Diabetic Macular Oedema: Comparing Two Different Treatment Approaches

The second most common macular disease after Macular Degeneration is “Diabetic Macular Oedema” (DMO).

The second most common macular disease after Macular Degeneration is “Diabetic Macular Oedema” (DMO). This involves swelling of the macula because of damage to the macular blood vessels, something which commonly occurs in people with diabetes (see Figure 1).
DMO is believed to occur in around 7% of people with diabetes.

Given that diabetes affects 5-10 % of Australians (in some indigenous communities the rates are up to 50%), DMO is a common cause of loss of vision.

In the past, laser treatment was primarily used to treat DMO. However, this did not improve vision in most eyes, and many people continued
to lose vision.
More recently, injections of specific medications into the eye have been developed to better control the swelling and damage. There are currently two main types of injections that are used to treat DMO:

  • Steroids 
  • Vascular Endothelial Growth Factor (VEGF) inhibitors.

The Save Sight Institute and Sydney Eye Hospital pioneered the development of steroid eye injections in the 1990s. Since 1997 the Clinical Research Unit of the Macula Research Group has conducted a series of major clinical trials to assess the visual outcomes of steroid injections for macular disease.

VEGF inhibitors, such as Avastin, Lucentis or Eylea, were first developed to treat wet Macular Degeneration, but it turns out that they are also effective for DMO. Although VEGF inhibitors and steroids are both reported to be effective in treating DMO, they also both have risks and side-effects. In order to better understand these, and to help medical practitioners make informed treatment choices for their patients, we decided to conduct a major clinical trial to directly compare VEGF inhibitors and steroids in the treatment of DMO.

The VEGF inhibitor analysed was Bevacizumab (‘Avastin’) and the steroid was a slow-release formulation of Dexamethasone (‘Dex-Implant’). The study was therefore called ‘BEVORDEX’.

Preliminary Results

Here we present the one year results of the BEVORDEX study (half way through its duration) which have recently been published in Ophthalmology, the leading professional journal in the field.

In 2010 we secured start-up funding from the National Health and Medical Research Council and, with the added assistance of our private patient donors, we were able to commence the study.
We enrolled 66 patients (88 eyes) over the following two years.

Half of the group received steroid injections while the other half received VEGF inhibitor injections.

We were primarily interested in the proportion of patients in each group whose vision improved by two or more lines on an eye chart. In both groups this has, to date, occurred in around 40% of eyes. 

Vision did not deteriorate in any eyes treated with the VEGF inhibitor, whereas it did in some eyes receiving steroid injections. This was primarily due to cataract formation, a well-know side effect of steroid injections.

Another common side-effect of steroid injections is increased intraocular pressure, which occurred in around half of the treated eyes.

While steroids have these increased risks, they have an advantage in that injections are required much less frequently and the effect on swelling appears to be stronger.

On average, eyes treated with steroids needed only three injections during the 12 month study. Eyes treated with the VEGF inhibitor required an average of eight injections during the same time period.

DMO is assessed by measuring the Central Macular Thickness (CMT) with an Optical Coherence Tomography (OCT) machine.

In normal eyes, the CMT is less than 300 microns. In the BEVORDEX study, participants had an average CMT of 500 microns before they started treatment.

Figure 2 shows that eyes treated with steroid injections (Dex-Implant) had a much greater reduction in DMO (measured by CMT) than eyes treated with the VEGF inhibitor (Bevacizumab ‘Avastin’). 

It also demonstrates for the first time that this particular steroid is only effective for four months. It was previously thought to last six months.

How does this trial reduce the risk of people going blind from macular disease? This is, of course, our primary objective in the Macula Research Group and we are proud of the progress we have made thus far and in being the first to conduct a study to compare these commonly used drugs directly.

In summary, our findings thus far indicate that steroid injections clearly have a stronger effect and last much longer than the VEGF inhibitor. However steroids also frequently caused cataracts and can result in increased intraocular pressure.

This study provides good evidence that steroids may be considered as first line treatment of eyes with DMO for those people who have already had their cataracts removed.

Steroids might also be considered for patients who wish to have as few injections as possible, or cannot be seen monthly, perhaps for geographical reasons.

The BEVORDEX study will complete its final two-year follow-up of all patients in October 2014.
This study has relied on private donations because, as is often the case, the initial NHMRC start-up funding was not enough to cover all costs involved in the study which has spanned 8,800 separate patient visits over four years.

We thank and acknowledge our loyal supporters, without whom this important research could not take place.

Figure 1A-1D: Images of diabetic macular oedema. A) colour photograph of a macula; B) retinal angiogram showing leakage of dye within the macula; C) Optical Coherence Tomography (OCT) thickness map; and D) OCT cross section of the macula showing marked swelling.

Figure 2: Mean central macular thickness by treatment type, for baseline and each of the 12 months of follow-up. Bevacizumab (Avastin) in green and Dexamethasone (Dex-Impant) in blue. The DEX implant reduced the macular thickness more effectively but was clearly wearing off after four months.

1A, B, C

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1D

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Figure 2

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Notes from the SSI Parents and Carers Day

Earlier this year the Save Sight Institute held an information day for parents and carers of children affected by eye disease and vision loss.

Earlier this year the Save Sight Institute held an information day for parents and carers of children affected by eye disease and vision loss.

Children’s vision, and its healthy development, is a priority area for the Save Sight Institute because of the substantial and long-term impact it has on the individual, on families and on the community as a whole.

Researchers at Save Sight Institute, across multiple research groups, are working hard to find better ways of preserving and restoring vision for children.

Attendees at the information day received information and support across a broad range of topics.

Insight News attended and provided an excellent summary of the days’ content in their October edition, and we are pleased to feature this story here.

50 Year Anniversary for Discipline of Ophthalmology at USYD

The Discipline of Clinical Ophthalmology and Eye Health last week celebrated 50 years of achievement and progress with a gala dinner held in the historic MacLaurin Hall at The University of Sydney.

The Discipline of Clinical Ophthalmology and Eye Health last week celebrated 50 years of achievement and progress with a gala dinner held in the historic MacLaurin Hall at The University of Sydney.

Attended by over 160 people, including ophthalmologists past and present, the guest list included leading researchers, academics, industry stakeholders and special guests including Dame Marie Bashir, Professor Ian Constable AO, Ken Coles AO and Emeritus Professor Frank Billson AO.

Hosted by Head of Discipline, Professor John Grigg, the night proved an excellent opportunity for many in the industry to reconnect and acknowledge the collective achievements of the ophthalmic profession in Australia over the past half-century.

A/Prof Grigg welcomed guests, saying “With its distinguished history and its exciting future, the Discipline of Clinical Ophthalmology is something I am very proud to be associated with. This is because of the remarkable teachers, researchers, clinicians and students who have made the profession what it is today. Together, we have played an integral role in caring for people with eye disease, and have had major and positive impacts on the lives of many individuals and families.”

Dean of Sydney Medical School, Professor Bruce Robinson, acknowledged and commended the history of strong leadership within the Discipline, starting with Dr Frank Claffy in 1964, followed by Dr Eddie Donaldson in 1971 and Professor Frank Billson from 1977.

Professor Robinson praised the Discipline’s bright future under the leadership of A/Prof Grigg, a tenure which has already been characterised by the introduction of innovative new models of teaching and learning and the continued integration of clinical care with basic science and clinical research.

Excellent graduate outcomes are evident in 70% of Master of Medicine (Ophthalmic Science) students being accepted to RANZCO training programmes (2005-2012) and 80% of their student research projects being published (2005-2011).

The recently introduced ‘Virtual Ophthalmology Clinic’ continues the Discipline’s commitment to leading the way when it comes to education and training. In conjunction with Sydney Eye Hospital, the Discipline also coordinates the annual Registrar Conference.

This year also marks ten years since the Discipline’s flagship Masters in Ophthalmic Science programme was introduced. Offered in partnership with The University of Otago in New Zealand, the programme has recently been expanded to include courses in ‘International Ophthalmology’ and ‘Cataract and Refractive Surgery’.

In 2013 the Discipline had its highest ever student cohort.

The Discipline of Clinical Ophthalmology and Eye Health now operates across eight clinical schools and incorporates two major eye research institutes: the Save Sight Institute and the Centre for Vision Research.

Research has expanded considerably since 1980 when the first NHMRC grant was awarded to researchers associated with the Discipline. Last year this had grown to approximately $7M in competitive grant funding.

There are now 12 major research units, and the clinic translation of research is especially evident in landmark projects such as the Blue Mountains Eye Study led by Professor Paul Mitchell. Also of note is the introduction of intravitreal triamcinolone and development of the multifocal visual evoked potential for objective assessment of optic nerve function.

The Discipline is recognised by the Excellence in Research Australia (ERA) Report which, since 2010, has consistently awarded it an ERA ranking of 5, the highest possible score for performing well-above international standards.

SSI welcomes delegates for Asia Pacific Exchange Programme (APEX)

Save Sight Institute has welcomed 11 doctors, researchers and clinicians from five different countries for the annual Asia Pacific Exchange Program (APEX).

Save Sight Institute has welcomed 11 doctors, researchers and clinicians from five different countries for the annual Asia Pacific Exchange Program (APEX). Sponsored by Bayer, attendees will hear from a range of distinguished ophthalmic experts on topics related to macular disease and its treatment.

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Building on the success of the knowledge sharing and professional collaboration that occurred at last year workshop, this years delegates have travelled from Malaysia, South Korea, Taiwan, Thailand and Singapore to learn about ophthalmology, and particular age-related macular degeneration, in the Australian context.

Hosted by Professor Peter McCluskey and Professor Mark Gillies, the two day programme is a comprehensive and challenging one, addressing topics such as:

  • AMD in the Australian setting
  • Intravitreal injections: Handling high volumes
  • AMD research updates
  • Hospital and private practice facilities tour
  • Patient support services avaialble
  • Intravitreal injection safety
  • Case studies and group discussions
  • Q&As
Guest speakers from the Macular Disease Foundation of Australia have been featured.

SSI research a highlight at 2014 American Academy of Ophthalmology (AAO) meeting

Research by the Macular Research Group at Save Sight Institute was a highlight of the recent 2014 meeting of the American Academy of Ophthalmology (AAO), the leading meeting of ophthalmic experts in the world.

Research by the Macular Research Group at Save Sight Institute was a highlight of the recent 2014 meeting of the American Academy of Ophthalmology (AAO), the leading meeting of ophthalmic experts in the world.

Known as the BEVORDEX study, the research involved a randomized clinical trial to evaluate the two major treatment options for Diabetic Macular Oedema (DMO).

About the study:.

The second most common macular disease after Macular Degeneration is “Diabetic Macular Oedema” (DMO).

This involves swelling of the macula because of damage to the macular blood vessels, something which commonly occurs in people with diabetes (see Figure 1). 

DMO is believed to occur in around 7% of people with diabetes. Given that diabetes affects 5-10 % of Australians (in some indigenous communities the rates are up to 50%), DMO is a common cause of loss of vision.

In the past, laser treatment was primarily used to treat DMO. However, this did not improve vision in most eyes, and many people continued to lose vision. More recently, injections of specific medications into the eye have been developed to better control the swelling and damage.

There are currently two main types of injections that are used to treat DMO:

  • Steroids 
  • Vascular Endothelial Growth Factor (VEGF) inhibitors. 

The Save Sight Institute and Sydney Eye Hospital pioneered the development of steroid eye injections in the 1990s. Since 1997 the Clinical Research Unit of the Macula Research Group has conducted a series of major clinical trials to assess the visual outcomes of steroid injections for macular disease.

b4

VEGF inhibitors, such as Avastin, Lucentis or Eylea, were first developed to treat wet Macular Degeneration, but they have also been found to be effective for DMO.

Although VEGF inhibitors and steroids are both reported to be effective in treating DMO, they also both have risks and side-effects. In order to better understand these, and to help medical practitioners make informed treatment choices for their patients, we decided to conduct a major clinical trial to directly compare VEGF inhibitors and steroids in the treatment of DMO.

The VEGF inhibitor analysed was Bevacizumab (‘Avastin’) and the steroid was a slow-release formulation of Dexamethasone (‘Dex-Implant’). The study was therefore called ‘BEVORDEX’.

Preliminary Results
The one year results of the BEVORDEX study (half way through its duration) have recently been published in Ophthalmology, the leading professional journal in the field.

In 2010 we secured start-up funding from the National Health and Medical Research Council and, with the added assistance of our private patient donors, we were able to commence the study. We enrolled 66 patients (88 eyes) over the following two years.

Half of the group received steroid injections while the other half received VEGF inhibitor injections.

We were primarily interested in the proportion of patients in each group whose vision improved by two or more lines on an eye chart. In both groups this has, to date, occurred in around
40% of eyes. Vision did not deteriorate in any eyes treated with the VEGF inhibitor, but it did in some eyes receiving steroid injections. This was primarily due to cataract formation, a well-known side effect of steroid injections.

Another common side-effect of steroid injections is increased intraocular pressure, which occurred in around half of the treated eyes.

While steroids have these increased risks, they have an advantage in that injections are required much less frequently and the effect on swelling appears to be stronger.

On average, eyes treated with steroids needed only three injections during the 12 month study. Eyes treated with the VEGF inhibitor required an average of eight injections during the same time period.

DMO is assessed by measuring the Central Macular Thickness (CMT) with an Optical Coherence Tomography (OCT) machine.

In normal eyes, the CMT is less than 300 microns. In the BEVORDEX study, participants had an average CMT of 500 microns before they started treatment.

Figure 2 shows that eyes treated with steroid injections (Dex-Implant) had a much greater reduction in DMO (measured by CMT) than eyes treated with the VEGF inhibitor (Bevacizumab ‘Avastin’).

It also demonstrates for the first time that this particular steroid is only effective for four months. It was previously thought to last six months.

How does this trial reduce the risk of people going blind from macular disease? This is, of course, our primary objective in the Macula Research Group and we are proud of the progress we have made thus far and in being the first to conduct a study to compare these commonly used drugs directly.

In summary, our findings thus far indicate that steroid injections clearly have a stronger effect and last much longer than the VEGF inhibitor. However steroids also frequently caused cataracts and can result in increased intraocular pressure.

This study provides good evidence that steroids may be considered as first line treatment of eyes with DMO for those people who have already had their cataracts removed.

Steroids might also be considered for patients who wish to have as few injections as possible, or cannot be seen monthly, perhaps for geographical reasons.

The BEVORDEX study has completed its final two-year follow-up of all patients (October 2014).

This study has relied on private donations because, as is often the case, the initial NHMRC start-up funding was not enough to cover all costs involved in the study which has spanned 8,800 separate patient visits over four years.

We thank and acknowledge our loyal supporters, without whom this important research could not take place. To support our research please click here and select ‘Macular Research Group’ from the dropdown box titled ‘Purpose’.

To download the full Spring Edition of the Macular News please click on the PDF link below.