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To identify priorities for future research into the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris, we conducted a Priority Setting Partnership using James Lind Alliance methodology. The top 10 priorities identified in this PSP represent the key questions that patients, carers and healthcare professionals have about the treatment of these diseases and which future research will hopefully address.

This study quantifies the performance of an international cohort of cornea specialists in image-based differentiation of bacterial and fungal keratitis, identifying significant regional variation and establishing a reference standard for comparison against machine learning models.

Background and AimsPolyhexamethyl biguanide (PHMB), a widely used topical treatment for Acanthamoeba keratitis (AK), is unlicensed with no formal safety assessment. This study evaluated its safety and tolerability.MethodsA prospective, randomised, double-masked controlled trial in 90 healthy volunteers. Subjects were treated with topical 0.04%, 0.06%, 0.08% PHMB or placebo (vehicle) 12× daily for 7 days, then 6× daily for 7 days. The rates of dose-limiting adverse events (DLAEs) leading to interruption of dosing, mild adverse events (AEs) (not dose limiting) and incidental AEs (unrelated to treatment) were compared. The primary outcome was the difference between treatments for DLAE rates.Results5/90 subjects developed DLAE within ConclusionThese findings are reassuring for PHMB 0.02% users. They also suggest that higher PHMB concentrations may show acceptable levels of tolerance and toxicity in AK subjects, whose susceptibility to AE may be greater than for the normal eyes in this study. Given the potential benefits of higher PHMB concentrations for treating deep stromal invasion in AK, we think that the use of PHMB 0.08% is justified in treatment trials.Trial registration numberNCT02506257.

This study was designed to establish risk factors for the development of Acanthamoeba keratitis (AK) for daily disposable (DD) contact lens (CL) users compared with daily wear (DW) reusable lens users and for risks unique to DD users. This is important because, in many major economies, CL use is the principal cause of microbial keratitis, of which AK accounts for approximately 50% of cases with sight loss. Determining these AK risks informs practitioner advice and consumer behavior.Case-control study.Cases and controls were recruited from an Accident and Emergency Department serving South-East England. Cases were new CL users with AK recruited retrospectively from January 2011 to February 2013 and prospectively thereafter until August 2014. Controls were recruited prospectively from February 2014 to June 2015.Analysis of a self-administered questionnaire.Independent risk factors and population attributable risk percentage (PAR%) for AK.A total of 83 AK cases and 122 controls were recruited; DD use was reported by 20 (24%) cases and 66 (54%) controls. In multivariable analyses adjusted for potential confounders, the odds of AK was higher for DW reusable soft lenses (odds ratio [OR], 3.84; 95% confidence interval [CI], 1.75-8.43) and rigid lenses (OR, 4.56; 95% CI, 1.03-20.19) than for DD lenses. Within the DD-using subset, AK was associated with the following modifiable risk factors: less frequent professional follow-up visits (OR, 10.12; 95% CI, 5.01-20.46); showering in lenses (OR, 3.29, 95% CI, 1.17-9.23); lens reuse (OR, 5.41; 95% CI, 1.55-18.89); and overnight wear (OR, 3.93; 95% CI, 1.15-13.46). The PAR% estimated that 30% to 62% of cases could be prevented by switching from reusable soft lens to DD lens use.Acanthamoeba keratitis risks are increasedthreefold in DW reusable lens users versus DD lens use. Acanthamoeba keratitis risks for DD lens users can be minimized by adherence to safe use guidelines (no reuse, overnight wear, or contamination by water). Safe CL use can be improved by increasing the prominence of risk avoidance information from manufacturers and regulators. Because AK accounts for half of severe keratitis in CL users, these measures can be expected to have public health benefits.

AimsTo test the hypothesis that Acanthamoeba keratitis (AK) outcomes differ for different topical antiamoebic therapies (AAT) and to provide the detailed patient outcome data.MethodsA retrospective cohort study of 227 patients developing AK between 25 July 1991 and 10 August 2012. Inclusion criteria required a complete record of AAT treatment for both the primary outcome of a medical cure rate at 12 months and the secondary outcome of Snellen visual acuity ≤6/24 and/or surgical intervention. Analysis used multivariable regression to control for differences in baseline disease characteristics for both primary and secondary outcomes with unadjusted analyses for other outcomes. Subjects were categorised for analysis both by the AAT used at baseline and also by mutually exclusive AAT (patients exposed to all the drugs in each group, and no others, for some period). AAT categories were PHMB monotherapy, PHMB+diamidine, PHMB+chlorhexidine+diamidine, diamidine monotherapy and other AAT.ResultsAnalysis by baseline AAT showed no notable difference between treatments for both a medical cure at 12 months in 60.79% (138/227) or for a poor outcome in 49.34% (112/227). When AATs were analysed by mutually exclusive groups, PHMB monotherapy provided the best outcomes. These findings are subject to bias requiring careful interpretation. Overall cure rates for the 214 subjects with resolved outcomes were 94.27% (214/227), median time to cure 5 months (IQR 3.25–9.00 months) and range 1–26.24 months.ConclusionPHMB 0.02% monotherapy for the initial treatment of AK is as effective as biguanide+diamidine combination therapy. Chlorhexidine monotherapy was too infrequent for comparison. The outcome data are the most detailed available.

Background/aimsAcanthamoeba keratitis (AK) is a chronic debilitating corneal infection principally affecting contact lens (CL) users. Studies were designed to test claims that the UK incidence may have increased in 2012–2014 and to evaluate potential causes.MethodsAnnualised incidence data were collected from January 1984 to December 2016. Case-control study subjects were recruited between 14 April 2011 and 05 June 2017. Reusable CL users with AK were recruited retrospectively and prospectively. Controls were reusable CL users, recruited prospectively, with any disorder other than AK. Multivariable analysis of questionnaire data measured independent risk factors for AK.ResultsThe current outbreak of AK started in 2010–2011 with an incidence threefold higher than in 2004–2009. Risk factors for AK were: Oxipol disinfection, CLs made of group IV CL materials, poor CL hygiene, deficient hand hygiene, use of CLs while swimming or bathing, being white British, and for those in social classes 4–9.ConclusionAK is a largely preventable disease. The current outbreak is unlikely to be due to any one of the identified risk factors in isolation. Improving CL and hand hygiene, avoiding CLs contamination with water and use of effective CL disinfection solutions, or daily disposable CLs, will reduce the incidence of AK. In the longer-term, water avoidance publicity for CL users can be expected to reduce the incidence further. Ongoing surveillance of AK numbers will identify changes in incidence earlier. Evaluation of Acanthamoeba contamination in end-user drinking water would contribute to our understanding of regional variations in the risk of exposure.

Background/aimsTo determine demographic and clinical features of patients withAcanthamoebakeratitis (AK) that are independent risk factors both for bad outcomes and for severe inflammatory complications (SIC).MethodsA retrospective audit of medical records of AK cases at Moorfields Eye Hospital from July 2000 to April 2012, including 12 earlier surgical cases. Cases with a bad outcome were defined as those having one or more of the following: corneal perforation, keratoplasty, other surgery (except biopsy), duration of antiamoebic therapy (AAT) ≥10.5 months (the 75th percentile of the whole cohort) and final visual acuity ≤20/80. SICs were defined as having scleritis and/or a stromal ring infiltrate. Multivariable analysis was used to identify independent risk factors for both bad outcomes and SICs.ResultsRecords of 194 eyes (194 patients) were included, having bad outcomes in 93 (48%). Bad outcomes were associated with the presence of SIC, aged >34 years, corticosteroids used before giving AAT and symptom duration >37 days before AAT. The development of SIC was independently associated with aged >34 years, corticosteroids used before giving AAT and herpes simplex virus (HSV) keratitis treatment before AAT.ConclusionsThe prompt diagnosis of AK, avoidance of a misdiagnosis of HSV keratitis and corticosteroid use before the exclusion of AK as a potential cause of keratitis are essential to the provision of a good outcome for patients and for the avoidance of SIC. Older age is an unmodifiable risk factor that may reflect differences in the immune response to AK in this patient subset.

Author(s): Ung, Lawson; Acharya, Nisha R; Agarwal, Tushar; Alfonso, Eduardo C; Bagga, Bhupesh; Bispo, Paulo Jm; Burton, Matthew J; Dart, John Kg; Doan, Thuy; Fleiszig, Suzanne Mj; Garg, Prashant; Gilmore, Michael S; Gritz, David C; Hazlett, Linda D; Iovieno, Alfonso; Jhanji, Vishal; Kempen, John H; Lee, Cecilia S; Lietman, Thomas M; Margolis, Todd P; McLeod, Stephen D; Mehta, Jod S; Miller, Darlene; Pearlman, Eric; Prajna, Lalitha; Prajna, N Venkatesh; Seitzman, Gerami D; Shanbhag, Swapna S; Sharma, Namrata; Sharma, Savitri; Srinivasan, Muthiah; Stapleton, Fiona; Tan, Donald Th; Tandon, Radhika; Taylor, Hugh R; Tu, Elmer Y; Tuli, Sonal S; Vajpayee, Rasik B; Van Gelder, Russell N; Watson, Stephanie L; Zegans, Michael E; Chodosh, James

This review is in two sections. The first section summarises 35 conditions, both common and infrequent, causing cicatrising conjunctivitis. Guidelines for making a diagnosis are given together with the use of diagnostic tests, including direct and indirect immunofluorescence, and their interpretation. The second section evaluates our knowledge of ocular mucous membrane pemphigoid, which is the commonest cause of cicatrizing conjunctivitis in most developed countries. The clinical characteristics, demographics, and clinical signs of the disease are described. This is followed by a review and re-evaluation of the pathogenesis of conjunctival inflammation in mucous membrane pemphigoid (MMP), resulting in a revised hypothesis of the autoimmune mechanisms causing inflammation in ocular MMP. The relationship between inflammation and scarring in MMP conjunctiva is described. Recent research, describing the role of aldehyde dehydrogenase (ALDH) and retinoic acid (RA) in both the initiation and perpetuation of profibrotic activity in MMP conjunctival fibroblasts is summarised and the potential for antifibrotic therapy, using ALDH inhibition, is discussed. The importance of the management of the ocular surface in MMP is briefly summarised. This is followed with the rationale for the use of systemic immunomodulatory therapy, currently the standard of care for patients with active ocular MMP. The evidence for the use of these drugs is summarised and guidelines given for their use. Finally, the areas for research and innovation in the next decade are reviewed including the need for better diagnostics, markers of disease activity, and the potential for biological and topical therapies for both inflammation and scarring.

Purpose: Over a third of patients with Acanthamoeba keratitis (AK) experience severe inflammatory complications (SICs). This study aimed to determine if some contact lens (CL) wearers with AK were predisposed to SICs due to variations in key immune genes. Methods: CL wearers with AK who attended Moorfields Eye Hospital were recruited prospectively between April 2013 and October 2014. SICs were defined as scleritis and/or stromal ring infiltrate. Genomic DNA was processed with an Illumina Low Input Custom Amplicon assay of 58 single nucleotide polymorphism (SNP) targets across 18 genes and tested for association in PLINK. Results: Genomic DNA was obtained and analyzed for 105 cases of AK, 40 (38%) of whom experienced SICs. SNPs in the CXCL8 gene encoding IL-8 was significantly associated with protection from SICs (chr4: rs1126647, odds ratio [OR] = 0.3, P = 0.005, rs2227543, OR = 0.4, P = 0.007, and rs2227307, OR = 0.4, P = 0.02) after adjusting for age, sex, steroids prediagnosis, and herpes simplex keratitis (HSK) misdiagnosis. Two TLR-4 SNPs were associated with increased risk of SICs (chr9: rs4986791 and rs4986790, both OR = 6.9, P = 0.01). Th-17 associated SNPs (chr1: IL-23R rs11209026, chr2: IL-1β rs16944, and chr12: IL-22 rs1179251) were also associated with SICs. Conclusions: The current study identifies biologically relevant genetic variants in patients with AK with SICs; IL-8 is associated with a strong neutrophil response in the cornea in AK, TLR-4 is important in early AK disease, and Th-17 genes are associated with adaptive immune responses to AK in animal models. Genetic screening of patients with AK to predict severity is viable and this would be expected to assist disease management.

Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and their management through all phases of SJS/TEN, from acute to chronic. We hope this effort will assist ophthalmologists in their management of SJS/TEN, so that patients with this complex and debilitating disease receive the best possible care and experience the most optimal outcomes in their vision and quality of life.

Purpose To describe the epidemiology, clinical features, and treatment outcomes of Acanthamoeba sclerokeratitis (ASK). Design Retrospective case series. Participants All cases of both Acanthamoeba keratitis (AK) and ASK identified between January 1, 2000, and January 8, 2011, at Moorfields Eye Hospital. Methods Acanthamoeba keratitis was defined as the presence of AK with concurrent ipsilateral scleral inflammation. Topical steroids and oral nonsteroidal anti-inflammatory drugs (NSAIDs) were used as the first line of treatment. In unresponsive cases, oral NSAIDs were replaced by oral prednisolone with cyclosporine, azathioprine, or mycophenolate as steroid-sparing agents. Cyclosporine was combined with azathioprine or mycophenolate in cases unresponsive to only 1 of these drugs alone. Main Outcome Measures Epidemiology, clinical phenotype, response to therapy, resolution of inflammation, visual outcome, corneal transplantation, and enucleation rate. Results From a series of 178 patients with AK, 36 eyes of 33 patients (18.5%) developed ASK. A total of 25 of 33 patients (76%) with ASK were tertiary referrals. The incidence of the disease in greater London was 0.13 per million, and the incidence in this population of patients with AK was 33 of 178 (18.5%). Mild scleritis/limbitis responsive to topical steroids and oral NSAIDs was present in 11 of 36 eyes (31%), and moderate/severe scleritis, requiring systemic immunosuppressive therapy, was present in 25 eyes (69%). Before the initiation of ASK treatment, 2 of 36 eyes (6%) had corrected distance visual acuity (CDVA) ≥20/40. The length of ASK treatment was 15.3±20.7 months. The follow-up after discontinuation of scleritis treatment was 27.2±31.8 months. An improvement in visual acuity was recorded in 23 of 36 eyes (64%). At the final visit, 13 of 36 eyes (36%) had CDVA ≥20/40. Control of scleral inflammation and pain was achieved in all but 2 eyes (2 enucleations). Cataract developed in 10 of 36 eyes (28%), and 14 of 36 eyes (39%) developed a persistent epithelial defect. Keratoplasty was performed in 21 of 36 eyes (58%), 9 therapeutic/tectonic and 12 for visual rehabilitation. Six eyes had more than 1 keratoplasty. The mild scleritis group had better outcomes in terms of visual improvement and need for keratoplasty. Conclusions Acanthamoeba sclerokeratitis is associated with poor clinical outcomes. Management of ASK with anti-inflammatory/immunosuppressive treatment is usually effective in reducing both scleral inflammation and symptoms and possibly reduces the number of enucleations.

Purpose: To investigate therapeutic ocular surface medium (TOSM), a potential physiological tear replacement therapy, for persistent epithelial defect (PED). Methods: 11 eyes of 10 patients with PED for ≥2 weeks without improvement despite conventional treatment were enrolled in a prospective pilot study of TOSM over 1 month. Results: Healing of the PED occurred in 3 out of the 11 eyes at 1, 2 and 4 weeks, respectively. At week 4, 2 eyes were almost healed (PED area ≤0.5 mm2). In 4 of the remaining 6 eyes, the PED area was reduced. Failure occurred in 1 case with end-stage ocular cicatricial pemphigoid and severe dry eye, and 1 patient withdrew due to a mild allergic reaction. There were no serious or irreversible side effects with TOSM. Conclusions: TOSM is a potential novel physiological therapy for PED that, unlike autologous serum, has the potential to be easily manufactured and widely available.

Purpose To describe the long-term outcomes of peripheral hypertrophic subepithelial corneal degeneration. Design Retrospective case series. Participants Twenty-two patients under the care of the External Disease Service, Moorfields Eye Hospital. Methods All patients matching clinical diagnostic criteria were included. Symptomatic patients were managed either conservatively or were offered superficial keratectomy in progressive cases where symptom control was inadequate. All excised tissue was examined histologically. Main Outcome Measures Clinical phenotype, symptoms, recurrence rate after surgery, and histopathologic results. Results Twenty-two white patients (20 women and 2 men; age range, 27–88 years; median age, 42 years) had peripheral, usually bilateral (20/22 [91%]), elevated circumferential peripheral subepithelial corneal opacities and adjacent abnormal limbal vasculature, with or without pseudopterygia in 9 patients (41%), among whom 7 (32%) patients had bilateral disease. Apart from the abnormal vasculature, there were no signs of chronic ocular surface inflammation. Symptoms were ocular surface discomfort in 10 patients (45%), reduced vision in 4 patients (18%), and both of these in 5 patients (23%). Three patients (14%) were asymptomatic. There was no treatment in 6 patients (27%), topical lubricants in 8 patients (36%), spectacles in 1 patient (5%), and superficial keratectomy in 7 patients (32%; 5 bilateral), which was repeated for incomplete primary excision in 1 eye of 2 patients (9%) and for a bilateral recurrence in 1 patient (5%). Median follow-up after excision was 5 years (range, 1–11 years). Histopathologic changes were similar to those observed in pterygia (vascular component) and Salzmann's nodular degeneration (corneal component). Conclusions Peripheral hypertrophic subepithelial corneal degeneration is an uncommon, usually bilateral, idiopathic disorder, occurring mostly in white women with a distinct phenotype. The condition was first described in 2003. Further cases among some patients have been described in more recent case series of Salzmann's nodular degeneration and diffuse keratoconjunctival proliferation, as well as in the previously described familial pterygoid corneal degeneration. Surgical excision was required in 30% of patients in this series, with infrequent short-term recurrences. The cause is uncertain. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose This study investigated independent risk factors and causative organisms in microbial keratitis in daily disposable contact lens (CL)-wearers. Methods A multisite prospective case-control study was undertaken. Cases were daily disposable CL-wearers attending Moorfields Eye Hospital with microbial keratitis and those reported through a one-year surveillance study in Australia and in New Zealand. A population-based telephone survey identified daily disposable CL-wearing controls. Subjects completed a questionnaire describing CL-wear history, hygiene and demographics. The sample used for risk factor analysis was weighted in proportion to the CL-wearing population at each location. Corneal scrape results were accessed. Independent risk factors were determined using multiple binary logistic regression. Causative organisms in different CL-wear modalities were compared using a chi-squared test. Results 963 daily disposable CL-wearers were identified, from which 67 cases and 374 controls were sampled. Independent risk factors were; wearing CLs every day compared with less frequent use (OR 10.4x; 95% CI 2.9–56.4), any overnight wear (OR 1.8x; 95% CI 1.6–2.1), less frequent hand washing (OR 1.8x; 95% CI 1.6–2.0), and smoking (OR 1.3x; 95% CI 1.1–1.6). Certain daily disposable CLs (OR 0.2x; 95% CI 0.1–0.2) had protective effects. Environmental organisms were less frequently recovered with daily disposable CLs (20%), compared with other modalities (36%; p

Corneal transplantation or keratoplasty has developed rapidly in the past 10 years. Penetrating keratoplasty, a procedure consisting of full-thickness replacement of the cornea, has been the dominant procedure for more than half a century, and successfully caters to most causes of corneal blindness. The adoption by specialist surgeons of newer forms of lamellar transplantation surgery, which selectively replace only diseased layers of the cornea, has been a fundamental change in recent years. Deep anterior lamellar keratoplasty is replacing penetrating keratoplasty for disorders affecting the corneal stromal layers, while eliminating the risk of endothelial rejection. Endothelial keratoplasty, which selectively replaces the corneal endothelium in patients with endothelial disease, has resulted in more rapid and predictable visual outcomes. Other emerging therapies are ocular surface reconstruction and artificial cornea (keratoprosthesis) surgery, which have become more widely available because of rapid advances in these techniques. Collectively, these advances have resulted in improved outcomes, and have expanded the number of cases of corneal blindness, which can now be treated successfully. Femtosecond-laser-assisted surgery, bioengineered corneas, and medical treatment for endothelial disease are also likely to play a part in the future.

Purpose: To investigate therapeutic ocular surface medium (TOSM), a potential physiological tear replacement therapy, for moderate to severe dry eye.Methods: Forty-six patients with symptoms of moderate to severe dry eye despite maximal standard therapy were enrolled in a prospective pilot study of TOSM over 1 month (n = 10) and a randomized, double-masked, controlled trial of TOSM versus saline (placebo) over 2 months (n = 36). The primary outcome measure was conjunctival rose bengal staining.Results: An improvement in conjunctival rose bengal staining by >= 3 points occurred in 7 of 10 patients receiving TOSM in the pilot study (P = 0.017) and in 8 of 18 patients (44%) in the randomized trial (P = 0.982). In the pilot study, subjective dry eye symptoms significantly improved (P = 0.005). TOSM significantly improved the blepharitis score (P = 0.002) and conjunctival impression cytology (P = 0.028) in the randomized controlled trial. There were no serious or irreversible side effects with TOSM.Conclusions: TOSM is a physiological tear replacement for dry eye that, unlike autologous serum, can be easily manufactured, could be widely available, and may also be beneficial for blepharitis.

This review will focus on the diagnostic features of atopic keratoconjunctivitis (AKC), its relationship to atopic dermatitis, the immunopathogenesis, and therapy, and will include strategies used for the management of severe disease unresponsive to conventional therapy.Recent research has demonstrated the importance of various cytokines (IL-33), proteins (thymic stromal lymphopoetin) and effector cells (conjunctival epithelial cells, eosinophils and basophils) in the pathogenesis of chronic ocular inflammation. Current evidence supports the use of tacrolimus and cyclosporin A, topically or systemically, as well tolerated and effective steroid sparing agents.Recalcitrant AKC may be a blinding condition. Understanding the immunopathogenesis of atopic dermatitis and AKC has already influenced therapy and is essential to the development of future immunomodulatory treatments. The successful management of AKC requires the use of topical cromones, antihistamines and calcineurin inhibitors. Severely affected patients also require systemic immunosuppressive therapy. The current challenge is to find more specific topical and systemic immunomodulatory therapies with a better side-effect profile.

Purpose To assess the relative risks of acute, nonulcerative complications with recently introduced contact lens (CL) wear modalities (compared with the previously most common soft lens wear schedule), and to identify any other associated factors. Design A 2-year prospective case-control study commencing in December 2003. Participants Cases were 877 CL wearers attending Moorfields Eye Hospital with CL-related disorders other than microbial keratitis. Controls were 1069 hospital controls who were CL wearers presenting with a disorder unrelated to CL wear, and 639 population-based controls who were CL wearers randomly selected from the Moorfields catchment area. Hospital patients completed a self-administered questionnaire; population controls were interviewed by telephone. Testing The relative risks of developing the CL-related disorders with different CL types were evaluated. For the more common disorders, multivariable analysis was undertaken. Main Outcome Measures The relative risk of developing an acute, nonulcerative, CL-related disorder. Results Compared with planned replacement soft CL, daily disposable lenses significantly reduced the risk of toxic/hypersensitivity (odds ratios for CL solution disorders and papillary conjunctivitis 0.1 and 0.5; P P = 0.05, respectively) and metabolic disorders (0.4; P = 0.04), but the most commonly used brand was associated with increased risks of sterile keratitis (2.7×; 95% confidence interval [CI], 1.7–4.1; P P P P = 0.005), mechanical disorders (1.8×; 95% CI, 1.1–2.8; P = 0.015), and attendance with any nonulcerative complication (1.9×; 95% CI, 1.5–2.6; P Conclusions Neither of the 2 recently introduced CL modalities—daily disposable and silicone hydrogel lenses—reduced the overall risk of acute nonulcerative disorders. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

Many corneal surgeons are making the transition from penetrating keratoplasty to endothelial keratoplasty techniques such as Descemet's stripping endothelial keratoplasty and Descemet's stripping automated endothelial keratoplasty in the routine treatment of corneal endothelial failure. Donor dislocation is the commonest complication of these newer techniques. We set out to determine whether preoperative lens/iris diaphragm integrity might influence the rate of donor dislocation and whether donor endothelial failure was more common after surgical intervention for donor dislocation.A retrospective multisurgeon comparative case series from a large teaching and referral center.Ninety-three eyes of 85 patients: consecutive cases of Descemet's stripping endothelial keratoplasty (n = 77) or Descemet's stripping automated endothelial keratoplasty (n = 16) performed between March 2004 and January 2007.A retrospective review of case notes.The number of eyes with an open communication between the anterior and posterior chambers (an iridectomy or lens capsular defect not covered by a posterior chamber intraocular lens), the number of eyes requiring surgical intervention to correct donor dislocation, and the number of eyes with donor endothelial failure within the follow-up period.Complete data sets were available for analysis in 89 eyes. The median follow-up interval at the time of the audit was 7 months (range 1-34 months). Donor dislocation was significantly more common (P = 0.017) in eyes with an open communication between the anterior and posterior chambers, occurring in 11 of 25 cases (44%) versus 12 of 64 cases (19%) with an intact iris/lens diaphragm. Early endothelial failure was significantly more common (P = 0.011) in cases requiring additional surgical intervention for donor dislocation, occurring in 6 of 21 cases (29%) after successful surgical reattachment of a dislocated donor disc versus 4 of 67 cases (6%) in which no additional intervention was required.Donor dislocation after endothelial keratoplasty is more common in cases with an open communication between the anterior and posterior chambers. The risk of donor endothelial failure is increased in cases of donor dislocation. Trainee surgeons and surgeons in making the transition from penetrating keratoplasty should initially select cases with an intact lens/iris diaphragm.

Objective To establish the absolute risk of contact lens (CL)-related microbial keratitis, the incidence of vision loss and risk factors for disease. Design A prospective, 12-month, population-based surveillance study. Participants New cases of CL-related microbial keratitis presenting in Australia over a 12-month period were identified through surveillance of all ophthalmic practitioners (numerator). Case detection was augmented by records' audits at major ophthalmic centers. The denominator (number of wearers of different CL types in the community) was established using a national telephone survey of 35 914 individuals. Testing Cases and controls were interviewed by telephone to determine subject demographics and CL wear history. Visual outcomes were determined 6 months after the initial event. Annualized incidence and confidence intervals (CI) were estimated for different severities of disease and multivariable analysis was used in risk factor analysis. Main Outcome Measures Annualized incidence (with CI) of disease and vision loss by CL type and wear modality and identification of independent risk factors. Results We identified 285 eligible cases of CL-related microbial keratitis and 1798 controls. In daily wear rigid gas-permeable CL wearers, the annualized incidence per 10 000 wearers was 1.2 (CI, 1.1–1.5); in daily wear soft CL wearers 1.9 (CI, 1.8–2.0); soft CL wearers (occasional overnight use) 2.2 (CI, 2.0–2.5); daily disposable CL wearers 2.0 (CI, 1.7–2.4); daily disposable CL wearers (occasional overnight use) 4.2 (CI, 3.1–6.6); daily wear silicone hydrogel CL wearers 11.9 (CI, 10.0–14.6); silicone hydrogel CL wearers (occasional overnight use) 5.5 (CI, 4.5–7.2); overnight wear soft CL wearers 19.5 (CI, 14.6–29.5) and in overnight wear of silicone hydrogel 25.4 (CI, 21.2–31.5). Loss of vision occurred in 0.6 per 10 000 wearers. Risk factors included overnight use, poor storage case hygiene, smoking, Internet purchase of CLs, Conclusions Incidence estimates for soft CL use were similar to those previously reported. New lens types have not reduced the incidence of disease. Overnight use of any CL is associated with a higher risk than daily use. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. Part I summarizes the epidemiology and immunopathogenesis of SJS/TEN and discusses systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN and enhance their care of patients with this complex and often debilitating disease. Part II (April 2016 issue) will focus on ophthalmic manifestations.

Purpose To describe the presentation, management, and outcome of 5 patients who presented with main-port or side-port wound infection after uneventful clear corneal cataract surgery. Setting Ophthalmic Surgery Centre, Chatswood, and Department of Ophthalmology, Prince of Wales Hospital, Randwick, Australia, and Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. Methods This retrospective case series comprised 5 patients who had uneventful clear corneal phacoemulsification surgery and developed either a main-port or side-port wound infection. The clinical features, microbiologic studies, management, and results are reported. Results The median age of the patients was 79 years. Infection of the main-port incision occurred in 3 cases and of the side port in 2 cases. The patients presented from a few days to several weeks after uneventful phacoemulsification. In 2 cases, the bacteria Pseudomonas aeruginosa and Staphylococcus aureus were isolated. In 1 case, the fungus Aspergillus was isolated and required extensive medical and surgical treatment. In the other 2 cases; empiric antimicrobial therapy was given because no organism was isolated in 1 case, and in the other milder case, microbiological investigations were not performed. Final visual acuity was 6/4 in 2 cases and 6/5, 6/12, and 6/18 in 1 case each. Conclusions Bacterial or fungal wound infection can present within days or even several weeks following clear corneal cataract surgery. Patients with ocular discomfort or blurred vision after such surgery should be advised to report promptly. Rapid identification and appropriate management of patients with clear corneal wound infection can result in good visual outcomes.

Mucous membrane pemphigoid with ocular involvement (MMPO) is a sight-threatening autoimmune disease that may lead to severe conjunctival cicatrization and keratopathy. The peak age of onset is in the seventh decade, although the disease may also occur in younger patients (60 years). This study was designed to evaluate the clinical features of young patients with MMPO and to assess the clinical outcome when compared with patients in the70 age group.Retrospective, comparative, interventional case series.Eighteen patients under the age of 60 years and 18 patients above the age of 70.Patients with documented MMPO were identified from the External Diseases Immunosuppression Database.Stage of disease (Foster, Mondino), visual acuity, and ocular complications (lid, conjunctival, corneal) were evaluated at presentation, the time when immunosuppression was commenced, and final follow-up. Disease progression, control of ocular inflammation with systemic immunosuppression, the incidence of mucocutaneous lesions, and surgical intervention were also assessed.Patients in the 2 groups (young and classic age groups) were observed for 61 (range, 29-218) and 69 (range, 12-193) months, respectively (P = 0.94). Median ages at the start of immunosuppression were 48.7 (range, 29-60) and 77.6 (range, 71-85) years. Mucocutaneous involvement was more common in the young than in the classic age group (13 [72%], 7 [39%]; P0.05). Ocular staging (Mondino, Foster) at presentation, the start of immunosuppression, and final follow-up was more advanced in the younger patients. There was no statistical difference in visual acuity, individual ocular complications, or incidence of surgical intervention between the 2 groups throughout the course of the study.Younger patients with MMPO present with more severe ocular and systemic disease and, despite immunosuppression, progress more rapidly.

Cicatricial pemphigoid is the most common of the immunobullous disorders causing conjunctival cicatrization and is an autoimmune disease in which the ocular component of the immunopathology is directed at the conjunctival basement membrane. The disease is usually bilateral and more common in females, with most cases occurring between 30-90 years, and most often in the seventh decade. The disease occasionally occurs in children. Tear deficiency is a major cause of symptoms, although loss of vision is usually due to surface failure before the onset of aqueous tear deficiency, which occurs late in the progression of the disease. Management of the dry eye must be integrated with the management of the other components of both the ocular surface disease and inflammation. Management requires plastic surgery for the lid and lash malposition, tetracyclines and lid hygiene for the accompanying blepharitis. For the dry eye, the use of lubricants without preservatives is important, to avoid toxicity, and lubricant ointment is helpful for the relief of symptoms in terminally dry eyes without the capacity for surface wetting. Contact lenses, either large limbal diameter rigid gas permeable or gas permeable scleral lenses, are useful for treating dry eye and improving vision in some patients. Control of the conjunctival inflammation is mandatory to prevent disease progression and usually requires systemic immunosuppressive therapy.

Purpose To investigate whether modern phacoemulsification surgery results in more damage to the corneal endothelium than extracapsular cataract extraction (ECCE), and to examine which preoperative, operative, and postoperative factors influence the effect of cataract surgery on the endothelium. Design Randomized controlled trial. Participants Five hundred patients 40 years or older were randomized into 2 groups (ECCE, 249; phacoemulsification, 251). Methods Central corneal endothelial cell counts, coefficient of variation of cell size, and hexagonality were assessed before surgery and up to 1 year postoperatively. Main outcome measure Endothelial cell count. Results Four hundred thirty-three patients completed the trial. The initial preoperative mean cell count for the entire sample was 2481 (standard error [SE]: 18.6), reduced at 1 year postoperatively to 2239 (SE: 23.5). An average 10% reduction in cell count was recorded by 1 year postoperatively. There was no such change in hexagonality or in the coefficient of variation. There was no significant difference in overall percentage cell loss between the 2 treatment groups. Factors associated with excessive cell loss (≥15% by 1 year) were a hard cataract (odds ratio [OR]: 2.1, 95% confidence limits: 1.1–4.1; P = 0.036), age (OR: 1.04, P = 0.005), and capsule or vitreous loss at surgery (OR: 2.38, P = 0.106). Phacoemulsification carried a significantly higher risk (OR: 3.7, P = 0.045) of severe cell loss in the 45 patients with hard cataracts relative to ECCE (52.6% vs. 23.1%; chi-square test, P = 0.041), with both procedures achieving similar postoperative visual acuity outcomes. Conclusions No significant difference in overall corneal endothelial cell loss was found between these 2 operative techniques. The increased risk of severe cell loss with phacoemulsification in patients with hard cataracts suggests that phacoemulsification may not be the optimal procedure in these cases, and that ECCE should be preferred.

Corneal toxicity is caused by chemical trauma and by iatrogenic and factitious disease, which are often overlooked, and which are reviewed here. The clinical signs of iatrogenic disease are usually nonspecific and identical to those resulting from other causes of surface disease. Factitious disease is either the result of mechanical trauma or the abuse of toxic eye drops. One epidemiological study, in a tertiary setting, identified 13% of keratoconjunctivitis cases as iatrogenic. Healing was prolonged taking 7-93 (median 28.5) days. Pathogenic mechanisms vary widely with different drugs and include subclinical scarring, pseudopemphigoid, drug-induced ocular cicatricial pemphigoid, and toxic follicular reactions. There is little readily available data either on the probability of the development of adverse reactions or for the comparison of different drugs. The assessment of the toxicity of topical drugs is currently by the Draize test in rabbits. New in vitro tests on human corneal epithelial cell cultures include ATP assays for cell viability, scanning EM of epithelial microvilli, and vital staining to assess cell membrane permeability and intracellular esterase. Despite their simplicity, these test systems can correlate well with clinical toxicity and provide a toxicity index for drug comparisons. Treatment requires drug withdrawal or substitution by non-preserved and less toxic preparations. Factitious injury is rare, difficult to diagnose, and should only be considered when all other diagnoses have been excluded. Prevention requires a high level of awareness of the potential for iatrogenic disease, particularly in the high-risk setting of chronic ocular surface disease.

Purpose To characterize the risk factors, clinical course, treatment outcome and the association between in vivo resistance and in vitro sensitivity for subjects with persistently culture-positive Acanthamoeba keratitis. Design Retrospective noncomparative case series. Participants Eleven subjects with repeatedly positive cultures for Acanthamoeba treated between January 1990 and December 2000, were reviewed. Only subjects with 2 or more positive cultures, availability of the clinical data, and availability of the last Acanthamoeba isolate were included in this study. Methods The medical records were analyzed, and the last isolate from each case was tested in vitro for the antiamoebic drugs used clinically: polyhexamethylene biguanide (PHMB), chlorhexidine, propamidine and hexamidine. Main outcome measures Risk factors, the clinical outcome and in vitro cysticidal drug sensitivity assay. Results Eleven subjects (11/180, 6.1%) had 2 or more positive cultures of whom 8 eyes of 8 subjects (8/180, 4.45%) were included in this study. Seven of eight (87%) subjects were diagnosed over 1 month from onset (late diagnosis). The most common presenting findings were diffuse stromal infiltrate (5/8, 62.5%), ring infiltrate (5/8, 62.5%), and corneal ulceration (3/8, 37.5%). The clinical course of the disease in all subjects consisted of recurrent episodes of corneal and scleral inflammation, with a mean duration of 13.4 ± 9 months. All subjects received PHMB, and 5/8 (62.5%) chlorhexidine too; hexamidine was used in combination in 6/8 (75%), and propamidine in 1/8 (12.5%). All subjects had topical steroids, and 5/8 (62.5%) systemic immunosuppression. The disease resolved with corneal scarring in 3/8 (37.5%) subjects, corneal (or impending) perforation treated with therapeutic keratoplasty in 4/8 (50%), and enucleation in 1/8 (12.5%). Final visual acuity was 0.43 ± 0.37. In vitro most isolates were resistant to propamidine, hexamidine was cysticidal in high concentrations, and PHMB and chlorhexidine had excellent sensitivity profiles. Conclusions In our large series of Acanthamoeba keratitis with a positive microbiologic diagnosis at presentation, nearly 5% developed recurrent episodes of corneal and scleral inflammation with viable Acanthamoeba in the cornea despite prolonged treatment with biguanides and/or diamidines. There was no correlation between in vitro drug sensitivities and the in vivo response for biguanides.

Aim: To determine the changes in postkeratoplasty astigmatism induced by lamellar keratotomy. Methods: A prospective, non-randomised comparative trial of patients undergoing a hinged lamellar corneal flap for treatment of significant astigmatism after penetrating keratoplasty. Uncorrected visual acuity, best corrected visual acuity, refraction, and corneal topography were assessed at 1 and 3 months after the lamellar keratotomy. Results: 17 eyes in 16 patients (13 M, 3F) were included in the study (mean age 48.2 years; range 20-86 years). Six of 17 eyes (35.3%) changed more than 1 dioptre (D) in spherical equivalent by 3 months. Nine of 17 eyes (52.9%) changed more than 1 D in sphere by 3 months. 12 of 17 eyes (70.6%) changed more than 1 D in refractive cylinder. Seven patients of 15 (46.7%) changed more than 1 D in corneal power as measured topographically. Five of 17 eyes (29.4%) changed in refractive cylinder axis more than 15 degrees and this was similar to the change measured topographically of four of 15 eyes (26.7%). Vector analysis showed 60% of eyes had a surgically induced astigmatism (SIA) vector of more than 1 D, including a net corneal astigmatism decrease of more than 1 D in four eyes and increase of more than 1 D in two eyes at 3 months after surgery. Complications of the lamellar keratotomy included two partial buttonholes and one partial wound dehiscence. Conclusions: The creation of a lamellar flap alone can have significant effects on the astigmatism following penetrating keratoplasty. LASIK for correction of postkeratoplasty astigmatism may be more accurately performed as a two stage procedure rather than a single stage, after the corneal effects of the lamellar keratotomy have stabilised.

Objective: This study describes the clinical features, management, and outcome of 19 patients who had severe Acanthamoeba sclerokeratitis (ASK) unresponsive to conventional management, requiring systemic immunosuppression to control disease. Design: Retrospective, noncomparative, interventional case series. Participants: Records of all patients with Acanthamoeba keratitis treated at Moorfields Eye Hospital between 1989 and 2000 were reviewed. From more than 200 patients, 19 who developed ASK treated with systemic immunosuppression were identified. Main Outcome Measures: Visual acuity, level of pain, and degree of inflammation were recorded after immunosuppressive treatment. Results: ASK requiring immunosuppression occurred in 20 eyes of 19 patients (11 males and 8 females). The mean age (mean ± standard deviation) at onset was 38.6 ± 13.2 years. On presentation, best-corrected visual acuity was counting fingers or worse in 11 eyes (55%), 6/18 to 6/60 in 5 eyes (25%), and 6/12 or better in 4 eyes (20%). The mean time between onset of initial symptoms of Acanthamoeba keratitis and commencement of systemic immunosuppression was 4.8 ± 3.5 months. The mean duration of immunosuppression required to control inflammation was 7.2 ± 3.9 months. Severe scleritic pain remained uncontrolled in two patients and resulted in enucleation. Best-corrected visual acuity at final follow-up was counting fingers or worse in eight eyes (40%), 6/18 to 6/60 in six eyes (30%), and 20/40 or better in six eyes (30%). The mean follow-up period after resolution of inflammation was 24.3 ± 20.9 months (range, 0.2-59.7 months). Conclusions: ASK is an uncommon complication of Acanthamoeba keratitis. The scleritis associated with this infection seems to be an immune-mediated response. After topical amebicidal treatment, systemic immunosuppression may be required to control the pain and tissue destruction associated with ASK.

AUTHOR:e-mail address please Aim: To determine the incidence, regional variation in frequency, outcome, and risk factors for acanthamoeba keratitis (AK) in England and Wales. Methods: AK cases presenting from 1 October 1997 to 30 September 1999 were identified by the British Ophthalmic Surveillance Unit active reporting system. Clinical and patient postal questionnaire data were analysed. Results: 106 reported cases met study criteria. The annual incidence for the 2 years was 1.26 and 1.13 per million adults and, for contact lens (CL) wearers, 21.14 and 17.53 per million. There was marked regional variation in incidence (0 to 85.13 per million adult CL wearers), with CL wearers in the south having a ninefold increased risk of AK compared with those resident in the north (95% confidence limits: 2.2–38.9, p Conclusions: The incidence was considerably higher than most previous estimates, and was static. The geographical variation in incidence may be partly related to the increase in risk associated with hard water. The fact that water quality can have such an effect on the risk of AK suggests that many CL wearers must be letting tapwater come into contact with their lenses or storage cases. Improved education for CL wearers and practitioners about hygiene practice and the variable efficacy of contact lens systems could be expected to reduce the incidence of this disease.

To report the risk factors for and outcomes of therapeutic and optical keratoplasty in the management of Acanthamoeba keratitis (AK).Retrospective case series.A total of 50 eyes of 196 patients with retrievable medical records, diagnosed with AK at Moorfields Eye Hospital, London, underwent keratoplasty between January 1991 and April 2012.Patient demographics, initial clinical examination findings, and management details were collected. The ophthalmic characteristics of patients who underwent keratoplasty for AK were compared with those who did not. Patients undergoing therapeutic keratoplasty were compared with those undergoing optical keratoplasty for baseline characteristics, management details, and visual outcomes. A multivariate logistic model was used to derive the odds ratios of a poor visual outcome in all keratoplasty patients.Poor visual outcome was defined as final visual acuity of 20/200 or worse. Secondary outcomes of interest included number of clinic visits and the need for additional intraocular surgery.Of the 196 AK patients, a total of 50 patients (25.5%) underwent penetrating or anterior lamellar keratoplasty, 10 of whom (20%) underwent repeat procedures. Of these 50 patients, 26 (52%) had therapeutic keratoplasty, predominantly for corneal perforation. The remaining 24 patients (48%) underwent optical keratoplasty for visual rehabilitation. Thirty-seven (80.4%) patients in the keratoplasty group initially were misdiagnosed as having herpes simplex keratitis versus 59 (41.8%) patients who did not require a keratoplasty (P0.001). Final visual outcomes were significantly better in the optical group compared with the therapeutic group, with 13 (54.2%) achieving visual acuity of 20/30 or better versus 7 (26.9%), respectively. On multivariate analysis, beginning therapy at a hospital other than Moorfields and undergoing a therapeutic, rather than an optical, keratoplasty were associated significantly with a poor visual outcome from keratoplasty.The prognosis of keratoplasty differs markedly when performed for therapeutic purposes compared with visual rehabilitation. Where possible, keratoplasty should be delayed until such time as the eye is uninflamed and medically cured of Acanthamoeba.

AIM To examine the efficacy of systemic cyclosporin A (CSA) in preventing rejection and graft failure in high risk keratoplasty (PK). METHODS A retrospective case-control study with 49 patients in both the CSA group and the control group. The patients receiving CSA were at high risk of graft rejection and failure. Controls were identified from surgical audit books and had high risk characteristics. RESULTS There was no statistical difference in preoperative risk factors and the use of postoperative topical steroids between the two groups. The median follow up in the CSA group was 22 months and 27 months in the control group. One or more rejection episodes occurred in 18 out of 49 (36.7%) cases in the CSA group and 26 out of 49 (53.1%) in the control group. Graft failure from all causes occurred in 16 (32.7%) CSA patients and 18 (36.7%) control patients. Four (8.2%) of the CSA group compared to eight (16.3%) in the control group failed because of rejection. 22 (44.9%) out of 49 patients in the CSA group had side effects. In five (10.2%) patients, CSA was stopped because of the side effects; eight patients had elevated serum urea and creatinine and four developed hypertension. Minor side effects reported include gum hyperplasia, increased sweating, backache, nausea, feeling unwell, oral candidiasis, cramps, and paraesthesia of the extremities. CONCLUSION These results suggest that the benefit of CSA over conventional therapy in preventing rejection episodes and subsequent graft failure is only moderate and did not reach statistically significant levels in this study. Considering the high frequency of side effects and the cost of CSA, a randomised control trial may be necessary to determine the true value of CSA in high risk penetrating keratoplasty.

The cornea provides the eye with protection and the refractive properties essential for visual acuity. The transparent epithelium is highly specialized with basal and stratified squamous cells that are renewed throughout life from a stem cell population. The stem cells are thought to reside at the corneal limbus and may be maintained by a variety of intrinsic and extrinsic factors such as the local environment, survival factors, and cytokines. A number of markers have been localized to the limbus in an attempt to identify stem cells; however, definite stem cell identification remains elusive. During homeostasis and following injury to the corneal epithelium, the limbal stem cells divide to produce daughter transient amplifying cells that proliferate, migrate, and differentiate to replace lost cells. However, this cannot occur if the stem cell population is depleted. Limbal stem cell deficiency then results in corneal re-epithelialization by the neighboring conjunctiva, causing pain, poor vision, and even blindness. This review will focus on corneal epithelial stem cells in ocular surface repair and regeneration. The current knowledge of stem cell biology in the corneal epithelium, clinical consequences of stem cell deficiency, and therapeutic strategies aimed at reversing stem cell deficiency will be discussed.

Purpose: Penetrating keratoplasty for silicone oil keratopathy is associated with high risks and limited visual prognosis. This study examined the outcomes and factors influencing graft failure. Methods: A retrospective, non-comparative, interventional case series of patients attending Moorfields Eye Hospital, London. Results: A total of 24 penetrating keratoplasties were performed in 17 patients (13 men and four women) from 1991 to 2000. The mean age of patients undergoing surgery was 43.6 years (range 17-84 years, SD ± 21.0). Silicone oil was removed before or during the time of initial penetrating keratoplasty in nine patients (52.9%) and left in situ in eight patients (47.1%). Ten out of 24 grafts survived (41.7%). The median duration of graft survival was 21 months (range 2 weeks-98 months) with median duration of follow up 33 months (range 2-100 months). At final follow up, the number of patients with a clear graft who had oil removed before or during the time of penetrating keratoplasty was seven out of 10 (70.0%). Risk factors for graft failure included hypotony, multiple keratoplasty, corneal neovascularization, rejection episode, silicone oil left in situ and postoperative glaucoma. Conclusions: Management of these complex patients requires a combined approach from anterior segment and vitreoretinal subspecialties. The long-term success of the graft can be improved if silicone oil is removed prior or during the time of penetrating keratoplasty.

Objective Bacterial biofilm formation has been implicated in the pathogenesis of infectious crystalline keratopathy. Biofilm cannot be visualized by electron microscopy without the addition of a fixative that stabilizes the polysaccharide-rich bacterial extracellular matrix that surrounds the bacterial colonies in a biofilm. We used ruthenium red as a fixative to evaluate corneal biopsy specimens for the presence of bacterial biofilm in three cases of infectious crystalline keratopathy (ICK) and five cases of chronic microbial keratitis without crystalline changes. Design Case series with clinicopathologic correlation. Participants Eight patients underwent corneal biopsy or therapeutic keratoplasty as part of their management for chronic unresponsive microbial keratitis. Methods The corneal specimens removed were trisected for microbiology, pathology, and transmission electron microscopy (TEM). The TEM specimens were fixed in 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer with 0.05% ruthenium red. Main outcome measures Demonstration of bacterial biofilm with TEM. Results TEM demonstrated organisms with a surrounding extracellular matrix consistent with a bacterial biofilm in the three cases of ICK but not in the five other cases of chronic microbial keratitis. Conclusions The presence of biofilm in ICK can be demonstrated with TEM with appropriate fixation techniques that stabilize the bacterial extracellular matrix. Biofilm stains intensely with periodic acid–Schiff because of the polysaccharide-rich extracellular matrix and weakly with Gram stain because of the high proportion of nonviable organisms. Biofilm formation occurs in ICK but probably not in chronic bacterial keratitis without crystalline changes. Secretion of an extracellular matrix by bacteria to form a biofilm is a response to a nutrient-deprived environment in which growth and replication is depressed. The extracellular matrix of the biofilm may mask bacterial antigens, explaining the relative lack of inflammatory response in these infections. It may also be one of the mechanisms explaining the resistance to in vivo antimicrobial therapy when in vitro sensitivities have been proven.

Aims: To identify the extent of nosocomial adenovirus keratoconjunctivitis (AKC) and assess the effect of a new infection-control policy. Methods: Nosocomial AKC was defined as AKC in patients attending the hospital within 3 weeks of a previous visit for an unrelated non-infective condition. An audit of culture-proven nosocomial AKC was carried out from October 1998 to September 1999 to establish its extent in our outpatient department. A new infection-control policy for AKC was introduced in June 2001 that differed from the previous policy by segregating suspected AKC cases in a separate waiting area and examination room, and by expediting their examination, to reduce their exposure to both staff and patients in the common waiting areas. In October 2002, AKC was made an index infection and subjected to continual quarterly audit; the figures for this until December 2005 are reported. Results: In the 1998–9 audit, before the introduction of the new infection-control measures, 48.4% (75/155) AKC infections were nosocomial. In the 12 months following the introduction of the quarterly audit in October 2002, 22.7% (5/22) were nosocomial, but thereafter the numbers of nosocomial cases dropped to 3.4% (8/235). Conclusion: Introduction of audit of nosocomial AKC infection identified that there was chronic cross-infection in the Moorfields Eye Hospital Accident and Emergency Department. This was controlled by the introduction of patient segregation, as an additional infection-control measure, which has almost eliminated nosocomial AKC transmission in the hospital.

BACKGROUND—Pterygium is a common problem and after surgical removal may recur in up to 80% of cases, depending on the technique of primary excision. Recurrent pterygia can be aggressive and repeated excision may result in severe conjunctival scarring and shortening, resulting in insufficient conjunctiva to perform further grafting and lid surgery. When there is insufficient autologous conjunctiva, mucous membrane must be obtained from other sites. Full thickness buccal mucous membrane grafts have been described, but they may result in a beefy red appearance, with graft contraction and a poor tear film. METHOD—The use of split thickness buccal mucous membrane grafts is described in three patients with recurrent pterygium, two in combination with lamellar keratoplasty. β Irradiation was used as adjuvant therapy in all cases. RESULTS—In all three cases an acceptable cosmetic appearance was achieved, with no recurrence of the pterygium, and a good range of eye movements. CONCLUSIONS—It is recommended that split thickness buccal mucosal grafts, combined with β irradiation, should be considered in complex cases of pterygium recurrence when there is insufficient autologous conjunctiva and conjunctival shortening with restricted eye movements. Keywords: pterygium; split thickness buccal mucous membrane graft; β irradiation

AIM—To investigate the frequency, outcomes, and risk factors for acanthamoeba keratitis (AK) in England during the past 4 years. METHODS—An ophthalmologist in 12 of the 14 regional health authorities (RHAs) coordinated identification of patients in their region presenting with AK between 1 October 1992 and 30 September 1996. Clinical and postal patient questionnaire data were analysed. RESULTS—243 patients (259 eyes) with an AK diagnosis were identified, equating to an annualised incidence of 0.14 per 100 000 individuals. UK resident patients for each year numbered 50, 71, 73, and 32 respectively. Among patients with sufficient data 170/237 (72%) were diagnosed early (within 30 days of presentation), 197/218 (90%) were treated with polyhexamethyl biguanide and/or chlorhexidine, and 40/243 (16%) underwent surgery. Visual acuities of 6/12 or better were achieved by 222/259 (86%) eyes, including 84 eyes of patients under review or lost to follow up. Non-contact lens (CL) wearers were associated with delayed diagnosis, increased need for surgery and a poorer visual outcome (only 10/18 eyes, 56%, achieved 6/12 acuity). 225/243 (93%) patients were CL wearers, and 205/243 (84%) were soft CL (SCL) users. Among SCL user respondents, previously identified risk factors—swimming with CL (47/138, 34%), non-sterile CL rinsing (11/138, 8%), omitted disinfection (85/138, 62%), and chlorine release disinfection (65/138, 47%)—were identified for 125/138 (91%) patients. CONCLUSIONS—Earlier diagnosis and more effective medical therapy have improved the prognosis for most AK patients. The study demonstrates the highly preventable nature of the disease: 91% of the SCL wearers could have avoided the disease by refraining from inadvisable practices, and a marked fall in frequency was seen after intensive media attention to AK, possibly in conjunction with increasing penetrance of new CL products. Since the frequency of AK appears to be largely determined by the ever changing trends in CL use, continued monitoring is indicated. Keywords: keratitis; Acanthamoeba; multicentre survey; England

AIMS—A case-control study was performed to evaluate soft contact lens (SCL) wear modality as a risk factor for microbial keratitis. METHODS—Contact lens wearers presenting as new patients to Moorfields Eye Hospital accident and emergency department during a 12 month period completed a self administered questionnaire detailing demographic data and contact lens use habits. Cases were patients with a clinical diagnosis of SCL related microbial keratitis. Controls were SCL users attending with disorders unrelated to contact lens wear. Odds ratios (estimates of relative risks) and 95% confidence limits (CL) were calculated through multivariable logistic regression analysis. RESULTS—There were 89 cases and 566 controls. A substantially increased risk with 1-4 weekly disposable SCL compared with non-disposable SCL was identified among both daily wear (DW) (odds ratio =3.51, 95% CL 1.60-7.66, p=0.002) and extended wear (odds ratio 4.76, 95% CL 1.52-14.87, p=0.007) users after adjustment for demographic, lens use and hygiene variables. Other significant factors among DW users were "occasional" overnight use, use of chlorine based (as opposed to other chemical) systems in combination with poor storage case hygiene, and irregular disinfection. CONCLUSION—Properties of some disposable SCL may be partly responsible for these excess risks. It is also possible, however, that this finding is largely a reflection of widespread complacency among patients and practitioners with respect to disposable SCL fitting and use. Keywords: microbial keratitis; disposable contact lenses

Cicatricial conjunctivitis may be a sequel to systemic disorders (eg, Stevens-Johnson syndrome, cicatricial pemphigoid) or local disorders such as chemical burns. The cicatrisation is often associated with corneal epithelial changes that cause visual loss. These have been attributed to encroachment of the conjunctival epithelium over the cornea. However, the epithelial anomalies are poorly understood. We investigated the corneal epithelial changes in cicatricial conjunctivitis with an immunohistochemical study of intermediate filaments in normal and pathological specimens. Our results show that the normal corneal epithelium is immunoreactive for cytokeratin 3 (CK 3) but not cytokeratin 19 (CK 19), whereas normal conjunctival epithelium is CK 3 negative and CK 19 positive. Conjunctiva artificially transposed over the cornea (after therapeutic conjunctival flap reconstruction) retained the normal pattern of conjunctival cytokeratin expression (CK 3 negative, CK 19 positive). Conversely, the entire corneal epithelium exhibited the normal cytokeratin pattern (CK 3 positive, CK 19 negative) in 82% of Stevens-Johnson, 80% of cicatricial pemphigoid, and 69% of chemical burns specimens. The findings suggest that conjunctival encroachment is not responsible for the changes at the corneal surface in cicatricial conjunctivitis and that the abnormal corneal epithelium is derived from native corneal cells in these diseases.

Background: Ofloxacin is a potent broad-spectrum fluoroquinolone antibiotic commercially available as a topical ophthalmic preparation. The authors compared ofloxacin (0.3%) as a single therapy with their conventional dual therapy of specially prepared, fortified gentamicin (1.5%) and cefuroxime (5.0%) drops for the treatment of suspected microbial keratitis. Methods: The authors enrolled 122 patients with a clinical diagnosis of microbial keratitis in a prospective, randomized, controlled, double-masked study to compare the two therapies. The ofloxacin drops were decanted into identical-looking bottles to the conventional treatment and dispensed with a second bottle containing saline only. The initial and subsequent assessments noted any risk factors, the size and location of the ulcer, and any evidence of corneal and conjunctival toxicity. All ulcers were scraped for microbiologic culture, and isolated organisms were tested for sensitivity to the trial antibiotics. For statistical analysis, a "cure" was defined as complete healing of the ulcer (no epithelial defect). A ratio of the two outcome proportions and its confidence limits was used to compare the two treatment groups. Multiple regression analysis using Poisson models was used to adjust for confounding factors that may have modified the outcome ratios. Results: There was no difference in the treatment success between the two treatments, with 67.9% of the conventional treatment group and 62.1 % of the of loxacin group being cured within 14 days (ratio, 1.09; [95% confidence interval, 0.83-1.43]; P = 0.59). However, there was significantly more toxicity encountered with the conventional treatment group (50.8% vs. 10.2%; ratio, 5.00 [95% confidence interval, 2.25-11.11 ]; P Conclusions: The authors found that the treatment outcomes with ofloxacin monotherapy compared favorably with their conventional therapy and were associated with less toxicity.

Contact lens case contamination has become an enigma, both because its role in the pathogenesis of lens-related keratitis has remained uncertain, and because current contact lens disinfection systems have been ineffective in eliminating it. This lecture reviews the evidence regarding the role of lens case contamination in the pathogenesis of keratitis and examines the reasons for the failure of disinfection systems to minimise lens case contamination.

Recurrent corneal erosions can occur as a sequel of trauma, of dystrophies or spontaneously. Therapeutic options include topical lubricating and desiccating agents, therapeutic contact lenses, anterior stromal puncture and, most recently, phototherapeutic keratectomy. At present there are no studies available assessing the value of these different therapeutic options.Fifteen eyes of 12 patients underwent therapeutic excimer photoablation after failure of other forms of treatment (lubricating agents in all cases, therapeutic contact lenses in 8, anterior stromal puncture in 2). Ablation depth was 5 microns, except in patients with stromal dystrophy or myopia (6 eyes), who had a deeper ablation.After a first photokeratectomy 9 eyes remained asymptomatic (mean follow-up 12.8 months), 2 eyes had persistent symptoms and 4 had recurrent corneal erosions after 1-24 months. The chance of success after one treatment was 60% after 12 months as calculated by the Kaplan-Meier method.The method of photoablation as applied in this study has a similar chance of success to other surgical methods such as anterior surgical stromal puncture. Patients included in this study, however, were highly selected and were refractory to other forms of treatment.

The role of the three principal epidemiological study designs-- descriptive, cohort and case-control studies--for the evaluation of risk, is illustrated by describing their use for the investigation of microbial keratitis. Descriptive studies have identified potential risk factors and causes of microbial keratitis by both case reports and case series; trauma, ocular surface diseases and, latterly, contact lenses have been identified as potential risk factors. These studies have also shown that Pseudomonas aeruginosa and Acanthamoeba are particularly associated with contact lens wear. However, these studies are limited because they cannot be used to quantify risk. Cohort studies, in which the number of cases of a disease developing in a defined and initially unaffected population are identified, are usually inappropriate for assessing rare conditions because the size of the study often has to be too large, and follow-up too long, to generate sufficient numbers of cases. Some of the disadvantages of this study type can be overcome by sampling techniques and have been successfully carried out to obtain incidence figures for microbial keratitis. Case-control studies use multivariable analyses to examine the risk of microbial keratitis associated with various factors. This is an economical study design for investigating rare diseases because a group of subjects with the disease is compared with a control group from the same population who are unaffected. The selection of an appropriate control group is a difficult problem in epidemiology but this study design has been crucial in identifying risk factors and potential causes of microbial keratitis.