidal neovascularizations (CNV) in course of AMD was limited to photodynamic therapy with verteporfin (PDT). The new approach to CNV treatment is to discover and eliminate factors, which directly induce CNV development. Extended studies have allowed to employ inhibitors of vascular endothelial growth factor (VEGF) for a treatment of neovascular AMD. Numerous of anti-VEGF compounds are still under developing in pre-clinical or phase-1/2 clinical studies whereas 2 of them have completed phase 3 of clinical trials. The newest compound that was launched on drug market is ranibizumab (Lucentis). Ranibizumab is a recombinant humanized IgG1 isotype, monoclonal antibody fragment designed for intravitreal use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A). It has been proved on the base of MARINA and ANCHOR clinical trials that treatment ranibizumab is effective and save for patients treated for CNV secondary to AMD. PURPOSE: Interventional case series. MATERIAL AND METHODS: 67 eyes of 67 patients with all angiographic subtypes of wet AMD were treated with 0.5 mg of intravitreal ranibizumab, injected monthly for first 3 doses. Next doses were injected according to specified re-treatment criteria as assessed in monthly follow-up. RESULTS: Mean change in visual acuity (VA) was +12.4 ETDRS letters. Percent of patient losing less than 15 ETDRS letters was 93.2%. Percent of patient gaining VA more than 3 ETDRS letters was 43.4%. CONCLUSIONS: Intravitreal ranibizumab is effective in treatment of CNV due to AMD. A significant number of patients have improved theirs VA. Implementation of anti-VEGF therapy for treatment of ocular diseases gave a new hope for patient that previously couldn't be treated with any of method.     

Pegaptanib sodium in treatment of choroidal neovascularization secondary to age-related macular degeneration. One year results

PURPOSE: Prospective, noncomparative (nonrandomized, uncontrolled), consecutive interventional case series study--to evaluate the efficacy of intravitreal pegaptanib sodium in the treatment of choroidal neovascularization due to age-related macular degeneration in treatment-naive patients. MATERIAL AND METHODS: 38 eyes of 38 patients were treated with intravitreal pegaptanib. All angiographic subtypes of lesions were qualified to the treatment. Intravitreal injections were performed every 6 weeks at the discretion of the treating ophthalmologist. Retreatment criteria were based on evaluation of presence of submacular fluid and/or increase in macular thickness seen in OCT, new retinal hemorrhage, and loss of visual acuity (VA). RESULTS: The VA outcomes were assessed at 48-th week of the study. The mean change in VA for all lesions was a loss of 9.4 ETDRS letters. Percent of patients losing less than 15 ETDRS letters in predominantly classic subgroup was 68%, minimally classic--65% and pure occult--72%. 7% of patients gained more than 1 ETDRS lines of VA whereas 2% more than 3 ETDRS lines. 8.5% of patients lost 30 and more ETDRS letters at 48-th week of the study. Results were better for smaller (<4 DA) lesions, eyes with better (> 54 ETDRS letters) baseline VA and for pure occult lesions. CONCLUSIONS: Pegaptanib sodium effectively preserve vision in approximately 70% of patients with wet AMD in 1-year period of observation. Eyes with more advanced lesions seen at baseline have an increased risk of worse VA outcomes.     

First clinical experience with anecortave acetate (Retaane)

BACKGROUND: Anecortave acetate is an angiostatic cortisene which is injected as a posterior juxtascleral depot and has been shown to be effective in the treatment of exudative age-related macular degeneration (AMD). The compound is not yet approved in Switzerland but can be used as "compassionate use" in individual cases. PATIENTS AND METHODS: An uncontrolled case series with standardised documentation of ETDRS visual acuity, near acuity, need for magnification and fluorescein angiography was performed. RESULTS: 22 eyes of 19 patients (8 male, 11 female, average age 78.8 years) were treated with a posterior juxtascleral depot injection (PJD) of 15 mg anecortave acetate. The mean change in visual acuity after 3 months in eyes treated with anecortave acetate was -2.6 ETDRS letters corresponding to 0.52 Snellen lines. 3/20 eyes gained more than 1 line. 11/20 eyes showed stable visual acuity (+/- 1 Snellen line, +/- 5 ETDRS letters). 5/20 eyes developed moderate vision loss (one to two Snellen lines, 6-10 ETDRS letters). 1/20 lost 18 ETDRS letters (> 3 Snellen lines). There were no moderate or severe adverse events. CONCLUSIONS: A PJD of 15 mg anecortave acetate is safe and well tolerated. In eyes with occult CNV without recent progression or with residual neovascular activity after photodynamic therapy anecortave acetate may be an alternative therapeutic option before considering intravitreal anti-VEGF agents due to the much less invasive character and lower risk profile.     

A randomized controlled clinical trial on the efficacy of radiation therapy in the control of subfoveal choroidal neovascularization in age-related macular degeneration: radiation versus observation

· Background: The results of several pilot studies concerning radiation therapy for age-related subfoveal choroidal neovascularization (CNV) have been published recently. Although positive treatment results have been described, it is not known whether this therapy alters the natural course of eyes with neovascular age-related macular degeneration (AMD). A randomized controlled clinical trial was conducted in which radiation therapy was compared with observation in patients with subfoveal neovascular AMD. · Methods: Seventy-four patients with a recent drop in central vision due to subfoveal age-related CNV were randomized to either radiation treatment or observation. Patients with either classic, occult or mixed type CNV were included. Eyes in the treatment group received a radiation dose of 24 Gy in four fractions of 6 Gy. Evaluation of data concerning visual acuity (VA) and fluorescein angiography occurred at 3, 6 and 12 months after inclusion. · Results: At 12 months of follow-up 52.2% of the observation group versus 32.0% of the irradiation group had lost 3 or more lines of VA (P=0.03, log rank test). More severe visual decline, 6 lines or more, was observed in 40.9% of the observation versus 8.8% in the irradiation group (P=0.002 using log rank test). At 12 months 39.6% of the observation group and 20.0% of the treatment group had VA of less than 0.1 (P=0.08, log rank test). The size of the CNV membrane doubled in 25.2% of eyes in the observation group versus 20.0% in the treatment group at 12 months (P=0.5, log rank test). No side effects were observed. · Conclusion: Preservation of VA was significantly better in the treatment group compared with the control group at 12 months. Nevertheless we noted a drop in central vision of 3 or more lines in a substantial proportion of the treatment group. Radiation therapy does not prevent visual loss in all patients with age-related subfoveal CNV, and whether the treatment benefit at 12 months will persist has to be awaited. Received: 26 September 1997 Accepted: 11 November 1997