Presumed Bietti crystalline dystrophy with optic nerve head drusen: a case report

Bietti crystalline dystrophy typically occurs in the second to fourth decades of life, with symptoms of reduced visual acuity with or without nyctalopia [1, 2]. Ocular examination revealed crystalline retinal deposits in the posterior fundus and crystalline corneal deposits near the limbus in nearly one-third of patients [2]. These crystals show hyperreflectivity on near-infrared (NIR) retinal images in spectral-domain optical coherence tomography (SD-OCT). These crystals can be seen in all retinal layers but are most prominent between retinal pigment epithelium and Bruch’s membrane [3, 4]. Bietti crystalline dystrophy is a typically autosomal recessive disorder caused by mutations in the CYP4V2 gene that result in defective ocular fatty acid metabolism in retinal pigment epithelium and the formation of crystalline deposits [5‐7]. In the advanced stages of the disease, retinal crystals may not be evident owing to the atrophy of retinal pigment epithelium [2]. In this study, we report on a case of Bietti crystalline dystrophy associated with optic nerve head drusen.

A 39-year-old Iranian woman suffered from progressively reduced vision in both eyes that had started 2 years prior to presentation. Her parents were relatives, but there was no family history of ocular disease in the patient’s first- and second-degree family. The patient’s medical history and drug history were unremarkable. Blood testing and urine analysis were performed to rule out cystinosis and crystalluria. Written informed consent was obtained from the patient. A complete ocular examination—including optical coherence tomography (OCT), OCT angiography (OCT-A), infrared (IR) imaging, fundus autofluorescence (FAF) imaging, and electroretinography (ERG)—was performed.

Bietti crystalline dystrophy is primarily a retinal dystrophy caused by a CYP4V2 mutation and is presumed to affect fatty-acid omega-hydroxylase activity in retinal pigmented epithelium and accumulation of yellow-white crystalline-like deposits [1, 2, 8]. These crystals can also be found in the peripheral cornea near the limbus [2]. This disease is frequently inherited as an autosomal recessive pattern, but an autosomal dominant pattern has also been seen within family members who have the disease [1, 5, 7]. These patients typically become symptomatic during the third decade of life via bilateral slowly progressing vision loss, nyctalopia, and visual field constriction. The rapid deterioration of vision in these patients should increase suspicion of the development of cystoid macular edema, choroidal neovascularization, and macular hole formation [9, 10]. In the early stage of the disease, retinal crystals are prominently found in the posterior retina with minimal retinal pigment epithelium atrophic changes in the macula. With progression of the disease, the retinal pigment epithelium atrophic changes in the macular area worsen, and the presence of retinal crystals decreases in the posterior pole while increasing outside the vascular arcades and peripheral retina. In the advanced stage of the disease, extensive retinal pigment epithelium atrophic changes are seen throughout the fundus, and retinal crystals may not be evident [2, 10]. These crystals could be found in all layers of the retina, but, as with our patient, they are more numerous between retinal pigment epithelium and Bruch’s membrane [4]. These crystals are better visualized on NIR fundus images, and they are hyperreflective on SD-OCT images [4]. SD-OCT images also show outer retinal tubulation in many patients with Bietti crystalline dystrophy, even in the early stages of the disease. Other posterior segment findings in these patients are choriocapillaris atrophy, choroidal sclerosis, and the disruption of outer retinal hyperreflective bands [2, 4, 11]. Outer retinal tubulation and the disruption of the ellipsoid band on SD-OCT images (both of which were seen in our case) predict poor visual outcomes in these patients [11]. The sensitivity and specificity of NIR images for detecting retinal crystals and sensitivity of SD-OCT for detecting outer retinal tubulation in these patients are high, but outer retinal tubulation is not specific for this disease [3, 4, 9, 11]. Retinal pigment epithelium atrophic changes are better visualized on FAF images as areas of reduced autofluorescence due to the atrophy of retinal pigment epithelium. Fluorescein angiography in the early stages of the disease typically shows window defects due to the atrophy of outer retinal layers and retinal pigment epithelium; however, as the disease progresses, choriocapillaris atrophy causes early hypofluorescence and late hyperfluorescence due to the staining of underlying sclera [4, 12]. Fluorescein angiography and OCT-A could help establish diagnoses of choroidal neovascularization as a complication of the disease in a proper clinical context. Full-field ERG studies typically show diminished photopic and scotopic responses [2, 3]. The clinical examination and multimodal imaging of our patient were typical for Bietti crystalline dystrophy. The patient’s medical and drug histories were negative, and blood tests for cystinosis and urine analysis yielded normal results. Bietti crystalline dystrophy was diagnosed without applying genetic testing to confirm the diagnosis.

Optic nerve head drusen is a clinical condition that is usually asymptomatic and found incidentally but may be associated with retinal hemorrhage and visual field defects [13]. Optic nerve head drusen mainly consists of calcified hyaline bodies and occurs in up to 2% of the general population [13]. Optic nerve head drusen typically appears as hyperreflectivity on SD-OCT images and hyperautofluorescence on FAF images, as seen in our patient.

To the best of our knowledge, this is the first report on the association between optic nerve head drusen and Bietti crystalline dystrophy.