Toshihiko Uno

A new method for tear film stability analysis using videokeratography

PURPOSE To report a new tear film stability analysis system using videokeratography. DESIGN Observational case series. METHODS New videokeratography software for TMS-2N (topographic modeling system; TOMEY Corporation, Nagoya, Japan) was developed that can automatically capture consecutive corneal surface images every second for 10 seconds. Forty-eight adult volunteers (80 eyes) were recruited for this study, and all subjects were examined with the new system. Corneal topographs were analyzed for tear breakup time (TMS-BUT) and the ratio of breakup area to entire color-code area (TMS-BUA) was calculated. Routine methods for tear film breakup time evaluation using slit-lamp microscope and fluorescence staining (SLE-BUT) were performed for comparison purposes. Regressive correlations of TMS-BUT or TMS-BUA with SLE-BUT were analyzed. Based on SLE results, subjects were separated into two groups with normal and short BUT, respectively. TMS-BUT and TMS-BUA were compared with SLE-BUT data with regard to the sensitivity and specificity of evaluation of dry eye symptoms. RESULTS Topographic modeling system-tear breakup time (TMS-BUT) had a positive correlation with SLE-BUT (R = 0.7219, P <.0001), whereas TMS-BUA showed a negative correlation (R = 0.6317, P <.0001). Among 34 eyes with normal SLE-BUT, 11 eyes (32.35%) displayed abnormal TMS-BUT, 9 (81.82%) of which were associated with dry eye symptoms. The sensitivities of TMS-BUT and TMS-BUA were 97.5% and 95%, respectively, significantly higher than that of SLE-BUT (75%), with P =.008 and 0.01, respectively. Topographic modeling system-BUT and TMS-BUA displayed a similar rate of specificity in comparison with SLE-BUT. CONCLUSIONS This new videokeratography system is a noninvasive and objective method with increased sensitivity for tear film stability analysis.

National survey on bullous keratopathy in Japan.

Purpose: To present the results of a national survey on bullous keratopathy (BK) in Japan. Methods: A cross-sectional national survey was conducted for 963 eyes with BK seen between 1999 and 2001 by members of the Japan Cornea Society. Demographic characteristics, type of surgery, complications, and postoperative outcome were analyzed. Results: BK accounted for 24.2% (963 eyes) of total keratoplasties performed during the period. Graft clarity was maintained in 77.4% of cases, and immunologic rejection and elevated intraocular pressure was noted in 10.8% and 15.3%, respectively. Cataract surgery was the most common cause of BK (n = 428, 44.4%), and phacoemulsification and aspiration were performed in approximately 40% of cases. BK secondary to laser iridotomy (LI) was the second most common cause of BK (n = 225, 23.4%). LI was performed as a prophylactic measure in approximately one half of these cases. BK developed with a mean duration of 6.8 years after LI. Fuchs dystrophy was the cause of BK in 18 eyes (1.9%). Conclusions: The causes of BK in Japan are considerably different from those in other Western countries. LI-related BKs showed a remarkably high number, whereas Fuchs dystrophy was observed only rarely.

Expression of MAGE genes in ocular melanoma during progression from primary to metastatic disease

Primary melanomas that form within the eye have a unique pattern of disease progression as compared with melanomas that form within the skin. A high percentage of patients (approximately 50%) develop metastatic tumors that occur predominately in the liver. An unusual characteristic of ocular melanomas is the prolonged disease-free interval that extends for many years between the development of primary and metastatic tumors. It is estimated that the shortest interval between dissemination of tumor cells from the eye and the appearance of clinically detectable metastases is 6 years. A recent report indicated that fresh uveal melanoma tissue and metastatic tumor biopsies failed to express melanoma antigen gene (MAGE)-1, MAGE-2, or MAGE-3. In the present study, we examined the expression of MAGE genes on fresh and cultured tumor cells obtained from an ocular melanoma patient during different stages of progressive disease. MAGE gene expression was determined by reverse transcription-polymerase chain reaction using MAGE-1, MAGE-2 and MAGE-3 specific primers. Our results demonstrate that primary ocular tumor tissue and cultured tumor cells both express significant levels of MAGE-1, 2, and 3 at the time of enucleation. A high percentage of tumor cells within the primary tumor appear to express MAGE as demonstrated by consistent MAGE expression in 16 tumor cell clones. Metastatic liver tumors that developed 3 years after enucleation and 18 years after the initial formation of the primary tumor also expressed high levels of MAGE-1, -2, and -3. MAGE was expressed on fresh tumor tissue from a single biopsy and cultured tumor cells obtained from three of four different metastatic tumor nodules. When the MAGE-negative metastatic tumor cells were treated with the demethylating agent 5-Aza-2-Deoxycytidine (5-Aza-dC), transcription of MAGE-1 was restored, indicating the MAGE genes were not deleted. Our results demonstrate that in some patients, MAGE genes are expressed on primary and metastatic ocular melanomas.

In Vivo Confocal Microscopic Evidence of Keratopathy in Patients with Pseudoexfoliation Syndrome

PURPOSE To measure the density of cells in different layers of the cornea and to determine whether morphologic changes of the subbasal corneal nerve plexus are present in eyes with the pseudoexfoliation (PEX) syndrome. METHODS Twenty-seven patients with unilateral PEX syndrome and 27 normal controls were investigated. All eyes underwent corneal sensitivity measurements with an esthesiometer and in vivo confocal microscopic study. Densities of the epithelial, stromal, and endothelial cells were measured. The density and tortuosity of the subbasal corneal nerve plexus were also evaluated. RESULTS Eyes with PEX syndrome had significantly lower cell densities in the basal epithelium (P = 0.003), anterior stroma (P = 0.007), intermediate stroma (P = 0.009), posterior stroma (P = 0.012), and endothelium (P < 0.0001) than in the corresponding layers of normal eyes. PEX eyes also had lower subbasal nerve densities and greater tortuosity of the nerves than normal eyes. Fellow eyes of patients with PEX also had significantly lower densities of the basal epithelial and endothelial cells than the normal eyes. Corneal sensitivity was significantly decreased in PEX eyes, and this was significantly correlated with the decrease of basal epithelial cell and subbasal nerve densities. CONCLUSIONS These results have shed light on understanding of the pathogenesis of decreased corneal sensitivity in eyes with PEX syndrome. PEX syndrome is probably a binocular condition for which keratopathy of the fellow eye also requires observation.

Efficacy of commercial soft contact lens disinfectant solutions against Acanthamoeba

PurposeTo investigate the relative efficacy of Japanese commercial soft contact lens disinfectant solutions against Acanthamoeba trophozoites and cysts.Materials and methodsEight types of multipurpose solution (MPS), two types of hydrogen peroxide solution, and one povidone–iodine solution were evaluated to determine their effect against Acanthamoeba trophozoites and cysts (ATCC 50514). Acanthamoeba cysts were cultured in encystment medium for either 1 or 2 weeks (1 and 2-week-old cysts). The trophozoites and cysts were treated with each disinfectant solution for 0, 2, 4, 8, or 24 h. After performing four tenfold serial dilutions of each test solution, dilutions were cultured for 10 days. The number of surviving organisms was calculated using the trimmed Spearman–Karber method.ResultsAmong the MPS tested, only four were effective against trophozoites after treatment for 4 h, and none was effective against 2-week-old cysts. Hydrogen peroxide had a significant effect on trophozoites and 1-week-old cysts, but not on 2-week-old cysts. In contrast, povidone–iodine caused a 2.6 log reduction in 2-week-old cysts.ConclusionsMPS were found to have limited efficacy against trophozoites and no efficacy against 2-week-old cysts. Only povidone–iodine had any efficacy against 2-week-old cysts.

DNA of cytomegalovirus detected by PCR in aqueous of patient with corneal endotheliitis after penetrating keratoplasty.

Purpose: Corneal endotheliitis often leads to severe endothelial dysfunction and can be caused by herpes simplex virus (HSV), varicella zoster virus (VZV), and other viruses (eg, the mumps virus). We report a case of corneal endotheliitis caused by cytomegalovirus (CMV) that developed after a penetrating keratoplasty. Methods: A complete ophthalmologic examination was performed on a patient with corneal endotheliitis that developed after a penetrating keratoplasty. To determine the cause of the endotheliitis, polymerase chain reaction (PCR) was used to amplify the DNA of HSV, VZV, and CMV in samples of the aqueous humor. Results: Slit-lamp biomicroscopy showed a moderate stromal edema in the upper temporal part of the transplanted cornea along with keratic precipitates (KPs) arranged in a coin-shaped pattern. Repeated treatments with steroids and acyclovir were only temporarily successful. PCR detected the DNA of CMV in an aqueous sample, and the treatment was switched to topical and systemic application of ganciclovir. This resulted in the disappearance of the KPs and resolution of the stromal edema within 2 weeks. Conclusions: From the PCR results and the favorable response to ganciclovir, the corneal endotheliitis was most likely caused by cytomegalovirus in this case.

Ocular distribution of intravenously administered micafungin in rabbits

The ocular distribution of micafungin (MCFG), which has antifungal activity against Candida and Aspergillus species, was followed after the systemic administration of MCFG in rabbits. After MCFG (10 mg/kg) plus fluconazole (FLCZ; 10 mg/kg) was administered intravenously, the rabbits were killed, and MCFG and FLCZ concentrations in retina-choroid, vitreous humor, and plasma were determined by high performance liquid chromatography or liquid chromatography/mass spectrometry. The mean concentrations of MCFG in the retina-choroid at 0.25, 0.75, 4, 8, and 24 h after administration were 20.18, 15.97, 13.19, 6.27, and 0.75 μg/g, respectively, and were comparable with the MCFG plasma concentrations. The MCFG concentrations in retina-choroid and plasma exceeded the minimal antifungal inhibitory concentrations for endophthalmitis, although MCFG was not detected in the vitreous humor. These results suggest that the intravenous administration of MCFG is an effective treatment for endogenous fungal endophthalmitis when the causative fungus is localized in the retina and choroid.

Suture-Related Keratitis Caused by Corynebacterium macginleyi

ABSTRACT We report two cases of suture-related keratitis following penetrating keratoplasty. In both cases, Corynebacterium macginleyi was isolated from corneal specimens. Scanning electron microscopy revealed that corynebacteria could aggregate and form a biofilm. The MICs of sulbenicillin and fluoroquinolones were high for both isolates. Our findings show that C. macginleyi can cause keratitis with biofilm formation.

Effectiveness of in vivo confocal microscopy in detecting filamentous fungi during clinical course of fungal keratitis.

Purpose: To determine the effectiveness of laser confocal microscopy in detecting filamentous fungi in the cornea of patients with fungal keratitis (FK) and in evaluating the effectiveness of the treatment. Methods: The corneas of 6 patients clinically diagnosed with FK were examined with the Heidelberg Retina Tomograph II-Rostock Cornea Module (HRT II-RCM). Three of these patients were also monitored periodically with the HRT II-RCM after antifungal treatment. Results: The HRT II-RCM examination showed interlocking and branching, white, septated, hyphae-like lines in the cornea of all patients. All 6 patients had positive corneal smears and/or laboratory cultures. Three patients were monitored with HRT II-RCM after antifungal treatment. One patient, whose initial smear was negative, was diagnosed by HRT II-RCM before the positive culture results. In another case, the epithelial regeneration was impaired even 3 weeks after the initial treatment and HRT II-RCM revealed a mass of hyphae in the corneal ulcerated lesion. These findings indicated the necessity of surgical debridement. After the surgical debridement, the corneal epithelial defect was healed. HRT II-RCM was able to detect the morphological changes of hyphae after antifungal treatment and helped in the treatment modifications during the clinical course in all 3 patients. Conclusions: These results indicate that HRT II-RCM can be used to diagnose FK and to monitor the effect of therapy on FK.

Corneal Higher Order Wavefront Aberrations After Hyperopic Laser in situ Keratomileusis

PURPOSE To evaluate the changes in corneal higher order wavefront aberrations after hyperopic laser in situ keratomileusis (LASIK). METHODS In a prospective case series, 15 eyes of 12 patients who had hyperopic LASIK were evaluated. Corneal topography was obtained before and after hyperopic LASIK with a Nidek EC 5000 laser using 5.5/8.0 ablation zones. Using anterior corneal height data, the changes in corneal higher order wavefront aberrations were calculated. RESULTS The surgery significantly increased both corneal coma-like aberration (preoperative/6 months postoperative, 0.054/0.147 [172% increase] for 3-mm pupil and 0.381/1.076 [182% increase] for 6-mm pupil) and corneal spherical-like aberration (preoperative/6 months postoperative, 0.039/0.067 [72% increase] for 3-mm pupil and 0.297/0.959 [223% increase] for 6-mm pupil). The surgery significantly decreased Zernike coefficient 12 and the polarity of corneal spherical aberration changed from preoperative positive value to negative postoperatively. For a 3-mm pupil, the achieved changes in spherical equivalent refraction significantly correlated with the induced changes in the corneal coma-like aberration (R = 0.629, P = .010), but not with those in corneal spherical-like aberration (R = 0.408, P=.133) or Zernike coefficient 12 (R = -0.301, P = .282). For a 6-mm pupil, the achieved changes in spherical equivalent refraction significantly correlated with the induced changes in the corneal spherical-like aberration (R = 0.862, P < .0001) and Zemike coefficient 12 (R = -0.872, P < .001) but not with those in corneal coma-like aberration (R = 0.449, P = .094). CONCLUSIONS Hyperopic LASIK significantly increases corneal coma-like and spherical-like aberrations and changes corneal spherical aberration from a positive to negative value.