Author: Ameen Marashi, MD
Documentation of age as patients with Stargardt disease presented as early as five and later than 60 years old along with visual loss, including the duration and location as patients may be presented with central visual loss and scotoma.
Patients may suffer from dyschromatopsia (red-green); nevertheless, the documentation of visual field defects and slow dark adaptation is essential.
Social history, such as smoking, should be obtained along with investigating medication and family history to document the relatives that are suffering from Stargardt disease.
Most of the cases of Stargardt disease are autosomal recessive with gene ABCA4 genotype which can be presented in different severity which can range from Stargardt disease (in 95% of cases) to cone-rod dystrophy (in 30% of cases) and maybe presented with retinitis pigmentosa in severe cases (in 8% of cases) .
A list of ocular examination should set
1) Best-corrected visual acuity (BCVA) for near and far is an essential step that can be performed by a trained optometrist or certified ophthalmologist to document the visual impairment, which can be as good as 20/20 to 20/400.
2) A slit-lamp examination done with a thorough exam of clarity and regularity of the cornea and to rule out any conjunctival abnormality, along with an iris exam with a crystalline lens exam to rule out cataract or intraocular lens (IOL) to document the position and clarity of the posterior capsule.
3) Intra Ocular Pressure (IOP) documentation; in cases of increased IOP, then gonioscopy is necessary, Note when high IOP spotted a corrected IOP documented after central corneal thickness measurement.
4) Bilateral dilated fundus exam is essential as Stargardt disease is bilateral disease and most likely symmetrical; however, fundus exam should include a detailed examination of the optic disc, macula, posterior pole, a mid-peripheral and peripheral retinal exam with specialized indirect wide-field lenses using slit-lamp biomicroscopy or indirect ophthalmoscopy to document the following:
Usually, pisciform flecks have a yellow or dirty white color with or without pigmentation and presented at the macula, which has an oval shape that contacts each other creating net-like, which can be within two discs areas from the center of the macula or spread up to the equator. However, the closer the flecks to the fovea, the smaller in size.
Some cases of Stargardt disease are not presented with flecks, while others presented with small flecks mixed featuring subretinal fibrosis.
The flavimaculatus variant has numerous flecks and may be presented with small fibrotic nodules and usually presented with good visual acuity.
The vermillion variant may appear with crystal flecks overlying RPE atrophy with obscuring the underlying choroid.
RPE atrophy can be seen in some cases with edges of atrophy resembling the beaten metal or sometimes bull’s-eye; however, the RPE atrophy is not limited to the macula and can be in the periphery simulating choroideremia.
It is an essential tool to document the presence of Stargardt disease in young patients who are not cooperative for clinical examination and can be very helpful in documenting the progression and type of Stargardt disease along with different pathological macular changes such as subretinal fibrosis, and atrophy.
Optical Coherence Tomography (OCT)
OCT cross-sections show disruption and loss of the ellipsoid zone with or without RPE atrophy, but OCT can show the flecks level .
Fundus Fluorescein Angiography (FFA)
FFA shows a silent choroid, which is blocking the underlying choroid (up to 62 % of cases) due to lipofuscin accumulation in the RPE layer.  However, silent choroid is not always presented in FFA, and sometimes the FFA photos captured by the digital camera can produce a contrast artifact between the choroidal and retinal circulation that simulates the dark choroid. Therefore, genetic workup may be more accurate to diagnose Stargardt disease than FFA.
Along with silent choroid, the area of flecks may appear hypofluorescence in early phases while hyperfluorescence due to staining in late phases.  A window defects may be noticed due to RPE atrophy at the center of the macula in cases presented with old flecks, which have a sharp contrast to the adjacent silent choroid. However, retinal vessels will show sharp contrast with silent choroid as well.
Note that the physician should obtain signed consent explaining the rare complications of FFA, including death 1/200000, and FFA facility should have an emergency plan in situ.
Fundus Autofluorescence (FAF)
FAF is a useful noninvasive tool to diagnose patients with Stargardt disease even in very early stages as the accumulation of lipofuscin will show increased FAF. In contrast, areas showing decreased FAF are usually areas of RPE atrophy as decreased FAF means a low metabolic activity of RPE. Therefore, FAF with OCT is very important to diagnose and stage Stargardt disease.
ERG can be normal or subnormal, but ERG is very handy to predict the type of Stargardt disease as for patients presented with early peripheral photoreceptor loss that means that patient is at risk for more visual loss in the future. In cases presented with more moderate ABCA4 mutation ERG will show selective cone abnormalities, while for severe ABCA4 mutation, ERG will simulate findings in retinitis pigmentosa .
Managing patients with Stargardt disease
There is no approved treatment for Stargardt disease; patients should be advised to wear sunglasses in bright light exposure and to use low vision aid to improve quality of life. Patients are advised to quit smoking as it may dim vision while smoking and avoid vitamin A supplements intake as it increases the bisretinoid in the retina, i.e., it would increase the accumulation of lipofuscin.
Follow up and prognosis
-Flecks tend to be stable, but some may increase in size and number and develop RPE atrophy, which may get pigmented with time.
-Numerous flecks located non-central to the macula have a more long term poor prognosis to minimal flecks located centrally.
-As the patient gets older, the vision gets worse  as for patients are 19 years old at least one eye has the vision 20/40 for 53% of cases and in age 29 only 32% where only 22% in age 39  in general 25% of patients will have vision around 20/40 where only 4% will have vision less than 20/400 .
-Patients should understand that in ABCA4 severe mutation that Stargardt disease can progress to retinitis pigmentosa during the natural course of the disease.
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These guidelines were reviewed and updated in September 2020