A Case of Strabismus Fixus With Extremely Long Axial Length Results in Improvement of Limitation of Abduction by the Yokoyama Procedure.

Acquired strabismus in high myopia is typically fixed in the positions of adduction and depression, with restrictions in both abduction and elevation. As a treatment for myopic strabismus fixus, the Yokoyama procedure is effective. We report a case of strabismus fixus with a long axial length (34 mm), in which abduction limitation was improved by the Yokoyama procedure with medial rectus recession. A 68-year-old woman was referred for strabismus fixus in her right eye. Her right eye was fixed in the positions of adduction and depression, with restrictions in both abduction and elevation. The axial length of her right eye was extremely long 33.97mm. Magnetic resonance imaging (MRI) showed that the posterior eyeball of her right eye had dislocated out of the superotemporal muscle cone, and she was diagnosed with strabismus fixus with high myopia. She underwent the Yokoyama procedure in her right eye, and medial rectus recession was performed at the same time because abduction limitations remained at the end of the Yokoyama procedure. After surgery, there was a small residual esotropia, but abduction beyond the midline was possible, and the patient's satisfaction was high. A combination of the Yokoyama procedure and medial rectus recession for a patient with myopic strabismus fixus with long axial length resulted in good improvement of ocular misalignment and limitation of abduction.

The practical and educational value of scleral buckling with chandelier illumination.

PURPOSE: To compare the surgical results in cases of primary rhegmatogenous retinal detachments between standard scleral buckling (SSB) and scleral buckling with chandelier illumination (SBC) and to analyse the differences in SBC surgical results between an experienced ophthalmologist and inexperienced ophthalmologists. METHODS: Consecutive surgical case series of 155 eyes that underwent scleral buckling were retrospectively reviewed and divided into four groups: SSB performed by an experienced ophthalmologist (n = 54), SBC performed by an experienced ophthalmologist (n = 52), SBC performed by inexperienced ophthalmologists (n = 40) and SSB performed by inexperienced ophthalmologists (n = 9). Then, these four groups were compared. RESULTS: No significant differences were observed between SSB and SBC procedures both performed by the experienced ophthalmologist with regard to demographics, preoperative findings, contents of the surgery, intraoperative complications, retinal reattachment, postoperative findings and postoperative complications. Between SBC performed by the experienced ophthalmologist and SBC performed by the inexperienced ophthalmologists, no significant differences were found regarding intraoperative complications, retinal reattachment, postoperative findings and postoperative complications. Between SSB and SBC procedures both performed by the inexperienced ophthalmologist, a significant difference was found regarding intraoperative complications. CONCLUSION: There were no significant differences in surgical results between SSB and SBC when both were performed by the experienced ophthalmologist. In addition, the surgical results were equal between the experienced ophthalmologist and the inexperienced ophthalmologist as far as SBC was concerned. Learning scleral buckling skills by using SBC is a reasonable course of action for inexperienced ophthalmologists.

Long-read sequencing for non-small-cell lung cancer genomes.

Here, we report the application of a long-read sequencer, PromethION, for analyzing human cancer genomes. We first conducted whole-genome sequencing on lung cancer cell lines. We found that it is possible to genotype known cancerous mutations, such as point mutations. We also found that long-read sequencing is particularly useful for precisely identifying and characterizing structural aberrations, such as large deletions, gene fusions, and other chromosomal rearrangements. In addition, we identified several medium-sized structural aberrations consisting of complex combinations of local duplications, inversions, and microdeletions. These complex mutations occurred even in key cancer-related genes, such as STK11, NF1, SMARCA4, and PTEN The biological relevance of those mutations was further revealed by epigenome, transcriptome, and protein analyses of the affected signaling pathways. Such structural aberrations were also found in clinical lung adenocarcinoma specimens. Those structural aberrations were unlikely to be reliably detected by conventional short-read sequencing. Therefore, long-read sequencing may contribute to understanding the molecular etiology of patients for whom causative cancerous mutations remain unknown and therapeutic strategies are elusive.

MoMI-G: modular multi-scale integrated genome graph browser.

BACKGROUND: Genome graph is an emerging approach for representing structural variants on genomes with branches. For example, representing structural variants of cancer genomes as a genome graph is more natural than representing such genomes as differences from the linear reference genome. While more and more structural variants are being identified by long-read sequencing, many of them are difficult to visualize using existing structural variants visualization tools. To this end, visualization method for large genome graphs such as human cancer genome graphs is demanded. RESULTS: We developed MOdular Multi-scale Integrated Genome graph browser, MoMI-G, a web-based genome graph browser that can visualize genome graphs with structural variants and supporting evidences such as read alignments, read depth, and annotations. This browser allows more intuitive recognition of large, nested, and potentially more complex structural variations. MoMI-G has view modules for different scales, which allow users to view the whole genome down to nucleotide-level alignments of long reads. Alignments spanning reference alleles and those spanning alternative alleles are shown in the same view. Users can customize the view, if they are not satisfied with the preset views. In addition, MoMI-G has Interval Card Deck, a feature for rapid manual inspection of hundreds of structural variants. Herein, we describe the utility of MoMI-G by using representative examples of large and nested structural variations found in two cell lines, LC-2/ad and CHM1. CONCLUSIONS: Users can inspect complex and large structural variations found by long-read analysis in large genomes such as human genomes more smoothly and more intuitively. In addition, users can easily filter out false positives by manually inspecting hundreds of identified structural variants with supporting long-read alignments and annotations in a short time. SOFTWARE AVAILABILITY: MoMI-G is freely available at https://github.com/MoMI-G/MoMI-G under the MIT license.

Scleral buckling procedure with chandelier illumination for pediatric rhegmatogenous retinal detachment.

PURPOSE: To assess the treatment of pediatric patients with rhegmatogenous retinal detachment (RRD) by scleral buckling with chandelier illumination. METHODS: Three eyes were treated in three patients, healthy boys aged 7 years, 12 years, and 11 years, with RRD, macular involvement, and small retinal holes, of which two were preoperatively undetectable. Conventional scleral buckling with cryoretinopexy was performed under the contact lens for vitreous surgery or noncontact wide-angle viewing system using 27-gauge twin chandelier illumination. RESULTS: The only known predisposing factor for retinal detachment was myopia stronger than 3 D with lattice retinal degeneration in two of the three patients. Retinal reattachment was achieved in all cases without intra- or postoperative complications. However, visual recovery was limited in one of the three patients. CONCLUSION: Scleral buckling with chandelier illumination is effective for pediatric RRD, especially if the retinal hole is difficult to detect preoperatively. However, visual recovery was sometimes limited because of macular involvement due to late diagnosis, which is one of the characteristic features of pediatric RRD.

Familial cases of Norrie disease detected by copy number analysis.

PURPOSE: Norrie disease (ND, MIM#310600) is an X-linked disorder characterized by severe vitreoretinal dysplasia at birth. We report the results of causative NDP gene analysis in three male siblings with Norrie disease and describe the associated phenotypes. METHODS: Three brothers with suspected Norrie disease and their mother presented for clinical examination. After obtaining informed consent, DNA was extracted from the peripheral blood of the proband, one of his brothers and his unaffected mother. Exons 1-3 of the NDP gene were amplified by polymerase chain reaction (PCR), and direct sequencing was performed. Multiplex ligation-dependent probe amplification (MLPA) was also performed to search for copy number variants in the NDP gene. RESULTS: The clinical findings of the three brothers included no light perception, corneal opacity, shallow anterior chamber, leukocoria, total retinal detachment and mental retardation. Exon 2 of the NDP gene was not amplified in the proband and one brother, even when the PCR primers for exon 2 were changed, whereas the other two exons showed no mutations by direct sequencing. MLPA analysis showed deletion of exon 2 of the NDP gene in the proband and one brother, while there was only one copy of exon 2 in the mother. CONCLUSION: Norrie disease was diagnosed in three patients from a Japanese family by clinical examination and was confirmed by genetic analysis. To localize the defect, confirmation of copy number variation by the MLPA method was useful in the present study.

Histopathologic analysis of the internal limiting membrane surgically peeled from eyes with diffuse diabetic macular edema.

PURPOSE: To investigate the pathogenesis of diffuse diabetic maculae edema (DME). METHODS: Internal limiting membrane (ILM) specimens were surgically peeled from 16 eyes of 15 patients with diffuse DME (diabetic retinopathy (DR) group) and from 12 eyes of 12 patients without diabetes (non-DR group). The specimens were then examined by light microscopy (LM), transmission electron microscopy (TEM), and immunohistochemistry. RESULTS: Examination by LM revealed numerous cells on the inner surface of the ILM specimens in the DR-group, among which five different cell types (glial cell, fibroblast-like cell, macrophages, neutrophils, and lymphocytes) were confirmed. Examination by TEM revealed that the thickness of the peeled ILMs in the DR group was significantly greater, and four types of cellular element (glial, fibroblast-like, macrophages, and lymphocytes) were confirmed on the surface of the vitreous side of the specimens. The existence of glial cells and macrophages was confirmed by immunohistochemistry. CONCLUSIONS: In diffuse DME, the ILM is thickened and a variety of cellular elements, especially numerous kinds of inflammatory cell, adhere to the inner surface of the ILM. To attenuate diffuse DME, vitrectomy combined with ILM peeling to remove the inflammatory cells and the physical barrier might be effective.

A case of oculodentodigital dysplasia syndrome with novel GJA1 gene mutation.

PURPOSE: To report a case of oculodentodigital dysplasia syndrome (ODDD) with a heterozygous mutation in GJA1 (connexin 43) gene. METHODS: A 9-year-old girl visited our hospital complaining of visual disturbances. The patient had microphthalmia, a small nose with hypoplastic alae nasi, and syndactyly. Visual acuity with prescribed glasses improved to 0.5 (1.2) OU 2 months after the first visit. She was satisfied with the new glasses and the improvement in visual acuity. Genomic DNA was extracted from leukocytes of the patient's peripheral blood in accordance with standard procedures, after obtaining parental informed consent. We amplified GJA1 exon 2 from her genomic DNA by the PCR method, and sequenced the product using the dye terminator method. RESULTS: S5C (c. 13A > T), a novel mutation in exon 2 of GJA1, was found in the patient. The parents had no mutation of GJAI, nor was there any sign of abnormality in other family members. No similar mutation could be found in the 50 genotyped normal subjects in the control group. CONCLUSIONS: A novel GJA1 mutation was detected in a Japanese ODDD patient. Glaucoma complications associated with ODDD have already been reported. Careful long-term monitoring and treatment are also necessary.

Bilateral anterior granulomatous keratouveitis with sunset glow fundus in a patient with autoimmune polyglandular syndrome.

AIM: To report the case of a patient with bilateral anterior granulomatous keratouveitis and sunset glow fundus. METHOD: Review of case record. RESULTS: A 15-year-old patient had bilateral anterior granulomatous keratouveitis and sunset glow fundus similar to findings in Vogt-Koyanagi-Harada disease (VKH). However, the patient also suffered additional autoimmune disease against endocrine glands. In addition to anti-thyroid antibody and anti-glutamic acid decarboxylase antibody, anti-melanocyte autoantibody was detected in serum from this patient. The authors finally diagnosed autoimmune polyglandular syndrome. CONCLUSION: If resistance against treatment exists for VKH, particularly in pediatric cases, this disease should be considered and other endocrine disorders examined.

[A clinical study of intraocular malignant lymphoma].

PURPOSE: We investigated whether vitreous cytology and the measurement of intravitreous cytokine were useful for the diagnosis of intraocular malignant lymphoma. SUBJECTS AND METHODS: 8 eyes of 5 patients with suspected intraocular malignant lymphoma during the past 15 months. 3 vitreous samples were collected from 3 patients at the time of pars plana vitrectomy. Polymerase chain reaction(PCR) amplification and flowcytometric analysis(FACS) of the vitreous samples were performed. Interleukin (IL)-10 and IL-6 concentrations were measured. RESULTS: Vitreous cytology showed increased atypical B lymphocytes. The vitreous IL-10/IL-6 ratio was higher than 1 in all cases. Monoclonal rearrangement of the immunoglobulin heavy chain gene and the light chain restriction of immunoglobulin were detected. CONCLUSION: The detection of the monoclonality of infiltrated cells into the vitreous by PCR amplification and FACS, and the measurements of IL-10 and IL-6 concentrations in the vitreous fluid may be useful in the diagnosis of intraocular malignant lymphoma.

[Retinopathy of prematurity in extremely low birth weight infants: a Tokyo multicenter study].

OBJECTIVE: To investigate how the increase in survival rate in extremely low birth weight (a birth weight of 1,000 g or less) infants had affected the incidence of retinopathy of prematurity (ROP) and the frequency of laser treatment. METHODS: We retrospectively reviewed the medical records of 122 surviving premature infants with birthweights less than 1,000 g to determine the severity of ROP observed at 16 neonatal intensive care units in Tokyo between April and October 2002. RESULTS: The survival rate was 85.6%. The mean gestational age was 26.74 weeks and the mean birth weight was 782.25 g. One-hundred-and-five infants (86.1%) developed ROP, fifty (41.0%) received laser treatment, and six (4.9%) had retinal detachment. The median postmenstrual age (gestational age at birth plus chronological age in weeks, PMA) at the onset of ROP was 32.5 weeks, and the first laser treatment was performed at the median PMA of 35.7 weeks. CONCLUSIONS: In these extremely low birth weight infants, there was an increase in the survival rate and in the incidence of severe ROP that progressed to the stage that required treatment.

A case of Kniest dysplasia with retinal detachment and the mutation analysis.

PURPOSE: To report a case of Kniest dysplasia with retinal detachment associated with a novel type II collagen gene (COL2A1) mutation. DESIGN: Interventional case report. METHODS: DNA was isolated from peripheral lymphocytes, and mutational analysis was carried out using polymerase chain reaction and direct sequencing. RESULTS: A 14-year-old Japanese boy was diagnosed with Kniest dysplasia, and ophthalmic examination revealed a retinal detachment in the right eye. He was successfully treated by vitrectomy and silicon oil injection, and his visual acuity improved from 0.01 to 0.22. DNA analysis of COL2A1 revealed a single base-pair substitution at position +5 of intron 20. CONCLUSION: Vitrectomy and silicon oil injection were effective in reattaching the retinal detachment in a Kniest dysplasia patient. The genetic alteration found in this patient suggested that this prevented the normal splicing of COL2A1, resulting in an abnormal type II collagen product.