[Characteristics of Fifty Cases of Pituitary Tumors in Eyes Diagnosed with Glaucoma].

PURPOSE: To determine the characteristics of 50 cases of pituitary tumor. METHODS: The medical records of 50 cases of pituitary tumor found in glaucoma patients treated between June 2013 and June 2014 were reviewed. RESULTS: There were 37 women and 13 men whose average age was 55.7 years with a range of 24 to 79 years. The glaucoma was unilateral in 19 and bilateral in 31. The pituitary tumors were classified as Rathke's Cleft Cyst (RCC) in 38 cases (76%), RCC with Cushing disease in 5 (10%), adenoma in 4 (8%), adenoma + growth hormone (GH) producing tumors in 2 (4%), and RCC with adenoma in 1 (2%). Of the 50 patients, 23 were treated by surgery (46%), 2 (4%) by hormone supplement therapy, 2 (4%) rejected therapy, and 23 (46%) were followed without treatment. The visual field defects corresponded with typical pituitary visual field defects in 26 (52%) cases, with that typical of unilateral glaucoma in 6 (23%), and with that typical of bilateral glaucoma in 20 (77%) cases. The major symptom was headaches in 24 (48%), headache with dizziness in 10 (20%), dizziness in only 8 (16%), and no complaints in 8 (16%). CONCLUSIONS: Fifty patients diagnosed with glaucoma had concurrent pituitary tumors. Special attention must be paid to glaucoma patients who complain of headaches with and without dizziness.

Optic Neuritis Caused by Rathke's Cleft Cyst in Young Adult.

We report a case of right optic neuritis caused by Rathke's cleft cyst (RCC) in a young adult. A 15-year-old boy presented with reduced visual acuity in the right eye. He was diagnosed with optic neuritis in the right eye 4 years earlier at other clinics before he was referred to our department. During our one-year examinations, the cause of the reduced vision in his right eye could not be determined conclusively. At the age of 17 years, a RCC was detected by a neurosurgeon who specialized in hypophyseal diseases. He underwent microscopic transsphenoidal resection of the cyst, and his vision recovered to 1.2 and he has had no recurrence for at least 9 months. We suggest that repeated rupturing of the RCC was the cause of the optic neuritis, and a RCC can be successfully treated by surgery even after 3 years of optic neuritis.

Magnetic resonance imaging in case of cortical apex syndrome caused by varicella zoster virus.

We present a case of orbital apex syndrome that developed after a re-activation of varicella zoster virus. The magnetic resonance imaging showed signs of a diffuse inflammation of the ipsilateral orbital cavity, external ocular muscles and optic nerve. Pattern visually evoked cortical potentials were non-recordable by stimulating the affected eye.

Pattern visual evoked potentials in Japanese patients with multiple sclerosis without history of visual pathway involvement.

A delay of the peak latency of the pattern visual evoked cortical potentials (pVEP) is accepted as one of the paraclinical evidence for a diagnosis of multiple sclerosis (MS). The purpose of this study was to evaluate the pVEPs in Japanese patients with MS without a history of visual pathway involvement. We studied the medical records of 29 MS patients without any history of visual pathway involvement, and with visual acuity correctable to > or = 20/20. The Goldmann visual fields, pupillary light reflexes, and optic disks were normal in all. pVEPs elicited by 3 rev/s (transient) and 12 rev/s (steady-state) were recorded from the MS patients and compared with those recorded from normal subjects. The latency of the P100 component of the transient pVEPs was significantly prolonged in 9/29 (31%) MS patients. A phase lag in the steady-state pVEPs was found in 6/29 (21%) MS patients, and the mean amplitude was significantly smaller. The incidence of cases with abnormal pVEPs is lower than that reported from Europe and United State. This difference is possibly due to racial differences, and the use of different criteria for diagnosing optic neuritis.

Effect of chronic hyperglycemia on intraocular pressure in patients with diabetes.

PURPOSE: To investigate the effect of chronic hyperglycemia on intraocular pressure (IOP) in patients with diabetes. DESIGN: Cross-sectional study. METHODS: We prospectively measured the IOP by Goldmann applanation tonometry in patients with diabetes with mild hyperglycemia (glycosylated hemoglobin A1c (HbA1c) < or = 6.5%), moderate hyperglycemia (6.5% < HbA1c < 8.0), and severe hyperglycemia (HbA1c > or = 8.0%). None of the patients with diabetes had diabetic retinopathy, secondary glaucoma, ocular or laser therapy, or history of glaucoma. The HbA1c level determined within three months of the IOP measurement was used. Statistical analysis was performed by Mann-Whitney U test. P < .05 was considered significant. RESULTS: The mean IOP in the mild group (n = 58) was 15.5 +/- 2.5 mm Hg, which was statistically significantly lower than that of the severe group (16.6 +/- 2.4 mm Hg; P = .013; n = 60). CONCLUSIONS: Chronic hyperglycemia is associated with increased IOP in patients with diabetes.

Macular and retinal nerve fiber layer thickness in Japanese measured by Stratus optical coherence tomography.

The purpose of this study was to determine the thickness of the macula and the retinal nerve fiber layer (RNFL) in Japanese subjects by Stratus optical coherence tomography (OCT), and to compare the findings with the normative data of subjects from the United States of America (USA). Sixty-one eyes from 31 healthy subjects were used for the measurement of the macular thickness, and 60 eyes from 30 healthy subjects were used for the RNFL thickness measurements. The values obtained from the Japanese subjects were compared with the corresponding values in healthy subjects from the USA. The superior, nasal, temporal, and inferior macular sectors and the mean and inferior areas of the RNFL in the Japanese subjects were significantly thicker than the corresponding areas of normal subjects in the USA (272 +/- 13 vs 255 +/- 17 mum, 274 +/- 12 vs 267 +/- 16 mum, 262 +/- 12 vs 251 +/- 13 mum, 268 +/- 13 vs 260 +/- 15 mum; p < 0.0001, 104 +/- 11 vs 100 +/- 12 mum, 134 +/- 20 vs. 126 +/- 18 mum; p = 0.0167, 0.0047, respectively). In conclusion, the significantly thicker macular regions and RNFL in the Japanese indicate not only that there are racial differences in retinal thicknesses but also that the normative values provided by the Stratus OCT should not be used for different races.

Up-regulation of genes for oxidative phosphorylation and protein turnover in diabetic mouse retina.

Diabetic retinopathy is one of the most frequent complications of diabetes and is a leading cause of vision loss in adulthood. To better understand the molecular pathophysiology of diabetic retinopathy, we performed comprehensive gene expression analysis of the mouse retina under diabetic conditions with an in-house cDNA microarray system that was designed to be suitable for the small amount of RNA available from a single mouse retina. Diabetes was induced in male C57BL/6 mice by an intraperitoneal injection of streptozotocin, and the changes in retinal mRNA levels were examined in three pairs of diabetic and age-matched control mice at 1 and 3 months after the injection of streptozotocin. Northern blot analysis with amplified total cRNA confirmed the increase in mRNA levels of several selected genes. Most of the significantly up-regulated genes could be classified into two functional categories: oxidative phosphorylation and protein turnover. All mitochondrial DNA-encoded and most of the nuclear DNA-encoded genes for oxidative phosphorylation were up-regulated in the diabetic retina. This was in sharp contrast with a previous report of a down-regulation of these genes in skeletal muscles of streptozotocin-induced diabetic mice and type 2 diabetic humans. Genes for protein synthesis and ubiquitin were also up-regulated in the diabetic retina, suggesting the increase in turnover rates for at least a part of the protein population. Taken together, the diabetic retina appears to be in a state activated for intermediary metabolism, presumably because of an increase in insulin-independent glucose influx. These results provide insights into possible preventive and therapeutic intervention of diabetic retinopathy.

Histopathological study of a case with branch retinal vein occlusion.

A retinal specimen from a 68-year-old patient with glaucoma and branch retinal vein occlusion was examined by light and electron microscopy. The venous and arterial lumina were filled with erythrocytes, and many erythrocytes extravasated into the venous wall. We suggest that constant rubbing of endothelial cells of the occluded vein results in damage and erythrocyte extravasation was caused by diapedesis.

Clinical characteristics of Japanese children with optic neuritis.

The clinical characteristics of children with optic neuritis have been reported to be different from that of adults and to vary among different races. To determine the clinical characteristics of Japanese children with optic neuritis, we examined the medical records of 41 children who were diagnosed with optic neuritis at the Department of Ophthalmology of Chiba University Hospital between January 1979 and December 2001. Information on the sex, age of onset, laterality, initial visual acuity, final visual acuity, recent infections and immunizations, and presence of systemic neurologic diseases, such as multiple sclerosis or acute disseminated encephalomyelitis, was obtained. These findings revealed that the clinical features of optic neuritis in children were similar to those reported earlier. The percentage of optic neuritis cases that developed multiple sclerosis in children was similar to that for children in Europe and North America, and this percentage was not lower than that in adults in our clinic. These findings can be taken as the characteristics of optic neuritis of children in Japan.

Binocular summation in visual evoked cortical potential in patients who have significantly different P100 peak latencies in their two eyes.

PURPOSE: To determine whether binocular summation in visual evoked cortical potential (VEP) is present in patients who have significantly different P100 peak latencies in their two eyes. METHODS: Twelve patients with unilateral optic neuritis (ON) and 11 normal controls were studied. All of them had visual acuity of > or = 20/20 in both two eyes and good stereoacuity. Transient and steady-state VEPs were recorded with monocular and binocular pattern-reversal stimulation. RESULTS: In normal controls, the binocular summation ratio was 1.05 with transient stimulation and 1.21 with steady-state stimulation, and in ON patients it was 1.19 and 1.30, respectively. In ON patients, the peak latency of P100 components was delayed significantly when the affected eye was stimulated, but with binocular stimulation the waveform was very similar to that when the fellow eye was stimulated. CONCLUSION: Binocular summation of VECP is not present in ON cases with large differences in the peak latency between the two eyes even if they have good stereoacuity. Binocular summation may not be correlated with stereopsis in adults whose binocular function has already matured.

Seventeen cases of central serous chorioretinopathy associated with systemic corticosteroid therapy.

PURPOSE: To determine the relationship between the clinical characteristics of patients with central serous chorioretinopathy (CSC) and systemic corticosteroid therapy. METHODS: The medical records of 17 cases of CSC that developed during systemic corticosteroid treatment from 1987 to 1999 at Chiba University Hospital were reviewed. The relationship of CSC to the age, gender, laterality, and disease requiring the corticosteroid treatment, and the dose and duration of corticosteroid therapy were examined. RESULTS: There were 6 men and 11 women, and 2 of these developed bilateral and 15 developed unilateral CSC. The duration from the beginning of corticosteroid treatment to the onset of CSC ranged from 3 days to 23 years; 9 patients developed CSC within 1 year after the beginning of the corticosteroid medication and 6 patients after more than 8 years. The amount of corticosteroid medication at the onset of CSC ranged from 5 to 1,000 mg/day equivalent prednisolone units. There was a significant correlation between age at the onset of CSC and the daily dosage of corticosteroid. CONCLUSION: Even small amounts of daily corticosteroids (5-10 mg/day) can cause CSC, especially in elderly patients. These findings indicate that we need to monitor patients undergoing corticosteroid treatment carefully.

Adenovirus-mediated gene transfer of Bcl-xL impedes neurite regeneration in vitro.

Mouse retinal explants were transfected with recombinant adenovirus vector carrying the green fluorescent protein (GFP) gene and the rat bcl-xL gene (Adeno-Bcl-xL) to determine its ability to protect retinal ganglion cells against apoptotic cell death and to promote retinal ganglion cell neurite regeneration. Adeno-Bcl-xL-incubated retinas had reduced apoptosis compared to controls. However, neurite regeneration in adeno-treated retinas was less than that of vector-free retina. These results suggest that the usefulness of adenovirus vectors for gene therapy for retinal ganglion cells may be limited.

Adenovirus-mediated gene transfer of Bcl-xL impedes neurite regeneration in vitro.

Mouse retinal explants were transfected with recombinant adenovirus vector carrying the green fluorescent protein (GFP) gene and the rat bcl-x(L) gene (Adeno-Bcl-xL) to determine its ability to protect retinal ganglion cells against apoptotic cell death and to promote retinal ganglion cell neurite regeneration. Adeno-Bcl-xL-incubated retinas had reduced apoptosis compared with controls. However, neurite regeneration in adeno-treated retinas was less than that of vector-free retina. These results suggest that the usefulness of adenovirus vectors for gene therapy for retinal ganglion cells may be limited.

The effect of caspase inhibitors and neurotrophic factors on damaged retinal ganglion cells.

To elucidate the role of caspase inhibitors and neurotrophic factors in retinal ganglion cell (RGC) death and regeneration, we cultured mouse retinal explants in the presence of caspase-1, -3, -8, or -9 inhibitors, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in serum-free culture media. We quantified apoptosis by TUNEL staining in RGCs and assessed the number of regenerating neurites. Apoptosis of RGCs treated with all caspase inhibitors or with neurotrophic factors was significantly reduced and the number of regenerating neurites was significantly greater than controls (p < 0.05). Our findings indicate that caspase-1, -3, -8, -9 play a critical role in explanted RGC death and may be ideal targets of neuroprotection and regeneration of damaged RGCs.

Diagnosis of autosomal dominant retinitis pigmentosa by linkage-based exclusion screening with multiple locus-specific microsatellite markers.

PURPOSE: To describe a hierarchical approach for efficient genetic diagnosis of autosomal dominant retinitis pigmentosa (adRP). METHODS: Forty di-, tri-, or tetra-nucleotide repeats tightly linked to 10 genes known to be responsible for adRP were identified from the human genome sequence and used as markers in multiplex amplification and genotyping, followed by linkage analysis. Discordance of cosegregation of markers and the disease excluded the majority of the examined genes as candidates, and mutation screening for the remaining genes was performed. RESULTS: With this strategy, examination of an adRP-affected family indicated that 3 of 10 candidate genes segregated concordantly with the disease. Further searches for mutations revealed a novel insertion and deletion in the last exon of a splicing factor gene, PRPF8. CONCLUSIONS: This systematic approach facilitates the molecular diagnosis of adRP, which is known to have a highly heterogeneous genetic background.

Accelerated aging of senescence accelerated mice R-1 demonstrated by flash visually evoked cortical potentials.

To determine the physiological alterations of visual functions induced by aging, the latency of the N40 peak of the flash visual evoked cortical potentials at several stimulus frequencies were analyzed from senescence accelerated mice (SAM). The senescence prone (P-8) and senescence resistant (R-1) SAM lines were studied. In both the P-8 and ICR (the standard outbred albino laboratory mouse also called CD-1) mice, the peak latency was not significantly different at 6 and 12 months of age. In contrast, there was a prolongation of the peak latency in the R-1 line at 12 months compared to that at 6 months. We conclude that there is an acceleration of the aging process in the R-1 line for visually evoked responses. Thus, the R-1 line might be an independent line suited for the study of aging effects on visual functions.

Comparison of Yatabe-Guilford personality test results in retinitis pigmentosa and glaucoma patients.

PURPOSE: To determine the psychological state and personality traits of patients with retinitis pigmentosa (RP) or glaucoma so that a closer and better relationship can be developed with the patients. METHODS: The Yatabe-Guilford personality test was administered to 75 RP patients and 42 glaucoma patients. The latter group included 29 cases of primary open-angle glaucoma, 6 of primary angle-closure glaucoma, and 7 of normal-tension glaucoma. The patients were being treated at the Department of Ophthalmology, Chiba University Hospital. As controls, 47 age-matched volunteers were tested. RESULTS: A comparison of these three groups showed that the proportions of patients with cyclic tendency, rhathymia, and lack of cooperativeness traits were significantly higher in the RP group than in the glaucoma group. The lack of cooperativeness value was especially higher in the RP than in the glaucoma group and the control group (Fisher exact test, P <.05). On the other hand, the nervousness value was significantly higher in the glaucoma group than in the RP group and than in controls (Fisher exact test, P <.05). Factors of sex, age, type of disease, corrected visual acuity, and central visual fields did not influence the profiles of the RP and glaucoma groups. CONCLUSION: RP patients had relatively well-stabilized personalities and were optimistic, while glaucoma patients tended toward nervousness in comparison with RP patients and controls.

Visual field indexes for version 3.0 of frequency doubling perimetry in patients with glaucoma.

PURPOSE: A new version of frequency doubling perimetry was compared to a former version in patients with glaucoma. DESIGN: Prospective observational study. METHOD: Thirty-two patients with glaucoma were examined twice sequentially in one eye with threshold c-20 of frequency doubling perimetry version 2.6. Within 3 months, the same eye was again examined twice sequentially, this time using the new version 3.0. Mean deviation, pattern standard deviation, short-term fluctuation, intraocular pressure at examination, and test duration were compared between versions. RESULTS: No significant difference was found in mean deviation, pattern standard deviation, intraocular pressure, or short-term fluctuation between versions. CONCLUSIONS: Version 3.0 took less time to perform the threshold test than did version 2.6. Version 3.0 of the frequency doubling perimetry program took less time to perform and showed similar values of visual field indexes when compared with version 2.6.

Protective action of nipradilol against ischemia-induced retinal damage in rats.

The purpose of this study was to investigate whether nipradilol, a beta-blocker having both vasodilating and alpha(1)-blocking activities, can protect retinal cells from the injury induced by ischemia and reperfusion. Rats were anesthetized and, after an intravitreal injection of nipradilol, the intraocular pressure was raised for 45 min to induce retinal ischemia and reperfusion. Before, and 3 and 7 days after the ischemia, electroretinograms were recorded. After the ischemia, the mean amplitude of the b-waves in rats receiving 5 microl of 1.0 x 10(-6) M nipradilol was significantly larger than of controls (injected with phosphate-buffered saline). Histologically, the reduction in the number of retinal ganglion cells (1.0 x 10(-6) M), and the thickness of the inner and outer plexiform layers and the inner nuclear layer (1.0 x 10(-6), 10(-7) and 10(-8) M) was suppressed by nipradilol. These results indicate that nipradilol protected the retina against retinal ischemia and reperfusion and should be considered for therapeutic use in cases of transient retinal ischemia.

Effect of body temperature on electroretinogram of mice.

PURPOSE: To investigate the ERG alterations induced by changes in body temperature in mice. METHODS: Three-week-old BALB/c mice were used. Rectal temperature was measured with a digital thermometer and taken as the body temperature. In experiment 1, the body temperature was kept at 33 degrees C, and the ERGs elicited by a constant stimulus intensity were recorded every 5 minutes. In experiment 2, the body temperature was lowered in five steps from 38 degrees C to 33 degrees C, 28 degrees C, 23 degrees C, and 18 degrees C. At each body temperature, ERGs elicited by different stimulus intensities were recorded. RESULTS: In experiment 1, the mean amplitudes and implicit times of both the a- and b-waves did not change significantly. In experiment 2, the amplitude of both the a- and b-waves decreased significantly with a decrease in body temperature, and the implicit times of the a- and b-waves were prolonged with a decrease in body temperature. CONCLUSIONS: Body temperature greatly affects the amplitude and timing of the ERG. Great care must be taken to maintain as normal a body temperature as possible when using the ERG to evaluate the retina, especially in small animals such as mice.