Safety and Efficacy of Benzalkonium Chloride-optimized Tafluprost in Japanese Glaucoma Patients With Existing Superficial Punctate Keratitis.

PURPOSE: To evaluate the safety and efficacy of benzalkonium chloride (BAK)-optimized tafluprost (with a BAK concentration reduced from 0.01% to 0.001%) in glaucoma patients with existing superficial punctate keratitis (SPK). PATIENTS AND METHODS: A prospective, multicenter, open-label study was designed to compare BAK-optimized tafluprost administered over 12 weeks relative to other preserved prostaglandin analogs previously administered in Japanese glaucoma patients. Thirty patients with SPK graded at <6 points by area density (AD) scoring in 1 eye were recruited. The primary outcome measure was change in AD score at 12 weeks after the switch in treatment compared with that at baseline. Secondary outcome measures included changes in tear film breakup time (TBUT), hyperemia score, and intraocular pressure (IOP). Four patients were excluded from analysis because of treatment discontinuation. RESULTS: Mean AD score±SD decreased significantly from 3.4±0.9 to 1.8±1.8 after the switch (P<0.0001). Mean TBUT increased significantly from 6.3±3.3 to 8.0±4.2 seconds (P<0.01). Mean hyperemia score remained unchanged, whereas mean IOP decreased significantly from 15.6±2.6 to 14.4±2.0 mm Hg (P<0.01). For patients previously treated with BAK-preserved latanoprost (n=17) or bimatoprost (n=2), mean AD score decreased significantly from 3.4±0.9 to 1.8±1.8 (P<0.01) and mean TBUT increased significantly from 6.4±3.6 to 8.2±4.3 seconds (P<0.01); no such changes were apparent for patients previously treated with sofZia-preserved travoprost (n=7). CONCLUSIONS: BAK-optimized tafluprost is a treatment option to improve the condition of the ocular surface and to maintain IOP control in glaucoma patients with existing SPK who have been previously treated with other BAK-preserved prostaglandin analogs.

Cyclo-meta-phenylene revisited: nickel-mediated synthesis, molecular structures, and device applications.

From a one-pot nickel-mediated Yamamoto-type coupling reaction of m-dibromobenzene, five congeners of [n]cyclo-meta-phenylenes were synthesized and fully characterized. The [n]cyclo-meta-phenylenes possessed a commonly shared arylene unit and intermolecular contacts but varied in packing structures in the crystalline solid state. Columnar assembly of larger congeners yielded nanoporous crystals with carbonaceous walls to capture minor protic or aliphatic solvent molecules. The concise and scalable synthesis allowed exploration of the macrocyclic hydrocarbons as bipolar charge carrier transport materials in organic light-emitting diode devices.

Effect of preoperative duration of stromal edema in bullous keratopathy on early visual acuity after endothelial keratoplasty.

PURPOSE: To clarify the relationship between visual acuity after Descemet-stripping automated endothelial keratoplasty (DSAEK) and the preoperative duration of stromal edema. SETTING: Yamaguchi University Hospital, Yamaguchi, Japan. DESIGN: Comparative case series. METHODS: Patients who had DSAEK were divided into 2 groups based on whether the preoperative duration of stromal edema was less than 12 months (Group A) or more than 12 months (Group B). No patient had postoperative conditions that might have affected postoperative visual outcomes. Postoperatively, the corrected distance visual acuity (CDVA) was measured and the morphology of the anterior cornea evaluated by in vivo laser confocal microscopy. RESULTS: The postoperative CDVA in Group A ranged from 20/50 to 20/16 at 3 months and from 20/66 to 20/16 at 6 months; the maximum CDVA was 20/40 to 20/13. The postoperative CDVA in Group B ranged from 20/66 to 20/40 at 3 months and 6 months; the maximum CDVA was 20/66 to 20/33. The structure of the anterior cornea was normal in patients in Group A but was abnormal with fibroblastic cells in the anterior stroma in patients in Group B. CONCLUSIONS: Patients with a preoperative duration of stromal edema of more than 12 months had pathologic changes in the corneal stroma that may have adversely affected visual acuity after DSAEK. Given that stromal edema, including that associated with bullous keratopathy, has been proposed to be a progressive condition, DSAEK may be most effective when performed early after the onset of edema, before the occurrence of pathologic changes in the stroma.

In vivo observation of Langerhans cells by laser confocal microscopy in Thygeson's superficial punctate keratitis.

PURPOSE: To characterize the cornea of individuals with Thygeson's superficial punctate keratitis (TSPK) at the cellular level by laser confocal biomicroscopy. METHODS: Both corneas of three patients with TSPK referred to Yamaguchi University Hospital were imaged with a laser confocal biomicroscope. Morphological changes were evaluated for each layer of the cornea. RESULTS: The number of Langerhans cells was greatly increased in the basal cell layer of the focal corneal epithelium and in Bowman's layer in the four eyes affected by TSPK. Aggregates of these cells were associated with the subepithelial nerve plexus. Langerhans cells were also evident in the unaffected eyes of the two patients with unilateral TSPK, although their numbers were much smaller than those in the affected eyes. Topical treatment with betamethasone phosphate resulted in the virtual disappearance of Langerhans cells from the affected eyes. CONCLUSION: The prominent association of Langerhans cells with TSPK suggests that the activation of these cells by inflammatory conditions might contribute to the pathogenesis of this disorder.

Structures of the corneal limbus detected by laser-scanning confocal biomicroscopy as related to the palisades of Vogt detected by slit-lamp microscopy.

PURPOSE: To examine the relations between specific structures detected at the corneal limbus by confocal biomicroscopy with palisades of Vogt detected by slit-lamp microscopy METHODS: Twenty-five eyes of 25 normal participants were examined. The presence or absence of the palisades of Vogt and limbal pigmentation were assessed by slit-lamp microscopy. The presence or absence of four structures in the corneal limbal area--hyperreflective parallel trabecular extensions, borders of bright-cell groups and dark-cell groups, hyperreflective cells and bright corpuscular particles with dendritic cell-like morphology--were assessed by confocal biomicroscopy. The relations between the presence of these four structures and the presence of either the palisades of Vogt or limbal pigmentation of the palisade ridges were evaluated by the chi-squared test. RESULTS: Only the presence of hyperreflective parallel trabecular extensions was significantly related to the presence of the palisades of Vogt (P < 0.01). The presence of hyperreflective cells was not significantly related to the presence of limbal pigmentation. CONCLUSION: The hyperreflective parallel trabecular extensions observed by confocal biomicroscopy may correspond to the palisades of Vogt detected by slit-lamp microscopy. Further studies are needed to determine whether confocal biomicroscopy can be used to diagnose and monitor the clinical course of limbal stem cell deficiency.

Quantitative evaluation of corneal epithelial oedema by confocal microscopy.

BACKGROUND: To develop a novel quantitative index for evaluation of corneal epithelial oedema, the pixel intensity of confocal microscopic images was measured derived from the basal cell layer (BCL) of the corneal epithelium in normal eyes, eyes before and after cataract surgery, and eyes affected by bullous keratopathy. METHODS: Five eyes of five normal volunteers, 14 eyes of 11 cataract patients and 12 eyes of 12 bullous keratopathy patients were examined by confocal microscopy. The cataract patients underwent cataract surgery, and they were examined by confocal microscopy, corneal pachymetry, and anterior fluorometry both before and at various times after surgery. The pixel intensity of BCL images obtained by confocal microscopy was measured and expressed as the BCL index. RESULTS: The coefficient of variation for repeated (five times) measurement of the BCL index in each of the five normal eyes was 3.4%. The BCL index was 54.8 5.3 (mean SD) before surgery, increased significantly to 65.2 10.0 on the day after surgery, and gradually decreased thereafter in the cataract patients. The time-course of the BCL index coincided well with that of corneal thickness and anterior fluorometry value. The BCL index in eyes affected by bullous keratopathy was significantly increased at 95.0 6.4. CONCLUSION: The BCL index was increased after cataract surgery and in eyes affected by bullous keratopathy, conditions associated with corneal epithelial oedema. This quantitative measure obtained by confocal microscopy may prove useful in the clinical evaluation of corneal epithelial oedema.

Noninvasive direct detection of ocular mucositis by in vivo confocal microscopy in patients treated with S-1.

PURPOSE: S-1 is an oral antineoplastic agent that contains a prodrug of 5-fluorouracil and has adverse effects on skin, alimentary tract mucosa, and the ocular surface. We investigated the effects of S-1 on the corneal epithelium by in vivo confocal microscopy and histopathologic analysis. METHODS: Twelve patients with eye problems related to S-1 treatment participated in the study. Twenty eyes of ten subjects were evaluated by laser-scanning confocal microscopy. Corneal epithelial debridement as a diagnostic therapy and histopathologic analysis were performed for five eyes of three subjects affected in the pupillary zone of the cornea. RESULTS: Slitlamp examination revealed a local limbal abnormality characterized by epithelial invasion toward the center of the cornea in all 24 eyes. In vivo confocal microscopy revealed an altered structure of the corneal epithelium with abnormal epithelial cells and inflammation. One of five specimens subjected to cytologic diagnosis showed moderate dysplasia. Hematoxylin and eosin staining showed that each abnormal epithelial sheet lacked the stratified structure of the normal corneal epithelium. Immunofluorescence analysis revealed the presence of cells positive for one, both, or neither of cytokeratins 12 and 4 in each lesion. CONCLUSIONS: S-1 can induce ocular mucositis with dysplasia, likely affecting cellular functions, including differentiation, of the corneal epithelium. In vivo confocal microscopy allowed the noninvasive detection of cellular changes in the cornea as an adverse effect of S-1 administration.

In vivo biopsy by laser confocal microscopy for evaluation of traumatic recurrent corneal erosion.

PURPOSE: Laser in vivo confocal microscopy noninvasively provides images that are equivalent to high quality histology. We have now applied this technique to identify pathological characteristics of traumatic recurrent corneal erosion (RCE). METHODS: Six eyes of six patients with traumatic RCE were studied. Corneas were examined with a slit lamp biomicroscope and with a laser in vivo confocal microscope (Heidelberg Retina Tomograph II-Rostock Cornea Module or HRTII-RCM) at various times after the onset of the most recent recurrence of corneal erosion. RESULTS: Brightly reflective granular structures were detected by the HRTII-RCM system in the basal and wing cell layers of the corneal epithelium in all eyes affected by recurrent erosion. Activated keratocytes and scattered fine particles were also apparent in the shallow stroma of five of the six affected eyes. These features were not observed in the normal cornea. CONCLUSIONS: The HRTII-RCM system allows detection of characteristic abnormal structures in the cornea of individuals with traumatic RCE. The presence of granular structures in the corneal epithelium as well as persistent inflammation in the shallow stroma may contribute to the deterioration of the corneal epithelial cell alignment and to the weakening of adhesion between the basal epithelial cells and the basement membrane in RCE lesions.

A case of bilateral corneal epithelial dysplasia characterized by laser confocal biomicroscopy and cytokeratin immunofluorescence.

PURPOSE: To describe a case of bilateral corneal epithelial dysplasia in which each lesion was characterized by both laser confocal biomicroscopy and cytokeratin immunofluorescence. METHODS: A 52-year-old Japanese woman with bilateral corneal epithelial dysplasia was treated by corneal epithelial debridement. We observed the affected area with laser confocal biomicroscopy before and after treatment and examined the immunofluorescence of cytokeratins to examine the characteristics of the abnormal epithelial cells. RESULTS: Laser confocal biomicroscopy revealed the atypical epithelial cells in all layers of the corneal epithelium as well as the reconstituted normal structure of the corneal epithelium after epithelial debridement. Immunofluorescence of cytokeratin 12 (K12) and K4 revealed the presence of four types of cells (those positive for one, both or neither of these cytokeratins) in each lesion. CONCLUSION: Cells expressing both K12 and K4 probably represented dysplastic cells that had invaded the cornea via the limbus and adopted characteristics of corneal epithelial cells. Cells lacking both K12 and K4 were probably either undifferentiated cells or epithelial cells in which cytokeratin expression had not been initiated.

Development of an instrument for measurement of light scattering at the corneal epithelial basement membrane in diabetic patients.

PURPOSE: Diabetic complications are associated with abnormality of the basement membranes. We have developed a light-scattering detection system (LSDS) specifically for measurement of light scattering at the corneal epithelial basement membrane, and have determined the reproducibility and clinical significance of the results obtained by the LSDS in diabetic patients. METHODS: Thirty nondiabetic controls and 40 diabetic subjects participated in the study. Light scattering at the corneal epithelial basement membrane was measured with the LSDS. RESULTS: The measurement of light scattering at the corneal basement membrane was found to be reproducible. The LSDS index (mean +/- SD) was 28.1 +/- 4.8 in controls, 35.7 +/- 6.3 in mild diabetic retinopathy subjects, and 42.7 +/- 8.6 in severe diabetic retinopathy subjects. This demonstrated that the LSDS index at the corneal basement membrane is proportional to the extent of diabetic retinopathy. CONCLUSIONS: Measurement of light scattering at the corneal epithelial basement membrane is possible with the LSDS, is relatively easy to perform, and is reproducible. The LSDS may prove suitable for the early detection of diabetic ocular complications.