Spotlight Case: Two Sparkling Retinas

Bryan M. Roth, MD

Christina Y. Weng, MD, MBA

Case history

Color fundus photographs demonstrate numerous small white-yellow crystalline deposits in the posterior pole extending just beyond the arcades. There is mild posterior pole pigment mottling. The vessels and optic nerve are unremarkable.

A 41-year-old Caucasian female presented with a 1-year history of glare in both eyes, worse at night. She denied any ocular history. Medical history was significant only for conductive hearing loss on the left with associated stapes replacement 3 years ago. She denied any medication use or illicit drug use. She works as a dance professor and denies any toxic exposure.

On examination, her best-corrected visual acuity (BCVA) was 20/20 in both eyes. The intraocular pressure and pupillary examinations were normal. Color vision was tested; she was able to distinguish 2/10 Ishihara plates in the right eye and 1/10 plates in the left eye.

Anterior examination was unremarkable with clear cornea and clear lens OU. Dilated fundus examination demonstrated numerous fine, white-yellow crystalline deposits in the posterior pole extending just beyond the arcades. Optic nerves appeared pink and sharp, and the vessels appeared normal. Optical coherence tomography (OCT) revealed severe ellipsoid zone atrophy with foveal sparing. There were hyperreflective foci scattered throughout all retinal layers (Figure 1). Fundus autofluorescence demonstrated heterogeneous hypoautofluorescence of the posterior pole (Figure 2). ERG performed at an outside institution demonstrated a reduction in amplitudes of both photopic and scotopic responses (images not shown). 

Figure 1. Spectral-domain optical coherence tomography (SD-OCT) revealed severe ellipsoid zone atrophy with foveal sparing. Hyperreflective foci were scattered throughout all retinal layers.

Figure 2. Fundus autofluorescence demonstrated heterogeneous hypoautofluorescence in the posterior pole.

What's your diagnosis?

Bilateral, symmetric crystalline retinopathy in this middle-aged patient led to a differential diagnosis that includes primary ocular disorders, systemic disorders, and drug-induced disorders. Classically, systemic disorders include oxalosis (both primary and secondary due to ethylene glycol poisoning or methoxyflurane anesthesia), infantile cystinosis, hyperornithinemia, and Sjo╠łgren-Larsson syndrome. Drug-induced etiologies include tamoxifen, canthaxanthine (oral tanning agent), and rarely, nitrofurantoin. Embolic particles including calcium, cholesterol, or talc would present intravascularly as opposed to the findings above.

Given the presentation in an otherwise healthy patient (unlikely a systemic disorder) without evidence of relevant drug use, primary ocular disorders such as calcified macular drusen and Bietti’s crystalline dystrophy were highest on the differential. Unlike drusen which are found beneath the retinal pigment epithelium (RPE), the crystals here were deposited throughout all layers of the retina. This, as well as the classic sparkling appearance and corresponding RPE atrophy, point to a diagnosis of Bietti’s crystalline dystrophy (BCR).

Discussion

Bietti’s crystalline dystrophy is a rare chorioretinal degenerative disease characterized by crystal deposition in the retina (as well as the cornea sometimes [1] leading to progressive nyctalopia and vision loss. The disease was first discovered by Italian physician Dr. G.B. Bietti in 1937 [2]. Although patients from a multitude of ethnicities have been described, BCR has been reported to be more common in East Asian populations [3]. Prior studies have demonstrated that the formation of retinal crystals is followed by gradual atrophy of the RPE [4]. BCR can be misdiagnosed as retinitis pigmentosa (RP), and represents 3% of all non-syndromic RP patients with frequency increasing to 10% when considering autosomal recessive RP [5]. Typical onset is in the 2nd to the 4th decade of life. Despite the excellent central visual acuity at present in the patient described above, many with Bietti’s are legally blind by their 5th to 6th decades [1].

The genetics of BCR are a current area of study; BCR is thought to be primarily autosomal recessive, although sporadic autosomal dominant cases have also been reported. There is a demonstrated association with the CYP4V2 mutation, which impairs oxidation of fatty acids, and it is thought that the crystalline deposits are actually a lipid compound [6]. There is no known clinically significant systemic manifestation and no known treatment at present.

Take-home points

  1. BCR is a rare chorioretinal degenerative disease characterized by crystalline deposition in the retina (and sometimes in the cornea), often leading to progressive nyctalopia and loss of visual acuity.
  2. The differential diagnosis for crystalline retinopathies includes primary ocular disorders, systemic disorders, and drug-induced disorders. These can be differentiated based on appearance, intravascular presence of crystals, systemic comorbidities, and history of pertinent drug use. A thorough history is beneficial.
  3. Bietti’s is characterized on exam by multiple, fine yellow-white crystals located primarily in the posterior pole, often with associated atrophy of the photoreceptor, RPE, and choroidal layers. On OCT imaging, there are multiple hyperreflective lesions in both the inner and outer retina. 

   References

  1. Kaiser-Kupfer MI, Chan CC, Markello TC, et al. Clinical biochemical and pathologic correlations in Bietti’s crystalline dystrophy. Am J Ophthalmol. 1994; 118(5):569-582.
  2. Bietti G. Uber familiares Vorkommen von retinitis punctata albescens (verbunden mit dystrophia marginalis cristallinza cornea”). Glitzern des Glaskorpers und anderen degenerativen Augenveranderungen Klin Monatsbl Augenheilkd. 1937;99:737-756.
  3. Hu DN. Ophthalmic genetics in China. Ophthal Paediat Genet. 1983;2:39–45.
  4. Mansour AM, Uwaydat SH, Chan CC. Long-term follow-up in Bietti crystalline dystrophy. Eur J Ophthalmol. 2007;17(4): 680–682.
  5. Mataftsi A, Zografos L, Millá E, Secrétan M, Munier FL. . Bietti's crystalline corneoretinal dystrophy: a cross-sectional study. Retina. 2004; 24(3):416-426.
  6. Li A, Jiao X, Munier FL, et al. Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. AmJ HumGenet. 2004;74(5): 817-826.

 

Financial Disclosures:

Dr. Roth: None

Dr. Weng: Allergan (C)

 

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