Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

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 expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on.

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.

UK guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016.

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.

Salivary IgA and IgG antibodies to bullous pemphigoid 180 noncollagenous domain 16a as diagnostic biomarkers in mucous membrane pemphigoid.

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 alternative to serum for diagnosis of MMP. METHODS: Precoated BP180-NC16a ELISA plates were used to test serum, and whole and parotid saliva for IgG, IgA and secretory IgA antibodies. Patients with MMP (n = 64) provided matched serum and whole saliva. In addition 18 of the MMP patients also provided matched parotid saliva. Healthy controls (n = 50) provided matched serum and whole saliva and 6 of these additionally provided matched parotid saliva. An additional 16 disease controls provided matched serum, and whole and parotid saliva. RESULTS: In whole saliva, IgG antibodies were detected in 11/64 (17%), IgA in 23/64 (36%) and a combined positivity in 29/64 (45%). In parotid saliva, IgA antibodies were found in 8/18 (44%). Serum IgG antibodies were detected in 27/64 (42%), serum IgA antibodies in 18/64 (28%) and a combined positivity in 33/64 (52%). Combined use of serum and saliva increased detection of specific antibodies by 30%. Control samples were all negative (positive predictive value of 100% for all tests). The negative predictive values were 62% for IgA saliva, 65% for IgG serum, 59% for IgA serum and 56% for IgG saliva. CONCLUSIONS: IgG and IgA antibodies may provide a suitable diagnostic marker in MMP. Assay of salivary IgA antibodies to NC16a offers a similar diagnostic predictive value to serum.

Clinical study of therapeutic ocular surface medium for persistent epithelial defect.

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 mm(2)). 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.

Incidence, presenting features, and diagnosis of cicatrising conjunctivitis in the United Kingdom.

PURPOSE: Cicatrising 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 Ophthalmological Surveillance Unit at diagnosis and at 12 months follow-up. RESULTS: A total of 50 (61%) ocular mucous membrane pemphigoid (OcMMP), 16 (20%) Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS-TEN) and 16 (20%) other causes of CC, equating to an incidence of 0.8, 0.2, and 0.2 per million, respectively, were reported. Although diagnosis of SJS-TEN was usually within a median of 7 days of symptom-onset, that for OcMMP and other CC was a median 225 days for both. At diagnosis, 64/163 (39%) eyes had moderate/severe conjunctival inflammation, and 102/164 (62%) had symblepharon formation. Although 43/82 (52%) patients were commenced on immunosuppression or had this therapy modified, at follow-up there was an increase in the number of symblepharon, despite control of inflammation (P<0.001). Mortality only occurred in the SJS-TEN group (4/16 (25%)). CONCLUSION: CC has a substantial morbidity and for non-SJS-TEN causes, diagnosis is frequently delayed. The proportion of patients given immunosuppressive therapy to prevent disease progression may be less than optimal. These data highlight the need for developing patient access to specialist-designated centres with expertise in CC.

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom.

PURPOSE: 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 hospitals in the United Kingdom. PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed. RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation. CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.

Ipsilateral rotational autokeratoplasty: a review.

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 (IRA). This review describes the indications, technique, and outcomes of IRA. IRA is only indicated for patients with a localised opacity leaving a minimum diameter of 4-5 mm of uninvolved clear cornea. For these few patients in whom the procedure is practicable, the surgery can be planned by manipulating digital images to estimate the trephine size and location and/or by the use of formulas. IRA may not provide either as good spectacle acuity or as good quality of vision as penetrating keratoplasty because of higher astigmatism and a reduced corneal pupillary clear zone, but these disadvantages are often outweighed when the risk of allograft rejection is high, as in paediatric patients and those with vascularised corneas. The main benefits of IRA are the retention of host endothelium, thereby eliminating both the risk of endothelial rejection and the prolonged attrition of endothelial cell numbers that occurs following penetrating keratoplasty, and the reduced requirement for postoperative steroid therapy with its associated complications.

Identification and control of nosocomial adenovirus keratoconjunctivitis in an ophthalmic department.

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.

Cicatrising conjunctivitis with anti-basement membrane autoantibodies in ectodermal dysplasia.

AIMS: 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 combined with clearance of bacterial colonisation. METHODS: Conjunctival and buccal immunohistopathology, and serological analysis using a panel of epithelial basement membrane zone proteins including the bullous pemphigoid antigen 180 (BP180) were carried out as part of an ocular pemphigoid work-up in each patient. The degree of photophobia, conjunctival inflammation and visual acuity were monitored to evaluate the response to immunosuppression. The mean duration of follow-up was 31 (SD 6) months. RESULTS: Four of the six patients showed positive immunopathology: direct immunofluorescence testing of the conjunctiva in one patient demonstrated linear IgA deposition along the basement membrane zone, and IgG and IgM in the buccal mucosa of another patient. Circulating autoantibodies to BP180 were detected in two other patients. Treatment with systemic immunosuppression, combined with clearance of bacterial colonisation, reduced the severity of photophobia and degree of conjunctival inflammation in 5/6 (83%) patients. CONCLUSIONS: Systemic immunosuppression, used as steroid-sparing therapy, combined with clearance of bacterial colonisation can control inflammation and disabling photophobia, and allow improvement in vision, in a subgroup of ectodermal dysplasia patients who have severe cicatrising conjunctivitis which shares clinical and immunopathological features with ocular mucous membrane pemphigoid.

Risk factors for microbial keratitis with contemporary contact lenses: a case-control study.

OBJECTIVE: To assess the relative risks (RR) of microbial keratitis (MK) for contemporary contact lens (CL) types and wearing schedules. DESIGN: A 2-year prospective case-control study begun in December 2003. PARTICIPANTS: Cases were 367 CL wearers attending Moorfields Eye Hospital with proven or presumed MK. Controls were 1069 hospital controls, who were CL wearers 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-based controls were interviewed by telephone. TESTING: Multivariate analysis was done both for all cases of MK, and for the moderate and severe MK subgroups alone. MAIN OUTCOME MEASURES: The RR for developing MK, and vision loss, for all lens types compared with planned replacement soft lenses (the referent). RESULTS: Compared with planned replacement soft lenses (the referent), the RR of MK was significantly increased with daily disposable (DD) CLs (RR, 1.56x [95% confidence interval (CI), 1.1-2.1]; P = 0.009) and differed between different brands of DD lens, was reduced for rigid lenses (RR, 0.16x [95% CI, 0.06-0.4]; P<0.001), and no different for silicone hydrogel or other types of soft lens. Although the risk of MK was higher overall among DD lens users, the risk of vision loss was less than for planned replacement soft CL users (P = 0.05); no DD lens users lost vision to the level of >or=20/40. The RR for overnight wear, for any lens type, was 5.4 times higher (95% CI, 3.3-10.9; P<0.001). Comparison of the DD soft CL types with planned replacement soft lenses (the referent), showed significant differences between brands for the risk of MK. CONCLUSIONS: The risk of MK has not been reduced in users of DD and silicone hydrogel CLs. However, vision loss is less likely to occur in DD than in reusable soft CL users. Different brands of CL may be associated with significantly different risks of keratitis; understanding these differences should lead to the development of safer soft lenses. These findings suggest that lens/ocular surface interactions may be more important in the development of corneal infection than oxygen levels and CL case contamination.

Legeais BioKpro III keratoprosthesis implantation: long term results in seven patients.

AIMS: The long term results of the Legeais BioKpro III keratoprosthesis are presented for seven patients with severe corneal scarring. METHODS: The study took place at Moorfields Eye Hospital, London. Patients had either end stage ocular surface disease or corneal opacification after multiple failed graft surgery, with the potential for significant visual improvement. After insertion the device was covered with a conjunctival flap or buccal mucous membrane graft, which was later opened to expose the optic. The outcome measures were vision, complications, and retention of the device. RESULTS: The BioKpro III was inserted into seven patients with severe corneal scarring: ocular cicatricial pemphigoid, measles keratitis, thermal injury, Stevens-Johnson syndrome, aniridia, chemical injury, and congenital rubella. The follow up was 18-48 months. The keratoprosthesis failed in six, because of extrusion occurring 2-28 months postoperatively. Retroprosthetic membranes occurred in three patients, and endophthalmitis in one. Vision improved from hand movements to 6/12 in the only patient who retained the KPro; however he was troubled by mucus accumulation on the optic. CONCLUSIONS: The one success has been in a patient with thermal burns. The remaining results have been poor, with the KPro extruding in six of the seven patients.

Scleral-fixated posterior chamber intraocular lenses in non-vitrectomized eyes.

OBJECTIVE: To assess the long-term outcome of scleral-fixated sutured posterior chamber intraocular lens (SPCIOL) implantation in non pars plana vitrectomised eyes (1) to evaluate the long-term visual outcome, (2) to identify preoperative risk factors for poor visual outcomes, and (3) to identify the incidence of vitreoretinal complications. METHOD: A retrospective review of 65 eyes, which had not undergone pars plana vitrectomy prior to scleral-fixated SPCIOL implantation. RESULTS: In all, 65 eyes of 61 patients were analysed. The median follow-up period was 16 months (range 1-68 months). At final follow-up, 43 (66%) eyes had unchanged or improved BCVA at final follow-up. A total of 20 (31%) eyes had at least a two line improvement and eight (12%) eyes had at least a two line deterioration in final BCVA. No significant preoperative risk factors for a poor visual outcome were identified. In all, 24 eyes (37%) had per- and postoperative adverse events. These eyes were significantly more likely to have a poor visual outcome. Three eyes (4.6%) had a retinal detachment in the postoperative period, all of which had no perception of light at final follow-up. CONCLUSIONS: This study confirmed that while scleral-fixated SPCIOL intraocular lens implantation might be beneficial, there is a significant risk of per- and postoperative complications leading to loss of best-corrected vision in some eyes.