Prolonged ocular hypotension: would ciliary tissue transplantation help.

AIMS: Ocular hypotony and phthisis bulbi from persistent fistulae, ciliochoridal detachments, or inflammation, that cannot be treated currently. However, complete shutdown of the ciliary epithelium is rare. Secreting, transplanted ciliary tissue could restore the IOP to a level where further visual damage would not occur or even be reversed. METHODS: Allografts of ciliary epithelium and its substrate were placed on to the surface of the iris of normal albino rabbits. The progress of the transplanted tissue was followed in the untreated animals, those who had been immunosuppressed and those who had been immunosuppresed together with cold whole body perfusion for up to 55 days. Changes were assessed by slit-lamp observation, luconyl blue staining, fluoresceine angiography, and these were compared with the histology and electron microscopic appearances. RESULTS: Transplants survived the period of ischaemia in the anterior chamber. They started to be revascularised within 4 days and were completely revascularised in 12 days. Untreated animals showed classical rejection phenomena. However, the ciliary epithelial tissue in those animals who were immunosuppressed and had been subjected to whole body perfusion remained normal and were secreting aqueous, as judged by the histological and electron microscopic appearances. CONCLUSIONS: Perfused allografts of ciliary tissue will survive in the normal anterior chamber of the immunosuppressed rabbit, and the electron microscopic evidence indicates that the tissue is producing aqueous. If this can be shown to be adequate in the damaged eye, then ciliary transplantation could be a valuable tool in the management of severe intractable hypotony.

HLA-DR17 and Mooren's ulcer in South India.

OBJECTIVE: To investigate the association between Mooren's ulcer and human leucocyte antigen (HLA) type DR17(3) in patients from the Tamil Nadu State of South India. METHODS: Blood samples from 38 patients with Mooren's ulcer and 45 age- and sex-matched controls were obtained prospectively. HLA-DR and HLA-DQ typing was performed by PCR using sequence-specific primers. RESULTS: Fifteen (40%) of the patients with Mooren's ulcer tested positive for HLA-DR17(3) compared with seven (16%) of the controls (p = 0.01). Seventeen (45%) of the patients also tested positive for the closely linked HLA-DQ2 compared with 11 (24%) of controls (p = 0.05). When adjusted for multiplicity, the correlation between HLA-DR17(3) and Mooren's ulcer remained significant (p = 0.03). CONCLUSIONS: These data demonstrate an association between HLA-DR17(3) and Mooren's ulcer in South Indian patients, supporting autoimmune theories about the pathogenesis of the disorder.

Ciliary tissue transplantation in the rabbit.

Irreversible damage of the ciliary body can be responsible for prolonged ocular hypotony and phthisis bulbi, which, currently, cannot be treated. The aim of this study was to achieve survival of morphologically normal ciliary tissue (CT) transplants in the anterior chamber of a rabbit's eye. Outbred female New Zealand albino rabbits received CT allografts, which were placed on to the surface of the host iris. We evaluated the influence of ciclosporin (CsA), VEGF and donor perfusion on graft survival. Operated eyes were assessed clinically and histologically, and revascularization of the grafts was determined by fluorescein angiography. All grafts became dark and ischemic during the first five to seven days after transplantation. Reperfusion of the grafted tissue was complete at approximately ten days after transplantation. In untreated animals, transplants became infiltrated by inflammatory cells, which led to destruction of the tissue. This was prevented by systemic use of CsA. Transplants treated with VEGF prior to transplantation had fewer ischemic areas but epithelial cell survival was not improved. Whole body donor perfusion prior to preparation of the grafts resulted in less inflammation and, histologically, in a better quantity and quality of the epithelial cells in the CT transplants. Ciliary tissue can be successfully transplanted but the ciliary epithelium suffers from ischemia and in untreated animals the whole transplant is rejected in the classical fashion. If the donor is perfused and the host immunosuppressed, histologically normal ciliary epithelium can be preserved together with rapid revascularization, minimal inflammation and good survival of the transplant, although fibrosis continued to occur during the two months after transplantation.

Smoking delays the response to treatment in episcleritis and scleritis.

PURPOSE: To evaluate the influence of smoking on comorbidity, treatment, visual and general outcome in patients with scleritis. METHODS: The smoking habits of 103 patients with a diagnosis of episcleritis or scleritis were evaluated. These patients were treated by one ruling protocol at the Leiden University Medical Center between 1997 and 2000. Medical records of each patient were evaluated in detail. Data on possible factors concerning smoking were collected by postal questionnaire. RESULTS: Of all 103 patients diagnosed with either episcleritis or scleritis, 41 (39.8%) were smoking during treatment of the scleral inflammation. In total, 19 patients (18.4%) had a smoking history while 43 (41.7%) patients have never smoked. The response to any of the given medications could be delayed by at least 4 weeks in many smoking patients (odds ratio (OR) 5.4 [95% confidence interval 1.9-15.5]), particularly those with posterior scleritis. Smoking patients above the age of 48 years were even more likely to respond belatedly to any given therapy (OR 6.6 [2.1-20.7]). However, having a smoking history did not delay the response. Furthermore, smoking did not worsen the visual prognosis and was not associated with additional recurrences or ocular complications after successful treatment. CONCLUSIONS: Although scleritis patients who smoked during treatment eventually responded, there was frequently over a month's delay before the medication became effective when compared to nonsmokers. This was irrespective of the type of disease or given therapy. As a consequence, smokers required more intensive therapy than those who did not smoke.

Dual sampling for the detection of female Chlamydia trachomatis infection with a polymerase chain reaction test.

Using a polymerase chain reaction method of detection, the value of taking urethral and endocervical specimens to screen for female Chlamydia trachomatis infection and to test for cure of that infection was audited. In the population of 130 women being screened, 19 (14.6%) had a positive result in either or both specimens. Eighteen infections (94.7%) were detected on the urethral sample and 16 (84.2%) on the endocervical sample. In the population of 40 women being tested for cure, C. trachomatis was detected in nine. The urethral sample was positive in 9/9 (100%) and the endocervical sample in 7/9 (77.8%). Analysis of those nine cases showed that seven had failed to take their treatment properly or had been at risk of re-infection.

Orbital myositis in scleritis.

AIMS: To investigate the association between scleritis and myositis. METHODS: Retrospective, non-comparative case series. Records and ultrasonograms were examined of 132 patients, with a diagnosis of episcleritis or scleritis, who attended the ophthalmology department at Leiden University Medical Center between 1997 and 2000. 103 were eligible for comprehensive examination. Medical records were evaluated. Ultrasonography was performed in all patients diagnosed with episcleritis or scleritis. Clinical features, precipitating factors, systemic associations, ocular complications, treatment, and outcome of each patient were assessed. RESULTS: Of the 103 patients, 27 (26.2%) had episcleritis and 76 (73.8%) had scleritis. Myositis was found to be present in 11 patients. It was present in 14.5% of all patients with scleritis and 30.5% of those in whom the posterior sclera was affected. The presence of the associated myositis did not worsen the visual prognosis and the presence of myositis was not associated with other systemic diseases. There were no cases of unilateral scleritis with bilateral orbital myositis. During an attack ocular complications were more common in patients with scleritis and myositis (64%) than in patients with scleritis alone (30.4%), indicating a more diffuse and potentially dangerous inflammation. There was no evidence that the inflammatory changes in the orbit had spread to involve the sclera, so it is assumed that the muscle changes are an extension of a generalised response to intense inflammation of the episclera and sclera. CONCLUSION: This study found a frequent association between myositis and scleritis. Prognosis for vision was not affected by coexistence of myositis.

Arylthiazylamides: syntheses, structures, and bonding properties.

Air-sensitive, thermally unstable tris(dimethylamino)sulfonium (TAS) salts (3) of the title anions [ArNSN]- have been prepared from corresponding sulfurdiimides Ar-N=S=N-SiMe3 (2) by Si-N bond cleavage with [(Me2N)3S]-[Me3SiF2]- (TASF). They are characterized by low-temperature X-ray crystallography as Z isomers. Because of the very short terminal S-N distance (144.2 (3h)-147.9 (3i)pm) and the relatively long internal S-N distance (158.3 (3i)-160.3 (3c) pm) the [ArNSN]- ions should be regarded as thiazylamides 1b, rare species containing a S triple bond N triple bond. A bonding model is developed and the experimental results are compared with those of restricted Hartree-Fock (RHF), density functional theory (DFT), and Møller-Plesset second-order (MP2) calculations.

A 7 year prospective comparative study of three topical beta blockers in the management of primary open angle glaucoma.

AIM: To determine the long term efficacy of monotherapy with topically applied beta blocking agents and to determine whether selective beta blockers were able to preserve the visual field more effectively than non-selective agents. METHOD: A prospective randomised, open, comparative study of three topically applied beta blockers-timolol, betaxolol, and carteolol-was carried out on 153 patients (280 eyes) with newly diagnosed open angle glaucoma. Those patients who were not withdrawn were followed by the same observers for a minimum of 2 years and a maximum of 7 years, with clinical observations, Goldmann tonometry and 24.2 Humphrey visual field analysis. RESULTS: All three drugs lowered the IOP significantly from untreated levels but betaxolol took up to 12 months in some instances to reach the maximum pressure reduction. After 7 years only 43% of the eyes begun on timolol, 34% of those started on carteolol, and 29% of those on betaxolol were still being treated with these medications alone. Visual fields were analysed throughout the trial by CPSD and MD and at the end by linear regression analysis (PROGRESSOR). The visual fields remained the same without apparent improvement or deterioration throughout the period of follow up. Eight patients (11 eyes) were withdrawn because of continuing field loss in spite of reduction in IOP (six using carteolol and five using betaxolol). CONCLUSIONS: Analysis shows that less than half the eyes initially treated with topical beta blockers might be expected to still be being treated with their original medication after 5 years. The rest required either additional medication or trabeculectomy. There was no statistically significant improvement or deterioration in the visual fields over a 7 year period. On the evidence of this trial there are no particular advantages in using selective beta blockers.

Structure of the SO(2)F(-) anion, a problem case.

Recently, room-temperature crystal structures of SO(2)F(-) in its K(+) and Rb(+) salts were published in Z. Anorg. Allg. Chem. 1999, 625, 385 and claimed to represent the first reliable geometries for SO(2)F(-). However, their almost identical S-O and S-F bond lengths and O-S-O and O-S-F bond angles are in sharp contrast to the results from theoretical calculations. To clarify this discrepancy, the new [(CH(3))(2)N](3)SO(+) and the known [N(CH(3))(4)(+)], [(CH(3))(2)N](3)S(+), and K(+) salts of SO(2)F(-) were prepared and their crystal structures studied at low temperatures. Furthermore, the results from previous RHF and MP2 calculations were confirmed at the RHF, B3LYP, and CCSD(T) levels of theory using different basis sets. It is shown that all the SO(2)F(-) salts studied so far exhibit varying degrees of oxygen/fluorine and, in some cases, oxygen-site disorders, with [(CH(3))(2)N](3)SO(+)SO(2)F(-) at 113 K showing the least disorder with r(S-F) - r(S-O) = 17 pm and angle(O-S-O) - angle(F-S-O) = 6 degrees. Refinement of the disorder occupancy factors and extrapolation of the observed bond distances for zero disorder resulted in a geometry very close to that predicted by theory. The correctness of the theoretical predictions for SO(2)F(-) is further supported by the good agreement between the calculated and the experimentally observed vibrational frequencies and their comparison with those of isoelectronic ClO(2)F. A normal coordinate analysis of SO(2)F(-) confirms the weakness of the S-F bond with a stretching force constant of only 1.63 mdyn/A and shows that there is no highly characteristic S-F stretching mode. The S-F stretch strongly couples with the SO(2) deformation modes and is concentrated in the two lowest a' frequencies.

Using a national guideline: an audit of the management of gonorrhoea in Newcastle upon Tyne.

The management of cases of gonorrhoea in the Genitourinary Medicine Department (GUM) of Newcastle upon Tyne in 1999 was audited. The sensitivity of microscopy in diagnosis was 90.4% for male urethral gonorrhoea and 26.6% for female genital gonorrhoea. The sensitivity of laboratory culture was 98.5%. Screening for Chlamydia trachomatis co-infection or treating for presumed co-infection was done in 98% of cases of gonorrhoea and the rates of co-infection were 36.4% in women and 8% in men. Effective first-line therapy was given to 95.4% of cases of genital gonorrhoea. Re-attendance for tests of cure within one month of treatment was achieved in 68.2%. Discussion of partner notification was documented in 94.3% of cases of genital gonorrhoea. In 65% of cases of gonorrhoea, there was documented attendance of sexual partners. The value of a national guideline with auditable targets is discussed.

TAS+(Z)-Me3CNSN- and TAS+(E)-Me3SiNSN-: does the anion-cation interaction influence the configuration?

TAS+ salts (TAS = (Me2N)3S) of the sulfur diimide anions Me3XNSN- (X = C (1a), Si (1b)) were prepared by Si-N bond cleavage from the corresponding sulfur diimides Me3XNSNSiMe3 and TAS-fluoride ((Me2N)3S+Me3SiF2-) and characterized by X-ray crystallography and multinuclear NMR spectroscopy. According to the experimentally determined bond lengths and theoretical calculations, the Me3XNSN- anions are best described as thiazylamides Me3X-N-S identical to N rather than sulfur diimides Me3X-N=S=N. In agreement with the calculated and experimentally determined structures of the isoelectronic thionylimides RNSO, 1a adopts the Z-configuration, which is electronically favored due to anomeric effects. The electronically disfavored E-configuration of 1b in the solid state can be explained by weak anion-cation interaction.

HLA and Mooren's ulceration.

BACKGROUND: Mooren's ulcer is a progressive intractable destructive peripheral ulceration of the cornea, probably of autoimmune aetiology. The disease is rare in the northern hemisphere but is more common in southern and central Africa and the Indian subcontinent. Although rare, its predominance in certain racial groups and their second generation migrants worldwide indicates a genetic as well as a geographic predisposition. The highly polymorphic human leucocyte antigens (HLA) confer genetic susceptibility to several autoimmune disorders. Therefore, a possible link between Mooren's ulcer and HLA type was investigated. METHODS: Patients (n=22) with non-infective destructive peripheral corneal inflammatory disease were recruited worldwide. Differential diagnosis confirmed Mooren's ulceration in 12 cases. HLA typing (HLA-A, B, C, DRB, DQB) was performed by serology and PCR using sequence specific primers. The patients came from varied ethnic backgrounds and their HLA typing results were compared with published data from ethnically matched control populations. RESULTS: Of the 12 patients with Mooren's ulcer, 10 (83%) were HLA-DR17(3) positive (including all nine patients of Asian, Indonesian, and black African origin), and 10 (83%) were HLA-DQ2 positive. The frequency of HLA-DR17(3) and DQ2 was higher in the Mooren's ulcer group compared to published data from ethnically matched control populations, where the expected antigen frequencies range between 5% and 40%. CONCLUSION: These results suggest a possible association between HLA-DR17(3) and/or DQ2 and susceptibility to Mooren's ulcer.

Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients.

OBJECTIVE: To document the clinical features, systemic associations, and visual outcome in a large number of patients with posterior scleritis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: There were 137 patient records showing patients with a diagnosis of posterior scleritis who were attending or had attended the scleritis clinic at Moorfields Eye Hospital between 1974 and 1996. Ninety-nine records were suitable for detailed analysis. METHODS: The medical records and B-mode ultrasound examinations were reviewed. MAIN OUTCOME MEASURES: The clinical features, systemic associations, treatment, and outcome of each patient were determined. RESULTS: Posterior scleritis occurred at all ages. The mean age at onset was 49.3 years. Posterior scleritis began before age 40 in 30% of patients and was twice as common in women as in men. The B-mode ultrasound examination showed diffuse and nodular changes in the posterior sclera. Necrotizing posterior scleritis was not identified. Twenty-nine percent of patients had an associated systemic disease that included systemic vasculidites, autoimmune diseases, and lymphoma. Such patients more commonly had nodular changes on B-mode ultrasound examination. Early treatment controlled posterior scleral inflammation and limited visual loss. Thirty-one percent of patients lost two or more lines of vision. Statistical analysis revealed that patients older than age 50 had an increased risk of having an associated systemic disease and were more likely to experience visual loss. Patients with associated systemic disease required more aggressive immunosuppressive therapy and more frequently had accompanying anterior scleritis. There was no association between unilateral, bilateral, or recurrent disease and the presence of systemic disease or visual loss from posterior scleritis. CONCLUSIONS: The B-mode ultrasound examination reveals that posterior scleritis occurs far more often than previously thought and can lead to rapid and permanent visual loss. All patients with posterior scleritis must be assumed to be at risk of visual loss. Forty percent of patients had no anterior scleral inflammation, and 9% had no detectable physical signs. All patients need to be investigated for an associated systemic disease and all require early treatment to minimize loss of vision.

Neisseria gonorrhoeae in Newcastle upon Tyne 1995-1997: increase in ciprofloxacin resistance.

Fluoroquinolones and third generation cephalosporins are the most effective antimicrobial agents for the treatment of gonorrhoea. However, clinically significant resistance to fluoroquinolones in Neisseria gonorrhoeae has been reported worldwide including Britain. The aim of this analysis was to study the factors relating to ciprofloxacin resistance and treatment failure. A total of 201 patients attending the Newcastle Genitourinary Medicine (GUM) clinic from 1995-1997 who were diagnosed with culture positive gonorrhoea was analysed. Treatment failure rates for ciprofloxacin were determined and the minimum inhibitory concentration (MIC) was measured for all cases of treatment failure. The case notes of all patients who had strains with MICs of ciprofloxacin in the resistant range (>0.05 microg/ml) were reviewed to determine the clinical outcome. The ciprofloxacin resistance with treatment failure was seen in 5% (8/160). All the 8 cases of treatment failure were heterosexual and had isolates resistant to penicillin and 4 cases (50%) were also resistant to tetracycline. All were sensitive to spectinomycin and ceftriaxone. Most of the cases probably acquired their infection from the Far East. As ciprofloxacin resistance seems to be associated with overseas exposure, changes in the standard treatment of gonorrhoea are not justified but consideration should be given to appropriate alternatives when the infection may have arisen from where such resistant strains are endemic. Monitoring fluoroquinolone resistance is now essential for ensuring adequate treatment of infections with resistant strains and for maximizing the time of usage of fluoroquinolones to treat gonorrhoea.

Latanoprost in the treatment of glaucoma and ocular hypertension.

Latanoprost (Xalatan) is a prostaglandin F(2alpha) analog prodrug which is activated when hydrolyzed in the cornea and plasma. Latanoprost reduces the intraocular pressure (IOP) by increasing uveoscleral outflow. Other locally applied medications reduce IOP either by increasing the outflow of fluid through the trabecular drainage system or by reducing the production of fluid in the eye. Latanoprost, which is used topically in the eye at the low dose of 0.005% once daily, has been shown in phase III studies carried out in Scandinavia, the U.K. and the U.S. to be capable of lowering the IOP in patients with open-angle glaucoma and ocular hypertension by 35%. This low IOP is maintained over at least a 2-year period. Latanaprost is as effective, or possible slightly more effective than timolol in its pressure reducing effects. Additional pressure reduction can be achieved by adding latanoprost to existing glaucoma medications. Because latanoprost is rapidly metabolized outside the eye, systemic side effects do not occur. Increased iris pigmentation occurs in at least 10% of hazel (but not blue or dark-eyed patients). So far no ocular problem has occurred because of the increased production of pigment which is not released from the iris. Isolated cases of cystoid macular edema have occurred, so that anyone complaining of reduction of vision while using the drug should be fully investigated.

Latanoprost. Two years' experience of its use in the United Kingdom. Latanoprost Study Group.

OBJECTIVE: The aim of the study was to assess the efficacy and safety of latanoprost in the long-term treatment of glaucoma. DESIGN: The study was designed as a randomized, 6-month double-masked parallel group, multicenter study comparing latanoprost with timolol followed by an 18-month open-label, multicenter study in which all patients were treated with latanoprost. PARTICIPANTS: In total, 277 patients were treated with latanoprost for up to 24 months. INTERVENTION: For the first 6 months of treatment, latanoprost (0.005%) administered once daily was compared with timolol (0.5%) administered twice daily. Patients then received latanoprost (once daily) for an 18-month follow-up period regardless of their initial treatment. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured over the 24-month treatment period, and any ocular-systemic symptoms or adverse events were evaluated. RESULTS: Latanoprost significantly reduced (P < 0.001) IOP by approximately 8 mmHg from pretreatment values, and this reduction was maintained over the 24-month treatment period with no sign of upward drift. Latanoprost is apparently free of any systemic side effect. The most significant ocular side effect with latanoprost was an increase in iris pigmentation, which occurred in 51 patients. CONCLUSIONS: Latanoprost, administered once daily, is effective and well tolerated for the long-term treatment of patients with open-angle glaucoma or ocular hypertension.

Phase III latanoprost studies in Scandinavia, the United Kingdom and the United States.

Three large, masked, multicenter studies are reviewed comparing the safety and efficacy of 0.005% latanoprost eyedrops given once daily to 0.5% timolol eyedrops given twice daily for six months in patients with elevated intraocular pressure (IOP). A total of 829 patients were recruited from centers in Scandinavia, the United Kingdom (UK) and the United States of America (USA). In addition, data are reviewed from the first 198 of these patients to complete an additional six months of latanoprost treatment in an openlabel study. In all centers, both latanoprost and timolol were very effective in reducing the diurnal IOP. In the UK, both drugs reduced the IOP by 34%. In the USA, latanoprost was more effective than timolol, reducing IOP by 27% compared to 20%. In Scandinavia, latanoprost was given for three months in the evening and for three months in the morning while timolol was given twice daily for six months. Latanoprost given in the evening reduced IOP (35% reduction) significantly (p < 0.001) more than latanoprost given in the morning (31% reduction) and timolol given twice daily (27% reduction). Darkening of the iris color occurred in 7% of eyes treated with latanoprost for six months. A clinical evaluation of eyes with increased pigmentation, as well as preclinical studies; suggest that this side effect is a cosmetic problem in patients treated unilaterally. Other side effects were slight and not clinically significant. After one year of treatment with latanoprost in 198 patients, the IOP reduction of 32% was maintained. There was no loss of efficacy and no significant increase in the incidence of side effects or adverse events other than iris color darkening, which occurred or was suspected in 12%. These results demonstrate that latanoprost is a valuable drug for the treatment of chronic open angle glaucoma.

Management of Mooren's ulceration.

Although the diagnosis may be difficult when a patient first presents with Mooren's ulceration, the clinical appearances are characteristic and should not be confused with other conditions which cause corneal ulceration. Based on the clinical presentation and the low-dose anterior segment fluorescein angiographic findings, there seem to be three distinct varieties of Mooren's ulceration: (1) Unilateral Mooren's ulceration (UM), characterised by an excessively painful progressive corneal ulceration in one eye in elderly patients, associated with non-perfusion of the superficial vascular plexus of the anterior segment. (2) Bilateral aggressive Mooren's ulceration (BAM), which occurs in young patients, progresses circumferentially and, only later, centrally in the cornea. Angiography shows vascular leakage and new vessel formation which extends into the base of the ulcer. (3) Bilateral indolent Mooren's ulceration (BIM), which usually occurs in middle-aged patients presenting with progressive peripheral corneal guttering in both eyes, with little inflammatory response. There is no change from the normal vascular architecture on angiography except an extension of new vessels into the ulcer. The management differs in each of these varieties.