Background

The macula is the central region of the retina situated at the posterior pole of the eye, between the superior and inferior temporal arteries, 3 mm lateral (temporal) to the optic disc. It is 5.5 mm in diameter and contains within it the 1.5 mm diameter fovea and, within that, the foveola, a 0.35 mm area that houses the highest concentration of cone photoreceptors in the retina (to the exclusion of rods) and is concerned with enabling maximal, central visual acuity. There are no vessels overlying the foveola which is entirely supplied by the underlying capillaries of the choroid.

Evaluation of the macula^[1]

Symptoms associated with macular dysfunction

• Impairment of central vision is the main symptom associated with macular disease. This may be characterised as something appearing to obstruct the central vision or a blurred patch (eg the words in the middle of a sentence).
• Metamorphopsia: this common symptom describes a distortion of images - notably of straight lines ('if you look at the window, do all the sides of the frame look straight?')
• Distortion of image size may occasionally occur. They may appear bigger (macropsia) or smaller (micropsia). This may in turn give rise to diplopia, as there is a discrepancy between the image perceived in the healthy eye and in the diseased eye.

Assessment of macular function

• Visual acuity - the most important test is the assessment of visual acuity. Note the distant acuity using a Snellen chart, making sure that you have identified any past history of previous visual acuity problem (eg amblyopia) - 'Is this about normal for you?'. If you have access to a near vision booklet, assess the near vision too. Ask the patient to hold the booklet at about 30 cm (about an arm's length) and, using their usual reading glasses, read the short passages, one eye at a time.
• Amsler grid - there are several forms of Amsler grids but the most common one is a 10 cm by 10 cm grid printed on a plain white paper. It is evenly divided into 0.5 cm by 0.5 cm squares and has a small black dot at its centre. The steps to using it are:
  • Ask the patient to cover one eye and hold the grid about 30 cm away from them, preferably resting on a surface so that they can draw on the paper.
  • 'What is at the centre of the paper?' Failure to see the dot suggests a central scotoma.
  • (If there is no central scotoma): 'I want you to focus on the central dot and tell me whether you can see all four corners of the big box out of the corner of your eye'.
  • 'Still focusing on the central dot: 'Are any of the small boxes missing? Where? Can you shade out the area where they are missing?'
  • 'Finally, whilst still focusing on the central dot: 'Do any of the lines appear distorted? Where? Can you draw over those lines that are not straight?'
  • Rest and then test the fellow eye.
  Abnormalities of any of the answers suggests macular pathology. Patients can use the grid at home and test themselves (remind them to do one eye at a time).

Examination of the macula

• Ophthalmoscopy - the macula is seen as a dark circular patch between the vascular arches, the fovea being about 1 disc diameter lateral to the disc itself. The foveola is usually seen as a bright pinpoint yellow reflex at the centre of the macula. The macula is right in front of your line of vision if you ask the patient to look directly at the light. However, this may be uncomfortable and it is best left until the end of the fundoscopic examination.
• Slit-lamp biomicroscopy - this will be carried out in the ophthalmology clinic; it provides a good view of the macula and the underlying retinal pigment epithelium.
• Fluorescein angiography - this involves the observation of the passage of fluorescein dye through the retinal and choroidal circulation. Fluorescein is injected peripherally and, a few seconds later, a series of photographs is taken of the fundus through dilated pupils. Both eyes are photographed for comparison - the affected eye first. It enables the identification of abnormal blood vessels, loss of blood vessels, blockages and leaks. Most patients experience a temporary discolouration of the skin (yellow tinge) and urine (orange tinge) and some may experience nausea and vomiting. Uncommon but more serious adverse effects include allergy and anaphylaxis (and therefore these patients are asked to wait in clinic for some time after the angiography to monitor for this).
• Indocyanine green angiography - this is based on a similar principle to fluorescein angiography but enables a better visualisation of the choroidal circulation. It may be performed simultaneously with fluorescein angiography. Adverse effects are less common and include sneezing, pruritus, nausea and vomiting. Syncope, backache and local skin necrosis may occasionally occur. It is contra-indicated in patients with an iodine allergy or in those who are pregnant.
• Optical coherence tomography (OCT)^[2] - this provides a cross section view of the retina, including the macula. It gives information on various retinal layers and generates a 3-D image of the macula and optic disc. It is invaluable in assisting the diagnosis of macular (and glaucomatous) pathology and is increasingly available in most eye departments. It is a quick, easy and painless measurement.

Macular disorders^[1][3]

A range of problems can affect the macula. The most common of these in this country can be seen in the separate article Age-related Macular Degeneration. Other macular problems with separate articles include Macular Oedema, Macular Holes and Forster-Fuchs' Retinal Spot (myopic maculopathy).

Outlined below is a summary of some of the other problems affecting the macula.

Central serous chorioretinopathy (CSCR)

• Description^[4] - also known as central serous retinopathy (CSR), this condition is characterised by fluid leakage at the level of the retinal pigment epithelium (which lies just beneath the photoreceptors) in the macular area. It is usually idiopathic but may be associated with systemic hypertension, systemic and inhaled steroids and with pregnancy. There is a 5% prevalence in Cushing's syndrome.^[2] There are also interesting psychological associations typically described: patients are more likely to have type A personalities, conversional neuroses and be using psychopharmacological medications. Stress or a disturbing psychological event precedes the onset of CSCR in about 90% of patients. However, more recently, there has been some debate over these apparent psychological links.^[5]
• Presentation^[3] - the patient (typically aged between 20 and 45, and eight times more likely to be male) complains of acute blurring of the vision which may range from a mild central disturbance to a severe drop (eg 6/60). Colours may appear washed out and there can be a central scotoma. It is usually unilateral. Metamorphopsia and image size distortion are also common. Examination reveals a decrease in visual acuity and, very occasionally, a relative afferent pupillary defect (RAPD - although presence of this prompts the thought of optic neuritis). Examination of the fundus reveals a well demarcated, localised serous detachment of the neurosensory retina from the retinal pigment epithelium in the macular region.
• Management - usually, reassurance and conservative management. Some patients with non-resolving CSCR require laser treatment after 4-6 months. Photodynamic therapy is also emerging as a possible treatment option in certain patients.^[2]
• Outcome^[1] - this tends to be excellent with spontaneous and full recovery usually occurring between 1 and 6 months. 85% of acute cases retain 6/6 vision but 30-50% of cases recur.^[6] Occasionally, the course is prolonged (6-12 months) and in about 5% of cases, it becomes chronic (>12 months). Only the latter is associated with permanent impairment of visual ability and, in these patients, the history has often been atypical and there may be bilateral pathology.

Macular epiretinal membrane

• Description - this is the phenomenon where neural support cells grow over the macula to form a membrane (epiretinal gliosis). This may be idiopathic or occur secondary to retinal surgical procedures, retinal vascular disease, intraocular inflammation or trauma. The membrane may be thin (cellophane maculopathy) or thickened and contracted (macular pucker).
• Presentation - these middle-aged to elderly patients may be asymptomatic or present with a decrease in visual acuity (mild in cellophane maculopathy, eg 6/9, more in macular pucker, eg 6/12 or worse). Examination reveals a glistening membrane over the macula ± retinal wrinkles radiating out from the macula.
• Management - cellophane maculopathy does not need treatment but macular pucker may benefit from surgery involving peeling off the membrane.^[2] Any underlying problem will also be addressed.
• Outcome - visual acuity may not necessarily be improved but any image distortion may be helped by surgery. Poor prognostic features include long duration on symptoms prior to surgery, underlying macular co-pathology and low preoperative visual acuity.^[2]

Choroidal folds

• Description - these arise as a consequence of choroidal congestion, scleral folding or contraction of one of the neuroretinal membranes. The condition is usually idiopathic but can also arise due to orbital disease (eg thyroid eye disease), choroidal tumours (eg melanomas), ocular hypotony (eg following certain kinds of surgery) and a number of other reasons.
• Presentation - patients will predominantly complain of metamorphopsia but ,depending on the underlying cause and the extent of the folds, they may also complain of a decreased visual acuity. Parallel grooves (like wrinkled clingfilm) can be seen stretching across the retina.
• Management - this depends on the underlying cause.
• Outcome - this depends on the underlying cause.

Best's disease (vitelliform macular dystrophy)

• Description - this belongs to a group of hereditary fundus dystrophies known as the 'inherited pattern dystrophies'. This rare condition is inherited in an autosomal dominant pattern.
• Presentation - asymptomatic or decreased vision - this may be in childhood, early adulthood or it may not be detected until later on in life when there is another reason to carry out a fundal examination. It is characterised by well-defined, round yellow lesions which are often compared to an egg yolk (followed by a scrambled egg appearance, then atrophy).^[6] It is a bilateral condition.
• Management - there is no effective treatment but laser is sometimes used to address complications such as neovascular membrane formation.
• Outcome - this depends on the type but ranges from excellent (adult vitelliform macular dystrophy) to poor (juvenile Best's disease: there is progressive macular scarring from the fifth decade of life which can eventually lead to legal blindness).

Other macular dystrophies^[2]

There are a number of other recognised macular dystrophies in addition to Best's disease. Generally, they tend to cause loss of photoreceptors with accumulation of debris around the retinal pigment epithelium. There is currently no effective treatment for these diseases and the emphasis will be on diagnosis and appropriate counselling with supportive care as required. Conditions that fall into this category include:

• Stargardt's disease/fundus flavimaculatus (two clinical presentations of the same disease)
• Adult vitelliform degeneration
• Familial drusen
• Dominant cystoid macular oedema
• Cone degenerations

Additionally, there are a number of other very rare conditions.

Idiopathic polypoidal choroidal vasculopathy

• Description - this condition is characterised by an abnormality of the choroidal vessels which predisposes them to bleeding (giving rise to the term posterior uveal bleeding syndrome), particularly around the macular region.
• Presentation - the patient (more often non-Caucasian) presents with sudden, painless, unilateral visual impairment. Retinal pigment epithelial or full thickness retinal detachments may be observed on examination ± vitreous haemorrhage.
• Management - some patients benefit from laser treatment.
• Outcome - this is usually good with spontaneous resolution of the haemorrhage.

Maculopathy in optic disc pit

• Description - an optic disc pit is a rare congenital abnormality associated with a visual field defect. Occasionally, the macula becomes involved in this condition: it accumulates subretinal fluid (possibly from the subarachnoid space, possibly from the vitreous) and this may eventually be associated with a retinal pigment epithelial detachment.
• Presentation - these patients present at puberty with a progressive, painless visual impairment. The optic disc pit itself may be asymptomatic and so this may be the first time this diagnosis is made.
• Management - some patients are observed at three-monthly intervals; others benefit from laser treatment. Occasionally, surgery (removal of the vitreous or gas injection) may be advocated.
• Outcome - this depends on the degree of macular involvement and the need for treatment.

Solar maculopathy

• Description - solar radiation can cause photochemical effects in the retina as a result of looking directly or indirectly at the sun.
• Presentation - this is 1-4 hours after exposure; the patient complains of impairment of central vision ± metamorphopsia ± a central scotoma. Examination reveals a variously impaired visual acuity and there may be small unilateral or bilateral yellow spots around the macula. About two weeks later, these are surrounded by mottling.
• Management - observation.
• Outcome - the outcome is usually good with recovery to normal or near-normal visual acuity within six months. Mild symptoms may persist.

Macular conditions arising in association with systemic problems^[1][3]

Angioid streaks^[7]

• Description - these arise as a result of degenerative structural abnormalities in the layers of the neuroretina and manifest themselves as crack-like dehiscences associated with calcium deposition. These structural changes arise as a result of systemic disease in 50% of cases. Such diseases include pseudoxanthoma elasticum, Ehlers-Danlos syndrome, rarely Paget's disease of bone and some haemoglobinopathies (eg sickle cell disease).
• Presentation - initially asymptomatic or slight decrease in vision but, over time, this becomes quite marked. There will be bilateral linear brown lesions on fundoscopy which intercommunicate in a ring-like fashion and, eventually, the optic nerve will be affected too. There are often associated fundal findings.
• Management - initially observation alone may do. However, some patients may benefit from laser photocoagulation and surgery (removal of the neovascular membrane).
• Outcome - ultimately, this is poor, as the streaks creep over the fovea, cause exudative leaks in the macula, and associated haemorrhage. This occurs in over 85% of patients.

Cancer-related maculopathy

• Description - this rare condition tends to occur in patients with small cell lung carcinoma and occasionally other epithelial tumours. It may be the first manifestation of these tumours. It is characterised by an autoimmune photoreceptor destruction but there are no ocular metastases.
• Presentation - gradual onset of dimming of the vision and associated shimmering photopsia (flashes of light). There may be bizarre visual images seen and night blindness. The symptoms are bilateral (but may be asymmetrical) and progressive with little to see on fundus examination.
• Management - there may be a response to systemic steroids.
• Outcome - the prognosis is poor, both visually and systemically.

Drug-induced maculopathies^[2]

A number of maculopathies can manifest themselves as a result of systemic drug intake. The optimal management for these conditions is discontinuation of the medication where possible and observation in the ophthalmology outpatient clinic. Many resolve in time.

• Chloroquine and hydroxychloroquine - these both have the potential for retinotoxicity and may also result in corneal deposits. The retinopathy is related to the total cumulative dose and is more marked with chloroquine. Patients present with decreased vision (which may be severe in end-stage chloroquine maculopathy - less than 6/60 - and characterised by a 'bull's eye' macular lesion: a well defined red centre surrounded by a mottled yellow periphery), abnormal colour vision and difficulty in adjusting to darkness (nyctalopia). There may also be a scotoma. The Royal College of Ophthalmologists recommends that:^[8]
  • Visual acuity be recorded prior to starting these drugs.
  • For hydroxychloroquine <5 years' duration: if there is any reported visual impairment or eye disease on enquiry pre-treatment, arrange a visit to an optometrist. If there are any visual/eye symptoms during treatment, refer to an ophthalmologist with the view to stopping treatment.
  • For hydroxychloroquine > 5 years' duration or for chloroquine, a regular ophthalmic review is recommended (which should be negotiated between ophthalmologists and rheumatologists).
• Vigabatrin - in around a third of cases, a visual field defect develops which is largely asymptomatic but optic atrophy may occur. The visual field defects are generally static once established - they do not progress but do not resolve on drug withdrawal. The Royal College of Ophthalmologist recommends organising a baseline visual field test which needs to be repeated every six months for the first three years of treatment and then annually thereafter.
• Phenothiazines^[1] - drugs used in the treatment of schizophrenia can cause pigmentary changes affecting the macula, characterised by brown clumping of pigment ± loss off retinal pigment epithelium. Patients on these medications may be asymptomatic or present with blurred vision, browning of the vision or difficulty in seeing at night. Current prescribing practice should not lead to retinopathy.
• Toxic crystalline maculopathy - tamoxifen, canthaxanthin and methoxyflurane occasionally cause toxic retinopathy when taken in higher doses. They tend to manifest themselves as a decrease in visual acuity and are seen as tiny, glistening deposits arranged in a ring around the macula. This may lead to a mild drop in visual acuity but current prescribing practices rarely lead to retinopathy.
• Defereoxamine - this may lead to a decrease in visual acuity associated with nyctalopia. It can occur at any dosage level (there has been a report of it occurring after a single dose).
• Anti-microbials - didanosine (used in the treatment of HIV) can cause retinopathy in children, and clofazimine (anti-mycobacterial) can cause an extensive bull's-eye maculopathy with pigment deposit and atrophy.
• Cocaine^[9] - ocular complications of topical (intranasal) cocaine abuse are rare but have been described. This is characterised by impaired colour vision on substance withdrawal.

Valsalva maculopathy

• Description - intraocular bleeding can occasionally occur as a result of a sudden, severe increase in intrathoracic or intra-abdominal pressure.
• Presentation - the patient may complain of sudden distortion of central vision in one or both eyes and fundoscopy reveals a small, isolated macular haemorrhage in one or both eyes.
• Management - conservative.
• Outcome - excellent.