Treatment of neovascular age-related macular degeneration with pegaptanib and boosting with bevacizumab or ranibizumab as needed

BACKGROUND AND OBJECTIVE: Neovascular age-related macular degeneration presents a therapeutic challenge. The efficacy of pegaptanib sodium, a selective inhibitor of vascular endothelial growth factor 165, was examined as a therapeutic mainstay combined with "as needed" boosts of nonselective vascular endothelial growth factor blockade with bevacizumab or ranibizumab. PATIENTS AND METHODS: A retrospective chart review of outcomes of patients treated with pegaptanib and later boosted with bevacizumab or ranibizumab was conducted. Visual acuity, optical coherence tomography, and fluorescein angiography findings were recorded and assessed. RESULTS: During a mean follow-up of 12.1 months, an average of 7.8 injections of pegaptanib 0.3 mg, 1.4 injections of bevacizumab 1.25 mg, and 0.9 injections of ranibizumab 0.5 mg were administered to 17 eyes. In all, 47% of eyes gained 3 or more lines of visual acuity and 76% gained 0 or more lines. CONCLUSION: Pegaptanib as a mainstay of neovascular age-related macular degeneration therapy with an occasional boost of bevacizumab or ranibizumab appears to be an effective treatment option.     

Inhibitors of vascular endothelial growth factor (VEGF) in the management of neovascular age‐related macular degeneration: a review of current practice

We review the fundamental changes that are now occurring to the management of neovascular (wet) age‐related macular degeneration (AMD). An improved understanding of the role of vascular endothelial growth factor (VEGF) in the genesis of choroidal neovascular membranes has led to the creation and use of intravitreous anti‐VEGF antibodies (bevacizumab and ranubizumab) and an aptamer (pegaptanib) in the treatment of these lesions. These new intravitreous injections for AMD have supplanted previous treatments in both efficacy and safety and are now the standard of care for neovascular AMD. We discuss the biochemistry of the anti‐VEGF pathway. While there is substantial evidence for the use of ranubizumab and pegaptanib, the intravitreous administration of bevacizumab has not been tested in randomised controlled clinical trials. We review the evidence base for all three agents and the patho‐physiological basis for adverse reactions to intravitreous VEGF blockade.     

Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration

Angiogenesis has a causal role in many diseases, including neovascular age-related macular degeneration (AMD). Identification of key regulators of angiogenesis, including vascular endothelial growth factor (VEGF), fibroblast growth factor 2, pigment epithelium-derived growth factor, angiopoietins and extracellular matrix molecules, has facilitated the development of novel therapeutic agents that target the underlying pathological angiogenic process. Among these, VEGF serves as a "master switch" for many ocular neovascular conditions through its promotion of endothelial cell proliferation and survival, vascular permeability and ocular inflammation. Two anti-VEGF agents are now clinically available: bevacizumab, an antibody for metastatic colorectal cancer, and pegaptanib sodium, an aptamer for neovascular AMD. Unlike bevacizumab, which binds all VEGF isoforms, pegaptanib targets only VEGF165, the isoform responsible for pathological ocular neovascularization and thus an ideal target for treatment of AMD. Although other therapies targeting angiogenesis in AMD are in clinical development, to date, pegaptanib is the only therapy approved by the Food and Drug Administration of the United States for the treatment of all neovascular AMD and represents a valuable addition to the hitherto limited options available for patients.     

Optical coherence tomography findings during pegaptanib therapy for neovascular age-related macular degeneration

BACKGROUND: To evaluate macular thickness measured by optical coherence tomography (OCT) during pegaptanib therapy for neovascular age-related macular degeneration (AMD). METHODS: For this prospective, nonrandomized, observational case series, 41 eyes from 41 patients with neovascular AMD received intravitreous pegaptanib (1 mg) injections repeated every 6 weeks. The primary outcome measure was central foveal thickness measured by OCT. Secondary outcomes were fluorescein angiographic leakage and visual acuity. RESULTS: Mean thickness of the central area on OCT decreased from 340 +/- 24 microm to 299 +/- 14 microm after 12 weeks of pegaptanib injections. This represents a reduction in thickening of 32%. Fluorescein angiograms with definite leakage decreased from 100% to 81%, and mean visual acuity decreased from 20/116 to 20/120. CONCLUSIONS: Intravitreal injections of pegaptanib at 6-week intervals result in a moderate reduction of central foveal thickness in eyes with subfoveal neovascular AMD. This presents a modest effect relative to that reported with other anti-angiogenic agents.     

Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration: a short-term study

PURPOSE: To report the short-term study of intravitreal bevacizumab (Avastin) in the treatment of neovascular age-related macular degeneration (AMD). DESIGN: Interventional, consecutive, prospective case series. METHODS: One hundred and two eyes of 102 patients with neovascular AMD received monthly intravitreal bevacizumab (Avastin) (1.25 mg) until resolution of macular edema, subretinal fluid, and/or pigment epithelial detachment. Outcome measures included visual acuity (VA) and central retinal thickness as defined from optical coherence tomography (OCT). RESULTS: Mean VA was 20/80 and OCT central retinal thickness was 251.0 +/- 74.6 microm before injection and improved to 20/63 and 214.9 +/- 41.7 microm at six weeks (P < .001), 20/50 and 204.8 +/- 33.6 microm at 10 weeks (P < .001), and remained stable at 20/50 and 210 microm after 14 weeks (P < .05). No significant ocular or systemic side effects were observed. CONCLUSIONS: Intravitreal bevacizumab (Avastin) appears to be beneficial and well tolerated in the treatment of neovascular AMD in the short term. Further comparative evaluation against other antivascular endothelial growth factor (VEGF) agents and dosing schedule is warranted.     

Intravitreal bevacizumab (Avastin) treatment of neovascular age-related macular degeneration

PURPOSE: To report the change in visual acuity and central retinal thickness by optical coherence tomography (OCT) after intravitreal injections of bevacizumab for the treatment of neovascular age-related macular degeneration (AMD). METHODS: A retrospective case series in a university-based practice evaluated patients with subfoveal choroidal neovascularization (CNV) due to AMD. Patients received intravitreal injections (1.25 mg) of bevacizumab and were monitored monthly with determination of best-corrected ETDRS visual acuity and OCT for persistence of retinal thickening. Eyes were retreated on an "as needed" basis, defined by presence of intraretinal or subretinal fluid. Patients were monitored every 2 months to 3 months for persistence of angiographic leakage. RESULTS: Seventy-nine eyes of 74 consecutive patients received the initial injection of bevacizumab between August 1, 2005, and January 30, 2006. Sixty-eight eyes (86%) of 64 patients had at least 3 months of follow-up. Mean central retinal thickness +/- SD decreased from 304 +/- 83 microm at baseline to 237 +/- 105 microm at 3 months (P = 0.00002). Mean ETDRS visual acuity gained 4 letters from 20/100 at baseline to 20/80-1 at 3 months (P = 0.040). Twenty eyes (25%) appeared to have a sustained response to a single injection and did not require further injections through 3 months. Two patients had a potentially drug-related adverse event (ischemic stroke and myocardial infarction). No serious injection-related adverse events occurred. CONCLUSIONS: Intravitreal bevacizumab injection affects a rapid decrease in retinal thickness to normal or near-normal levels and improvement in visual acuity in eyes with CNV due to AMD. The sustainability of changes in retinal thickness and visual acuity in response to bevacizumab treatment warrant further investigation and long-term follow-up.     

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment*

Objective: To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Design: Retrospective, consecutive, interventional case series. Participants: Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Methods: Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Results: Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455?µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p?p?=?0.029). In patients with PED, there was a mean 27.9% reduction in height (p?=?0.046) at eight weeks’ follow-up. Conclusions: Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.     

Enhanced efficacy associated with early treatment of neovascular age-related macular degeneration with pegaptanib sodium: an exploratory analysis

PURPOSE: To assess the vision benefit of treating early subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) with pegaptanib sodium. METHODS: Exploratory analyses of week 54 vision outcomes (VEGF Inhibition Study in Ocular Neovascularization study) of subject subgroups with early disease who received 0.3 mg of pegaptanib (Groups 1 [n = 34] and 2 [n = 30]) or sham injections (usual care). Two sets of clinical characteristics typical of early disease defined the subgroups. RESULTS: Baseline characteristics were generally well balanced between treatment arms. Pegaptanib responder rates (loss of <15 letters of visual acuity) were 76% and 80% in treatment Groups 1 and 2 versus 50% and 57% for usual care Groups 1 and 2 (P = 0.03 and P = 0.05), respectively. Compared with subjects assigned to pegaptanib, those in Groups 1 and 2 receiving usual care on average lost 11.1 letters and 12.7 letters more of visual acuity (P < 0.01 and P < 0.006), respectively. Subjects assigned to usual care were approximately 10 times more likely to have severe vision loss than were those treated with pegaptanib (Group 1, 29% vs. 3%, respectively; P < 0.01). In Group 1, 12% of pegaptanib-treated subjects gained > or =15 letters of visual acuity versus 4% receiving usual care; 20% of Group 2 pegaptanib-treated subjects gained > or =15 letters of visual acuity versus none of the usual care subjects. CONCLUSION: Early detection and treatment with pegaptanib may result in superior vision outcomes in patients with neovascular AMD.     

Early effects of systemic and intravitreal bevacizumab (avastin) therapy for neovascular age-related macular degeneration

PURPOSE: The purpose of this study was to evaluate the early treatment response following systemic and intravitreal bevacizumab therapy in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: In a prospective cohort study 12 eyes with neovascular AMD were treated with 5 mg/kg systemic bevacizumab, and 13 eyes with 1 mg intravitreal bevacizumab. Systemic therapy was given three times at 2-week intervals, intravitreal therapy up to three times at 4-week intervals. Patients were evaluated according to best corrected visual acuity (VA) and optical coherence tomography (OCT) at baseline as well as at week 1, week 4 and week 12 after therapy. Fluorescein angiography (FA) was performed at baseline and week 12. RESULTS: Systemic and intravitreal bevacizumab therapy showed a treatment response within one week. Visual acuity improved at week 1 by 4.9 letters from baseline in the systemic and by 6.9 letters in the intravitreal treatment group. Central retinal thickness (CRT), as measured by OCT decreased by 51.9 microm and 176.4 microm, respectively. At month 3 a persistent treatment effect was detectable. Mean gain in visual acuity was 11 letters in the systemic and 8.3 letters in the intravitreal group, CRT had decreased by 100 microm and 153.8 microm, respectively. Leakage as evaluated by FA was significantly reduced or absent in all patients. CONCLUSION: The early treatment responses following systemic and intravitreal bevacizumab appear to be similar. Both groups show improvement in VA and decrease in CRT within 1 week and up to 3 months. Long-term follow-up is required to evaluate the safety and treatment durability of both treatment modalities using bevacizumab.     

Retinal pigment epithelial tears after intravitreal bevacizumab injection for exudative age-related macular degeneration

Purpose: To determine the incidence of and the risk factors for the development of retinal pigment epithelial (RPE) tears after intravitreal bevacizumab (Avastin) injection for the treatment of exudative age‐related macular degeneration (AMD). Methods: A retrospective, multicentre, consecutive interventional case series of all patients with subfoveal exudative AMD treated with intravitreal bevacizumab between August 2005 and April 2007. The main outcome measures were pre‐ and post‐RPE tear visual acuity and choroidal neovascular membrane lesion types, incidence of tears and time from first injection until development of the tear. Results: A total of 920 eyes with exudative AMD were treated with intravitreal bevacizumab. Fifteen eyes from 15 patients developed a RPE tear for an incidence of 1.6%. The average patient age was 79 years. Fourteen of the fifteen eyes (93%) had an occult subfoveal choroidal neovascular membrane. Forty‐seven per cent (7/15) of the RPE tears occurred within the first 6 weeks of treatment, and all tears occurred within the first 18 weeks of treatment initiation. The mean pre‐injection visual acuity was 20/100 with a mean post‐tear visual acuity of 20/200. In all 10 eyes in which the tear involved the fovea, the final visual acuity was poor. Six of the 15 eyes continued with bevacizumab/ranibizumab (Lucentis) injections after tear development, and four of these six eyes continued to have visual improvement. Conclusion: RPE tears occur after intravitreal bevacizumab injections for exudative AMD in approximately 1.6% of eyes and can cause severe vision loss. Maintenance of therapy may help preserve vision after RPE tear development.     

Intravitreal bevacizumab (Avastin) iniections for neovascular age-related macular degeneration (AMD)--preliminary results

PURPOSE: To evaluate effects of intravitreal bevacizumab on visual acuity and angiographic lesions characteristics in patients with neovascular AMD and to report safety of such treatement. MATERIAL AND METHODS: 32 patients with confirmed choroidal neovascularisation (CNV) and AMD were treated. Patients received 2 intravitreal bevacizumabu (1.25 mg) iniections on 1-3 months basis. Control ophthalmic evaluations included visual acuity measurements with EDTRS charts, intraocular pressure measurements, complete ophthalmic examination in slit lamp, fluorescein angiography and blond pressure measurements. RESULTS: In 18 patients (56%) visual acuity improvement at a mean 3 lines on EDTRS charts was observed, in 9 patients (28%) visual acuity did not change and in 5 (16%) cases decreased visual acuity (about 1,5 lines in EDTRS charts) was noted. Mean follow-up period was 3 months after second injection. In most study eyes fluorescein angiography revealed a marked reduction in leakage from CNV. Apart from one case with endophthalmitis symptoms after second bevacizumab injection, we did not observed systemic or ocular adverse effects of the applied treatment. CONCLUSIONS: Short-term results suggest that intravitreal bevacizumab is relatively safe form of AMD treatement and is associated with improvement in visual acuity and reduction in angiographic leakage in most patients with neovascular AMD. Further evaluation of the long-term effectiveness of this treatment is warranted.     

Pegaptanib and ranibizumab for neovascular age-related macular degeneration: a systematic review

AIMS: To assess the clinical effectiveness of pegaptanib sodium and ranibizumab for neovascular age-related macular degeneration (AMD). METHODS: A systematic review of randomised controlled trials (RCTs) identified through searching 12 electronic databases, bibliographies and consultation with experts and manufacturers. RCTs were eligible if they assessed the effects of pegaptanib or ranibizumab with best supportive care, sham injection or photodynamic therapy (PDT) on patients with subfoveal choroidal neovascularisation associated with wet AMD and examined outcomes including visual acuity and adverse events. RESULTS: Three RCTs of ranibizumab (MARINA, ANCHOR, FOCUS) and two of pegaptanib (VISION study) met the inclusion criteria. The RCTs included patients with different lesion types. The studies showed statistically significant benefit on different measures of visual acuity for patients receiving pegaptanib, ranibizumab or ranibizumab with PDT compared to control (sham injection, PDT or sham injection with PDT) after 12 months. These differences appeared to be clinically significant. Although adverse events were common among those receiving pegaptanib or ranibizumab, they were considered mild to moderate in nature. Meta-analysis of ranibizumab trials and indirect comparison of the two drugs were not possible due to differences in the study populations' lesion types. However, results from the RCTs of ranibizumab tended to show a greater effect on visual acuity than results from the RCT of pegaptanib. CONCLUSIONS: Pegaptanib and ranibizumab appear to slow or stop the progression of neovascular AMD. Uncertainty remains over the relative benefits of pegaptanib compared with ranibizumab and other unlicensed drugs (eg, Avastin), due to the nature of the evidence. Head-to-head RCTs and economic evaluations comparing these alternatives are needed.     

Bevacizumab and Neovascular Age Related Macular Degeneration: Pathogenesis and Treatment

The pathogenesis of neovascular age related macular degeneration (AMD) is multifactorial including inflammation and angiogenesis leading to choroidal neovascularization (CNV). Therapy against vascular endothelial growth factor (VEGF) has revolutionized the treatment of neovascular AMD. Intravitreal off-label use of bevacizumab proved to be safe. This literature review was conducted to study improvement in visual acuity, change in central retinal thickness (CRT), safety, pharmacodynamics, and possible resistance to intravitreal bevacizumab over a one-year period in eyes with neovascular AMD. We reviewed articles between 1997 and January 2010 that included at least 30 patients with AMD who received intravitreal bevacizumab monotherapy for at least 1 year. The mean number of letters gained, decrease in CRT, and number of injections were 8 letters, 125.3?µm, and 4.3 injections, respectively. Further, randomized prospective clinical trials are needed to determine the efficacy and safety of intravitreal bevacizumab in the treatment of neovascular AMD.     

Bevacizumab and neovascular age related macular degeneration: pathogenesis and treatment

The pathogenesis of neovascular age related macular degeneration (AMD) is multifactorial including inflammation and angiogenesis leading to choroidal neovascularization (CNV). Therapy against vascular endothelial growth factor (VEGF) has revolutionized the treatment of neovascular AMD. Intravitreal off-label use of bevacizumab proved to be safe. This literature review was conducted to study improvement in visual acuity, change in central retinal thickness (CRT), safety, pharmacodynamics, and possible resistance to intravitreal bevacizumab over a one-year period in eyes with neovascular AMD. We reviewed articles between 1997 and January 2010 that included at least 30 patients with AMD who received intravitreal bevacizumab monotherapy for at least 1 year. The mean number of letters gained, decrease in CRT, and number of injections were 8 letters, 125.3 μm, and 4.3 injections, respectively. Further, randomized prospective clinical trials are needed to determine the efficacy and safety of intravitreal bevacizumab in the treatment of neovascular AMD.     

Pegaptanib for the treatment of age-related macular degeneration

Although neovascular (wet) age-related macular degeneration (AMD) only accounts for 10-20% of all AMD, the majority (about 90%) of severe vision loss associated with AMD is due to this form. Results from recent studies have implied that vascular endothelial growth factor (VEGF), particularly VEGF(165), plays a predominant role in the development of ocular neovascularization and vascular leakage secondary to AMD. Thus VEGF is an important therapeutic target in neovascular AMD. Pegaptanib, an anti-VEGF aptamer, can selectively bind with VEGF(165) and inhibit both the growth of blood vessels and vascular leakage, and was approved by the Food and Drug Administration in the United States as the therapy for the treatment of all subtypes of neovascular AMD in December 2004. This review summaries the mechanism, preclinical and clinical studies, and adverse events of pegaptanib treatment.     

Clinical experience in the treatment of neovascular age-related macular degeneration with pegaptanib

BACKGROUND: Intravitreal anti-VEGF therapy with Pegaptanib was effective in neovascular AMD in the VISION study. We report our experience with Macugen for the treatment of occult or minimally classic choroidal neovascularisation (CNV) due to age-related macular degeneration (AMD). PATIENTS AND METHODS: 35 eyes of 35 patients with occult CNV or minimally classic CNV due to neovascular AMD not eligible for PDT were treated with intravitreal injection of 0.3 mg Pegaptanib. An average of 2.74 injections per patient was administered. Before, and every 3 months after treatment, visual acuity, intraocular pressure measurement, angiography and OCT examinations were performed. One month after treatment only visual acuity, intraocular pressure measurement, and OCT examinations were performed. Visual acuity measurements and an eye examination were done on the first and second day after injection, after 4-6 weeks and at months 3 and 6. RESULTS: Intravitreal Pegaptanib was well tolerated and we had no complications. Mean visual acuity was 0.38 +/- 0.23 at baseline, after one month 0.38 +/- 0.26, at 3 months it was 0.39 +/- 0.22 and at 6 months 0.41 +/- 0.26. OCT examinations showed a decrease in central retinal thickness from 277 microm to 254 microm. In 91.4 % of the eyes the visual acuity was stabilised or improved. No patient had an elevated intraocular pressure after 6 months. CONCLUSIONS: Intravitreal therapy with Pegaptanib was safe and effective. The majority of patients showed a stabilisation in all the assessed parameters. In clinical practice unselective VEGF inhibition should be considered carefully for patients with high cardiovascular risk profile or thromboembolic events in the history.     

Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration

PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). METHODS: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. RESULTS: Fifty-three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P < 0.001) and the mean central retinal thickness decreased by 99.6 microm (P < 0.001). CONCLUSION: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.     

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 bevacizumab in the treatment of neovascular age-related macular degeneration, 6- and 9-month results

PURPOSE: To evaluate 6- and 9-month follow-up data including the effect on vision and anatomic outcome in patients treated with intravitreal bevacizumab for neovascular age-related macular degeneration (AMD). STUDY DESIGN: Interventional consecutive retrospective case series. Patients received intravitreal bevacizumab for the treatment of neovascular AMD including choroidal neovascular membranes, pigment epithelial detachment, and macular haemorrhage. Ophthalmic evaluation included log MAR or Snellen acuity, ophthalmic examination, optical coherence tomography, and fluorescein angiography. Repeat injections were given in the presence of persistent leakage or retinal oedema. Change in vision and foveal thickness from baseline was evaluated using the paired Student's t-test. RESULTS: A total of 112 eyes of 111 patients received injections. Median follow-up was 5 months (range: 1-12 months). Mean log MAR vision pre-injection was 0.84+/-0.03 (n=112); at 3 months was 0.69+/-0.05 (P<0.0001, n=84); at 6 months was 0.74+/-0.06 (P<0.05, n=51); and at 9 months was 0.69+/-0.08 (n=29, P=0.09). Thirteen of 17 patients who received only one injection maintained improved or stable vision at 6 months. Mean baseline foveal thickness was 291+/- 9.72 microm (n=56); at 3 months was 282.7+/-28 (P<0.05, n=31); and at 6 months was 249.7+/-10.3 (P<0.05, n=12). One case of endophthalmitis, three submacular haemorrhages, and three retinal pigment epithelial (RPE) tears occurred. CONCLUSION: Intravitreal bevacizumab is an effective treatment for neovascular AMD, resulting in improved vision and foveal anatomy at 6 months and even up to 9 months. This treatment is well tolerated in the majority of patients but adverse events may include endophthalmitis, RPE tears, and submacular haemorrhage.     

Retinal pigment epithelial tears after single administration of intravitreal bevacizumab for neovascular age-related macular degeneration

PURPOSE: To analyse retinal pigment epithelial (RPE) tears following single administration of intravitreal bevacizumab for neovascular age-related macular degeneration (AMD) during early follow-up. METHODS: Interventional, retrospective, non-comparative case series included 397 patients (409 eyes) of the 746 consecutive patients that met the eligibility criteria. Standardized visual acuity testing, fluorescein angiography, and optical coherence tomography were performed. Data collected included status of the fellow eye, previous treatment, subtypes of choroidal neovascularization (CNV), size and composition of the lesion. Multiple linear regression modelling was used to explore the effect of baseline parameters on the RPE tears. Primary end point was occurrence of RPE tears within 6 weeks after therapy. RESULTS: Fifteen of the 409 eyes (3.6%) developed RPE tear (95% confidence interval: 2.2-6.0, odds ratio: 26.3). The statistical modelling showed significant association between RPE tear and occult without classic CNV/predominantly haemorrhage vspredominantly/minimal classic CNV (P=0.019), as well as medium or large (>4 disc area) vssmall size of the total lesion (P=0.038). Previous treatment and status of the fellow eye did not statistically influence the risk of RPE tears. CONCLUSIONS: An RPE tear can develop in up to 3.6% of eyes with neovascular AMD following single administration of intravitreal bevacizumab in a short-term follow-up. Medium and large lesion size and occult without classic and predominantly haemorrhagic subtype of CNV were important predictive factors. Preoperative assessment of the lesion characteristics may help in identifying the risk of individual patients with neovascular AMD before intravitreal bevacizumab treatment.