Sparkling retina: Multimodal imaging in Bietti crystalline dystrophy

A 27-year-old man of East Asian descent with complaints of flashes and floaters was referred for evaluation of dominant drusen. Fundus examination revealed scattered yellow crystalline deposits throughout the retina in both eyes. Multimodal imaging further demonstrated patchy outer retinal thinning. The clinical picture is highly consistent with Bietti crystalline dystrophy (BCD), a rare autosomal recessive dystrophy characterized by bilateral white and yellow lipid deposits in the retina, with a higher prevalence in individuals of Italian or East Asian descent. Progressive retinal pigment epithelium (RPE) and choriocapillaris atrophy in BCD leads to significant visual impairment, including reduced visual acuity, dyschromatopsia, nyctalopia, visual field loss, and abnormal retinal electrophysiology. Gene panel testing confirmed the presence of a homozygous CYP4V2 mutation. Baseline electrophysiology results are pending.

Case report

A 27-year-old Chinese man was referred by his local optometrist following a suspicion of dominant drusen in both eyes. The patient reported occasional, long-standing floaters in both eyes, stable over time, with no subjective deterioration in visual acuity. His medical history was unremarkable aside from ongoing finasteride use. No prior ocular history was noted.

Presenting visual acuities were 20/25 OD and 20/50 OS, with no improvement on pinhole testing. IOPs were within normal limits at 9 mm Hg OD and 10 mm Hg OS. Objective refraction measured –3.50 D OD and –3.25/–0.50 × 135 OS. Anterior segment examination was unremarkable bilaterally with absence of crystals in anterior segment tissue. Dilated fundus examination revealed scattered crystalline deposits across the posterior pole in both eyes without vascular attenuation or peripheral spiculation changes. The peripheral retina appeared normal. Kinetic perimetry (Goldmann) was unrestricted in both eyes.

Family history

The patient’s pedigree reveals no known history of a familial ocular condition, blindness, or known consanguinity. Both of his parents are from different towns in southern China. Neither his paternal grandparents nor his maternal grandfather had any visual troubles before passing. His 2 older siblings, parents, and maternal grandmother have no visual complaints.

Multimodal imaging findings

Optos ultrawidefield imaging

Ultrawidefield retinal imaging (Optos) captured a 200-degree field of view. In red-green mode, bright yellow deposits were visible scattered throughout the retina, with a notable concentration at the macula. Fundus autofluorescence (FAF) mode, using 532 nm green-spectrum illumination to assess RPE metabolic integrity, revealed the deposits as hyperpigmented flecks distributed across the fundus, a finding indicative of metabolic disruption at the level of the RPE (Figure 1).¹

Heidelberg Spectralis OCT

Spectral-domain OCT (Heidelberg Spectralis) demonstrated outer retinal atrophy with ellipsoid zone attenuation, with only faint residual signal preserved at the fovea (Figure 2). Crystals, appearing as hyperreflective foci, were scattered across the entire retinal thickness. Heidelberg FAF, using a slightly shorter blue-wavelength laser at 488 nm, similarly highlighted hyperfluorescent lesions across the entire retina, consistent with diffuse RPE dysfunction (Figure 3).

Multicolor imaging provided further structural analysis through simultaneous acquisition using 3 distinct wavelengths: blue reflectance (488 nm) to evaluate the vitreoretinal interface and inner retina, green reflectance (518 nm) to highlight the inner retinal layers and retinal vasculature, and infrared reflectance (820 nm) to assess the outer retina and choroid (Figures 4-5).² All 3 modalities revealed hyperreflective flecks, with a notable increase in the number of flecks at longer wavelengths, suggesting that the deposits extend into and are concentrated within the deeper retinal layers and RPE/choroid complex.

Management and follow-up

The patient was referred for full-field electroretinography (ffERG) and pattern electroretinography (pERG) to document baseline retinal function and assess the extent of photoreceptor involvement. Genetic testing detected a homozygous CYP4V2 mutation, confirming the diagnosis. A follow-up appointment was scheduled to review testing results, complete genetic counseling, and formulate a long-term management plan.

Discussion

Bietti crystalline dystrophy

BCD is a rare autosomal recessive dystrophy caused by mutations in the CYP4V2 gene, which encodes an important enzyme involved in fatty acid metabolism.³ It is characterized by bilateral white and yellow lipid deposits scattered throughout the retina. Perilimbal corneal stromal deposits can also be observed in approximately 25% to 33% of affected individuals.⁴ Progressive RPE and choriocapillaris atrophy leads to significant visual dysfunction, including reduced visual acuity, dyschromatopsia, nyctalopia, visual field constriction, and abnormal electrophysiology. As the condition progresses, retinochoroidal degeneration begins at the posterior pole and extends peripherally over time. Concurrently, the number of visible crystals tends to diminish as atrophy advances.⁵ A rare but significant complication includes choroidal neovascularization (CNV).⁴ Diagnosis is most often made in the second or third decade of life. Although BCD has been documented across various ethnic groups, including individuals of Middle Eastern, African, and North and South American descent, it shows a significantly higher prevalence in those of Italian or East Asian, particularly Chinese and Japanese descent.⁴

Currently, there is no approved treatment for BCD. Genetic counseling and CYP4V2 testing are essential components of both formal diagnosis confirmation and long-term care planning. Management is centered on a comprehensive oculovisual assessment, including color vision testing, visual field analysis, and dilated fundus examination. Electrophysiology serves as a critical tool for monitoring disease progression. Given the progressive nature of BCD, referral to low-vision services is warranted to optimize functional vision, and psychological support should be considered. Long-term ophthalmological follow-up is necessary to document disease progression and monitor for CNV, which may require prompt intervention.

Differential diagnoses

Cystinosis

Cystinosis is a rare autosomal recessive disorder caused by mutations in the CTNS gene, resulting in dysfunction of a key transporter responsible for exporting cystine out of the lysosome.⁶ This leads to accumulation of cystine crystals throughout the body, affecting the kidneys, muscles, brain, and eyes. Ocular manifestations include crystal deposition in the conjunctiva, cornea, retina, choroid, and RPE.⁵ Cystinosis is classified into 3 subtypes: infantile, intermediate, and adult. Infantile nephropathic cystinosis is the most common and severe form. It presents within the first year of life with growth retardation, renal dysfunction, and characteristic corneal and conjunctival crystals causing photophobia and blepharospasm.⁵ Retinal involvement leads to progressive visual loss and field constriction. The 2 milder forms, intermediate nephropathic cystinosis and adult ocular cystinosis, generally lack significant retinal involvement and present primarily with corneal and conjunctival deposits.⁷ Cystinosis was ruled out given the absence of any systemic features in this patient, in addition to the absence of anterior segment crystals.

Sjögren-Larsson syndrome

Sjögren-Larsson syndrome is a rare autosomal recessive disorder of fatty acid metabolism caused by mutations in the ALDH3A2 gene.⁸ Abnormal accumulation of fatty alcohols and aldehydes disrupts cell membrane integrity, predominantly affecting the eyes, skin, and central nervous system.⁵ Funduscopically, bilateral yellow lipid deposits can be seen in the inner nuclear layer of the fovea and parafovea, which may increase in number over time and be accompanied by RPE atrophy and macular depigmentation.⁵ Additional ocular findings may include microphthalmia and congenital cataract.⁵ Systemic features include short stature, short fingers and toes, and speech deficits.⁷ The onset is typically around 2 years of age. This diagnosis was excluded, given the absence of cataract, axial length shortening, and associated systemic findings in this young adult.

Primary hyperoxaluria

Primary hyperoxaluria is a rare autosomal recessive disorder of glyoxylate metabolism resulting in oxalate accumulation, which can cause severe renal disease.⁹ Ocular involvement includes calcium oxalate crystal deposition across the conjunctiva, iris, ciliary body, retina, RPE, choroid, and optic nerve.⁵ Retinal crystals tend to be more prominent in the perifoveal area and decrease toward the periphery, involving predominantly the outer retina.⁵ This diagnosis was excluded, given the presence of outer retinal atrophic changes and signs of photoreceptor dystrophy.

Drug-induced crystalline retinopathies

Tamoxifen retinopathy presents with bilateral perifoveal white-yellow crystalline deposits and is associated with the use of tamoxifen, a selective estrogen receptor modulator used in hormonal therapy for breast cancer.¹¹ Cumulative toxicity, typically seen after 2 or more years of use at 20 mg/day, can affect approximately 12% of patients, causing cystoid macular edema, inner retinal hyperreflective deposits, telangiectasia, and irreversible visual loss.¹¹ Onset is typically in the fourth or fifth decade of life. Management involves prompt discontinuation of tamoxifen, and some evidence supports anti-VEGF or corticosteroid injections, though these are not formally approved treatments.¹¹

Talc retinopathy is associated with repeated intravenous injection of crushed oral medications in which talc serves as a filler, most commonly methylphenidate and various narcotic formulations.¹² Upon entering the systemic circulation, talc microparticles are unable to traverse the retinal capillary bed and accumulate within arterioles and capillaries of the posterior pole, producing a characteristic pattern of small, glistening, yellow-white crystalline deposits clustered in the perimacular region. Progressive vascular occlusion may lead to peripheral retinal neovascularization.⁵

Canthaxanthin retinopathy arises from excessive ingestion of canthaxanthin, a carotenoid found notably in food dyes and self-tanning products.¹³ It classically presents as golden crystalline deposits in the perifoveal area. Prognosis is generally favorable following discontinuation of the product, with deposits resolving over time.¹³

All 3 drug-induced retinopathies were excluded, as the patient denied use of tamoxifen, intravenous medications, or products containing canthaxanthin or talc.

Conclusion

After thorough clinical evaluation and multimodal imaging, this patient's presentation is highly consistent with BCD. The characteristic bilateral crystalline retinal deposits, RPE atrophy, outer retinal loss on OCT, and the patient's demographic profile as a young adult of East Asian descent with no systemic disease all strongly support this diagnosis. Gene panel testing confirmed a homozygous CYP4V2 mutation. Baseline electrophysiology results are pending. This case highlights the importance of multimodal imaging in practice for early identification of rare inherited retinal dystrophies and the value of prompt referral for genetic and subspecialty comanagement.

Financial disclosure

The authors declare no conflict of interest.

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