Hiroshi Tsuneoka

Feasibility of ultrasound cataract surgery with a 1.4 mm incision

Purpose: To study the feasibility of performing ultrasound (US) phacoemulsification cataract surgery through a 1.4 mm incision using conventional phacoemulsification equipment but removing the infusion sleeve from the US tip. Setting: Department of Ophthalmology, Jikei University, Tokyo, Japan. Methods: The infusion sleeve was removed from a 20 gauge US tip, and the sleeveless tip was inserted in a 1.4 mm incision in a postmortem porcine eye, providing infusion through a side port; phacoemulsification was performed with the US tip occluded. Temperature at the incision site was measured with a thermometer to determine whether a thermal burn occurred during the process. A hooked infusion cannula with a widened inner channel and 3 apertures was used to stabilize the anterior chamber depth. Results: Ultrasound phacoemulsification produced almost no temperature elevation at the incision site as long as the infusion liquid was adequately circulated around the US tip. With the 20 gauge US tip, an adequate volume of leakage was maintained through the 1.4 mm incision; no thermal burns developed at the incision site. The use of a hooked infusion cannula made it possible to stabilize the anterior chamber and to apply the bimanual nucleofractis technique to emulsify and aspirate the lens nucleus. Conclusion: Using a sleeveless 20 gauge US tip, US cataract surgery was safely performed through a 1.4 mm incision without producing thermal burns at the incision site.

Ultrasonic phacoemulsification using a 1.4 mm incision: clinical results

Purpose: To evaluate the intraoperative complications and postoperative results of bimanual phacoemulsification and aspiration using a sleeveless phaco tip inserted through an ultra‐small incision. Setting: Department of Ophthalmology, Jikei University, Tokyo, Japan. Methods: This study comprised 637 eyes having cataract extraction using conventional phacoemulsification equipment. A 20‐gauge phaco tip with the sleeve removed was inserted through a 19‐gauge corneal incision. A 20‐gauge hooked cannula with the wall thinned to increase the inner diameter was used for infusion. After the crystalline lens was removed, the incision was widened to 2.8 to 4.1 mm and and an intraocular lens (IOL) was implanted. Study parameters were operating time, amount of infusion solution used, incidence of intraoperative complications, and early postoperative results. Results: The mean operating time was 8 minutes 42 seconds. Although the nuclear hardness was grade 4 or above in 35 eyes, there were no cases of thermal burn. The amount of infusion solution and the rate of postoperative decrease in corneal endothelial cell density did not differ greatly from results of conventional methods. This technique induced considerably less corneal astigmatism than surgery using conventional corneal incisions. Conclusions: A sleeveless phaco tip was used to perform successful bimanual phacoemulsification using conventional phaco machines and familiar surgical techniques. The cataracts were safely removed through an incision of 1.4 mm or smaller that was widened for IOL insertion.

Subfoveal choroidal thickness in multiple evanescent white dot syndrome

Background:  Multiple evanescent white dot syndrome (MEWDS) is an inflammation of the choriocapillaris, which typically presents with unilateral vision loss and is characterised by the presence of multiple yellow‐white spots in the posterior pole to the midperipheral fundus. This study was conduced to evaluate subfoveal choroidal thickness between the acute and convalescent phases in two patients with MEWDS.

Ultrasmall-incision bimanual phacoemulsification and AcrySof SA30AL implantation through a 2.2 mm incision.

&NA; Phacoemulsification and aspiration were performed with a sleeveless ultrasound tip through an ultrasmall incision (1.2 to 1.4 mm) using a 20‐gauge irrigating hook through a side port to infuse the anterior chamber. After the lens was extracted, the incision was enlarged to 2.2 mm and a single‐piece intraocular lens (AcrySof® SA30AL, Alcon) with an optic diameter of 5.5 mm was inserted. By modifying the new injector system, the AcrySof SA30AL could be inserted through a 2.2 mm incision in 100% of cases (63 eyes) in which it was feasible to use a thin lens having a central thickness of less than 20 diopters (D). A 2.2 mm incision was also used successfully in 54% of cases (42 of 78 eyes) that required a lens with a central thickness of 20 D or higher.

Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury.

Spermidine acts as an endogenous free radical scavenger and inhibits the action of reactive oxygen species. In this study, we examined the effects of spermidine on retinal ganglion cell (RGC) death in a mouse model of optic nerve injury (ONI). Daily ingestion of spermidine reduced RGC death following ONI and sequential in vivo retinal imaging revealed that spermidine effectively prevented retinal degeneration. Apoptosis signal-regulating kinase-1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase kinase kinase and has an important role in ONI-induced RGC apoptosis. We demonstrated that spermidine suppresses ONI-induced activation of the ASK1-p38 mitogen-activated protein kinase pathway. Moreover, production of chemokines important for microglia recruitment was decreased with spermidine treatment and, consequently, accumulation of retinal microglia is reduced. In addition, the ONI-induced expression of inducible nitric oxide synthase in the retina was inhibited with spermidine treatment, particularly in microglia. Furthermore, daily spermidine intake enhanced optic nerve regeneration in vivo. Our findings indicate that spermidine stimulates neuroprotection as well as neuroregeneration, and may be useful for treatment of various neurodegenerative diseases including glaucoma.

Whole Exome Analysis Identifies Frequent CNGA1 Mutations in Japanese Population with Autosomal Recessive Retinitis Pigmentosa

Objective The purpose of this study was to investigate frequent disease-causing gene mutations in autosomal recessive retinitis pigmentosa (arRP) in the Japanese population. Methods In total, 99 Japanese patients with non-syndromic and unrelated arRP or sporadic RP (spRP) were recruited in this study and ophthalmic examinations were conducted for the diagnosis of RP. Among these patients, whole exome sequencing analysis of 30 RP patients and direct sequencing screening of all CNGA1 exons of the other 69 RP patients were performed. Results Whole exome sequencing of 30 arRP/spRP patients identified disease-causing gene mutations of CNGA1 (four patients), EYS (three patients) and SAG (one patient) in eight patients and potential disease-causing gene variants of USH2A (two patients), EYS (one patient), TULP1 (one patient) and C2orf71 (one patient) in five patients. Screening of an additional 69 arRP/spRP patients for the CNGA1 gene mutation revealed one patient with a homozygous mutation. Conclusions This is the first identification of CNGA1 mutations in arRP Japanese patients. The frequency of CNGA1 gene mutation was 5.1% (5/99 patients). CNGA1 mutations are one of the most frequent arRP-causing mutations in Japanese patients.

Health- and vision-related quality of life in patients receiving infliximab therapy for Behçet uveitis

Objective To evaluate the changes in health-related and vision-related quality of life (HR-QoL and VR-QoL) in patients with Behçet uveitis (BU) receiving infliximab therapy. Methods Twenty patients with recurrent BU attacks were enrolled. All patients were treated with infliximab. We evaluated the mean number of uveitis attacks and the mean score of extraocular manifestations by Behçet disease current activity form (BDCAF) during the 6 months before and the 6 and 12 months after initiation of infliximab. The EuroQol-5D questionnaire (EQ-5D) and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were self-administered in all patients before treatment and, 6 and 12 months after treatment. Patients’ pre- and post-treatment EQ-5D and NEI VFQ-25 scores were compared. Results By the 6- and 12-month follow-up, the frequency of uveitis attacks and the BDCAF scores was significantly decreased compared with the 6 months before starting infliximab (p<0.0001). Fully completed questionnaires were received from all patients. Infliximab therapy was associated with a significant improvement of the EQ-5D (p<0.0001), NEI VFQ-25 composite score (p=0.0001), general health score (p=0.0001) and mental health score (p=0.0001). This result shows a significant decrease in inflammatory activity of the disease and consequently improvement in HR-QoL and VR-QoL scores with a rising response pattern in all dimensions. Conclusions Relief of uveitis attacks and extraocular manifestations by infliximab therapy significantly improved the HR-QoL and VR-QoL in patients with BU.

A Novel Haplotype with the R345W Mutation in the EFEMP1 Gene Associated with Autosomal Dominant Drusen in a Japanese Family

PURPOSE To describe ophthalmic and molecular genetic findings in a family of Japanese patients with Malattia leventinese (ML)/Doyne honeycomb retinal dystrophy (DHRD), also known as autosomal dominant drusen. METHODS Four patients with ML/DHRD, including a 42-year-old female proband, were ascertained. The proband underwent complete ophthalmic examinations, including fundus and electrodiagnostic investigations, and Humphrey visual field (VF) perimetry. Mutation screening of the EFEMP1 gene and haplotype analysis were performed in the family, an Indian ML/DHRD family, and a branch of 1 of 39 ML/DHRD families in the United States, in which all affected patients shared a common haplotype. RESULTS A heterozygous missense mutation (p.R345W) was identified in all four Japanese patients and in affected patients of the other two families. This mutation was the only mutation that has been exclusively found in the gene. The disease haplotype in the Japanese family was different from those of the other two families. Clinically, central retinas were prominently affected in the proband and her mother, and subsequently the proband developed subfoveal choroidal neovascularization in the left eye, whereas her younger sister with the mutation, who was asymptomatic, exhibited only fine macular drusen. Long-term follow-up of Humphrey VF and multifocal-electroretinography (mfERG) in the proband also revealed progressive attenuation of macular function in the right eye. CONCLUSIONS This is the first report to describe a Japanese family with variable expressivity of ML/DHRD, in which a novel disease haplotype was identified. Humphrey VF and mfERG testing may be helpful in determining the long-term outcome of macular function.

White matter consequences of retinal receptor and ganglion cell damage.

PURPOSE Patients with Leber hereditary optic neuropathy (LHON) and cone-rod dystrophy (CRD) have central vision loss; but CRD damages the retinal photoreceptor layer, and LHON damages the retinal ganglion cell (RGC) layer. Using diffusion MRI, we measured how these two types of retinal damage affect the optic tract (ganglion cell axons) and optic radiation (geniculo-striate axons). METHODS Adult onset CRD (n = 5), LHON (n = 6), and healthy controls (n = 14) participated in the study. We used probabilistic fiber tractography to identify the optic tract and the optic radiation. We compared axial and radial diffusivity at many positions along the optic tract and the optic radiation. RESULTS In both types of patients, diffusion measures within the optic tract and the optic radiation differ from controls. The optic tract change is principally a decrease in axial diffusivity; the optic radiation change is principally an increase in radial diffusivity. CONCLUSIONS Both photoreceptor layer (CRD) and retinal ganglion cell (LHON) retinal disease causes substantial change in the visual white matter. These changes can be measured using diffusion MRI. The diffusion changes measured in the optic tract and the optic radiation differ, suggesting that they are caused by different biological mechanisms.

Retinal cone and rod photoreceptor cells exhibit differential susceptibility to light‐induced damage

J. Neurochem. (2012) 121, 146–156.