Pt Khaw

Activation and suppression of fibroblast function

The fibroblast is the central player in the wound repair and scarring processes that occur in the anterior segment of the eye. Glaucoma filtration surgery is the ultimate example of the importance of the wound healing process, as this process is the major determinant of the success of this procedure. We highlight the role of the fibroblast, and discuss some of the growth factors stimulating fibro-blast proliferation, migration and extracellular matrix production in the wound environment. We also review current methods of suppressing fibroblast proliferation, the new concepts that have arisen from laboratory studies, and future directions of investigation and treatment.

A pilot study of a system for grading of drainage blebs after glaucoma surgery

Purpose:To develop and evaluate a novel bleb grading scheme for clinical and photographic evaluation. Method:A system for grading bleb photographs using widely applicable parameters was designed, and reference color photographs printed. A prospective masked agreement study was undertaken comparing slit lamp examination with mono and stereo photographs; 36 eyes of 28 patients with previous glaucoma surgery were graded according to defined parameters on a 1 to 10 scale clinically at the slit lamp by four ophthalmologists and two optometrists. Standardized stereo and mono photographs of the blebs were taken on the same day. The photographs were graded at least one week later in a masked fashion by the same observers, with grading of mono and stereo photographs also separated by one week. Analysis was performed to determine the variability and agreement between slit lamp results and photographic results, and to identify the presence of systematic bias. Results:High levels of agreement were found between slit lamp and both stereo and mono photographs for vascularity indices, bleb wall thickness, and bleb elevation. Lower levels of agreement were found for the relative components of demarcated versus diffuse areas of the bleb, and for the total width of the bleb. The interquartile range for the median difference between slit lamp and photograph grading was −1.0 to 1.0 for all criteria except diffuse component (−2.0 to 2.0), and the median difference for all scores was 0.0. The median interobserver difference for all criteria was 0.0; the quartile range for all scores was between −0.5 and 1.0 except for diffuse component and width assessments whose quartiles fell in the −1.75 to 1.0 range. Examiners agreed with photographic grading within ± 1 in more than 80% of gradings for vascularity and bleb height, within ± 1 in more than 75% of gradings for bleb wall thickness, within ± 2 in 61% of bleb width assessments, and ± 2 in 59% of diffuse component. Conclusion:This bleb grading system is reproducible clinically and photographically. High levels of agreement between scores for photographs versus slit lamp examination were found for most categories, with good interobserver agreement for both photograph and slit lamp grading. Further refinement of scoring and reference photographs is required for optimization, especially for grading of bleb morphology.

Angle-closure glaucoma in East Asian and European people. Different diseases?

In contrast to the pattern of disease in Europeans, primary angle closure has a higher prevalence and tends to be asymptomatic in East Asians. The higher prevalence is attributed to differences in anterior chamber and angle anatomy. Several studies suggest that central anterior chamber depth is shallower in East Asians than in Europeans, although this is not universally accepted. It is debated whether pupil block is the predominant mechanism of angle closure in Asian people. Meaningful comparison between studies is currently hindered by differences in patient selection, examination technique, and case definition; however, the major scientific deficiency is the paucity of prospective followup data to give an insight into natural history of the disease. This review examines the data on prevalence, risk factors, and mechanism of angle closure. Special consideration is given to limitations of methodology in research to date, with the intention of developing more robust data in future studies.

Skin and oral fibroblasts exhibit phenotypic differences in extracellular matrix reorganization and matrix metalloproteinase activity

Background Oral mucosal wounds are characterized by rapid re‐epithelialization and remodelling. In vitro, oral mucosal fibroblasts exhibit a fetal phenotype with increased extracellular matrix reorganizational ability, migration and experimental wound repopulation when compared with skin fibroblasts.

Modulation of wound healing after glaucoma surgery.

The healing process after glaucoma filtration is the main determinant of surgical failure and, even more important, the final intraocular pressure. The ability to fully control wound healing may ultimately give us the ability to set the intraocular pressure in the low teens for all patients undergoing glaucoma filtration surgery. The authors review the changes in how to use antimetabolites to improve safety, and many of the exciting new areas of progress, including growth factor neutralization and future molecular therapies to control wound healing.

Defining "occludable" angles in population surveys: drainage angle width, peripheral anterior synechiae, and glaucomatous optic neuropathy in east Asian people.

Background/aim: A current consensus in epidemiological studies of primary angle closure (PAC) is to diagnose the condition only if the posterior (usually pigmented) trabecular meshwork is seen for less than 90° of the angle circumference, termed an “occludable angle.” The authors sought to assess the validity of this epidemiological classification by exploring the relation between drainage angle width, peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy (GON). Methods: 918 Mongolians and 995 Chinese Singaporeans, both groups aged 40 years and older were examined in two population based surveys. Gonioscopic angle width was graded in five categories (0 = closed to 4 = wide open) according the scheme described by Shaffer. Cases with secondary PAS were excluded. Results: The rate of PAS was between 0.3% and 1.7% in people with wide angles (grades 3 and 4). In those with grade 2 angles, PAS were seen in between 8% of eyes. In eyes with grade 1 angles, the rate rose to 17% in Chinese Singaporeans, and 31% in Mongolians. The odds of PAS were higher in people with narrower angles. However, there was a greater absolute number of people with PAS whose drainage angles were classified as “not occludable” than those classified “occludable.” Conclusions: The traditional view that primary angle closure becomes a significant possibility in drainage angles of ⩽ grade 2 (approximately 20°) is valid in east Asians. The definition of an “occludable” angle examined here excludes many people with PAS. This probably serves to underemphasise the role of PAC in population surveys of glaucoma prevalence in Asian people.

Anterior chamber flare after trabeculectomy and after phacoemulsification

AIMS To evaluate and compare prospectively the anterior chamber inflammatory response after phacoemulsification cataract surgery and after trabeculectomy with peripheral iridectomy. METHODS Anterior chamber inflammation was measured using the Kowa FM-500 laser flare meter in 131 patients undergoing trabeculectomy and 148 patients undergoing phacoemulsification cataract extraction with intraocular lens implantation. Flare was measured before surgery and on each postoperative visit up to 12 months. RESULTS Before surgery there was no significant difference in flare readings between the two groups. Following trabeculectomy flare returned to baseline levels 4 weeks after surgery, while following phacoemulsification cataract extraction it remained significantly higher at week 6 (p<0.006) and month 3 (p<0.05). CONCLUSIONS Anterior chamber inflammation is more prolonged after cataract surgery than after trabeculectomy. This may have implications for the timing of trabeculectomy in relation to cataract surgery.

Silicone oil concentrates fibrogenic growth factors in the retro-oil fluid

Aim: To determine whether silicone oil concentrates protein and growth factors in the retro-oil fluid. Methods: A laboratory analysis of intraocular fluid and vitreous specimens obtained from patients undergoing removal of silicone oil, revision vitrectomy, or primary vitrectomy for macular hole, proliferative vitreoretinopathy (PVR), or retinal detachment. Patients were prospectively recruited from routine vitreoretinal operating lists. Vitreous cavity fluid and vitreous samples were analysed for the presence of transforming growth factor beta (TGF-β2), basic fibroblast growth factor (bFGF), interleukin 6 (IL-6), and total protein using either commercially available enzyme linked immunosorbent assays (ELISA) or protein assay kits. Results: The median levels of bFGF, IL-6, and protein in the retro-oil fluid were raised (p<0.05) compared to all the other vitreous and vitreous cavity fluid samples. bFGF, IL-6, and protein levels were raised in PVR vitreous compared to non-PVR vitreous. TGF-β2 levels were not significantly raised in retro-oil fluid or in PVR vitreous. Conclusions: The concentration of fibrogenic (bFGF) and inflammatory (IL-6) growth factors and protein is raised in retro-silicone oil fluid. This may contribute to the process of retro-oil perisilicone proliferation and subsequent fibrocellular membrane formation.

MMP inhibition prevents human lens epithelial cell migration and contraction of the lens capsule

Purpose: The development of posterior capsule contraction following cataract surgery is caused by the activity of residual lens epithelial cells. Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes, which are essential for cell migration and cell mediated contraction following wound healing. The authors investigated whether inhibiting MMP activity can reduce lens epithelial cell migration and as a result, lead to a reduction in cell mediated capsule contraction. Methods: Human donor lens capsules were cultured and treated with a broad spectrum MMP inhibitor, Ilomastat (GM6001). MMP-2 and MMP-9 production were determined by ELISA. Cell migration onto the posterior capsule and capsule contraction were digitally measured. Results: MMP inhibition significantly reduced lens epithelial cell migration onto the posterior capsule (p<0.05), and a reduction in capsule contraction was observed (p<0.05). Conclusions: Ilomastat significantly reduced lens epithelial cell migration onto the posterior capsule surface and inhibited capsule contraction. MMP inhibition may have a role in the therapeutic treatment of posterior capsule opacification.

Beta irradiation: new uses for an old treatment: a review

AbstractBeta radiation has a long history as a treatment modality in ophthalmology. It is a convenient and practical method of applying radiation and has the advantage of minimal tissue penetration. There has been a recent resurgence in the use of beta radiation in other areas in medicine, such as the prevention of restenosis after coronary artery stenting. Beta radiation has been shown in vitro and in vivo to inhibit proliferation of human Tenons fibroblasts, which enter a period of growth arrest but do not die. Effects on the cell cycle controller p53 have been shown to be important in this process.In ophthalmology, beta radiation has been used widely for the treatment of pterygium and is under evaluation for treatment of age-related macular degeneration and for controlling wound healing after glaucoma drainage surgery. In this latter role, beta radiation may be particularly appropriate for use in developing countries to improve the results of trabeculectomy while potentially avoiding some of the side effects of other antimetabolites.