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Aim: To identify the risk factors for, and to report the microbiological findings and clinical outcomes of, severe microbial keratitis (MK)., Methods: This was a retrospective study of all cases of presumed MK admitted to a tertiary referral center over a 2-year period (September 2001 to August 2003). Data recorded included demographic data, details relating to possible risk factors, results of microbiological studies, clinical findings at presentation, and clinical and visual outcomes., Results: Ninety patients were admitted with a diagnosis of presumed MK during the study period. The mean age of patients was 45 +/- 32 years, and the male to female ratio was 47:43 (52.2%:47.7%). Predisposing risk factors for MK included contact lens wear (37; 41.1%), anterior segment disease (19; 21.1%), ocular trauma (13; 14.4%), systemic disease (5; 5.6%), and previous ocular surgery (1; 1.1%). Cultured organisms included gram-negative bacteria (17; 51.5%), gram-positive bacteria (11, 33.3%), acanthamoeba (2; 6.1%), and fungi (1; 3%). Visual acuity improved significantly after treatment [mean best-corrected visual acuity (+/-standard deviation) at presentation: 0.76 (+/-0.11); mean best-corrected visual acuity at last follow-up: 0.24 (+/-0.07); P < 0.001]. Secondary surgical procedures were required in 18 (20%) cases, and these included punctal cautery (1; 1.1%), tissue glue repair of corneal perforation (2; 2.2%), tarsorrhaphy (9; 9.9%), Botulinum toxin-induced ptosis (1; 1.1%), penetrating keratoplasty (3; 3.3%), and evisceration (2; 2.2%)., Conclusions: Contact lens wear remains a significant risk factor for severe MK. MK remains a threat to vision and to the eye, but the majority of cases respond to prompt and appropriate antimicrobial therapy.

Background/aims: The aetiology of Thygeson's superficial punctate keratitis (TSPK) remains elusive. A viral aetiology has been suggested by the absence of bacterial infection and clinical resemblance to other viral keratopathies. We report the results of polymerase chain reaction analysis for the detection of herpes simplex virus (HSV) 1 and 2, herpes zoster virus, varicella zoster virus (VZV) and adenovirus from corneal epithelial samples from patients with active signs and symptoms of TSPK., Methods: Schirmer strip impressions were taken from the epithelium of eight patients with a known history of TSPK and symptoms and signs of active disease. Three patients were recruited as positive controls (two with herpes simplex keratitis and one with herpes zoster ophthalmicus). Samples from a further three patients acted as negative controls. All 14 samples underwent polymerase chain reaction testing for HSV 1, HSV 2, VZV and adenovirus., Results: DNA corresponding to the expected viral DNA was amplified from all three positive control samples. The three negative control samples showed no evidence of viral DNA. Similarly, all samples from patients with TSPK showed no evidence of the presence of HSV 1, HSV 2, VZV or adenovirus., Conclusion: We conclude that HSV, VZV and adenovirus are not present in the epithelium of patients with TSPK. These results are considered in light of existing theories regarding the aetiology and treatment of this condition.

One in four patients attending ophthalmic clinics report symptoms of dry eye, making it one of the most common complaints seen by ophthalmologists. Aqueous-layer deficiency is the most common form of dry eye and is frequently caused by decreased secretion of tears by the lacrimal glands. Evaporative dry eye is often secondary to meibomian gland disease and results in a defective lipid layer. Tear replacement or preservation using artificial tears and/or punctal occlusion are the mainstay of treatment. Newer forms of therapy were designed to modify the underlying disease process. These include the use of topical cyclosporin A, autologous serum, and sodium hyaluronate drops, which suppress underlying inflammation, provide growth factors, and prevent the onset of squamous metaplasia in ocular surface epithelium. Hormonal therapy might have a role in the future of dry eye therapy.

Background/aims: Certain degenerative eye conditions occur predominantly nasally, at the limbal region, and are associated with solar ultraviolet radiation (UVR) induced damage. The relative contribution to the in vivo ocular flux of (a) the reflection of UVR incident on the skin of the nose onto the nasal limbus, and (b) the focusing of UVR incident on the temporal side of the cornea onto the nasal limbus were examined., Methods: A novel photodiode sensor array was used to measure the UVR field across the eye. In addition, a novel spectrometer set-up was used to measure the spectrum of radiation refracted across the cornea. The efficacy of UVR blocking hydrogel contact lenses in filtering incident UVR was assessed in vivo., Results: Qualitative and quantitative data indicated an increase nasally of UVR. Photodiode readings showed a net UVR increase from the temporal to the nasal side. Transmission curves showed that most UVR incident on the limbal region is either absorbed by, or transmitted through, the ocular tissues. This radiation is filtered by UVR blocking soft contact lens., Conclusions: An increased UVR flux on the nasal side of the eye, due to reflection off the nasal skin, was identified in vivo. Any UVR passing through the cornea is either absorbed by the conjunctiva and/or transmitted through it onto the sclera where it is absorbed. UVR blocking hydrogel contact lenses can eliminate these sources of UVR.

Corneal melting disease is, as illustrated, a very severe problem for patients. Correct diagnosis and aggressive management is critical. Help from general physicians and rheumatologists as required is essential, given that the medications used have significant toxic effects.

Congenital hereditary endothelial dystrophy (CHED) is a corneal disorder that presents with diffuse bilateral corneal clouding. Vision may be severely impaired, and many patients require corneal transplantation. Both autosomal dominant (AD) and autosomal recessive (AR) forms of the disorder have been described. The gene responsible for AD CHED (HGMW-approved symbol CHED1) has been mapped to the pericentromeric region of chromosome 20. Investigating a large, consanguineous Irish pedigree with autosomal recessive CHED, we have previously excluded linkage to this AD CHED locus. We now describe a genome-wide search using homozygosity mapping and DNA pooling. Evidence of linkage to chromosome 20p was demonstrated with a maximum lod score of 9.30 at a recombination fraction of 0.0 using microsatellite marker D20S482. A region of homozygosity in all affected individuals was identified, narrowing the disease gene locus to an 8-cM region flanked by markers D20S113 and D20S882. This AR CHED (HGMW-approved symbol CHED2) disease gene locus is physically and genetically distinct from the AD CHED locus., (Copyright 1999 Academic Press.)

Vernal keratoconjunctivitis therefore, if managed properly, can be controlled. Inaccurate diagnosis or staging of the disease, together with inaccurate treatment will however, result in changes which can jeopardize sight and may even necessitate corneal surgery at a later date.

Background: Congenital hereditary endothelial dystrophy (CHED) is a corneal dystrophy characterised by diffuse bilateral corneal clouding resulting in impaired vision. It is inherited in either an autosomal dominant (AD) or autosomal recessive (AR) manner. The AD form of CHED has been mapped to the pericentromeric region of chromosome 20. Another endothelial dystrophy, posterior polymorphous dystrophy (PPM), has been linked to a larger but overlapping region on chromosome 20. A large, Irish, consanguineous family with AR CHED was investigated to determine if there was linkage to this region., Methods: The technique of linkage analysis with polymorphic microsatellite markers amplified by polymerase chain reaction (PCR) was used. In addition, a DNA pooling approach to homozygosity mapping was employed to demonstrate the efficiency of this method., Results: Conventional genetic analysis in addition to a pooled DNA strategy excludes linkage of AR CHED to the AD CHED and larger PPMD loci., Conclusion: This demonstrates that AR CHED is genetically distinct from AD CHED and PPMD.

Aims/background: To identify an HLA association with pseudoexfoliation of the lens capsule to support the hypothesis that there is a genetic predisposition to pseudoexfoliation. A randomised trial would be ideal for establishing a relation but is more costly and time consuming to conduct. Case-control studies provide an alternative method of establishing a relation., Methods: The study group comprised 128 subjects who presented to a major eye centre with pseudoexfoliation. Data from blood donors representative of the population of Ireland were used to form a control group., Results: An HLA association with pseudoexfoliation is identified for 14 antigens. Eleven antigens (HLA A1, A33, B8, B47, B51, B53, B57, B62, DR3, DR12, and DR13) are significantly more common in the pseudoexfoliation group while three antigens (HLA B12, B17, and DR2) are significantly less common. Four HLA antigens are strongly associated, with odds ratios of over 7.5., Conclusion: The strength of this HLA association is supportive evidence for a genetic component to the development of pseudoexfoliation of the lens capsule.

Aims: This study was designed to assess the relative efficacy of topical ganciclovir 0.15% gel and acyclovir 3% ointment in the treatment of herpes simplex dendritic keratitis., Methods: Both treatment modalities were administered on a five times daily basis to patients suffering from herpes simplex keratitis. Patients were assigned randomly to one of the two treatment groups for the purpose of the trial. They were then examined on days 2, 7, 10, and 14 to assess the rate of healing of the dendritic ulceration., Results: There was no statistically significant difference detected in the rate of healing between the two treatment groups over the course of the trial., Conclusions: Review of the relative efficacy of topical ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis showed that both treatment modalities were equally effective in their ability to heal the viral induced corneal ulceration. There were no significant side effects or adverse effects reported for either treatment modality.

We developed an in vitro model to assess the adherence of human lens epithelial cells to three types of intraocular lenses: poly(methyl methacrylate) (PMMA), heparin-surface-modified PMMA (HSM-PMMA), and polyHema. Lenses were incubated with a fixed number of human lens epithelial cells. Adherent cells were counted after 72 hours in culture. Scanning electron microscopy showed significantly fewer cells adhering to the HSM-PMMA and polyHema lenses than to the PMMA lenses (P < .01). Repeat experiments on cell lines established from different donors confirmed these findings.

Posterior capsule opacification is still a major complication of both extracapsular cataract extraction and phacoemulsification. We evaluated the effects of the anti-proliferative agent daunomycin on cultured human and bovine lens epithelial cell viability and proliferation. After ten minutes of exposure, low concentrations of the agent markedly inhibited the proliferation of both cell types. The calculated LD50 for the drug against human cells was 2.20 micrograms/ml and against the bovine cells was 0.38 microgram/ml. The bovine cells appeared to be slightly more susceptible to the drug's effects, although this difference was not marked. Our results indicate that daunomycin is a potent inhibitor of both human and bovine lens epithelial cells in the laboratory.

An international multicentre study assessed the clinical and antibacterial efficacy of a new topical ophthalmic formulation of the quinolone antimicrobial agent ciprofloxacin and compared it with that of tobramycin ophthalmic solution in patients with blepharitis and blepharoconjunctivitis. The study consisted of a randomised double-masked between-group evaluation of 464 patients, 230 of whom were treated with ciprofloxacin and 234 with tobramycin. There was qualitative and quantitative bacteriology, and clinical assessment of ocular symptoms and signs before and after a seven-day course of treatment. Bacteriological cultures demonstrated eradication or reduction of potentially pathogenic bacteria in 93.7% of eyes (ciprofloxacin) versus 88.9% of eyes (tobramycin), seven days after starting treatment. Clinically more than 80% of patients in both treatment groups were cured or improved after seven days. No statistically significant differences were observed between the two treatment groups. No serious side-effects were observed after use of either antimicrobial agent. Ciprofloxacin ophthalmic solution appears safe and effective. The spectrum of activity and clinical efficacy of this new formulation are discussed in comparison with currently used antimicrobial agents.

The effect of topical cyclosporin A on conjunctival T cells was studied in nine patients with secondary Sjögren's disease. Patients had conjunctival biopsies performed before and after a 6-week course of topical cyclosporin. Epithelium and substantia propria in the Sjögren's patients before treatment showed significantly more CD4+ cells than specimens taken from nine age- and sex-matched controls. Following treatment with topical cyclosporin, there was a significant reduction in the number of CD4+ cells in both the conjunctival epithelium and substantia propria. Despite the fact that the treatment resulted in immunopathological improvement, the clinical benefit was not as favorable. Our results suggest that topical cyclosporin may have a local immunosuppressive effect on the conjunctiva in patients with Sjögren's disease.

The results of this clinical study demonstrate that ciprofloxacin ophthalmic solution 0.3% is as safe and as effective as 0.5% chloramphenicol ophthalmic solution in the treatment of conjunctivitis and blepharitis of bacterial aetiology. Both agents achieved microbiological improvement rates in excess of 90% after 1 week's treatment. On ciprofloxacin 93.5% of patients were judged clinically cured or improved versus 84.6% on chloramphenicol after 1 week. There were no serious adverse affects. One patient in each group suffered drug-related side-effects (chemosis, erythema) which resolved on discontinuation or changing of therapy. Cirpofloxacin is not associated with the rare, but serious, side effect of aplastic anaemia which is associated with chloramphenicol use. On the evidence of this study ciprofloxacin would appear to be an appropriate agent for general use as a topical ophthalmic formulation.

There is a broad spectrum of ocular allergy. In the mild forms it is no more than an inconvenience, but severe forms such as eczematous kerato-conjunctivitis can be sight-threatening. However, with proper understanding of the diseases and constructive management, most patients can be satisfactorily controlled.

Thirty patients with first episode disciform keratitis and with no previous steroid exposure were randomly assigned to double blind treatment with 3% acyclovir ointment and 0.1% betamethasone (Betnesol) drops or acyclovir ointment and matching placebo. In the steroid group 14 of the 15 patients healed in a mean time of 21.8 days. In the placebo group eight of the 13 patients healed in a mean time of 34.5 days. The difference in mean healing time between the two groups was significant (p < 0.05). The cumulative rate of healing was also quicker in the steroid group when compared with the placebo group (p < 0.001). Other clinical parameters improved more favourably in the combination treatment group. Four patients, two in either group, experienced a mild transient punctate epitheliopathy, but no other serious adverse effects were noted. There has been no significant difference in the recurrence rate between the two groups after a mean follow-up period of approximately 3 years.

135 patients were entered into a 28-day randomized double-masked multicentre study comparing the efficacy and short-term safety of lodoxamide 0.1% ophthalmic solution (Alomide--Alcon Laboratories), a mast cell stabilizer, with sodium cromoglycate 2% ophthalmic solution (Opticrom--Fisons Pharmaceuticals) in the treatment of allergic eye disease. Patients given lodoxamide 0.1% showed a significantly more rapid and greater improvement in their signs and symptoms of allergic eye disease than patients given sodium cromoglycate 2%. Both treatments were found to be safe, and side-effect profiles were comparable between the two treatment groups, although the overall incidence of side-effects in this study was found to be less frequent in the lodoxamide-treated group.

We looked at the electron microscopic appearances of the corneal endothelium following neodymium:YAG (Nd:YAG) laser iridotomy in a patient with a shallow anterior chamber. An area of denuded endothelial cells approximately 500 microns in diameter was produced when no contact lens was used. The area of cell loss was reduced by approximately 50% when an Abraham YAG goniolens was used. We conclude that the use of a positive plus contact lens can help minimize cell loss following Nd:YAG laser iridotomy.

Herpes simplex disciform keratitis is a difficult condition. The general feeling is that it is an immune disease, mediated by the virus, possibly located in the endothelial cells. It is frequently combined with inflammation in the trabecular meshwork and with uveitis. There is some controversy in relation to treatment and it has been suggested that anti-virals will control herpetic disciform keratitis, particularly if the patient has never had steroids previously. The authors of this paper have, in the past, published data which showed that Acyclovir, with corticosteroid, was necessary in the management of disciform keratitis. The data suggested that Acyclovir on its own was not effective. It remained to be answered whether Acyclovir on its own would be effective in patients who never had steroids for any reason previously. This paper demonstrates clearly that it is necessary, irrespective of whether patients have had steroids in the past or not, to combine corticosteroids with Acyclovir in the management of herpetic disciform keratitis. Acyclovir, on its own, is shown to be ineffective. It has also been suggested that Acyclovir is non-toxic. In a general way this is true, but the authors suggest that Acyclovir ointment does produce a punctate keratitis in patients with tear film disease, and that oral Acyclovir is preferable in such patients.

It is well established that 2% Sodium Cromoglycate is an effective treatment for a number of allergic eye diseases. It has been shown to be non-toxic. It can be used longterm and in serious allergic problems it is a useful adjunctive therapy to steroids. The main problem with Sodium Cromoglycate is that the recommended dosage is a four times daily application and patient non-compliance is common. One of the main objectives of any therapy is to reduce the frequency of dosage and the current study has been designed to investigate the efficacy of a 4% solution of Sodium Cromoglycate, used twice daily, versus a 2% solution used four times daily in seasonal allergic conjunctivitis. A multicentre study, therefore, was carried out to assess the efficacy of both drugs and to assess any possibility of side effects. In addition, a unit dose was used, thus eliminating preservatives and it was used specifically in seasonal allergic conjunctivitis in the pollen season. This study showed that 4% Sodium Cromoglycate used twice daily was at least as affective as 2% Sodium Cromoglycate used four times daily.

The results of a randomised double-blind clinical trial of 0.1% bromovinyldeoxyuridine (BVDU) and 1% trifluorothymidine (TFT) in 60 patients with corneal dendritic ulceration are presented. There was no significant difference between BVDU and TFT in terms of numbers of ulcers healed (p = 0.61), mean healing time (p = 0.065), and cumulative healing rate (p = 0.058). No serious side effects were observed, though transient stinging was recorded in five patients receiving TFT and in three patients receiving BVDU. One patient in the group treated with TFT developed a punctate epitheliopathy.

Three cases of histologically proven limbal xanthogranuloma are presented. All three cases presented with a yellow raised swelling at the limbus and no other ocular or systemic abnormality. A simple excision of the lesion was carried out in all cases and histological examination revealed features typical of xanthogranuloma. Two patients had a recurrence at the original site, necessitating keratectomy, with insertion of a lamellar graft. We suggest that a primary keratectomy with insertion of a lamellar graft should be performed in cases of limbal xanthogranuloma in order to lessen the risk of recurrence and to provide a better cosmetic result.

Fifty patients with corneal dendritic ulceration were randomly entered into a double blind clinical trial comparing BVDU eyedrops with TFT eyedrops. Of those receiving TFT 100% healed in a mean time of 6.7 days, while 92% of those receiving BVDU healed in a mean time of 8.7 days. There was no statistical difference between the two groups in terms of numbers healed, but BVDU was significantly slower in terms of days to heal. After a mean follow-up period of 7.5 months there has been one recurrence in each group.

A 65-year-old man developed ocular cicatricial pemphigoid. He was treated with topical and systemic immunosuppressive agents. Three months later, he was found to have metastatic oesophageal carcinoma. To our knowledge, the association of ocular cicatricial pemphigoid and oesphageal carcinoma has not previously been described.

Forty patients with disciform keratitis were randomly assigned to double-blind treatment with 3% acyclovir and 0.01% betamethasone drops or acyclovir and matching placebo. All patients who received the combination healed in a median time of 21 days, while 11 of 19 patients who received acyclovir alone were withdrawn because their condition remained static or worsened (p less than 0.001). The combination therapy produced a faster rate of healing (p = 0.004); other clinical parameters also improved more favourably in the combination treatment group. Three patients had mild transient punctate keratopathy, but no serious adverse effects were seen despite treatment for a median duration of 28 days in the acyclovir group and 38 days in the combined therapy group. A combination of acyclovir and dilute steroid drops is effective in the management of disciform keratitis.

A double blind comparative study of oral acyclovir and acyclovir ophthalmic ointment was carried out on 29 patients with simple herpetic dendritic corneal ulceration. Patients were randomly allocated to the study. Healing was achieved in all fourteen patients treated with acyclovir ointment, and in fourteen out of fifteen patients treated with oral acyclovir. The mean healing time of 5.6 days was identical for both patient groups. There was no significant systemic or local side effects recorded in either group. The level of acyclovir in tear fluid was measured, and in patients receiving oral acyclovir the level was in excess of the ED50 of herpes simplex virus type 1.

The results of a randomised double-blind clinical trial of 3% acyclovir and 0.5% idoxuridine (IDU) ophthalmic ointments in 60 patients with corneal dendritic ulceration are presented. Ulcers in all 30 patients treated with acyclovir healed compared with 22 (76%) of 29 patients treated with IDU (P < 0.01). Patients treated with acyclovir healed more rapidly (average 4.4 days) than those who received IDU (average 9.2 days) (P < 0.01). No serious side effects were observed, though transient stinging was recorded in 8 patients receiving acyclovir and in 2 patients receiving IDU. Other side effects in the IDU treated group were watering in 2 patients and superficial punctate erosions in 6 patients.

Fifty-one patients were treated in a dual-centre, double-blind comparison of acyclovir and adenine arabinoside in herpetic amoeboid (geographic) corneal ulceration. Twenty-four of the 25 patients receiving acyclovir healed in a mean time of 12.2 days, while 24 of the 26 patients treated with adenine arabinoside healed in a mean time of 11.0 days. There was no statistically significant difference between the two groups in terms of healing. A second analysis, excluding any patients who had received antiviral treatment immediately prior to entry into the study, showed that 18 of the 19 who received acyclovir healed in an average of 11.7 days and 18 of the 19 recipients of adenine arabinoside healed in a mean time of 11.2 days. Again the difference was not statistically significant.

A double-blind comparative trial of acyclovir (ACV) and adenine arabinoside (ARA-A) in combination with dilute betamethasone was carried out in 30 patients with herpetic disciform keratitis. Of those receiving ACV and betamethasone, 86.7% healed in a mean time of 22.5 days, while 76.9% of those receiving the Ara-A combination healed in a mean time of 26.7 days. There was no statistical difference between the two treatment groups for efficacy parameters. However, the proportion of patients developing superficial punctate keratopathy (SPK) was significantly greater in the Ara-A treatment group.

Two techniques are described which enable a rapid diagnosis of herpes simplex keratitis to be made. The tests, antibody/antigen reactions, were shown to be accurate and sensitive in the 119 patients examined. A result is available within four hours with the indirect peroxidase-antiperoxidase method and within one hour with the direct method. The techniques are relatively inexpensive, though labour intensive. Negative reactions were found in treated cases and in those with some delay in the histochemical staining.

Acyclovir is an effective and relatively non-toxic antiviral agent which has recently been introduced for the treatment of herpes virus infections in man. When combined with dilute steroid, acyclovir heals herpetic disciform keratitis and preliminary results of a double-blind clinical trial suggest that it may be more effective and less toxic than adenine arabinoside in the treatment of this condition.

Sixty patients with simple dendritic corneal ulceration were randomly assigned to double blind treatment with either acyclovir tablets (400 mg) or acyclovir ophthalmic ointment administered five times daily. There was no significant difference in the proportions of patients healed in either treatment group (88.9% on oral acyclovir and 96.6% on acyclovir ointment). The median healing time was five days in both groups. No systemic or significant local side effects were noted in either treatment group. Trough levels of acyclovir in the tear fluid of those who received the oral preparation were within or above the range of mean in-vitro ID50 levels for herpes simplex virus type 1. We conclude that oral administration of acyclovir (400 mg, five times daily) may be an effective alternative to topical therapy in selected patients.

Seven patients, who satisfied the criteria laid down by Mason and Barnes (1969) for inclusion under the heading Behçet's disease, were assessed clinically and investigated with particular reference to immune status and blood fibrinolytic activity. In one patient in whom it was possible to obtain an eye for examination, there was evidence, on microscopic examination, of an immune vasculitis as well as clot formation, particularly in the veins. All the patients were treated with fibrinolytic agents and the favourable results obtained with this treatment suggest that it should be considered as the first line of therapy in what is otherwise a very difficult condition to manage.

Herpes simplex keratitis accounts for 50 percent of patients presenting at our corneal clinic. Studies of the use of acyclovir in dendritic and geographic ulceration and disciform keratitis are presented. In a double-blind study of acyclovir and idoxuridine in 60 patients with dendritic keratitis, acyclovir was shown to be superior and produced no serious side effects. Patients with geographic ulcers have been treated on an open basis with acyclovir and the drug was found to be effective. A combination of acyclovir and dilute steroid drops appeared to be as effective as currently available treatments in the management of disciform keratitis. Double-blind studies are now in progress to evaluate acyclovir in geographic and disciform keratitis.

An 18-year-old white man presented with a non-painful yellow raised swelling on the inferior limbus of his right eye. Systemic and ocular examination revealed no other abnormalities. The lesion was dealt with by simple excision, but when it recurred fairly soon it was removed in toto and replaced by a lamellar graft, without recurrence. Histological examination revealed a typical xanthogranuloma. The question is, why should a healthy male with no other manifestations develop a lesion like this on his limbus?

The clinical and pathological presentation of Behçet's disease are discussed. Necrotising arteriolitis and phlebitis with thromboses are demonstrated when a rare enucleation specimen became available for examination in this condition. Immunohistochemical studies show mural IgG, IgA, and C3 deposits in episcleral and some choroidal veins. The value of the clinical use of fibrinolytic agents is discussed.