Outcome of phacoemulsification in patients with uveitis.

AIMS: To examine the visual outcome and identify risk factors for postoperative uveitis, macular oedema and neodymium-doped yttrium aluminium garnet (Nd:YAG) capsulotomy after phacoemulsification and intraocular lens (IOL) implantation in patients with uveitis. METHOD: This is a retrospective review of the medical records of 101 eyes of 101 patients. One eye was randomly selected for inclusion in patients who had bilateral surgery. Patients with juvenile arthritis, keratouveitis and lymphoma-associated uveitis were excluded. RESULTS: At the first postoperative and final visits, visual acuity was significantly better (p<0.001), and 64.4% and 71.3% of patients, respectively, had achieved >or=2 Snellen's lines of visual improvement. The cumulative probability of doubling of the visual angle was 52% over 6 years of follow-up, and this occurred at a higher rate in the presence of preoperative retinal or optic nerve lesions (HR (95% CI) 4.49 (1.41 to 14.29)). Within 3 months after operation, uveitis was more likely to develop in female patients (OR (95% CI) 6.21 (1.41 to 27.43)) and in the presence of significant intraoperative posterior synechiae (OR (95% CI) 8.43 (1.09 to 65.41)); macular oedema was more likely to develop in patients who developed postoperative uveitis (OR (95% CI) 7.45 (1.63 to 34.16)). Nd:YAG capsulotomy occurred at a higher rate in patients aged

Outcome of graft free Molteno tube insertion.

AIMS: To determine the long term outcome of Molteno implants inserted using a modified surgical technique that eliminates the need for a donor scleral graft. METHODS: Retrospective case series involving a medical record analysis of 35 consecutive patients undergoing first Molteno implant surgery for refractory glaucoma. The main outcomes included life table analysis of intraocular pressure control following surgery and frequency of intraoperative and postoperative complications. RESULTS: There were no complications related specifically to the modified method of tube placement. Medium term intraocular pressure control was similar to other series. CONCLUSIONS: This simplified method for the insertion of Molteno implants eliminates the need for a donor scleral graft while maintaining the implant's ability to control intraocular pressure.

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.

Behçet's disease in Japan and in Great Britain: a comparative study.

Behçet's disease (BD) is an important cause of visual morbidity throughout the world, but shows striking differences in racial predilection. Despite important advances in the therapeutic management of acute intraocular inflammation, the long-term impact of these new strategies on visual outcome of BD and their efficacy in different ethnic groups is unknown. A comparative study of patient characteristics, clinical ocular features and inflammatory score, and current therapy was undertaken on all patients fulfilling the International Study Group criteria for Behçet's disease and the Behçet's Disease Research Committee of Japan, who attended the Uveitis Clinics of Moorfields Eye Hospital (n=19) and Kurume University School of Medicine (KUS) (n=35) during a continuous consecutive four-week period. Japanese patients were significantly older (43.2+/-11.8 years) than the patients seen in London (35.4+/-8. 9 years). There was a predominance of male patients in both groups. All patients seen in KUS were Japanese, while the patients in London included 12 Caucasians, five Middle Eastern, one African, and one Asian. No significant differences were seen between the two populations in the duration of systemic disease or systems affected by the disease, such as mouth ulcers, genital ulcers, skin lesions including erythema nodosum, or arthritis. The duration of ocular disease was similar in both centres: around seven years. There was, however, a significant difference in the number of eyes with active anterior uveitis (59.7% KUS vs 18.4% London (chi-square: 5.4; p=0.006)) and/or posterior uveitis (31.3% KUS vs 18.4% London (chi-square: 5.42; p<0.02)). No significant differences were found in the number of eyes with optic disc swelling or optic atrophy and in each centre the number of eyes with vision greater than 6/9 or worse than 6/60 were the same. The treatment schedules were very different between the two centres. More patients were treated with topical steroids in Japan (68.7% KUS vs 10.5% London (chi-square: 30.5; p=0.001), but a similar number used concomitant intraocular pressure-lowering agents. More patients received systemic steroids in London (84.2% London vs 17% KUS (chi-square: 20.25; p<0.001)). Three patients received systemic steroids alone, five had prednisolone and cyclosporin, four had prednisolone and azathioprine, and four had triple therapy with prednisolone, cyclosporin, and azathioprine. Only one patient used colchicine. Cyclosporin use was similar in London and KUS (47.4% and 42.8%, respectively). In Japan, three patients used prednisolone alone and three tacrolimus (FK506). In addition, two patients, who were on steroids alone, took colchicine as well. More patients in Japan had undergone surgery for cataract and glaucoma (chi-square: 4.0; p=0.045). In KUS, seven of 67 eyes had cataract surgery. A further three eyes had visually significant cataract and two eyes had undergone glaucoma surgery. In contrast, no patients in London had undergone any surgery up to and including this period.

Long-term follow-up of trabeculectomy with intraoperative 5-fluorouracil for uveitis-related glaucoma.

PURPOSE: To determine the effect of intraoperative application of 5-fluorouracil (5-FU) on the long-term outcome of trabeculectomy in uveitis-related glaucoma. DESIGN: An open, prospective, noncomparative case study to evaluate the use of intraoperative application for 5 minutes of 25 mg/ml 5-FU in primary trabeculectomy for uveitis-related glaucoma. PARTICIPANTS: Fifty eyes of 43 consecutive patients were enrolled in the study. METHODS: Data were recorded prospectively on specifically designed forms at visits every 3 months after surgery. MAIN OUTCOME MEASURES: The intraocular pressure, need for additional medication, and the need for repeat surgery were the criteria that determined the outcome of surgery. RESULTS: No significant intraoperative, postoperative, or late complications of 5-FU administration were noted. Successful filtration was achieved in 82% of eyes at 1 and 2 years after surgery. The success rate was 67% at 5 years. Failure was significantly more common and occurred earlier in patients of black ethnic origin. No deleterious effect on control of uveitis in relation to surgical intervention was observed. CONCLUSIONS: Intraoperative application of 5-FU appears to be a long-term, safe, and effective adjunct to trabeculectomy in uveitis-related glaucoma.

PCR-based evidence of bacterial involvement in eyes with suspected intraocular infection.

PURPOSE: To assess the usefulness of polymerase chain reaction (PCR) in detection of bacteria in ocular samples. METHODS: Thirty-seven samples (aqueous and vitreous) were collected from 25 eyes showing typical symptoms and clinical signs of bacterial endophthalmitis. Ocular samples were also collected from 38 eyes that underwent routine surgery and from 15 eyes with intraocular inflammation due to nonbacterial causes. Panbacterial PCR was performed with a nested pair of 16S rRNA gene primers. Subsequent bacterial identification was completed for 18 paired samples (nine eyes) using restriction fragment length polymorphism (RFLP) and DNA sequencing. RESULTS: A 100% concordance was obtained between PCR and culture-positive samples. A PCR product was amplified from all 37 intraocular samples from eyes with suspected infection, whereas only 15 of 22 vitreous samples and 5 of 15 aqueous samples were culture positive. Culture-negative PCR-positive samples contained a preponderance of gram-negative bacterial sequences. Cloning and DNA analysis revealed 30 DNA sequences and included eight bacterial 16S rDNA, which currently remain unidentifiable. The presence of bacterial DNA was associated with an inflammatory response suggestive of infection and not colonization. All 15 samples from inflamed eyes with diverse uveitis diagnoses were PCR negative. The false-positive rate, due to contamination during sampling, was 5%. CONCLUSIONS: Bacterial DNA was detected in all patients with typical clinical signs of endophthalmitis. Gram-negative organisms seem to play a much more important role in the pathogenesis of this disease than previously thought. PCR-based techniques have great value in the confirmation of the diagnosis of bacterial endophthalmitis especially in culture-negative eyes.

Symptomatic intraocular inflammation in multiple sclerosis.

PURPOSE: The aim of this study was to determine the type and outcome of uveitis in patients with multiple sclerosis. METHODS: A retrospective study of 16 patients attending the uveitis clinic who had a clinically definite diagnosis of multiple sclerosis and symptomatic intraocular inflammation. The type of uveitis and complications present as well as the outcome of therapeutic intervention, either medical or surgical, was determined. RESULTS: Chronic, bilateral anterior uveitis was present in six patients. Secondary cataracts requiring surgery occurred in 10 eyes, and trabeculectomy was done on five eyes for secondary glaucoma. Symptomatic vitritis (visual blurring and/or visually significant floaters) occurred in eight patients and was bilateral in four. Occlusive peripheral retinal vasculitis with subsequent areas of ischaemia and neovascularization requiring panretinal laser photocoagulation developed in eight eyes, five of which also required vitrectomy. Other posterior segment complications included macular oedema (four) and epiretinal membrane involving the macula (two). Five patients required systemic steroids for control of posterior uveitis. The median visual improvement following cataract surgery or vitrectomy was 3 Snellen lines to a median visual acuity of 6/18. CONCLUSIONS: A wide range of clinical patterns of uveitis, which may be both symptomatic and sight-threatening, occur in patients with multiple sclerosis. In addition, the complications of uveitis may cause significant visual morbidity, much of which is amenable to appropriate surgical intervention. It is important that these potentially remediable conditions are recognized and treated to ensure that patients with multiple sclerosis retain optimum visual function.

Rapid detection and identification of Candida, Aspergillus, and Fusarium species in ocular samples using nested PCR.

A protocol for the rapid detection of fungal DNA in ocular samples, derived from three species, Candida albicans, Aspergillus fumigatus, and Fusarium solani, has been developed. Two novel panfungal primers complementary to 18S rRNA sequences present in all three species were designed. Panfungal PCR was followed by three nested PCRs utilizing species-specific primers. PCR sensitivity ranged from 50 to 100 fg of free DNA and between one and two C. albicans organisms. In addition, we also developed a rapid and reliable DNA extraction protocol. This protocol minimized DNA loss during extraction, whilst removing compounds from vitreous and aqueous fluids that have previously been shown to have inhibitory effects on PCR. Preliminary results obtained after testing the protocol on three patient samples support culture results and medical history. However, one patient was PCR positive but culture negative, suggesting that the sensitivity of this protocol may exceed that of traditional culture techniques. This system, therefore, constitutes an additional protocol that may significantly aid patient management in cases where fungal endophthalmitis is suspected.

PCR-RFLP-mediated detection and speciation of bacterial species causing endophthalmitis.

PURPOSE: To determine the usefulness of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the identification and speciation of bacteria causing endophthalmitis. METHODS: PCR-RFLP was performed on 53 strains of 14 bacterial species (eight Gram positive and five Gram negative) collected from both keratitis and endophthalmitis patients. Two pairs of oligonucleotide primers based on the 16S rDNA gene were used to PCR-amplify 1.2- and 1.0-kb fragments of bacterial genomic DNA. RFLPs within the PCR product were used to speciate the organisms. RESULTS: The sensitivity of the nested PCR amplification reaction was one organism. All bacteria tested could be identified and speciated using RFLP analysis except for Escherichia coli and Serratia marcescens, which could not be interdifferentiated using RFLP. Molecular analysis of two vitreous samples from two eyes with typical signs of bacterial endophthalmitis confirmed the presence of E. coli in the vitreous from a culture-positive case with E. coli endophthalmitis and revealed the presence of Staphylococcus epidermidis in the vitreous of a culture-negative case. CONCLUSIONS: It is expected that this technique will provide a useful laboratory tool for future microbiologic diagnosis of patients presenting with endophthalmitis, especially for those eyes that prove culture negative.

Increased CD4+ expression and decreased IL-10 in the anterior chamber in idiopathic uveitis.

PURPOSE: To compare cell types and cytokines in aqueous humor from patients with uveitis either occurring in association with a systemic disease or apparently isolated and not associated with a systemic disease. METHODS: Cells were collected by centrifugation of fresh aqueous humor from uveitis and controls, and immunofluorescence techniques were performed with markers for T cells, B cells, and monocytes. Cytokines were measured in the aqueous supernatants, and serum samples were assayed for soluble interleukin-2 receptors. RESULTS: When aqueous samples from idiopathic uveitis were compared with those from uveitis associated with a systemic disease, there were increases in CD3+, CD4+ (p = 0.001), and activated CD4+ T cells (p = 0.02) and a decrease in B cells (p = 0.0013). This was not reflected in the peripheral blood where there were no differences in the cell types or in soluble interleukin-2 receptor levels. No cells were obtainable from control aqueous. Interleukins-10 and -12, interferon-gamma, and transforming growth factor-beta2 were detected in aqueous supernatants. Interleukin-10 was reduced (p = 0.024) in uveitis in comparison with controls. CONCLUSIONS: The results suggest a selective recruitment of CD4+ T cells within aqueous humor but only in idiopathic uveitis. In both disease groups there was a decrease in the immunoregulatory cytokine interleukin-10, which might enable an immune response to occur in an otherwise highly immunosuppressive microenvironment. Increases in activated CD4+ T cells combined with depressed interleukin-10 levels could partially explain why, for example, in acute anterior uveitis, the inflammatory disease is often more severe.

Characterization of phenotype and cytokine profiles of T cell lines derived from vitreous humour in ocular inflammation in man.

Intermediate uveitis (IU) and Fuchs' heterochromic cyclitis (FHC) are two chronic ocular inflammatory disorders. They differ considerably in ocular morbidity, which is higher in IU. T cell lines were derived from the vitreous humour (VH) and peripheral blood (PB) of 10 patients with IU and four patients with FHC. There was a predominance of CD8+ in all the lines. However, there was a significantly higher percentage of CD4+ T cells in the T cell lines derived from VH of IU (32.0 +/- 8.6%) compared with FHC patients (19. 2 +/- 8.9%) (P = 0.04). The VH-derived T cell lines (VDTC) produced significantly higher levels of IL-2, interferon-gamma (IFN-gamma) and IL-10, but not IL-4, compared with PB-derived T cell lines (PBDTC) in both entities. There was significantly higher IL-2 production by VDTC from IU when compared with FHC patients (1810 +/- 220 pg/ml versus 518 +/- 94 pg/ml; P = 0.009), which could account for the more aggressive clinical features of this condition. In contrast IL-10 production was significantly higher by the VDTC from FHC compared with IU patients. The high IL-10 production by T cells infiltrating VH of FHC patients could down-regulate the inflammatory responses, thereby contributing to the benign clinical course seen in these patients. The accumulation of T cells with differing cytokine profiles in the VH suggests an important role for these cytokines in the pathogenesis of these chronic uveitides.

Assessment of visual outcome after cataract surgery in patients with uveitis.

OBJECTIVE: To assess the outcome of cataract surgery in eyes of patients with uveitis. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: A total of 90 eyes of 76 patients fulfilled the enrollment criteria. INTERVENTION: All patients had their surgery performed using standard cataract extraction techniques. Unless contraindicated, preoperative systemic steroids were administered to all patients with posterior disease, chronic anterior uveitis, with known macular edema, and those in whom outcome of cataract surgery on the fellow eye had been poor. RESULTS: Patients were divided into those with anterior disease (n = 53) and those with posterior disease (n = 37). Overall, 81 (90%) of 90 eyes showed improvement in vision (median +4 Snellen lines). In those with anterior disease, the development of severe uveitis in the first week postsurgery was associated with a greater incidence of macular edema (P = 0.014). The single largest diagnosis in those with posterior disease was that of panuveitis (n = 24). This group showed the poorest visual outcomes in this study. The majority of patients, however, were noted to have visual loss secondary to conditions present before surgery. CONCLUSION: Cataract surgery in eyes with uveitis leads to an improvement of vision in the majority of cases. Severe postoperative uveitis is the most common postoperative complication and is associated with a significant risk of macular edema in those with anterior disease. In the posterior group, poor visual outcome after surgery is most commonly the result of preoperative vision-limiting conditions.

Polymerase chain reaction and restriction fragment length polymorphism mediated detection and speciation of Candida spp causing intraocular infection.

PURPOSE: To determine the usefulness of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis in the identification and speciation of Candida spp that causes ocular infection. METHODS: Oligonucleotide primers based on the cytochrome P450 L1 A1 demethylase gene were used to successfully amplify by PCR a single 1.0-kb and a single 500-bp DNA fragment from C. albicans, C. tropicalis, C. krusei, C. glabrata, C. parapsilosis, and C. pelliculosa genomic DNA. RFLPs within the PCR product were identified after restriction enzyme digestion. RESULTS: The sensitivity of the amplification reaction after two rounds of PCR was 10 fg genomic C. albicans DNA or one copy of the gene. No amplification product was obtained when DNA from C. guilliermondii, Aspergillus fumigatus, Fusarium solani, human leukocytes, or 10 species of bacteria was used as a template. Experiments with spiked normal vitreous demonstrated equal sensitivity as long as the volume of vitreous did not exceed 20% of the total PCR volume. RFLP analysis of the PCR product generated from each species obtained from the first- and second-round amplification products enabled species identification after digestion with specific endonucleases. Application of the technique to four clinical samples was successful. CONCLUSIONS: It is expected that the simplicity of the DNA extraction technique allied with the broad specificity of the outer primers for all ophthalmically relevant Candida spp and the sensitivity of the second-round PCR will aid in the detection of fungal DNA in small intraocular samples. PCR-RFLP analysis has great potential in the rapid detection and identification of Candida spp and in the provision of a useful laboratory tool for the future.

Characterization of T cells and cytokines in the aqueous humour (AH) in patients with Fuchs' heterochromic cyclitis (FHC) and idiopathic anterior uveitis (IAU).

FHC and IAU are two forms of anterior uveitis which are localized to the eyes with no evidence of systemic involvement. However, FHC has distinct clinical features and differs from IAU in that the inflammation is low grade, steroid non-responsive, and has a less aggressive clinical course. To try to dissect the mechanism for this difference the phenotypes of the cells in the AH and blood (PB) and the cytokines present in the AH in patients with FHC and IAU were compared. Three-colour flow cytometry was performed on the cells isolated from the AH and PB. Percentage of cells bearing the following markers were determined: CD3, CD4, CD8, CD4/CD25, CD8/CD25, CD19 and CD14. The cytokines IL-4, IL-10, IL-12 and interferon-gamma (IFN-gamma) were assayed by ELISA. In both groups T cell numbers were higher in the AH than PB, although the distribution of T cell subsets in PB was similar. In the AH, CD8+ T cell numbers were higher in FHC than in IAU (P = 0.003), whilst CD4+ numbers were higher in IAU than FHC (P = 0.01). AH cytokine profiles were different in the two groups: IFN-gamma levels were higher and IL-12 levels lower in the FHC group than IAU (P = 0.02), whilst IL-10 levels tended to be higher in the FHC group (P = 0.5). We suggest that different local mechanisms governing the balance of T cell/cytokine-mediated inflammation in the anterior segment may underlie clinical differences such as chronicity and response to steroids in these disorders.

Paecilomyces lilacinus endophthalmitis with secondary keratitis: a case report and literature review.

A case of endogenous fungous endophthalmitis with secondary pupillary block glaucoma and corneal invasion requiring penetrating keratoplasty is reported. Initially Paecilomyces lilacinus was isolated from a vitreous and a lens aspirate, but a second vitreous tap revealed Aspergillus fumigatus and P lilacinus. This case highlights the difficulty of diagnosing endogenous fungous endophthalmitis presenting without risk factors and the difficulties of managing such cases using the antifungous agents available. To our knowledge, this is the first case report documenting a progression to stromal keratitis from endogenous endophthalmitis secondary to P lilacinus.

Assessment of a standard treatment protocol on visual outcome following presumed bacterial endophthalmitis.

AIMS: The aim of this prospective study was, firstly, to judge the effect of early aggressive treatment with a standardised regimen of high dose broad spectrum intraocular and systemic antibiotics on visual outcome and, secondly, to assess the sensitivity of isolated organisms to the treatment regimen utilised. METHODS: Thirty two consecutive patients presenting with presumed bacterial endophthalmitis were treated and completed follow up. In every case, intraocular sampling was undertaken and treatment with intraocular vancomycin, amikacin, and systemic ciprofloxacin was commenced immediately, followed by systemic steroids 1 day later. RESULTS: In 69% of patients vision improved with 47% achieving a final visual acuity of 6/36 or better and 31% achieving 6/12 or better. Of the intraocular samples taken from post-surgical and post-traumatic cases, 10/27 (37%) and 3/5 (60%) were culture positive, respectively. All the bacteria isolated were sensitive to at least one of the three antibiotics used. CONCLUSIONS: The study demonstrated that the combination of vancomycin, amikacin, and ciprofloxacin is adequate as a standard regimen for the treatment of most patients with suspected bacterial endophthalmitis. The prognosis for a good visual outcome, however, remains poor with 15/27 (55%) post-surgical and 2/5 (40%) post-traumatic cases achieving a final acuity of 6/60 or less.