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.     

Complement factor H Y402H polymorphism and characteristics of exudative age‐related macular degeneration lesions

Purpose: The Y402H polymorphism of the complement factor H (CFH) gene is associated with age‐related macular degeneration (AMD) in many populations. The reported genotype?phenotype correlations in the CFH Y402H polymorphism have not been pronounced and no studies on the effect of the polymorphism on the subgroups within wet AMD have been performed. In this study, we wanted to evaluate whether the CFH Y402H polymorphism has an effect on clinical variables in recent exudative AMD lesions. Methods: The study included 172 patients with exudative AMD. The size of AMD lesions and the presence and area of other AMD lesion variables were recorded in fluorescein angiography (FA) and analysed in relation to the Y402H genotypes. Results: The median lesion size (classic + occult choroidal neovascularization [CNV] + serous pigment epithelium detachment [PED] + haemorrhage, if present) was 8.15 mm² in patients homozygous for the CFH risk allele (CC), 7.50 mm² in heterozygous patients (CT), and 7.05 mm² in those with the normal genotype (TT) (p = 0.599). Areas of classic and occult CNV, combined, without serous PED or haemorrhage were 6.37 mm², 5.00 mm² and 5.18 mm², respectively (p = 0.407). There was a trend for CC patients to have more frequently minimally classic and less frequently predominantly classic lesion composition than CT or TT subjects. Conclusions: We detected no clear impact of the CFH Y402H polymorphism on recent exudative AMD lesion characteristics. Although the complement cascade is implicated in CNV formation and scarring processes in the retina, the Y402H polymorphism appears relatively neutral in these functions.     

Relationship between reticular pseudodrusen and choroidal thickness in intermediate age‐related macular degeneration

Importance

Reticular pseudodrusen (RPD) is strongly associated with late age‐related macular degeneration (AMD) but their aetiology remains unknown. RPD have been associated with reduced choroidal thickness (ChT) but most studies are limited by small sample size and varying severity of AMD.

Background

To investigate the relationship between choroidal thickness and RPD in eyes with intermediate AMD (iAMD), controlling for variables known to influence ChT.

Design

Retrospective cohort study.

Participants

Participants were recruited from Centre for Eye Research Australia.

Methods

Colour fundus photographs, fundus auto fluorescence, near‐infrared and spectral‐domain ocular coherence tomography (OCT) were graded for RPD. ChT was measured from enhanced‐depth imaging OCT scans at the centre of fovea, 1500 and 3000 μm nasal, temporal, superior and inferior from centre of fovea.

Main Outcome Measures

ChT between RPD and non‐RPD group.

Results

A total of 297 eyes from 152 subjects were included. A total of 84 (28%) had RPD and were older than non‐RPD group (75.1 ± 5.4 years and 68.7 ± 6.9 years, respectively; P < 0.001). In unadjusted analysis, the RPD group was significantly associated with thinner choroids across all measured locations (P ≤ 0.022). After adjustment for variables, the presence of RPD was no longer associated with ChT (P ≥ 0.132 for all locations) but age (P < 0.001) and refractive error (P = 0.002) remained significantly associated with ChT.

Conclusions and Relevance

Age and refractive error, rather than RPD, was significantly associated with reduced ChT in eyes with iAMD. Choroidal insufficiency may be a less important variable in RPD aetiology than previously considered.     

Photodynamic therapy with verteporfin in age‐related macular degeneration: a systematic review of efficacy,safety, treatment modifications and pharmacoeconomic properties

Photodynamic therapy (PDT) with verteporfin has been used less comprehensively in the treatment of exudative age‐related macular degeneration (AMD), and specifically of choroidal neovascularization (CNV), since the advent of antiangiogenic therapies. Recently, there has been a renewed interest in PDT as an adjunct to these and other agents in the treatment of neovascular AMD. In light of this new development and the European Medicines Evaluation Agency’s (EMEA) recent labelling decision to rescind approval for the use of PDT in occult CNV lesions, the present systematic review was undertaken to revisit the evidence supporting its clinical application. Photodynamic therapy provided the first pharmacological treatment for patients suffering from subfoveal CNV, the major cause of severe vision loss in AMD. Key clinical trials evaluating efficacy and safety have examined patients with all lesion subtypes, with the primary labelled indication (i.e. lesions containing a classic component of ≥ 50% ) deriving from the results of the Treatment of Age‐related Macular Degeneration with Photodynamic Therapy (TAP) Study. The subsequent TAP Study Group post hoc categorization of lesions as predominantly classic is open to question, however, as it appears that the overall efficacy in this group only may have reflected the especially strong response in 100% classic lesions. Based on a subgroup analysis of the Verteporfin in Photodynamic Therapy Study, the indication for PDT subsequently was expanded in some jurisdictions, including that of the EMEA, to include occult lesions with no classic component. However, the subsequent Visudyne in Occult Study found no benefit in 100% occult lesions, resulting in the EMEA rescinding its approval for this indication.     

Illumination and reading performance in age‐related macular degeneration

Background: Previous studies have compared low vision reading performance at optimal task illuminance and consulting room illuminance (500 to 600 lux). However, it is uncertain the extent to which low vision reading performance can be improved when task illumination is increased from levels more representative of those found in the typical living room (50 lux) to levels likely to maximise performance. Methods: Reading performance of 20 subjects with age‐related macular degeneration (AMD) was assessed for a range of print sizes using sentence reading charts at six levels of task illuminance (50 to 5,000 lux). Subjects read without low vision devices. Results: Sentence reading acuity and critical print size improved by a factor of two over the 50 to 5,000 lux range, while maximum reading rate improved by a factor of 1.4. For the majority of subjects (70 per cent), the optimal task illuminance (determined objectively) was higher (median 3,500 lux) than the subjectively preferred task illuminance (median 2,450 lux). Reading performance was significantly better at the optimal illuminance than at illuminances equivalent to those found in the domestic environment (50 lux) or consulting room (600 lux). Conclusions: The majority of AMD patients will require task illumination of at least 2,000 lux to maximise reading performance. Optimal illumination should be determined individually for each patient using both objective measures of performance, such as reading acuity, and subjective assessments of visual comfort.     

Leucocyte telomere length in age‐related macular degeneration

Purpose: To evaluate the association between telomere length and age‐related macular degeneration (AMD). Methods: Circulating leucocyte telomere length and the proportion of telomeres <5 kb were analysed in blood DNA samples taken from 121 patients with exudative AMD (83%), large drusen (14%) or central geographic atrophy (3%). Controls consisted of 77 age‐matched subjects without AMD. The AMD status was assessed by a masked analysis of fundus photographs or angiographs. Telomere length was measured by Southern blotting. Results: Mean (SD) telomere length was 7.76 kb (0.68) in AMD patients and 7.83 (0.69) in controls (p = 0.485). The corresponding proportions of telomeres <5 kb were 10.60 (2.76) and 10.05 (2.64) (p = 0.197). In this material, there was no correlation between telomere length and age, gender or smoking status. There were no differences between the major AMD risk single‐nucleotide polymorphisms (SNPs) of the CFH, HTRA1 or C3 genes, expect for somewhat longer telomeres in controls with the C3 risk SNP. There were no differences in telomere length between patients with drusen or exudative AMD. Conclusions: Telomere length is not associated with exudative AMD or high‐risk drusen.