Author: Ameen Marashi, MD
Documentation of age as patients with best macular dystrophy (BVMD) presented between 3 and 15 to 60 years old along with visual loss, including the duration and status; however, when the patient complains from recent visual loss, then a history of ocular or head trauma should be ruled out as well.
It is crucial to investigate family history to document the relatives that are suffering from BMD as most of the cases of BVMD are autosomal dominant with a genetic mutation of the BEST1 gene with incomplete penetrance and different variable expressivity.
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, BVMD patients usually presented with hypermetropia [1].
2) A slit-lamp examination done with a thorough exam of clarity and regularity of the cornea and to rule out any conjunctival abnormality such injection of conjunctival vessels should be documented, and any other inflammations of the conjunctiva or eyelids documented, along with iris exam and to rule out narrow-angle along with 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 is essential as high IOP may be associated in severe cases of BMD patients due to angle-closure glaucoma. [2] 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 BVMD 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:
In stage one, there would be only subtle macular changes at the level of RPE in the form of a small honeycomb structure.
In stage two, a central egg yolk like lesion, which can be elevated with a round or horizontally oval shape with different sizes from a few hundred micrometers to millimeters.
In stage three, the yellow material gravitates inferiorly in the subretinal space forming pseudohypopyon.
In stage four is when the yellow material broke down, forming scrambled-egg like appearance which features subretinal and sub RPE fibrosis with or without hyperpigmentation and RPE atrophy
In stage five is when there are RPE and retinal atrophy
In stage six is when there is choroidal neovascularization
Usually, BVMD is a central solitary lesion, but sometimes fundus appear as multiple lesions and can be located beyond the temporal arcades.
Some cases presented with foveal sub-RPE central fibrosis in the form of a nodule.
The fundus exam should document the presence of subretinal hemorrhages.
It is an essential tool to document the presence of BVMD in young patients who are not cooperative for clinical examination and can be very helpful in documenting the progression and staging of BVMD along with different pathological macular changes such as subretinal hemorrhage, fibrosis, and atrophy.
OCT cross-sections show homogenous subretinal material with thickened cone outer segments in egg yolk like lesions. [4] However, in pseudohypopyon lesion, there would be hyporeflective subretinal fluid adjacent to hyperreflective subretinal mass presenting the vitelliform material. In a scrambled-egg like lesion, there would be a mix of hypo and hyperreflective lesions with disruption of the ellipsoid zone or/and interdigitation zone. [5] In advanced stages will show RPE atrophy and subretinal and sub-RPE fibrosis, as the retina may appear thin. However, in cases of BVMD complicated with choroidal neovascularization, there would be subretinal amorphous mass with subretinal fluids and disruption of the ellipsoid zone with macular edema [6].
In cases, there is central nodular fibrosis; there would be a pillar projected from sub RPE space toward the subretinal space in the form of hyperreflective cone adjacent to subretinal fluids, which some suggest it as originated from choroidal neovascularization.
OCTa can clearly show the presence of choroidal neovascularization, which is more prominent in the outer retina slab than choriocapillaris slab; however, OCTa is essential for cases suspected to be complicated with choroidal neovascularization were not clearly shown by FFA and OCT.
FFA may show in early stages, and young patients a blocked fluorescence due to the hydrophobic nature of the vitelliform lesion. Still, as the patient ages and vitelliform lesion progresses, it will become hydrophilic and become hyperfluorescent, and stain in late phases, which would look like pigment epithelial detachment. In pseudohypopyon stage, the area of subretinal fluid and vitelliform lesion would show hyperfluorescence on FFA while the area yellow pigment would show hypofluorescence. However, the FFA is very useful to rule out the presence of subretinal choroidal neovascularization as it shows delineated hyperfluorescence in early stages, which will have a fuzzy border at the late stages. In advanced atrophic cases, the FFA will show RPE atrophy in the form of window defect [6].
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.
FAF is crucial to diagnose BEST disease and differentiate it from other CSCR and ARMD.
FAF exhibits a different pattern in different BEST disease stages in the vitelliform stage; Best disease will appear as uniformly increased autofluorescence. However, in cases of pseudohypopyon stage, the FAF will show increased autofluorescence at the lesion's inferior segment, while scrambled egg stage, the increased autofluorescence will appear at the border of the lesion with decreased autofluorescence at the center. In contrast, the atrophic stage will appear as decreased autofluorescence [11].
EOG may look abnormal even if there are no retinal findings or in stage one; however, EOG shows in BVMD the light peak to dark trough less than 1.5 in Adren ratio, while ERG will appear normal in BVMD.
- Patients complicated with choroidal neovascularization are treated with monthly intravitreal VEGF blockade agents [7] until stabilization of vision and resolving subretinal hemorrhage achieved. As sub-retinal fluid may not always resolve completely, especially in cases that have nodular fibrotic pillars.
-Patients having subretinal blood due to ocular or head trauma can be followed up as subretinal hemorrhage may resolve spontaneously with the acceptable visual outcome. Therefore, protective eyeglasses should be worn in case the patient is playing sport or at risk of modest head or eye trauma [8].
-In cases presented with angle-closure glaucoma, a YAG laser iridotomy is indicated.
-Vision in BVMD can be preserved for the sixth decade in which the subretinal vitelliform lesion may flatten with time, but the visual loss can occur in patients complicated with subretinal fibrosis or choroidal neovascularization. However, it would have a better prognosis from the sub-retinal scar formed with age-related macular degeneration [9].
- Visual acuity changes from 20/20 to 20/60 in the second and third stages, wherein the fourth stage, the vision may drop to 20/120. However, patients with BVMD may have at least vision 20/40 in 77% of cases, and 19% of cases will lose two lines of vision within 8 to 10 years due to subretinal scar formation or atrophic changes [10].
-When BVMD is presented with poor vision in one eye, the other eye usually has a better visual prognosis, though it is essential to advise the patient to wear protective eyeglasses.
-The patient should report any visual acuity changes such as metamorphopsia, and this can be done by the patient to perform the Amsler test regularly.
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These guidelines were reviewed and updated in January 2021