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Endogenous endophthalmitis is a rare complication of acute meningitis. A healthy 82-year-old woman suddenly developed septic bacteremia and meningitis owing to Staphylococcus aureus (methicillin-susceptible Staphylococcus aureus); she presented with a high fever and drowsiness. Improvement of these initial symptoms unveiled impaired bilateral visual acuity. Detailed ophthalmological assessments diagnosed it as probable endogenous endophthalmitis, which was immediately treated with vitrectomy. Subsequently, the patient totally recovered without any neurologic or ophthalmic sequela.

A 40-year-old woman with renal dysfunction for 2 years was admitted to our hospital suffering from a headache. Family history revealed that her mother had a headache, renal dysfunction, and brain infarction in younger age. She had a retinal hemorrhage, a retinal atrophy, pitting edema in her lower extremities. Her neurological findings were unremarkable. Brain imaging showed multiple white matter lesions accompanied with calcifications and slightly enhancement. Kidney biopsy showed the thrombotic microangiopathy, Gene analysis demonstrated a causative mutation in three-prime repair exonuclease-1 (TREX1) gene, c.703_704insG (p.Val235GlyfsX6), thereby we diagnosed her as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is an autosomal dominant condition caused by C-terminal frame-shift mutation in TREX1. TREX1 protein is a major 3' to 5' DNA exonuclease, which are important in DNA repair. While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. There are no treatments based evidences in RVCL. We administered cilostazol to protect endothelial function, and her brain lesions and renal function have not become worse for 10 months after. It is necessary to consider RVCL associated with TREX1 mutation if a patient has retinal lesions, white matter lesions accompanied with calcifications, and multiple organ dysfunction.

Kawasaki disease (KD), an acute childhood panvasculitis, presents a variety of ocular complications as well as conjunctival injection among the principal symptoms. However, most pediatricians are unfamiliar with the ophthalmological complications of KD. A 2-year-old girl was referred to us from the ophthalmology department due to injected bulbar conjunctivae and optic disc swelling. She had familial exudative vitreoretinopathy as an underlying disease and the ocular findings had been made by chance while the patient was receiving an eye examination. Although she was afebrile at the time of her first medical interview, KD was diagnosed based on the presence of four of the principal symptoms including fever and dilatation of the coronary arteries. Intravenous immunoglobulin (IVIG) therapy was administered on Day 15 from the onset of fever. After IVIG administration, her laboratory test results showed rapid improvement but her optic disc swelling continued for six months. Eye complications in KD generally occur in the anterior segment, and recovery occurs within two months. Past reports have shown that in three of seven KD cases with optic disc involvement, optic disc swelling lasted over two months. This is the second case in which the condition lasted six months.

An 81-year-old man had undergone radical nephrectomy for a renal cell carcinoma (RCC) in October 1998. Twelve years postoperatively, he developed diplopia and photophobia. Orbital metastasis of RCC was suspected and sunitinib treatment was given for 16 months. Computer tomography revealed a partial response of metastatic tumor for the first 2 months and stable disease for the next 12 months. However, it enlarged in the last 2 months. Total resection of right metastatic orbital tumor with deep lateral orbital decompression was done in January 2012. He has been well and without any local recurrence, distant metastasis or vision loss for 24 months.

Purpose: To investigate the ability of patients with strabismus and/or amblyopia to see 3D images., Methods: A questionnaire survey conducted for children aged 6 to 19 years and adults aged 20 to 39 years on their experience of viewing 3D images (movies, motion attractions, television, games), asking whether they could see stereoscopically, with or without adverse effects. A retrospective investigation of ophthalmological examinations was followed., Results: Of 507 cases, 342 had had the experience of veiwing 3D images. In 212 (62%) cases of strabismus and/or amblyopia, stereopsis was lacking in 17 to 18% of the subjects for movies, in 6 to 7% for attractions, in 32% in children and 50% in adults for television and 23% in children and 17% in adults for games. Adults complained of a higher rate of adverse effects, 65% for movies and 75% for games, as compared with 34% for movies and 26% for games in children(p < 0.01). The lack of stereopsis for games and movies was higher in the subgroup of Fly (-) and convergence insufficiency (p < 0.05)., Conclusions: Since many patients with strabismus and/or amblyopia found some difficulty in stereoscopic viewing, precise examinations for stereopsis and convergence are needed to assess individual aptitude for 3D viewing.

Purpose: To investigate the role of specific secretary IgA antibodies on lipopolysaccharide (LPS-sIgA) and exotoxin A (ETA-sIgA) in tear fluid produced by immunoresponse to P. aeruginosa., Subjects and Methods: Subjects were divided into 3 groups; 41 eyes of 41 normal volunteers without a history of using contact lenses (CL) as controls, 32 eyes of 32 CL users without adverse events as a healthy CL wearer group (CL group), and 12 eyes of 12 patients with CL-related corneal ulcers from which P. aeruginosa was isolated (ulcer group). Tear fluid was obtained using filter paper, and the concentration of LPS-sIgA and ETA-sIgA in samples was determined using enzyme-linked immunosorbent assay (ELISA)., Results: The lower limit of concentration for LPS-sIgA and ETA-sIgA was 1.24 and 1.24 (U/mL), respectively. The positive eyes which exceeded this lower limit in LPS-sIgA were 17 of 22 eyes in the control group (median concentration 2.00U/ml, range 1.28 to 7.20), 15 of 25 eyes in the CL group (median 1.76 U/ml, range 1.24 to 6.92) and 1 of 12 eyes in the ulcer group (1.80 U/ml). The number of eyes which exceeded the lower limit in ETA-sIgA was 36 of 41 eyes in the control group (median concentration 6.56 U/ml, range 1.36 to 182), 28 of 32 eyes in the CL group (median 5.40 U/ml, range 1.56 to 29.20) and 5 of 12 eyes in the ulcer group (median 1.72 U/ml, range 1.40 to 2.16). There was no significant difference in LPS-sIgA and ETA-sIgA between the control group and the CL group, but they were significantly lower in the ulcer group than in the control group (p < 0.01, Steel's test)., Conclusion: Tear fluid in normal, healthy CL wearers contains LPS-sIgA and ETA-sIgA which acts as a barrier to P. aeruginosa infectious keratitis.

Purpose: To evaluate binocular and monocular reading ability in glaucoma patients with good visual acuity and to examine its relationship with central visual field sensitivity., Methods: Glaucoma patients(35 individuals, mean +/- SD : 51.8 +/- 12.9 years) with a decimal visual acuity in each eye of >or=1.0, reading ability was tested both binocular and monocular using Japanese version of Minnesota Reading Acuity Chart (MNREAD-J). Reading ability parameters were calculated for maximum reading speed (MRS), critical print size (CPS), and reading acuity (RA). The results were compared with those of people with normal vision; differences in reading ability under varied testing conditions and correlations between visual field sensitivity and each parameter were examined., Results: Under binocular reading conditions, MRS, CPS, and RA were decreased significantly in glaucoma patients compared with normal controls (p = 0.00044, p = 0.00004, p = 0.00028, respectively). Under monocular reading conditions, glaucoma patient MRS and RA were decreased significantly in comparison with normal controls (p=0.00155, p= 0.00142). In glaucoma patients undergoing binocular reading tests, MRS was greatest in the paracentral bottom right quadrant of the worse eye (r = 0.41709, p= 0.04447). The CPS decreased in proportion to the extent of the difference between both eyes in the mean deviation value and the visual field sensitivity of the paracentral bottom left (r = 0.40693, p = 0.02699 and r=0.41478, p=0.02384). RA improved in proportion to the extent of the difference between both eyes in the visual field sensitivity of the upper left (r = 0.33557, p=0.04799)., Conclusion: In glaucoma patients, binocular reading is not necessarily useful in cases of visual field sensitivity differences.

Purpose: To compare one-year treatment outcomes of intravitreal injections of pegaptanib sodium and bevacizumab for myopic choroidal neovascularization (m-CNV)., Subjects and Methods: 28 patients (28 eyes) with subfoveal m-CNV were assigned alternately to undergo intravitreal pegaptanib 0.3 mg (group P: n = 14) or bevacizumab 1.25 mg (group B: n = 14) between December 2009 and February 2010 and followed-up for one year. Both groups were evaluated every 6 weeks, and injections were repeated when exudate was observed in the macula. Visual acuity, retinal sensitivity within central 12 degrees, greatest linear dimension (GLD) and blood pressure were measured before treatment and at one year. Mann-Whitney U test was used for intergroup comparison, and the Wilcoxon test for comparing pre- and post-treatment data., Results: No significant differences in mean log-MAR visual acuity and mean blood pressure at one year were observed between the two groups. Mean greatest lesion dimension was reduced significantly in both groups. Mean retinal sensitivity was improved significantly only in group B. The number of injections was significantly smaller in group B., Conclusion: Although changes in visual acuity at one year did not differ significantly between the two groups, bevacizumab improved mean retinal sensitivity with fewer injections than pegaptanib, suggesting that intravitreal bevacizumab may be more effective than pegaptanib for m-CNV.

Purpose: To investigate the influence of optic disc area on the progression of visual field (VF) defects in normal-tension glaucoma (NTG). We evaluated the correlation between the right-left differences of the progression of VF defects and those of the intraocular pressure and the ocular anatomical factors., Methods: Thirty two eyes of 16 NTG patients with a significant difference between the left and right optic disc area, were followed up for more than 5 years after diurnal variation analyzed with Heidelberg Retina Tomograph (HRT), and without myopic disc shape. The left and right eyes of the patients were allocated to two groups, a group with a relatively smaller eye disc and a group with relatively larger eye disc. They were studied regarding the probability of VF stability using the Kaplan-Meier life-table analysis. In addition, a comparison of clinical factors was evaluated between the two groups (Mann-Whitney U test)., Results: The probability of VF stability at the 107-month follow-up was 60 +/- 13% (mean +/- SE)in patients with small disc area, and 25 +/- 11% in patients with large disc area. Optic disc area was found to have significant influence on the progression of VF defects (p = 0.022, log-rank test). In clinical factors, no statistically significant difference except disc area was found between the two groups., Conclusions: These findings suggest that optic disc area is associated with the progression of VF defects in patients with NTG.

Purpose: To evaluate the efficacy of Gram-Fungiflora Y double staining for corneal scraping samples collected by impression in diagnosing infectious keratitis., Subjects and Methods: Two hundred and thirteen eyes of 192 patients suspected of having infectious keratitis were retrospectively studied for the sensitivity and specificity of Gram-Fungiflora Y based on final diagnosis., Results: Of 165 infectious keratitis eyes, 107 had bacterial keratitis, 54 had fungal keratitis, and 15 had Acanthamoeba keratitis. Of these, 147 eyes were positive for one or other of the pathogens by the double staining method (overall sensitivity/specificity was 89.1% (95% confidence interval 83.1%-93.2%)/ 79.1% (64.6%-89.0%)). Sensitivity/specificity of the double staining for each of the pathogens was 88.8% 82.1% for bacterial keratitis, 81.4%/98.1% for fungal keratitis and 80.0%/97.0% for Acanthamoeba keratitis., Conclusion: The double staining method for impression specimens was effective in diagnosing infectious keratitis with high sensitivity, and was especially useful for the diagnosis of fungal or Acanthamoeba keratitis.

Objective: To evaluate ophthalmologic outcomes 1 year after intravitreal pegaptanib sodium injection in patients with myopic choroidal neovascularization (CNV)., Subjects and Methods: We investigated 31 eyes of 30 patients who had been given intravitreal pegaptanib sodium (0.3 mg) injections for subfoveal or juxtafoveal myopic CNV at 6-week intervals from July through December 2009. We compared visual acuity, retinal sensitivity within the central 12 degrees and maximum lesion diameter, and quantified metamorphopsia using M-CHARTS (Inami Co., Tokyo) both before and after the intravitreal injections. The Wilcoxon test was applied to identify statistically significant differences., Results: Mean logMAR visual acuity was 0.49 +/- 0.38 before and 0.47 +/- 0.35 after treatment (p = 0.56); the corresponding values for mean retinal sensitivity were 7.48 +/- 3.69 dB and 8.15 +/- 4.18 dB (p = 0.24). Mean maximum lesion diameter was significantly reduced from 1,217 microm to 1,041 microm after treatment (p = 0.0021). Mean metamorphopsia scores were significantly improved after treatment, i.e., 0.85 +/- 0.68 to 0.50 +/- 0.39 for vertical lines (p = 0.016); 0.81 +/- 0.74 to 0.47 +/- 0.41 for horizontal lines (p = 0.017). The average number of injections was 3.1. No patient experienced adverse events associated with treatment., Conclusion: Visual acuity and retinal sensitivity were maintained, while metamorphopsia was improved 1 year after intravitreal pegaptanib sodium injections for myopic CNV.

Optical coherence tomography (OCT) provides a new dimenstion in ophthalmology because it allows evaluation of the pathology in vivo, and provides information to assist the management of macular disease and glaucoma. It is necessary to differentiate the diagnosis of glaucoma from diseases of the optic nerve and of the visual pathway. This study evaluates the usefulness of OCT in detecting disorders of the optic nerve and visual pathway. In addition, the pathogenesis of glaucomatous optic neuropathy (GON), the most common optic neuropathy, was investigated by focusing on the dynamics of aquaporin. I. Evaluation of optic nerve and visual pathway disorders by optical coherence tomography. The swinging flashlight test is an easy, sensitive, objective test to detect relative afferent pupillary defects (RAPD). The number of RAPD detected by the swinging flashlight test was closely correlated with the ratio of retinal nerve fiber layer thickness (RNFLT) between the two eyes of 20 cases of unilateral optic atrophy. OCT could assess the amount of RAPD that reflected an asymmetrical functional disturbance of the optic nerves, as a structural difference. The time courses of RNFLT and ganglion cell complex (GCC) changes' were observed immediately following the time of injury in 4 cases of traumatic optic neuropathy. OCT revealed that both the RNFLT and GCC decreased rapidly from 2 weeks after the injury until 20 weeks later. The RNFLT decreased significantly in the horizontal direction in comparison to the perpendicular direction in 34 eyes from the cases of optic chiasm syndrome. This means that OCT could quantitatively detect the band atrophy of the optic disc in optic chiasm syndrome. Measuring the RNFLT showed a thinning of RNFLT in the perpendicular direction in comparison to the horizontal direction in ipsilateral eyes and thinning in the horizontal direction in comparison to the perpendicular direction in the contralateral eyes in optic tract syndrome. Measuring the GCC showed a thinning of the GCC in the temporal hemifield to the central fovea of the ipsilateral eyes, and thinning of the GCC in the nasal hemifield of the contralateral eyes. This means that OCT could detect the structural changes of hourglass atrophy in the ipsilateral eye and band atrophy in the contralateral eye at the optic disc as well as the homonymous hemianopia in the visual field. OCT was useful in evaluating the optic nerve and visual pathway disorders, but there were also some limitations. The thinning area of RNFLT measured by OPTVue and Cirrus were in entirely opposite directions in cases of optic chasm syndrome. The reason was attributed to the better performance of RTVue in measuring a thin RNFLT on the nasal side of the optic disc in comparison to Cirrus. The specific characteristics of the instruments should be considered when the results of OCT are evaluated. II. Dynamics of aquaporin in the optic nerve Aquaporin (AQP) is a membrane protein that forms a water channel to facilitate water crossing the plasma membrane. AQP-4 was originally thought to be expressed in the optic nerve, but it is expressed only in the retrobulbar medullated region of the optic nerve and the expression of AQPs in the optic disc has not been detected. This study investigated the expressions of AQPs in the optic nerve in rat, monkey and human. The results demonstrate that only AQP-9 was expressed at the unmedullated pre-lamina cribrosa and lamina cribrosa regions, and both AQP-4 and AQP-9 were expressed at the medullated retrobulbar region. Astrocytes were observed to express AQP-9, because AQP-9 immunoreactivity was identical to that of glial fibrillary acidic protein. Elevated intraocular pressure substantially reduced AQP-9 expression in the optic nerve, whereas expression of AQP-4 was not changed in rat eyes. The same phenomena were also observed in the monkey eye with ocular hypertension as well as human eye with glaucoma. AQP-9 is an aquaglyceroporin that allows solutes such as lactate rather than water to cross the cell membrane. The astrocyte-to-neuron lactate shuttle hypothesis has been proposed, in which lactate transported from astrocytes is used by neurons as an energy substrate. Reduction of AQP-9 expression in the optic nerve head under elevated intraocular pressures might be closely related to the pathogenesis of GON.

Purpose: To investigate the chemokine profile in tears of patients with infectious keratitis., Subjects and Methods: Subjects were 32 eyes of 16 patients with infectious keratitis and 5 eyes of 5 healthy volunteers as a control. The patients with infectious keratitis were classified into two groups of eyes: 10 with bacterial keratitis and 6 with Acanthamoeba keratitis. Tear fluid was obtained from both eyes of the patients with infectious keratitis and from the right eyes of the control subjects using filter paper. Chemokine concentration (unit: Odu/mm2) and its profile in tears was analyzed using an antibody-array., Results: In terms of chemokine profile in the bacterial keratitis group, the expression volume of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in the diseased eyes was significantly higher than in the healthy eyes (p < 0.05). The expression volume of mucosae-associated epithelial chemokines (MECs) in the diseased eyes of the bacterial keratitis group was significantly lower than in the healthy eyes of that group (p < 0.05). In the Acanthamoeba keratitis group, chemokines were not significantly increased in the diseased eyes compared with those in the healthy eyes. However, MCP-1 was increased in tears of the Acanthamoeba keratitis group. Regarding the chemokine ratio, the IL-8/MEC ratio in the diseased eyes of the Pseudomonas keratitis group and the MCP-1/IL-8 in the diseased eyes of the Acanthamoeba keratitis group showed a significantly high level (p < 0.05)., Conclusion: We concluded that the analyses of the chemokine profile and chemokine ratio in the tears of infectious keratitis patients is useful as a clinical tear laboratory test to interpret the pathologic condition of infectious keratitis

Purpose: To evaluate the efficacy of subjective symptoms, objective findings, and of a total tear IgE test kit in the diagnosis of allergic conjunctival diseases (ACD)., Subjects and Methods: The subjects were 223 patients with ACD, diagnosed according to the clinical practice guidelines for allergic conjunctival diseases in 28 medical facilities in Japan. The ACD patients were divided into the following five groups: 84 patients with seasonal allergic conjunctivitis (SAC), 52 patients with perennial allergic conjunctivitis (PAC), 41 patients with atopic keratoconjunctivitis (AKC), 38 patients with vernal keratoconjunctivitis (VKC) and 8 patients with giant papillary conjunctivitis (GPC). All cases were examined for clinical ACD, subjective symptoms, objective findings by the clinical score and by a total tear IgE test. An eosinophil examination by conjunctival smear was also performed in 87 ACD patients., Results: The most prevalent subjective symptoms were itching (81.6%) and hyperemia (77.6%). The clinical scores of the objective findings in the patients with SAC, PAC, AKC, VKC and GPC were 16.3 +/- 3.8 (mean +/- SD) points, 16.2 +/- 2.8, 19.8 +/- 6.5, 23.1 +/- 5.3, and 21.4 +/- 3.9, respectively. In the total tear IgE test 72.2% of the ACD patients were positive; i.e., the ratios were 61.9% in SAC, 65.4% in PAC, 80.5% in AKC, 94.7% in VKC, and 75.0% in GPC. In the examination of eosinophils in the 87 ACD patients, 42.5% (37 eyes) were positive, i.e., the ratio was 20.0% in SAC, 36.8% in PAC, 53.3% in AKC, 75.0% in VKC and 33.3% in GPC. The rate of agreement between the total tear IgE test and the examination of eosinophils was kappa = 0.28 (Cohen kappa coefficient)., Conclusion: Because of the high positive ratio in patients quasi-definitively diagnosed with ACD, we conclude that the total tear IgE test is useful as an auxiliary method for diagnosing ACD.

Polypoidal choroidal vasculopathy (PCV) is characterized by a branching vascular network with polypoidal lesions under the retinal pigment epithelium (RPE). In Japan, it is classified as a specific form of exudative age-related macular degeneration. However, several issues which we investigated regarding the pathogenesis and treatment of PCV remain unresolved. We investigated the pathogenesis, clinical findings and treatment of PCV. 1. Indocyanine green angiographic findings. There were two different patterns on indocyanine green angiograms. In the first pattern, both feeder and draining vessels were visible and network vessels showed characteristic findings of choroidal neovascularization (CNV). Points of focal dilatation on marginal vessels were comprised of polypoidal lesions. In the second pattern, neither feeder nor draining vessels were visible and there were few network vessels. The points of deformation of network vessels appeared to be polypoidal lesions. The former represents a deformation of CNV, i.e. polypoidal CNV; the latter is thought to result from abnormalities of the choroidal vessels, i.e. PCV in the strict sense. 2. Pathological findings of PCV in the strict sense. The histopathological characteristics of PCV in the strict sense, which had been eliminated by vitrectomy, were dilatation and hyalinization of vessels, massive exudative changes in blood plasma, basement membrane-like deposits and scant granulomatous tissue. These vessels were located beneath Bruch's membrane. The findings indicate that PCV in the strict sense arises from hyalinized arteriolosclerosis of choroidal vessels. 3. Optical coherence tomographic findings. A break was found in the high reflective line which revealed Bruch's membrane. Low reflective tissue was observed at the break corresponding to a feeder vessel. The high reflective line which corresponded to the retinal pigment epithelium was uneven, and highly elevated portions of the RPE corresponded to thick network vessels and polypoidal lesions. Feeder vessels are thought to invade via Bruch's membrane to form network vessels and polypoidal lesions at the termini of the network vessels, both of which push the RPE upward. Therefore, polypoidal CNV is thought to represent a deformation of the CNV under the RPE. In PCV in the strict sense, an irregular thickened line with highly reflective substances adhering to the lower portion of it, curved downward corresponding to the site at which the network vessel filling began. A dimple in the RPE was observed which paralleled the curve of the line. The RPE was pushed upward, corresponding to the network vessels. Judging from the results of histopathological studies, abnormal vessels may be pushed up the RPE secondary to an increase in intravascular pressure due to the presence of several dilated vessels and by massive exudation from these vessels within the choroid at network vessels. The dimple in the RPE might be attributable to intra-choroidal pressure being decreased at the point at which network vessel filling began. 4. Genetic findings. There were significant differences in all distributions of ARMS 2 (A69S) between the polypoidal CNV and control groups. In contrast, the distribution of ARMS 2 (A69S) did not differ between the PCV in the strict sense group and the control group. The ARMS 2 (A69S) gene is closely related to age-related macular degeneration. Polypoidal CNV was thought to be associated with age-related macular degeneration. 5. Treatment of subfoveal PCV. Mean visual acuity improved 1 year after photodynamic therapy (PDT). Good visual acuity, small lesion size of the network of vessels with polypoidal lesions, and the absence of subfoveal polypoidal lesions were pre-PDT predictors that corresponded to the improvement in vision. However, mean visual acuity had decreased to a level similar to that prior to PDT at 2 and 3 years after treatment. In PCV in the strict sense, the branching vascular network persisted after PDT, and polypoidal lesions frequently recurred at the termini. The branching vascular network sometimes expanded and was accompanied by polypoidal CNV or classic CNV. These results indicate that repeated PDT, as monotherapy, has limitations as a long-term treatment for PCV in the strict sense. Intravitreal injection of ranibizumab for eyes with a visual acuity of 0.6 or more, which is not a good indication for PDT, achieved improvement in mean visual acuity 1 year after the treatment, though the frequency of polypoidal lesion regression was low. This procedure seems to be useful for eyes with good visual acuity for a period of at least one year. 6. Conclusion. Using indocyanine green angiography, optical coherence tomography and genetic testing, PCV was classified into 2 groups, polypoidal CNV and PCV in the strict sense. PCV in the strict sense was characterized by arteriolsclerosis histopathologically. Polypoidal CNV is thought to represent deformation of CNV under the RPE in age-related macular degeneration, while PCV in the strict sense is thought to be due to choroidal vessel abnormalities. The long-term efficacy of repeated PDT as monotherapy, for subfoveal PCV was limited. Further evaluation is necessary to establish a treatment algorithm for PCV.

Glaucomatous optic neuropathy is a primary pathological condition responsible for visual dysfunction due to glaucoma. However, how intraocular pressure and other risk factors lead to glaucomatous optic neuropathy is not fully understood. Given that static or kinetic visual field tests for evaluating visual dysfunction in glaucomatous optic neuropathy are a subjective assessments based on a psychophysical principle, the development of a tool for objective assessment of the visual field is needed. In this study, we attempt to elucidate the pathophysiology of glaucomatous optic neuropathy and to refine a modality for the objective assessment of the visual dysfunction due to it. Aquaporin (AQP) water channels are located primarily in the plasma membrane. These proteins form either a homo- or hetero-tetramer and allow water to cross the plasma membrane bi-directionally. The transmembrane water movement through AQPs is critically involved in the maintenance of normal neuronal activity. Among the 13 isoforms indentified so far, AQP-4 is known to be expressed in the retrobulbar portion of the optic nerve. However, the optic nerve head, the primary pathological site of glaucomatous optic neuropathy, reportedly does not express AQP-4. We found that in control rats, astrocytes throughout the optic nerve express AQP-9. The chronic elevation of intraocular pressure due to cauterization of three episcleral veins substantially reduced both gene expression and immunoreactivity of AQP-9, whereas it did not change the AQP-4 gene or protein expression in the retrobulbar portion of the optic nerve. These findings are implicated in the chronic elevation of intraocular pressure in astrocytes. Similar findings were also observed in the eyes of a monkey with angle-laser-induced ocular hypertension and of a human with primary open-angle glaucoma. AQP-9 was also expressed in the cell bodies of retinal ganglion cells in control rats and its expression was significantly reduced in the eyes of rats with ocular hypertension. Recently, the astrocyte-to-neuron lactate shuttle hypothesis has been proposed. This hypothesis suggests that lactate generated by glucose during glycolysis in astrocytes is used by neurons as an energy substrate. Given that AQP-9 belongs to an aquaglyceroporin subfamily and allows solutes other than water (e.g., lactate) to cross the plasma membrane, chronic ocular hypertension may perturb this physiological passage of lactate. Thus, lactate as the energy substrate may be unable to be transported from astrocytes to retinal ganglion cells at the cell bodies and axons due to the reduction of AQP-9 expression by astrocytes at the optic nerve head and retinal ganglion cells. The multifocal visual evoked potential (mfVEP) is an objective visual field test, which enables the recording of cortical potential corresponding to 60 local retinal areas simultaneously. Evidence is accumulating that the signal-to-noise ratio (SNR) has been enhanced by recording mfVEPs from multiple channels at the same time. However, previous studies evaluated the mfVEPs mostly in Caucasians. It has not yet been proven whether this strategy is applicable to Japanese people who have a skull frame that may be different from that of Caucasians. We calculated the relative position of the calcarine landmark for electrode placement during the mfVEP recording, from brain MRI images of 200 individuals, which were found to be 1 cm lower than those reported in Caucasians with a statistical significance. Then, we recorded mfVEPs from 110 normal controls using three channels and conducted receiver-operating characteristic (ROC) curve analysis of the overlap of SNR distribution at signal and noise windows. We found that a combination of one horizontal channel straddling the inion with either one of the two perpendicular vertical channels yielded the largest area under the ROC curve (AUC). Next, we showed that the SNR-AUC exhibited a similar diagnostic performance to, and a significant correlation with, a total deviation of the Humphrey visual field in 56 eyes with mild to moderate glaucomatous damage, which exhibited a mean deviation of -15 dB or less, and in 62 control eyes. In contrast, a topographical agreement in defining abnormal locations based on probability plots between the Humphrey visual field and mfVEP testing was moderate. The SNR-AUC may be used as a global index, analogous to the mean deviation of the Humphrey visual field, to quantify diffuse functional loss due to glaucomatous optic neuropathy, in contrast to the previously proposed cluster analysis of the mfVEP probability plots, which is a strategy more suitable to diagnosing local sensitivity loss.

Purpose: To investigate, using tear fluid analysis, the effects of topical 0.1% tacrolims therapy on the pathophysiology of vernal keratoconjunctivitis (VKC)., Subjects and Methods: Subjects were 6 eyes of 6 patients with VKC who underwent topical 0.1% tacrolims treatment twice a day and 5 eyes of 5 healthy volunteers as a control. Using the filter paper method, the tear fluid of the patients was sampled both before and 4 +/- 2 weeks after the treatment and once from the control subjects. Eosinophil cationic protein (ECP) in the tears was examined by the chemiimmunoluminescent enzyme immunoassay method and the chemokine profile of the tears was analyzed using an antibody-array., Results: In terms of the chemokine profile, growth related oncogene (GRO) -alpha, eotaxin-2 and thymus and activation-regulated chemokine (TARC) in the VKC were elevated compared with those in the controls, but they decreased significantly after the treatment (p<0.05). ECP concentrations in the tears were 3092 +/- 1658 ng/ml (average +/- S. D.) for the pretreatment base-line and 464 +/- 775 for the posttreatment. ECP values for the pre-treatment time were statistically significantly higher than those for the post-treatment in 5 patients (p<0.05)., Conclusion: Topical tacrolims treatment of VKC can suppress allergic inflammation associated chemokines such as eotaxin-2 and TARC.

Purpose: To determine the causative agents of ocular infection of external adnexa and anterior segments due to selected criteria., Subjects and Methods: Between September 22, 2007 and August 25, 2008, 890 bacterial strains were collected from 476 patients in 18 facilities nationwide participating in the Drug Sensitivity for Ocular Infection Study Group. Usual aerobic and anaerobic cultures, enrichment cultures, smears, and measurements of bacterial quantity were performed and the determination of causative agents was made from the results of smears and culture, the presence of polymorphonuclear cells and bacterial quantity. The selection was divided into two categories, causative agents and presumed causative agents. Staphylococcus aureus, Moraxella bacilli, Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Neisseria gonorrhoeae were distinctively considered as specified bacteria., Results: Among 890 strains, 18.8% were determined to be causative agents, and 15.1% were determined to be presumed causative agents. Among the bacteria detected in normal flora, 2.0% of Staphylococcus epidermidis, 2.6% of Propionibacterium acnes, and 38.3% of Corynebacterium spp. were determined to be causative agents., Conclusion: To determine the causative agents, the results of smears and bacterial quantity should be considered together with culture results. Bacteria constituting normal flora have the potential of becoming causative agents.

Purpose: To investigate the effects of optic disc area to visual field (VF) defects of normal-tension glaucoma (NTG), the correlation between the right-left differences of VF defects and those of diurnal variations of intraocular pressure and the ocular anatomical factors were evaluated in patients with NTG., Methods: One hundred eighteen eyes of 59 NTG patients with the right-left difference value of mean deviation (MD) of between 2 dB and 12 dB obtained with Humphrey field analyzer program 30-2 were enrolled in the study. The correlation between the right-left differences of MD values and those of refraction, axial length, central cornea thickness, diurnal variation of intraocular pressure, and disc area measured with Heidelberg Retina Tomograph were evaluated by multiple regression analysis., Results: The multiple correlation coefficient was 0.520, and the coefficient of determination was 0.271. The right-left differences of axial length (p = 0.041) and disc area(p = 0.002) were judged to be the statistically significant factors correlated with those of VF defects., Conclusions: These results suggest that the right-left differences of axial length and disc area are associated with the right-left differences of VF defects in patients with NTG.

1., Purpose: Slit-lamp microscopy is a principal ophthalmic clinical method, because it provides microscopic findings of the anterior segment of the eye noninvasively. Its findings, however, are qualitative and there are large inter-observer variations in their evaluation. Furthermore, slit-lamp microscopy provides morphological findings, but a functional evaluation is difficult. We developed two novel methods that establish a qualitative methodology of the slit-lamp microscope and the pathophysiology of the anterior segment of the eye. One is the flare-cell photometer to evaluate flare and cells in the aqueous humor of the eye and the other is an immunohistochemical examination method using tear fluid to evaluate ocular surface disorders. The comprehensive evaluation of these studies is herein overviewed. 2. INNOVATION OF THE FLARE-CELL PHOTOMETER AND ITS CLINICAL SIGNIFICANCE: The breakdown of the blood-aqueous barrier (BAB) causes an increase in protein (flare) and leakage of blood cells (cell) into the aqueous humor of the eye and the severity of BAB breakdown has a positive correlation with the intensity of flare and cells. The flare and cells in the aqueous can be observed qualitatively by slit-lamp microscopy. These findings are primarily distinguished in optics by light scattering. Therefore, detection of the intensity of light scattering due to flare and cells can evaluate the BAB function. The flare-cell photometer comprises 3 novel components: a laser beam system as an incident light, a photomultiplier to detect scattered light intensity and a computer-assisted system to operate the whole system and analyze detected scattered light signals due to flare and cells. The instrument enables us to quantitatively analyze the flare and cells non-invasively and accurately with a wide dynamic measurement range, resulting in a repeated examination of each individual case. It also enables the evaluation of inflammation in the aqueous not only postoperatively but also in endogenous uveitis, evaluation of the effects of anti-inflammatory drugs on BAB and evaluation of aqueous humor dynamics. Furthermore, repeating the examination can minimize inter-individual variations and reduce the number of animals in animal experiments. 3., Pathophysiological Evaluation Methods of Ocular Surface Using Tear Fluid: Sampling of tears can be performed noninvasively, but the obtainable volume is limited. Therefore, a determination of targeting biomarkers and a development of their micro-volume analysis methods play a crucial role in pathophysiological studies of the ocular surface. Targeting biomarkers should be determined according to the various specified bioactive substances such as eosinophil cationic protein (ECP), cytokines and others. A number of microvolume analysis methods, such as chemiluminescent enzyme immunoassay, immunochromatography, micro-array system and polymerase chain reaction method are used. Objective disorders in the studies include allergic conjunctivitis and infectious diseases such as herpetic keratitis. Quantitative evaluation methods for ECP concentration, antigen-specific secretory IgA in allergic diseases and herpetic keratitis, herpes simplex virus-DNA and cytokine and chemokine profile in tear fluid sampled by filter paper method were investigated. We developed a clinically applicable quantitative immunochemical method for ECP concentration in tear fluid. The results revealed that tear fluid analysis using the above mentioned methods is a clinically useful to investigate the pathophysiology of the ocular surface. 4., Conclusion: Laser flare-cell photometer and tear fluid analysis are potent clinical quantitative methods to investigate the pathophysiology of the anterior segment of the eye.

Applied methodologies on genetics have progressed rapidly in recent years. Single nucleotide polymorphism based candidate gene strategy and whole genome scanning technology can provide unprecedented insights into complex diseases, including asthma and atopic dermatitis. The acquisition of genomic information by the genome-wide association studies(GWAS) revolutionized the detection of causative genes. Insights obtained from these discoveries have changed our ways of understanding allergic diseases, and provide new perspectives of allergic conjunctivitis. In this review, genetics and molecular mechanisms of both common allergic diseases and ocular allergy are discussed, with special emphasis on GWAS.

Purpose: To resolve the problems of visual acuity assessment in grading the vision of the physically handicapped as proposed by the Subcommittee for Promoting the Realization of a Cohesive Society with the Visually Disabled, Science Council of Japan, a method suitable for assessing visual disturbances, and the relationship between the degree of visual disturbances and the degree of difficulty in activities of daily life are clarified., Subjects and Methods: 151 persons with age-related macular degeneration were studied. Examination methods for measuring visual acuity and reading performance were studied, and interviews using the daily living task dependent on vision (DLTV) questionnaire were performed. The correlations between total DLTV score and each examination method were analyzed. The median total DLTV score for each grade of visual acuity of the better eye was calculated., Results: Spearman's correlation coefficient between distance corrected visual acuity of the better eye and total DLTV score was 0.76. Median DLTV scores for visual acuities (better eye) of 0.2, 0.3, 0.4, 0.5 were 65, 73.5, 62, 79 respectively., Conclusion: Visual acuity can be assessed by measuring distant corrected visual acuity of the better eye and setting the upper limit of visual disturbance at either 0.3 or 0.4.

Background: Rifabutin-associated uveitis has been recognized and established overseas, but there have been no reports of its occurance in Japan. We report a case of rifabutin-induced hypopyon uveitis in a patient with acquired immunodeficiency syndrome (AIDS)., Case: A 45-year-old Filipino man with AIDS and pulmonary tuberculosis was on highly active antiretroviral therapy (HAART; lopinavir/ritonavir, zidovudine/lamivudine) and anti-tuberculosis therapy (isoniazid, rifabutin). At 11 weeks after starting rifabutin administration, unilateral acute uveitis with hypopyon developed, which progressed to bilateral uveitis by the following day. Funduscopic examination revealed no vitreo-retinal abnormalities. The uveitis resolved after discontinuation of the rifabutin and initiating topical corticosteroids and mydriatic therapy. No recurrence of the uveitis was noted during a 5-month follow-up period., Conclusion: Rifabutin-associated uveitis with hypopyon should be considered as one possible causes of uveitis.

We report a case of Fisher syndrome accompanied by ocular flutter. A 19-year-old man presented with diplopia and vertigo, associated with preceding symptoms of common cold. Since symmetric weakness of abduction in both eyes, truncal ataxia, diminution of tendon reflexes, and gaze nystagmus were noted, he was diagnosed as having Fisher syndrome. Ocular flutter also was noticed during horizontal gaze. Serum anti-GQ1b antibody and anti-GM1 antibody were detected. He was followed without therapy and the symptoms resolved. The accompanying ocular flutter may suggest that a central nervous system disorder may also be present in Fisher syndrome.

Background: Chronic myeloid leukemia (CML) during childhood is rare, and only been a few cases showed visual disturbances as an initial symptom. We report a pediatric CML case diagnosed by bilateral visual loss., Case: An 11-year-old boy complained of visual loss in both eyes. His best corrected visual acuity was 0.5 in the right eye and 0.2 in the left. Fundus examination showed disc swelling, dilated and tortuous retinal veins and multiple elevated retinal lesions with hemorrhages of various size from one-forth to four disc diameters in both eyes. He was diagnosed as having CML by leucocytosis and systematic work-up including Philadelphia chromosome-positive, BCR-ABL kinase domain in peripheral blood and bone marrow. The ocular findings improved after treatment with hydroxyurea, leukocytaphresis and imatinib. His best corrected visual acuity improved to 0.7 in both eyes., Conclusion: Recent leukemia therapy including imatinib is effective not only for ocular lesions but also to induce hematological remission in childhood CML.

Purpose: To extract amblyogenic factors in eyes with an early-onset type of developmental glaucoma despite good post-operative intraocular pressure (IOP) control., Materials and Methods: Subjects were 24 eyes of 14 patients that underwent successful trabeculotomy by 3 years of age and had their best-corrected visual acuity (BCVA) development monitored for at least 5 years or more after surgery. Principal factor analysis was performed on final logarithmic BCVA, age at operation, corneal diameter, corneal opacity, Haab's striae, spherical equivalent of final refractive error, final astigmatic degree, axial length, preoperative IOP, final vertical cup per disc ratio, and either presence or absence of eccentric fixation. Latent variables that had an eigenvalue of 1 or more underwent an orthogonal rotation with the varimax method in order to yield factor loadings of these 11 parameters., Results: The parameters that had absolute factor loading values of 0.6 or more in a latent variable including final BCVA were final BCVA, fixation status, refractive error, and Haab's striae. Two-variable comparisons also supported the significant association of the latter three parameters with final BCVA., Conclusions: Amblyogenic factors in eyes with an early-onset type of developmental glaucoma were eccentric fixation, myopic refractive error, and the presence of Haab's striae.

Background: Orbital lymphangioma can result in ocular emergencies due to acute enlargement, leading to painful proptosis, compressive optic neuropathy, exposure keratopathy, restrictive ocular motility and increased intraocular pressure. Treatment methods and clinical courses of two cases with orbital lymphangioma are reported, one with orbital decompression therapy and the other with intralesional injection of OK-432 therapy. CASE 1: An 8-year-old girl had multilocular cystic orbital intracornal lymphangioma. Emergency operation was deemed necessary because the patient presented with the painful proptosis, the compressive optic neuropathy, and increased intraocular pressure due to acute enlargement, we put the orbital inferior wall was decompressed by inserting an intact inframedial orbital strut. The proptosis vanished completely and visual acuity loss improved. CASE 2: A 2-year-old girl had multilocular cystic orbital intra and extracornal lymphangioma. She had severe proptosis and exposure keratopathy. The extracornal cystic lesion was treated with an intralesional injection of OK-432. On the 7th day after injection, the patient presented with painful severe proptosis. Aspiration of the fluid in the cystic lesion was performed, and the drain was preserved. After the treatment, both the severe proptosis and the exposure keratopathy improved., Conclusions: Inferior wall decompression was performed on case 1 while keeping the inframedial orbital strut. Although the eye movement disorder was low at the time, the medial and lateral wall decompression improved. In case 2, the extracornal cystic lesion was treated with an intralesional injection of OK-432 Judging from the results of that clinical course, the injection of OK-432 to the intracornal lesion could prove dangerous to the visual performance. Although OK-432 is predictably-effective against lymphangioma, it should not perform be applied without careful consideration.

Purpose: To evaluate the efficacy of photodynamic therapy (PDT) for subfoveal choroidal neovascularization(CNV) secondary to age-related macular degeneration(AMD) one year after PDT., Patients and Methods: 106 eyes of 106 AMD patients with subfoveal CNV detected by fluorescein angiography (FA). Best-corrected visual acuity, color fundus photography, FA and indocyanine green angiography were performed before and 1 year after treatment. Visual acuity and CNV size before PDT were compared with those 1 year after treatment. Pre-PDT factors predicting a visual acuity of 0.4 or more 1 year after this treatment were evaluated., Results: Visual acuity improved or was maintained in 84 of the 106 eyes. The size of CNV decreased significantly (p < 0.001). A visual acuity of 0.4 or more 1 year after PDT was predicted by an acuity of 0.4 or more (p = 0.01) and occult with no classic CNV (p = 0.04) prior to PDT., Conclusions: PDT is effective for maintaining or improving visual acuity and obliteration of CNV for 1 year or longer. Factors predicting a visual acuity of 0.4 or more 1 year after PDT were an acuity of 0.4 or more and occult with no classic CNV prior to PDT.

Unlabelled: Fisher syndrome with optic neuropathy has been rarely reported. We report a 78-year-old Frenchman with Fisher syndrome. The patient complained of dizziness and bilateral blurred vision. His corrected visual acuity was 0.03 in the right eye, and 0.02 in the left eye. Deep tendon reflexes were absent. A few days later, bilateral complete external ophthalmoplegia appeared. Both pupils were dilated and pupillary reflexes were absent. Serum anti-GQlb antibodies and anti-GT1a antibodies were detected. After intravenous immunoglobulin treatments, all neurological symptoms including optic neuropathy and external ophthalmoplegia disappered except for pupillary dilatation associated with light-near dissociation. Tonic pupil indicated disorder of the peripheral nervous system., Conclusion: Fisher syndrome may complicate optic neuropathy.

Purpose: Primary position downbeat nystagmus is a vertical nystagmus with a rapid phase downwards presenting in any gaze. We evaluated causative lesions, etiology, and incidence by age groups., Materials and Methods: Twenty-five patients with primary position downbeat nystagmus were enrolled in this study. Their causative lesions, etiology, and frequency by age group were investigated. We divided the patients into 3 groups depending on age; under 30, from 30 to 60, and over 60 years., Result: Cerebrovascular disorder was diagnosed in 5 patients. Four patients had cerebellar degeneration. Three patients had multiple sclerosis or Arnold-Chiari malformation. Two patients had cerebellar tumor. In the young group under 30, etiology was mainly cerebellar tumor or multiple sclerosis. Especially cerebellar tumor was limited to this group. In the middle age group, there was no distinctive tendency. In the older group over 60 years, cerebrovascular disorder was predominant. In 10 patients with intracranial lesions, the foci were located in the cerebellum, pons, or medulla oblongata., Conclusion: The causes of primary position down beat nystagmus tended to be age-dependent. The locations of causative lesions were the cerebellum and the inferior brain stem.

Purpose: The anterior ocular segment topography in angle-closure glaucoma was studied using the non-contact three-dimensional anterior segment analyzer Pentacam., Subjects and Methods: The central anterior chamber (AC) depth, mid-peripheral AC depth, peripheral AC depth, AC volume, central AC depth/ocular axial length ratio and angles of a narrow angle group (47 eyes of 29 patients), a post laser iridotomy (LI) group (43 eyes of 30 patients), and an open-angle glaucoma (OAG) group (37 eyes of 21 patients) were measured and compared. In addition, changes in the parameters before and after LI (13 eyes of 9 patients) were investigated., Results: The AC volume for the narrow angle group (74.5 +/- 21.1 microl) was significantly smaller than for the other groups (post LI group: 96.4 +/- 21.4 microl; OAG group: 144.2 +/- 31.6 microl, p<0.001). The most significant association was detected between AC volume and the peripheral AC depth. Only two parameters, AC volume and peripheral AC depth, increased significantly after LI (p< 0.001)., Discussion: Measurement of the AC volume and the peripheral AC depth using Pentacam is useful for evaluating the anterior ocular segment topography in narrow angle eyes.

Purpose: To determine the normal retinal nerve fiber layer (RNFL) thickness as measured by optical coherence tomography (OCT), and to evaluate the relationship between RNFL thickness in healthy Japanese and their age., Methods: One hundred healthy Japanese subjects were enrolled. The RNFL thickness was measured using OCT with three circle scans 3.4 mm in diameter., Result: The mean thickness of RNFL measured around the optic disc was 108 +/- 13.5 microm. The average RNFL thickness in the temporal, superior, nasal, and inferior quadrants was 80 +/- 15.9 microm, 132 +/- 20.7 microm, 80 +/- 17.0 microm and 136 +/- 20.0 microm, respectively. There was a statistically significant negative correlation between age and the average RNFL thickness around the disc, and in the temporal quadrant. Using 30-degree segments, there were negative correlations between age and RNFL thickness in temporal-superior and temporal-inferior segments., Conclusion: RNFL thickness in healthy Japanese subjects measured by OCT decreased with age in the temporal-superior and temporal-inferior quadrants. Our results suggested that the regional and age-related differences in RNFL thickness must be taken into consideration before making clinical interpretations of the RNFL abnormalities measured by OCT.

Purpose: In glaucoma patients, to compare the correlations among parameters measured by Heidelberg Retina Tomography(HRT) and retinal nerve fiber layer thickness (RNFLT) measured by GDx-variable corneal compensation (GDx-VCC) and optical coherence tomography (OCT), and to assess the relationship among these structural parameters, and visual field damage., Methods: A unilateral eye of 110 patients with open-angle glaucoma were included in this study. Each individual was analyzed by HRT (version 3.04), GDx-VCC (version 5.3.2), and OCT-1 (version A6 X1). The correlations among these parameters regarding global area, superior sector, and inferior sector were obtained from the 3 instruments and compared. The correlations among the mean deviation (MD) in the Humphrey field analysis and the parameters in global area from the 3 instruments were calculated., Results: The MD showed quadratic regressions to each global parameter (GDx-VCC; 0.625 (nerve fiber indicator): OCT 0.616 (average RNFLT); HRT, 0.501 (rim area)). Most parameters in OCT and GDx-VCC had highly significant correlations. The rim area showed the highest correlation in each sector to RNFLT with GDx-VCC or OCT among HRT parameters., Conclusions: These structural parameters derived from GDx-VCC, OCT and HRT analyses had bilinear correlation to the MD. Retinal nerve fiber loss detected on GDx-VCC and OCT correlated linearly with the neuroretinal rim area measured by HRT. These instruments may be useful in monitoring structural changes in glaucoma.

Background: The management of conjunctival malignant melanoma remains controversial. Interferon-beta (IFN-beta) is a well-known antineoplastic agent against cutaneous malignant melanoma., Case: A 44-year-old man was referred to Kobe University, Hospital for treatment of pigmented lesions in the corneal limbus of his right eye, first recognized in 2000 and growing gradually., Findings: There were two pigmentary neoplastic lesions in the conjunctiva of his right eye, one at 9 o'clock in the limbus and the other at the inferior bulbar conjunctiva close to the fornix. Primary acquired melanosis (PAM) extended widely over the bulbar conjunctiva and the corneal surface. These findings led to the clinical diagnosis of conjunctival malignant melanoma. Systemic work-up did not detect any other neoplastic lesion., Course: The melanotic lesions were resected and histopathologically malignant melanoma was diagnosed. Microscopically, the tumor cells were present at the surgical margin. Melanoma recurred a half-year later at 3 o'clock in the limbus of the right eye. IFN-beta (3 million units/) was injected subconjunctivally 22 times. Side effects observed were as follows: corneal epithelial erosion, increase of the corneal thickness, lid swelling, conjunctival congestion, subconjunctival hemorrhage, and liver dysfunction. These findings were transient. Melanotic lesions, including PAM, diminished 6 months after the end of treatment., Conclusion: This therapeutic trial of local therapy using the subconjunctival administration of IFN-beta demonstrated excellent efficacy for the treatment of conjunctival malignant melanoma. Local and systemic side effects were seen, though transient, suggesting the necessity of long-term follow-up study.

Purpose: Central visual functions of two children with idiopathic optic neuritis were analyzed and followed in the course of the disease by using multifocal visually evoked potentials (mVEP) and other ophthalmological tests., Subjects and Methods: Two girls 10 and 11 years of age with unilateral optic neuritis participated in this study. At the initial onset of the disease, visual acuity of the patients was below 20/400 and severe central visual field impairment was found in the affected eyes. There were no abnormal neurological or radiological findings suggesting multiple sclerosis in these patients. The mVEPs were recorded with a stimulus of 37 hexagons composed of black and white triangles subtending 35 degrees of visual angle., Results: The amplitude of mVEPs from many stimulating locations was severely reduced in the course of the recovery of these patients. Although visual acuity and perimetric sensitivity in the affected eyes recovered to normal after steroid pulse therapy, the amplitude of mVEPs still remained 1/3 to 1/2 of that of the opposite healthy eye. The mVEPs gradually recovered to near the level of the opposite healthy eyes at the latest examination., Conclusions: Recovery from the central visual impairment due to infantile optic neuritis is more gradual than that suggested by subjective ophthalmological examinations. There is still optic nerve dysfunction after visual acuity and visual field have recovered to normal. The mVEP is one of the most sensitive tools for detecting optic nerve dysfunction in patients with optic neuritis.

Background: It is relatively rare to encounter a case of neovascular glaucoma induced by malignant lymphoma metastasized into the eyeball., Case: A 79-year-old woman initially visited our ophthalmology clinic with the chief complaint of blurring of vision in the left eye which was affected by neovascular glaucoma. She had a history of systemic malignant lymphoma, first diagnosed from skin biopsy and treated to complete remission 3 years previously. A metastatic brain lesion, detected 2 months before her initial visit to our clinic, was cured by radiotherapy., Findings: By ultrasound biomicroscopy (UBM) we detected abnormal thickening of the temporal half of the ciliary body of her left eye. Cytological examination of the aqueous humor revealed invasion by malignant cells of presumed lymphocyte origin. Radiation therapy to the left eye normalized the intraocular pressure in a week, followed by a reduction in the neovascularization of the iris and the thickening of the ciliary body., Conclusion: This case showed that metastatic malignant lymphoma in the eye could result in neovascular glaucoma and that UBM is useful to detect and to observe lesions in the iris and ciliary body.

Background: Leber hereditary optic neuropathy (LHON) is a maternally transmitted, bilateral optic neuropathy. Although mitochondrial (mt) DNA mutations are known to be associated with the maternal inheritance, there are few reviews on how they lead to optic neuropathy. In addition, low penetrance and male preponderance cannot be accounted for by mtDNA mutations alone., Methods: Presumable molecular mechanisms of LHON due to mtDNA mutations were reviewed based on cellular and molecular studies. Environmental factors regulating LHON expression were also extracted from pedigree analyses., Result: Histopathologically, LHON, comprises apoptosis of retinal ganglion cells and chronic inflammation of the retrobulbar optic nerve. Trans-mitochondrial cybrid studies demonstrated that mtDNA mutations cause an increase in the production of reactive oxygen species. Over the last 50 years, the penetrance in females has been greatly reduced in both Japanese and Caucasian pedigrees. Smoking, over-consumption of alcohol, and sex hormones may control LHON expression., Conclusions: These findings indicate that LHON is not a monogenetic disease, but that LHON transmits a predisposition to develop optic neuropathy and requires additional factors triggering phenotypic expression. Therapeutic intervention including gene therapy should be further investigated.

Purpose: To evaluate the functions of the macular area in patients with branch retinal vein occlusion (BRVO) by using multifocal electroretinograms (mERG) and optical coherence tomography(OCT)., Methods: mERGs were recorded from 18 eyes of 18 patients with BRVO. An array of 103 hexagonal elements was displayed on a monitor. The latency (ms) and response density (nV/deg2) of mERGs were measured for 7 central locations. The peak and troughs were labeled N1, P1 and N2, respectively. OCT was used to measure the foveal retinal thickness., Results: Statistically significant correlation was found between visual acuity(log MAR) and P1-N1 response density (r = - 0.629, p < 0.05) and N2 latency(r = 0.619, p < 0.05). Foveal retinal thickness had the significant statistic correlations with P1-N1 response density (r = -0.750, p < 0.0001), P1-N2 response density (r = -0.520, p < 0.05) and N2 latency (r = 0.488, p < 0.05)., Conclusions: In 18 BRVO patients, mERGs from the central retinal area were significantly correlated with foveal retinal thickness measured by OCT and with visual acuity. The mERG recording is sensitive to morphological changes and functional disorders induced by BRVO.

Background: We report a patient with acute angle-closure glaucoma secondary to annular ciliochoroidal detachment after unsutured cataract surgery., Case: An 82-year-old man was diagnosed with bilateral shallow central anterior chamber depth, flat peripheral anterior chamber, and elevated intraocular pressure. One day previously he had undergone uncomplicated unsutured cataract surgery in the right eye and eight days previously, in the left eye. Ultrasound biomicroscopy revealed annular ciliochoroidal detachment in both eyes. Treatment with intravenous methyl prednisolone deepened the anterior chamber and reduced intraocular pressure., Conclusion: Annular ciliochoroidal detachment may lead to anterior rotation of the ciliary body and angle-closure. This clinical entity is indistinguishable from malignant glaucoma when the fundus cannot be visualized.

Purpose: To analyze the retinal nerve fiber layer thickness(NFLT) as measured by optical coherence tomography(OCT) in glaucomatous eyes with hemifield defect and to evaluate the most effective parameter for the diagnosis of glaucoma with OCT., Methods: One hundred eighty four(184) normal eyes(128 subjects) and 108 open-angle glaucomatous eyes(87 subjects) with superior or inferior hemifield defects verified by Humphrey field analyzer(HFA) were measured for NFLT with OCT. The correlations between NFLT and mean deviation on HFA were calculated. In combination with normal eye data, receiver operating characteristic curve(ROC curve) and AUC(area under the curve) of each NFLT in the affected hemifield were evaluated for the diagnosis of glaucoma., Results: NFLT in both affected and unaffected hemifields was significantly correlated with mean deviation in HFA. An average of four 30 degrees segments close to the temporal side in the affected hemifield (parameter A120) had the highest correlation(r = 0.571) and the highest AUC(0.948) among all parameters., Conclusions: NFLT in the unaffected visual field decreases with the progression of glaucomatous damage. We suggest that the parameter A120 is the best indication in a diagnosis of glaucoma when measuring NFLT by OCT.

Background: We report two rare cases of Senior-Loken syndrome, one with fundus lesions simulating Coats disease. CASE 1: A 14-year-old boy had juvenile nephronophthisis and bilateral retinitis pigmentosa with retionochoroidal atrophy and salt and pepper fundus. Electroretinogram (ERG) showed non-recordable changes and the Goldmann perimeter showed ring scotomas. CASE 2: A 14-year-old boy had bilateral retinitis pigmentosa and juvenile nephronophthisis with continuous ambulatory peritoneal dialysis. Additionally, both eyes showed massive exudates seen in Coats disease in the entire periphery, exudative retinal detachment, proliferative changes in the inferior periphery, yellow opacitas corporis vitrei, keratoconus, and cataract. The left eye had vitreous hemorrhages. Both eyes received vitreous surgery and endophotocoagulation. After the surgery the left eye showed neovascular glaucoma and a cyclophotcoagulation was performed. The massive edema in the superior retina of both eyes disappeared and intra-ocular pressure in the left eye was normalized. However, despite these treatments, both eyes finally had no light perception., Conclusion: Case 1 was a typical SLS, and case 2 was a rare one with fundus lesions simulating Coats disease, keratoconus, and cataract. We suspect the exudative changes resulted from various vessel changes and choroidal circulatory disturbance of renal retinopathy, retinal vascular damage, and destruction of blood-retinal barrier with retinitis pigmentosa, the inflammatory changes of vessels, and other things.

Background: We report a patient who was diagnosed as having steroid-induced glaucoma after radial keratotomy(RK) and suffered from severe visual field defect., Case: A 29-year-old man underwent RK for both eyes. After the operation, he was treated for six months with topical medication including 0.1% and 0.01% betamethasone without measuring intraocular pressure(IOP). When he consulted an ophthalmologist, his IOP was 43 mmHg in the right eye and 51 mmHg in the left eye. At our initial examination, his IOP was 8 mmHg in the right eye and 10 mmHg in the left eye with 750 mg acetazolamide peroral, 0.5% timolol maleate, and latanoprost eyedrops. There were RK 16 incisions on the cornea and we found severe glaucomatous visual field loss. Finally we performed trabeculotomy in both eyes for IOP control with conservative therapy., Conclusion: As the keratorefractive surgery becomes popular, we must be careful of problems, such as steroid-induced glaucoma, and the change of refraction following the change of IOP.

Object: To compare the results of vitrectomy for phakic cases and those of aphakic cases with proliferative diabetic retinopathy (PDR) accompanied by rubeosis iridis., Materials & Methods: We reviewed 34 eyes of 24 cases that underwent vitrectomy for proliferative diabetic retinopathy with rubeosis iridis., Result: Phakic eyes needed significantly more reoperations (p < 0.001) than aphakic eyes. Aphakic eyes had significantly more successful visual results (p < 0.05) and better control of intraocular pressure (p < 0.005) than phakic eyes., Conclusion: This study showed the possibility that phakic eyes had more ischemic retina producing more angiogenic factors than aphakic eyes which had the same grade of rubeosis iridis. Phakic eyes with pre-operative rubeosis iridis need thorough clearance of ocular ischemia by panretinal photocoagulation.

The present TNM classification of ophthalmic malignant tumors (lid cancer, malignant melanoma of the lid, conjunctival cancer, conjunctival malignant melanoma, uveal malignant melanoma, retinoblastoma, orbital sarcoma and lacrimal gland cancer) has been explained according to the UICC in a book edited by M. H. Harmer and J. A. Oosterhuis. Five studies concerning the difference in clinical results with and without a treatment were shown to confirm the meaning and importance of TNM classification of ophthalmic malignancies.