EXTEND III: Efficacy and safety of ranibizumab in South Korean and Taiwanese patients with subfoveal CNV secondary to AMD

BACKGROUND: The purpose of this study was to investigate the efficacy and safety of intravitreal ranibizumab 0.5?mg in South Korean and Taiwanese patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: This was a 12-month, open-label, single-arm, multi-center, phase III study. Ninety-five patients (Taiwanese: 51; South Korean: 44) were included in the study. Key outcome measures assessed included: mean change in best-corrected visual acuity (BCVA) from baseline to months 4 (primary endpoint) and 12 (secondary endpoint); other secondary endpoints comprising categorized mean change in BCVA from baseline at month 4 and month 12, mean change in BCVA from baseline at month 4 and month 12 per baseline characteristics; and incidence of ocular and non-ocular adverse events and serious adverse events (SAEs) at month 12. RESULTS: The mean BCVA change improved significantly (p?相似文献   

EXTEND‐I: safety and efficacy of ranibizumab in Japanese patients with subfoveal choroidal neovascularization secondary to age‐related macular degeneration

Purpose: To evaluate the efficacy and safety of intravitreal ranibizumab for subfoveal choroidal neovascularization (CNV) secondary to age‐related macular degeneration (AMD) in Japanese patients. Methods: This open‐label, multicentre, Phase I/II study enroled patients into Group A (single injection of ranibizumab nonrandomized doses of 0.3 or 0.5 mg followed by 11 monthly injections of the same dose) and Group B (12 monthly injections of ranibizumab randomized to 0.3 or 0.5 mg). The primary efficacy endpoint was the mean change from baseline in best‐corrected visual acuity (BCVA) score at Month 6. Safety was evaluated in all patients who received ranibizumab. Results: Of 88 patients enroled, 12 entered Group A (six per dose) and 76 entered Group B (0.3 mg: n = 35; 0.5 mg: n = 41). Mean change from baseline in BCVA was significantly increased for both doses (Group B) at Month 6 (0.3 mg: +8.1 letters, p = 0.0006; 0.5 mg: +9.0 letters, p < 0.0001) and Month 12 (0.3 mg: +9.5 letters, p = 0.0001; 0.5 mg: +10.5 letters, p < 0.0001). At Month 12, one patient (0.3 mg) and 0 patients (0.5 mg) lost ≥15 letters, while 37.1% (0.3 mg) and 31.7% (0.5 mg) of patients gained ≥15 letters. Ocular serious adverse events (SAEs) of the study eye were reported in 1 and 2 patients in the 0.3‐ and 0.5‐mg groups, respectively. Nonocular SAEs were experienced by 2 and 5 patients in the 0.3‐ and 0.5‐mg groups, respectively. No cases of endophthalmitis were reported. Conclusion: Ranibizumab was effective and well tolerated in Japanese patients with subfoveal CNV secondary to AMD.     

Combination treatment of photodynamic therapy with verteporfin and intravitreal ranibizumab in patients with retinal angiomatous proliferation

Purpose: To investigate the efficacy and safety of initial photodynamic therapy (PDT) with a ranibizumab loading dose of three monthly intravitreal injections and a subsequent PRN ranibizumab regimen in the treatment of retinal angiomatous proliferation (RAP). Methods: In this 12‐month prospective case series, 15 patients underwent PDT followed by 3 intravitreal ranibizumab injections at monthly intervals. At monthly follow‐up examinations, further single ranibizumab injections were given in case of any intra‐ or subretinal fluid on optical coherence tomography (OCT), visual loss ≥5 letters or signs of activity on fluorescein or indocyanine green angiography. Results: Best‐corrected visual acuity (BCVA) improved from 58.1 ± 13.2 at baseline by 9.2 letters (SD ± 8.5; p = 0.004) at 6 months and by 8.7 letters (SD ± 11.4; p = 0.017) at 12 months. Neither at 6 nor at 12 months, any patient had lost ≥15 letters. The mean number of injections per patient was 4.8 (SD ± 1.4) in the first year of therapy after PDT. The average time to first retreatment was 3.7 months (range 1–7 months). No serious adverse events, such as endophthalmitis or retinal detachment, were noted. Conclusion: PDT with 3 ranibizumab loading injections and subsequent ranibizumab as needed resulted in a significant gain of 8.7 ± 11.4 letters at month 12. This regimen is safe and efficacious, but even in a population of mostly early stages of RAP, retreatment rates remained high.     

An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration

PURPOSE: To evaluate an optical coherence tomography (OCT)-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD). DESIGN: Open-label, prospective, single-center, nonrandomized, investigator-sponsored clinical study. METHODS: In this two-year study, neovascular AMD patients with subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal thickness of at least 300 microm as measured by OCT were enrolled to receive three consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Thereafter, retreatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 microm, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab. RESULTS: At month 12, the mean visual acuity improved by 9.3 letters (P < .001) and the mean OCT central retinal thickness decreased by 178 microm (P < .001). Visual acuity improved 15 or more letters in 35% of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary. CONCLUSION: This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the Phase III clinical studies, but required fewer intravitreal injections. OCT appears useful for determining when retreatment with ranibizumab is necessary.     

Effect of intravitreal bevacizumab (Avastin®) in neovascular age‐related macular degeneration using a treatment regimen based on optical coherence tomography: 6‐ and 12‐month results

Purpose: To study the effect of intravitreal bevacizumab therapy on visual and anatomical outcomes in patients with neovascular age‐related macular degeneration (AMD) within a follow‐up period of 6 and 12 months. Methods: A retrospective analysis of 102 eyes of 102 consecutive patients with neovascular AMD evaluated repeated intravitreal bevacizumab (1 or 2.5 mg) injections. Retreatment was performed following an optical coherence tomography (OCT)‐based regimen. Ophthalmic examination included best‐corrected visual acuity (BCVA), dilated fundus examination and OCT imaging. Data were analysed at baseline, 6 months (24 weeks) and 12 months (48 weeks) after treatment initiation. Results: BCVA remained stable at 6 months (mean: 0.00 ± 0.41 logMAR; p = 0.95) and 12 months (mean: +0.02 ± 0.43 logMAR; loss of ～ 1 letter; p = 0.70) after the first treatment. OCT retinal thickness decreased by a mean of ?37.8 ± 101.6 μm (p < 0.05) compared to baseline at month 6 and ?38.6 ± 93.3 μm (p < 0.05) at month 12. A mean of 2.6 ± 1.2 injections were needed to obtain absence of fluid by OCT, and the time to recurrence was 23 ± 11 weeks thereafter. There was no difference in BCVA and OCT outcomes between treatment‐naive eyes and eyes that had undergone prior treatment. Conclusion: The 6‐ and 12‐month follow‐up of repeated intravitreal bevacizumab therapy in eyes with neovascular AMD demonstrated stabilization of vision and no safety concerns. An OCT‐based retreatment strategy appears appropriate in the management of patients treated with intravitreal bevacizumab.     

Decisional answer tree analysis of exudative age-related macular degeneration treatment outcomes

The use of intravitreal ranibizumab in exudative age-related macular degeneration (eAMD) has become commonplace. We aim to investigate the early predictors of this treatment outcome. Seventy-one treatment-naive eyes of 71 patients with eAMD of all lesion subtypes who received intravitreal ranibizumab treatment and completed 12 months of follow-up were included. All patients were loaded with three injections of ranibizumab at monthly intervals. Further injections were given if clinically indicated based on logMAR best-corrected visual acuity (BCVA) and optical coherence tomography findings. Casenotes of eligible patients were reviewed retrospectively. The main outcome measure was logMAR BCVA change at month 12. The mean number of injections given over 12 months was 5.4 ± 1.9. A total of 88.7 % of the patients achieved visual stabilisation (loss of <15 letters) and 15.0 % achieved visual improvement (gain of ≥15 letters). The mean letter change at 12 months was +0.3 letters. Regression analysis showed that baseline BCVA and letter change at month 3 predicted visual acuity outcome at month 12 (baseline BCVA: t = 6.97, p < 0.001; letter change: t = 5.84, p < 0.01) but age, gender and eAMD in the fellow eye were not predictive. Finally, a decisional answer tree model demonstrated that letter change at month 3 was a strong predictor of visual outcome at month 12 with an overall accuracy of 69 %. We found that letter change from baseline at month 3 was strongly predictive of visual outcome at month 12.     

A three‐year follow‐up of ranibizumab treatment of exudative AMD: impact on the outcome of carrying forward the last acuity observation in drop‐outs

Purpose: To analyse a 3‐year clinical patient cohort of ranibizumab treatment of exudative age‐related macular degeneration (AMD), to investigate the impact on visual outcome of carrying forward the last acuity observation in drop‐outs and to explore possible differences between the early and the late phase of the study. Methods: A retrospective study of 312 eyes with neovascular AMD. The patients were followed up monthly, received three initial monthly injections of 0.5 mg ranibizumab and were re‐treated pro re nata (PRN). Time‐domain optical coherence tomography (TD‐OCT) was used until spectral‐domain (SD)‐OCT was introduced during the last year of enrolment. Sixty‐five patients were discontinued from the study. Primary outcome: change in best corrected visual acuity (BCVA). Results: Best corrected visual acuity was 58.4 (CI 56.9–59.9) ETDRS (Early Treatment Diabetic Retinopathy Study) letters. At three months, it had increased by 4.1 letters (p = 0.0004), at 12 months by 1.8 letters, at 24 months by 1.0 letter and at 36 months by 0.1 letter. However, if the last available acuity of drop‐outs was carried forward one step and included, acuity had increased by 3.9 letters at 3 months (p < 0.0001) and by 1.0 letter at 12 months but had decreased by 3.8 letters at 24 months (p = 0.019) and by 4.1 letters (p = 0.003) at 36 months. At 24 months, the result was significantly (p = 0.030) less favourable when drop‐outs were included. In patients enrolled during the late phase, BCVA was 59.3 (CI 56.7–62.0). It had increased by 5.7 letters (p < 0.0001) at three months and by 5.8 letters at 12 months (p = 0.0016). In patients enrolled during the early phase, BCVA was 57.9 (CI 55.0–60.8). At three months, it had increased by 3.5 letters (p = 0.0008), but at 12 months, it had decreased by 2.3 letters (ns). The result at 12 months was significantly (p = 0.0033) better for the late than for the early phase. The number of injections was also significantly (p = 0.011) higher in the late phase. Adverse events were similar to those in earlier clinical trials. Conclusions: The results of this 3‐year cohort showed that the initial average acuity could be maintained over 36 months, which was comparable to those of many other clinical cohorts. However, if the last available acuity of drop‐outs was carried forward one step and included, the acuity figures would have fallen significantly. The results in patients enrolled during the late phase of the study were fairly similar to those in clinical trials.     

Treatment patterns,visual acuity and quality‐of‐life outcomes of the WAVE study – A noninterventional study of ranibizumab treatment for neovascular age‐related macular degeneration in Germany

Purpose: To evaluate effectiveness, tolerability and safety of repeated intravitreal injections of 0.5 mg ranibizumab for the treatment of neovascular age‐related macular degeneration in routine medical practice in Germany. Methods: A noninterventional study with 3470 patients treated in 274 medical centres according to German guidelines, with monthly intravitreal injections of 0.5 mg ranibizumab during upload (3 months) followed by a maintenance phase (9 months) with reinjections if medically indicated. Results: Mean injection rate was 4.34 (SE = 0.05; median = 3.0). Best‐corrected visual acuity (BCVA) remained stable (mean change 0.02 LogMAR, SE = 0.01, p = 0.0169) and central retinal thickness (CRT) decreased (by ?78.9 μm, SE = 2.95 μm, p < 0.0001). The NEI‐VFQ 25 summary score showed a positive stabilization with a mean change of 0.73 (SE = 0.37, p = 0.0501) compared with baseline. Adverse events were documented for 6.5% of the patients with 3.9% of these events being classified as serious. Conclusions: The number of administered intravitreal injections of ranibizumab over the first year of treatment was very low but still achieved a stabilization of BCVA, a reduction in CRT and maintained vision‐related quality of life. The management of patients with neovascular AMD in Germany needs to be improved to achieve better treatment results.     

Efficacy of 12‐month treatment of neovascular age‐related macular degeneration with intravitreal bevacizumab based on individually determined injection strategies after three consecutive monthly injections

Purpose: To report the results of intravitreal treatment with bevacizumab in neovascular age‐related macular degeneration (AMD) after a loading dose (LD) of three monthly injections followed by an optical coherence tomography (OCT)‐guided strategy, based on best‐corrected visual acuity (VA) and number of injections required over 1 year. Methods: A series of consecutive cases of 149 eyes of 147 patients received three or more intravitreal injections of bevacizumab (1.25 mg) for neovascular AMD over a 1‐year period. The patients underwent ophthalmological examinations: measurement of the VA, fluorescein angiography, dilated fundus examination at baseline; VA, OCT and dilated fundus examination at monthly follow‐up visits. Repeated injections were given each month for the first 3 months (LD); thereafter, injections were only administered if leakage or macular oedema were present. Results: Mean baseline VA was 51 ± 14 letters, which improved to 58 ± 15 letters (p < 0.0001; n = 149) at first evaluation (15 ± 2 weeks), 59 ± 15 letters (p < 0.0001; n = 143) at second evaluation (25 ± 2 weeks) and 57 ± 16 letters (p < 0.0001; n = 132) at third evaluation (51 ± 3 weeks). The baseline mean central retinal thickness (344.6 μm) and total macular volume (8.6 mm³) decreased at first evaluation, to 219.0 μm (p < 0.0001) and 7.2 mm³ (p < 0.0001), respectively. The mean number of injections per patient treated for 1 year was 5.1 (range 3–9). No systemic side‐effects were noted. Conclusion: Treatment of neovascular AMD with intravitreal bevacizumab administered in LD of three monthly injections and followed by an OCT‐guided strategy provides functional and anatomical improvements for up to 1 year.     

Long‐term results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age‐related macular degeneration

Purpose: To study the effect of intravitreal (IVT) ranibizumab on the retinal arteriolar diameter in patients with neovascular age‐related macular degeneration (AMD). Methods: Ten eyes of 10 patients with previously untreated neovascular AMD were included. All eyes had three monthly IVT injections of ranibizumab and then were retreated as needed, based on visual acuity and optical coherence tomography (OCT) criteria. The diameter of the retinal arterioles was measured in vivo with a retinal vessel analyser (RVA) before the first IVT injection, 7 and 30 days after the first, the second and the third injection, and at month 12 of follow‐up. Results: A significant vasoconstriction of the retinal arterioles was observed following each one of the first three IVT injections of ranibizumab. Thirty days following the first, second and third injection, there was a mean decrease of 8.4 ± 3.2%, 11.9 ± 4.5% and 18.5 ± 7.2%, respectively, of the retinal arteriolar diameter compared with baseline (p < 0.01). At month 12, the vasoconstriction was still present with a mean decrease of 19.1 ± 8.3% of the retinal arteriolar diameter compared with baseline (p < 0.01). Median number of ranibizumab injections was 4 (range 3–10). There was no correlation between the number of injections and percentage diameter decrease at month 12 (r = ?0.54, p > 0.1). There was no significant change in mean arterial pressure (MAP) during the period of follow‐up (p > 0.05). Conclusions: These results suggest that IVT ranibizumab induces sustained retinal arteriolar vasoconstriction in eyes with neovascular AMD.     

Effects of combination therapy with verteporfin photodynamic therapy and ranibizumab in patients with age‐related macular degeneration

Purpose: This open‐label, prospective, small‐scale study investigated the benefits of same‐day verteporfin and intravitreal ranibizumab in patients with predominantly classic, minimally classic or occult subfoveal choroidal neovascularization (CNV) secondary to age‐related macular degeneration. Methods: Patients received verteporfin at baseline and at month 3, if leakage persisted. Ranibizumab (0.5 mg) was given at baseline and months 1, 2 and 3, and thereafter at monthly intervals if required. Same‐day ranibizumab was given ≥ 1 hr after verteporfin. Results: Fifteen patients [11 male, four female; mean age 75.5 years (range 54–94 years)] were treated. At day 360, mean visual acuity (VA) had improved by 10.9 letters. An increase of ≥ 15 and ≥ 30 letters (i.e. ≥ 3 and ≥ 6 lines) was observed in seven (47%) patients and one patient (7%), respectively. Mean central retinal thickness (CRT) decreased by 85 μm. At days 7, 14 and 30, CNV perfusion was absent in 14/15 patients. Mean lesion area had reduced from baseline by 23.1% at day 120, 25.5% at day 180 and 23.6% at day 360. There were no visual safety concerns and intraocular pressures remained normal. Only two serious adverse events were recorded over the 12‐month period, and neither was considered to be related to treatment. Conclusion: Same‐day verteporfin plus ranibizumab improved VA, reduced CRT, prevented CNV perfusion and reduced lesion area safely over 12 months. Further investigation is warranted to confirm whether this combination improves long‐term vision and reduces the need for retreatment.     

Visual acuity outcomes in ranibizumab-treated neovascular age-related macular degeneration; stratified by baseline vision

Background: Ranibizumab (Lucentis, Novartis, Basel, Switzerland) is currently indicated for use in neovascular age‐related macular degeneration (NVAMD). This study assessed the real‐life outcomes based on baseline visual acuity when treated with intravitreal ranibizumab on a three + pro re nata (PRN) dosing schedule for NVAMD. Design: This retrospective chart‐review was conducted at King's College Hospital. The patients were stratified into three groups based on baseline Early treatment diabetic retinopathy study (ETDRS) letters: 27 with poor visual acuity (24–34 letters), 33 with intermediate visual acuity (35–54 letters) and 27 with good visual acuity (≥=55 letters). Methods: All patients received a three + PRN dosing schedule of ranibizumab injections (0.5 mg per 0.05 mL) based on changes in visual acuity and macular thickness on optical coherence tomography (OCT) and all patients completed 12‐month follow up. Main Outcome Measures: The mean change in visual acuity at 12 months in the three groups. Results: Mean gain in ETDRS letters at 12 months was +14.00 (P < 0.0001), +7.10 (P = 0.012) and +2.85 (P = 0.19), and mean number of injections was 5.30, 6.12 and 5.70 in the poor, intermediate and good baseline vision group, respectively, over the 12‐ month follow‐up period. Conclusions: Poor baseline visual acuity (24–34 ETDRS letters) is a predictor of maximum gain in visual acuity. However, eyes with better baseline visual acuity (55 letters) had a better final visual acuity.     

Intravitreal ranibizumab for macular oedema secondary to retinal vein occlusion: a retrospective study of 34 eyes

Purpose: To evaluate the efficacy and the safety of intravitreal ranibizumab injection (Lucentis) in eyes with macular oedema secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Methods: The files of consecutive patients (34 eyes, 15 CRVO, 19 BRVO) were retrospectively analysed. Intravitreal injections of 0.5 mg ranibizumab were administered; retreatment was based on acuity visual changes and optical coherence tomography findings. Patients received 2–4 injections (mean, 2.1). Mean follow‐up was 7 months. Results: After the first injection, mean best‐corrected visual acuity (BCVA) improved from 20/160 to 20/80 and mean central retinal thickness (CRT) decreased significantly from 549 to 301 μm (p < 0.01). For each injection, BCVA improvement was on average nine letters (p < 0.01) and macular oedema reduction was 195 μm CRT (p < 0.01). The decrease in CRT was similar in CRVO and BRVO, but the improvement in BCVA was larger in BRVO. No local or systemic adverse effect was detected. Final visual acuity was correlated to initial visual acuity and to visual acuity measured after the first injection. The change in CRT was correlated to the number of injections and to initial CRT. Conclusion: Intravitreal injections of ranibizumab appeared to be a safe and effective option in the treatment of macular oedema secondary to retinal vein occlusion. Nevertheless, because the natural course has demonstrated a possible improvement in vision in almost one quarter of affected eyes at 3 years, further controlled and prospective studies are necessary to compare this treatment to the natural course with a longer follow‐up.     

Significant improvements in near vision,reading speed,central visual field and related quality of life after ranibizumab treatment of wet age‐related macular degeneration

Purpose: To investigate the effects on near visual acuity, reading speed, central visual field and related quality of life of ranibizumab treatment of wet age‐related macular degeneration (AMD). Methods: The study was a prospective, non‐comparative consecutive case series, followed for 3 months and investigator‐driven. Thirty eyes of 30 patients with wet AMD were included, mean age 75 years (range 69–95 years). In addition to a full ophthalmological examination – including best‐corrected visual acuity (BCVA; Early Treatment Diabetic Research Study chart), fundus biomicroscopy, fundus photography, fluorescein angiography, indocyanine green angiography (occult cases) and ocular coherence tomography – near visual acuity, reading speed, central visual field and quality of life for related activities were also investigated at baseline and at 3 months after ranibizumab treatment. Results: Mean BCVA increased from 62 ± 11 to 66 ± 14 letters at 3 months (7%; p = 0.018). Near vision improved from 9 ± 5 to 6 ± 3 points (33%; p = 0.0006) and reading speed increased from 59 ± 40 to 85 ± 50 words/min (44%; p < 0.0001). The mean deviation from normal of the visual field improved from ?9 ± 7 to ?6 ± 5 dB (33%; p < 0.0001). Quality of life improved for distance activities from 54 ± 28 to 63 ± 28 points (17%; p < 0.0001) but significantly (p = 0.024) more for near activities, from 49 ± 26 to 63 ± 26 points (29%; p < 0.0001). Reading newspaper text in the group in which the better eye was treated showed the highest increase in quality of life score of all: 116%. Conclusion: The increase in BCVA after ranibizumab treatment is well established. The present study also showed significant improvements in other important visual qualities, such as near visual acuity, reading speed, central visual field and several activities influencing quality of life. The improvement was greater for near activities than for distance activities. Therefore, the beneficial effects of ranibizumab treatment shown here are more extensive than those reported previously.     

Bevacizumab versus ranibizumab in the treatment of exudative age-related macular degeneration

The purpose of this article is to describe functional and morphological short-term results in patients with exudative age-related macular degeneration (AMD) of all subtypes, treated with intravitreal bevacizumab versus intravitreal ranibizumab. This was a retrospective case-controlled series of 30 patients treated with intravitreal bevacizumab and 30 patients treated with intravitreal ranibizumab for exudative AMD. All patients received three initial injections every 4 weeks. Best corrected visual acuity (BCVA) as well as greatest linear dimension (GLD) of the CNV in fluorescein angiography and central retinal thickness (CRT) in optical coherence tomography (OCT) were monitored 2–4 months after last injection. BCVA stabilized and slightly increased from logMAR 0.74 to 0.62 in the bevacizumab group, and from logMAR 0.76 to 0.58 in the ranibizumab group (P < 0.05 for each group). No statistical difference was seen between both groups at any time-point. CRT was significantly reduced in both groups at last follow-up. In contrast, GLD did not change significantly. Patients with exudative AMD of all subtypes benefit from intravitreal anti-VEGF injections. No significant difference between bevacizumab and ranibizumab is seen in the short-term follow-up.     

Retinal pigment epithelium tears after intravitreal injection of ranibizumab for predominantly classic neovascular membranes secondary to age‐related macular degeneration

Acta Ophthalmol. 2010: 88: 736–741

Abstract.

Purpose: Retinal pigment epithelium (RPE) tear is an extremely rare complication in patients with classic neovascular membranes without RPE detachment. We evaluate their incidence and functional outcome following treatment with intravitreal ranibizumab. Methods: Observational study of 72 consecutive patients (74 eyes) treated at Jules Gonin University Eye Hospital, Lausanne, with intravitreal ranibizumab 0.5 mg for classic choroidal neovascularization (CNV) between March 2006 and February 2008. Best‐corrected visual acuity (BCVA), fundus examination and optical coherence tomography were recorded monthly; fluorescein angiography was performed at baseline and repeated at least every 3 months. Results: RPE tears occurred in four (5.4%) eyes temporal to the fovea, after a mean of four injections (range 3–6). Mean baseline BCVA was 0.25 decimal equivalent (logMAR 0.67) and improved despite the RPE tear to 0.6 decimal equivalent (logMAR 0.22). Conclusion: RPE tears following intravitreal ranibizumab injections for classic CNV can occur in about 5% of patients, even in the absence of baseline RPE detachment. Nevertheless, vision may improve provided the fovea is not involved.     

Fixed bimonthly aflibercept in naïve and switched neovascular age-related macular degeneration patients: one year outcomes

AIM: To determine real life clinical outcomes in poorly responsive and treatment-naïve neovascular age related macular degeneration (nvAMD) patients using bimonthly fixed dosing aflibercept regimen. METHODS: This was a retrospective study of 165 eyes with nvAMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata (PRN) ranibizumab/bevacizumab due to poor response (107 eyes), or treatment-naïve (58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline were assessed using the Wilcoxon signed-rank test. The proportion of patients maintaining BCVA (<15 letters loss) at 12mo was also evaluated. RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and naïve aflibercept groups respectively (P<0.01). BCVA was maintained in 95.3% of switched and 96.6% of naïve patients. CRT at month 12 showed a decrease of -6.16 µm in the switched group and -35.36 µm in the naïve group (P<0.01). Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections (naïve group), 7.5 injections (switched group) and 4 clinic visits per year. CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-naïve and poorly responsive nvAMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.     

Visual improvement in central retinal vein occlusion (CRVO) following intravitreal injections of bevacizumab (Avastin®)

Acta Ophthalmol. 2010: 88: 836–841

Abstract.

Purpose: To perform a prospective study on central retinal vein occlusion (CRVO) to evaluate whether visual acuity can be improved and macular oedema reduced in response to intravitreal injections of bevacizumab. Methods: The case material comprised 13 patients (aged 34–79 years), duration of CRVO was 2 weeks to 6 months, baseline ETDRS visual acuity 0.06–0.4 (mean Snellen 0.13, derived from logMAR value) and intraocular pressure (IOP) 12–20 (mean 15.2) mmHg. Clinical examination, including optical coherence tomography (OCT), was carried out at baseline and every 6 weeks, digital fluorescein angiography at baseline, at 3 months and 6 months. Intravitreal injections of bevacizumab (1.25 mg) were given under microscopic control at baseline and every 6 weeks during the 6‐month follow‐up. Results: Following one intravitreal injection of bevacizumab, average visual acuity improved by 13 ETDRS letters at 1 month (p < 0.05) and in response to 4 injections by 24 letters (logMAR 0.48) at 6 months (p < 0.05). Foveal thickness as measured by OCT decreased from 596 μm at baseline to 288 μm at 6 months (p < 0.05) concomitant with resorption of intra‐ and subretinal fluid. IOP ranged from 10 to 24 (17.3) mmHg at 6‐month follow‐up. No adverse events occurred. Conclusions: In response to four intravitreal injections of bevacizumab during 6 months, a substantial improvement in visual acuity and reduction in central retinal thickness were achieved. A randomized clinical trial is warranted to further evaluate the efficacy and safety of this treatment modality.     

Intravitreal ranibizumab (Lucentis®) in the treatment of retinal angiomatous proliferation (RAP)

Background  Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. Methods  Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. Results  Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 μm, and decreased significantly to a mean of 224 μm (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 μm (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period. Conclusions  Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.     

Retrospective study of an as required dosing regimen of intravitreal bevacizumab in neovascular age‐related macular degeneration in an Australian population

Purpose: To investigate the efficacy of intravitreal bevacizumab for the treatment of neovascular age‐related macular degeneration (AMD) using an as required dosing regimen. Methods: A retrospective study of 210 patients (231 eyes) with choroidal neovascularization resulting from neovasacular AMD. Patients were treated with 1.25 mg intravitreal bevacizumab at a vitreoretinal practice in Adelaide, South Australia. Patients were followed up at 2–4 weeks and then at 1‐month intervals; repeat injections were offered in the event of recurrence. Recurrence was defined as either a decrease of best‐corrected visual acuity or an increase in macular oedema, subretinal fluid or intraretinal fluid on optical coherence tomography, after complete or partial resolution in previous follow‐up visits. Patient data were collected for 12 months of follow up or until the patient's treatment was changed to ranibizumab. Results: Significant improvement in visual acuity and central retinal thickness was demonstrated at 1 month with an improvement of vision from logMAR equivalent 0.76 to 0.68 (P < 0.001) and a decrease of central retinal thickness from 306 µm to 244 µm (P < 0.001). This overall improvement was continued throughout the 12‐month follow‐up period; however, follow up was poor with 12‐month data available for only a small number of patients (7.8%). Ocular and systemic side‐effects were rare at 3.5% and 0.4%, respectively. Conclusion: Eyes with neovascular AMD treated with intravitreal bevacizumab for up to 12 months had significant functional and anatomical improvement. Further studies need to confirm the long‐term safety and efficacy of this treatment.