Combined orbital floor betamethasone and depot methylprednisolone in uveitis.

PURPOSE: To evaluate the outcome of orbital floor injection of betamethasone and methylprednisolone in the management of uveitis, with particular reference to its efficacy in avoiding increase in systemic immunosuppressive drugs. METHODS: A sample of all patients attending the Uveitis Service at Moorfields Eye Hospital was carried out over a three-month period. All patients who had received one or more orbital floor injections of betamethasone (4 mg) and methylprednisolone (Depo-Medrone; 40 mg) in the management of their uveitis were identified and the case notes reviewed. RESULTS: A total of 48 patients who had received 75 orbital floor injections were identified during the sample period. Most patients had either panuveitis (n = 24) or pars planitis (n = 14). One-month post-injection visual acuity (VA) had improved by at least one Snellen line after 33/75 injections (44%) and at least two lines after 11/75 (15%), was unchanged after 25 (33%), but had deteriorated in 14 (19%). VA was not recorded after 3/75 injections. The only complications recorded were periorbital haemorrhage (n = 1) and complaints of persistent pain after an injection (n = 1). Symptoms (pain and subjective vision) improved after 36/75 injections (47%), were unchanged after 24 (32%), and were reported as worse after five (7%). Additionally, three patients reported an improvement in symptoms which lasted less than one month. Signs other than VA were improved after 28/75 (37%), were unchanged after 38 (51%), and deteriorated after only one injection. Of the 31 patients given orbital floor injections to avoid systemic therapy, seven (23%) subsequently went on to require it, and the clinical course then improved in 45%. CONCLUSIONS: Combined orbital floor injection of betamethasone and methylprednisolone can result in improved visual acuity, symptoms, and signs of inflammation in uveitis, and may therefore avoid the necessity for increased systemic medication.

Surgical removal of choroidal neovascular membranes after laser photocoagulation for diabetic maculopathy.

PURPOSE: Choroidal neovascularisation (CNV) occurs rarely following laser photocoagulation for macular oedema in diabetic retinopathy, and its management is not well established. We report the clinical course and visual outcomes in a series of patients who underwent surgical extraction of the CNV membrane. METHODS: A retrospective review of 4 cases was carried out. RESULTS: Two women and 2 men, mean age 59.5 (range 58-62) years, were reviewed. The CNV developed 2-24 (mean 11) months after laser coagulation and resulted in decreased visual acuity to between 6/60 and HM. All underwent pars plana vitrectomy, extraction of the CNV membrane and fluid-air exchange. Follow-up ranged between 9 and 48 months. In 2 patients, the vision improved by 4 and 1 Snellen lines respectively and remained stable, in 1 patient it improved by 1 line initially but then regressed to CF, and in 1 patient it remained unchanged. Recurrence of CNV occurred in only 1 patient. Histological characteristics were those of CNV without evidence of photoreceptors. CONCLUSIONS: This study shows that surgical removal of post-laser CNV is technically feasible despite the previous laser scars and may have beneficial outcome. This surgical approach may provide a therapeutic option in such patients.

Giant retinal tears resulting from eye gouging in rugby football.

A 29 year old myopic man sustained two separate giant retinal tears in his right eye following deliberate eye gouging during a rugby tackle. These were successfully repaired by vitrectomy and intraocular silicone oil injection. Although the postoperative course was complicated by pupil block glaucoma, he regained corrected visual acuity of 6/5 after oil removal. This injury highlights the potentially sight threatening nature of this type of rugby injury and the importance of early referral for specialist treatment.

Outcome of acanthamoeba keratitis treated with polyhexamethyl biguanide and propamidine.

OBJECTIVE: This study investigates the clinical outcome of Acanthamoeba keratitis treated with polyhexamethyl biguanide (PHMB) and propamidine isethionate (Brolene). DESIGN: A retrospective review of all patients treated for Acanthamoeba keratitis between September 1992 and February 1995 was carried out. All patients were treated with PHMB 0.02% and propamidine 0.1% hourly for 3 days, the frequency reduced to four to six times daily according to clinical response. MAIN OUTCOME MEASURES: Age, gender, result of laboratory investigation, duration of disease before diagnosis, visual acuity (VA) pretreatment and post-treatment, need for keratoplasty, and presence of adverse reaction were measured. RESULTS: One hundred eleven cases were identified in 105 patients (60 male, 45 female; mean age, 32). Ninety-two percent of infections were in contact lens wearers. The clinical diagnosis was confirmed by corneal culture or histopathology in 64 cases (57.7%). The diagnosis was made "early" (within 28 days) in 65 cases (58.6%). Twenty-one (18.9%) were "intermediate" (28 days-2 months) and 20 (18%) were "late" (> 2 months) diagnoses. Overall post-treatment VA was 6/12 or better in the majority (88/111, 79.3%) of cases, and 18 (16.2%) had VA of 6/36 or worse. The VA of > or = 6/12 was achieved by 90.8% of the early, 71.4% of the intermediate, and 65% of the late groups. Clinical relapses occurred in 19 patients on reducing the therapy. Treatment toxicity was never serious and consisted only of stinging or superficial punctate keratopathy. Keratoplasty was indicated in only ten patients, and disease activity was controlled adequately in all patients before grafting. CONCLUSIONS: Combined treatment with PHMB and propamidine is well tolerated, nontoxic, and effective. Typically, visual outcome is favorable and the requirement for keratoplasty reduced markedly.

Conventional routine clinical review may not be necessary after uncomplicated phacoemulsification.

AIM: To determine the clinical intervention rate during routine review after uncomplicated phacoemulsification. METHODS: A review of case notes in 651 consecutive cases of uncomplicated phacoemulsification from 1994 (< or = 5.5 mm self sealing wound) was performed. The intervention rate at scheduled routine review visits and at unscheduled visits to the eye casualty service in the first 120 postoperative days was recorded. Interventions were defined as departures from predetermined postoperative care protocols. RESULTS: Clinical interventions were reported in 2.8% (95% confidence interval 1.5 to 4.1%) of (n = 1652) routine follow up visits. Many of these interventions were avoidable or trivial; 90% of patients had no postoperative intervention at any visit. 7.3% of patients made unscheduled visits to the emergency service. The intervention rate in this group was 50% (35.9 to 64.1%). CONCLUSIONS: The intervention rate in routine clinical review after uncomplicated modern cataract surgery is low. Alternatives to conventional postoperative review, including shared care with non-ophthalmologists and improved perioperative patient education with an open channel for self referral, should be evaluated.

Topical anaesthesia for phacoemulsification surgery.

Although phacoemulsification with only topical anaesthesia is possible, the level of any discomfort perceived by the patient is unknown. Topical anaesthesia eliminates any risk of inadvertent ocular or orbital injury. Twenty-four patients undergoing phacoemulsification under only topical anaesthesia (g. amethocaine 1%) were compared with 23 patients undergoing the same procedure with peribulbar anaesthesia (5 ml lignocaine 2%, 5 ml bupivacaine 0.5% and 75 units hyaluronidase). Perceived pain on administration of the anaesthesia, per-operatively and post-operatively was assessed by a nursing officer using a visual analogue scale (0-10). It was found that there was no difference in pain score between the two groups on induction of anaesthesia. Per-operatively and post-operatively scores were higher in the topical group than in the peribulbar group (p < 0.05, Mann-Whitney U-test), though most of these were within the range 0-3, ('no pain' to 'slight pain'). There was no difference in the amount of analgesia dispensed to the two groups on the ward post-operatively. In conclusion, topical anaesthesia provides adequate anaesthesia for phacoemulsification. Although a small increase in the level of discomfort was observed, the pain levels reported were small and may not be clinically significant when set against the reduced incidence of anaesthetic-related complications.

Epidemiology of blindness and visual impairment in the kingdom of Tonga.

Data on the prevalence and causes of blindness and visual impairment in Polynesians are not readily available nor are they population based. This survey was designed to obtain an accurate estimate of blindness and its causes in Tonga. A sample of 4056 persons, aged 20 years and over, was selected by stratified cluster sampling. Participants received a screening, visual acuity examination, and, if visually impaired, were referred for detailed ophthalmic examination to determine the cause. The prevalence of bilateral blindness in the study population was 0.47% and all affected were aged over 50 years. It is estimated that the national prevalence of bilateral blindness, adjusted for the sample weight applied in the selection procedure, is 0.56% (95% confidence interval 0-1.13). Monocular blindness was three times more frequent. Cataract was responsible for 68.4% of bilateral and 30.3% of monocular blindness. Risk factors for life time experience of cataract included age and diabetes (self-reported). Neither smoking nor the presence of pterygium were independently associated with cataract. Increasing years of education were protective against cataract for women, but not men. Corneal opacity from infection or trauma, and diabetes were responsible for most of the remaining visual impairment. While these results do not represent a significant public health problem by world standards they do provide a basis for planning blindness prevention programmes in the region.

Growth-rate-independent killing by ciprofloxacin of biofilm-derived Staphylococcus epidermidis; evidence for cell-cycle dependency.

Cell culture methods that allow culture of Staphylococcus epidermidis biofilms at controlled growth rates were used to examine susceptibility to ciprofloxacin. Changes in biofilm susceptibility, dependent upon growth rate, were compared with those for suspended populations grown in chemostat, and also for newly-formed daughter cells shed from the biofilm during its growth and development. Susceptibility increased for intact and resuspended biofilms, and also for planktonic cultures, with increases in growth rate. The dependence of susceptibility upon growth rate was greatest for slow growing cells (mu, 0.01-0.15/h). At any particular growth rate, biofilms appeared more susceptible than their planktonic counterparts. Newly-formed daughter cells were relatively tolerant to ciprofloxacin at all rates of growth. Lack of growth rate dependency for the newly-formed cells suggested a role for the cell-division cycle in determining resistance. This was confirmed by examining the susceptibility of S. epidermidis throughout batch cultures with cell division synchronized. Perfusion of various steady-state biofilms with ciprofloxacin demonstrated killing of the adherent population even at much reduced rates of growth.

Effect of biofilm culture upon the susceptibility of Staphylococcus epidermidis to tobramycin.

Biofilms of Staphylococcus epidermidis were cultured at various specific growth rates, and susceptibilities to tobramycin were compared with those of equivalent plank-tonic populations. In all instances, susceptibility increased significantly with increasing specific growth rate. However, resuspension of the biofilms increased susceptibility, suggesting some involvement of the glycocalyx in reducing antibiotic permeation of the biofilm. Cells that dispersed spontaneously from the biofilms at steady state were particularly susceptible to this agent. Since such cells correspond to newly-divided daughter cells, the relationship between tobramycin susceptibility and the phase in the division cycle was investigated. Susceptibility was enhanced in cultures dividing synchronously shortly before, during and shortly after cell separation. Perfusion of actively-growing S. epidermidis biofilms with tobramycin also demonstrated increased susceptibility with increasing growth rate, but also showed rapid recovery following removal of the agent.

Adhesion molecules are expressed in the human retina and choroid.

Immunoperoxidase staining of samples of normal human retina and choroid was performed to demonstrate selected adhesion molecules in vivo. Intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-3 (LFA-3) and endothelial leucocyte adhesion molecule-1 (ELAM-1) were expressed on retinal vascular endothelium and ICAM-1 and ELAM-1 in the region of the external limiting membrane. The very late antigen-2 (VLA-2) was found around the retinal ganglion cells and in the inner and outer fibre layers. The endothelium on the choriocapillaris showed moderate staining of ICAM-1, and slight staining of LFA-3 and ELAM-1. The presence of these molecules in this distribution strongly suggests they have an important role in the pathogenesis of immunologically mediated ocular conditions.

The expression of adhesion molecules in the human retina and choroid.

This study examines the expression of some selected adhesion molecules likely to be important in the migration of leucocytes across the blood-retinal and blood-aqueous barriers in samples of normal human retina and choroid by immunoperoxidase staining. ICAM-1, LFA-3 and ELAM-1 were expressed on retinal endothelium and ICAM-1, ELAM-1 and CD44 in the region of the external limiting membrane. VLA-2 was found around the retinal ganglion cells and in the inner and outer fibre layers and is likely to be important in maintaining the structural integrity of the retina. The endothelium on the choriocapillaris showed moderate staining of ICAM-1, and slight staining of LFA-3 and ELAM-1. These molecules may have an important functional role in the pathogenesis of many immunological ocular conditions, including uveoretinitis and corneal allograft rejection.

Surface characteristics and adhesion of Escherichia coli and Staphylococcus epidermidis.

Surface hydrophobicity, surface electrokinetic potential and the ability to adhere to nitric-acid cleansed glass surfaces has been assessed throughout the growth, in batch culture, of Escherichia coli and Staphylococcus epidermidis. In both instances adhesiveness and surface hydrophobicity decreased in early- to mid-exponential phase. Cell surface charge, on the other hand became more electro-negative for E. coli but electro-neutral for Staph. epidermidis as the cells proceeded to divide. Adhesiveness correlated directly with surface electronegativity and hydrophobicity for Staph. epidermidis but inversely with surface electro-negativity for E. coli.

Inhibition of somatomedin-like activity by serum from streptozotocin-diabetic rats: prevention by insulin treatment and correlation with skeletal growth.

Diabetes mellitus was induced in rats by streptozotocin. This gave rise to a loss of somatomedin activity in serum. The loss of somatomedin activity was due to the presence of inhibitors associated with serum proteins having mol wts of less than 1, 1-10, 30-50, and 300 K. Whereas less than 1, 1-10, and 30-50 kilodalton fractions were not inhibitory in control and insulin-treated animals, greater than 300 kilodalton fraction was inhibitory in control and insulin-treated animals; the inhibitory activity of this fraction in diabetic animals was significantly greater than that in controls and insulin-treated animals. The appearance of these inhibitors in diabetic animals was accompanied by reduced skeletal growth. Treatment of diabetic animals with insulin abolished the somatomedin-inhibitory activity of serum and corrected the skeletal growth deficit. Serum inhibitors of somatomedin may, therefore, be involved in the causation of some of the complications of diabetes, including impaired skeletal growth.

The effect of continuous subcutaneous insulin infusion therapy on morphological and biochemical abnormalities of peripheral nerves in experimental diabetes.

Diabetes mellitus was induced in rats by the administration of streptozotocin and observations have been made over a period of 2 months in 3 groups of animals: controls, untreated diabetics and diabetics treated with continuous subcutaneous insulin infusion (CSII) therapy, using a 14-day Alzet osmotic minipump. Optimal control of day-to-day and 24-h blood glucose levels was achieved in diabetic animals treated with CSII. Body weight and skeletal growth, assessed by measurements of tibial length, were decreased in untreated diabetic rats and were normalized by insulin treatment. The concentrations of glucose, sorbitol and fructose in the nerves of diabetic animals were significantly increased and that of myoinositol significantly decreased; CSII therapy normalized these levels to those of age-matched controls. External myelinated fibre diameter in the tibial nerve was significantly less in untreated diabetic rats as compared with age-matched controls. In the insulin-treated group, fibre diameter significantly increased as compared with untreated diabetics and there was no significant difference between insulin-treated and control animals. Teased fibre preparations from the tibial nerve revealed very few abnormal fibres in all the three groups and no significant difference was detected between any of the groups. Continuous subcutaneous insulin infusion therapy, therefore, corrected biochemical abnormalities and also normalized myelinated fibre diameter in the peripheral nerves of experimental diabetic animals. The paradoxical excess of axonal degeneration that has been reported with conventional insulin treatment was not observed.

The effect of insulin treatment on myelinated nerve fibre maturation and integrity and on body growth in streptozotocin-diabetic rats.

Diabetes mellitus was produced in rats by the administration of streptozotocin and observations made over a period of 2 months. Four groups of animals were studied: onset and end controls, untreated diabetic rats and rats treated daily with a long-acting insulin preparation. Body weight increased in the end controls and insulin-treated diabetic animals to a similar degree over the observation period but was reduced in the untreated diabetic rats. Skeletal growth, assessed by measurements of tibial length, was also reduced in the untreated diabetic rats and partially corrected by insulin treatment. Myelinated fibre diameter in the tibial and sural nerves increased over the observation period in the controls, but the increase was less in the untreated animals and the growth deficit was not corrected by insulin treatment. Myelinated fibre numbers did not alter in the tibial or sural nerves between the onset and end controls. Numbers were significantly less in the tibial nerves of both the untreated and insulin-treated diabetic rats as compared with the two control groups; in the sural nerves, fibre numbers did not differ significantly between the four groups. Finally, the number of degenerating axons, assessed in teased fibre preparations, was very small in the control and untreated diabetic animals but was significantly increased in the insulin-treated group. Measurements of plasma glucose concentrations did not suggest that the axonal degeneration could be related to hypoglycaemia. The explanation for this paradoxical effect of insulin therapy is uncertain. It may be dependent upon fluctuations in blood glucose levels or other metabolic actions of insulin apart from its hypoglycaemic effect.

Ultrastructural observations on myelinated fibres in the tibial nerve of streptozotocin-diabetic rats: effect of insulin treatment.

Four groups of male Sprague-Dawley rats aged 11 weeks and weighing approximately 450 g were studied over 16 weeks: onset and end controls, untreated diabetics and diabetics treated with a daily subcutaneous injection of Ultralente insulin. Good metabolic control was achieved in the insulin-treated group as judged by daily blood glucose estimations, glycosylated haemoglobin levels (HbA1c) and body weight. Cross-sectional myelinated fibre area significantly increased between onset and end controls; growth thus occurred. In the untreated diabetic rats the values were significantly less when compared with age matched controls and not different to onset controls. The values for the insulin-treated diabetic group did not show a significant increase when compared with untreated diabetics and onset controls and were intermediate between end controls and untreated diabetics without any significant difference when compared with either group. Cross-sectional axonal area was significantly less in the untreated diabetic group as compared with age matched controls and this was corrected by insulin therapy, as there was no difference between end controls and insulin-treated diabetic group. Insulin treatment corrects the reduction in axon size but total myelinated fibre size is not normalised. It seems that in addition to the axon, the myelin sheath and Schwann cells are also affected and these may be less influenced by insulin therapy.