ABSTRACT

A 44-year-old female patient without any known systemic or ocular disease presented with progressive visual loss and night vision disturbance. Visual acuity was 0.6 in the right eye and 0.2 in the left eye. Tiny, yellow crystalline deposits were seen on fundus examination. In addition, areas of retinal pigment epithelium and choriocapillaris atrophy were detected. Rod and cone responses were depressed in full-field flash electroretinogram. Multifocal electroretinogram testing showed severe foveal function disturbance with less severe but still depressed responses toward the periphery. Multiple hyperreflective lesions were detected in the retina in optical coherence tomography. We aimed to present the role of ocular electrophysiology by comparing the patient’s signs and symptoms with her ocular electrophysiological test results.

Introduction

Bietti crystalline corneoretinal dystrophy (BCD) is a rare disorder characterized by yellow deposits in the retina and progressive atrophy of the retinal pigment epithelium (RPE) and the choriocapillaris. Bietti first described corneal crystals in 1937 in a report of three cases exhibiting shiny yellow retinal deposits and RPE atrophy. Lipid aggregates resulting from abnormal lipid metabolism form these crystal deposits, which may also be seen in the conjunctiva, fibroblasts and lymphocytes.^1,2Although some cases have crystals in the paralimbal superficial corneal stroma, corneal depositions are not typical and corneal involvement is not one of the diagnostic criteria.³In BCD, symptoms including declining visual acuity and disruptions in night and peripheral vision emerge in the third and forth decades.¹Recent studies have demonstrated that the condition is associated with mutations in the CYP4V2 gene on chromosome 4q35.^4,5,6CYP4V2 encodes the cytochrome P450 enzyme group; mutations in this gene result in lipid metabolism dysfunction at the cellular level.⁷Histopathologic studies have revealed complex lipid inclusions and crystals in the choroidal fibroblasts as well as generalized choroidal atrophy.²

With this case report, we aimed to discuss multifocal electroretinogram (mfERG) and electroretinogram (ERG) findings in BCD.

Discussion

Our patient’s symptoms included bilateral progressive vision loss and more recently, difficulty distinguishing figures in the dark. Studies in the literature concerning BCD have reported pathologic ERG responses at non-detectable levels,^1,12,13a- and b-wave amplitude attenuation on scotopic strong flash ERG,¹⁴reduced rod b-wave amplitude,^1,15attenuated a- and b-wave amplitudes on photopic ERG,^15,16decreased 30-Hz flicker amplitude,^1,16and abnormal S-cone ERG findings.¹⁵There are also studies demonstrating retinal dysfunction using focal and mfERG, despite normal ERG findings.^16,17

Our patient’s rod b-wave amplitudes were lower than normal in the right eye and within normal range in the left eye. Attenuated amplitude and prolonged latencies were detected in both a- and b-wave combined rod-cone responses. Photopic response showed reduced amplitudes and extended peak times in both cone and 30 Hz flicker responses in both eyes. These electrophysiological findings indicate widespread outer retinal dysfunction.

MfERG represents the electrical response to cone stimulation, usually from the central 30-40 degree field of the retina, and originating mostly from bipolar cell activity. MfERG provides local retinal function data from 61, 103 or 241 retinal sectors. Our patient showed pathologic cone responses on ERG in both eyes, and mfERG revealed markedly attenuated amplitudes in both eyes, particularly in central sectors. Because BCD is a progressive condition, observing different electrophysiological responses in the the different stages of the disease is understandable. However, in patients showing normal ERG results in the early stages of the disease, retinal function can be assessed using mfERG. We believe the utilization of mfERG is especially advisable in monitoring progression in cases with central involvement as mfERG shows the function of cone cells, which are more concentrated in the central retina. Therefore, a BCD diagnosis should not immediately be ruled out in cases exhibiting normal photopic and scotopic responses on ERG. It must be kept in mind that ERG results may be within normal limits in early BCD and that local retinal dysfunction may be detected with mfERG.

In our patient, the hyperreflective areas detected on OCT did not correspond directly to the retinal crystalline deposits, whereas Ayata et al.⁹showed these hyperreflective areas to be consistent with the crystalline deposits. Although a clear relationship between retinal crystalline deposits and visual prognosis could not be determined, patients with widespread crystalline deposits in the sensorial retina have lower visual acuity.¹⁸We believe that the cystic alterations, which are more common in the outer layers, are instances of outer retinal tubulation. Zweifel et al.¹⁹first described this OCT finding as the result of morphological changes occurring after damage to cells in the photoreceptor layer in retinal degenerative diseases, and determined that this finding can be seen in BCD. Pennesi et al.²⁰hypothesized that these lesions are crystalline deposits that have been encapsulated by the retinal pigment epithelium. In terms of the clinical significance of these lesions, on B-scan OCT they can be mistaken for cystic macular edema, and their tubular structure can be more clearly visualized in C-scan sections on en face OCT. We believe the alterations observed in the choroid are an optical illusion created by these tubular alterations in the outer retinal layer.

Conclusion

Evaluated together with other cases presented in the literature, our mfERG and ERG findings indicate widespread dysfunction of the outer retinal layers in BCD. As mfERG demonstrates central retinal function, this technique can be utilized as an objective assessment method when following macular function in BCD.