BIETTI CRYSTALLINE DYSTROPHY WITH BILATERAL MACULAR HOLES Shu-Xing Ji, MD, PhD, Xiao-Lei Yin, MD, PhD, Xiang-Ge He, MD, PhD, Rong-Di Yuan, BA, Jian Ye, MD, PhD, Shao-Zhang Liu, BA, Xue-Mei Gan, BA, Yan Dong, BA
Objective: Bietti crystalline dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits. However, Bietti crystalline dystrophy is extremely unusually associated with macular hole formation. A 32-year-old man with Bietti crystalline dystrophy and bilateral macular holes is described. Design: Case report and literature review. Results: Clinical and angiographic features, optical coherence tomography results, electroretinographic findings, and visual evoked potentials are reported. Conclusion: Bietti crystalline dystrophy can occur with bilateral macular holes, but the cause is unclear. RETINAL CASES & BRIEF REPORTS 3:361–363, 2009
From the Department of Ophthalmology, Daping Hospital, Third Military Medical University, Daping, Chongqing, People’s Republic of China.
choriocapillaris (Fig. 3). Electroretinography showed minimal, if any, rod responses and severely subnormal cone responses, and the visual evoked potentials were severely decreased. Formal visual field testing was not performed.
B
ietti crystalline dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits. However, Bietti crystalline dystrophy is extremely unusually associated with macular hole formation. We describe a 32-year-old man with Bietti crystalline dystrophy and bilateral macular holes.
Discussion Bietti crystalline dystrophy is a rare inherited eye disease named for Dr. G.B. Bietti, who described 3 patients with similar symptoms in 1937.1 The disease usually occurs in the second or third decade of life and is characterized by sparkling yellow crystals in the superficial paralimbal cornea, yellow, shiny deposits scattered over the fundus, and progressive atrophy of the retina, choriocapillaris, and choroid. The characteristic retinal crystals are observed in all cases, but the associated corneal dystrophy is not a consistent feature of the disease.2 Many studies have demonstrated that Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2.3–5 Richards et al6 used transmission electron microscopy and found circulating lymphocytes crystals and granular osmophilic material of unknown composition contained within abnormal lysosomes. These crystals are similar in appearance and location to those seen in cholesterol ester storage disease, suggesting that Bietti crystalline corneoretinal dystrophy may be due to a systemic abnormality of lipid metabolism7; however, biochemical studies do not support cholesterol or cholesterol esters as the stored compound.2
Case Report A 32-year-old man presented with a 2-year history of decreased vision in both eyes accompanied by constriction of the visual fields to confrontation. Best-corrected visual acuity was 2/60 in the right eye and 3/60 in the left eye. Results of anterior segment examination of both eyes were normal. Funduscopic examination showed bilateral, numerous, tiny, refractile yellow white crystalline deposits scattered throughout the posterior pole and the midperiphery in association with diffuse retinal pigment epithelium (RPE) atrophy and pigment accumulation (Fig. 1). Optical coherence tomography disclosed bilateral macular holes and that the RPE– choriocapillaris complex was thickened and hyperreflective, corresponding to dense crystalline deposits (Fig. 2). Fluorescein angiography revealed retinal pigmentary epithelium alterations and atrophy of the Supported by the National Nature Scientific Foundation (30400487), International Cooperation Project of Guangdong Province (2004B50301002). Reprint requests: Xiao-Lei Yin, Department of Ophthalmology, Daping Hospital, Third Military Medical University, 10, Changjiang Zhilu, Daping, Chongqing, 400042, People’s Republic of China; e-mail: [email protected] or [email protected]
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Fig. 1. Color photography: A, right eye; B, left eye. Small yellowish white sparkling spots and choroidal sclerosis throughout the fundus are shown. Fig. 3. Fluorescein angiography (A, right eye; B, early stage of left eye) shows alteration of the retinal pigment epithelium (RPE) and loss of the choriocapillaris. The RPE is diffusely altered with scattered hypofluorescent spots, corresponding to RPE pigmentary changes and to filling defects of the choriocapillaris.
Fig. 2. Optical coherence tomography: A, right eye; B, left eye. Full-layer macular hole is shown, and the retinal pigment epithelium– choriocapillaris complex is thickened and hyperreflective, corresponding with dense crystalline deposits.
On the basis of the clinical findings, Yuzawa et al8 divided this disease into 3 stages: Stage 1, RPE atrophy with uniform fine white crystalline deposits is observed at the macular area. Stage 2, RPE atrophy extends beyond the posterior pole. Choriocapillaris atrophy in addition to RPE atrophy appears markedly at the posterior pole. Crystalline deposits in the lesion vary in shape and size and have a tendency to be confluent. The number of crystalline deposits is less in the advanced atrophic areas of the RPE– choriocapillaris complex. Stage 3, RPE– choriocapillaris complex atrophy is observed throughout the fundus. Full-field electroretinograms are classified as follows in accordance with the guidelines of the International Society for Clinical Electrophysiology of
BIETTI CRYSTALLINE DYSTROPHY WITH BILATERAL MACULAR HOLES
Vision9: group A, rod dysfunction only with normal rod implicit times and normal cone function; group B, rod and cone dysfunction but normal implicit times; group C, severe rod and cone dysfunction with abnormal implicit times; group D, no observable response and extinguished electroretinogram. We describe a patient with Bietti crystalline dystrophy who had the above-mentioned characteristics (except crystals in the superficial paralimbal cornea), an obvious macular hole in both eyes, and subnormal electroretinogram: stage 3, group C (according to standards8,9). The cause of the macular holes is unclear. Key words: Bietti crystalline dystrophy, Bietti crystalline corneoretinal dystrophy. References 1.
Bagolini B, Loli Spada G. Bietti’s tapetoretinal degeneration with marginal corneal dystrophy. Am J Ophthalmol 1968;65: 53–60.
2.
3.
4.
5.
6.
7.
8. 9.
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Harrison RJ, Acheson RR, Dean-Hart JC. Bietti’s tapetoretinal degeneration with marginal corneal dystrophy (crystalline retinopathy): case report. Br J Ophthalmol 1987;71:220–223. Li A, Jiao X, Munier FL, et al. Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. Am J Hum Genet 2004;74:817–826. Wada Y, Itabashi T, Sato H, et al. Screening for mutations in CYP4V2 gene in Japanese patients with Bietti’s crystalline corneoretinal dystrophy. Am J Ophthalmol 2005;139:894–899. Kelvin YC, Lee AHC, Koh TA, et al. Characterization of Bietti crystalline dystrophy patients with CYP4V2 mutations. Invest Ophthalmol Vis Sci 2005;46:3812–3816. Richards BW, Brodstein DE, Nussbaum JJ, et al. Autosomal dominant crystalline dystrophy. Ophthalmology 1991;98:658– 665. Wilson DJ, Weleber RG, Klein ML, et al. Bietti’s crystalline dystrophy. A clinicopathologic correlative study. Arch Ophthalmol 1989;107:213–221. Yuzawa M, Mae Y, Matsui M. Bietti’s crystalline retinopathy. Ophthalmic Paediatr Genet 1986;7:9–20. Marmor MF, Holder GE, Seeliger MW, Yamamoto S. Standard for clinical electroretinography (2004 update). Doc Ophthalmol 2004;108:107–114.
Objective: Bietti crystalline dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits. However, Bietti crystalline dystrophy is extremely unusually associated with macular hole formation. A 32-year-old man with Bietti crystalline dystrophy and bilateral macular holes is described. Design: Case report and literature review. Results: Clinical and angiographic features, optical coherence tomography results, electroretinographic findings, and visual evoked potentials are reported. Conclusion: Bietti crystalline dystrophy can occur with bilateral macular holes, but the cause is unclear. RETINAL CASES & BRIEF REPORTS 3:361–363, 2009
From the Department of Ophthalmology, Daping Hospital, Third Military Medical University, Daping, Chongqing, People’s Republic of China.
choriocapillaris (Fig. 3). Electroretinography showed minimal, if any, rod responses and severely subnormal cone responses, and the visual evoked potentials were severely decreased. Formal visual field testing was not performed.
B
ietti crystalline dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits. However, Bietti crystalline dystrophy is extremely unusually associated with macular hole formation. We describe a 32-year-old man with Bietti crystalline dystrophy and bilateral macular holes.
Discussion Bietti crystalline dystrophy is a rare inherited eye disease named for Dr. G.B. Bietti, who described 3 patients with similar symptoms in 1937.1 The disease usually occurs in the second or third decade of life and is characterized by sparkling yellow crystals in the superficial paralimbal cornea, yellow, shiny deposits scattered over the fundus, and progressive atrophy of the retina, choriocapillaris, and choroid. The characteristic retinal crystals are observed in all cases, but the associated corneal dystrophy is not a consistent feature of the disease.2 Many studies have demonstrated that Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2.3–5 Richards et al6 used transmission electron microscopy and found circulating lymphocytes crystals and granular osmophilic material of unknown composition contained within abnormal lysosomes. These crystals are similar in appearance and location to those seen in cholesterol ester storage disease, suggesting that Bietti crystalline corneoretinal dystrophy may be due to a systemic abnormality of lipid metabolism7; however, biochemical studies do not support cholesterol or cholesterol esters as the stored compound.2
Case Report A 32-year-old man presented with a 2-year history of decreased vision in both eyes accompanied by constriction of the visual fields to confrontation. Best-corrected visual acuity was 2/60 in the right eye and 3/60 in the left eye. Results of anterior segment examination of both eyes were normal. Funduscopic examination showed bilateral, numerous, tiny, refractile yellow white crystalline deposits scattered throughout the posterior pole and the midperiphery in association with diffuse retinal pigment epithelium (RPE) atrophy and pigment accumulation (Fig. 1). Optical coherence tomography disclosed bilateral macular holes and that the RPE– choriocapillaris complex was thickened and hyperreflective, corresponding to dense crystalline deposits (Fig. 2). Fluorescein angiography revealed retinal pigmentary epithelium alterations and atrophy of the Supported by the National Nature Scientific Foundation (30400487), International Cooperation Project of Guangdong Province (2004B50301002). Reprint requests: Xiao-Lei Yin, Department of Ophthalmology, Daping Hospital, Third Military Medical University, 10, Changjiang Zhilu, Daping, Chongqing, 400042, People’s Republic of China; e-mail: [email protected] or [email protected]
361
362
RETINAL CASES & BRIEF REPORTSℜ
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2009
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VOLUME 3
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NUMBER 4
Fig. 1. Color photography: A, right eye; B, left eye. Small yellowish white sparkling spots and choroidal sclerosis throughout the fundus are shown. Fig. 3. Fluorescein angiography (A, right eye; B, early stage of left eye) shows alteration of the retinal pigment epithelium (RPE) and loss of the choriocapillaris. The RPE is diffusely altered with scattered hypofluorescent spots, corresponding to RPE pigmentary changes and to filling defects of the choriocapillaris.
Fig. 2. Optical coherence tomography: A, right eye; B, left eye. Full-layer macular hole is shown, and the retinal pigment epithelium– choriocapillaris complex is thickened and hyperreflective, corresponding with dense crystalline deposits.
On the basis of the clinical findings, Yuzawa et al8 divided this disease into 3 stages: Stage 1, RPE atrophy with uniform fine white crystalline deposits is observed at the macular area. Stage 2, RPE atrophy extends beyond the posterior pole. Choriocapillaris atrophy in addition to RPE atrophy appears markedly at the posterior pole. Crystalline deposits in the lesion vary in shape and size and have a tendency to be confluent. The number of crystalline deposits is less in the advanced atrophic areas of the RPE– choriocapillaris complex. Stage 3, RPE– choriocapillaris complex atrophy is observed throughout the fundus. Full-field electroretinograms are classified as follows in accordance with the guidelines of the International Society for Clinical Electrophysiology of
BIETTI CRYSTALLINE DYSTROPHY WITH BILATERAL MACULAR HOLES
Vision9: group A, rod dysfunction only with normal rod implicit times and normal cone function; group B, rod and cone dysfunction but normal implicit times; group C, severe rod and cone dysfunction with abnormal implicit times; group D, no observable response and extinguished electroretinogram. We describe a patient with Bietti crystalline dystrophy who had the above-mentioned characteristics (except crystals in the superficial paralimbal cornea), an obvious macular hole in both eyes, and subnormal electroretinogram: stage 3, group C (according to standards8,9). The cause of the macular holes is unclear. Key words: Bietti crystalline dystrophy, Bietti crystalline corneoretinal dystrophy. References 1.
Bagolini B, Loli Spada G. Bietti’s tapetoretinal degeneration with marginal corneal dystrophy. Am J Ophthalmol 1968;65: 53–60.
2.
3.
4.
5.
6.
7.
8. 9.
363
Harrison RJ, Acheson RR, Dean-Hart JC. Bietti’s tapetoretinal degeneration with marginal corneal dystrophy (crystalline retinopathy): case report. Br J Ophthalmol 1987;71:220–223. Li A, Jiao X, Munier FL, et al. Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. Am J Hum Genet 2004;74:817–826. Wada Y, Itabashi T, Sato H, et al. Screening for mutations in CYP4V2 gene in Japanese patients with Bietti’s crystalline corneoretinal dystrophy. Am J Ophthalmol 2005;139:894–899. Kelvin YC, Lee AHC, Koh TA, et al. Characterization of Bietti crystalline dystrophy patients with CYP4V2 mutations. Invest Ophthalmol Vis Sci 2005;46:3812–3816. Richards BW, Brodstein DE, Nussbaum JJ, et al. Autosomal dominant crystalline dystrophy. Ophthalmology 1991;98:658– 665. Wilson DJ, Weleber RG, Klein ML, et al. Bietti’s crystalline dystrophy. A clinicopathologic correlative study. Arch Ophthalmol 1989;107:213–221. Yuzawa M, Mae Y, Matsui M. Bietti’s crystalline retinopathy. Ophthalmic Paediatr Genet 1986;7:9–20. Marmor MF, Holder GE, Seeliger MW, Yamamoto S. Standard for clinical electroretinography (2004 update). Doc Ophthalmol 2004;108:107–114.
