Anne Cook

Review of patients with basal cell nevus syndrome.

Purpose: To review patients with basal cell nevus syndrome (BCNS), documenting presentation, referrals, treatment patterns, and associated morbidity. Methods: Cross-sectional review and retrospective data collection of 39 patients with BCNS. Patients from the BCNS support group were invited to be examined. Demographics, presenting features, associated pathologies, and treatment modalities were recorded. Demographic data, age at presentation, age at diagnosis, spectrum of ophthalmic and periocular disease, treatment modalities used, and periocular deformities developed were reviewed. Results: Thirty-nine patients were included with age range of 5 to 72 years. Presenting clinical features included odontogenic keratocyst in 17 patients and basal cell carcinoma in 13 patients; less common presentations were with congenital malformations (n = 2), with ophthalmic associations (n = 3), and at genetic counseling (n = 4). Seventeen of the 39 patients confirmed a parental diagnosis of BCNS. Basal cell carcinoma developed in 18 of the 28 patients before the age of 30, confirming the reported early age of onset. Periocular basal cell carcinoma was reported in 24 of 39 patients (61%), with recurrent disease reported in 17 of these 24 (71%), despite a variety of treatment modalities used. Associated ophthalmic features were multiple eyelid cysts (15 patients), strabismus (9 patients), myopia (5 patients), hyperopia (7 patients), cataracts (5 patients), myelinated nerve fibers (3 patients), amblyopia (3 patients), and nystagmus and iris transillumination defects (2 patients each). All patients were involved in multidisciplinary medical care. Conclusions: Patients with BCNS frequently have ophthalmic manifestations, particularly periocular basal cell carcinoma. Multidisciplinary care is essential in the care of the patient with BCNS. Early diagnosis of BCNS may allow for skin protection and surveillance at an earlier age.

Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED) trial: A multi-centre, double-masked, factorial randomised controlled trial

BackgroundMedical management of thyroid eye disease remains controversial due to a paucity of high quality evidence on long-term treatment outcomes. Glucocorticoids are known to be effective initially but have significant side-effects with long-term use and recrudescence can occur on cessation. Current evidence is conflicting on the efficacy of radiotherapy and non-steroid systemic immunosuppression, and the majority of previous studies have been retrospective, uncontrolled, small or poorly designed.The Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease (CIRTED) trial was designed to investigate the efficacy of radiotherapy and azathioprine in combination with a standard course of oral prednisolone in patients with active thyroid eye disease.Methods/designPatients with active thyroid eye disease will be randomised to receive (i) azathioprine or oral placebo and (ii) radiotherapy or sham-radiotherapy in this multi-centre, factorial randomised control trial. The primary outcome is improvement in disease severity (assessed using a composite binary measure) at 12 months and secondary end-points include quality of life scores and health economic measures.DiscussionThe CIRTED trial is the first study to evaluate the role of radiotherapy and azathioprine as part of a long-term, combination immunosuppressive treatment regime for Thyroid Eye Disease. It will provide evidence for the role of radiotherapy and prolonged immunosuppression in the management of this condition, as well as pilot data on their use in combination. We have paid particular attention in the trial design to establishing (a) robust placebo controls and masking protocols which are effective and safe for both radiotherapy and the systemic administration of an antiproliferative drug; (b) constructing effective inclusion and exclusion criteria to select for active disease; and (c) selecting pragmatic outcome measures.Trial registrationCurrent controlled trials ISRCTN22471573

Life expectancy following orbital exenteration

Orbital exenteration is a physically debilitating procedure that may be a necessity in the management of orbital malignancy. It requires a sensitive multidisciplinary approach, both preoperatively and postoperatively. Providing life expectancy information for patients during preoperative counselling is pertinent to informed consent and in addressing patients’ expectations. A retrospective review from one tertiary care centre was undertaken for a cohort of patients who were exenterated for orbital malignancy between 1998 and 2010. The cases were identified using an International Classification of Diseases 10th Revision (ICD-10)-derived database and were analysed using Prism statistical software (V.5.04). Cause of death was ascertained by liaising with the general practitioner and the National Registrar Office for Births, Deaths, and Marriages, Southport, UK. In total, 41 men and 32 women were identified. Mean age was 72 years with 47 cases living and 26 deceased at the time of review. The overall 5-year survival rate in this study was 64%. Kaplan–Meier analysis for basal cell carcinoma (BCC) against non-BCC returned a p value of 0.0199, with an HR of 0.3927 (CI 0.1788 to 0.8626). Kaplan–Meier analysis for cleared against non-cleared margins returned a p value of 0.2890, with an HR of 0.6571(CI 0.3024 to 1.428). Our results represent the highest 5-year survival data to date. However, the overall prognosis for patients who undergo orbital exenteration for malignancy remains poor. We hypothesise that the causes are multi-factorial. We recommend a multidisciplinary approach to the care of these patients, involving head and neck teams, oncology and other appropriate specialties, to optimise outcomes for this vulnerable patient group.

Difference in response to botulinum toxin type A treatment between patients with benign essential blepharospasm and hemifacial spasm

Background:  Botulinum toxin (BTX) is the first‐line treatment in managing benign essential blepharospasm (BEB) and hemifacial spasm (HFS). We wished to assess the difference in duration of effect and the number of BTX treatments required to treat patients with BEB and HFS.

Eyelid avulsion repair with bi-canalicular silicone stenting without medial canthal tendon reconstruction

Aims To evaluate the functional and cosmetic success rate of combined canalicular laceration and eyelid avulsion repairs using the bi-canalicular Crawford stent, without the concomitant placement of a medial traction suture to repair medial canthal tendon (posterior limb) avulsion. Methods Retrospective, non-comparative consecutive case series of 40 consecutive patients with traumatic eyelid avulsion injuries associated with canalicular laceration from 1997 to 2003 who underwent surgical repair using the bi-canalicular Crawford stent were included. All patients underwent surgical repair of the canalicular laceration under general anaesthesia using the bi-canalicular stent. Meticulous anastomosis of the torn canaliculus was undertaken. No attempt was made to suture the avulsed medial canthal tendon (posterior limb) to the periosteum of the posterior lacrimal crest. Results Blunt trauma was the most common mechanism of injury and the inferior canaliculus was most commonly involved. Of the 37 patients who attended postoperative follow-up, 24 patients had no subjective symptoms of epiphora. Minimal, mild and moderate epiphora was present in seven, five and one patient respectively. Thirty-three patients had excellent cosmetic repositioning of the lid; two developed medial ectropia and a further two patients had lid margin notching but good lid position. Eight patients had premature stent loss. Conclusions Bi-canalicular stenting achieved excellent cosmetic results in eyelid avulsion injuries, by facilitating adequate tissue realignment without the need for a posterior lacrimal crest fixation suture. Good functional results were achieved and were comparable with previous studies.

Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial

BACKGROUND Standard treatment for thyroid eye disease is with systemic corticosteroids. We aimed to establish whether orbital radiotherapy or antiproliferative immunosuppression would confer any additional benefit. METHODS CIRTED was a multicentre, double-blind, randomised controlled trial with a 2 × 2 factorial design done at six centres in the UK. Adults with active moderate-to-severe thyroid eye disease associated with proptosis or ocular motility restriction were recruited to the trial. Patients all received a 24 week course of oral prednisolone (80 mg per day, reduced to 20 mg per day by 6 weeks, 10 mg per day by 15 weeks, and 5 mg per day by 21 weeks) and were randomly assigned via remote computerised randomisation to receive either radiotherapy or sham radiotherapy and azathioprine or placebo in a 2 × 2 factorial design. Randomisation included minimisation to reduce baseline disparities in potential confounding variables between trial interventions. Patients and data analysts were masked to assignment, whereas trial coordinators (who monitored blood results), pharmacists, and radiographers were not. The radiotherapy dose was 20 Gy administered to the retrobulbar orbit in ten to 12 fractions over 2 to 3 weeks. Azathioprine treatment was provided for 48 weeks at 100-200 mg per day (dispensed as 50 mg tablets), depending on bodyweight (100 mg for <50 kg, 150 mg 50-79 kg, 200 mg for ≥80 kg). The primary outcomes were a binary composite clinical outcome score and an ophthalmopathy index at 48 weeks, and a clinical activity score at 12 weeks. The primary analysis was based on the intention-to-treat allocation and safety was assessed in all participants. This study is registered with ISRCTN, number 22471573. FINDINGS Between Feb 15, 2006, and Oct 3, 2013, 126 patients were recruited and randomly assigned to groups: 31 patients to radiotherapy plus azathioprine, 31 to sham radiotherapy and azathioprine, 32 to radiotherapy and placebo, and 32 to sham radiotherapy and placebo. Outcome data were available for 103 patients (54 for sham radiotherapy vs 49 for radiotherapy and 53 for placebo vs 50 for azathioprine), of whom 84 completed their allocated treatment of radiotherapy or sham radiotherapy and 57 continued to take azathioprine or placebo up to 48 weeks. There was no interaction betweeen azathioprine and radiotherapy (pinteraction=0·86). The adjusted odds ratio (ORadj) for improvement in the binary clinical composite outcome measure was 2·56 (95% CI 0·98-6·66, p=0·054) for azathioprine and 0·89 (0·36-2·23, p=0·80) for radiotherapy. In a post-hoc analysis of patients who completed their allocated therapy the ORadj for improvement was 6·83 (1·66-28·1, p=0·008) for azathioprine and 1·32 (0·30-4·84, p=0·67) for radiotherapy. The ophthalmopathy index, clinical activity score, and numbers of adverse events (161 with azathioprine and 156 with radiotherapy) did not differ between treatment groups. In both groups, the most common adverse events were mild infections. No patients died during the study. INTERPRETATION In patients receiving oral prednisolone for 24 weeks, radiotherapy did not have added benefit. We also did not find added benefit for addition of azathioprine in the primary analysis; however, our conclusions are limited by the high number of patients who withdrew from treatment. Results of post-hoc analysis of those who completed the assigned treatment suggest improved clinical outcome at 48 weeks with azathioprine treatment. FUNDING National Eye Research Centre, Above and Beyond, and Moorfields Eye Charity.

Recurrence rates of periocular basal cell carcinoma following Mohs micrographic surgery: a retrospective study.

The incidence of basal cell carcinoma (BCC) has increased during the previous decade. Mohs micrographic surgery (MMS) is the gold standard technique for BCCs. The aim of this study was to investigate the recurrence rate of periocular BCCs following MMS in a regional Mohs treatment facility in the United Kingdom.

Reliability and Effectiveness of the Manchester Orbital Exenteration Wound Assessment Tool: Inter-Observer Agreement

ABSTRACT Aim: To evaluate the inter-observer agreement of the Manchester Orbital Exenteration Wound Assessment Tool (MOEWAT), a tool designed to facilitate grading of healing in exenterated sockets, scores from clinical photographs of exenterated sockets. Methods: Existing MOEWAT system was modified to allow grading of clinical photographs. Photographs of 36 different patients at different stages of healing following exenteration were identified. Scores for two masked observers, who independently graded the photographs were compared. The inter-observer agreement of scores was assessed using a Bland-Altman plot, with the average agreement and 95% confidence interval around the mean computed. Results: The average age of the 36 patients was 66 ± 29 years. Photographs were taken 32 ± 16 months after exenteration. Across all photographs, the averages score given by the first observer (4.3 ± 2.2) and second observer (3.4 ± 1.5) were similar (t = –1.9; p = 0.07). From the Bland-Altman plot, the mean difference in score (0.8 ± 1.8) was close to zero, with 95% confidence limits for agreement are indicated by the dashed lines and spanning from −2.6 to 4.3. Conclusion: MOEWAT can be successfully used to stage wound healing in exenterated sockets, with good inter-observer agreement.