Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age-related macular degeneration

Background The purpose of the study is to report data on short-term safety of intravitreal bevacizumab treatment and its effect on visual function, central retinal thickness, and angiographical changes of occult choroidal neovascularization due to age-related macular degeneration. Methods A consecutive interventional case series of 30 patients with active subfoveal occult choroidal neovascularization secondary to age-related macular degeneration was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline and subsequent injections following standardized criteria. At baseline and follow-up visits patients had visual acuity assessment, intraocular pressure measurement, fluorescein angiography, and optical coherence tomography imaging. Results No serious ocular or systemic adverse events were identified. A significant increase of intraocular pressure or signs of retinal toxicity or endophthalmitis were not detected in any patient. Optical coherence tomography revealed significant decrease (p < 0.001) in central retinal thickness after 1 week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1 week and improvement was maintained at week 12 in the majority of patients. Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 or more lines was seen in 14 of 30 patients; one patients showed improvement of 6 lines. No patient had severe vision loss of 6 lines or more; moderate vision loss of 3 lines was seen in one patient. Re-injections of bevacizumab according to standard criteria were performed one to two times during the follow-up period of 12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks). Conclusions Short-term results suggest that intravitreal injection of bevacizumab is well tolerated and for the majority of patients with occult choroidal neovascularization in AMD results in improvement of visual acuity, decrease in central retina thickness, and reduction of angiographic leakage of the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic option for selected patients with exudative AMD. Randomized prospective multicenter trials seem justified to further evaluate long term effects and impact of intravitreal bevacizumab on different subtypes of AMD compared to established therapies.     

Resolution of macular oedema in occult choroidal neovascularization under oral Sorafenib® treatment

Purpose: To report on the effect of oral nexavar (Sorafenib^®) treatment in one patient with neovascular age‐related macular degeneration (AMD) and advanced renal cell cancer (RCC). Methods: After two intravitreal injections of bevacizumab (1.25 mg) for occult choroidal neovascularization (CNV) in AMD, the patient was started on oral Sorafenib^® (400 mg twice daily) treatment for RCC. Results: Visual acuity (VA) was 20/80 in the left eye and optical coherence tomography (OCT) demonstrated persistent central thickening to 251 µm after bevacizumab. After 6 weeks of oral Sorafenib^® treatment, VA had increased to 20/70 and a significant decrease in retinal thickness to 208 µm was observed on OCT. The patient remained stable during a further 3 months of follow‐up. Conclusions: Resolution of macular oedema and stabilization of VA under oral treatment with the multikinase inhibitor Sorafenib^® was observed. This observation warrants further investigation.     

Grid laser treatment of occult choroidal neovascularization in age related macular degeneration

Laser photocoagulation treatment of occult choroidal neovascularization (CNV) in age related macular degeneration has been up to now discouraging. We report a randomized clinical trial comparing grid laser treatment versus the natural course in 24 eyes with this kind of neovascularization. In 12 eyes a low energy scatter photocoagulation was applied to the areas of presumed CNV and abnormal retinal pigment epithelium, sparing the fovea. The follow-up ranged from 1 to 3 years. At the three months follow-up visit, the subretinal exudation appeared reduced in 40% of the treated eyes and in none of the control eyes. During the period of follow-up the occult CNV turned to classic CNV in 4 treated and in 4 untreated eyes. At the last examination (average follow-up 18 months), anatomical and functional conditions were not significantly different in the two groups. Our data fail to show a beneficial long-term effect of grid laser treatment for occult CNV; no iatrogenic complications were seen in our series.Presented at the 3rd International Symposium on Ocular Circulation and Neovascularization, Paris, May 21–23, 1992.     

Subthreshold transpupillary thermotherapy for subfoveal occult choroidal neovascularization secondary to age-related macular degeneration

Purpose. To describe the long term outcome of patients with subfoveal, occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with subthreshold transpupillary thermotherapy. Methods. 82 eyes of 82 consecutive patients with subfoveal occult CNV secondary to AMD were treated with subthreshold transpupillary thermotherapy. Best corrected visual acuity, fundus photography, fluorescein and indocyanine green angiography were performed. Results. All patients have been followed for at least 24 months. At the final follow-up visit, 75.6% of patients had stable or improved visual acuity and 24.4% had worsened visual acuity. No overtreatment side effects were found. Conclusion. Subthreshold transpupillary thermotherapy seems effective in stabilizing visual acuity in patients affected by occult, subfoveal CNV even on a long-term basis.     

Intravitreal bevacizumab versus ranibizumab for the treatment of retinal angiomatous proliferation

Purpose: To evaluate the effects of intravitreal bevacizumab and ranibizumab treatments in retinal angiomatous proliferation (RAP). Methods: Fifty patients affected by RAP were randomly assigned either to intravitreal bevacizumab injection (IVBI) or intravitreal ranibizumab injection (IVRI). After a loading phase including three consecutive monthly injections, the retreatment was administered in cases of persistent RAP. The primary outcome measures were the mean changes in BCVA between the two treatment groups, and the proportion of eyes gaining 1 and 3 lines at the end of the follow‐up. Secondary outcomes included central macular thickness (CMT) changes and progression to more advanced stages of RAP. Results: Fifty patients affected by stage 1 and 2 RAP were recruited. Twenty‐six and 24 patients received IVBI and IVRI, respectively. At the baseline, mean best corrected visual acuity (BCVA) values were 0.59 ± 0.21 (LogMAR ± SD, approximately corresponding to 20/80 Snellen Equivalent‐SE) in IVBI group and 0.66 ± 0.33 (approximately 20/90 SE) in IVRI group with no statistical difference. At 12‐month examination, both groups showed a statistically significant improvement in the BCVA, with a final mean value of 0.43 ± 0.24 (approximately 20/54 SE) in IVBI group and 0.50 ± 0.32 (approximately 20/63 SE) in the IVRI group. A BCVA gain of 1 and 3 lines was registered in 20 and 8 eyes, respectively, in the IVBI group. Similarly, 17 and 7 eyes showed an improvement of 1 or 3 lines, respectively, in the IVRI group. The CMT reduced significantly from baseline to 12‐month examination in both groups. A lower proportion of eyes with complete pigment epithelium detachment resolution was noted in the IVBI group than in the IVRI group (40% versus 90%). Conclusions: Our study shows that both IVBI and IVRI are equally effective in improving the BCVA over a 1‐year follow‐up in eyes affected by stage 1 and 2 RAP.     

Complement factor H Y402H gene polymorphism and response to intravitreal bevacizumab in exudative age‐related macular degeneration

Purpose: To determine whether different complement factor H (CFH) genotypes play a role in treatment of age‐related macular degeneration (AMD) with intravitreal bevacizumab. Methods: In this prospective study, we included 197 patients with exudative AMD and treated with 1.25 mg intravitreal bevacizumab at 6‐week intervals until choroidal neovascularization (CNV) was no longer active. In all patients, ophthalmological examinations, visual acuity, optical coherence tomography (OCT), fundus photography and fluorescein angiography were performed. Single nucleotide polymorphism (SNP) genotyping was performed using restriction fragment length polymorphism (RFLP) analysis of polymerase chain reaction (PCR) products. Results: Age, gender and baseline mean visual acuity were similar among the three CFH genotypes. There was no significant difference in underlying lesion type of CNV, lesion size, number of injections or macula thickness. When examining the effect of genotype on post‐treatment visual acuities, we observed a significant worse outcome for distance and reading visual acuity in the CFH 402HH genotype group. The number of patients who lost 3 or more lines in distance and reading visual acuity testing was significantly higher in the CFH 402HH (41%, 46%) genotype group than in patients with the CFH 402YY (28%, 26%) and CFH 402YH (26%, 24%) genotype. Conclusions: In addition to the higher risk for exudative AMD in patients with the CFH 402HH genotype that was found in previous studies, our results show that the CFH 402HH genotype also correlates with lower visual acuity outcome after treatment with bevacizumab, suggesting that pharmacogenetics of CFH plays a role in response to treatment of wet AMD.     

Intravitreal bevacizumab for subfoveal choroidal neovascularization secondary to age-related macular degeneration in an Indian population

Purpose To investigate the 6-month safety profile and clinical outcomes of intravitreal bevacizumab for treating subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Methods We performed a prospective nonrandomized interventional study of 40 consecutive patients (40 eyes) with subfoveal CNV due to AMD. Patients underwent standard ophthalmic examination, optical coherence tomography, and fundus fluorescein angiography. All patients were administered one or more intravitreal injections of bevacizumab (1.25 mg) as primary therapy. Outcomes were also analyzed in subgroups based on lesion type (classic or occult) and lesion size (≤3000 μm or >3000 μm). Results At the 6 months’ follow-up, mean best-corrected visual acuity (BCVA) improved from 20/160 to 20/100 (P = 0.014), and the mean contrast sensitivity improved from 0.38 to 0.62 (P = 0.001). The mean greatest linear diameter and mean central macular thickness significantly decreased from 3.79 mm to 2.4 mm (P = 0.0001) and from 438.5 μm to 363 μm (P = 0.0001), respectively. Visual acuity gain of 15 letters or more was seen in 20% of patients, and the gain was more in the small-lesion subgroup (31.5%) than in the large-lesion subgroup (9.5%). No significant adverse effects were observed. Conclusion Intravitreal bevacizumab is a safe and effective modality for treatment of CNV secondary to AMD. A significant improvement in BCVA with intravitreal bevacizumab was observed for all lesion types.     

Photodynamic therapy with intravitreal application of triamcinolone acetonide in age‐related macular degeneration: functional results in 54 patients

Purpose: This study aimed to investigate the functional results, efficacy and complications after photodynamic therapy (PDT) combined with intravitreal triamcinolone acetonide injection (IVTA) in patients with choroidal neovascularization (CNV) caused by age‐related macular degeneration (AMD). Methods: A retrospective analysis of clinical data for 54 patients with CNV resulting from AMD was carried out. All patients had a follow‐up of 12 months. The patients were treated with standardized PDT and IVTA (4 mg) as a first‐line treatment or following PDT failure. Visual acuity (VA), greatest linear diameter (GLD) of the CNV and foveal thickness were evaluated. Results: Mean VA at baseline was 0.8 logMAR (0.4–1.4). After 12 months VA improved (> 2 lines) in 20.4% of patients and stabilized (± 2 lines) in 64.8%. There was no statistical significance in VA outcome between patients undergoing first‐line treatment and patients with PDT failure; however, fewer PDT treatments were required to stop CNV activity in patients undergoing first‐line treatment. At 12 months, a reduction in foveal thickness was seen in 67.7% of patients and a reduction in CNV GLD in 32.7%. Complications occurred in 22% of patients and included a transient rise in intraocular pressure, cataract and sterile hypopyon. Conclusions: Our analysis shows that fewer PDT treatments were required to stop CNV activity when triamcinolone was used as first‐line treatment. We can thus conclude that PDT combines synergistically with IVTA and the combination may lead to a cost reduction compared with PDT therapy alone. The overall complication rate of 22% is high and must be compared with complication rates caused by new intravitreal anti‐VEGF (vascular endothelial growth factor) drugs in combination with PDT.     

Combined intravitreal bevacizumab and triamcinolone in exudative age‐related macular degeneration

Acta Ophthalmol. 2010: 88: 630–634

Abstract.

Purpose: We report on the combined application of intravitreal bevacizumab and triamcinolone acetonide for treatment of exudative age‐related macular degeneration (AMD). Methods: The clinical interventional case‐series study included 16 patients (16 eyes) with exudative AMD who had previously received 3.5 ± 1.8 mono‐injections of bevacizumab (1.5 mg) without significant improvement in visual acuity (VA) or reduction in macular exudation. All patients underwent a combined intravitreal injection of bevacizumab (1.5 mg) and triamcinolone acetonide (about 20 mg). Main outcome measures were VA and macular thickness as determined by optical coherence tomography. All patients were re‐examined at 2–3 months after the intervention. Results: Visual acuity improved significantly (p = 0.03) from 0.80 ± 0.40 logMAR prior to the combined injection to 0.65 ± 0.42 logMAR at 3 months after the injection. An improvement of ≥ 1 Snellen line was found in eight subjects, an increase of ≥ 2 lines in five subjects, and an improvement of ≥ 3 lines in two subjects. One patient lost 1 line and one patient lost 3 lines. Central retinal thickness decreased significantly from 272 ± 62 μm to 220 ± 47 μm (p = 0.03). At the 6‐month follow‐up examination, central retinal thickness had increased again to 319 ± 142 μm, which was not significantly (p = 0.30) different from baseline measurements. Conclusions: The combined intravitreal application of bevacizumab and triamcinolone may temporarily be helpful in the treatment of exudative AMD if previous intravitreal bevacizumab mono‐injections have failed to improve vision and reduce macular oedema.     

玻璃体腔内注射曲安奈德联合光动力疗法治疗脉络膜新生血管所致的黄斑萎缩

目的:报道经玻璃体腔内注射高剂量曲安奈德(triamcinolone acetonide,TA)联合光动力学疗法(photodynamic therapy,PDT)治疗老年性黄斑变性( age related macular degeneration, AMD)的脉络膜新生血管(choroidal neovascularization,CNV)后发生的脉络膜毛细血管萎缩。方法:我们采用非随机回顾性干涉治疗病例。在阿利坎特学院眼科,连续观察51眼(实验组)玻璃体腔内的注射(19.4±2.1)mg/0.1mL TA联合PDT治疗AMD的全部中心凹下型CNV患者,经过2a的随访,检查黄斑部脉络膜毛细血管和视网膜色素上皮细胞(RPE)萎缩情况。同时,采用单独PDT治疗的连续30眼患者作为对照组,其年龄,性别和AMD的CNV类型及大小与实验组相匹配。结果:随访24mo后,在治疗区域21/47眼(45%,实验组)和7/30眼(23%,对照组)发展成黄斑部RPE和脉络膜毛细血管萎缩(P=0.04,卡方检验)。实验组平均最大萎缩区域的直径为(5044±1666)μm,而对照组为(4345±1550)μm。在实验组中,RPE萎缩患者的平均最佳矫正视力为(0.87±0.33),而非RPE萎缩患者的平均最佳矫正视力为(0.66±0.26) (P=0.11,秩和U检验)。结论:玻璃体腔内注射大剂量TA联合PDT治疗可能会增加RPE和脉络膜毛细血管萎缩的风险。     

Macular atrophy after combined intravitreal triamcinolone and photodynamic therapy to treat choroidal neovascularization

AIM: To report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD). METHODS: The present study was retrospective about non-randomized interventional case series. Fifty-one consecutive eyes with subfoveal (all types) CNV associated with AMD were treated by PDT and intravitreal (19.4±2.1)mg per 0.1mL TA at the Alicante Institute of Ophthalmology. The appearance of macular choriocapillaris and retinal pigment epithelium (RPE) atrophy was considered at two years follow-up. Thirty consecutive eyes treated by PDT alone, matched for age, sex, and type and size of CNV were considered as control group. RESULTS: Twenty-one of 47 eyes in the study group (45%) and 7 of 30 eyes in the control group (23%) developed macular RPE and choriocapillaris atrophy in the treated area at month 24 (P=0.04, Chi-square test). The greatest diameter of the atrophic areas averaged (5044±1666)μm in the study group vs (4345±1550)μm in the control group. Mean final best corrected visual acuity (logarithm of minimal angle of resolution) was (0.87±0.33) in the cases with RPE atrophy vs (0.66±0.26) in the cases with no RPE atrophy in the study group (P=0.11, Mann-Whitney U test). CONCLUSION: The association of high doses of intravitreal TA and PDT may increase the risk for RPE and choriocapillaris atrophy.     

Intravitreal bevacizumab for choroidal neovascularization secondary to Vogt-Koyanagi-Harada syndrome

Background  Vogt-Koyanagi-Harada (VKH) syndrome is characterized by bilateral diffuse uveitis associated with auditory, neurological, and cutaneous signs and symptoms. VKH syndrome is a cell-mediated autoimmune disease against melanocytes. Choroidal neovascularization (CNV) occurs in 15% of VKH patients and is associated with poor visual prognosis. Cases  We report on two patients with VKH syndrome and CNV that were treated with intravitreal bevacizumab. Observations  One of the VKH patients also had an extrafoveal CNV membrane and underwent multiple intravitreal injections of bevacizumab in combination with laser photocoagulation, with subsequent improvement in visual acuity. The second had a subfoveal CNV that responded to a single intravitreal injection of bevacizumab. Conclusion  Intravitreal bevacizumab may be a useful drug to treat CNV in eyes with VKH syndrome.     

Intravitreal bevacizumab (Avastin) for neovascular age‐related macular degeneration using a variable frequency regimen in eyes with no previous treatment

Purpose: To evaluate a variable frequency regimen with intravitreal bevacizumab for treatment of neovascular age‐related macular degeneration (AMD) in eyes that have not received any previous treatment. Methods: Retrospective review of patients with neovascular AMD who were treated with three consecutive monthly intravitreal injections of bevacizumab (1.25 mg) and retreated based on the PrONTO study criteria. Outcome measures included visual acuity (VA) and central retinal thickness. Subgroup analysis was conducted to identify pretreatment characteristics that could determine visual outcome with treatment. Results: A total of 109 eyes of 109 patients were treated. The mean age was 82 years, and the mean follow‐up period was 9.4 months (range 6–12 months). At baseline, the mean VA was 45.6 letters (6/37.5) and mean central retinal thickness 343 µm. This improved to 51 letters (6/30) (P < 0.001)) and 231 µm (P < 0.001) at 6 months. At 6 months, VA was improved by at least five letters in 50%, remained stable in 30% and worsened by at least five letters in 20% of patients. Patients with large intraretinal cysts on optical coherence tomography before treatment had an increased risk of worse vision (odds ratio 10.5, 95% confidence interval 1.69–64.99; P = 0.018). Conclusions: The majority of patients had improvement or stability of VA regardless of the angiographic type of choroidal neovascularization. Intravitreal bevacizumab with this tailored regimen is beneficial in the treatment of neovascular AMD in the short term. The presence of large intraretinal cysts on optical coherence tomography is a poor prognostic factor for visual improvement with this treatment.     

玻璃体腔内注射Avastin治疗老年性黄斑变性引起的脉络膜新生血管

年龄相关性黄斑变性(age-related macular degeneration,AMD)是一种严重威胁老年人视功能的眼底疾病,随着抗VEGF药物(avastin)的诞生,治疗该病显现出蓬勃的发展趋势,它不但可以延缓脉络膜新生血管(choroidal neovascularization,CNV)的进展,还可以提高视力。现将avastin治疗AMD中CNV的相关应用作一综述。     

Natural history of choroidal neovascularization after surgical induction in an animal model

Purpose: To study an expanded time course of surgically induced choroidal neovascularization (CNV) in a porcine model applying fluorescence angiography and immunohistology. Methods: Twenty‐two porcine eyes underwent vitrectomy, a retinal bleb was raised and the detached retina perforated using endodiathermy. Bruch’s membrane was perforated with a retinal perforator at a site where the overlying neuroretina was normal. Eyes were enucleated in a time interval between 30 min and 42 days after the perforation, and the pigs were subsequently killed. Immediately prior to enucleation, fundus photographs and fluorescein angiograms were obtained. Sections of paraffin‐embedded eyes were immunohistochemically stained. Results: On fluorescein angiography, membranes aged 14 days or less exhibited leakage in 10/11 cases while the remaining showed persistent staining. The propensity to leak diminished with time and only 1/3 of the oldest membranes leaked. In eyes enucleated immediately after surgery, neuroretinas overlying the induced lesions were intact without apparent atrophy of cells. At day 3, macrophages and myofibroblasts formed membrane‐like structures in the subretinal space. At day 7, the outer surface of the membrane was covered by retinal pigment epithelium (RPE) cells and the neuroretinas had suffered damage in the form of outer segment loss. In the time period 14–42 days, the CNV membrane became completely enveloped by RPE cells. The degree of membrane vascularization increased with time and was at its maximum after 42 days. Intact outer segments were identified over the oldest membranes. Conclusion: The formation of surgical CNV membranes followed the normal reparatory pathway and the degree of vascularization of CNV membranes continued to increase during the 42 days. However, propensity to leak diminished with time. We believe that this was because of the fact that RPE cells completely enveloped older membrane and thus prevented leakage from the newly formed vessels. Photoreceptor outer segments, which had atrophied after 7 days, were able to regenerate over CNV membranes and could be identified again after 42 days.     

Indocyanine green guided laser photocoagulation in patients with occult choroidal neovascularisation

AIMS: To determine whether indocyanine green (ICG) guided laser photocoagulation of occult choroidal neovascularisations (OCNV) is beneficial for patients with occult choroidal neovascularisation secondary to age related macular degeneration (AMD). METHODS: A prospective pilot study was performed in 21 eyes with OCNV secondary to AMD that could be identified extrafoveolarly or juxtafoveolarly in an early ICG angiographic study. Laser photocoagulation was applied to the neovascular membrane identified in the early ICG angiographic study. RESULTS: Visual acuity ranged from 20/400 to 20/20 (logMAR 0.54 (SD 0.29) before and hand movements and 20/30 (logMAR 0.81 (0.69)) at the last follow up after laser photocoagulation. During the follow up (30 (13) months) vision improved in four eyes (two lines), in seven eyes the initial visual acuity could be stabilised (two lines), in five eyes vision dropped moderately (three to five lines), and in five eyes vision decreased severely (six or more lines). Recurrences (seven patients) or persistent CNV (six patients) was observed in 13 patients. CONCLUSION: This preliminary study of ICG guided laser photocoagulation of occult extrafoveal and juxtafoveal choroidal neovascularisations suggests that this technique may improve the visual prognosis of these patients. Further prospective controlled studies are necessary to confirm these data.     

Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to ARMD: a preliminary multifocal-ERG and OCT study

Purpose To evaluate by MFERG and OCT the macular function before and after intravitreal use of bevacizumab (Avastin) in eyes suffering from CNV due to ARMD. Methods Eighteen eyes with subfoveal CNV due to ARMD were studied before and after intravitreal use of bevacizumab with MFERG and OCT. The post treatment follow up was three months. Results Before treatment, OCT shows an increase of the retinal thickening of the fovea and the electrical response densities in the fovea and parafovea were decreased in all patients. Three months after treatment, OCT showed a real resolution of the subretinal fluid. The electrical responses in the fovea and parafovea remained the same or slightly improved in some cases. The intraocular pressure remained normal and no inflammation was observed. Conclusion The intravitreal use of bevacizumab may provide anatomical correlates that support the concept of disease amelioration but the functional improvement of the macula three months after treatment is not obvious. However the method is promising and needs further evaluation.