John K Dart

University College London | UCL · Institute of Ophthalmology

Dear Editor, Bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV) are autoimmune blistering diseases that present with mucocutaneous blistering and erosions. Although distinct diseases, they share clinical and immunological features, and many treatments are common to all three. In recent years, the body of high-qual...

Background: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. Objectives: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary...

Objectives This study was designed to establish risk factors for the development of Acanthamoeba keratitis (AK) for daily disposable contact lens (DD) users compared to 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 (MK) of...

Aims To evaluate the sensitivity and specificity of polymerase chain reaction (PCR), in vivo confocal microscopy (IVCM) and culture for microbial keratitis (MK) diagnosis. Methods 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 availa...

Cicatricial conjunctival diseases (CCDs), are a diverse group of ocular surface diseases characterized by chronic scarring of the conjunctiva. These diseases can cause significant ocular morbidity. They are life-long once acquired and can be debilitating, painful diseases leading to visual loss. A recent international consensus of ocular surface di...

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 prospective...

Background and Aims Polyhexamethyl 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. Methods A prospective, randomised, double-masked controlled trial in 90 healthy volunteers. Subjects were treated with topical 0.04%,...

Objective To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathological diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients. Design Prospective cross-sectional study. Subjects and controls 76 patients with MMP involving ocular and non-ocular sites...

Purpose: This study was designed to validate a semi-quantitative clinical assessment tool for cicatrising conjunctivitis (CC). Methods: Fifty-five patients (109 eyes) with mucous membrane pemphigoid (MMP) and 31 patients (61 eyes) with Stevens-Johnson syndrome (SJS) were included. Three methods were used for validation: (1) comparison of inter-a...

Aims To test the hypothesis that Acanthamoeba keratitis (AK) outcomes differ for different topical antiamoebic therapies (AAT) and to provide the detailed patient outcome data. Methods A 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 f...

Purpose: The pathogenesis of Ocular mucous membrane pemphigoid (OcMMP) traditionally considering as systemic autoimmune dysregulation leading to chronic inflammation at affected sites such as ocular membrane. New evidence suggests this dysregulation inflammation may be related to gene mutation. In order to investigate the suspicion risk genes in O...

Background/aims Acanthamoeba 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. Methods Annualised incidence data were collected from January 1984 to December 2016. Case...

Neurotrophic keratitis/keratopathy (NK), a rare degenerative corneal disease, lacks effective pharmacologic therapies.1 Because NK pathology involves trigeminal nerve damage and loss of corneal innervation, nerve growth factor (NGF) is surmised to promote healing of NK.2 Preliminary studies with murine NGF demonstrated efficacy for treating corneal...

Purpose: To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Design: Phase 2 multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patie...

Purpose: To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis. Design: Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT0187769...

Background/aims To determine demographic and clinical features of patients with Acanthamoeba keratitis (AK) that are independent risk factors both for bad outcomes and for severe inflammatory complications (SIC). Methods A retrospective audit of medical records of AK cases at Moorfields Eye Hospital from July 2000 to April 2012, including 12 earli...

Purpose: This study explored the validity of the First International Consensus on Mucous Membrane Pemphigoid (MMP) guidance, which recommends that clinically indistinguishable patients, who have direct immunofluorescence (DIF)-negative biopsies, be excluded from a diagnosis of MMP. Misdiagnosis, or delayed diagnosis, of MMP with ocular involvement...

Background: Mucous membrane pemphigoid (MMP) is a rare, chronic, and often aggressive subepidermal autoimmune blistering disease potentially affecting several mucous membranes with blisters and secondary erosions and scars. The pathogenesis of MMP is poorly understood, and the contribution of genetic predispositions, other than HLA class II allele...

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-...

2008 Dart et al Ophthalmology. (PDF)

2008 Stapleton et al Ophthalmology. (PDF)

Univariate analysis. (XLSX)

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 o...

Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase (ALDH) family 1 is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fi...

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the diagnosis and management of the full spectrum of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap in adults during the acute phase of the disease. The document aims to: Offer an appraisal of all relevant lite...

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 2005-6 outbreak of contact lens (CL) associated Fusarium keratitis, there may have been a rise in CL associated filamentary FK in the United Kingdom. This re...

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the diagnosis and management of the full spectrum of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap in adults during the acute phase of the disease. The document aims to: Offer an appraisal of all relevant litera...

SJS/TEN is rare and few health care professionals are confident in the recognition and management of the disorder. There is widely divergent practice amongst different specialities and healthcare settings, and limited information on outcomes. These guidelines, aim to provide recommendations on the diagnosis and management of SJS/TEN, to inform clin...

Purpose: To examine the impact of topical corticosteroid use after the start of antiamoebic therapy (AAT) on the outcomes of Acanthamoeba keratitis (AK) therapy. Design: Cohort study. Participants: A total of 196 patients diagnosed with AK at Moorfields Eye Hospital, London, between January 1991 and April 2012. In 13 patients with bilateral AK...

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...

Background: Mucous membrane pemphigoid (MMP) is an uncommon mucocutaneous immunobullous disorder. Use of saliva for diagnosis by enzyme-linked immunosorbent assay (ELISA) using the noncollagenous (NC) domain 16a of bullous pemphigoid antigen II (BP180) is not well described. Objective: To establish whether whole or parotid saliva is a suitable a...

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 i...

Lens brand did not have an effect on ocular temperature (F = 1.220, p = 0.308), but ocular temperature decreased towards the end of the day (8 h: 36.1 ± 1.60 • C; 12 h: 35.3 ± 0.80 • C; 16 h: 35.2 ± 0.9 • C; F = 19.497, p < 0.001). Conclusions: The tear stability over the contact lens surface differed between lens types and may have a role in prote...

Purpose To report delayed onset-peripheral ulcerative keratitis (PUK) following alkali injury Design Retrospective case series. Methods Setting Single institution (Cornea and External Disease Service, Moorfields Eye Hospital). Participants 6 eyes of 5 patients with PUK and associated anterior scleritis that had a history of ocular alkali injury...

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...

Acanthamoeba keratitis is a rare cause of infectious keratitis. It is often diagnosed late because of both its insidious onset and confusion with herpes simplex keratitis. The diagnosis must be considered in all indolent cases of keratitis, particularly in contact lens users and in those cases that have not responded to antibiotics or antivirals. P...

Objective To examine the impact of topical corticosteroid use before the diagnosis of Acanthamoeba keratitis (AK) on final visual outcomes and to determine the prognostic factors predicting poorer outcomes. Design Cohort study. Participants A total of 209 eyes of 196 patients with retrievable medical records, diagnosed with AK at Moorfields Eye H...

The purpose of this retrospective study was to evaluate the clinical outcome of patients affected by Acanthamoeba keratitis treated with unlicensed drugs. PHMB was the most used medication in this study.

Mucous membrane pemphigoid (MMP) is a rare systemic autoimmune disease that affects many of the mucous membranes and the skin. The precipitating factors are usually unknown; there is some genetic susceptibility. The pathogenesis is now quite well understood and involves loss of tolerance to basement membrane antigens, leading to the development of...

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...

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 patient...

Objective: To evaluate the off-label use of subconjunctival bevacizumab for corneal neovascularisation (CoNV). Methods: 30 patients with recent-onset CoNV from various causes were randomly assigned into a double-masked, placebo-controlled trial. Each received three 0.1 ml injections containing either 2.5 mg bevacizumab or 0.9% saline at monthly...

To determine the association of single nucleotide polymorphisms (SNPs) of defensin 1B and toll-like receptor 4 with contact lens keratitis susceptibility and severity, and to understand the factors that influence study participation. Retrospective, case-control study. Ninety cases of keratitis and 185 controls recruited from studies conducted at Mo...

PurposeCicatrising conjunctival disorders are uncommon, and are difficult to diagnose and manage. This study was designed to assess the annual incidence and underlying diagnosis of patients with cicatrising conjunctivitis (CC) within the United Kingdom.Methods Clinical data of newly diagnosed cases of CC were reported via the British Ophthalmologic...

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 form...

To establish risk factors for moderate and severe microbial keratitis among daily contact lens (CL) wearers in Australia. A prospective, 12-month, population-based, case-control study. New cases of moderate and severe microbial keratitis in daily wear CL users presenting in Australia over a 12-month period were identified through surveillance of al...

To investigate whether single nucleotide polymorphisms (SNPs) in interleukin (IL)-1β, IL-6, and IL-12β are associated with the susceptibility and severity of contact lens-related keratitis. Retrospective, case control study. One hundred twelve cases of keratitis and 225 controls were recruited from studies conducted at Moorfields Eye Hospital and i...

Objective To evaluate the off-label use of subconjunctival bevacizumab for corneal neovascularisation (CoNV). Methods 30 patients with recent-onset CoNV from various causes were randomly assigned into a double-masked, placebo-controlled trial. Each received three 0.1 ml injections containing either 2.5 mg bevacizumab or 0.9% saline at monthly inter...

Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care...

Purpose: Cicatrising conjunctivitis (CC) includes a group of rare, potentially sight-threatening disorders for which early diagnosis and appropriate treatment are essential. A study was designed to determine the minimum incidence of CC disorders in the United Kingdom. Methods: Newly diagnosed cases of CC were reported via the British Ophthalmol...

To describe the history and clinical presentation of a case of primary epibulbar molluscum contagiosum in multiple myeloma, after penetrating keratoplasty. A 70-year-old man, with previously diagnosed multiple myeloma and atopic dermatitis and keratoconjunctivitis, presented 6 months after right penetrating keratoplasty with white multilobular nodu...

Ocular mucous membrane pemphigoid is an immunobullous disease in which excessive conjunctival fibrosis causes blindness, and the pathogenesis of scarring is incompletely understood. To establish whether profibrotic fibroblasts with an altered phenotype exist in ocular mucous membrane pemphigoid, we compared the functional characteristics of pemphig...

To investigate therapeutic ocular surface medium (TOSM), a potential physiological tear replacement therapy, for moderate to severe dry eye. 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, control...

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),...

To evaluate the long-term results of autologous submandibular gland transplantation in eyes with cicatrizing conjunctivitis and to determine biomechanical and biochemical features of the resulting salivary tear film. Prospective, observational case series. Fifteen eyes with cicatrizing conjunctivitis with a viable autologous submandibular gland tra...

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. Confocal images were selected for 62 eyes with culture- or biopsy-proven infections. The cases comprised 26 Acanthamoeba, 12 fungus, three Microsporidia,...

Interleukin-13 (IL-13) is the dominant effector cytokine of fibrosis in pulmonary and liver disease. Excessive conjunctival fibrosis in the immunobullous disease ocular mucous membrane pemphigoid (MMP) causes blindness; the pathogenesis of scarring in this disease is incompletely understood. To determine whether IL-13 is involved in conjunctival fi...

To describe the current management of Acanthamoeba keratitis (AK). A perspective based on the literature and author experience. Early diagnosis and appropriate therapy are key to a good prognosis. A provisional diagnosis of AK can be made using the clinical features and confocal microscopy, although a definitive diagnosis requires culture, histolog...

The authors aimed to produce a new tear substitute capable of providing both lubrication and nutrition, based on a novel nutrient-containing therapeutic ocular surface medium (TOSM). Viscous substances, including hypromellose (HPMC), carbopol, and sodium hyaluronate (SH) were added to the TOSM at various concentrations. Three commercial preservativ...

First, to determine whether tumor necrosis factor-(TNF)-alpha is expressed in the conjunctiva of ocular mucous membrane pemphigoid (MMP) and the consequences of systemic immunosuppressive treatment on this expression. Second, to investigate the in vitro effects of TNFalpha on human conjunctival fibroblasts. The expression of TNFalpha in conjunctiva...

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. A 2-year prospective case-control study commencing in December 2003. Cases were 877 CL wearers attending Moorf...

Corneal opacity is a major cause of monocular blindness and, after cataract, is also a leading cause of blindness worldwide. Keratoplasty techniques for the treatment of corneal opacities include deep anterior lamellar allokeratoplasty, penetrating allokeratoplasty, penetrating bilateral autokeratoplasty, and ipsilateral rotational autokeratoplasty...

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...

To report circulating and mucosa-deposited anti-basement membrane zone autoantibodies in a series of six ectodermal dysplasia patients with severe bilateral cicatrising conjunctivitis and blindness due to both corneal disease and intractable surface inflammation. We also report clinical improvement with steroid-sparing systemic immunosuppression co...

To identify the extent of nosocomial adenovirus keratoconjunctivitis (AKC) and assess the effect of a new infection-control policy. 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 1...

Ocular mucous membrane pemphigoid presents some of the most challenging dilemmas in anterior segment management. Diagnosis is made difficult by the insensitivity of immunopathological investigations and the differential diagnosis of other scarring conjunctival disorders. The management of the associated ocular surface disease involves control of bl...

Eye is the official journal of the Royal College of Ophthalmologists. It aims to provide the practising ophthalmologist with information on the latest clinical and laboratory-based research.

To describe a clinical grading system for epidemiological investigation of presumed contact lens related microbial keratitis (MK) and investigate the relationship to associated costs and disease duration. Eligible cases identified via surveillance required positive culture or presence of at least one clinical criterion: part of the lesion within th...