Yasuhiro Ohkuma

Autosomal dominant occult macular dystrophy with an RP1L1 mutation (R45W).

Purpose. To characterize clinical features in occult macular dystrophy (OMD) patients with the RP1L1 gene mutation (p.R45W), one of two previously described mutations in Japanese OMD patients. Methods. Mutational screening of the RP1L1 gene was performed via polymerase chain reaction and direct sequencing for seven unrelated probands (one autosomal dominant and six sporadic probands) with OMD. A comprehensive ophthalmic examination was performed, including Cirrus optical coherence tomography. Full-field electroretinography (ERG), multifocal ERG, and focal macular ERG were performed. Results. The heterozygous mutation (p.R45W) was found in only one female proband with autosomal dominant OMD, whose mother was also diagnosed with OMD and carried the mutation. Ophthalmoscopy showed bilateral normal fundi in the proband but subtle retinal pigment epithelium mottling in the mother. Both the proband and her mother had typical OMD findings: decreased visual acuity and markedly reduced central responses in the multifocal ERG and focal macular ERG. Although full-field ERG revealed normal rod and standard combined responses, photopic and 30-Hz flicker responses were slightly reduced in both the proband and her mother. Optical coherence tomography revealed that the external limiting membrane and inner segment-outer segment boundary were disorganized despite normal macular thickness in the proband, whereas the mother exhibited macular thinning with discontinuous reflectivity of the external limiting membrane and inner segment-outer segment boundary. Conclusions. The clinical phenotypes differed between the proband and her mother and were indistinguishable from other sporadic or RP1L1-unassociated OMD patients, suggesting that mutation-dependent clinical features may not be present.

Three-year visual outcome of photodynamic therapy plus intravitreal bevacizumab with or without subtenon triamcinolone acetonide injections for polypoidal choroidal vasculopathy

Purpose To compare the 3-year visual outcome after double therapy of photodynamic therapy (PDT) with intravitreal bevacizumab (IVB) and triple therapy of PDT combined with IVB and subtenon triamcinolone acetonide (STTA) injections for polypoidal choroidal vasculopathy (PCV). Design Retrospective, comparative, interventional case series. Methods Medical records for 36 eyes in 36 patients (33 men, 3 women; mean age 73.5 years old; range 63–82 years old) with treatment-naive subfoveal PCV were reviewed retrospectively. Of the 36 eyes, 17 were treated with double therapy and 19 with triple therapy. Results The change in visual acuity after triple therapy was significantly better than that after double therapy (p<0.05). At 36 months, improvement in visual acuity was seen in 5 eyes (29.4%) in the double therapy group and 10 eyes (52.6%) in the triple therapy group. Retreatment using the initial treatment was performed for six eyes (35.3%) in the double therapy group and five eyes (26.3%) in the triple therapy group, and treatment-free period was significantly longer in the triple therapy group (p<0.05). The mean number of additional antivascular endothelial growth factor therapy was higher in the double therapy group. Post-treatment vitreous haemorrhage or retinal pigment epithelium tear occurred only in the double therapy group, in one eye (5.9%) and one eye (5.9%), respectively. Conclusions Initial therapy consisting of a single session of PDT combined with IVB and STTA improves vision in treatment-naive subfoveal PCV. Compared with double therapy, this triple therapy may be more effective for PCV.

Pedicle Internal Limiting Membrane Transposition Flap Technique for Refractory Macular Hole.

BACKGROUND AND OBJECTIVE To determine the efficacy of the pedicle internal limiting membrane (ILM) transposition flap technique for refractory macular holes (MHs) in which the inverted ILM flap technique cannot be performed. PATIENTS AND METHODS The pedicle ILM flap transposition technique was conducted by transconjunctival microincision vitrectomy. The authors attempted to peel the remaining ILM inferior from the MH to create an ILM flap. This ILM was still attached to the retina at the upper part of the MH and covered the MH. Finally, fluid-gas exchange was performed. After surgery, patients remained face-down for 1 week. This procedure was performed in two eyes. RESULTS There were no adverse events, and MHs were closed successfully in both study eyes. CONCLUSION The pedicle ILM flap transposition technique has the potential to improve functional and anatomical outcomes in patients with refractory MHs.

Mutation analysis of BEST1 in Japanese patients with Best's vitelliform macular dystrophy

Purpose To describe the clinical and genetic features of Japanese patients with Bests vitelliform macular dystrophy (BVMD). Patients and methods This study examined 22 patients, including 16 probands from 16 families with BVMD. Comprehensive ophthalmic examinations were performed, including dilated funduscopy, full-field electroretinography (ERG) and electro-oculography (EOG). BEST1 mutation analysis was performed by Sanger sequencing. Results All 16 probands exhibited characteristic BVMD fundus appearances, abnormal EOG, and normal ERG responses with the exception of one diabetic retinopathy proband. Genetic analysis identified 12 BEST1 variants in 13 probands (81%). Of these, 10 variants (p.T2A, p.R25W, p.F80L, p.V81M, p.A195V, p.R218H, p.G222E, p.V242M, p.D304del and p.E306D) have been previously reported in BVMD, while two variants (p.S7N and p.P346H) were novel, putative disease-causing variants. Single BEST1 variants were found in 12 probands. The one proband with compound heterozygous variants (p.S7N and p.R218H) exhibited typical BVMD phenotypes (pseudohypopyon stage and vitelliruptive stage in the right and left eyes, respectively). Conclusions Twelve different variants, two of which (p.S7N and p.P346H) were novel, were identified in the 13 Japanese families with BVMD. Compound heterozygous variants were found in one proband exhibiting a typical BVMD phenotype. Our results suggest that BEST1 variants do play a large role in Japanese patients with BVMD.

Retinal angiomatous proliferation associated with risk alleles of ARMS2/HTRA1 gene polymorphisms in Japanese patients.

Background The purpose of this study was to investigate the association between ARMS2/HTRA1, CFH, and C3 gene polymorphisms and retinal angiomatous proliferation (RAP), an infrequent and severe form of exudative age-related macular degeneration, which is characterized by intraretinal neovascularization. Methods Diagnosis of RAP was based on fundus photographs, images of fluorescein and indocyanine green angiographies, and optical coherence tomography findings. Six single nucleotide polymorphisms (SNPs), A69S (rs10490924) in ARMS2, rs11200638 in HTRA1, I62V (rs800292) in CFH, Y402H (rs1061170) in CFH, R80G (rs2230199) in C3, and rs2241394 in C3, were genotyped in eight Japanese patients with RAP. Results The two SNPs in the ARMS2/HTRA1 were in complete linkage disequilibrium. The frequency of the risk T allele in ARMS2 (the risk A allele in HTRA1) was 93.8% in the RAP patients. The frequency of homozygosity for the risk genotype TT of ARMS2 (the risk genotype AA of HTRA1) was 87.5%. The frequency of the non-risk allele (A) of I62V was 100%. The frequencies of risk alleles of Y402H, R80G, and rs2241394 were 12.5%, 0%, and 18.8%, respectively. Conclusion Our results suggest that the risk alleles of the ARMS2/HTRA1 SNPs may be associated with development of RAP and play a major role in the pathogenesis of intraretinal angiogenesis.

Efficacy of reduced-fluence photodynamic therapy for serous retinal pigment epithelial detachment with choroidal hyperpermeability

Background Very few reports have addressed methods of treatment for idiopathic serous (IS) pigment epithelial detachment (PED). Objective The purpose of this report was to describe clinical courses of two patients with ISPED in whom reduced-fluence photodynamic therapy (RFPDT) was performed. Case reports Two patients (a 38-year-old woman and a 42-year-old man) were diagnosed with ISPED. In both patients, indocyanine green angiography revealed an area of choroidal vascular hyperpermeability including hyperfluorescent PED, which was evident at the subfoveal area. Both patients underwent RFPDT at an energy of 25 J/cm2. The PED was seen to have resolved 1 month after the treatment and visual acuity was maintained or improved. There was no posttreatment recurrence of PED after 6 months to 1 year, and no treatment-related adverse events were observed. Conclusion RFPDT may be an effective and safe method of treatment for ISPED with choroidal vascular hyperpermeability.

Trisection technique for the extraction of dislocated intraocular lenses through a small surgical incision

&NA; We describe a trisection technique for extracting a dislocated IOL through a small surgical incision. The dislocated IOL is brought into the anterior chamber and cut into 3 equal segments, with a negligible risk for the segments falling into the vitreous cavity. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Fundus autofluorescence findings of acute posterior multifocal placoid pigment epitheliopathy with chronic thyroiditis and splenectomy.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) was first described by Gass in 1968, as a disease that shows rapid loss of vision due to multifocal, yellow-white, placoid lesions at the level of the pigment epithelium and choroid. The mechanism of APMPPE primarily involves inflammation of the choriocapillaris, with a secondary acute effect on the retinal pigment epithelium that occurs without affecting the intermediate and large choroidal vessels. Several ophthalmic examinations, such as fluorescein angiography, indocyanine green angiography, optical coherence tomography and fundus autofluorescence imaging can be used to diagnose and obtain additional information about APMPPE. Fundus autofluorescence imaging has proven to be a useful non-invasive tool, as the fundus autofluorescence signal primarily originates from the lipofuscin accumulation within the retinal pigment epithelium, which reflects its function. Fundus autofluorescence imaging in APMPPE is reported to show characteristic findings that include hypoautofluorescent lesions during the acute phase and increasing hyperautofluorescence during the recovery phase. In this report, we describe a case of unilateral and recurrent APMPPE with a medical history of chronic thyroiditis and splenectomy. Unique fundus autofluorescence findings were observed throughout the clinical course in this patient. CASE REPORT

A novel heterozygous splice site OPA1 mutation causes exon 10 skipping in Japanese patients with dominant optic atrophy

Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan; Department of Ophthalmology, Kanagawa Children’s Medical Center, Yokohama, Japan; Laboratory of Visual Physiology, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan; Research Center for Medical Science, Core Research Facilities for Basic Science (Molecular Genetics), The Jikei University School of Medicine, Tokyo, Japan

Retinal Ganglion Cell Loss in X-linked Adrenoleukodystrophy with an ABCD1 Mutation (Gly266Arg)

Abstract The authors here report a single case of a 10-year-old male patient who presented with severe vision loss associated with progressive demyelination. The patient was diagnosed with X-linked childhood cerebral adrenoleukodystrophy (ALD). Genetic analysis demonstrated a missense mutation (Gly266Arg) in exon 1 of the ABCD1 gene. His corrected visual acuity confirmed the absolute lack of light perception in both eyes. Funduscopy revealed severe pallor of the optic disc in both eyes. Spectral-domain optical coherence tomography showed thinning of the retinal ganglion cell and inner plexiform layers (GCL and IPL). Thinning of the GCL and IPL may be due to transneuronal retrograde degeneration of ganglion cells secondary to optic tract demyelination.