Altered Patterns of Fungal Keratitis at a London Ophthalmic Referral Hospital: An Eight-Year Retrospective Observational Study.

PURPOSE: In previous studies of fungal keratitis (FK) from temperate countries, yeasts were the predominant isolates, with ocular surface disease (OSD) being the leading risk factor. Since the 2005-2006 outbreak of contact lens (CL)-associated Fusarium keratitis, there may have been a rise in CL-associated filamentary FK in the United Kingdom. This retrospective case series investigated the patterns of FK from 2007 to 2014. We compared these to 1994-2006 data from the same hospital. DESIGN: Retrospective observational study. METHODS: All cases of FK presenting to Moorfields Eye Hospital between 2007 and 2014 were identified. The definition of FK was either a fungal organism isolated by culture or fungal structures identified by light microscopy (LM) of scrape material, histopathology, or in vivo corneal confocal microscopy (IVCM). Main outcome measure was cases of FK per year. RESULTS: A total of 112 patients had confirmed FK. Median age was 47.2 years. Between 2007 and 2014, there was an increase in annual numbers of FK (Poisson regression, P = .0001). FK was confirmed using various modalities: 79 (70.5%) by positive culture, 16 (14.3%) by LM, and 61 (54.5%) by IVCM. Seventy-eight patients (69.6%) were diagnosed with filamentary fungus alone, 28 (25%) with yeast alone, and 6 (5.4%) with mixed filamentary and yeast infections. This represents an increase in the proportion of filamentary fungal infections from the pre-2007 data. Filamentary fungal and yeast infections were associated with CL use and OSD, respectively. CONCLUSIONS: The number of FK cases has increased. This increase is due to CL-associated filamentary FK. Clinicians should be aware of these changes, which warrant epidemiologic investigations to identify modifiable risk factors

Drug induced cicatrizing conjunctivitis: A case series with review of etiopathogenesis, diagnosis and management

Drug induced cicatrizing conjunctivitis (DICC) is defined as a disease in which conjunctival cicatrization develops as a response to the chronic use of inciting topical and, rarely, systemic medications. DICC accounts for up to one third of cases of pseudopemphigoid, a large group of cicatrizing conjunctival diseases sharing similar clinical features to those of mucous membrane pemphigoid (MMP) but generally without the morbidity of progressive scarring or the need for systemic immunosuppression. The preservatives in topical anti-glaucoma medications (AGM) are the most frequently implicated inciting causes of DICC although topical antivirals, vasoconstrictors and mydriatics and some systemic drugs have been implicated. The literature review summarizes the classification, epidemiology, etiopathogenesis, histopathology, clinical presentation, diagnosis, management, and treatment outcomes of DICC in the context of a case series of 23 patients (42 eyes) with AGM induced DICC, from India and the UK. In this series all subjects reacted to preserved AGM with one exception, who also reacted to non-preserved AGM. At diagnosis >70% of eyes showed punctal scarring, inflammation, and forniceal shortening. Pemphigoid studies were negative in the 19/23 patients in whom they were carried out. DICC can be classified as non-progressive, progressive with positive pemphigoid immunopathology or progressive with negative pemphigoid immunopathology. It is unclear whether progressive DICC is a stand-alone disease, or concurrent (or drug induced) ocular MMP. Progressive cases should currently be treated as ocular MMP. The diagnosis can be made clinically when there is rapid resolution of symptoms and inflammation, usually within 1–16 weeks, after withdrawal of suspected inciting medications, ideally by temporary substitution of oral carbonic anhydrase inhibitors. If the response to withdrawal is uncertain, or the progression of inflammation and scarring continues then patients must be evaluated to exclude concurrent (or drug induced) MMP, and other potential causes of CC, for which the treatment and prognosis is different. Management, in addition to withdrawing inciting medications, may require short-term treatment of conjunctival inflammation with steroids, treatment of associated corneal disease with contact lenses or surface reconstructive surgery, control of intra-ocular pressure with non-preserved AGM and, in some, surgery for glaucoma or for trichiasis and entropion

Comparison of culture, confocal microscopy and PCR in routine hospital use for microbial keratitis diagnosis.

To evaluate the sensitivity and specificity of polymerase chain reaction (PCR), in vivo confocal microscopy (IVCM) and culture for microbial keratitis (MK) diagnosis. Retrospective review of PCR, IVCM and culture results for MK diagnosis at Moorfields Eye Hospital between August 2013 and December 2014. Results PCR results were available for 259 MK patients with concurrent culture for 203/259 and IVCM for 149/259. Sensitivities and specificities with 95% confidence intervals [95% CI] were calculated for Acanthamoeba keratitis (AK) and fungal keratitis (FK), by comparison with culture, for both IVCM and PCR. For AK, FK and bacterial keratitis (BK) sensitivities were calculated, for each diagnostic method, by comparison with a composite reference standard (a positive result for one or more of culture, PCR or IVCM having a specificity of 100% by definition). For the latter, sensitivities with [95% CI] were: for AK, IVCM 77.1% [62.7-88.0%], PCR 63.3% [48.3-76.6%], culture 35.6 [21.9-51.2]; for FK, IVCM 81.8% [48.2-97.7%], PCR 30.8% [9.09-61.4%], culture 41.7% [15.2-72.3%]; for BK, PCR 25.0% [14.7-37.9%], culture 95.6% [87.6-99.1%]. Conclusion IVCM was the most sensitive technique for AK and FK diagnosis but culture remains our gold standard for BK. These findings reflect results to be expected from service providers to UK ophthalmology units and demonstrates the need at our centre for ongoing diagnostic result audit leading to the potential to improve PCR diagnosis. Both FK and AK are now common in the UK; ophthalmology units need to have all these techniques available to optimise their MK management

Managing ocular surface disease: a common sense approach

Many diseases can cause ocular surface disorders. The poster on pages 50–51 provides an overview of the most common diseases, and other articles in this issue focus on the management of individual diseases. In this article, the authors offer a systematic strategy for the overall management of ocular surface diseases

Effect of cataract surgery on the corneal endothelium: modern phacoemulsification compared with extracapsular cataract surgery.

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 (> or =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

Diagnostic accuracy of microbial keratitis with in vivo scanning laser confocal microscopy

Aims To determine the accuracy of diagnosing microbial keratitis by masked medical and non-medical observers using the Heidelberg Retina Tomograph II/Rostock Cornea Module in vivo confocal microscope. Methods Confocal images were selected for 62 eyes with culture- or biopsy-proven infections. The cases comprised 26 Acanthamoeba, 12 fungus, three Microsporidia, two Nocardia and 19 bacterial infections (controls). The reference standard for comparison was a positive tissue diagnosis. These images were assessed on two separate occasions by four observers who were masked to the tissue diagnosis. Diagnostic accuracy indices, kappa statistic and percentage agreement values were calculated. The Spearman correlation coefficient (r(s)) was calculated for the number of correct diagnoses versus duration of disease. Results The highest sensitivity and specificity values were 55.8% and 84.2%, respectively, and the lowest sensitivity and specificity values were 27.9% and 42.1%, respectively. The highest positive and lowest negative likelihood ratios were 2.94 and 0.59, respectively. Agreement values were: fair to moderate (kappa 0.22-0.44) for reference standard versus observer diagnosis, moderate to good in intraobserver variability (repeatability, kappa 0.56-0.88) and poor to moderate in interobserver variability (reproducibility, kappa 0.15-0.47). The correct diagnosis was associated with duration of disease for Acanthamoeba keratitis (r(s) = 0.60, p = 0.001). Conclusions The diagnostic accuracy of microbial keratitis by confocal microscopy is dependent on observer experience. Intraobserver repeatability was better than interobserver reproducibility. Difficulty in distinguishing host cells from pathogenic organisms limits the value of confocal microscopy as a stand-alone tool in diagnosing microbial keratitis

The top 10 research priorities for the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris in the UK: results of a James Lind Alliance Priority Setting Partnership

To identify priorities for future research into the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris, we conducted a Priority Setting Partnership (PSP) 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