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D Siriwardena

Publications and source records attributed to D Siriwardena.

13 recordsLinked to original sources
PubMed2004

National survey of antimetabolite use in glaucoma surgery in the United Kingdom.

AIMS: To assess the pattern of use of antimetabolites in trabeculectomy surgery by all consultant ophthalmologists in the United Kingdom. METHODS: A postal questionnaire of 12 questions regarding antimetabolite use in trabeculectomy surgery was sent to all 749 consultant ophthalmologists in the United Kingdom. The consultants were asked to estimate the number of trabeculectomies they performed per year, how often they used 5-fluorouracil (5-FU) in primary and redo surgery, their usual method of administration of 5-FU, how often they used mitomycin (MMC) in primary and redo surgery, and their usual dosage regimen of MMC. Factors that influenced the decision to use or not use antimetabolites were also assessed. RESULTS: The response rate of consultants returning the questionnaire was 82% (615 out of 749); 87% (533) of these consultants perform trabeculectomy surgery. Of these 533 consultants, 98 (18%) never use an antimetabolite. Most consultants (82%) use antimetabolites, but use them infrequently (only 9% using antimetabolites in more than half their cases). The preferred antimetabolite is 5-FU rather than MMC. Of the 435 consultants performing trabeculectomy surgery and using antimetabolites, 402 (93%) use 5-FU and 179 (41%) use MMC. Various factors influenced the decision to use or not use an antimetabolite, but experience of complications associated with their use was a factor for 34% of consultants. CONCLUSION: The use of antimetabolites, particularly MMC, in the United Kingdom is much less than in America or Japan, where trabeculectomy with MMC is the surgical procedure preferred by glaucoma specialists.

Antimetabolites↗
PubMed2002

Interventions for acute non-arteritic central retinal artery occlusion.

BACKGROUND: Acute central retinal artery occlusion occurs as a sudden interruption of the blood supply to the retina and results in an almost complete loss of vision in the affected eye. There is no generally agreed treatment regimen although a number of therapeutic interventions have been proposed. OBJECTIVES: The objective of this review is to examine the effects of treatments used for acute non-arteritic central retinal artery occlusion. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register - CENTRAL/CCTR, which contains the Cochrane Eyes and Vision Group specialised register (Cochrane Library Issue 4, 2001), MEDLINE (1966 to August 2001) and EMBASE (1980 to September 2001). We searched the reference lists of relevant papers for trials. SELECTION CRITERIA: We included only randomised controlled trials in which one treatment aimed to re-establish blood supply to the retina in people with acute central retinal artery occlusion was compared to another treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the search results for trials to be included in the review. Discrepancies were resolved by discussion. MAIN RESULTS: We found no randomised controlled trials that met our inclusion criteria. REVIEWER'S CONCLUSIONS: There is currently not enough evidence to decide which, if any, interventions for acute non-arteritic central retinal artery occlusion would result in any beneficial or harmful effect. Well-designed randomised controlled trials are needed to establish the most effective treatment.

Humans↗
PubMed2002

In vivo production of interferon beta by human Tenon's fibroblasts; a possible mediator for the development of chronic conjunctival inflammation.

BACKGROUND: Chronic inflammation may develop from failure of the immune system to deactivate itself during resolution of the wound healing response, and is recognised as a major risk factor for trabeculectomy failure. Fibroblast/T cell interactions may contribute to aggressive scarring. Our previous research showed that in vitro human Tenon's fibroblast produced interferon beta was responsible for preventing T cell apoptosis, suggesting that this interaction could contribute to the development of chronic inflammation. METHODS: Immunohistological techniques were used to investigate the in vivo components of this particular fibroblast/T cell interaction in conjunctival biopsies from glaucoma patients undergoing filtration surgery. RESULTS: Fibroblast produced interferon beta and T lymphocytes were identified in human conjunctiva. CONCLUSION: The components of fibroblast mediated prevention of T cell apoptosis were identified in vivo, suggesting that the development of this interaction is possible and that it may contribute to the development of chronic inflammation and excessive scarring.

Aged↗
PubMed2001

Optic disc changes following trabeculectomy: longitudinal and localisation of change.

AIMS: To determine whether there were any changes in the optic disc at 2 years after trabeculectomy. To determine the factors that most influenced change and whether change was localised to any region of the optic disc. METHODS: 95 patients undergoing routine trabeculectomy as part of the ongoing Moorfields/MRC 5-fluorouracil trial were recruited into the study. Eyes were imaged preoperatively (4 (SD 3) weeks) with the Heidelberg retina tomograph (HRT, Heidelberg Engineering), and at 3 months (SD 2 weeks), 1 year (SD 1 month), and 2 years (SD 1 month) after surgery. Parameters investigated for change were rim area, rim volume, and maximum cup depth. The predefined segment analysis available on the HRT analysis software was used to determine segmental change. RESULTS: The images of 70 patients were analysed. Intraocular pressure reduced from 22.25 (SD 3.76) mm Hg, at the time of preoperative imaging to 15.27 (SD 4.96) mm Hg at 3 months, 14.38 (SD 3.89) mm Hg at 1 year, and 13.80 (SD 3.54) mm Hg at 2 years after trabeculectomy. An increase in rim area and rim volume was present at all time points after surgery, but was only found to be statistically significant at 2 years after surgery. Maximum depth of cup reduced by month 3 and month 12, but showed a slight increase at 2 years after surgery, although this was still lower than the preoperative measure. Segmental analysis found a significant change in rim volume in the nasal, inferonasal, superonasal, and superotemporal regions at 2 years after surgery. No significant regional localisation for change was found at any other time point or in any other parameter investigated. CONCLUSIONS: Reversal of disc cupping is present at 2 years after trabeculectomy. The factor most influencing change is reduction of intraocular pressure. Segmental analysis showed that change in rim volume was greatest in the nasal, inferonasal, superonasal and superotemporal regions at 2 years.

Aged↗
PubMed2000

Effects of tempol, a membrane-permeable radical scavenger, in a gerbil model of brain injury.

There is evidence that the excessive generation of reactive-oxygen radicals contributes to the brain injury associated with transient, cerebral ischemia. This study investigates the effects of tempol, a small, water-soluble molecule, that crosses biological membranes, on the brain injury caused by bilateral occlusion and reperfusion of both common carotid arteries in the gerbil (BCO). Treatment of gerbils with tempol (30 mg/kg i.p. at 30 min prior to reperfusion and at 1 and 6 h after the onset of reperfusion) reduced the formation of post-ischemic brain oedema. Tempol also attenuated the increase in the cerebral levels of malondialdehyde (MDA) and the hippocampal levels of myeloperoxidase (MPO) caused by cerebral ischemia and reperfusion. The immunohistochemical analysis of the hippocampal region of brains subjected to ischemia-reperfusion exhibited positive staining for nitrotyrosine (an indicator of the generation of peroxynitrite) and poly(ADP-ribose) synthetase (PARS) (an indicator of the activation of this nuclear enzyme secondary to single strand breaks in DNA). In gerbils subjected to BCO, which were treated with tempol, the degree of staining for nitrotyrosine and PARS was markedly reduced. Tempol increased survival and reduced the hyperactivity (secondary to the ischemia-induced neurodegeneration) caused by cerebral ischemia and reperfusion. The loss of neurons from the pyramidal layer of the CA1 region caused by ischemia and reperfusion was also attenuated by treatment of gerbils with tempol. This is the first evidence that the membrane-permeable, radical scavenger tempol reduces the cerebral injury caused by transient, cerebral ischemia in vivo.

Animals↗
PubMed2000

The tyrosine kinase inhibitor tyrphostin AG126 reduces the development of acute and chronic inflammation.

Protein tyrosine kinases help to regulate the expression of many genes that play important roles in inflammation. Here we investigate the effects of the tyrosine kinase inhibitor tyrphostin AG126 in two animal models of acute and chronic inflammation, carrageenan-induced pleurisy and collagen-induced arthritis. We report here that tyrphostin AG126 (given at 1, 3, or 10 mg/kg i.p. in the pleurisy model or 5 mg/kg i.p. every 48 hours in the arthritis model) exerts potent anti-inflammatory effects in animal models of acute and chronic inflammation in vivo. These include the inhibition of pleural exudate formation and mononuclear cell infiltration (pleurisy model) and the development of clinical signs and tissue injury (arthritis model). Furthermore, tyrphostin AG126 reduced the staining for nitrotyrosine and poly (ADP-ribose) polymerase (by immunohistochemistry) and the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated rats and in the joints from collagen-treated rats. Thus, we provide the first evidence that prevention of the activation of protein tyrosine kinases reduces the development of acute and chronic inflammation, and that inhibition of the activity of certain tyrosine kinases may represent a novel approach for the therapy of inflammation.

Acute Disease↗
PubMed2000

Calpain inhibitor I reduces the development of acute and chronic inflammation.

There is limited evidence that inhibition of the activity of the protease calpain I reduces inflammation. Here we investigate the effects of calpain inhibitor I in animal models of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis). We report here for the first time that calpain inhibitor I (given at 5, 10, or 20 mg/kg i.p. in the pleurisy model or at 5 mg/kg i.p every 48 hours in the arthritis model) exerts potent anti-inflammatory effects (eg, inhibition of pleural exudate formation, mononuclear cell infiltration, delayed the development of the clinical signs and histological injury) in vivo. Furthermore, calpain inhibitor I reduced (1) the staining for nitrotyrosine and poly (ADP-ribose) polymerase (immunohistochemistry) and (2) the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated rats and in joints from collagen-treated rats. Thus, prevention of the activation of calpain I reduces the development of acute and chronic inflammation. Inhibition of calpain I activity may represent a novel therapeutic approach for the therapy of inflammation.

Acute Disease↗
PubMed2000

Modulating conjunctival wound healing.

Advances in molecular and cell biology have led to an expansion in our knowledge and understanding of the processes involved in wound healing. We review existing and potential therapies modulating the conjunctival scarring response, with particular reference to glaucoma filtration surgery. We discuss how the refinement of present antimetabolite regimens can minimise complications and improve surgical results, and advocate their use in carefully selected patient groups. Perhaps the most promising approach is targeting biological molecules. Hence, use of fully human neutralising monoclonal antibodies to the growth factor TGF beta has potential as a useful strategy for modifying conjunctival scarring. Combination therapies may also afford an improved therapeutic index. It is hoped that future therapies can offer safer, more specific, focal and titratable treatment, with far-reaching clinical applications.

Antimetabolites↗
PubMed2000

Wound healing modulation after glaucoma surgery.

Recent developments in molecular and cell biology have made a major impact on our understanding of the wound healing process and its modification. In this article, the spectrum of therapies that are either currently available or have potential application as modulators of the scarring response following glaucoma surgery are reviewed. Refinement of existing antimetabolite regimens can improve surgical results, especially in carefully selected patient groups. However, the most promising new approach appears to be using molecular-based therapies, such as fully human neutralizing monoclonal antibodies, designed to target specific molecules in the scarring response. Such strategies ultimately offer the potential of safer, more specific, focal, and titratable treatment, with far-reaching clinical applications.

Animals↗
PubMed2000

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.

Aged↗
PubMed1996

Misdiagnosis of acute angle closure glaucoma.

When acute glaucoma presents in its classical form, the diagnosis is fairly simple to make. However, atypical presentations are not uncommon and the diagnosis can be missed. This inevitably leads to a delay in treatment which can permanently compromise visual function. We have studied which doctors are most likely to make a misdiagnosis and calculated the resulting delay in treatment. All patients with acute glaucoma attending Whipps Cross eye unit between 1991 and 1994 were identified and their notes obtained. Thirty-eight patients were found to have a had diagnosis of acute closed angle glaucoma. In only 39.5% was the diagnosis correctly made by the referring practitioner and a misdiagnosis resulted in a mean delay of treatment of 5.8 days. General practitioners were the most likely group to have difficulty making the diagnosis, while casualty officers were most likely to make the correct diagnosis. Because acute glaucoma can present without its typical features, there needs to be a high index of suspicion for this diagnosis. This diagnosis does not require expensive equipment or a high level of training--all our patients had a significant reduction in vision. Any patient who has a red eye and a subjective reduction in vision should be referred to an ophthalmologist the same day.

Acute Disease↗