Treatment of chronic diabetic macular oedema with intravitreal fluocinolone acetonide implant; real-life analysis of outcomes during overall treatment period.

PURPOSE: To assess the clinical efficacy of the fluocinolone acetonide (FA) intravitreal implant (Iluvien, Alimera Sciences) over a 12-month period in a population resistant to treatment with first-line anti-VEGF agents. METHODS: This study is a retrospective cohort study assessing functional and anatomical outcomes in 13 eyes of 12 patients treated for diabetic macular oedema (DMO) with a single fluocinolone implant (FA) (Iluvien) under real-world conditions. The follow-up period includes the time of first intravitreal treatment (incl anti-VEGF or short-lasting steroids) given until 12 months post FA implant insertion. Primary outcomes were best corrected visual acuity (BCVA), measured using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale, and central foveal thickness (CFT), measured using Topcon 3DOCT-2000 (Topcon Inc) SD-OCT imaging. Mean BCVA and CFT were measured before anti-VEGF treatment, after anti-VEGF treatment, at the time of Iluvien implant insertion, and 6 and 12 months after Iluvien implant insertion. The t-paired sample test was used to ascertain statistical significance of changes in comparison of two samples while the ANOVA analysis was used in comparison of three or more samples. RESULTS: The baseline BCVA (SD) of the cohort prior to initiation of anti-VEGF treatment was 47.45 (12.27) ETDRS letters whilst the mean CFT (SD) was 579 (203) microns. Following completion of anti-VEGF therapy, the mean improvement in vision was 8.9 ETDRS letters (p = 0.1) whilst the mean reduction in CFT was 197 microns (p = 0.028). Mean BCVA (SD) at the time of insertion of the FA implant was 55.15 (11.16) ETDRS letters and mean (SD) CFT at time of insertion of the FA was 454.62 µm (109.51). Following the 12-month treatment period with the FA implant, BCVA (SD) was 62.15 (10.25) ETDRS letters (p = 0.0331) and the mean (SD) CFT was 404.36 µm (142.92), a change of -50.26 µm from baseline (p = 0.0369). CONCLUSIONS: This study has shown that statistically significant improvements in BCVA and CFT can be achieved over a 12-month period with the Iluvien implant. The implant has been shown to be a safe option in the treatment of DMO and may have a role to play in achieving good functional and anatomical outcomes in DMO while also reducing the frequency of follow-up appointments required to maintain stable vision in the working-age population.

Intravitreal injections: past trends and future projections within a UK tertiary hospital.

AIMS: To describe past trends and future projections for the number of intravitreal injections being administered at a large tertiary hospital in London, United Kingdom. METHODS: Retrospective data from Moorfields Eye Hospital were collected using the electronic medical record system. Descriptive statistics were used to visualise overall trends. Time series forecasting was used to predict the number of injections that will be administered up to and including the year 2029. RESULTS: The number of injections has increased nearly 11-fold from 2009 to 2019, with a total of 44,924 injections delivered in 2019. The majority of injections were given for the treatment of neovascular age-related macular degeneration. Aflibercept formed 87% of injections administered in 2019. The number of injections is predicted to continue to increase every year, with nearly 83,000 injections forecasted in the year 2029. CONCLUSION: The demand for intravitreal injections has increased substantially over the last decade and is predicted to further increase. Healthcare systems will need to adapt to accommodate the high demand. Other solutions may include longer-acting therapies to reduce the treatment burden.

One-year real-life results on effect of intravitreal aflibercept in patients with diabetic macular oedema switched from ranibizumab.

PURPOSE: To assess visual and optical coherence tomography-derived anatomical outcomes of treatment with intravitreal aflibercept (Eylea®) for diabetic macular oedema in patients switched from intravitreal ranibizumab (Lucentis®). DESIGN: Retrospective, cohort study. PARTICIPANTS: Ninety eyes (of 67 patients) receiving intravitreal anti-vascular endothelial growth factor therapy were included. METHODS: This is a retrospective, real-life, cohort study. Each patient had visual acuity measurements and optical coherence tomography scans performed at baseline and 12 months after the first injection of aflibercept was given. MAIN OUTCOME MEASURES: We measured visual acuities in Early Treatment Diabetic Retinopathy Study letters, central foveal thickness and macular volume at baseline and at 12 months after the first aflibercept injection was given. RESULTS: Ninety switched eyes were included in this study. The mean (standard deviation) visual acuity was 63 (15.78) Early Treatment Diabetic Retinopathy Study letters. At baseline, the mean (standard deviation) central foveal thickness was 417.7 (158.4) µm and the mean macular volume was 9.96 (2.44) mm3. Mean change in visual acuity was +4 Early Treatment Diabetic Retinopathy Study letters (p = 0.0053). The mean change in macular volume was -1.53 mm3 in SW group (p = 0.21), while the change in central foveal thickness was -136.8 µm (p = 0.69). CONCLUSION: There was a significant improvement in visual acuity and in anatomical outcomes in the switched group at 12 months after commencing treatment with aflibercept for diabetic macular oedema.

Intravitreal aflibercept for diabetic macular oedema in real-world: 36-month visual acuity and anatomical outcomes.

BACKGROUND/AIMS: To assess structural and functional outcomes of treatment with intravitreal aflibercept (®Eylea) for diabetic macular oedema in treatment-naïve patients. METHODS: Sixty-four eyes receiving intravitreal anti-vascular endothelial growth factor therapy were included in the data analysis of this retrospective, real-life study which follow-up was 3 years. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline, 12, 24 and 36 months. Patients were initiated on a loading phase of five 1-monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians' discretion. RESULTS: The mean number of aflibercept injections received over 3 years was 12.59. At baseline, the mean visual acuity (standard deviation) (Snellen) was 61.45 (16.30) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 422 (138) µm, while the mean macular volume (standard deviation) was 9.51 (2.01) mm3. At 36 months, the mean visual acuity (standard deviation) (Snellen) was 68.34 (13.66) (20/50) Early Treatment Diabetic Retinopathy Study letters (p = .0003). Mean central foveal thickness (standard deviation) was 303 (106) µm (p < .0001) and mean macular volume (standard deviation) was 8.35 (1.62) mm3 (p = .0022) at 36 months. Sixteen (25%) eyes gained ≥15 ETDRS letters at month 36, and 33 (52%) eyes had a decrease in central foveal thickness of ≥ 100 µm at the same time. CONCLUSION: There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 36 months after commencing treatment for diabetic macular oedema in real-life settings. The good vision and anatomical outcomes were maintained over second and third year of treatment with mean 2.93 and 2.57 intravitreal injections, respectively.

Four-year outcomes of aflibercept treatment for neovascular age-related macular degeneration: Results from real-life setting.

BACKGROUND: To assess long-term structural and functional outcomes of intravitreal aflibercept (Eylea®) treatment for neovascular macular degeneration (nAMD) in a real-word setting. DESIGN AND METHODS: This was a retrospective, single-centre, non-randomized interventional cohort analysis. Data from treatment-naive patients with nAMD funded for treatment with intravitreal aflibercept in the period between 1 September 2013 and 28 February 2014 and who finished 4-year follow-up entered the analysis. Epidemiological data, visual acuity (VA) measured on ETDRS charts and injection numbers were recorded. Spectral domain optical coherence tomography (SD-OCT) data including presence or absence of macular fluid and automated central subfield macular thickness (CSMT) at year 1, 2, 3 and 4 were also recorded. RESULTS: Ninety-four eyes of 89 patients finished 4-year follow-up. The mean number of aflibercept injections received over 4 years was 19.3. At baseline, the mean VA (SD) (Snellen) was 54.1 ± 15.5 (20/100) ETDRS letters whilst the mean CSM (SD) was 296 ± 81 µm. At 4 years, the mean VA (SD) (Snellen) was 60.4 ± 20.0 (20/63) ETDRS letters (p < 0.0001). Mean CSMT (SD) was 218 ± 79 µm (p < 0.0001). Thirty-three percent of eyes gained ⩾15 ETDRS letters at end of 4 years, and 66 (70%) eyes had no macular fluid at the end of the follow-up. CONCLUSION AND RELEVANCE: The results suggest that good long-term morphological and functional treatment outcomes can be achieved using intravitreal aflibercept for nAMD in a real-life clinical setting.

Intravitreal aflibercept for diabetic macular oedema: Moorfields' real-world 12-month visual acuity and anatomical outcomes.

OBJECTIVES: To assess structural and functional outcomes of treatment with intravitreal aflibercept (Eylea®) for diabetic macular oedema in treatment-naive patients. DESIGN: This is a retrospective, real-life, cohort study. PARTICIPANTS AND METHODS: In all, 92 diabetic patients (102 eyes) receiving intravitreal anti-vascular endothelial growth factor therapy were included. A total of 99 aflibercept-treated eyes were included in the statistical analysis. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline and 12 months. Patients were initiated on a loading phase of five monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians' discretion. RESULTS: The mean number of aflibercept injections received was 6.92. At baseline, the mean visual acuity (standard deviation; Snellen) was 59.7 (16.1) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 431 (129) µm, while the mean macular volume (standard deviation) was 9.53 (1.79) mm3. At 12 months, the mean visual acuity (standard deviation; Snellen) was 69.6 (15.2; 20/40) Early Treatment Diabetic Retinopathy Study letters (p < .0001). Mean central foveal thickness (standard deviation) was 306 (122) µm (p < .0001) and mean macular volume (standard deviation) was 8.43 (1.58) mm3 (p < .0001) at 12 months; 33 (33.67%) eyes gained ⩾15 Early Treatment Diabetic Retinopathy Study letters at month 12, and 50 (55.55%) eyes had a decrease in central foveal thickness of ⩾100 µm. CONCLUSION: There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 12 months after commencing treatment for diabetic macular oedema in real-life settings.

INCIDENCE AND LONG-TERM VISUAL ACUITY OUTCOMES OF RETINAL PIGMENT EPITHELIUM TEARS AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To report the incidence of retinal pigment epithelium tears in eyes treated with aflibercept for neovascular age-related macular degeneration and compare it with ranibizumab, and to describe long-term visual outcomes of retinal pigment epithelium tears after intensive anti-vascular endothelial growth factor treatment. METHODS: Retrospective analysis of clinical charts, spectral domain optical coherence tomography and fundus fluorescein angiography imaging of consecutive naive patients treated with intravitreal aflibercept or ranibizumab for neovascular age-related macular degeneration. RESULTS: Eight hundred consecutive eyes were included in the study (300 treated with ranibizumab and 500 with aflibercept) with 34.0 ± 9.1 months of follow-up. The incidence of tears in the aflibercept group was 3.2% and 2.3% after ranibizumab (P = 0.52). Twenty-nine eyes with retinal pigment epithelium tears were followed for a mean of 30.76 months. Visual acuity at baseline was 20/100 (50.7 ± 19.3 Early Treatment Diabetic Retinopathy Study letters) and 20/200 (36.1 ± 26.1 Early Treatment Diabetic Retinopathy Study letters) at the end of follow-up. The mean number of injection was 7.3 at 12 months and 13.9 ± 8.1 at the end of the study. The number of injections positively correlated with the final visual outcome. CONCLUSION: There was a low rate of retinal pigment epithelium tears after aflibercept injections, similar to ranibizumab. The correlation between the number of anti-vascular endothelial growth factors received and visual outcomes supports the need for continuing anti-vascular endothelial growth factor therapy.

Exploring Sex and Laterality Imbalances in Patients Undergoing Laser Retinopexy.

IMPORTANCE: Studies have consistently reported a small preponderance of rhegmatogenous retinal detachments in males and in right eyes, which might suggest interesting differences in ocular anatomy relating to sex and laterality. However, an important potential confounding factor is that epidemiologic studies do not consider retinal tears that do not lead to detachment. This study used the electronic patient records from a large eye hospital to explore whether any sex and laterality imbalances were present in patients who underwent laser retinopexy. OBSERVATIONS: Analysis was conducted from December 1, 2014, to March 1, 2015. Of 6760 patients who underwent retinopexy between May 21, 1996, and October 27, 2014, sex had been recorded for 5854 patients (3346 males and 2508 females) and laterality recorded for 3780 eyes (1990 treatments in the right eye and 1790 in the left eye). The proportion of males was 57.2% (95% CI, 55.9%-58.4%) and the proportion of right eyes was 52.6% (95% CI, 51.1%-54.2%). For sex and laterality, the 95% CIs did not overlap the 50% mark, indicating that the imbalance was likely not owing to chance. CONCLUSIONS AND RELEVANCE: Our study showed that laser retinopexy was performed more often in males and in right eyes. This imbalance is in the same direction as that seen for retinal detachments, suggesting that males and right eyes may have an anatomical predisposition toward retinal tears and detachment, possibly related to a slightly greater average axial length.

A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3.

OBJECTIVE: To report the 2-year outcomes of the BOLT study, a prospective randomized controlled trial evaluating intravitreous bevacizumab and modified Early Treatment Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant macular edema (CSME). METHODS: In a 2-year, single-center, randomized controlled trial, 80 patients with center-involving CSME and visual acuity of 20/40 to 20/320 were randomized to receive either bevacizumab or MLT. PRIMARY OUTCOME: difference in ETDRS best-corrected visual acuity (BCVA) between arms. SECONDARY OUTCOMES: mean change in BCVA, proportion gaining at least 15 and at least 10 ETDRS letters, losing fewer than 15 and at least 30 letters, change in central macular thickness, ETDRS retinopathy severity, and safety outcomes. RESULTS: At 2 years, mean (SD) ETDRS BCVA was 64.4 (13.3) (ETDRS equivalent Snellen fraction: 20/50) in the bevacizumab arm and 54.8 (12.6) (20/80) in the MLT arm (P=.005). The bevacizumab arm gained a median of 9 ETDRS letters vs 2.5 letters for MLT (P=.005), with a mean gain of 8.6 letters for bevacizumab vs amean loss of 0.5 letters for MLT. Forty-nine percent of patients gained 10 or more letters (P=.001) and 32% gained at least 15 letters (P=.004) for bevacizumab vs 7% and 4% for MLT. Percentage who lost fewer than 15 letters in the MLT arm was 86% vs 100% for bevacizumab (P=.03). Mean reduction in central macular thickness was 146 µm in the bevacizumab arm vs 118 µm in the MLT arm. The median number of treatments over 24 months was 13 for bevacizumab and 4 for MLT. CONCLUSIONS: This study provides evidence supporting longer-term use of intravitreous bevacizumab for persistent center-involving CSME. APPLICATION TO CLINICAL PRACTICE: Improvements in BCVA and central macular thickness seen with bevacizumab at 1 year were maintained over the second year with a mean of 4 injections. TRIAL REGISTRATION: eudract.ema.europa.eu Identifier: 2007-000847-89

A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2.

PURPOSE: To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME). DESIGN: Prospective, randomized, masked, single-center, 2-year, 2-arm clinical trial. PARTICIPANTS: A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT. METHODS: Subjects were randomized to either ivB (6 weekly; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months). MAIN OUTCOME MEASURES: The primary end point was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms. RESULTS: The baseline mean ETDRS BCVA was 55.7+/-9.7 (range 34-69) in the bevacizumab group and 54.6+/-8.6 (range 36-68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3+/-10.4 (range 34-79) in the bevacizumab group and 50.0+/-16.6 (range 8-76) in the laser arm (P = 0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (P = 0.0002). The odds of gaining > or =10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3-19.7; P = 0.019). At 12 months, central macular thickness decreased from 507+/-145 microm (range 281-900 microm) at baseline to 378+/-134 microm (range 167-699 microm) (P<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481+/-121 microm (range 279-844 microm) to 413+/-135 microm (range 170-708 microm) (P = 0.02). The median number of injections was 9 (interquartile range [IQR] 8-9) in the ivB group, and the median number of laser treatments was 3 (IQR 2-4) in the MLT group. CONCLUSIONS: The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia.