Sachiko Kuroiwa

Pathological features of surgically excised polypoidal choroidal vasculopathy membranes

The histopathological features are reported of surgically excised specimens from five patients with polypoidal choroidal vasculopathy, which had been diagnosed by indocyanine green angiography. On stereomicroscopy, four of the five cases demonstrated large choroidal arterioles with an inner elastic layer. Disruption of the inner elastic layer and arteriosclerotic changes of the vessels were identified by light microscopy. Transmission electron microscopy demonstrated increased deposition of basement membrane‐like material, together with collagen fibres, in the arteriolar walls. This study indicates that large choroidal arterioles and venules can be found in excised specimens from patients with polypoidal choroidal vasculopathy and arteriosclerosis is an important pathological feature.

ATP binding cassette transporter retina genotypes and age related macular degeneration: an analysis on exudative non-familial Japanese patients

AIM To determine whether mutations in the Stargardt’s disease gene, ATP binding cassette transporter retina (ABCR) affect the occurrence of age related macular degeneration (AMD) in Japanese non-familial patients. METHODS 80 unrelated Japanese patients with AMD (67 males and 13 females; mean age, 67.2 years) diagnosed by indocyanine green angiography and 100 age matched control subjects were studied. Among the AMD patients, 70 (87.5%) had choroidal neovascularisation of exudative type. Genomic DNA was purified from the total blood and 10 exons (exons 11, 23, 29, 32, 34, 37, 41, 43, 44, and 49) that have been reported to contain AMD associated mutations were amplified by polymerase chain reaction (PCR). The amplicons were analysed by the single strand conformation polymorphism (SSCP) method. The nucleotide sequencing of the amplicons was determined when necessary. RESULTS Of the 10 exons, aberrant patterns of SSCP were detected in three exons—exons 29, 41, and 43. In exon 29, an aberrant pattern was found in seven of 80 patients (8.8%) and eight of 100 controls (8%). Sequencing of the PCR products revealed a heterozygous T1428M mutation which has been previously reported as one of the AMD associated mutations. Statistical analysis showed that there was no significant difference in the occurrence of this mutation between these AMD patients and the control groups (p = 0.86). In exons 23, 41, and 43, polymorphisms and sequence variations were found. CONCLUSION No data to support the association between the ABCR gene mutations and AMD of Japanese patients, especially that of the exudative type, were obtained in this molecular genetic analysis.

Polypoidal choroidal vasculopathy with large vascular network

AbstractPurpose. To report characteristics of polypoidal choroidal vasculopathy (PCV) of large vascular networks that expand across the retinal vascular arcade. Methods. Among 60 consecutive eyes diagnosed as having PCV by fluorescein and indocyanine green (ICG) angiography, 12 eyes (9 patients) showed large lesions. The clinical and angiographic features of these 12 eyes were studied retrospectively. Results. Cases of large PCV typically showed dilated network vessels, which spread radially, and multiple polypoidal dilations at the end of the network vessels. Most of the polypoidal dilations formed clusters resembling bunches of grapes and caused large serous and/or hemorrhagic pigment epithelial detachments (PEDs). Among the 12 eyes, 5 showed rapid expansion of the lesions and became large PCVs within 3–24 months. In these eyes, ICG angiography revealed mesh-like choroidal vessels beneath the retinal pigment epithelium. Conclusion. PCV with a large vascular network that expands across the vascular arcade is not uncommon. Some of these cases seems to have characteristics of choroidal neovascularization rather than choroidal vasculopathy. It is not easy to distinguish such cases from exudative age-related macular degeneration even though they showed typical findings of PCV on ICG angiography.

Diagnosis of intraocular lymphoma by polymerase chain reaction

Abstract• Background: Cytopathological examinations have been used in the diagnosis of intraocular lymphoma. However, sometimes it is not easy to detect malignant cells in the biopsy specimens. We applied a method that identified monoclonal proliferation of B lymphocytes by using polymerase chain reaction (PCR) in the diagnosis of patients suspected to have intraocular B-cell lymphoma. • Methods: Threè specimens of the diagnostic vitrectomy were studied by cytological examination and by PCR to amplify the complementary determining region (CDR3) of immunoglobulin heavy chain (IgH) gene. As a positive control, a biopsy specimen of an orbital lymphoma was examined; four vitrectomy specimens from patients with diabetic retinopathy, proliferative vitreo-retinopathy, acute retinal necrosis (ARN) and macular hole were negative controls. • Results: On cytologic examination, no malignant cells were found in three specimens: suspected intraocular lymphoma and one ARN. In contrast, a discrete band that reflected monoclonal proliferation of B lymphocytes was detected by PCR in specimens from two patients and the positive control. Vitrectomy specimens from the negative controls, including ARN, did not show a discrete band on PCR. • Conclusions: Two cases of ocular malignant lymphoma were diagnosed by PCR identification of monoclonal proliferation of B lymphocytes. This method may be an additional diagnostic tool in the diagnosis of intraocular B-cell lymphoma.

A novel compound heterozygous mutation in the RDH5 gene in a patient with fundus albipunctatus.

PURPOSE To report a novel compound heterozygous mutation in the 11-cis retinol dehydrogenase (RDH5) gene in a patient with fundus albipunctatus. METHOD We examined the RDH5 gene genotype in members of a Japanese family. Clinical examination showed that the proband had fundus albipunctatus and his aunt had retinitis pigmentosa. The RDH5 gene was analyzed by direct genomic sequencing. RESULTS The proband had a compound heterozygotic missense mutation of Val177Gly (GTC-->GGC) and Arg280His (CGC-->CAC) in his RDH5 gene. His mother had the Arg280His mutation and his father had the Val177Gly mutation, but his fathers aunt who has typical retinitis pigmentosa had the wild type RDH5 gene. The occurrence of Val177Gly has not been reported in the RDH5 gene of fundus albipunctatus. CONCLUSION A novel compound heterozygous missense mutation in the RDH5 gene was found in a patient with fundus albipunctatus.

Lack of association of mutations of the bestrophin gene with age-related macular degeneration in non-familial Japanese patients

Abstract Background: Heterozygous mutations of the bestrophin gene are associated with Best macular dystrophy (BMD). The bestrophin gene is specifically expressed in the retinal pigment epithelium. BMD is a hereditary form of macular degeneration that may develop subretinal neovascularisation similar to the wet type of age-related macular degeneration (AMD). Purpose: To study whether mutations of the bestrophin gene occur in non-familial Japanese AMD patients. Methods: A total of 85 non-familial AMD patients (average age 67.5 years; 71 male, 14 female) diagnosed by indocyanine green angiography were screened. Among them, 69 patients (81%) were classified as having wet type AMD. Genomic DNA was purified from the total blood and used as the template for polymerase chain reaction (PCR). All the exons of bestrophin gene were amplified by PCR. Mutation analysis was performed by SSCP using the ABI Prism 310 Genetic Analyzer (Perkin Elmer). Nucleotide sequence was determined by direct sequencing of the PCR amplicons. As the control, 105 non-AMD patients (average age 62.0 years; 52 male, 53 female) were screened by the same method. Results: Only one AMD patient had a specific polymorphism in exon 2, but no mutations leading to amino acid substitutions were found. In exon 2 and 3, two further polymorphisms were detected in all AMD patients as well as normal controls. Conclusion: No mutations were found in the bestrophin gene in non-familial Japanese patients with AMD or in normal controls.