Macula - Clinical Research Unit

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The Clinical Research Unit of the Macula Research Group (within the Save Sight Institute ) is an internationally certified clinical trial unit that conducts randomised clinical trials in macula and retinal diseases. Research clinics are held in the Outpatients Department of the Sydney Eye Hospital.

We currently have a number of clinical trials in progress. Patients enrolled in our clinical trials undergo assessments and treatments which are provided free of charge in two research clinics headed by Professor Mark Gillies and Associate Professor Samantha Fraser-Bell. Patients are offered the option of emerging treatments under clinical trial protocols which may not be available for a number of years in Australia or the Public Health System.

In recent years our unit has been involved in clinical trials using Lucentis and Eylea which are now the worldwide gold standard treatments for Wet Age Related Macular Degeneration (AMD). Clinical Trial Patients had access to this treatment years before it became available in Australia.

In recent years our unit has been involved in clinical trials for the drugs Lucentis and Eylea which are now the worldwide gold standard treatments for Wet Age Related Macular Degeneration (AMD). Further trials were conducted to assess the effectiveness of these treatments in patients with macula oedema secondary to retinal vein occlusion (RVO). These trials effectively demonstrated patient improvement and led to approval for use by the Therapeutic Goods Administration (TGA). We have been instrumental in the coordination of clinical trials using an injectable slow release dexamethasone implant for macula oedema secondary to RVO. This drug is now marketed as Ozurdex and is approved for use in the USA and Europe. We continue to use this drug in ongoing clinical trials for Diabetic Macular Oedema.

Clinical Trial Patients had access to these treatments years before they became available as standard of care in clinical practice.

Patients enrolled in clinical trials conducted by the Macula Research Group receive the highest standard of care and follow up. Our clinical trials team, composed of the Principle Investigators, sub-investigators and study staff, provide well-planned, thorough patient care and coordination. We ensure the patient is fully informed of all processes and procedures which are to be conducted according to the clinical trial protocols. Some trials provide reimbursement towards the cost of patient travel to appointments.

Our clinical trials are conducted according to the strict guidelines of the ICH GCP (International Conference on the Harmonisation of Good Clinical Practice) and our staff are experienced and internationally certified in vision assessments and retinal imaging procedures. Study staff maintain current certifications across multiple reading centers worldwide in all retinal imaging procedures including optical coherence tomography, fluorescein angiography and retinal photography.

Current and Upcoming Trials

Age Related Macular Degeneration
Diabetic Retinopathy and Diabetic Macular Oedema
Macular Telangiectasia (MacTel)
Post Marketing Surveillance (FRB!)

Age Related Macular Degeneration (AMD)

Wet AMD

Age related macular degeneration damages the macula, which is the central part of the retina, the inner layer at the back of your eye. AMD causes more Australian adults to go blind every year than any other disease. This disease is characterised by drusen deposits, retinal pigment epithelium abnormalities, geographic atrophy and neovascular maculopathy. The advanced stages of the disease, which are associated with more severe vision loss, consist of either choroidal neovascularisation or geographic atrophy.

Wet AMD is a disease which affects fine, detailed central vision. Central vision is used for seeing detail in objects clearly and common daily tasks such as reading, driving and recognising people’s faces. In the wet form of macular degeneration, the damage to the eye is caused when abnormal blood vessels grow under the macula. These vessels can leak blood or fluid which then damages the macula and causes deterioration or loss of central vision. This can be quick and severe.

Wet AMD can be effectively treated and managed with administration of intravitreal (injected into the eye) anti-vascular endothelial growth factor (VEGF) agents. VEGF is a biological compound which is produced in the human eye, and is found at higher concentrations in diseases for which new blood vessels grow, such as wet macular degeneration. Anti-VEGF agents work by blocking VEGF in turn reducing the growth of abnormal vessels and cessation of leakage from the new vessel.

Dry AMD

Dry AMD clinically is characterised by the presence of drusen and/or geographic atrophy. Drusen can present in the form of hard or soft varieties. Hard drusen are round, discrete, yellow-white deposits. These are not necessarily limited to aging populations. Soft drusen have ill-defined borders and are usually larger than their hard counterparts. Soft drusen are age related and can be associated with the development of neovascularization, wet AMD. Drusen present at the macula will affect the central vision by causing metamorphopsia (straight lines to appear wavy), difficulty with reading and decreased contrast sensitivity.

The clinical features of geographic atrophy can be seen as defined areas of hypopigmentation or depigmentation due to absence or attenuation of retinal pigment epithelium. Large, usually not clearly seen choroidal vessels, can be more readily seen through atrophic patches. These patches can constrict a patient’s visual field and affecting the ability to read and navigate during activities of daily living.

As it currently stands, unlike wet AMD, there is no approved treatment for dry
AMD. Further research into this is active and ongoing. Vitamin supplementation, dietary modification and smoking cessation are advised approaches to slow the progression of dry AMD.

Please see below for an informative video on Geographic Atrophy supplied by Roche

04:15 minutes

AMD Clinical Trials

FILLY
• Status • Ongoing, no longer enrolling patients

The Filly study is an 18 month study that evaluates the efficacy and safety of an intravitreal drug injection (injection
into the eye) for geographic atrophy administered every 1 month or every 2 months, versus a sham control injection*.

*Sham control injections are a pretend injection used in research to be able to compare the study medication in
certain circumstances.
More Information

CHROMA
• Status • Ongoing, no longer enrolling

The CHROMA study is a two year study investigating the safety and efficacy of study medication administered four weekly or six weekly by intravitreal injections for geographic atrophy. The patients will be randomized to either receive the study medication four or six weekly or sham control injection* four or six weekly.
*Sham control injections are a pretend injection used in research to be able to compare the study medication in

More Information

ARIES
• Status • Ongoing, no longer enrolling

The ARIES study is a 2 year study to evaluate treat and extend regimes in patients with neovascular age-related macular degeneration using intravitreal (injection into the eye) Aflibercept injections. Suitable patients will be randomly assigned to one of 2 study groups – control or test group. Participants in the control group will receive treatment of 1 injection per month for 3 consecutive doses, followed by 1 injection every 2 months. Participants in the test group will receive treatment in intervals extended by 2 weeks each time (if disease is stable), starting at Week 16.

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HAWK
• Status • Ongoing, no longer enrolling

The HAWK study is a 2 year study to evaluate the efficacy and safety of study medication versus Aflibercept in subjects with neovascular age-related macular degeneration. Patient will be enrolled into one of three arms, Study Dose A (3mg), Study Dose B (6mg) or Aflibercept, and will receive this treatment intravitreally (injection into the eye).

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SEQUOIA
• Status • Ongoing, no longer enrolling

The SEQUOIA study is a 2 year study to assess the safety and efficacy of intravitreal injections (injections into the eye) of study drug with ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration (AMD). There are three treatment groups, one group with receive 2mg abicipar at the first visit, one month, 2 months followed by 8 weekly injection intervals. The second group will receive 2mg abicipar at the first visit, one month, three months followed by 12 weekly injection intervals. The third group will receive 0.5mg ranibizumap every four weeks.

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RIVAL
• Status • Ongoing, no longer enrolling patients

A two year trial studying the new onset of a type of dry macular degeneration called geographic atrophy in patients with (wet) age-related macular degeneration while they are receiving their standard of care treatment of ranibizumab (Lucentis) or aflibercept (Eylea). Eligible eyes must be treatment naïve, ie not previously had injections of Lucentis or Eylea (or other similar medications in the eye) prior to commencing the study.

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Diabetic Retinopathy and Diabetic Macular Oedema

The second most common macular disease after Macular Degeneration is "Diabetic Macular Oedema" (DMO). This involves swelling of the macula which is secondary to damage to the macular blood vessels, something which commonly occurs in people with diabetes. 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.

VEGF inhibitors, such as Avastin, Lucentis or Eylea, were first developed to treat wet Macular Degeneration, it is now evident that they are also effective treatments for DMO.

Diabetic Eye Disease Clinical Trials

SwitchDMO Study
• Status • Ongoing, no longer enrolling

Persistent swelling despite treatment with bevacizumab (Avastin) or dexamethasone implants (Ozurdex) occurs in some patients. This study assigns the opposite treatment to the one previously received. Therefore, eyes previously treated with Avastin will receive Ozurdex and eyes previously treated with Ozurdex will receive Avastin over a period of 6 months as needed. The study aims to assess whether the switch in treatments is beneficial.

More Information


Genetic Study of Diabetic Retinopathy
• Status • Complete

This is a non therapeutic NHMRC funded trial attempting to identify the genes contributing to diabetic retinopathy in Type I and Type II diabetics.

LADAMO
• Status • Enrolling Patients

Even though intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy has shown encouraging results in managing Diabetic Macular Oedema (DMO), it is not known why approximately 30% of patients respond incompletely to treatment. Recent studies have suggested peripheral retinal ischaemia (loss of blood supply to the retina) contributes to macula oedema in diabetes and retinal vein occlusions. Panretinal photocoagulation laser (PRP) is the current treatment for the leaking blood vessels that cause retinal ischaemia.

The LADAMO study is a 2 year multicentre clinical trial of laser therapy (PRP) to areas of peripheral retinal ischaemia combined with an intravitreal medication called Eylea, versus intravitreal Eylea only (without the PRP laser). The aim of the study is to test the hypothesis that laser therapy of peripheral retinal ischaemia reduces the overall number of intravitreal Eylea injections required to control DMO over a 24 month period.

More Information

NIRD
• Status • Enrolling Patients
Diabetic macular oedema (DMO) has in the past been treated with continuous wave thermal laser photocoagulation to areas of leak in the macula according to established guidelines which take into account the extent of the leak and its proximity to the centre of the macula, the "fovea".

This study looks at Near-infrared light (NIR) at power densities a hundred times lower than conventional thermal treatments that have been shown in animal models to promote the healing of injured cells, including blood vessels and neurons in the retina. Studies claim that NIR treatment augments cellular energy metabolism, enhances mitochondrial function, increases cytochrome C oxidase activity, stimulates antioxidant protective pathways and promotes cell survival.

This will be a 1 month pilot study, with outcome measures assessments at 2 months and further 3 and 6 month safety follow up.

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AUSSIEDEX
• Status • Ongoing, no longer enrolling

Previous studies have proven the positive responses of dexamethasone implants (Ozurdex) to suppress inflammatory responses resulting in diabetic macular oedema. It is put forward that Ozurdex has the benefit of prolonged treatment intervals as compared to the conventional 4 weekly anti-VEGF treatment. Therefore, this study aims to assess the retreatment regimen within the Australian population and provide further understanding of safety and efficacy of the drug.

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Macular Telangiectasia (MacTel)

Idiopathic Juxtafoveal Macular Telangiectasia (MacTel) is a condition of the retina about which little is known. It is a disorder of the blood vessels which supply the macula, the central part of the retina that lines the back of the eye and picks up the light like the film in a camera. The "fovea" in the center of the macula, has no blood vessels at all because they would interfere with central vision.

MacTel refers to a curious, very poorly understood condition of the blood vessels around the fovea (juxtafoveal) which become dilated and incompetent, like varicose veins but on a much smaller scale. While MacTel does not usually cause total blindness, it commonly causes loss of the central vision, which is required for reading and driving vision, over a period of 10-20 years.

MACTEL Clinical Trials

MacTel Study
• Status • Enrolling patients
http://www.mactelresearch.org

This study is an international survey across 25 sites worldwide, aiming to develop new treatments for MacTel through better understanding of its clinical features. In particular we will identify how loss of vision occurs and investigate whether there is a genetic factor that contributes to the disease. First degree relatives of the participants (primarily siblings; secondarily parents) are included in a family genetics sub-study. The Save Sight Institute and Sydney Eye Hospital are major centres in the study.

MacTel CNTF2
• Status • Ongoing, no longer enrolling patients

This international study of a Ciliary Neurotropic Factor (CNTF) implant in the eye is an international study and the first treatment study in Australia for Macular Telangiectasia. Patients must first be enrolled in the MacTel (Natural History) Study above. Patient Eligibility and More Information

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Back to Currrent and Upcoming Trials

Clinical Research Contacts

Principal Investigators Prof. Mark Gillies (02) 9382 7309
  A/Prof Samantha Fraser-Bell (02) 9382 7309

Clinical Research Unit Manager

To refer a patient, make a research appointment, for general enquiries or for more information on clinical trials

Maria Williams

(02) 9382 7309 or

Fax: 02 9382 7278

Email: retina@eye.usyd.edu.au


Mailing address & administrative office location

C/O Maria Williams
Macular Research Group
Save Sight Institute
Level 1, Room 116, South Block
Campus of Sydney Eye Hospital
8 Macquarie Street, Sydney NSW 2000

FIND US - Macular Research Clinic Directions

Macular research clinics are held on Tuesdays and Friday mornings in the Out Patients Department of Sydney Eye Hospital.

The Sydney Eye Hospital is a shared campus with Sydney Hospital and is located at 8 Macquarie St Sydney, next door to the State Parliament of NSW.

The Out Patients Department is in the Main Clinical Block, next door to the General Emergency Department of Sydney Hospital located at the rear of the campus.

Walk through the Sydney Eye Hospital Sliding Doors and turn left in to the Out Patients Department.

For Tuesday appointments follow the signs for Reception 2.

For Friday appointments follow the signs for Reception 2.

Macular - Research Clinics

Research Clinics

Publications

Mehta H, Gillies M, Fraser-Bell S.
Perspective on the role of Ozurdex (dexamethasone intravitreal implant) in the management of diabetic macular oedema.
Ther Adv Chronic Dis. 2015; 6:234-45.

Au CP, Fardell N, Williams M, Fraser-Bell S, Campain A, Gillies M.
Patient experiences in retinal trials: a cross-sectional study.
BMC Ophthalmol. 2015;15:80.

Kaidonis G, Burdon KP, Gillies MC, Abhary S, Essex RW, Chang JH, Pal B, Pefkianaki M, Daniell M, Lake S, Petrovsky N, Hewitt AW, Jenkins A, Lamoureux EL, Gleadle JM, Craig JE.
Common Sequence Variation in the VEGFC Gene Is Associated with Diabetic Retinopathy and Diabetic Macular Edema.
Ophthalmology. 2015;122:1828-36.

Mehta H, Gillies MC. Macular telangiectasia type 2 does not always have clinically detectable vasculopathy.
JAMA Ophthalmology. 2015. In press.

Shibeeb O, Vaze A, Gillies M, Gray T.
Macular oedema in idiopathic macular telangiectasia type 1 responsive to aflibercept but not bevacizumab. Case Rep Ophthalmol Med. 2014;2014:219792

O'Day RF, Barthelmes D, Zhu M, Wong TY, McAllister IL, Arnold JJ, Gillies MC.
Intraocular pressure rise is predictive of vision improvement after intravitreal triamcinolone acetonide for diabetic macular oedema: a retrospective analysis of data from a randomised controlled trial.
BMC Ophthalmol. 2014;14:123.

Gillies MC, Lim LL, Campain A, Quin GJ, Salem W, Li J, Goodwin S, Aroney C, McAllister IL, Fraser-Bell S.
A Randomized Clinical Trial of Intravitreal Bevacizumab versus Intravitreal Dexamethasone for Diabetic Macular Edema: The BEVORDEX Study.
Ophthalmology. 2014;121:2473-81.

Vaze A, Fraser-Bell S, Gillies M.
Reasons for discontinuation of intravitreal vascular endothelial growth factor inhibitors in neovascular age-related macular degeneration.
Retina. 2014:34:1774-8.

Vaze A, Fraser-Bell S, Gillies M.
Consequences of long-term discontinuation of vascular endothelial growth factor inhibitor therapy in the patients with neovascular age-related macular degeneration.
Acta Ophthalmol. 2014;92:e697-8.

Finger RP, Guymer RH, Gillies MC, Keeffe JE.
The Impact of Anti-Vascular Endothelial Growth Factor Treatment on Quality of Life in Neovascular Age-related Macular Degeneration.
Ophthalmology. 2014;121:1246-51.

O'Day R, Walton R, Blennerhassett R, Gillies MC, Barthelmes D.
Reporting of Harms by Randomised Controlled Trials in Ophthalmology.
Br J Ophthalmol. 2014;98:1003-8.

Tan MH, McAllister IL, Gillies MC, Verma N, Banerjee G, Smithies LA, Wong WL, Wong TY.
Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion.
Am J Ophthalmol. 2014;157:237-247

Kaidonis G, Abhary S, Daniell M, Gillies M, Fogarty R, Petrovsk N, Jenkins N, Essex R, Chang JH, Pal B, Hewitt AH, Burdon KP, Craig JE.
The Genetic Study of Diabetic Retinopathy: Recruitment methodology and analysis of baseline characteristics.
Clin Experiment Ophthalmol. 2014;42:486-93.

O'Day R, Gillies MC, Ahlenstiel G.
Ophthalmologic complications of antiviral therapy in hepatitis C treatment.
World J Gastroenterol. 2013;19:8227-8237.

Holz FG, Bandello F, Gillies M, Mitchell P, Osborne A, Sheidow T, Souied E,Figueroa MS.
LUMINOUS Steering Committee. Safety of ranibizumab in routine clinical practice: 1-year retrospective pooled analysis of four European neovascular AMD registries within the LUMINOUS programme.
Br J Ophthalmol. 2013;97:1161-7

O'Day R, Barthelmes D, Zhu M, Wong TY, McAllister IL, Arnold JJ, Gillies MC.
Baseline central macular thickness predicts the need for retreatment with intravitreal triamcinolone plus laser photocoagulation for diabetic macular edema.
Clin Ophthalmol. 2013;7:1565-70

Clemons TE, Gillies MC, Chew EY, Bird AC, Peto T, Wang JJ, Mitchell P, Ramdas WD, Vingerling JR.
Medical Characteristics of Patients with Macular Telangiectasia Type 2 (MacTel Type 2).
Ophthalmic Epidemiol. 2013;20:109-13

Powner MB, Gillies MC, Zhu M, Kristis Vevis K, Hunyor, AP, Fruttiger M.
Loss of Müller cells and photoreceptors in Macular Telangiectasia Type 2.
Ophthalmology. 2013;120:2344-52.

Charbel Issa P, Gillies MC, Chew EY, Bird AC, Heeren T, Peto T, Holz FG, Scholl HPN.
Macular Telangiectasia Type 2.
Prog Retin Eye Res. 2013;34:49-77

Zhu M, Krillis M, Gillies MC.
The relationship between inner and outer retinal cavitation and the integrity of the outer limiting membrane in Macular Telangiectasia Type 2.
Retina. 2013;33:1547-50.

Kemp A, Preen DB, Morlet N, Clark A, McAllister IL, Briffa T, Sanfilippo F, Ng JQ, McKnight C, Reynolds W, Gillies MC.
Myocardial infarction after intravitreal vascular endothelial growth factor inhibitors: a whole population study.
Retina. 2013;33:920-7

Liew G, Quin G, Gillies M, Fraser-Bell S.
Central serous chorioretinopathy: a review of epidemiology and pathophysiology.
Clin Experiment Ophthalmol. 2013;41:201-14

Quin G, Liew G, Ho IV, Gillies M, Fraser-Bell S.
Diagnosis and interventions for central serous chorioretinopathy: review and update.
Clin Experiment Ophthalmol. 2013;41:187-200

Sallo FB, Peto T, Egan C, Wolf-Schnurrbusch UE, Clemons TE, Gillies MC, Pauleikhoff D, Rubin GS, Chew EY, Bird AC.
MacTel Study Group. The IS/OS junction layer in the natural history of type 2 idiopathic macular telangiectasia.
Invest Ophthalmol Vis Sci. 2012;53:7889-95

McAllister IL, Gillies MC, Smithies LA, Rochtchina E, Harper CA, Daniell MD, Constable IJ, Mitchell P. Factors Promoting Success and Influencing Complications in Laser-Induced Central Vein Bypass. Ophthalmology. 2012;119:2579-86

Cherepanoff S, Killingsworth MV, Zhu M, Nolan T, Hunyor AP, Young SH, Hageman GS, Gillies MC. Ultrastructural and clinical evidence of subretinal debris accumulation in type 2 macular telangiectasia.
Brit J Ophthalmol. 2012;96:1404-9

Sallo FB, Peto T, Egan C, Wolf-Schnurrbusch UE, Clemons TE, Gillies MC, Pauleikhoff D, Rubin GS, Chew EY, Bird AC.
'En face' OCT imaging of the IS/OS junction line in Type 2 Idiopathic Macular Telangiectasia.
Invest Ophthalmol Vis Sci. 2012;53:6145-52

Salem W, Fraser-Bell S, Gillies M.
Clinical development of new treatments for diabetic macular oedema.
Clin Exp Optom. 2012;95:297-305.

Gillies MC, McAllister IL, Zhu M, Wong W, Louis D, Arnold JJ, Wong TY.
Intravitreal triamcinolone prior to laser treatment of diabetic macular edema: 24-month results of a randomized controlled trial.
Ophthalmology. 2011;118:866-72

Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jiao J, Li XY, Whitcup SM
Ozurdex GENEVA Study Group. Dexamethasone Intravitreal Implant in Patients with Macular Edema Related to Branch or Central Retinal Vein Occlusion Twelve-Month Study Results.
Ophthalmology. 2011;118:2453-2460

Powner MB, Gillies MC, Tretiach M, Scott A, Guymer RH, Hageman GS, Fruttiger M.
Perifoveal Müller Cell Depletion in a Case of Macular Telangiectasia Type 2.
Ophthalmology. 2010;117:2407-16

Gillies MC.
Bevacizumab in ophthalmology: the controversy moves forward.
Clin Experiment Ophthalmol. 2010;3:333-4

Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jacques ML, Jiao J, Li XY, Whitcup SM.
OZURDEX GENEVA Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion.
Ophthalmology. 2010;117:1134-1146

Gillies MC, Islam FM, Larsson J, Pasadhika S, Gaston C, Zhu M, Wong TY.
Triamcinolone-induced cataract in eyes with diabetic macular oedema: 3-year prospective data from a randomised clinical trial.
Clin Experiment Ophthalmol.2010;38:605-12

Parmalee NL, Schubert C, Merriam JE, Allikmets K, Bird AC, Gillies MC, Peto T, Figueroa M, Friedlander M, Fruttiger M, Greenwood J, Moss SE, Smith LE, Toomes C, Inglehearn CF, Allikmets R.
Analysis of candidate genes for macular telangiectasia type 2.
Mol Vis. 2010;16:2718-26

Kuo CH, Gillies MC, McCluskey P.
Intraocular Triamcinolone for Giant Cell Arteritis?
Arch Ophthalmol. 2010;128:1633.

Kuo CH, McCluskey P, Gillies M.
Pharmacotherapeutic efficacy of preservative-free intravitreal triamcinolone acetonide.
Expert Opin Pharmacother. 2010:155-66

McAllister I, Gillies M, Smithies L, Rochtchina E, Harper A, Daniell M, Constable I, Mitchell P
The Central Retinal Vein Bypass Study: A randomised controlled multi-centre trial of laser-induced chorioretinal venous anastomosis for non-ischaemic central retinal vein occlusion. Ophthalmology.2010;117:954-965

Clemons TE, Gillies MC, Chew EY, Bird AC, Peto T, Figueroa MJ, Harrington MW and the Macular Telangiectasia Research Group. Baseline Characteristics of Participants in the Natural History Study of Macular Telangiectasia (MacTel) MacTel Project Report No. 2. Ophthalmic Epidemiol. 2010;17:66-73

Gillies MC, McAllister IL, Zhu M, Wong W, Louis D, Arnold JJ, Wong TY. Pre-Treatment with Intravitreal Triamcinolone Prior to Laser for Diabetic Macular Edema: 6-Month Results of a Randomised, Placebo-Controlled Trial.
Invest. Ophthalmol. Vis. Sci. 2010;51:2322-2328



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