Yoshiko Takai

Concentration of vascular endothelial growth factor in aqueous humor of eyes with advanced retinopathy of prematurity before and after intravitreal injection of bevacizumab.

Purpose: To determine whether an intravitreal injection of bevacizumab alters the concentration of vascular endothelial growth factor (VEGF) in the aqueous humor of eyes with retinopathy of prematurity. Methods: Seven Stage 4 and three Stage 5 eyes of eight patients with retinopathy of prematurity were studied. Bevacizumab (0.75 mg/0.03 mL/eye) was injected intravitreally in six eyes of six patients after approval was obtained from the Institutional Review Board of Nagoya University Hospital and an informed consent was signed by the parents. Aqueous humor was collected just before the surgery or before the intravitreal injection of bevacizumab. Aqueous humor was also collected immediately before vitrectomy 4 to 48 days after the injection of bevacizumab. Aqueous humor was also collected from four patients undergoing congenital cataract surgery as controls. The concentration of VEGF was measured by enzyme-linked immunosorbent assay. Results: In the 4 control eyes, the concentration of VEGF in 2 eyes was 156 and 158 pg/mL and was not detectable in the other 2 eyes. The average concentration of VEGF was 1,109 pg/mL in the active Stage 4 eyes and 3,520 pg/mL in the active Stage 5 eyes. After bevacizumab injection, the unbound VEGF concentration was 60, 230, and 290 pg/mL in 3 eyes and not detectable in 1 eye. Conclusion: Intravitreal bevacizumab resulted in a marked decrease in the unbound VEGF concentration in eyes with retinopathy of prematurity.

Morphological study of acute zonal occult outer retinopathy (AZOOR) by multiplanar optical coherence tomography

Purpose:  We set out to determine whether morphological retinal changes occur in patients with acute zonal occult outer retinopathy (AZOOR).

Development of Stereoscopic Acuity: Longitudinal Study Using a Computer-based Random-dot Stereo Test

PurposeTo investigate the development of stereoscopic acuity (stereoacuity) in children longitudinally.MethodsSeven full-term normal infants whose age at the beginning of the study was between 12 and 23 weeks were studied. A computer-based random-dot test of stereoscopic vision (TV-Random Dot Stereo Test) was used to measure stereoacuity. The test was repeated at 2- to 3-month intervals until the children reached 2 years of age, and then every 6 to 12 months until they reached 5 years of age.ResultsAll of the infants were found to have a stereoacuity of 2480 seconds of arc (2480″) with this test by 26 weeks of age. The first reliable measurement of stereoacuity was obtained from a 16-week-old infant. Stereoacuity did not improve significantly between 6 and 12 months, but it improved rapidly after 12 months. All children had a stereoacuity of 100″ with the Titmus Stereo Tests at 5 years of age, but the best stereoacuity with the TV-Random Dot Stereo Test was 229″ at 28.9 months.ConclusionsThe development of stereoacuity studied longitudinally was similar to that obtained by cross-sectional studies. The TV-Random Dot Stereo Test is a useful program for measuring stereopsis in preverbal children. Jpn J Ophthalmol 2005;49:1–5

Two types of non-selective cation channel opened by muscarinic stimulation with carbachol in bovine ciliary muscle cells

In the ciliary muscle, the tonic contraction requires a sustained influx of Ca2+ through the cell membrane. However, little has hitherto been known about the route(s) of Ca2+ influx in this tissue that lacks voltage‐gated Ca2+ channels. To identify ion channels as the Ca2+ entry pathway we studied the effects of carbachol (CCh) on freshly isolated bovine ciliary muscle cells by whole‐cell voltage clamp. Experiments were carried out using pipettes filled with K+‐free solution containing 100 mm caesium aspartate, 5 mm BAPTA and 180 μm GTP (pH 7.0; the intracellular free Ca2+ concentration, [Ca2+]i= 70 nm). CCh evoked an inward current showing polarity reversal at a holding potential near 0 mV. Analysis of the current noise distinguished two types of non‐selective cation channel (NSCCL and NSCCS) with widely different unitary conductances (35 pS and 100 fS). The ratios of the permeabilities to Li+, Na+, Cs+, Mg2+, Ca2+, Sr2+ and Ba2+, estimated by cation replacement procedures, were 0.9: 1.0: 1.5: 0.2: 0.3: 0.4: 0.5 for NSCCL, and 1.0: 1.0: 1.8: 2.5: 2.6: 3.2: 5.0 for NSCCS. NSCCS, but not NSCCL, was strongly inhibited by elevation of [Ca2+]i. Both NSCCL and NSCCS were dose‐dependently inhibited by 1–100 μm SKF96365, La3+ and Gd3+, which also inhibited the tonic component of the contraction produced in muscle bundles by CCh without markedly affecting the initial phasic component. NSCCL and/or NSCCS may serve as a major Ca2+ entry pathway required for sustained contraction of the bovine ciliary muscle. RT‐PCR experiments in the bovine ciliary muscle (whole tissue) detected mRNAs of several transient receptor potential (TRP) channel homologues (TRPC1, TRPC3, TRPC4 and TRPC6), which are now regarded as possible molecular candidates for receptor‐operated cation channels.

Activation of non-selective cation conductance by carbachol in freshly isolated bovine ciliary muscle cells

Abstract In smooth muscle cells freshly isolated from the bovine ciliary body, effects of carbachol (CCh) on the membrane potential and current were examined by the whole-cell clamp method. The resting membrane potential of the muscle cells used was –60 ± 1 mV (n=111). Extracellular application of CCh (2 μM) depolarized the cells to –15 ± 5 mV (n=50) with an apparent increase in membrane conductance. Under voltage-clamp conditions, CCh (2 μM) evoked an inward current which exhibited inward-going rectification and reversed the polarity at about 0 mV. Removal of Na+ from the external solution caused a reduction of the amplitude of the current and a shift of the reversal potential to the negative direction. CCh was able to elicit an inward current even under a condition where Ca2+ was the only cation producing an inwardly directed electrochemical gradient. The current was not affected by verapamil or by tetrodotoxin. The CCh-induced current was inhibited by antimuscarinic agents with the affinity sequence: atropine ≈4–DAMP >> pirenzepine > AF-DX116, indicating that the response is mediated by a muscarinic cholinoceptor that belongs to the M3-subtype. Unlike the non-selective cation channel current in intestinal smooth muscles, which is activated by elevation of the intracellular Ca2+ concentration ([Ca2+]i), the current of the ciliary muscle was inactivated when the [Ca2+]i was increased. The conductance, which admits Ca2+, may serve as a pathway for Ca2+ entry required for contraction.

Macular oedema as a sign of preventable neurological disease in a 17-year-old man

over his left temple on left gaze. He did not have any visual disturbance, but reported an occasional loss of consciousness and a floating sensation. His medical history included measles at 8 months of age. At the first examination, his visual acuity was 1.5 in both eyes (OU). The findings in the slit-lamp examination were normal but ophthalmoscopy showed a linear arcuate lesion in the macular area of the left eye with a dot haemorrhage at the temporal margin (Fig. 1A,B). The retina around the lesion was oedematous, and the oedema extended to a prominent arteriovenous crossing at the superotemporal arcade (Fig. 1). The superotemporal artery was narrow, and the veins of the superior and inferior temporal areas were dilated (Fig. 1A,B). Optical coherence tomography (OCT3; Zeiss, Dublin, California, USA) showed a localized cavity that extended from the outer plexiform layer to the retinal pigment epithelial layer (RPE) but the defect did not extend into the choroid (Fig. 1C, a–f). There was a small hole in the nerve fibre layer (Fig. 1B, b,d) that appeared to be the cross-section of a dilated vessel. OCT Ophthalmoscopic (Ophthalmic Technologies Inc., Toronto, Ontario, Canada; Nidek Co. Ltd, Nagoya, Japan) scans parallel to the retinal surface showed a linear dark region that corresponded to the linear legion, and a hyper-intensity structure near the optic disc (Fig. 2A, d). Full blood counts and differential white cell count were within normal limits. Screening for the 12 most frequent parasites in Japan by multiple dot enzyme-linked immunosorbent assay (ELISA) was negative, thus eliminating a migrating larva as the cause of the lesion. Angioid streaks and traumatic choroidal rupture were eliminated as the cause of the lesion because OCT showed that the changes were confined to the retina. The retinal oedema disappeared in 1 week but the arcuate lesion remained (Fig. 2B, a). A cross-sectional image of the linear lesion showed a cavity that extended from the nerve fibre layer to the RPE (Fig. 2C). Scanning laser ophthalmoscopy (SLO) recorded 1 week later showed the retinal defect around the vessels (Fig. 2D). Six months later, the patient’s family noticed abnormal involuntary movements and an intellectual deterioration of the patient. He soon developed severe convulsions and required respiratory assistance. An examination of the cerebrospinal fluid showed an elevation of anti-measles antibodies (IgG 12.8 mg ⁄dl). Taking these findings together, a diagnosis of subacute sclerosing panencephalitis (SSPE) was made. At the final examination a year later, the patient’s fundus showed the linear scar but the venous congestion was not seen. The ocular manifestations of SSPE are: chorioretinitis with pigment clumping (De Laey et al. 1983; Zagami & Lethlean 1991), retinal vasculitis (Salmon et al. 1991) and serous macular detachment (De Laey et al. 1983). Retinal striae with oedema and pigment clumping (Zagami & Lethlean 1991) has also been reported. De Laey reported the results of a histopathological study of an eye belonging to a patient with SSPE (De Laey et al. 1983). The external plexiform layer was slightly oedematous, the RPE layer was thin with proliferation, and optic nerve showed hypercellularity in its supreficial temporal portion without any obvious ophthalmoscopic abnormalities. The linear lesion was detected as a rupture of the internal limiting membrane. In our patient, the alterations extended from the nerve fibre layer to the RPE layer. The external plexiform layer was thicker, and the RPE was partially obscured (Fig. 1B-f); it was too indistinct to say that it was depigmentation. The optic discs appeared normal but ocular pain with eye movements may be a sign of an occult inflammation of the optic disc. Zako et al. (2008) reported a marked decrease in foveal thickness in the OCT findings in a patient with SSPE. In our patient, the lesion was focal and the retinal thickness at the last examination was not decreased. Diagnosis ⁄ Therapy in Ophthalmology

Bilateral lacrimal caruncle lesions

ABSTRACT A 65-year-old man was referred to our hospital for the treatment of a lesion on the medial lacrimal canthus of both eyes. He had a history of perinuclear anti-neutrophil cytoplasmic antibodies, i.e., pANCA-positive interstitial pneumonia. Orbital magnetic resonance imaging excluded space occupying lesions, and laboratory testing excluded thyroid-related diseases. The masses were excised, and histopathological examinations showed sebaceous gland hyperplasia and inflammatory changes around the gland. In addition, the specimen from the left eye showed a retention cyst possibly caused by an infection. It was also possible that the use of steroid was involved in the development of the lesions. A relationship between the ANCA and the lesions was not completely eliminated.

Usefulness of Trial Fresnel Membrane Prisms before Prism Glasses Prescription to Improve Double Vision in Adults

【Purpose】To examine the usefulness of Fresnel membrane prisms (Fresnel membranes) used in a trial before prescribing prism glasses for adults to improve double vision. 【Subjects and Method】Subjects were 105 patients (age, ≥ 20 years) who visited Nagoya University Hospital between January 1st, 2010 and December 31st, 2013 and complained of experiencing double vision. Of 105, 66 underwent a trial using Fresnel membranes before receiving prescribed prism glasses and 39 received prescribed glasses without a trial. By reviewing the medical records of these patients, we retrospectively investigated the duration of the Fresnel membrane trial, patientʼ s prescription type after the trial, frequency of prism power change of the Fresnel membranes during the trial, and use of the prism glasses three months after the prescription. 【Results】Of the 66 patients who had undergone the trial, 21 were prescribed with Fresnel prism glasses, 20 received built-in prism glasses, 4 had combined Fresnel and built-in prisms, 16 did not need prisms because their double vision was resolved, and 5 were not prescribed with any prisms because they could not adjust to the prisms. Among the subjects who underwent the trial for more than 1 month, 74% experienced prism power change of the Fresnel membranes for more than once. All the subjects who had undergone the trial could continue to wear their prescription prism glasses three months after the prescription. On the other hand, of the 39 patients who had not undergone the trial, 29 could continue to wear the prescription glasses, 3 had to change the prescription, and 7 discontinued. As compared to the subjects without the trial, a significantly higher number of the subjects who had experienced the trial Fresnel prisms could continue to wear their prescription glasses (P < 0.01). 【Conclusion】Before the prescription of prism glasses for adults with diplopia, a trial using the Fresnel membranes prisms appeared to be useful to determine the accurate type and power of the prism glasses and to help the patients continue to wear the prism glasses.

Surgical correction of caruncular distortion after medial rectus resection.

Strabismus surgery can lead to successful eye alignment but may cause scarring and distortion of conjunctiva and adjacent structures in some cases. We report two patients who developed epiphora when the lacrimal caruncles became distorted after strabismus surgery. Both cases followed successful medial rectus muscle resections for exotropia. A simple excision of the caruncles improved the epiphora and produced a satisfactory appearance.