Lecture 7 ARMD (slides) PDF

Age-related macular degeneration (AMD) AOCP Gurvinder Chattha  Why do I need to know this? ▪ You will encounter patients with age-related macular degeneration ▪ Age-related macular degeneration can have a significant impact on a patients vision and quality of life ▪ Need to be able...

Age-related macular degeneration (AMD) AOCP Gurvinder Chattha  Why do I need to know this? ▪ You will encounter patients with age-related macular degeneration ▪ Age-related macular degeneration can have a significant impact on a patients vision and quality of life ▪ Need to be able to identify between the different types of age- related macula degeneration  What should I know after this? ▪ An overview of age-related macular degeneration ▪ Prevalence ▪ Risk factors ▪ Aetiology ▪ Clinical features  Age-related macular degeneration (AMD) ▪ Disease that affects the macula ▪ The central retinal region of our vision ▪ Responsible for detailed and colour vision ▪ Characterized by the presence of specific clinical findings, including drusen and RPE changes, in the absence of another disorder ▪ Later stages of the disease are associated with impairment of vision  OCT ▪ Non-invasive and non-contact imaging system ▪ High resolution cross-sectional images ▪ Measures light reflectance of structures ▪ High reflectivity structures can be depicted in a pseudo-colour image as red, intermediate as green-yellow and low reflectivity as blue-black Optical coherence tomography (OCT) ▪ OCT provides visualisation of the retinal anatomy ▪ Allows identification of retinal abnormalities which are present in AMD Healthy OCT scan  Anatomy ▪ Retina ▪ Layered structure with the ganglion (nerve cells) nearest the vitreous ▪ Photoreceptors rods and cones nearest the choroid ▪ Choroid is sandwiched between sclera and retina ▪ Choroid provides 2/3 nutrition to the retina and RPE  The macula ▪ Has the highest concentration of photoreceptors ▪ High central resolution ▪ Colour vision ▪ Horizontally oval, around 5mm in diameter ▪ The foveola forms the central floor ▪ Diameter of 0.35mm ▪ Thinnest part of the retina ▪ Entire thickness consists only of cone photoreceptors ▪ Most acute vision  Retinal pigment epithelium (RPE) ▪ The retinal pigment epithelium (RPE) maintains the photoreceptors ▪ RPE cells ▪ Absorb stray light ▪ Forms the outer blood retinal barrier ▪ Regenerates the visual pigment  Macula and RPE ▪ Macula has the highest concentration of photoreceptors ▪ Hence is the area where the RPE is the most metabolically active ▪ Hence the area most likely to suffer the consequence of RPE failure over time due to the accumulation of metabolic debris and lipofuscin  Choroid ▪ Sits below Bruch's membrane ▪ Made up of choroidal vessels that supply the outer retina ▪ Choroid is very important at the macula area where retinal circulation is absent  Bruch’s membrane ▪ Located in between the choroid and the RPE ▪ Involved in the controlled passage of nutrients and waste products to and from the retina ▪ Retinal pigment epithelium (RPE) ▪ Highly pigmented layer of the retina ▪ Sits between the neurosensory retina and Bruch's membrane ▪ The neurosensory retina ▪ Collection of retinal layers including the retinal nerve fiber layer down to the photoreceptor layers ▪ Foveal pit ▪ At the centre of the macular region ▪ Enables very detailed colour vision ▪ Has a large number of cone photoreceptors and no ganglion cells overlying them  Aeitology ▪ Part of the aging process - undigested metabolic debris and lipofuscin accumulates beneath the retina ▪ Between the layers known as Bruch's membrane and the RPE ▪ In younger healthy eye the debris is removed ▪ In older eyes it is not possible for debris to be removed and it forms drusen ▪ Thought there may also be an inflammatory response element to this  Risk factors ▪ Multi-factorial causes ▪ Genetically susceptible individuals ▪ Increasing age ▪ Increasing vulnerability as a result of a process known as oxidative stress  Risk factors ▪ Older age ▪ Presence of AMD in the other eye ▪ Family history of AMD ▪ Smoking ▪ Hypertension ▪ BMI of 30 kg/m2 or higher ▪ Diet low in omega 3 and 6, vitamins, carotenoid and minerals ▪ Diet high in fat ▪ Lack of exercise  Family history ▪ Genetics ▪ People with a family history of AMD are around 4 to 6 times more likely to develop late AMD than those without such family history  Smoking ▪ Smoking ▪ Strong evidence that smoking is a risk factor for AMD ▪ Those who smoke are 2 to 3 times more likely to develop late AMD than those who do not smoke ▪ Stopping smoking lowers the relative risk of AMD ▪ Important role for optometrists in advising people on how to get support  Hypertension ▪ An association between the presence of hypertension and late AMD  BMI and exercise ▪ NICE guidelines state that a BMI of 30 kg/m2 or higher and a lack of exercise are risk factors for AMD ▪ Risk of late AMD increases if a patient is overweight or obese ▪ Active lifestyle is also shown to have a protective affect against developing wet AMD  Nutrition ▪ A diet low in omega 3 and 6, vitamins, carotenoid and minerals is a risk factors for AMD ▪ Nutrition has been extensively researched as it is a risk factor that could be modified ▪ Nutrition will be discussed in more detail in AMD 2 lecture  Light exposure ▪ No significant evidence for increased risk of AMD due to light exposure  Race ▪ Evidence is inconclusive and is therefore not included in NICE guidelines ▪ Previous studies had suggested that Caucasians are at greater risk of AMD than people of African American ethnicity- now not included as a risk factor  Classification of AMD ▪ AMD: Age-related macular degeneration. ▪ Early AMD ▪ Late AMD (dry) ▪ Late AMD (indeterminate) ▪ Late AMD (wet active) ▪ Late AMD (wet inactive)  NICE guidelines ▪ National Institute for Healthcare and Excellence (NICE) ▪ Evidence-based recommendations developed by independent committees, including professionals and lay members, and consulted on by stakeholders ▪ NICE guideline [NG82] published January 2018 classify age- related macular degeneration ▪ nice.org.uk  Two main types of AMD ▪ Dry (non-exudative, non-neovascular) AMD ▪ Most common form (90%) ▪ Slower progression, usually bilateral ▪ Geographic atrophy (GA) is the advanced stage of dry AMD ▪ Wet (exudative, neovascular) AMD ▪ Much less common than dry ▪ More rapid progression to advanced sight loss ▪ Main manifestations are CNV and PED ▪ Recent years at least two additional conditions- retinal angiomatous proliferation (RAP) and polypoidal choroidal vasculopathy (PCV), have been included under the umbrella of neovascular AMD  Dry AMD ▪ Includes the early and intermediate stages of the disease ▪ Build-up of debris under the retina causes drusen formation and degeneration of the RPE ▪ Slow and progressive thinning and degeneration of the photoreceptors and the RPE gradually leads to failure of central vision ▪ 90% of people with dry AMD will only have mild or moderate gradual visual loss ▪ Although the less aggressive form, it still causes about 20% of AMD related severe visual loss  Drusen ▪ Clinical features of dry AMD ▪ Drusen ▪ Pigmentary abnormalities ▪ Hyperpigmentation ▪ Hypopigmentation ▪ The disease classification depends on drusen ▪ People with many large soft drusen are more likely to develop atrophy and severe visual loss ▪ Greater risk of developing wet AMD  Drusen ▪ Most people over the age of 40 years have at least one druse ▪ Drusen look like yellow spots around the macula  Hard drusen ▪ Small and well defined ▪ In early stages the person is likely to have no visual symptoms. ▪ Even if cases with very obvious and widespread hard drusen people may not experience any visual symptoms ▪ Using the NICE guidance [NG82] classification of a person with hard drusen and no other anomalies would be 'Normal eyes’.  Soft drusen ▪ Drusen can combine and form larger soft drusen ▪ Soft drusen can cause a decline in vision but it may also cause no visual symptoms at all ▪ Those with soft drusen are statistically more likely to develop AMD ▪ Using the NICE guidance [NG82] classification of a person with medium or large soft drusen (with or without other features) would be 'Early AMD'.  Geographic atrophy ▪ Geographic atrophy (GA) consists of one or more areas of RPE hypo-pigmentation ▪ There is loss of the overlying photoreceptors with clearly visible choroidal vessels and large area of retinal dysfunction ▪ About 10% of people with dry AMD develop GA ▪ Bilateral in 50% of cases ▪ Can experience severe visual loss ▪ Particularly if the atrophy is at the fovea ▪ Blank patch in the centre of vision Geographic atrophy  Clinical features of dry AMD ▪ Numerous soft drusen in the posterior pole surrounding the macula ▪ Soft drusen (fuzzy edges) ▪ Some of these soft drusen have coalesced ▪ (medium soft drusen: NG82 - Early AMD with a low risk of progression) ▪ (Large soft drusen: NG82 - Early AMD with a medium risk of progression)  Clinical features of dry AMD ▪ There are a number of large soft drusen ▪ Some hypopigmentated areas around macula area ▪ Presence of soft drusen and hypopigmentation increase this patients risk of developing wet AMD. ▪ (NG82 - Early AMD with a high risk of progression)  Clinical features of dry AMD ▪ Large patch of geographic atrophy to the right of the fovea. ▪ Patient may not be visually affected as the GA does not involve the fovea. ▪ (NG82 - Late AMD DRY) ▪ Small scattered hard drusen across the macula and into the superior arcades. It is likely the patient will have no visual symptoms. ▪ (NG82 - Normal eyes)  Drusen on OCT ▪ Appear as uneven raised areas of the RPE ▪ Drusen in this image are indicated with white arrows. ▪ Large drusen because the overlying photoreceptor (including the inner segment - outer segment) layer is being distorted  RPE atrophy ▪ Geographic atrophy ▪ Visible on OCT as loss of the highly pigmented RPE layer ▪ Increased hyper reflectivity below the retina (indicated in white) ▪ Loss of the overlying photoreceptors and inner retinal layers ▪ Retinal thickness is reduced. ▪ The drusen have also regressed and no longer visible in the marked section  Wet AMD ▪ Wet AMD affects about 10% of those who have AMD ▪ Important as it is potentially treatable ▪ If untreated it causes severe visual loss in 90% of cases  Wet AMD ▪ Caused by the growth of new vessels from the choroidal circulation ▪ A choroidal neovascular membrane develops intra-choroidally ▪ Actively proliferates and spreads through Bruch's membrane to the RPE and subretinal space. ▪ The end stage is loss of overlying photoreceptors and fibrosis (disciform scar)  Wet AMD ▪ These new vessels can leak fluid and bleed causing ▪ Sub-RPE fluid ▪ Sub-retinal fluid ▪ Intra-retinal fluid ▪ Haemorrhages ▪ Fluid usually causes distortion and rapid visual loss ▪ In some early cases vision can be preserved ▪ Most extreme Vision loss is usually due to large haemorrhages covering the macula  Wet AMD ▪ Fluid is most easily viewed using OCT ▪ May be visible as a raised area using indirect ophthalmoscopy ▪ Haemorrhages are usually visible with fundus photography or ophthalmoscopy ▪ Changes can be marked with obvious haemorrhages and/or exudates ▪ Can also be subtle changes with small haemorrhages or with no visible changes at all  Wet AMD ▪ If left untreated/treatment is not promptly begun- repeated leakage of fluid and blood can lead to fibrous scar formation ▪ Appears as a large elevated patch of scar tissue in the central macular area ▪ Will cause significant visual loss ▪ Disciform scar is classified by NG82 guidelines as Late AMD (wet inactive), and not to be confused with Late AMD (dry)  Clinical features of Wet AMD ▪ Retinal haemorrhage ▪ Can be seen at the centre of the macula ▪ Haemorrhage is faint - may not cause any severe visual symptoms ▪ Darker coloured retina surrounding the haemorrhage ▪ Suggests that this area may be raised due to fluid within the retina as well ▪ May cause distortion or visual symptoms  Clinical features of Wet AMD ▪ Large central haemorrhage covering the fovea ▪ Likely to reduce the VA significantly ▪ Large haemorrhage ▪ Strongly suggests there is a fluid leakage within the retina Clinical features of Wet AMD Number of haemorrhages surrounding the macula with a central darker coloured retina (suggesting fluid)  Sub-retinal fluid (SRF) ▪ On OCT SRF is visible as a dark space above the RPE but underneath the neurosensory retina (indicated by the arrow)  Intra-retinal fluid (IRF) ▪ On OCT IRF is visible as one or more dark spaces within the sensory retina ▪ Accompanied with distortion of the appearance of the overlying retinal layers ▪ IRF in this image ▪ Large disciform scar with surrounding haemorrhage ▪ This image shows drusen and, to the right of the white arrow, a pigmentary epithelial detachment (PED). The arrow is pointing to subretinal fluid. The overlying neurosensory retina can be seen as thicker.  RPE detachment (PED) ▪ Pigment epithelial detachment (PED) from the inner layer of Bruch membrane is caused by disruption of the physiological forces maintaining adhesion ▪ Can be: ▪ Drusenoid ▪ Serous ▪ Fibrovascular ▪ Haemorrhagic PED What can we see in this image?  Differential diagnosis ▪ There are some conditions that have similar presenting signs and symptoms to AMD ▪ Central serous chorio-retinopathy ▪ CSR  Central serous chorio-retinopathy (CSR) ▪ Similar presentation to wet AMD ▪ Sudden onset visual symptoms sometimes being reported as distortion ▪ Micropsia and/or a partial scotoma ▪ Appears as a raised area at the macula ▪ On OCT it is visible as a dark area of sub-retinal fluid i.e. below the sensory retina. ▪ This is a serous detachment Central serous chorio-retinopathy (CSR) ▪CSCR ▪Most commonly in younger ▪Male patients (mean onset 41 years old) ▪Can resolve without treatment over 4 to 6 weeks  Diabetic maculopathy ▪ Diabetic maculopathy ▪ DMO  Diabetic maculopathy ▪ Can also cause similar signs to AMD ▪ Visual changes tend to be more gradual and less severe ▪ Can present with haemorrhages at the macula and with intra-retinal fluid on OCT ▪ Differential diagnosis ▪ Important to look for diabetic changes elsewhere in the retina and to identify the difference between exudates (more likely with diabetic maculopathy) and drusen (AMD)  Summary ▪ People with AMD are generally over 55 years old ▪ People with dry AMD can develop treatable wet AMD ▪ Listen carefully to the symptoms ▪ Be acquainted with NICE guideline [NG82]. Age-related macular degeneration. Age-related macular degeneration (AMD) 2 AOCP Gurvinder Chattha  Why do I need to know this? ▪ You will encounter patients with age-related macular degeneration ▪ Age-related macular degeneration can have a significant impact on a patients vision and quality of life ▪ Need to be able to identify between the different types of age- related macula degeneration ▪ Need to able to manage these patients  What should I know after this? ▪ How to manage patients with AMD within optometric practice ▪ Appropriate optometric investigation ▪ Referral to ophthalmology ▪ Advice and information ▪ Referral to other services ▪ Current treatments for AMD  Two main types of AMD ▪ Dry (non-exudative, non-neovascular) AMD ▪ Most common form (90%) ▪ Slower progression, usually bilateral ▪ Geographic atrophy (GA) is the advanced stage of dry AMD ▪ Wet (exudative, neovascular) AMD ▪ Much less common than dry ▪ More rapid progression to advanced sight loss ▪ Main manifestations are CNV and PED ▪ Recent years at least two additional conditions- retinal angiomatous proliferation (RAP) and polypoidal choroidal vasculopathy (PCV), have been included under the umbrella of neovascular AMD  Symptoms ▪ Very important in guiding the investigations and management of a person with AMD ▪ Wet AMD ▪ Complain of sudden onset reduced vision or distortion ▪ Some types of wet AMD can develop slowly over a few months ▪ Dry AMD ▪ Slower progression and more gradual reduced vision, usually bilateral ▪ May describe a significant change in vision if they go on to develop wet AMD  What questions should we ask? ▪ Need a thorough description of the visual symptoms ▪ Which eye? ▪ Onset? sudden/gradual, slow/fast ▪ Duration? when did they start ▪ Vision loss? subtle or marked, central or peripheral, blurring or distortion  Medical and ocular history ▪ A thorough patient medical history ▪ General health ▪ Any other general health conditions that can cause retinal signs such as diabetes and hypertension ▪ Smoker or ex-smoker?  Ocular history ▪ Ocular history ▪ Previous signs of AMD or changes at the macula? ▪ Comparison with previous records or images ▪ Previous visual acuity ▪ Previous ophthalmological investigations or treatment?  Patient history ▪ Family history ▪ Is the patient driving? ▪ Have they already been registered as sight impaired? ▪ How does this impact on their daily life? ▪ Have they received any support from low vision services, social services or voluntary organisations?  Optometric examination ▪ Visual acuity ▪ Measure and record distance and near visual acuities (monocular and binocular) ▪ NICE guidelines suggest wet AMD is treatable if VA is between 6/12 and 6/96  Refraction ▪ Important to rule out refractive change as the cause of the reduced vision ▪ Wet AMD can cause a hyperopic shift due to fluid at the macula  RAPD ▪ Check for a Relative afferent pupillary defect (RAPD) to rule out other causes ▪ Artery occlusions ▪ Vein occlusions  Amsler ▪ Can be useful to help understand the person's visual loss ▪ However, its value at detecting treatable AMD is in doubt (only approximately a third of cases who went on to have treatment for sub-retinal membranes were detected using an Amsler chart)  OCT examination ▪ Normal OCT  OCT examination ▪ Drusen shown on OCT image  OCT examination ▪ Sub-retinal fluid - would require referral  Dilated fundus examination ▪ Record presence or absence of: ▪ Macular drusen ▪ Pigmentary changes (hypo/hyper) ▪ Retinal thickening (oedema and exudates) ▪ Any fluid ▪ Any haemorrhages ▪ Fibrosis  Dilated fundus exam ▪ Prior to dilation: ▪ Check anterior chamber angles ▪ Perform tonometry before and after dilation ▪ Ensure no previous reactions to drugs ▪ Dilate: ▪ Stereoscopic fundus examination with appropriate Volk lens ▪ Fundus photography and OCT if available  Management ▪ Dry AMD is not generally referred to ophthalmology ▪ Routine referral may be required ▪ The patient requests an ophthalmological opinion ▪ A certificate of visual impairment registration (CVI) is needed ▪ Low vision services are available ▪ Provide information and advice ▪ Regular review (at least every year)  Nutrition ▪ Substantial evidence from the Age-Related Eye Disease Study (AREDS, now known as AREDS1) and the follow-up AREDS2 ▪ Taking high-dose antioxidant vitamins and minerals on a regular basis can decrease the risk of the development of advanced AMD in individuals with certain dry AMD features  Nutrition ▪ Recommendation was made in AREDS1 that individuals aged over 55 should undergo examination for the following high-risk characteristics, and if one or more are present should consider antioxidant supplementation: ▪ Extensive intermediate- (≥63 µm to 125 µm) drusen. ▪ At least one large (≥ 125 µm) druse. ▪ GA in one or both eyes. ▪ Late AMD in one eye (greatest benefit in AREDS1)  Nutrition ▪ AREDS2 ▪ Regimen used in AREDS1 consisted of vitamin C, vitamin E, the beta- carotene form of vitamin A, and 80 mg daily of zinc (with copper to prevent zinc-induced copper deficiency). ▪ High zinc doses are potentially associated with genitourinary tract problems, and there are data suggesting that 25 mg of zinc may be the maximal level that is absorbed. ▪ Beta-carotene almost certainly increases the incidence of lung cancer in current and former smokers.  Nutrition ▪ The evidence if specific to how advance the AMD is: ▪ No AMD or early AMD: No evidence for reduced risk of developing AMD with nutritional supplements ▪ Intermediate AMD and/or late AMD in one eye: Moderate quality evidence for reducing risk of progression in patients who take AREDS or AREDS2 formulation or antioxidant supplements ▪ AREDS: vitamin C 500mg, vitamin E 400IU, beta-carotene 15mg +zinc and copper ▪ AREDS2: AREDS formulation plus either additional omega 3 fatty acids or additional lutein and zeaxanthin ▪ There is no additional benefit of AREDS2 compared to AREDS formulation in delaying progression of AMD. However, beta-carotene can be harmful to smokers, increasing the risk of lung cancer, and therefore AREDS2 formula with lutein/zeaxanthin rather than beta- carotene is preferable in these patients.  Nutrition ▪ May be a beneficial effect of certain foods in a natural diet in slowing the course of AMD ▪ Eat a balanced diet containing coloured fruit and vegetables including dark leafy vegetables ▪ Green leafy vegetable intake ▪ A lower risk of AMD ▪ Increase intake of oily fish ▪ Stop smoking ▪ Protective measures against exposure to excessive sunlight should be considered  Nutrition summary ▪ No evidence of supplements being of benefit in patients with no signs of AMD or those with early AMD. ▪ A healthy balanced diet with an increased intake of leafy green vegetables and oily fish can still be recommended ▪ Patients with intermediate or late AMD there is some evidence of delayed progression if AREDS or AREDS2 formulations are used  Smoking ▪ Smoking increases the risk of late AMD by approximately 2-3 times compared to those who do not smoke ▪ If a patient who smokes has any signs of AMD ▪ Risk should be explained ▪ Advice given on how to get support in stopping smoking ▪ Usually be accessed via their GP  SOS warning ▪ Patients with dry AMD can progress to Wet AMD - important to explain the symptoms of wet AMD to look out for: ▪ Sudden onset distortion or reduction in vision ▪ Need to understand the importance of these symptoms ▪ To seek optometric examination as soon as possible  Driving ▪ Important to inform patients if you suspect their vision is below the legal requirements for driving  Written advice and information ▪ Signposting to other resources available ▪ RNIB ▪ Macular Society ▪ College of Optometrists  Referral to other services ▪ Low Vision Services ▪ Community low vision service / HES low vision service ▪ Opportunity for patient to discuss their eye condition with the low vision practitioner ▪ Low vision assessment and the loan of low vision aids is free of charge  Referral to other services ▪ Social Services ▪ Referrals to social services are usually triaged as they are in healthcare ▪ URGENT - at risk to themselves/others ▪ May include falls, burns or problems with taking medications or crossing the road ▪ SOON - at risk of losing independence ▪ May include needing kitchen skills training or mobility training ▪ ROUTINE - gadgets and advice ▪ May include a big button phone or benefits advice  Referral to other services ▪ Any optometrist or ophthalmic medical practitioner can refer people to social service ▪ Patient can refer themselves, or a relative can do so on their behalf. ▪ Anyone requiring urgent referral should be referred directly rather than via the low vision services  WET AMD ▪ Wet AMD is potentially treatable ▪ Features or symptoms suggestive of wet AMD require urgent referral to ophthalmology ▪ NICE Guideline [NG82] states " refer within 1 day" with treatment offered "within 14 days of referral to the macula service" ▪ Local protocols may have specific referral requirements Referral form  Hospital examination ▪ Vision ▪ OCT ▪ Fundus fluorescein angiography (FFA) ▪ An imaging technique ▪ Intravenous injection of fluorescein solution into the retinal vasculature ▪ Used for examining the vascular circulation of the retina and choroid  Phases ▪ Choroidal phase (pre-arterial) ▪ Arterial phase ▪ Arteriovenous (capillary phase) ▪ Venous phase ▪ Late (re-circulation) phase  Normal fluorescein angiogram Early phases 1. Choroidal phase at around 9-15 secs – patchy choroidal filling 2. Arterial phase-arteries fill 3. Arteriovenous phase-arteries all full and now veins begin to fill 4. Venous phase-veins all full Then enter the mid and late phases  Abnormalities of angiogram ▪ Hypofluorescence ▪ Reduction or absence of normal fluorescence due to blockage ▪ Blood or abnormalities in choroidal or retinal perfusion e.g. occlusion or ischaemia  Abnormalities of angiogram ▪ Hyperfluorescence ▪ Increased transmission or abnormal presence of dye ▪ Transmission defect – atrophy or absence of RPE allowing choroidal fluorescence (‘window defect’) ▪ Pooling e.g. CSR ▪ Leakage of dye ie DMO, CMO, neovascularisation in PDR and AMD  Abnormalities in FFA hypofluorescence Blocking- blood/other opacities Filling defect – lack of retinal perfusion block fluoroscence due to capillary dropout, retinal artery occlusion and other causes  hyperfluorescence Window defect-due to Leakage- fluorescein permeates loss of RPE out of leaky blood vessels  Classic vs occult neovascular membranes in AMD ▪ Classic Characterized by well-demarcated hyperfluorescence in early phases on FFA and late leakage that obscures the boundaries of the lesion. These lesions grow from choroid through Bruchs between retina and RPE. ▪ Occult Il-defined staining or leakage in the late frames with stippled appearance These lesions are under the RPE  Current treatments ▪ Treatment is currently only available for wet AMD ▪ NICE approved treatments for wet AMD are: ▪ Anti VEGF drugs ▪ Photodynamic Therapy (PDT) (not as a first line treatment and rarely used)  Treatment ▪ Treatment options should be discussed including possible benefits and risks ▪ If suspected wet AMD ▪ Useful to explain to the patient that anti VEGF treatment involves an intravitreal injection ▪ Details of this procedure will be discussed in more detail in the hospital eye service  Anti-VEGF ▪ Vascular endothelial growth factor (VEGF) is a protein that triggers the formation of new blood vessels ▪ Anti VEGF drugs bind with VEGF to prevent the trigger for abnormal blood vessel growth and leakage ▪ Anti VEGF drugs are administered via intravitreal injection Anti-VEGF  Anti-VEGF ▪ NICE recommends for patients with: ▪ Evidence of progressive wet AMD ▪ VA between 6/12 and 6/96 ▪ No structural damage to the fovea ▪ From clinical experience: ▪ Refer patients with suspected wet AMD regardless of their level of vision ▪ Patients with VA better than 6/12 or worse than 6/96 may be considered for treatment off license in certain clinical circumstances ▪ Most patients are suitable for anti VEGF ~ 90%  Treatment regime ▪ Treat and extend is the most widely used treatment regime ▪ The patient receives 3 loading doses of the chosen drug each separated by 1 month ▪ Then receive a treatment every visit following the loading doses but the separation of these treatments would be decided based upon the OCT scan ▪ i.e. if there was no fluid on the OCT the time between injection would be extended and if there was lots of fluid on the scan then the time would be shortened between injections  Treatment regime ▪ PRN (pro re nata) regimes are still used but now less frequently ▪ The patient still receives the 3 initial loading doses but after this would be reviewed monthly and only receive an injection when there is fluid visible on OCT scan  Refractive error ▪ Spectacle prescription will often change following and during anti- VEGF treatment due to changes in retinal thickness ▪ Preferable not to give new glasses until after the 3 loading doses AND the hospital eye service (HES) considers the macular stable ▪ Use clinical judgement and liaise with the HES where possible  Anti-VEGF treatments ▪ There are three anti VEGF treatments currently available: ▪ Ranibizumab (Lucentis) ▪ Aflibercept (Eylea) ▪ After the loading dose is complete, Aflibercept is every 8 weeks, rather than 4 weeks ▪ Bevacizumab (Avastin) ▪ Not currently licensed for use in the eye but is used 'off label' in some units  Advice ▪ Vision stabilised in around 90% of patients ▪ Vision improves in around 1/3 of patients ▪ Vision decreases in around 10% of patients ▪ Frequent attendance is required for follow up ▪ 3 loading doses are required each separated by a month ▪ Frequency of the following treatments will be decided upon the level of fluid on the OCT scans ▪ Risk of intra-ocular infection and endophthalmitis  Photodynamic therapy (PDT) ▪ Photodynamic therapy (PDT) with verteporfin has largely been replaced by anti VEGF for more patients ▪ May be used either in combination with anti VEGF or PDT alone (rarely) ▪ It may also be used for a chronic central serous chorioretinopathy  Photodynamic therapy (PDT) action ▪ Intravenous injection of verteporfin (visudyne) ▪ Verteporfin preferentially taken up by the CNV membrane, not the retina, hence no retinal damage ▪ Drug is activated by low powered laser causing damage to proliferating cells and seals/regresses leaking vessels. ▪ Usually painless for the patient  Alternative treatments ▪ Thermal argon or diode laser ▪ Gene therapy ▪ New anti-VEGF drugs ▪ Brolucizumab (Beovu®)  Summary ▪ Two main types of AMD ▪ Dry AMD is not generally referred to ophthalmology ▪ Routine referral may be required ▪ The patient requests an ophthalmological opinion ▪ A certificate of visual impairment registration (CVI) is needed ▪ Low vision services are available ▪ Wet AMD ▪ Potentially treatable ▪ Features or symptoms suggestive of wet AMD require urgent referral to ophthalmology