[A questionnaire survey of indication for cataract surgery].

PURPOSE: Advances in cataract surgery merits changes in its indication as well as related preoperative eye examinations. This, however, has not been reported in Japan. We performed a questionnaire survey to provide data for these changes. METHOD: The subjects were 121 facilities in university hospitals and 1,413 randomly sampled doctors from 14,134 Japanese Ophthalmology Society members. The questionnaire involved the indications and pre-operative examinations for cataract surgery. The results were compared separately amang two groups: operating and non-operating facilities. RESULTS: The number of respondents was 552 (36%). Operating facilities were 72%, and the annual operation volume was an average of 568 cases (0-4,000). The most important item when the surgery was recommended was the degree of life inconvenience, followed by corrected visual acuity, and there was no difference between the two groups in either. As for the examination to determine the surgery, distant visual acuity, specular microscopy, near visual acuity and corneal topography were high. The highest value of corrected visual acuity was less than 0.7 to indicate surgery in both groups. However, there were significantly more operating facilities in which the corrected visual acuity for the indication of the surgery was 0.7 or more. There was little use of the interview list and image analysis equipment. CONCLUSION: There was no difference in the indications for cataract surgery and the pre-operative examinations between the two groups; the most important item among the indications was the degree of life inconvenience. The corrected visual acuity to indicate surgery in operating facilities was higher than in non-operating facilities.

A case of papilledema in Camurati-Engelmann disease treated effectively with prednisolone.

Camurati-Engelmann disease (CED) causes bone pain, muscle weakness, and cranial nerve symptoms due to abnormal thickening of the long bones of the limbs and the cortex of the skull. The pathophysiology of CED is a gain-of-function variant of transforming growth factor beta 1 (TGFB1). The ophthalmological symptoms of CED are usually caused by increased intracranial pressure and optic canal stenosis. Here, we report the case of a patient in whom prednisolone was effective against papilledema caused by CED. In this case, when papilledema was observed in both fundi, the patient showed increased bone pain, fever, and elevated CRP and ALP levels. Brain magnetic resonance imaging (MRI) revealed a high short tau inversion recovery (STIR) signal in both optic nerves, suggesting edematous changes. Prednisolone ameliorated bone pain, fever, and papilledema, resulting in a slight improvement of the visual function of the right eye. Our results suggest that prednisolone may be effective in treating ophthalmologic symptoms in addition to bone pain in patients with CED.

Cyclin-dependent kinase inhibitor p16 and p21 expression, and cell cycle change in human lens epithelial cell line SRA 01/04 following contact inhibition in normal culture.

PURPOSE: To describe the pattern of expression of the cyclin-dependent kinase inhibitors (CDKIs) p16, p21 and p27, and the cell cycle in SRA 01/04 cells relative to contact inhibition. METHODS: SRA 01/04 cells were grown to overconfluence under normal conditions. At various phases of the cell growth, cells were assayed by flow cytometry and Western blotting for the expression of CDKIs. RESULTS: Expression of p16 was detected from early logarithmic growth to stationary phases, during which the number of cells in G(0)/G(1) increased from 46 to 69%. Expression of p21 was detected only during the overgrowth phase, when 60% of the cells were in G(0)/G(1). Expression of p27 was not observed in SRA 01/04 cells. CONCLUSIONS: p16 expression was likely mediated by G(0)/G(1) arrest to induce contact inhibition in SRA 01/04. p21 expression may be related to withdrawal, and p27 deficiency may be related to the immortality of this cell line. It is possible for p16 to stop proliferation of lens epithelial cells like progressing posterior capsular opacification, by overexpression to mimic contact inhibition.

ST2 gene expression is proliferation-dependent and its ligand, IL-33, induces inflammatory reaction in endothelial cells.

ST2 gene products that are members of IL-1 receptor family are expressed in various cells such as growth-stimulated fibroblasts and Th2 helper T-cells, and recently, IL-33, which belongs to IL-1 family, was identified as the ligand for ST2L, the receptor type product of the ST2 gene. Subsequently, IL-33 and ST2L have been reported to be involved in Th2 immunity and inflammation, however, their functions on non-immunological cells are still obscure. Among non-immunological adhesive cells, vascular endothelial cells were reported to express both ST2 gene products and IL-33, therefore, we investigated the expression manner of the ST2 gene in vascular endothelial cells and the effect of IL-33 on endothelial cells. ST2 gene was expressed in each of the vascular endothelial cell types tested, and the expression was growth-dependent and down-regulated when the cells were differentiated to form vascular structures on the extracellular membrane matrix. IL-33 scarcely affected the growth and tube formation of the endothelial cells, but induced IL-6 and IL-8 secretion from endothelial cells with the rapid activation of extracellular signal-regulated kinase (ERK) 1/2, so IL-33 is supposed to involve in inflammatory reaction of vascular endothelial cells through its receptor, ST2L.

[Comparison in effectiveness of sterilization between chlorhexidine gluconate and povidone-iodine].

PURPOSE: To evaluate the positive value of bacterial cultures which were collected soon after various types of ophthalmic surgery, from eyelids and conjunctiva disinfected by dilute chlorhexidine gluconate or povidone-iodine solution. METHODS: This study evaluated 179 cases (mean age, 65.6 +/- 15.3) (210 eyes) who underwent cataract surgery, vitrectomy and scleral buckling performed by the same surgeon between April 2005 and December 2005. We divided all the cases into two groups: cases whose eyelids and conjunctiva were disinfected with dilute 0.05% solution of chlorhexidine gluconate, and the other cases whose eyelids were disinfected with 10% solution of povidone-iodine, and the conjunctiva was treated with 16 times dilute povidone-iodine solution. Soon after surgery, samples for bacterial culture were scraped from all eyelids and conjunctiva by swabs. RESULTS: From the eyelids, bacteria were detected from 39 of the 107 eyes in the chlorhexidine gluconate group, and 19 of the 103 eyes in the povidone-iodine group (p<0.01). There was no significant difference between the chlorhexidine gluconate and povidone-iodine groups with respect to the number of positive cases from the conjunctiva. However, a higher positive value in bacterial culture collected from eyelids was shown in the chlorhexidine gluconate group. CONCLUSIONS: Therefore, based on this result, we consider that povidone-iodine solution has a superior disinfectant effect compared to chlorhexidine gluconate.

A technique for preventing spontaneous loss of lacrimal punctal plugs.

PURPOSE: To describe a technique for the prevention of spontaneous loss of lacrimal punctal plugs. DESIGN: Interventional case series. METHODS: Four consecutive patients (10 puncta in seven eyes) with severe dry eyes who experienced repeated spontaneous plug loss underwent punctal occlusion by suturing plugs with 10-0 polypropylene sutures. RESULTS: All punctal plugs were fitted to lacrimal puncta by anchoring the sutures. Plug retention rate was 80% at 6 months after the procedure. CONCLUSION: Suturing punctal plugs is effective in the production of long-term punctal closure in patients with repeated spontaneous plug loss.

Detection of cytotoxic anti-LEDGF autoantibodies in atopic dermatitis.

In the last two decades, atopic dermatitis (AD) has been of increasing clinical significance in Japan. Eight-20% of patients with AD developed progressive cataracts (cataract-AD) and lens epithelial cells (LECs) were severely damaged. Lens epithelium-derived growth factor (LEDGF) is a newly isolated survival factor. In the presence of LEDGF, LECs survive well and in the absence of LEDGF, they become highly susceptible to stress. We investigated (1) whether auto-antibody (auto-Ab) to LEDGF is present in sera of AD patients and (2) whether depletion of LEDGF by the auto-Ab kills LECs. In sera from 26 patients with AD using ELISA, we found significantly higher levels of auto-Ab to LEDGF than that in a normal control group. Affinity purified auto-Ab to LEDGF from these sera killed LECs without complement activation. Levels of histamine in the AD group were significantly higher and levels of prostaglandin E2 were significantly lower than in the normal group. However, statistically there are no differences between sera from AD and cataract-AD in levels of Ab to LEDGF, histamine, prostaglandin E2 (PGE2), immunoglobulin E (IgE) and eosinophiles. We speculate that cataract-AD may be induced, in part, by a combination of high levels of serum histamine and eye rubbing which could break the blood-aqueous barrier to allow the entry of Ab to LEDGF into the privileged compartment, thus, reducing LEDGF levels, resulting in damage to LECs, and cataract formation.

Human lens epithelial cell damage and stimulation of their secretion of chemical mediators by benzalkonium chloride rather than latanoprost and timolol.

OBJECTIVE: To investigate the effects of latanoprost, timolol maleate, and benzalkonium chloride on cell damage and induction of the secretion of chemical mediators of stress and wound healing by human lens epithelial cells in culture. METHODS: Cells from a human lens epithelial cell line (SRA01/04) were cultured in Dulbecco minimum essential medium supplemented with 5% fetal bovine serum. The amounts of latanoprost (50 micro g/mL), timolol maleate (5 mg/mL), or benzalkonium chloride (200 micro g/mL) used in eyedrops, and x10 to x1000 dilutions thereof, were added to the medium. After 7 days' culture, cell morphological changes were assessed using phase-contrast microscopy, and cell-free culture supernatants were collected for prostaglandin E2 (PGE2), interleukin 1alpha (IL-1alpha), and interleukin 6 (IL-6) iodine I 125 radioimmunoassay, enzyme-linked immunosorbent assay, and chemiluminescent enzyme immunoassay, respectively. RESULTS: All cells that were cultured with the concentrations of latanoprost, timolol, or benzalkonium chloride used in eyedrops detached from the culture dish and died within 3 days. At a x10 dilution of latanoprost or timolol or a x100 dilution of benzalkonium chloride, no proliferation or elongation of the cells was observed. Secretions of PGE2, IL-1alpha, and IL-6 at x10 dilutions of latanoprost or timolol were 3 to 77 times higher than in controls, whereas they were 190 to 305 times higher at a x180 dilution of benzalkonium chloride. The amounts of these soluble mediators in culture supernatants depended on the dose of latanoprost, timolol, or benzalkonium chloride added. CONCLUSION: Our results indicate that benzalkonium chloride, used as the preservative in eyedrops containing latanoprost or timolol, is the agent most damaging to lens epithelial cells and most strongly stimulates the expression of soluble chemical mediators in these cells.

Prostaglandins and cystoid macular edema.

This review discusses the roles and interactions of prostaglandins and other possible chemical mediators in cystoid macular edema. Prostaglandins have been studied as a potential causative factor of cystoid macular edema following cataract/intraocular lens surgery. The authors' hypothesis and data with regard to the mechanisms of postoperative cystoid macular edema and other inflammatory conditions are presented. The effects of nonsteroidal anti-inflammatory drugs, which are antagonists of prostaglandin biosynthesis, on postoperative inflammatory conditions including cystoid macular edema are also reviewed. Lastly, a mechanism for the induction of cystoid macular edema by anti-glaucoma eyedrops, including prostaglandin analogs is proposed. The results from two clinical trials recently conducted by the authors suggest that the preservative rather than the active ingredient is the causative factor.

ESCRS Binkhorst lecture 2002: Pseudophakic preservative maculopathy.

Many antiglaucoma eyedrops are reported to cause cystoid macular edema (CME) in aphakia and pseudophakia. We review 4 clinical and laboratory studies that compare the incidence of CME in early postoperative pseudophakia in eyes that received preserved latanoprost and timolol, nonpreserved timolol, and the preserved and nonpreserved vehicle for these drugs and looked at the morphological damage to cells and the changes in the indicators of cytokine and prostaglandin (PG) synthesis caused by latanoprost and timolol and the preservative benzalkonium chloride. Based on the findings of these studies, which indicate that the preservative causes increased synthesis of PGs and other substances and intensified postoperative inflammation, the term pseudophakic preservative maculopathy is proposed for CME caused by antiglaucoma eyedrops.

A clinicopathologic case report of inflammatory pseudotumors involving the conjunctiva and lung.

BACKGROUND: Inflammatory pseudotumors are characterized histopathologically by aggregates of inflammatory lymphocytes, plasma cells, neutrophils, and fibroblasts. We report a rare case of inflammatory pseudotumor involving both the conjunctiva and lung. CASE: A 58-year-old man with a 6-year history of pulmonary inflammatory pseudotumor was referred to our hospital for evaluation of conjunctival swelling in the left eye and bilateral iritis. OBSERVATIONS: The subconjunctival tumor enlarged slowly, but regressed spontaneously. After partial resection of the subconjunctival and lung tumors, the presence was confirmed of aggregates of chronic inflammatory cells (lymphocytes, plasma cells, neutrophils, fibroblasts) without noncaseating epithelioid granuloma formation. Gene rearrangement testing ruled out malignancy. The patient was treated with oral corticosteroids for fever and primary biliary hepatic cirrhosis. Iritis signs subsided slightly in response to corticosteroids, but persisted. The temporal subconjunctival pseudotumor resolved without recurrence. CONCLUSIONS: This case was compatible histopathologically with inflammatory pseudotumor, and is a rare case of simultaneous occurrence in the lung and conjunctiva.

Inhibitory effects of Arg-Gly-Asp (RGD) peptide on cell attachment and migration in a human lens epithelial cell line.

Posterior capsule opacification (PCO) after cataract surgery is caused by growth of residual human lens epithelial (HLE) cells on the posterior capsule. We have shown that extracellular matrix (ECM) is an essential factor for HLE cell attachment and migration. The purpose of this study was to examine the inhibitory effects of Arg-Gly-Asp (RGD) peptide on cell attachment and migration in an HLE cell line. HLE cell line cells (SRA 01/04) that were obtained by transfection of large T antigen of SV40 were cultured in the absence of serum. The culture dishes were coated with type IV collagen, laminin or fibronectin, and Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) RGD peptide (0.1, 0.3, 1.0, 2.0 mg/ml) was added to the medium. The number of attached cells was counted after 90 min of incubation, and the inhibitory effects of GRGDSP RGD peptide on cell attachment were calculated. Cell attachment on the fibronectin-coated dishes was inhibited by GRGDSP RGD peptide at concentrations higher than 0.3 mg/ml; the inhibitory rate was 80% at a concentration of 2.0 mg/ml. The inhibition of cell attachment by GRGDSP RGD peptide on laminin-coated dishes appeared only at a concentration of 2.0 mg/ml, whereas no effects were observed on the type IV collagen-coated dishes. The inhibitory effects of GRGDSP RGD peptide on cell migration were measured in medium containing 2.0 mg/ml of GRGDSP RGD peptide after 1, 3, 5 and 7 days of culture. Cell migration was inhibited by GRGDSP RGD peptide from 1 day of culture on the fibronectin-coated dishes and from 5 days of culture on the laminin-coated dishes, whereas no effects were observed on the type IV collagen-coated dishes. GRGDSP RGD peptide inhibited cell attachment and migration on laminin and fibronectin that have RGD sequences. These data suggested that RGD peptide may have the potential to prevent PCO.

Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene.

The Pax6 gene plays crucial roles in eye development and encodes a transcription factor containing both a paired domain and a homeodomain. During embryogenesis, Pax6 is expressed in restricted tissues under the direction of distinct cis-regulatory regions. The head surface ectoderm-specific enhancer of mouse Pax6 directs reporter expression in the derivatives of the ectoderm in the eye, such as lens and cornea, but the molecular mechanism of its control remains largely unknown. We identified a Pax6 protein-responsive element termed LE9 (52 bp in length) within the head surface ectoderm-specific enhancer. LE9, a sequence well conserved across vertebrates, acted as a highly effective enhancer in reporter analyses. Pax6 protein formed in vitro a complex with the distal half of LE9 in a manner dependent on the paired domain. The proximal half of the LE9 sequence contains three plausible sites of HMG domain recognition, and HMG domain-containing transcription factors Sox2 and Sox3 activated LE9 synergistically with Pax6. A scanning mutagenesis experiment indicated that the central site is most important among the three presumptive HMG domain recognition sites. Furthermore, Pax6 and Sox2 proteins formed a complex when they were expressed together. Based on these findings, we propose a model in which Pax6 protein directly and positively regulates its own gene expression, and Sox2 and Sox3 proteins interact with Pax6 protein, resulting in modification of the transcriptional activation by Pax6 protein.