Pseudoxanthoma elasticum resulting in acute coronary syndrome.

Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder that causes elastic tissue degeneration in the skin, eyes, and cardiovascular system. Gastrointestinal bleeding and fundus hemorrhage are serious complications associated with PXE prognosis as well as cardiovascular involvement. This is a rare case of acute coronary syndrome in a PXE patient with high bleeding risk. Learning objective: Pseudoxanthoma elasticum (PXE) resulting in acute coronary syndrome (ACS) is rare. Given PXE patients are generally at very high bleeding risk, antithrombotic therapy as secondary prevention after ACS onset should be taken into full consideration.

In vivo confocal microscopic images of atypical amiodarone-induced keratopathy in patient with epithelial basement membrane dystrophy.

A 73-year-old man presented with bilateral corneal opacities. Slit-lamp biomicroscopy showed vortex and oval-shaped opacities. In vivo confocal microscopy (IVCM) showed findings characteristic of amiodarone-induced keratopathy along with epithelial basement membrane dystrophy (EBMD). The IVCM findings indicated that the oval-shaped opacities can be present with amiodarone-induced keratopathy in patients with EBMD.

Development of traumatic bilateral horseshoe-shaped macular tear without vitreous traction: Case report.

To report our findings in a case with bilateral horseshoe-shaped macular tears. Both eyes of a 68-year-old woman developed horseshoe-shaped macular tears in the absence of vitreous traction due to prior vitrectomy in one eye and a posterior vitreous detachment in the other eye. Vitrectomy with the inverted internal limiting membrane flap technique led to a successful closure of the macular tear bilaterally, and an improvement of her visual acuity in both eyes. The cause of horseshoe-shaped macular tear was most likely due to a retinal rupture from a blunt trauma.

Patient Preferences for Anti-Vascular Endothelial Growth Factor Treatment for Wet Age-Related Macular Degeneration in Japan: A Discrete Choice Experiment.

BACKGROUND: In Japan, intravitreal anti-vascular endothelial growth factor (anti-VEGF) dosing regimens for wet age-related macular degeneration (wAMD) include pro re nata, every 2 months, and treat-and-extend, resulting in different outcomes and patient burden. Although reflecting patient preferences in treatment decision-making is desirable, few studies have examined this in Japan. This study assessed the patients willingness to trade-off between different dosing regimens. PATIENTS AND METHODS: Patients with wAMD were recruited from four Japanese university hospitals to complete a face-to-face cross-sectional survey. In a discrete choice experiment, patients were asked to choose their preferred option from two anti-VEGF treatment profiles shown side-by-side across a series of choice tasks. The profiles varied on four attributes: number of injections in 12 months, number of physician consultations in 12 months, chance of 1-year visual acuity (VA) improvement, and chance of 2-year VA maintenance. Preference weights were estimated using hierarchical Bayes' models. RESULTS: Overall, 120 patients (30 treatment naïve and 90 anti-VEGF experienced) completed the survey. Patients were willing to accept an increase from three to approximately eight injections in 12 months to increase the chance of 1-year VA improvement from 25% to 40%. They would be willing to accept 11 injections in 12 months if the chance of 2-year VA maintenance increased from 80% to 96%. The most valued attributes were increasing the chance of 2-year VA maintenance and reducing the number of injections in 12 months, which were each about twice as important as decreasing physician consultations in 12 months and increasing the chance of 1-year VA improvement (p<0.001). Among the dosing regimens, patients most preferred treat-and-extend because of its higher chance of 2-year VA maintenance. CONCLUSION: Informing patients with wAMD about the likelihood of long-term VA maintenance when selecting treatment may increase the acceptance of an optimal treatment regimen and number of injections.

Mechanism of Proliferation of Cultured Human Corneal Endothelial Cells.

Because human corneal endothelial cells (HCECs) do not proliferate once the endothelial monolayer has formed, corneal wound healing is believed to be mediated by cell enlargement or migration, rather than by proliferation. However, the cellular mechanisms involved in wound healing by HCECs have not been fully determined. In this review, we focus on the effects of promyelocytic leukemia zinc finger (PLZF), a DNA-binding transcription factor, and transforming growth factor (TGF)-ß2 on the proliferation and migration of cultured HCECs. Involvement of the mitogen-activated protein kinase (MAPK) signaling pathway in the migration of HCECs was also investigated. Expression of PLZF mRNA decreased as cell-cell contact was disrupted and returned to the original level as cell-cell contact was re-formed. Assessment with a real-time cell electronic sensing system revealed that proliferation of cultured HCECs was inhibited after infection with Ad-PLZF and exposure to TGF-ß2. Migration of cultured HCECs was increased by TGF-ß2 through p38 MAPK activation. We conclude that PLZF expression in cultured HCECs is closely related to the formation of cell-cell contact and that TGF-ß2 suppresses proliferation of cultured HCECs, while promoting their migration through p38 MAPK activation.

Ocular Behçet's disease is less complicated with allergic disorders. A nationwide survey in Japan.

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. METHODS: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). RESULTS: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. CONCLUSIONS: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.

Therapeutic Effect of 0.1% Topical Tacrolimus for Childhood Interstitial Keratitis Refractory to Cyclosporine.

PURPOSE: To report our findings in a case of childhood refractory interstitial keratitis successfully treated with 0.1% topical tacrolimus. METHODS: A 12-year-old boy presented with a 3-year history of interstitial keratitis. For the recurrent interstitial keratitis he had been treated with topical and systemic acyclovir, steroids, and topical cyclosporine for 3 years. Our examinations revealed severe stromal infiltrates and neovascularization. Treatment was changed from topical 0.5% cyclosporine to topical 0.1% tacrolimus combined with topical acyclovir and betamethasone. RESULTS: After 2 weeks of treatment with topical tacrolimus, the degree of stromal infiltrates decreased. Although the improvements were slow, the stromal infiltrates resolved somewhat, and neovascularization and topical acyclovir and betamethasone were tapered and stopped in 18 months. Since then, the patient has not shown any recurrence for 9 months without medication. CONCLUSION: Our findings indicate that topical tacrolimus should be considered for treating refractory interstitial keratitis in children.

A case of herpetic keratitis after subconjunctival triamcinolone acetonide injection.

PURPOSE: We report a case of herpetic epithelial keratitis that developed after subconjunctival triamcinolone acetonide injection (STI). METHODS: A 65-year-old female with anterior uveitis and hypotony in her right eye was given a STI (2 mg/0.5 ml). After the injection, she developed redness and an ocular discharge. A clinical examination was performed and real-time polymerase chain reaction (PCR) was used to amplify the viral DNA in a corneal scraping. RESULTS: Slit-lamp biomicroscopy revealed a severe purulent discharge, conjunctival injection, and a geographic corneal ulcer in the right eye. Herpes simplex virus 1 DNA was identified in the corneal scraping using real-time PCR. Herpetic keratitis was diagnosed and topical acyclovir ointment as well as systemic valacyclovir were started. The inflammation subsided with this medication. CONCLUSION: We encountered a case of herpetic epithelial keratitis after a STI.

Involvement of P38MAPK in human corneal endothelial cell migration induced by TGF-ß(2).

Because human corneal endothelial cells do not proliferate once the endothelial monolayer is formed, corneal wound healing is thought to be mediated by cell enlargement or migration rather than proliferation. However, the cellular mechanisms involved in corneal wound healing have not been fully determined. Because transforming growth factor-ß(2) (TGF-ß(2)) isoform is present in high concentrations in normal human aqueous humor, it may play a role in human corneal endothelial cell wound healing. The purpose of this study was to determine the effect of TGF-ß(2) on the proliferation and migration of cultured human corneal endothelial cells (HCECs). To achieve this, we first examined the effect of TGF-ß(2) on the wound closure rate in an in vitro HCEC wound healing model. However, unexpectedly TGF-ß(2) had no effect on the wound closure rate in this model. Therefore, a real-time cell electronic sensing (RT-CES) system and the BrdU incorporation assay were used to determine the effect of TGF-ß(2) (0.1-10 ng/ml) on cultured HCEC proliferation during in vitro wound healing. The specificity of this effect was confirmed by adding the TGF-ß receptor I kinase inhibitor. TGF-ß(2) inhibited the proliferation of HCECs in a dose dependent way and was blocked by TGF-ß receptor I kinase inhibitor. Next, the Boyden chamber assay was used to determine how TGF-ß(2) (10 ng/ml) affect HCEC migration. Exposure to TGF-ß(2) increased cell migration, and a synergistic effect was observed when FGF-2 was added. To determine whether the mitogen-activated protein kinase (MAPK) signaling pathway is involved in the migration of HCECs, western blot analysis and Bio-Plex™ suspension array were used to detect phosphorylation of Erk1/2, p38, and JNK in HCECs stimulated by TGF-ß(2) and/or FGF-2. The effect of the p38 MAPK inhibitor, SB239063 (10 µM), on TGF-ß(2) and/or FGF-2-induced cellular migration was determined by the Boyden chamber assay. Both TGF-ß(2) and FGF-2-induced p38 phosphorylation, and a synergistic effect was observed with exposure to both growth factors. SB 239063 inhibited TGF-ß(2) and FGF-2-induced migration of HCECs. These results indicate that TGF-ß(2) reduces proliferation but stimulates migration of cultured HCECs. In addition, TGF-ß(2) and FGF-2 may have synergistic effects on the migration of HCECs mediated by p38 MAPK phosphorylation.

Coincidence of Varicella-Zoster Virus Anterior Uveitis in a Patient with Chandler's Syndrome.

PURPOSE: We report a patient who, based on the clinical manifestations, was originally diagnosed as having Chandler's syndrome and later developed varicella-zoster virus (VZV) DNA-positive anterior uveitis. METHODS: The patient with Chandler's syndrome who manifested anterior uveitis underwent a complete ophthalmologic examination. Polymerase chain reaction (PCR) was used to amplify the viral DNA in the aqueous humor to determine the cause of the intraocular inflammation. RESULTS: Slit-lamp biomicroscopy showed focal iris atrophy and peripheral anterior synechiae (PAS); specular microscopy of the corneal endothelium disclosed the hammered-silver appearance. Based on these clinical findings, we diagnosed this patient as having Chandler's syndrome. During the follow-up period, however, the inflammatory cells suddenly appeared in the anterior chamber with formation of keratic precipitates and an increased intraocular pressure (IOP). VZV DNA was displayed in the aqueous humor by PCR. Based upon the diagnosis of VZV anterior uveitis, corticosteroids and acyclovir were given topically and systemically. The inflammation subsided with these medications; however, trabeculectomy was finally needed to control the IOP due to PAS progression. CONCLUSION: The coincidence of VZV anterior uveitis with Chandler's syndrome may constitute an implication for the possible viral etiology of iridocorneal endothelial syndrome.

[The effectiveness of intravitreal administration of bevacizumab for choroidal neovascularization in retinal angioid streaks].

PURPOSE: To investigate the effectiveness of intravitreal administration of bevacizumab (IVB) for choroidal neovascularization (CNV) in retinal angioid streaks (AS). SUBJECTS AND METHODS: Five eyes of four subjects with CNV in AS were observed for an average followup period of 12 months. The average greatest linear diameter (GLD) of the AS was 4315 microm before treatment. IVB (1.0 mg or 1.25 mg) was performed a total of two times at eight week intervals, and additional bevacizumab was administered whenever exudative changes occurred. RESULTS: Visual acuity improved in one eye (20%), was maintained in two eyes (40%), and worsened in two eyes (40%). Recurrence of CNV was observed in two eyes (40%). Before treatment, the GLD was 2439, 2844, and 3654 microm in the three eyes in which visual acuity was maintained, and 5803 and 6837 microm in the two eyes with worsened visual acuity. Recurrence of CNV was observed in the two eyes with worsened visual acuity. CONCLUSION: Short-term CNV fibrosis and maintenance of visual acuity were achieved with IVB in cases in which the GLD was less than 3500 microm.

Role of insulin in regulation of Na+-/K+-dependent ATPase activity and pump function in corneal endothelial cells.

PURPOSE: The Na(+)-/K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. The role of insulin in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells was investigated. METHODS: Confluent monolayers of mouse corneal endothelial cells were exposed to insulin. ATPase activity was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate; Na,K-ATPase activity was defined as the portion of total ATPase activity sensitive to ouabain. Pump function was measured with the use of a Ussing chamber; pump function attributable to Na,K-ATPase activity was defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis and immunocytochemistry were performed to measure the expression of the Na,K-ATPase alpha(1)-subunit. RESULTS: Insulin increased the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. These effects were blocked by protein kinase C (PKC) inhibitors and protein phosphatases 1 and 2A inhibitor. Western blot analysis indicated that insulin decreased the ratio of the inactive Na,K-ATPase alpha(1)-subunit. Immunocytochemistry indicated that insulin increased the cell surface expression of the Na,K-ATPase alpha(1)-subunit. CONCLUSIONS: These results suggest that insulin increases the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. The effect of insulin is mediated by PKC and presumably results in the activation of PP1, 2A, or both, which are essential for activating Na,K-ATPase by alpha(1)-subunit dephosphorylation.

Effect of anterior chamber depth on shear stress exerted on corneal endothelial cells by altered aqueous flow after laser iridotomy.

Purpose. The study hypothesis was that shear stress caused by abnormal aqueous flow is one of the causes of corneal endothelial cell loss after laser iridotomy (LI). The shear stress exerted on the corneal endothelial cells (CECs) in anterior chambers (ACs) of different depths was calculated by a computational fluid dynamics program. The effect of shear stress was also examined on human corneal endothelial cells (HCECs) grown on microscope slides. Methods. Three-dimensional models of the AC were constructed, with and without an LI window, and AC depths of 2.8, 1.8, 1.5, and 1.0 mm. The speed of aqueous streaming through the LI window was obtained from animal studies and used to calculate the shear stress exerted on the CECs. Cultured HCECs attached to glass slides were subjected to different magnitudes of shear stress by exposing the cells to different flow rates of the culture solution. The number of cells remaining attached to the slide under each condition was determined. Results. The shear stresses were 0.14, 0.31, 0.48, and 0.70 dyn/cm(2) for models with AC depths of 2.8, 1.8, 1.5, and 1.0 mm, respectively. When cultured HCECs were subjected to shear stress within the range calculated by the three-dimensional models, the number of cells remaining attached to the glass slide decreased as the magnitude and duration of the shear stress increased. Conclusions. Shear stress exerted on CECs after LI may reach a magnitude high enough to cause cell damage and loss in eyes, especially in those with shallow anterior chambers.

The effects of dexamethasone on the Na,K-ATPase activity and pump function of corneal endothelial cells.

PURPOSE: The Na(+)- and K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. We investigated the possible role of dexamethasone in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells. METHODS: Confluent monolayers of mouse corneal endothelial cells were exposed to dexamethasone. ATPase activity of the cells was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate, with Na,K-ATPase activity being defined as the portion of total ATPase activity sensitive to ouabain. Pump function of the cells was measured with the use of an Ussing chamber, with the pump function attributable to Na,K-ATPase activity being defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis was examined to measure the expression of the Na,K-ATPase alpha(1)-subunit. RESULTS: Dexamethasone (1 or 10 microM) increased the Na,K-ATPase activity and pump function of the cultured cells. These effects of dexamethasone were blocked by cycloheximide, a protein synthesis inhibitor. Western blot analysis also indicated that dexamethasone increased the expression of the Na,K-ATPase alpha(1)-subunit, whereas it decreased the expression of the phospho-Na,K-ATPase alpha(1)-subunit. CONCLUSIONS: Our results suggest that dexamethasone stimulates Na,K-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells is mediated by Na,K-ATPase synthesis and increase in an enzymatic activity by dephosphorylation of Na,K-ATPase alpha(1)-subunits.

Role of promyelocytic leukemia zinc finger protein in proliferation of cultured human corneal endothelial cells.

PURPOSE: To review the role of promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor and negative regulator of cell cycling, in the proliferation of cultured human corneal endothelial cells (HCECs). METHODS: The expression pattern of PLZF mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative PCR in HCECs and normal human corneal epithelia. The effect of cell-cell contact on expression of the PLZF gene was studied after incubation of the cultured HCECs in EDTA. The proliferation rate of cultured HCECs was assayed by a real-time electronic sensing (RT-CES) system, and DNA microarray analysis was performed to find the PLZF-regulating genes in cultured HCECs infected with LacZ- and PLZF-carrying adenoviruses (Ad-LacZ, Ad-PLZF). RESULTS: PLZF mRNA was expressed in HCECs in vivo and in completely confluent HCECs but not in subconfluent HCECs in vitro. Real-time PCR showed that the expression of PLZF mRNA was decreased by approximately 20-fold when incubated with EDTA and returned to a normal level as the cell-cell contact reformed. Cell proliferation assay by the RT-CES system showed that infection of cultured HCECs with Ad-PLZF inhibited proliferation. CONCLUSIONS: These findings suggest that PLZF plays an important role in the suppression of proliferation of HCECs.

Effects of promyelocytic leukemia zinc finger protein on the proliferation of cultured human corneal endothelial cells.

PURPOSE: To determine whether the promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor and negative regulator during cell cycling, plays a role in the proliferation of cultured human corneal endothelial cells (HCECs). METHODS: The expressions of the mRNA and the protein of PLZF were determined by real-time PCR and western blot analysis, respectively. The changes in the expression of the PLZF gene of cultured HCECs were investigated at different times after cell-cell contacts were disrupted by incubation with EDTA. The cell proliferation rate was assessed with a real-time cell electronic sensing (RT-CES) system after cultured HCECs were infected with either PLZF or LacZ encoding adenovirus vector (Ad-PLZF or Ad-LacZ). The PLZF-regulating genes were analyzed by DNA microarray analysis in cultured HCECs infected with Ad-PLZF. RESULTS: The expression of the mRNA of PLZF was first detected when the cultured HCECs became confluent, and the relative amount of PLZF mRNA continued to increase for up to 5 days as the cell-cell contacts were formed more firmly. On the other hand, the expression of the mRNA of PLZF decreased about 20 fold 3 h after EDTA exposure, and gradually returned to the original level as the cell-cell contacts were reformed at 72 h after the exposure. The assessment using the RT-CES system showed that the proliferation of cultured HCECs was inhibited for up to 72 h when infected by Ad-PLZF. DNA microarray analysis revealed that the transforming growth factor-beta stimulated clone 22 (TSC-22) gene was up-regulated by 2.32 fold when infected by Ad-PLZF. CONCLUSIONS: These findings indicate that the expression of PLZF in HCECs is closely related to the formation of cell-cell contacts, and that PLZF may play a role in suppressing their proliferation.

Postoperative low-grade endophthalmitis caused by biofilm-producing coccus bacteria attached to posterior surface of intraocular lens.

We report a case of low-grade inflammation that developed in the anterior segment after cataract extraction with intraocular lens (IOL) implantation. The 57-year-old patient complained of blurred vision 2 weeks after phacoemulsification and IOL implantation in the right eye. Slitlamp biomicroscopy showed many nonpigmented keratoprecipitates. After antibiotic therapy failed, the IOL was removed and aqueous collected. Scanning electron microscopy of the IOL demonstrated many biofilm-producing cocci with slime on the IOL, and aqueous smears showed gram-positive cocci. Two weeks after removal of the IOL, the inflammation disappeared.

Following the migration of a Toxocara larva in the retina by optical coherence tomography and fluorescein angiography.

BACKGROUND: The Toxocara larva is known to migrate across the retina, but the layer in which it migrates and its effect on the retina has been unknown. CASE: An ocular Toxocara infection was diagnosed by an immunological test on a vitreous sample from a patient with a retinal lesion that had migrated. Optical coherence tomography (OCT) and fluorescein angiography (FA) were used in this investigation. OBSERVATIONS: Many small lesions were first detected in the peripheral retina, and vitrectomy was performed because of vitreous haze. Two peripapillary lesions were found during the vitrectomy. OCT of one lesion demonstrated a highly reflective mass located in the nerve fiber layer, and FA showed dye leakage from the lesion as well as hyperfluorescence of the disc. Three weeks later, another lesion was found in the macular area, and OCT and FA findings were the same as for the first lesions. Fluorescein leakage was also observed along the presumed path of the migrating larva. CONCLUSIONS: The movement of the lesion from the peripapillary area to the macular area suggested that a Toxocara larva had migrated across the retina. OCT images indicated that the larva moved in the nerve fiber layer, and FA showed that it caused severe inflammation along its pathway.