Ian Grierson

Long-term Morphologic Effects of Antiglaucoma Drugs on the Conjunctiva and Tenon's Capsule in Glaucomatous Patients

Conjunctival and Tenons capsule biopsies from two patient groups were quantitatively analyzed by light microscopy. Group A consisted of 20 patients with a primary glaucoma for whom surgery was a planned primary treatment modality. Group B was comprised of 20 patients with a primary glaucoma who had received at least two types of antiglaucoma topical medication, for a minimum of 1 year (mean, 7.7 years) before surgery. All slides were examined by two masked observers. A significant increase in the number of macrophages, lymphocytes, mast cells, and fibroblasts in the conjunctiva and Tenons capsule and a significant decrease in the number of epithelial goblet cells were seen in the group that received long-term drop therapy. These results suggest that exhaustive medical therapy, before surgery is offered, increases the number of tissue inflammatory cells. It is possible this may enhance the risk of external bleb scarring and filtration surgery failure.

The Place of Trabeculectomy in the Treatment of Glaucoma

Abstract: The purpose of treating glaucoma is to reduce intraocular pressure throughout the 24 hours to a level at which no further damage is done to the optic nerve head. We have reviewed the results of 424 trabeculectomies performed at our clinic from 1967 to 1977. We have found that although initial control of intraocular pressure was achieved in 74% with medical therapy, only 40% remained under adequate control over a five-year period. Trabeculectomy alone controlled the intraocular pressure in 86% of the 424 eyes requiring surgery. This percentage was increased to 98% by the use of additional medical and/or surgery. Regression analysis of the results showed that the intraocular pressure can be predictably reduced to a level approaching the episcleral tissue pressure. A detailed discussion of recent knowledge of the functional anatomy of the outflow system and the morphologic basis of drug actions on the trabecular meshwork indicates that the continued use of strong miotics or drugs that give rise to underperfusion of the outflow system can lead to progressive damage of the trabecular meshwork. Because of this, and because of the low complication rate of trabeculectomy, we feel that surgery should be undertaken as soon as simple medication (ie, pilocarpine 2% tid; timolol 0.5% bid or a combination of these) fails to control the intraocular pressure, or at any time, regardless of the intraocular pressure, that progressive field loss is confirmed.

Age-related depletion of the cell population in the human trabecular meshwork

The number of cells in the human trabecular meshwork was assessed for counting meshwork cell nuclei in semithin Araldite sections cut in the meridonal plane. The counts of nuclei decreased with increasing age and the decrease was associated with all regions of the meshwork. The appropriate regression equation and a mean length for meshwork nuclei was used to estimate cell numbers. At 20 years of age the estimated cell number for the whole meshwork was 763,000 which decreased to 403,000 cells by 80 years with a loss rate of 6,000 cells per year.

Retinal pigment epithelial cells in epiretinal membranes: an immunohistochemical study.

Immunohistochemical techniques were used to identify cells containing cytokeratins in sections or tissue-culture monolayers from ocular (reference) tissues and also from 22 epiretinal membranes obtained during closed microsurgery for macular pucker or massive preretinal retraction. Results of cytokeratin immunostaining in reference tissues indicated that this is a valuable means of determining the contribution and distribution of epithelial cells in epiretinal membranes, and that the epithelial cells in the membranes were probably derived from the retinal pigment epithelium. Epithelial cells were identified in 17 of the 22 epiretinal membranes, but they did not usually constitute the predominant cell type. We concluded that the fibroblasts or fibroblast-like cells thought to be responsible for the contraction of epiretinal membranes are seldom of retinal pigment epithelial origin. Biomicroscopic pigmentation of a membrane was shown to be a poor guide to its epithelial cell population.

Side effects associated with prostaglandin analog therapy.

Topical prostaglandin analogs, which have become first-line therapy in the medical management of glaucoma, have an excellent safety profile with regard to systemic side effects, but are associated with several ocular side effects. Some of these are common, with no apparent serious consequences other than cosmetic, whereas others are much less common but represent potentially sight-threatening side effects. The former group includes conjunctival hyperemia, elongation and darkening of eyelashes, induced iris darkening, and periocular skin pigmentation. The latter group of side effects, which are relatively rare and lack definitive causal relationship to prostaglandin analog therapy, includes iris cysts, cystoid macular edema, anterior uveitis, and reactivation of herpes simplex keratitis. Most of the literature regarding side effects associated with prostaglandin analogs involves the use of latanoprost, probably because it was the first to be studied. There is no evidence, however, aside from less conjunctival hyperemia with latanoprost, that the commercially available prostaglandin analogs differ significantly with regard to side effects.

Biomaterials used in the posterior segment of the eye.

The treatment of posterior segment eye disease and related conditions has improved greatly in recent years with the advent of new therapies, materials and devices. Vitreoretinal conditions, however, remain significant causes of blindness in the developed world. Biomaterials play a major role in the treatment of many of these disorders and the success rate of vitreoretinal surgery, especially in the repair of retinal detachment and related conditions, would increase with the introduction of new and improved materials. This review, which focuses on disorders that feature retinal detachment, briefly describes the anatomy of the eye and the nature and treatment of posterior segment eye disorders. The roles, required properties and suitability of the materials used in vitreoretinal surgery as scleral buckles, tamponade agents or drug delivery devices, are reviewed. Experimental approaches are discussed, along with the methods used for their evaluation, and future directions for biomaterial research in the posterior segment of the eye are considered.

Adverse effects of topical antiglaucomatous medications on the conjunctiva.

With selected patients glaucoma filtration surgery is highly successful. However, there is growing evidence that chronic topical medical therapy has a deleterious effect on surgical outcome. It has been suspected that topical drugs exert an adverse effect on the conjunctiva which results in altered postoperative wound healing. In this review the effect of previous topical antiglaucoma medication on the conjunctiva and the outcome of subsequent glaucoma filtration surgery are discussed.

Edible mushroom (Agaricus bisporus) lectin, which reversibly inhibits epithelial cell proliferation, blocks nuclear localization sequence-dependent nuclear protein import

The Galβ1–3GalNAcα (TF antigen)-binding lectin (ABL) from the common edible mushroom (Agaricus bisporus) has a potent anti-proliferative effect without any apparent cytotoxicity. This unusual combination of properties prompted investigation of its mechanism of action. In contrast to soluble lectin, agarose-immobilized, and hence noninternalizable ABL had no effect on proliferation of HT29 colon cancer cells. Electron microscopy of HT29 cells incubated with fluorescein- and gold-conjugated ABL showed internalization of the lectin into endocytotic vesicles and multivesicular bodies. Confocal microscopy showed perinuclear accumulation of fluorescein isothiocyanate-conjugated lectin, which also inhibits HT29 cell proliferation, raising the possibility that the lectin might interfere with nuclear pore function. Transport of heat shock protein 70 into the nucleus in response to heat shock was blocked by preincubation of HT29 cells for 6 h with 40 μg/ml ABL. In digitonin-permeabilized cells, nuclear uptake of bovine albumin conjugated to a nuclear localization sequence (NLS)-containing peptide was also inhibited by a 15-min preincubation with 40–100 μg/ml ABL. In contrast, serum-stimulated nuclear translocation of mitogen-activated protein kinase, which is NLS-independent, was not affected by pretreatment of cells with the lectin. These results suggest that the anti-proliferative effect of ABL is likely to be a consequence of the lectin trafficking to the nuclear periphery, where it blocks NLS-dependent protein uptake into the nucleus.

Hepatocyte growth factor/Scatter factor in the eye

Hepatocyte growth factor, also known as scatter factor (HGF/SF) is a multipotential cytokine which can produce a range of responses in target cells and its influence in the eye in health and disease is just beginning to be appreciated. Usually HGF/SF is synthesised by mesenchymally derived cells and targets and signals epithelial cells in a paracrine manner via their c-Met surface receptor. However, there is growing evidence for the existence of autocrine loops in a number of cell systems prominent among which are ocular cells such as the corneal endothelium, the lens epithelium, the retinal pigment epithelium (RPE) and others. Marked cellular proliferation is stimulated when activated HGF/SF is exposed to hepatocytes, renal epithelium, melanocytes and vascular endothelial cells but it is often a poor mitogen for other cell types. In target cells the cytokine promotes other bioactions such as junctional breakdown, shape change, cell scattering, directional and nondirectional migration, cell survival, invasive behaviour and/or tubule formation. These activities seem to depend on HGF/SF linking with the c-Met receptor and pathways to stimulate the various types of cytokine/receptor response are being unravelled at the present time. In corneal wound healing, HGF/SF is produced by stromal keratocytes and targets the repairing epithelium. HGF/SF is a constituent of tears, aqueous humour and vitreous humour at levels above that found in plasma although it is not clear how much is activated. Aqueous HGF/SF may well influence lens epithelial, corneal endothelial and trabecular meshwork cell survival. Vitreous levels of HGF/SF are elevated in proliferative vitreoretinopathy (PVR), where a target cell is the RPE and in proliferative diabetic retinopathy (PDR) where HGF/SF has been shown to be a major angiogenesis factor. Finally HGF/SF may be involved in the metastatic spread of tumour cells from uveal melanomata and in the formation of vascular channels in these tumours.

Racial differences in the results of glaucoma filtration surgery: are racial differences in the conjunctival cell profile important?

Conjunctival biopsies were obtained at the time of filtration surgery from 90 patients with glaucoma; 45 of these patients were black and 45 white. Forty nine of the patients (25 black, 24 white) had undergone a primary trabeculectomy. Comparisons between black and white patients were made with respect to the results of surgery and differences in conjunctival cell profile. In agreement with many authors, trabeculectomy was found to be less successful in black patients (67% compared with 80%), although this finding was not statistically significant by survival analysis. In addition, conjunctiva from black patients was found to contain a greater number of macrophages and a smaller number of both mast cells and goblet cells in comparison with white patients. There was a tendency for conjunctiva from black patients to contain more fibroblasts. Conjunctiva obtained from the patients whose filtration surgery subsequently failed was found to contain more fibroblasts, macrophages, and basal epithelial pale cells. A greater number of conjunctival macrophages and possibly fibroblasts in black patients may partially explain the tendency for a lower success rate of filtration surgery in this group of patients.