Managing common retinal disorders
The human retina is about 0.2mm thick and consists of millions of cells in several Layers.
Photoreceptors (rods and cones) lie outermost and are supported and nourished by the retinal pigment epithelium and vascular choroid. A variety of interneurons connect photoreceptors to ganglion cells, whose axons form the innermost layer of the retina and exit the eye as the optic nerve transmitting signals to the brain. The area of retina within the vascular arcades temporal to the optic disc is known as the macula, the centre of which is the fovea containing exclusively cone photoreceptors responsible for fine focus and colour vision.
The vitreous is a clear gel composed of a hydrated collagen and hyaluronic acid matrix. The posterior vitreous lies in intimate contact with the inner surface of the retina.
Posterior vitreous and retinal detachment
In posterior vitreous detachment (PVD), separation of the posterior vitreous gel from its attachment to the retinal surface is generally a spontaneous and natural ageing process, but may be precipitated by ocular surgery or trauma. The importance of this condition lies in the fact that traction on the retina as a result of PVD may cause retinal tears (rhegma) that can lead to ‘rhegmatogenous' retinal detachment (RD), which is more common in short-sighted (myopic) individuals.
PVD, retinal tears and RD can all cause a sudden onset of flashes (photopsia) with or without floaters (collagen debris or cells in the vitreous cavity), but may be asymptomatic. Visual acuity (VA) is usually unaffected in isolated PVD or retinal tears, but may be reduced if associated with vitreous haemorrhage.
If RD has occurred, visual field defects may be noted by the patient as a ‘shadow' or ‘curtain', and central vision is reduced if the macula becomes detached. Patients may give a history of high myopia, recent trauma, previous retinal detachment or intraocular surgery. These are all risk factors for RD.
Formally check VA (with distance spectacles if worn), pupils and visual fields. Fundoscopy using a direct ophthalmoscope does not give an adequate view of the peripheral retina to reliably exclude tears. However an optometrist may be able to detect a PVD, retinal tears or RD on dilated slit lamp examination. Consider migraine as a common differential of photopsia.
Primary care management
As it is difficult to distinguish between isolated PVD, retinal tears and RD in a primary care setting, patients with acute flashes or floaters should be referred the same day for ophthalmology review to exclude RD, and do not require initial optometry referral. Reassure patients that more than 90 per cent will not have a retinal tear or RD.
Those with long-standing floaters or occasional flashes may be reviewed by an optometrist or referred for routine ophthalmic review. A documented RD warning must be given such that the patient is advised to seek immediate attention should they experience a sudden change in floaters, flashing lights, shadows in the field of vision or visual loss.
Posterior vitreous detachment management
No active treatment is required for PVD alone. Patients should be advised that floaters usually become less noticeable with time. Very rarely, those with debilitating floaters undergo vitrectomy. If PVD is associated with vitreous haemorrhage (VH), close monitoring to exclude retinal tears is required until the haemorrhage is cleared. If the VH is dense, early vitrectomy may be recommended as in about a third of patients retinal tears capable of causing RD are found hidden behind the haemorrhage.
Acute U-shaped retinal tears require laser or cryotherapy, as prophylaxis against RD and consequent visual loss. Argon laser retinopexy is the treatment of choice to surround the retinal break, thereby creating an adhesive scar between the retina and underlying retinal pigment epithelium – this process takes up to
Cryotherapy may be required for some tears, especially if laser uptake is impaired by cataract or vitreous haemorrhage. A RD warning should be given after treatment as retinopexy may fail or fresh breaks may occur. Round holes in the retina often do not require treatment unless there is subretinal fluid or if the fellow eye has suffered retinal detachment.
Acute RD where the macula is still attached (macula-on) requires surgery as soon as possible (usually within 24 hours), while macula-off RD may be repaired less urgently as central visual loss has already occurred. In 80–90 per cent of cases, a single operation will result in successful reattachment of the retina.
Those with macula-on RD usually retain good vision, although a minority develop scar tissue at the macula (epiretinal membrane) post-operatively, which may reduce VA. The visual outcome following macula-off RD varies widely, but recovery to normal visual acuity and quality is not usually achieved.
Two main surgical methods are employed to repair RD depending on the type of detachment and the state of the vitreous. These are:
• Vitrectomy – in this ‘internal' approach, a vitreous cutter, light source and infusion cannula are inserted at the pars plana to remove the vitreous and relieve traction on the retina. The retina is then flattened and tears or holes are secured using cryotherapy or laser.
A slowly absorbing gas is injected at the end of the operation in order to tamponade the retina flat until the retinal breaks are secure. It is vital that patients are advised not to fly or travel to high altitude on land while gas is present in the eye, as expansion will precipitously raise the intraocular pressure (IOP) and can result in blindness.
Most patients require up to ten days of specific head posturing so the gas bubble floats to support the treated retinal breaks. In complex cases, silicone oil may be required instead of gas. The oil is usually removed three to six months later once the retina is secure.
• ‘Cryo-buckle' surgery – This ‘external' approach relies on suturing a silicone plastic explant (buckle) onto the scleral surface over the site of the retinal break to create an indent. This relieves vitreo-retinal traction and promotes reattachment. The fluid under the retina may be drained and retinal breaks are treated with cryotherapy. Sometimes gas is also injected to help tamponade the
Modern RD surgery is increasingly being performed under local anaesthetic and as day case procedures with low risks of sight-threatening complications.
Post-operatively, patients are treated with topical antibiotic and steroid drops. In the early post-operative course, raised intraocular pressure is common and further medication in the form of drops or oral acetazolamide may be required.
Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus characterised by capillary leakage and occlusion leading to retinal ischaemia. Prevalence increases with duration of diabetes.
DR is the leading cause of blindness among the working age population in developed countries. Visual loss may be due to diabetic maculopathy (damage to central vision by macula oedema or macular ischaemia) or proliferative diabetic retinopathy (new vessel formation causing vitreous haemorrhage or tractional retinal detachment).
Classification oF DR
Clinical grading of diabetic retinopathy and maculopathy aims to reflect the risk of visual loss. The classification system used by ophthalmologists is:
• Non-proliferative DR (NPDR). This is characterised by the absence of new vessel formation. It is classified as mild, moderate or severe on the basis of increasing features of retinal ischaemia: microanuerysms (dots), intraretinal haemorrhages (blots), venous changes (increased calibre, tortuosity or beading), intra-retinal microvascular abnormalities and cotton wool spots (infarcts of retinal nerve fibres). Mild and moderate DR correspond to background DR, whereas severe DR is also known as
• Proliferative DR (PDR) occurs when retinal ischaemia is sufficient to stimulate new vessel formation. Fine, friable vessels may appear at the optic disc (new vessels disc, or NVD) or elsewhere on the surface of the retina (new vessels elsewhere, or NVE).
Bleeding may result in vitreous haemorrhage and fibrovascular contraction can lead to tractional retinal detachment. In advanced PDR, new vessels can grow on the iris (rubeosis iridis) and often results in intractable glaucoma due to fibrovascular closure of the drainage angle in the eye.
• Diabetic maculopathy refers to leakage or ischaemia affecting the central retina and can occur in the absence of peripheral retinopathy. This is usually manifest as either focal or diffuse macular oedema – if within one optic disc diameter of the fovea, it is a threat to vision and referred to as clinically significant macula oedema (CSMO).
Other forms of diabetic maculopathy include ischaemic, tractional (due to vitreous adhesion and contraction at the macula) and mixed maculopathy. Flourescein angiography is used to identify areas of leakage and to exclude ischaemic maculopathy that generally does not benefit from treatment.
systemic factors in Diabetic retinopathy
The benefit of managing systemic risk factors in diabetes extends to retinopathy. Tight control of blood glucose and blood pressure delays onset and reduces risk of progression of DR in both type I and
type II diabetes mellitus (DM).1,2 A target HbA1c of <7 per cent is recommended in those with retinopathy but any reduction is of benefit. Patients should be warned that rapid improvement in glycaemic control may cause transient worsening of DR. The British Hypertension Society currently defines hypertension in DM as >140/90mmHg and recommends a treatment target of <130/80mmHg.
The use of ACE inhibitors or angiotensin receptor antagonists provides additional benefit to retinopathy progression over and above an anti-hypertensive effect. In addition, limited evidence suggests that hyperlipidaemia predisposes to maculopathy with hard exudates (lipid deposits), and that treatment of elevated serum lipids may induce regression of these exudates.
Timely laser photocoagulation is the mainstay therapy for diabetic macular oedema and proliferative retinopathy. Argon laser is usually performed on an outpatient basis, delivered using a slit lamp and a contact lens to stabilise the eye and focus the laser beam.
• Focal or grid laser stabilises vision and reduces the risk of moderate visual loss in CSMO by approximately 50 per cent.3 Gentle laser is applied to areas of leakage to stimulate resorption of fluid. Only a minority will show improvements in vision so early detection and treatment is vital to limit visual loss.
• Pan-retinal photocoagulation (PRP) halves the risk of severe visual loss in proliferative diabetic retinopathy.4 Heavy laser burns are scattered in the peripheral retina to reduce the metabolic requirement of the retina and hence reduce the ischaemic drive for new vessel formation. Multiple sessions are required for complete treatment, which if successful leads to regression of new vessels. PRP may be uncomfortable for the patient (especially with further treatments), night vision will be impaired and loss of peripheral visual field may prevent patients from meeting legal standards for driving.
Surgical intervention is indicated in proliferative diabetic retinopathy for:
• Persistent vitreous haemorrhage for three months or more in type I diabetes mellitus, or four to six months in type II DM. Earlier treatment may be considered in severe disease or for rapid visual rehabilitation.
• Tractional retinal detachment threatening or involving the fovea. Treatment is by vitrectomy to remove the vitreous and any haemorrhage together with careful dissection of proliferative fibrovascular membranes from the retina to relieve traction and completion of pan-retinal laser photocoagulation to stabilise disease activity. An additional indication for vitrectomy is for selected cases of tractional diabetic macular oedema unresponsive to other therapy.
The role of intravitreal steroid injections for treatment of diffuse macula oedema unresponsive to conventional laser is uncertain. Transient benefit for three to eight months has been reported but with the risk of serious complications, including infection, RD and glaucoma, randomised controlled trials are required to formally assess safety and efficacy.
National screening programme for DR
Early detection and treatment of DR is critical to reduce the risk of blindness. One of the aims of the diabetes National Service Framework is to offer screening for diabetic retinopathy to all those at risk by the end of 2007. A national digital photographic screening programme has therefore been introduced for patientswith diabetes aged 12 years or older.
Screening is being performed by a number of organisations including optometrists, hospitals or private screening providers based at hospitals, and mobile units, GP surgeries or in the community. Photos are graded using a simplified classification for DR and results are forwarded to both the patient and GP. Those with photographic evidence of potentially sight-threatening retinopathy or maculopathy (or if photos are upgradeable) will be referred to an ophthalmologist for further assessment and treatment.
For those already under the care of an eye clinic, the ophthalmologist is responsible for screening. Patient information leaflets are available to download from tinyurl.com/onsca
Diabetic retinopathy in pregnancy
A small number of women with diabetes will develop worsening of their retinopathy during pregnancy and remain at risk for up to a year post-partum. Preconception screening to assess baseline DR is important and minimum review in each trimester (12 weeks, 20–24 weeks and 30–34 weeks) and three to nine months post-natally. More frequent review is required in severe retinopathy, maculopathy or poor diabetic control.
Age-related macular degeneration
Age-related macular degeneration (AMD) is a major cause of visual impairment in the elderly with an estimated 20 per cent of those aged over 75-years-old in developed countries having visually significant disease.
Early AMD is usually asymptomatic or causes mild visual impairment. Also known as age-related maculopathy (ARM), it is characterised by abnormalities of the retinal pigment epithelium (RPE) and pale yellow deposits (drusen) between the RPE and choroid layers.
Late AMD includes so-called ‘dry' and ‘wet' varieties.
• Dry AMD is characterised by atrophy of the RPE and overlying retina. It typically causes a gradual loss of central vision, but may be asymptomatic if the fovea is spared.
• Wet AMD is less common than dry AMD and is defined by the development of new vessels beneath the retina (choroidal neovascular membranes or CNVM). These leak and bleed, which is why it is described as wet AMD. Eventually this results in scarring at the macula. Patients experience rapid loss of central vision and distortion (metamorphopsia). Two major forms of CNVM can be identified on fluorescein angiography – ‘classic' lesions are well defined and easily detected, whereas ‘occult' CNVM are less distinct.
Management of AMD
The loss of central vision from AMD impacts hugely on quality of life, especially with bilateral disease (patients with wet AMD in one eye have about a 50 per cent chance of the fellow eye becoming affected within five years). Management for most is supportive, including provision of
low-vision aids to allow individuals make the best use of the vision they have.
Current treatments for AMD are largely directed at minimising visual loss in wet AMD due to CNVM, and new and evolving therapies are likely to improve visual prognosis in this disease.
• Conventional argon laser. Ablation of CNVM with thermal laser is indicated for wet AMD where lesions are >100mmetres away from the fovea. Although the risk of severe visual loss is significantly reduced (especially for classic lesions >200mmetres from the fovea), the recurrence rate is 50 per cent with this treatment.
• Photodynamic therapy (PDT).
Sub-foveal CNVM may be selectively targeted (without further damaging the overlying retina) using a non-thermal diode laser (689nm) following intravenous administration of a photo-activated drug (verteporfin). Current NICE guidelines fund PDT for the treatment of subfoveal 100 per cent classic CNVM with vision of 6/60 or better.
Funding is also provided for treatment of predominantly classic (>50 per cent) lesions if part of a trial. Retreatment is often required, but the risk of moderate vision loss at two years in these subgroups is reduced from 69 per cent to 41 per cent. PDT may also be of some benefit for lesions composed of occult or minimally classic CNVM but the NHS does not currently fund these indications.
• Intravitreal VEGF inhibitors. A number of inhibitors of vascular endothelial growth factor (VEGF) administered as regular intravitreal injections have shown efficacy for the treatment of all angiographic types of CNVM in wet AMD.
Pegaptanib results in 70 per cent of patients losing fewer than 15 letters of visual acuity compared to 55 per cent in controls (all lesion types, NNT 6.7). Ranibizumab is an anti-VEGF antibody fragment that not only minimises visual loss but is the first treatment to potentially improve vision in patients with wet AMD. Similar results are being reported using the parent monoclonal antibody bevacizumab, which was initially developed for use in metastatic colon cancer. Serial intravitreal injections every four to six weeks is however associated with small but significant risks including endophthalmitis, retinal detachment
• Macular translocation as a treatment for wet AMD only is available in the UK on an investigational basis at present. The surgery involves repositioning the macula such that the fovea comes to lie on healthy RPE and choroid away from the visually destructive CNVM. While up to two-thirds of patients may experience visual improvement, significant complications such as RD may lead to visual loss.
• In patients with late AMD in one eye, antioxidant supplements (containing 500mg vitamin C, 400 IU vitamin E, 15mg beta-carotene, 80mg zinc, and 2mg of copper) have been shown to have some protective effect on the fellow eye tinyurl.com/fp2up .
Be aware that beta-carotene is contraindicated in smokers but preparations without beta-carotene are available. The benefit of antioxidants in patients with bilateral early AMD/drusen is less certain, as is the increase in macular pigment density with high dietary intake of lutein and zeaxanthin.
Primary care management
Patients with rapid onset of blurred or distorted vision require same-day referral for ophthalmology review to exclude treatable wet AMD or other acute pathology. Those with dry AMD tend not to describe acute visual loss and may be referred less urgently – initial review by an optometrist may be useful in these circumstances.
Smokers are at higher risk of developing AMD than non-smokers or ex-smokers, so ongoing advice and encouragement to give up smoking is important. Awareness of the increased risk of depression, anxiety and falls is important in patients with visual loss. Knowledge that AMD does not damage peripheral vision is reassuring to many who fear total blindness. Useful advice and information on counselling for patients can be obtained from the Macular Disease Society.
1 The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of
long-term complications in insulin-dependent diabetes mellitus. New Engl J Med 1993;32(14):977–86
2 Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352(9131):837–53
3 Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol 1985;103(12):1796–806
4 Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology 1981;88(7):583–600
1 The Retinopathy Screening Programme operates a support service for those involved in the planning, setting up and running of systematic retinopathy screening programmes nscretinopathy.org.uk
2 Diabetes UK is the largest organisation in the UK working for people with diabetes, funding research, campaigning and helping people live with the condition
3 The Macular Disease Society aims to build confidence for those with central vision impairment, as well as provide information and practical support for visually impaired people, their families, carers and health professionals maculardisease.org