A Trinity regimen with aflibercept for treatment-naïve neovascular age-related macular degeneration: 2-year outcomes

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the advantages of the Trinity regimen for treatment-naïve neovascular age-related macular degeneration (nAMD)....     

Short-term results for brolucizumab in treatment-naïve neovascular age-related macular degeneration: a Japanese multicenter study

Japanese Journal of Ophthalmology - To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a...     

Treatment of naïve lesions in neovascular age-related macular degeneration with pegaptanib

PURPOSE: To evaluate the safety and efficacy of pegaptanib sodium injection (Macugen, OSI Eyetech Pharmaceuticals) as primary therapy for previously untreated choroidal neovascular membranes (CNV) associated with wet age-related macular degeneration (AMD). METHODS: The authors retrospectively reviewed data of 90 patients with newly diagnosed wet AMD in which pegaptanib was used as primary therapy. Inclusion criteria included CNV of any angiographic subtype and size. Exclusion criteria included any lesion previously treated with photodynamic therapy (PDT), intravitreal triamcinolone, or thermal laser. Outcome measures included pre and post-treatment changes in best-corrected visual acuity, lesion size, lesion angiographic characteristics, and optical coherence tomography (OCT) measurements. Patients were injected every 6 weeks and fluorescein angiography (FA) and OCT imaging were performed after every three injections. Safety assessment was performed by complete ophthalmologic examination pre- and post-injection. RESULTS: Of the patients undergoing primary treatment with pegaptanib, the lesion characteristics were 80% (72/90) occult, 13% (12/90) minimally classic, and 7% (6/90) predominantly classic. Lesion sizes were 50% (45/90) 4 DA. The mean follow-up was 9.1 +/- 2 months (range 6-14 months). Gain of >or=3 lines of vision occurred in 20% (18/90) of patients, stabilization of vision (prevention of three lines of vision loss) occurred in 70% (63/90) of patients, and loss of >or=3 lines of vision occurred in 10% (9/90) of patients, resulting in a 90% response rate. In the patients who gained >or=3 lines of vision, the average number of injections was 3.5. One case of endophthalmitis was recognized. CONCLUSIONS: Pegaptanib as primary therapy for na?ve CNV lesions offers a 90% rate of improvement or stabilization of vision-outcomes that exceed those reported in the VISION trial.     

【In Press】 Real-life experience of ranibizumab therapy for neovascular age-related macular degeneration from Turkey

AIM: To report the real-life experience and clinical results of intravitreal ranibizumab injections to neovascular age-related macular degeneration (nAMD) in a single institution in Turkey. METHODS: A total of 101 eyes of 89 patients with nAMD treated with intravitreal ranibizumab injection, followed up for at least 24mo between 2009 and June 2014, which were evaluated retrospectively. A pro re Nata (PRN) treatment protocol was performed after the patients had received three, monthly loading injections. Best corrected visual acuity (BCVA) and central macular thickness measurements were evaluated at baseline and 3, 6, 12, 18, and 24mo. Number of injections and visits were also recorded. RESULTS: Of the 89 patients, 34 (38.2%) were male and 55 (61.8%) were female and the mean age was 74.0±9.5 (52-91)y. The mean follow-up period was 24.82±4.4 (24-29) mo. Mean number of visits was 8.4±1.12 (7-12) in the first year and 6.6±1.33 (4-12) in the second year. The mean number of injections was 5.8±1.6 (3-10) and 4.2±2.2 (0-9) in the first and second year, respectively. The mean BCVA was 59±15.8 at baseline by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The mean BCVA at 3, 12, and 24mo was 70.3±15.9, 67.9±14.3 and 67.3±16.9, respectively. Improvement in visual acuity for each of the visits from baseline was found to be statistically significant (p<0.01). Visual acuity in 9 eyes at month 3, 7 eyes at month 12, and 13 eyes at month 24 did not change. The mean central macular thickness (CMT) was 437.99±164.78 μm at baseline. The mean CMT was 348.05±138.47 μm, 349.24±139.79 μm, and 344.13±146.309 μm at months 3, 12, and 24, respectively. The decrease in CMT for each of the visits from baseline was found to be statistically significant (p<0.01). CONCLUSION: Anatomical and functional achievement are obtained in our study, but the mean number of injections and visits are found to be lower than the findings reported in randomized controlled clinical trials in the literature. However, the mean number of injections and visits in our study are compatible with the findings reported in real-life experience studies in the literature.     

Characteristics of treatment-naïve quiescent choroidal neovascularization detected by optical coherence tomography angiography in patients with age-related macular degeneration

Graefe's Archive for Clinical and Experimental Ophthalmology - To determine the characteristics of eyes with treatment-naïve quiescent choroidal neovascularization (CNV) detected by...     

Colour photographs for screening in neovascular age-related macular degeneration: are they necessary?

Aims

To investigate whether optical coherence tomography (OCT) with associated infra-red images provide enough information to determine treatment decisions in the management of neovascular age-related macular degeneration (nAMD), or whether retinal colour photography is also necessary.

Methods

In all, 87 OCT scans of 82 eyes with nAMD undergoing monitoring post ranibizumab treatment were taken using the Zeiss Stratus (Carl Zeiss Meditec, Jena, Germany; n=87) together with their corresponding infra-red images. Fundus colour photographs were also taken. These images were reviewed by an experienced assessor, and a ranibizumab treatment decision was made during a multidisciplinary team retinal image review meeting.

Results

In all, 30 OCT scans (34.5%) showed intraretinal or subretinal oedema. A total of 24 colour photographs (19.5%) demonstrated retinal haemorrhage. Corresponding OCT infra-red images gave poor sensitivity in detecting haemorrhages (0.176). In 16.7% of decisions to treat, haemorrhage alone was the deciding factor. Signs of disease activity seen only on colour photography were the deciding factor in clinical decisions for 8% of scans assessed.

Conclusions

The presence or increase of intra-retinal oedema is an important sign of activity triggering ranibizumab retreatment, but some eyes show signs of retinal haemorrhage without coexisting oedema. These haemorrhages are often only seen on either colour imaging or fundoscopy and are unclear or invisible on OCT scans and infra-red images. Therefore, although retinal colour photography creates additional expense, it is indispensable for making informed retreatment decisions, if patients are monitored using retinal imaging alone.     

【In Press】Assessment of the long-term visual and anatomical outcomes of ranibizumab to treat neovascular age-related macular degeneration

AIM: To investigate the long-term visual and anatomical outcomes of patients who underwent intravitreal ranibizumab monotherapy to treat neovascular age-related macular degeneration (AMD) and who were followed-up for at least 2y. METHODS: A total of 74 eyes of 74 patients who underwent ranibizumab monotherapy for neovascular AMD were included in this retrospective study. RESULTS: The average patient age was 72.1±6.5 (range, 57-85)y, the average follow-up time 46.2±13.1 (range, 24-75)mo, and the average number of visits 24.1±9.5 (range, 8-48). The mean number of injections in year 1 was 4.5, 1.6 in year 2, 0.9 in year 3, 0.4 on year 4, and 0.1 in the following years. Within the entire follow-up period, the mean number of injections was 7.6±4.4 (range, 2-21). The mean visual acuity was 48.1±15 (15-76) letters at baseline and 45.7±19 (range, 7-75) at year 5. The mean CMT was 303±78 (range, 178-552) µm at baseline and 251±51 (range, 138-359) µm at year 5. Scars developed in 47 (63.5%) eyes at the end of the follow-up period, and atrophy was evident in 6 (8.1%) eyes. CONCLUSION: Ranibizumab monotherapy can stabilize visual acuity for a mean period of 4y in patients with neovascular AMD.     

Vitrectomy in the management of diabetic macular edema in treatment-naïve patients

Objective

To determine the efficacy of vitrectomy in eyes with treatment-naïve diabetic macular edema (DME).

Optical coherence tomography angiography analysis of the choriocapillary layer in treatment-naïve diabetic eyes

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the capillary flow density (CFD) of choriocapillary (CC) microvasculature using optical coherence tomography...     

The use of real-world evidence for evaluating anti–vascular endothelial growth factor treatment of neovascular age-related macular degeneration

Randomized controlled trials are the gold standard in medical research, providing evidence of the efficacy of a treatment in well-defined patient populations. By contrast, real-world studies explore the effectiveness of treatments in routine clinical practice, often with diverse patient populations. Although both randomized controlled trials and real-world studies contribute to the understanding of the benefits and risks of therapies, they generate different types of data and serve complementary purposes. Real-world studies evaluating the management of neovascular age-related macular degeneration have shown that visual outcomes achieved with anti–vascular endothelial growth factor in clinical practice often differ from those derived from clinical trials, highlighting the importance of assessing such outcomes in real-world studies. Benefits include finding variations in treatment provision, leading to: service improvements; the understanding of the need for continued and higher than previously provided treatment frequency; and new treatment regimens such as treat-and-extend. There is potential for the scope of real-world studies to be expanded to include other patient outcomes, such as quality of life, thus providing decision-makers with additional information to complement the data collected in randomized controlled trials. Physicians, patients, and regulators stand to gain much from further development and the conduct of real-world studies. We provide an overview of the importance of real-world evidence in the management of neovascular age-related macular degeneration with anti–vascular endothelial growth factor therapy, describe sources of real-world evidence, and assess the relative strengths and limitations of randomized controlled trials and real-world studies.     

Patient preference of ranibizumab treatment regimen for neovascular age-related macular degeneration — monthly injections versus pro re nata

Purpose

To identify preference of treatment regimen in patients with anti-VEGF therapy for neovascular age-related macular degeneration (AMD) in real life.

Methods

A cross-sectional study was conducted in 200 patients receiving ranibizumab therapy on a pro re nata regimen with monthly controls. One hundred and twenty-four patients were recruited in a tertiary health care clinic, and 76 patients were recruited in a private practice. Patients were asked to respond to a 14-item questionnaire covering items such as treatment burden and preference for treatment: either monthly injections or pro re nata.

Results

Mean time under anti-VEGF treatment was 33.7 months, and the mean number of intravitreal injections was 17.7. Despite a high treatment burden in 60.3 % of patients, there was an acceptance rate for monthly examinations or injections of 93 %. The proportion of patients who favoured a PRN regimen was 53.0 %, whereas 37.9 % of patients favoured continuous injections. Major concern was recurrent disease activity in 54.5 %.

Conclusion

We identified two groups of patients of considerable size who would prefer either monthly injections or as-required. Overall, there was a high acceptance rate despite a high treatment burden. Nevertheless, efforts should be undertaken to improve examination and injection procedures and to consider the patient’s preference for a treatment regimen.     

Visual outcome of photodynamic therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy over 5 years of follow-up

Purpose

To evaluate the long-term effects of photodynamic therapy (PDT) on typical neovascular age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV).

Methods

This was a multicenter prospective study of 139 eyes from 136 patients (tAMD: 74 eyes; PCV: 65 eyes) who underwent PDT as the initial treatment. The change in best-corrected visual acuity (BCVA), predictive factors for the BCVA at 60 months, frequency of recurrence, and mean recurrence period were analyzed.

Results

The pre-PDT BCVA and greatest linear dimension (GLD) did not differ between the two groups. The mean BCVA (logMAR) was significantly improved at 6 months post-initial PDT (post-PDT) in the PCV group (?0.11, P = 0.0091). However, at 60 months post-PDT, the mean BCVA was significantly worse than baseline in the tAMD (+0.21, P = 0.0035) and PCV (+0.21, P = 0.0076) groups. Pre-PDT BCVA, age, and GLD were the factors significantly associated with the BCVA at 60 months post-PDT. Although the frequency of recurrence did not significantly differ between the two phenotype groups, the mean recurrence period was significantly longer in the PCV group than in the tAMD group (15.7 vs. 8.6 months, P = 0.0020).

Conclusions

PDT may not have benefits for visual acuity in cases of tAMD and PCV over 5 years of follow-up.     

Does lesion size determine the success rate of photodynamic therapy for age-related macular degeneration?

Photodynamic therapy (PDT) is a new evidence-based treatment modality available for choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). Eligibility for PDT is based on the morphological classification of the neovascular complex, the benefit being greater in classic with no occult lesions. Lesion size is also shown to be a predictive factor for treatment benefit. This retrospective case series looked at effect of initial and final lesion size on the visual outcome of patients with subfoveal classic with no occult CNV and found that increasing initial and final lesion size is associated with poorer visual outcome.     

Short-term intraocular pressure trends following intravitreal ranibizumab injections for neovascular age-related macular degeneration—the role of oral acetazolamide in protecting glaucoma patients

Purpose

To determine the effect of oral acetazolamide on lowering the peak and duration of intraocular pressure (IOP) rise in glaucoma and glaucoma suspect patients, following intravitreal injection of ranibizumab for neovascular age-related macular degeneration.

Methods

The study was an open-label, parallel, randomised, controlled trial (EudraCT Number: 2010-023037-35). Twenty-four glaucoma or glaucoma suspect patients received either 500 mg acetazolamide or no treatment 60–90 min before 0.5 mg ranibizumab. The primary outcome measure was the difference in IOP immediately after injection (T0) and 5, 10, and 30 min following injection. ANCOVA was used to compare groups, adjusting for baseline IOP. The study was powered to detect a 9-mm Hg difference at T0.

Results

The IOP at T0 was 2.3 mm Hg higher in the non-treated group (mean 44.5 mm Hg, range (19–86 mm Hg)) compared with the treated group (mean 42.2 mm Hg, range (25–58 mm Hg)), but was not statistically significant after adjusting for baseline IOP (P=0.440). At 30 min, IOP was 4.9 mm Hg higher in the non-treated group (mean 20.6 mm Hg, range (11–46 mm Hg)) compared with the treated group (mean 15.7 mm Hg, range (8–21 mm Hg)). This was statistically significant after adjusting for baseline IOP (P=0.013).

Conclusions

Although the primary end points were not reached, 500 mg oral acetazolamide, 60–90 min before intravitreal injection, results in a statistically significant reduction in IOP at 3O min post injection. Prophylactic treatment may be considered as an option to minimise neuro-retinal rim damage in high-risk glaucoma patients who are most vulnerable to IOP spikes and undergoing repeated intravitreal injections of ranibizumab.