While more invasive methods such as indocyanine green (ICG) angiography remain the gold standard for detecting abnormalities of the choroidal vasculature in normal eyes and disease states, EDI-OCT has become an important adjunctive clinical tool in providing three-dimensional anatomical information of the choroid.
Objective This was a pilot randomised controlled trial (RCT) to investigate the effect of post-operative face-down positioning on the outcome of macular hole surgery and to inform the design of a larger definitive study. Methods In all, 30 phakic eyes of 30 subjects with idiopathic full-thickness macular holes underwent vitrectomy with dye-assisted peeling of the ILM and 14% perfluoropropane gas. Subjects were randomly allocated to posture face down for 10 days (posturing group) or to avoid a face-up position only (non-posturing group). The primary outcome was anatomical hole closure. Results Macular holes closed in 14 of 15 eyes (93.3%; 95% confidence interval (CI) 68-100%) in the posturing group and in 9 of 15 (60%; 95% CI 32-84%) in the non-posturing group. In a subgroup analysis of outcome according to macular hole size, all holes smaller than 400 lm closed regardless of posturing (100%). In contrast, holes larger than 400 lm closed in 10 of 11 eyes (91%; 95% CI 58-99%) in the posturing group and in only 4 of 10 eyes (40%; 95% CI 12-74%) in the non-posturing group (Fisher's exact test P ¼ 0.02). Conclusion Post-operative face-down positioning may improve the likelihood of macular hole closure, particularly for holes larger than 400 lm. These results support the case for a RCT.
Endostatin, a fragment of the basement membrane component collagen XVIII, exhibits antiangiogenic properties in vitro and in vivo when high doses are administered. It is not known whether endogenous endostatin at physiological levels has a protective role as an inhibitor of pathological angiogenesis, such as choroidal neovascularization (CNV) in age-related macular degeneration. Using a laser injury model, we induced CNV in mice lacking collagen XVIII/endostatin and in control mice. CNV lesions in mutant mice were approximately 3-fold larger than in control mice and showed increased vascular leakage. These differences were independent of age-related changes at the choroid-retina interface. Ultrastructural analysis of the choroidal vasculature in mutant mice excluded morphological vascular abnormalities as a cause for the larger CNV lesions. When recombinant endostatin was administered to collagen XVIII/endostatin-deficient mice, CNV lesions were similar to those seen in control mice. In control mice treated with recombinant endostatin, CNV lesions were almost undetectable. These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular leakage. Endostatin may have a regulatory role in the pathogenesis of CNV and could be used therapeutically to inhibit growth and leakage of CNV lesions.
Intraocular inflammatory diseases are a common cause of severe visual impairment and blindness. In an acute mouse model of autoimmune retinal disease, we demonstrate that treatment with the HMG-CoA reductase inhibitor, lovastatin, suppresses clinical ocular pathology, retinal vascular leakage and leukocytic infiltration into the retina. Efficacy was reversed by co-administration of mevalonolactone, the downstream product of HMG-CoA reductase, but not by squalene which is distal to isoprenoid pyrophosphate metabolites within the cholesterol biosynthetic pathway. Lovastatin treatment over 7 days, which resulted in plasma lovastatin hydroxyacid concentrations of 0.098 ± 0.03μM, did not result in splenocyte production of Th2 cytokines but did cause a small reduction in antigen-induced T cell proliferation and a decrease in the production of IFN-γ and IL-10. Thus, contrary to expected outcome we demonstrate that it is possible to dissociate the therapeutic effect of statins from their activity on the Th1/Th2 balance. Statins inhibit isoprenoid pyrophosphate synthesis, precursors required for the prenylation and posttranslational activation of Rho GTPase, a key molecule in the endothelial ICAM-1 mediated pathway that facilitates lymphocyte migration. Consistent with inhibition of leukocyte infiltration in vivo, lovastatin treatment of retinal endothelial cell monolayers in vitro leads to inhibition of lymphocyte transmigration which may, in part, account for drug efficacy. Unlike lovastatin, atorvastatin treatment failed to attenuate retinal inflammatory disease despite showing significant clinical benefit in experimental autoimmune encephalomyelitis. These data highlight the potential differential activity of statins in different inflammatory conditions and their possible therapeutic use for the treatment of human posterior uveitis.
In the 1990s a number of authors have studied the refractive changes induced in the cornea as a result of the procedure.2-6 Several surgical modifications have been described, [7][8][9][10][11] each of which may theoretically influence the changes noted in the cornea following surgery. In 1995 we reported the intraocular pressure results following microtrabeculectomy, a small flap modification of the original design which we have utilised routinely since 1991.11 The scleral trapdoor at 2 × 2 mm is approximately one sixth of the area of the Cairns' procedure, and the 0.75 × 0.75 mm internal opening is just one seventh of the area of the original osteum. As a smaller sized operation theoretically should result in less surgical trauma, we performed a prospective study to investigate the changes in corneal curvature following microtrabeculectomy. We utilised vector analysis and vector decomposition techniques to determine the "with the rule" and "against the rule" changes induced in the cornea. Materials and methodsFollowing ethics committee approval and informed consent, a cohort of eyes requiring filtering surgery underwent microtrabeculectomy. None of the eyes had had previous ocular surgery. Full details of the surgical technique have been described elsewhere.11 Briefly, a limbus based conjunctival flap was fashioned commencing 4 mm from and exposing the limbus. SuYcient scleral cautery was then performed using a battery powered bipolar cautery (Mentor) over an area approximately 3 mm × 3 mm, suYcient to avoid haemorrhage during the procedure. A 2 mm × 2 mm scleral trap door was constructed, for this study centred at the 90 degree meridian, and an anteriorly sited 0.75 mm diameter internal sclerostomy was achieved with a Kelly punch (Storz). A small basal peripheral iridectomy was followed by two 10/0 nylon scleral trapdoor sutures and a running 10/0 gauge monofilament polyglycolic acid suture to the conjunctiva. Balanced salt solution (Alcon) and air were then injected into the anterior chamber via a paracentesis performed at the start of surgery. Postoperative medications routinely employed were atropine 1% drops three times a day and betamethasone 0.1% with neomycin sulphate 0.5% four times a day for the first week. At the 1 week review the atropine was stopped and the steroid/antibiotic reduced at the discretion of the clinician. All patients continued topical steroids for at least 1 month but for no longer than 3 months postoperatively. All surgery was performed by the same surgeon (SAV) who was experienced in the technique and no suture manipulations by laser or otherwise were used postoperatively.In order to provide the raw data for analysis, manual keratometry with a Javal/Schiotz keratometer and computerised corneal videokeratoscopy with the Eyesys corneal analysis system
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