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Therapeutic news of note


Rob Cummins
Research and Policy Manager, Macular Disease Foundation Australia


Anti-VEGF treatment regimens: which is best?

Debate continues globally regarding the optimal treatment regimen for people with wet AMD receiving anti-VEGF injections to reduce the significant treatment burden while maintaining optimal visual outcomes.

In Australia, the majority of ophthalmologists use a treat-and-extend regimen, which typically involves three initial doses given one month apart, with subsequent visits and injection intervals being extended by two weeks at a time, if the leakage has stabilised, up to a maximum interval of 12 weeks. If reactivation occurs, the interval is reduced to the last interval with no leakage.

In some countries, there has been a preference for a ‘PRN’ regimen where people are seen monthly and injections given only when there is evidence of leakage.

Two papers by Hatz and Prünte in Switzerland have provided additional evidence that Australia’s preference for the treat-and-extend approach may be preferable. In the first study,1 a retrospective analysis of 140 eyes from 140 patients, half the patients received ranibizumab via a treat-and-extend regimen and the other half a PRN regimen.

At baseline, both groups had similar mean best corrected visual acuity (20/51). The treat-and-extend approach resulted in fewer visits (8.6 vs 11.9) but more injections (8.6 vs 6) over a 12-month period. Most significantly, the visual outcomes for people receiving the treat-and-extend regimen were superior (mean BCVA of 20/35 vs 20/43, p = 0.015) at 12 months, with reduced central retinal thickness.

Both groups experienced an initial average improvement in vision but this improvement fell away after the initial three doses in the PRN group, with significant fluctuations in vision suggesting undertreatment. BCVA remained much more stable in the treat-and-extend group and the improvements were maintained until the end of the study at 12 months.

In a second study,2 the same clinicians measured responses in 146 eyes from 134 patients who were initiated on a PRN regimen (mean BCVA after an average 17 months treatment = 20/41), but were then switched to treat-and-extend. Following the switch, BCVA improved slightly to a mean 20/36 at six and 12 months, with reduced fluctuations in BCVA and decreased central retinal thickness.

Compared to a PRN approach, treat-and-extend can improve and stabilise visual outcomes, with fewer patient visits. Although treat-and-extend patients received more injections, compliance may potentially be improved as patients considered clinic visits more worthwhile as they knew they would be receiving an injection.

1. Hatz K, Prünte C. Acta Ophthalmologica 2016; online 24 March.

2. Hatz K, Prünte C. BJO 2016; online 11 January.


Do computers screens pose a blue light hazard?

Many media reports suggest that the blue light emitted by computer monitors, smartphones, tablets and LED lights poses a significant risk to the health of the retina and may increase the risk of diseases such as macular degeneration.

Much of the evidence for these claims is based on rodent models receiving a brief exposure to very high intensity blue light. How significant is this hazard?

Researchers at the Centre for Radiation, Chemical and Environmental Hazards in the UK measured the blue light exposure to a range of compact fluorescent and LED lights, computer monitors, laptops, smartphones and tablets, and compared this to the safe level of exposure to blue light proposed by the International Commission on Non-Ionizing Radiation Protection.

Even allowing for the possible long, extended viewing time of computers, smartphones and other devices, and using the most extreme viewing conditions such as close viewing with full intensity, none of the assessed sources suggested any cause for concern for public health.

The authors mentioned that the percentage transmission of blue light to the retina is age-related, with higher transmission for children. This study also did not assess the impact of blue light on circadian rhythm. Some other research has indicated that extensive use of blue-light emitting screens and lights in the evening may impact sleep patterns.

O’Hagan J et al. Eye 2016; online 15 January.


Novel eye chart may detect early MD

A major challenge with the management of macular degeneration is to be able to obtain an earlier diagnosis of those who are more likely to progress.

A team of scientists at Moorfields Eye Hospital and the University of Ulster has designed a modification of the conventional logMAR eye chart, which may be able to detect earlier changes in vision loss in age-related macular degeneration.

Regular eye charts also do not have the sensitivity or specificity to diagnose early changes or to monitor the progression of disease. Visual acuity often remains ‘normal’ in even later stage disease with the use of conventional eye charts.

The new Moorfields Acuity Chart is essentially a logMAR chart that uses high-pass filtered letters that are made from fine black and white stripes. The chart uses a grey background with the same mean luminance as the letters. Previous work by this group indicated that the high-pass letters are more equally readable than standard letters and that they seem to disappear when they are too small to be recognised.

Two versions of the Moorfields Acuity Chart were tested with 38 normal subjects and 80 people with a range of VA from AMD. Results were compared to two versions of the normal logMAR chart.

The difference between the Moorfields Acuity Chart and the regular logMAR chart was approximately 4.5 lines in people with AMD and better visual acuity (around 0.0 logMAR). In people without AMD but similar visual acuity, the difference between the two charts was only 1.5 lines.

Regular logMAR charts exhibit significantly greater test-retest variability in people with AMD compared to normal subjects, whereas the variability with the Moorfields Acuity Chart appeared to be unaffected by the presence of disease. A larger clinical trial is now being planned to confirm the initial study.

Shah N et al. BJO 2016; online 4 February.


Visual hallucinations in people with low vision

Charles Bonnet syndrome (CBS), the rather strange phenomenon of complex visual hallucinations in people with vision loss but no neurological or psychiatric problem, continues to be an under-recognised and poorly understood issue.

The prevalence of CBS from a study of 2,565 new low vision clients aged 40 years and older at a national low vision service in Canada, was published in the Canadian Journal of Ophthalmology.

Following carefully-worded questioning, 18.8 per cent of people attending the low vision clinic reported that they experienced hallucinations, forming visual images that they knew were not there. Perhaps surprisingly, about 15 per cent of people with only mild vision loss (BCVA between 6/6 and 6/17 in the better eye) experienced hallucinations. People with BCVA between 6/18 and 6/59 experienced a rate of hallucinations similar to those with worse vision (approximately 20-21 per cent).

Similar rates of CBS were reported by people with AMD, glaucoma, diabetic retinopathy and other eye diseases, suggesting that it is vision loss rather than a specific disease that results in CBS.

Interestingly, although not specifically commented on by the authors, it appears that patients require only what would be considered ‘significant’ loss of vision in one eye to experience CBS, given the significant incidence in patients with only mild visual loss in the better seeing eye. There was also no difference in the likelihood of reporting hallucinations in people aged older than 80 compared with those aged between 40 and 80 years.

More CBS was reported in females. The author suggested that this may have been due to a greater reluctance of males to report the condition. Despite the careful wording of the questioning of patients, the author suggested that the rates of CBS may be even higher than those reported as some people may have been reluctant to disclose their experiences.

Given the high proportion of CBS in people with even mild vision loss, the author recommends that health professionals need to be aware that many of their patients may be experiencing CBS, and that these people will benefit from reassurance that their experiences are not atypical and that they are not suffering from a mental health disorder.

Gordon K. Can J Ophthalmol 2016; 51: 3.


Effects of switching from ranibizumab to aflibercept in wet AMD

An Australian study conducted by the Fight Retinal Blindness! collaboration, reports the 12-month outcomes of switching from ranibizumab to aflibercept in wet AMD patients.

This observational study analysed data from a longitudinal online database of the ‘real-world’ outcomes in 384 eyes that had been treated with ranibizumab for at least 12 months prior to switching to aflibercept, although the median duration of prior ranibizumab treatment was almost 40 months. Patients were then followed for at least 12 months after switching. Eighty per cent of the eyes were graded with active neovascularisation at the time of switching, that is, these were mostly challenging or recalcitrant cases.

The mean number of injections in the first three months after the switch was 2.56, indicating that many people were given three, monthly injections at the switch. After 12 months on aflibercept, the number of eyes with active lesions had reduced from 80 per cent to 58 per cent, with most of this reduction occurring in the first two months after the switch.

At the time of switching, the median treatment interval with ranibizumab was 42 days. After 12 months on aflibercept, the median interval increased to 56 days. The net result of this was about one fewer injection per year on average for aflibercept. It is possible that the treatment interval may have increased even if patients had not switched.

Interestingly, the mean visual acuity at the time of switching (63.4 letters) did not change after 12 months (63.3 letters). As there was no control group, it is not possible to say whether vision would have been different if the patients had not switched. As a majority of patients had been treated with ranibizumab for some years, it is also likely that scar formation or geographic atrophy may have occurred in some people, limiting the potential for improvement.

A small (6.8 per cent) proportion of eyes were switched back to ranibizumab after a mean of 15 months and 10 injections of aflibercept. These eyes had typically experienced an average one-line drop in vision following the initial switch. A small number of these eyes regained their initial vision after switching back to ranibizumab, but the mean acuity in this group continued to decline, suggesting that a second switch does not confer any obvious benefit.

Despite the lack of a control group and the retrospective nature of this study, it suggests that in patients who have been treated with ranibizumab for an extended period (at least 12 months) but continue to have active lesions, there may be only a modest benefit to switching to aflibercept, in terms of slightly reducing injection frequency rather than any visual benefit.

What is not answered in this study is whether earlier switching of people who experience continually active lesions after say, six to 12 months, will provide a more meaningful benefit.

Barthelmes D et al. BJO 2016; online 18 March.

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