Ieuan Rees B.App.Sc.(Optom) (Hons)GradCertOcTher Specialty Contact Lens Practitioner Ophthalmic Medicines Prescriber Orthokeratologist, Behavioural Optometrist

Diabetes and the Eye Diabetic Retinopathy Diabetic Macula Oedema Diabetic retinopathy is the leading cause of new blindness in persons aged 25-74 Diabetic Macula Oedema Glaucoma Iris Neovascularisation Neuropathies Corneal Anomalies Hyperopic /Myopic Prescription Changes Extra-ocular Muscle Palsy Dry Eye Disease (50%) (reduced corneal sensitivity)

>70% with diabetes will develop changes to their eyes… within 15 years of diagnosis.

Optometry’s Role in Diabetic Eye Care Optometrists screen for DR appropriate skills diagnostic equipment accessible to the public. capacity and responsibility to increase patient awareness about the condition. Medicare item code (10915)

=>ischaemia and/or vessel leakage, causing swelling and bleeding. Diabetic changes in the Eye Diabetic retinopathy : Microvascular occlusion and leakage. Capillaropathy-Degeneration and loss of pericytes, proliferation of endothelial cells thickening of basement membrane and occlusion Haemotological changes=> Decreased blood flow =>ischaemia and/or vessel leakage, causing swelling and bleeding.

Capillary non perfusion and retinal hypoxia which may cause: Arteriovenous shunts (IRMA) Neovascularization caused by angiogenic growth factors (VEGF)

Who is at risk? All people with Type 1 or Type 2 diabetes are at risk of developing diabetic retinopathy. Over the same duration, type 1 may result in worse diabetic retinopathy The longer a person has diabetes, the greater the risk. (25% for 15 years) Poor control of blood sugar levels can increase the risk   Access Economics Pty Ltd. Clear Insight – The Economic Impact and Cost of Vision Loss in Australia, 1.2 Diabetic Retinopathy, August 2004,

Other Risk Factors Systemic Hypertension Hyperlipidaemia Renal disease Pregnancy (with prior Type 1 or Type 2 diabetes) Family History of DR Smoking

Controlling Diabetic Retinopathy Risk Intensive glucose therapy Reduces the onset of new DR by 75% Reduces the progression of DR by 50% HbA1c 6-7% 1% decrease in HbA1c associated with lowering the risk of retinopathy 40% progression to sight threatening DR 25% risk for laser 24% risk for blindness 15%

Controlling Diabetic Retinopathy Risk Tight BP control associated with lower risk of Retinopathy progression 35% Need for laser 35% Risk for vision loss 50% Others: Hyperlipidemia(lipidil) / Smoking and Alcohol consumption / Pregnancy / Body Mass Index / Inflammation

Evidence indicates that early detection of Diabetic Retinopathy by regular eye examination, is key to reducing vision loss and blindness from diabetes. It is estimated only ½ the Australians with diabetes have a regular eye exam and 1/3rd have never been checked. Often there are no symptoms of diabetic retinopathy until serious damage has occurred. Early diagnosis and treatment can prevent severe vision loss Eye examination every Year is recommended for people with diabetes.

Visual Acuity Assessment: Baseline and every appointment. Optometrical Evaluation of a Diabetic Patient Case History: type and duration of diabetes, past glycaemic control, medications systemic history, frequency/ results of self-monitored blood glucose and recent laboratory tests for HbA1C, serum lipids and proteinuria. Visual Acuity Assessment: Baseline and every appointment. Fundus (Stereoscopic) Examination: :-Dilated fundus examination and Digital image of the retina. Patient Education: Importance of regular eye examination /controlling systemic factors

Optometrical Evaluation of a Diabetic Patient Pupil reactions: Direct/consensual and near pupillary responses. Ocular motility: Extent, fluency and symmetry of ocular movements in all directions of gaze, ruling out eye movement anomalies. :-Onset and direction of diplopia is necessary. Degree and direction of diplopia. Visual field screening: Confrontation and/or visual field assessment as per Medicare guidelines. Refraction: On indication where patient reports a change in vision or visual function or where a change in habitual visual acuity is measured. Slit lamp biomicroscopy: Recommended at every visit to check for iris and corneal neovascularisation, diabetic cataract and corneal integrity. Tonometry: Link between vasculopathic conditions and glaucoma.

ETDRS : Early Treatment Diabetic Retinopathy Study. Mild Non Proliferative Diabetic Retinopathy (NPDR) Moderate Severe Very Severe Proliferative Diabetic Retinopathy (PDR) Early PDR High Risk PDR

Optometry Australia: Adopted the International Clinical Diabetic Retinopathy Disease Severity scale :-easily understandable scale to classify NPDR.

How to detect diabetic retinopathy? Direct Ophthalmoscopy Microaneurysms Dot and blot hemorrhages MA’s rupture in the deeper retinal layers Flame-shaped hemorrhages occur in the more superficial layer Retinal edema and hard exudates :-breakdown of the blood retinal barrier allowing leakage of serum protein and lipids 90D Un-dilated Slit Lamp Biomicroscopy

How to detect diabetic retinopathy? 90D Dilated Slit Lamp Biomicroscopy NB: Stereoscopic Imaging Cotton-wool spots are nerve fibre layer infarcts from occlusion of precapilary arteriole

How to detect diabetic retinopathy? 22D Full Field Binocular Indirect Ophthalmoscope:-Dilated Venous loops and beading frequently occur adjacent to area of non perfusion and reflect increased retinal ischaemia IRMA are collaterals without proliferation and can usually be found on the border of non perfused retina

How to detect diabetic retinopathy? Neovascularization Is the hall mark of PDR :- (NVD) Or (NVE) Standard Digital Retinal Photography 45 Degrees

ETDRS 7. Early Treatment Diabetic Retinopathy Study.

How to detect diabetic retinopathy? Optos: Optomap 200 Degree Digital Retinal Imaging Optic disc edema occurs in patients with type I or II diabetes mellitus

Optos takes digital diabetic retinopathy screening further

Computer generated colour image

Green Laser Image

Red Laser Image

RED Laser Zoom.

What can we see with Optomap 2000 Digital Retinal Imaging ?

Primary aim is to diagnose, Report to GP…(BDR: Fenofibrate) The Optometrist’s Role in Diabetic Retinopathy: Screening and Maintenance Primary aim is to diagnose, Report to GP…(BDR: Fenofibrate) Refer to Ophthalomologist… and consequently prevent / treat sight threatening DR retinopathy

How often should eye examinations occur? Dictated primarily by the baseline stage of the retinopathy and its rate of progression to proliferative diabetic retinopathy Only 5% patients with mild NPDR will progress to PDR in 1 year, monitoring every 6-12 months is appropriate As many as 27% of patients with mod NPDR would progress to PDR in I year, review every 4-8 months More than 50% of patients with severe NPDR would progress to PDR in one year, review 2-3 monthly BDR to PDR

BDR to Macula Oedema

LIPIDIL FIELD study fenofibrate had a statistically significant relative risk reduction in the need for laser treatment for maculopathy and proliferative retinopathy. ACCORD-Eye study :-statistically significant reduction in diabetic retinopathy progression in patients treated with fenofibrate and statin combination therapy compared to statin therapy alone. Fenofibrate slows progression of diabetic retinopathy and the need for more invasive treatment modalities in patients with type 2 diabetes, when there is pre-existing retinopathy. In October 2013, Australia became the first country in the world to approve the use of this medication for this specific indication.

The evidence indicates that only diabetic patients with some prior DR, whether mild or moderate may benefit at all from fenofibrate. An argument can be made that fenofibrate is more clinically efficacious in patients:- With moderately elevated Low-density lipoprotein (LDL) (2.2 – 2.9 mmol/L) Triglyceride lipase (TGL) (3.3 – 5.2mmol/L).

First round assessment of risks The risks of fenofibrate in the proposed usage are: It can be considered ineffective polypharmacy to treat patients with diabetes that show no DR. By delaying the use of fenofibrate to diabetic patients, the potentially unnecessary side effects, adverse drug reactions and drug interactions of fenofibrate are avoided. This includes the waste of resources in providing fenofibrate in population where it is not effective (diabetics without prior DR).

Lipidil is indicated for the reduction in the progression of diabetic retinopathy in patients with Type 2 diabetes and existing diabetic retinopathy. Lipidil does not replace the appropriate control of blood pressure, blood glucose and blood lipids in reducing the progression of diabetic retinopathy.

Diabetic Macula Oedema Diabetic Macular Oedema is the most common cause of moderate visual loss. Leaking micro-aneurysms, or diffusion from capillary incompetence results in intra-retinal fluid areas and can progress to cystoid macular oedema (CMO). Diabetic macular oedema (DMO) is retinal thickening within two disc diameters of the centre of macula.

If they are left untreated, sight problems will develop. Both proliferative diabetic retinopathy and diabetic macular oedema can be treated and managed if they are detected early enough. If they are left untreated, sight problems will develop.

The International clinical diabetic macular edema severity scale has devised a simpler classification of DME. Adopted by the Optometry Australia in 2014

DME and OCT:- Ocular Coherence Tomography Identify eyes at risk of vision loss from DME and can be useful to guide decisions on the timing of treatment initiation or retreatment, as well as the timing of follow up care for eyes that are being managed with observation

Normal Macular Cross-Section OCT Scan

Cystoid Macula Oedema Due to Diabetic Retinopathy: OCT Images

Vitrectomy Retinal Laser Photocoagulation has been the standard care for DME since the mid 1980.

Intravitreal Agents Intravitreal therapy has radically changed the management of diabetic macular edema Groups of drugs currently utilized are Corticosteroids (Triamcinolone) and Anti-Vascular Endothelial Growth Factor blockade (Anti-VEGF) (Lucentis and Avastin, Eylea))

Triamcinolone

EYLEA: Anti VEGF The VIVID/VISTA clinical trials and early experience with aflibercept in DME DME, diabetic macular oedema

Aflibercept: A specifically-designed anti-VEGF Soluble decoy VEGF receptor1 Binds VEGF-A and PlGF with higher affinity than their natural receptors Forms a stable, inert 1:1 complex with VEGF, binding both sides and preventing interaction with other molecules1 VEGFR-1 domain Aflibercept molecule VEGFR-2 domain Aflibercept/VEGF complex VEGF dimer Fc fragment PlGF, placental growth factor; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor. 1. Heier JS et al. 2009; Available at http://www.retinalphysician.com/articleviewer.aspx?articleid=102898. Accessed July 2014.

Mean change in BCVA from baseline (ETDRS letters) Initial rapid gains in visual acuity from baseline were maintained over 100 weeks Mean change in BCVA from baseline (ETDRS letters) 2 10 12 14 6 4 8 VIVID week 100 10.7 2q8* 11.4 2q4* 9.4 2q8* 10.5 2q4* 1.2 Laser 0.7 Laser 100 92 80 68 64 56 52 40 36 28 20 12 4 8 16 24 32 44 48 60 72 76 84 88 96 12.5 2q4* VISTA week 100 11.5 2q4* 11.1 2q8* 10.7 2q8* 0.2 Laser 0.9 Laser 100 92 80 68 64 56 52 40 36 28 20 12 4 8 16 24 32 44 48 60 72 76 84 88 96 BVCA is the primary endpoint. primary analysis was conducted at week 52, week 100 is exploratory only. Week Laser 2q4 2q8 *P<0.0001 vs. laser. VIVID: Laser: n=132; 2q4: n=136; 2q8: n=135; VISTA: Laser: n=154; 2q4: n=154; 2q8: n=151. Full analysis set (last observation carried forward). 2q4, 2 mg every 4 weeks; 2q8, 2 mg every 8 weeks after 5 initial monthly doses; BCVA, best corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study. Korobelnik J-F et al. Ophthalmology 2014; 121: 2247-2254; Brown DM et al, Ophthalmology 2015; 122: 2044-2052

Proportion of patients gaining ≥15 letters from baseline was maintained over 100 weeks VIVID Week 52 VISTA Week 100 ≥15 letters 60 40 Patients (%) 20 50 30 10 Laser 2q4 2q8 9.1 32.4* 33.3* 7.8 41.6* 31.1* 13.0 38.3* 33.1* 12.1 38.2* Secondary endpoint. primary analysis was conducted at week 52, week 100 is exploratory only . *P<0.0001 vs. laser. VIVID: Laser: n=132; 2q4: n=136; 2q8: n=135; VISTA: Laser: n=154; 2q4: n=154; 2q8: n=151. Full analysis set; last observation carried forward. 2q4, 2 mg every 4 weeks; 2q8, 2 mg every 8 weeks after 5 initial monthly doses. Korobelnik J-F et al. Ophthalmology 2014; 121: 2247-2254; Brown DM et al, Ophthalmology 2015; 122: 2044-2052

Proportion of patients losing ≥15 letters from baseline over 100 weeks 20 15 10 Patients (%) 5 Laser 2q4 2q8 2.2 12.9 1.5 9.1 0.6 0.7 9.7 3.2 10.6 0.0 VIVID Week 52 VISTA Week 100 ≥15 letters Laser 9.1%. 2q4 0.6%. 2q8 0.7%. All compared to baseline (LOCF); last observation carried forward. Laser 9.1%. 2q4 0.6%. 2q8 0.7%. All compared to baseline (LOCF); last observation carried forward. (P = 0.0008) 2q4 vs laser. (P = 0.0002) 2q8 vs laser. (P = 0.0220) 2q4 vs laser. (P = 0.0004) 2q8 vs laser. primary analysis was conducted at week 52, week 100 is exploratory only. Proportion of patients losing ≥ 15 letters is an additional efficacy endpoint VIVID: Laser: n=132; 2q4: n=136; 2q8: n=135; VISTA: Laser: n=154; 2q4: n=154; 2q8: n=151. Full analysis set; last observation carried forward. 2q4, 2 mg every 4 weeks; 2q8, 2 mg every 8 weeks after 5 initial monthly doses. Korobelnik J-F et al. Ophthalmology 2014; 121: 2247-2254; Brown DM et al, Ophthalmology 2015; 122: 2044-2052

Reduction in CRT from baseline was maintained through week 100 -66 VIVID -86 -196* -212* -195* -192* Mean change in CRT from baseline µm *P<0.0001 vs laser -73 VISTA -84 -191* -186* -183* *P<0.0001 vs laser Laser 2q4 2q8

Summary Optometry has the skills and equipment to diagnose diabetic retinopathy, diabetic macula oedema and other diabetes related eye conditions. OCT and OPTOS have enhanced our ability. (Both only available @ Buck & Todd) Treatments include PRP, Vitrectomy and Intravitreal Phamacological Agents. Management by the GP for glycaemic control, lipid control, cholesterol and hypertension control is essential. Fenofibrate should be considered at first sign of BDR.

Thank You Ieuan Rees B.App.Sc.(Optom) (Hons)GradCertOcTher Specialty Contact Lens Practitioner Ophthalmic Medicines Prescriber Orthokeratologist, Behavioural Optometrist Thank You Special Thanks: Dr Andre Horak ..Vision Eye Institute