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Friday / August 19.
HomemiophthalmologyMacular Degeneration: Exploring the Issues

Macular Degeneration: Exploring the Issues

With an ageing population, the number of Australians living with macular degeneration is on the rise. We explore the risks of blue light, the successes of anti-VEGF treatment and the association between antiplatelet/anticoagulant drugs and ocular bleeding.

Blue Light Hazards… or Not

Even under extreme long-term viewing, the blue light emitted from a range of lamps, and computer screens, tablets, laptops and smart phones presents no concern for public health, according to a paper published in Cambridge Ophthalmological Symposium.

JB O’Hagan et al assessed sources of blue light and compared them against the exposure likely to be received from staring at a blue sky on a cloudy day in December and a clear day in June in the United Kingdom and internationally recommended exposure limits. Measurements were carried out with an open field of view to maximise the amount of light collected.

The researchers found that incandescent, LED and CFL retrofit domestic lamps all exceeded, by factors of between four and eight times, the safe luminance value of 104 cd/m2 established by the International Commission on Non-ionising Radiation Protection (ICNIRP). (Luminance is a measure of the intensity of light that reaches the eye. Its unit of measure is candela per square metre (cd/m2).) The luminance of a 600mm square panel intended for office lighting was lower at 35 per cent of 104 cd/m2.

Technologies such as tablets and e-readers can be an invaluable resource for patients with low vision, in particular age-related macular degeneration

Domestic lamps emitted 10 to 20 per cent of the established safe blue light exposure limit, assuming intentional long-term viewing (410 000 s per day) with the panel lamp again performing best, emitting just 1.7 per cent of the blue light exposure limit. The researchers reported that blue light to luminance hazard ratios were similar for the domestic lamps, ranging from 2.3× 10-4 to 2.9×10-4Wlm-1, with the panel lamp having a ratio of 5.0 × 10-4Wlm-1.

When testing screens, all devices were set to maximum brightness. The study identified that “the highest luminance and blue light spectral irradiance occurred from a white screen”, and that “any other colours were generated by removing part of the emission from the device”.

The researchers also assessed an HDMI computer display switch, with three blue LED indicators, at a worst case viewing distance of 100 mm, and using the range of colours that can be generated from a Microsoft RGB. The researchers noted that the 104 cd m-2 guideline was not appropriate because LEDs are not white light sources. Additionally they noted that the LEDs were unlikely to be viewed close up for long enough to cause concern.

The researchers concluded that staring at a blue sky does not present a risk of eye injuries and that the spectrally weighted irradiance from lamps and digital devices assessed was lower than natural exposures. “Under even extreme long-term viewing conditions, none of the assessed sources suggested concern for public health. The worst assessed source consisted of three indicator LEDs, which were unlikely to be viewed close up or long enough to cause concern… The percentage transmission of blue light from the corneal surface to the retina is age related, with the transmission for children higher than for adults. Therefore, where such sources are uncomfortable to view for adults, they could be distressing for children.”

The authors noted that the study did not examine the impact of blue light on circadian rhythm and sleep quality.

Comment

There has been significant publicity and ‘hype’ regarding blue light exposure. The article by O’Hagan et al addresses this issue in an objective scientific fashion, and should provide great reassurance to patients concerned about blue light exposure. Technologies such as tablets and e-readers can be an invaluable resource for patients with low vision, in particular age-related macular degeneration. Patients often express concern that blue light exposure from screen-based devices may be doing them harm. Hopefully this article will serve to dispel some of the myths regarding blue light and allow patients with age-related macular degeneration and other macular conditions to use these devices safe in the knowledge that they are not causing any damage to their maculas.

Reference

O’Hagan JB, Khazova M, Price LL. Low-energy light bulbs, computers, tablets and the blue light hazard. Eye (Lond). 2016 Feb;30(2):230-3


Neovascular AMD: Long-term Outcomes of Treatment

A study of the largest series of long-term outcomes of patients receiving anti-VEGF treatment for neovascular age-related macular degeneration has demonstrated that patients followed in the Fight Retinal Blindness registry achieve world-leading long-term visual results.

The observational study, led by Professor Mark Gillies, reviewed the eyes of 1,043 patients treated by 23 ophthalmologists in Australia, New Zealand and Switzerland.

Mean age of patients was 79.1 years with a mean baseline of 55.1 logMAR letters. Six-hundred-forty-eight (53.5 per cent) eyes were treated with ranibizumab, 69 (5.7 per cent) with bevacizumab; and 495 eyes were treated with multiple agents (74.8 per cent ranibizumab injections; 10.5 per cent bevacizumab injections and 14.7 per cent aflibercept injections). Ranibizumab was the most common treatment as the study period spanned 2007–2010. Treatment schedules were determined by the treating ophthalmologist in consultation with the patient.

In total, 131 eyes continued follow-up for seven years with the mean final visual acuity among those patents 58.4 letters. The authors note that although this was 2.6 letters lower than their mean baseline VA, it was 3.3 letters better than the mean baseline VA for all patients in the study sample. Loss of 10 letters or more occurred in 42 of these eyes with geographic atrophy at the centre of the fovea accounting for 37 per cent of these.

A total of 663 eyes from 631 patients were lost to follow-up before five years. Reasons cited were the practitioner felt that further treatment was futile, patients declined further treatment, discomfort and difficulty attending, referral to another practice, more severe intercurrent illness and death.

The study found that “over the first year, the median number of injections administered was six per eye (mean, 6.1; SD, 2.9), with the largest group (47 per cent) receiving injections every four to five weeks. The median (and mean) number of injections in the second to fifth years were five (4.9; SD,3.1), five (4.9; SD, 3.5), six (5.4; SD, 3.3), and five (4.9; SD, 3.3), respectively. The number of injections in the sixth and seventh years remained similar at 5.5 (5.1; SD, 3.5) and five (4.7; SD, 3.4), respectively. After the first year of treatment, the proportion of eyes receiving treatments at four to five weeks, six to seven weeks, eight to nine weeks, and 10 weeks were approximately equal and remained similar through the seventh year.

“The median number of visits was nine in the first year (mean, 8.7; SD, 3.3). This declined after the first year to a median of seven for the second and third years. The median number of visits (and mean) for the fourth to seventh years was eight (7.9; SD, 3.7), 7 (7.4; SD, 3.6), 9 (8.3; SD, 3.5), and 8 (7.8; SD, 3.3), respectively.”

Comment

The Fight Retinal Blindness (FRB) Project is a world-leading registry project, which allows tracking of ‘real world’ data relating to treatments for macular degeneration. While much of our evidence-based practice is founded on the results of pivotal randomised controlled trials, which are considered the ‘gold standard’ of medical evidence, there are significant limitations to these studies. These include the lack of long-term follow-up, relatively limited numbers, and often a lack of generalisability of the results – for example, clinical trials often exclude ‘sicker’ patients with co-morbidities.

As highlighted by Gillies et al in comparing their results with those in the US and UK, there are significant differences in the short and long-term results of intravitreal anti-VEGF therapy around the world. The FRB results are dominated by Australian practices, which is significant given the differing nature of the Australian health care system from those in other countries. In particular, in contrast to many other countries, there is no disincentive to treatment. This is significant because it is well established that the major cause of poor visual outcomes in patient cohorts undergoing intravitreal anti-VEGF therapy for age-related macular degeneration is under-treatment. Thus treatment delivered in a largely fee-for-service environment such as Australia minimises the potential for under-treatment based on financial factors, which can be significant in other healthcare systems.

The FRB Project has also expanded to include a diabetic macular oedema module, which will allow similar tracking of ‘real world’ data for the newer intravitreal treatments for this condition. In addition the success of FRB has led to expansion of the Save Sight Registries, which now include Fight Corneal Blindness.

Despite the good results achieved for neovascular age-related macular degeneration in the FRB cohort by international standards, there is clearly still a lot more work to be done. A large number of patients are exiting treatment and are thus not available for long-term follow-up, and it is necessary to better define the reasons for these patients ceasing therapy. Macular atrophy is a significant cause of poor vision, and treatments for the atrophic form of age-related macular degeneration remain elusive. The role of anti-fibrotic therapy, in addition to anti-VEGF therapy, also remains to be defined.

Reference

Gillies MC, Campain A, Barthelmes D, Simpson JM, Arnold JJ, Guymer RH, McAllister IL, Essex RW, Morlet N, Hunyor AP, on behalf of the Fight Retinal Blindness Study Group. Long-Term Outcomes of Treatment of Neovascular Age-Related Macular Degeneration: Data from an Observational Study. Ophthalmology 2015;122(9):1837-1845


Antiplatelet and Anticoagulant Drugs, and AMD

A study of people with neovascular age related macular degeneration has found that those who are nonhypertensive and take the recommended dose of antiplatelet or anticoagulant drugs for appropriate medical indications are not at increased risk of retinal or sub retinal haemorrhage. However, patients with hypertension face a 1.5 fold increased risk of retinal or subretinal haemorrhage if taking antiplatelet or anticoagulant drugs, according to a review of participants in the Comparisons of age-related macular degeneration Treatments Trials (CATT) study.

According to the study authors, the findings were important because some patients with age-related macular degeneration may be concerned of the risk of worsening vision due to ocular hemorrhage. Additionally, ophthalmologists may be tempted to suggest patients avoid antiplatelet or anticoagulant drugs that could promote ocular bleeding.

Antiplatelet drugs such as aspirin, and anticoagulant drugs – such as warfarin and clopidogrel are commonly caused to treat and manage cardio vascular disease, the incidence of which is expected to continue to rise with the ageing population.

The study included 1,165 people with neovascular age-related macular degeneration from 43 clinical centres.

The authors wrote that among the 1,165 participants, 608 (52.2 per cent) used one or more antiplatelet or anticoagulant drugs at baseline, including 514 (44.1 per cent) with antiplatelet drugs only, 77 (6.6 per cent) with anticoagulant drugs only, and 17 (1.5 per cent) with both antiplatelet and anticoagulant drugs.

Among 608 participants who used antiplatelet or anticoagulant drugs, most (87.2 per cent) took one antiplatelet or anticoagulant drug. Among antiplatelet or anticoagulant drugs used, the most frequently used drugs were aspirin (69.4 per cent), warfarin (14.7 per cent), and clopidogrel (11.4 per cent).

The median duration of antiplatelet or anticoagulant use at enrolment was 6.6 years; duration of use was less than five years for 231 participants, five to 10 years for 177 participants, and more than 10 years for 200 participants.

The study reported associations between use, dosage or duration of use of antiplatelet and/or anticoagulant drugs and the presence or size of retinal or sub retinal haemorrhage were insignificant in patients who were not hypertensive. A higher proportion of people with hypertension who used antiplatelet or anticoagulant drugs had retinal or subretinal hemorrhage at baseline, however this was not associated with
the size of hemorrhage or new or recurrent retinal or subretinal
hemorrhage at years one or two.

Colour fundus photographs were used to determine the presence and size of retinal or sub retinal haemorrhaging.

Comment

Antiplatelet and antocoagulant medications are very common in the age-related macular degeneration population, and haemorrhagic complications of neovascular age-related macular degeneration can sometimes be severe and result in dramatic visual loss. This report gives important information regarding retinal and subretinal haemorrhage in a cohort of patients with very well controlled CNV due to age-related macular degeneration, as they were part of a randomised controlled trial (CATT). This compared different anti-VEGF regimens (bevacizumab vs ranibizumab, and monthly vs PRN dosing) and patients were closely monitored with monthly visits throughout the two-year study period.

While the association of hypertension with the presence of haemorrhagic lesions at baseline is not surprising, the study did provide reassuring results regarding onset of new subretinal haemorrhage during the first two years of treatment. It demonstrated that in this cohort of patients, more than 50 per cent of whom were on antiplatelet or anticoagulant medication, there was no association between incidence or severity of haemorrhage, and use of antiplatelet / anticoagulant medications.

Although hypertension was associated with an increased incidence of haemorrhage in patients on these medications, fortunately there was no association with the size of haemorrhage. Overall, 62 per cent of eyes had retinal or subretinal haemorrhage at baseline. The majority of haemorrhages at baseline (84 per cent) were small (less than one disc area) and only 7.5 per cent were greater than two disc areas.

Clinicians are often faced with the situation of patients and/or non-ophthalmic practitioners expressing concern that anti-platelet medications should perhaps be ceased due to an increased risk of haemorrhage, especially if they have a large subretinal haemorrhage on presentation with neovascular age-related macular degeneration. This study suggests that as long as patients are promptly commenced on intravitreal anti-VEGF therapy and their disease remains well controlled with injections, they can be reassured that there seems to be no significant increase in their risk of further haemorrhage, and that such medications should be continued.

Discussion of these medications should be included as part of routine communication between ophthalmologists and the other clinicians involved in the patient’s care – including optometrists, GPs, cardiologists and other specialists.

Although the CATT study had a large cohort for a randomised controlled trial (n=1,185), it would be of further reassurance if these findings were corroborated by additional evidence from other clinical trials, or larger registry studies in a ‘real world’ setting. It must also be borne in mind that these results only include the first two years of treatment, and this is a chronic condition often requiring lifelong therapy. Clinicians need to remain vigilant to ensure that patients continue with treatment / follow-up at appropriate intervals so that under-treatment does not occur, as this risks visual loss, not only from haemorrhage but other consequences of neovascular activity such as fibrosis and photoreceptor atrophy.

Reference

Ying G, Maguire MG, Daniel E, Grunwald JE, Ahmed O, Martin DF, on behalf of the Comparison of Age-Related Macular Degeneration Treatments Trials Research Group. Association between Antiplatelet or Anticoagulant Drugs and Retinal or Subretinal Hemorrhage in the Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology 2016;123:352- 360

Associate Professor Alex Hunyor MB BS (Hons), FRANZCO, FRACS is a Sydney-based vitreoretinal surgeon and macular specialist. He is a member of the Vitreoretinal Unit at Sydney Eye Hospital, Director at Retina Associates, and Associate Professor of Ophthalmology and member of the Macular Research Unit at the University of Sydney.


Correction

In the April issue of mivision’s Ophthalmology Insights, titled IOL Surgery Astigmastism Elimination by Dr. Rick Wolfe, on page 37, we published the following: “In 94 cases after using posterior corneal compensation and the T2, all but two cases had ≤0.50 D of refractive astigmatism. The two cases of 0.75 D of post-operative refractive astigmatism are my “complications” and are easily treated.”

This was incorrect. The statement should have read: “In 94 cases after using posterior corneal compensation and the T2, all but two cases had >0.50 D of refractive astigmatism. The two cases of 0.75 D of post-operative refractive astigmatism are my “complications” and are easily treated.”

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