While modern medicine has developed treatments for wet AMD, such as intravitreal injections of Lucentis or Avastin, one of the greatest challenges surrounding the disease remains accurate diagnosis, as wet AMD has several variants as well as many conditions that mimic the ailment. In the final of our three part series on macular degeneration, we look at diagnosis and treatment.
On top of issues around variants and other closely disguised ailments, some patients rebound off treatment, others respond poorly or not at all, and then there are those who develop new haemorrhage or exudation on treatment.
Differential diagnosis of wet AMD is the key to a good treatment outcome. History taking and clinical assessment are paramount. In particular it is crucial to examine the fundus with appropriate technology. In the first instance, the peripheral retina should be examined with a binocular indirect ophthalmoscope to exclude peripheral inflammatory pathology, tumours and other lesions.
At the slit lamp, a 60 dioptre non-contact lens should be used to provide a stereoscopic view of the macula. Many doctors find that digital photos done through a dilated pupil allow the luxury of extended appreciation of fine detail, particularly with red-free images. Of course, other modalities such as fluorescein angiography and OCT imaging are mandatory.
Differential diagnosis of wet AMD is the key to a good treatment outcome. History taking and clinical assessment are paramount
It is important to examine features such as size, type and distribution of haemorrhage as this will frequently point to the diagnosis. The presence of exudate, oedema, subretinal fluid, and mass lesions all indicate various pathologies.
Wet AMD Mimics
The main differential diagnoses include retinal vein occlusions, central serous retinopathy, choroidal haemangioma, macular telangiectasia, macular hole, inflammatory cystoid macular oedema, diabetic macular oedema, retinal artery macroaneurysm, and Best’s macular dystrophy. Branch and central retinal vein occlusions are common and are often mistaken for wet AMD, particularly if features of dry AMD co-exist in the same eye. Paramacular branch retinal vein occlusions may just produce small patchy haemorrhages near the macula causing confusion. Close inspection usually reveals that the haemorrhages respect the horizontal and are related to a single small vein, which may be compressed by an artery.
Larger vein occlusions have a sectorial distribution of haemorrhage but may have impressive bleeding into the macula itself with associated cystoid oedema. Typically, one will see a defined site of venous compression or some other features such as cotton wool spots. In long established venous occlusion, many of the signs disappear.
Shunt Vessels
One thing to look out for is the presence of shunt vessels. These are dilated veins that allow blood to bypass the occlusion. They are seen as tortuous vessels crossing the temporal raphe, or wriggling around the actual occlusion. Shunt vessels are also seen on the optic disc in central retinal vein occlusion. Fortunately, the treatment for vein occlusion is increasingly involving the use of anti-VEGF drugs and the visual prognosis for many patients with these conditions is improving.
Central Serous Retinopathy
Central serous retinopathy (CSR) is usually seen in young healthy adults and there may be a stress association. Other signs of AMD such as drusen will be absent. The retina is detached by clear fluid in the macula. A faint focal pigment change may be seen at the site of the ‘leak’. Chronic forms with a lot of pigmentary change may start to look like AMD.
Rarely, choroidal neovascularisation (CNVM) can complicate CSR causing haemorrhage to appear, making things confusing. The common form of CSR frequently requires no active management as it is self-limiting. Occasionally focal laser can be used for non-resolving cases, and Visudyne photodynamic therapy will help with chronic forms. If CNVM occurs, treat with Avastin.
Choroidal Haemangioma
Choroidal haemangioma is an uncommon problem and presents as an orange-red mass in the choroid with overlying retinal oedema and serous detachment. It may be under the macula or to one side. Angiography and OCT scanning will usually clinch the diagnosis. Treatment is with Visudyne photodynamic therapy.
Macular Hole
It’s not uncommon for idiopathic macular hole to cause diagnostic problems. The grey ring of oedematous retina around a central reddish spot of bare pigment epithelium may look a lot like CNVM. Scanning with OCT sorts this out very quickly. Macular hole repair is done by vitrectomy with peeling of the internal limiting membrane and injection of long lasting gas.
Macular Telangiectasia
Macular telangiectasia is marked by the presence of abnormal telangiectatic vessels associated with oedema and exudation. The hallmark sign is L-shaped retinal vessels nearby. There is no treatment deemed universally successful but one may try Avastin.
Macular Oedema
Macular oedema can obviously be found as an end stage to many processes, especially diabetic retinopathy. The diagnosis is usually easily made by the presence of microaneurysms and a history of the disease. Rarely, CNVM can develop in diabetes if previous laser treatment has been applied enthusiastically.
Diabetic macular oedema continues to provide treatment challenges with multi-modality therapy required. Retinal artery macroaneurysm can produce spectacular macular haemorrhage and the causative lesion may even be obscured, making diagnosis difficult. Again, fluorescein angiography is helpful in this situation.
Retinal artery occlusions can precipitate sudden visual loss but their signs are usually relatively specific, with oedematous, infarcted nerve fibre layer and a complete or partial cherry red spot. There is no good treatment for this sort of problem.
For many reasons, CNVM can also occur in patients without AMD. Highly myopic individuals develop CNVM in lacquer cracks, patients with pseudoxanthoma elasticum get new vessels in angioid streaks, and the various posterior uveitis syndromes can all cause neovascularisation. If you have a patient who is not responding to standard anti-VEGF therapy, check the diagnosis rigorously.
Wet AMD Variants
A variant of wet AMD is known as retinal angiomatous proliferation (RAP). It is a subset of CNVM typified by retinal capillary proliferation with telangiectasia. It is seen initially as small intraretinal neovascular membranes and small haemorrhages, followed by retinal oedema and then pigment epithelial detachments. It is more common in elderly female Caucasians. Patients with RAP lesions may require more aggressive therapy with anti-VEGF drugs and one may even need to consider alternating Lucentis with Avastin on a relatively tight timetable.
Another variant which frequently gives problems is the condition known as polypoidal choroidal vasculopathy (PCV). This is the presence of multiple, recurrent, haemorrhagic detachments of the retinal pigment epithelium and retina caused by unusual polypoid choroidal vascular abnormalities. It is seen most commonly in pigmented races with peak incidence in females aged between 50 and 65. The aetiology is not well understood. To make this diagnosis, an imaging technique known as indocyanine green angiography is required to accurately visualise the choroidal circulation. The condition may respond better to Visudyne photodynamic therapy but combining this with Lucentis can give a better outcome in some cases.
Regular Treatment Important
As we know from the major studies, monthly treatment with Lucentis is the gold standard for treatment of wet AMD. However, this is a difficult requirement to meet and it is common to try to reduce treatment frequency. It is now clear that treatment intervals greater than two to three months will often result in rebound phenomena, in which acuity drops and wet AMD signs return. If this occurs during management then repeat induction with monthly injections is usually needed to regain lost ground.
Haemorrhage Risks
New haemorrhage during treatment for wet AMD is not uncommon and causes consternation. It may be that treatment intervals have been overextended but equally there may be other issues. One particular problem is the occurrence of retinal pigment epithelial rips or tears. Typically, a dome-shaped pigment epithelial detachment (PED) is under some tension and the sheet of detached RPE may tear along a margin of the PED. This can occur spontaneously in untreated patients but may also complicate any form of therapy such as laser, PDT, or anti-VEGF injections. The rip may also traumatise vessels in the CNVM causing varying degrees of macular haemorrhage. The rip is seen as a ‘scroll’ of RPE pulled back from now bared choroidal vessels. If the rip occurs outside the macula, then symptoms may not be great unless haemorrhage is prominent. If the rip affects the fovea, then catastrophic visual loss follows. Opinion is still divided on whether to continue treatment following the occurrence of a rip. However, most specialists are now choosing to resume anti-VEGF therapy.
Massive subretinal haemorrhage can occur without a rip or following Valsalva manoeuvre. Predominantly subretinal haemorrhage affecting the macula can sometimes be displaced by intravitreal injections of clot-lysing agents such as tissue plasminogen activator with gas bubbles to massage the blood away from the fovea.
Treating Vitrectomised Eyes
Finally, eyes that have had previous vitrectomy surgery have ‘lost’ the reservoir for drugs that the vitreous gel normally provides. Any drug injected into a vitrectomised eye will have a greatly and unpredictably reduced half-life. Patients in this situation will require closer monitoring and possibly reduced intervals between treatments.
Further information on AMD is available from the Macular Degeneration Foundation on (AUS) 1800 111 709 or www.mdfoundation.com.au. Alternatively, contact Vision Australia: (AUS) 1300 847 466 or www.visionaustralia.org.au.
Dr. David McKay trained at the Sydney Eye Hospital before graduating with the Fellowship of the Royal Australian College of Ophthalmologists in 1988.
He undertook further training in surgery and diseases of the retina at the Lions’ Eye Institute in Perth, WA before working in the U.S.A. in ocular oncology with Professor Jerry Shields. Dr. McKay returned to Sydney in 1991. He is in private practice in Sydney and in Bathurst and Orange, in central western New South Wales.
