Publications by authors named "Daniel G Ezra"

72 Publications

Unravelling the Complex Anatomy of the Tear Trough and Lower Eyelid Folds: A Review of Cadaveric Studies in the Literature.

J Craniofac Surg 2022 Aug 10. Epub 2022 Aug 10.

Adnexal Department, Moorfields Eye Hospital.

The lower eyelid tear trough deformity is a common cosmetic concern which is the result of multiple anatomic changes in the lower eyelid, usually resulting from age. A sound understanding of the underlying anatomy is vital to inform surgeons about the ideal treatment options for rejuvenation of this region and to minimize the risk of complications. Cadaveric studies provide unique insight into underlying anatomic changes. Here we review the relevant published cadaveric studies relating to the tear trough deformity and its treatment.
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http://dx.doi.org/10.1097/SCS.0000000000008756DOI Listing
August 2022

Introducing the 'Benign Eyelid Lesion Pathway': 1 year experience of synchronous tele-oculoplastics in a tertiary hospital.

Eye (Lond) 2022 Jul 4. Epub 2022 Jul 4.

Adnexal Department, Moorfields Eye Hospital NHS Foundation Trust, 162 City Rd, London, EC1V 2PD, UK.

Background: Patients with benign eyelid lesions make up a large proportion of referrals to the oculoplastic service and lend themselves well to telemedicine with assessments heavily reliant on history, observation-based examination and photographs to enable management decision-making. Our tertiary unit set up tele-oculoplastics clinics for all new patients referred for benign eyelid lesions comprising tele-consultation with antecedent patient photograph: Benign Eyelid Lesion Pathway (BELP). One year on, we describe a retrospective analysis of 974 patients looking at distinct parameters of effectiveness.

Methods: We retrospectively collected data from electronic patient records (EPR) for BELP patients from July 2020 to August 2021 (n = 974). We analysed time efficiency (referral time to treatment plan, consultation duration in minutes, average waiting times, number of patients seen per clinician and DNA rate), accessibility, safety (via video surveillance clinic) and theatre utilisation.

Results: 57.3% (n = 558) were listed for a surgical procedure direct from tele-consultation with 94.9% (n = 513) of these proceeding to surgery; 22.8% (n = 222) were discharged, 10.7% (n = 104) had further video follow-up and 6.7% (n = 65) required face-to-face follow-up. Our results showed efficient referral-to-treatment times, waiting times, consultation times and non-attendance rate. There was only a 2.57% non-attendance rate. There was no missed diagnosis of a malignancy of a presumed benign lesion.

Conclusion: Tele-oculoplastics provides a streamlined, safe, effective, and logistically convenient way to review benign eyelid lesions. With the increased waiting times for referral to biopsy of eyelid lesions, this clinic shows it is imperative to provide digital accessibility for patient assessment and booking to operating theatre.
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http://dx.doi.org/10.1038/s41433-022-02166-4DOI Listing
July 2022

Rituximab for thyroid-associated ophthalmopathy.

Cochrane Database Syst Rev 2022 06 16;6:CD009226. Epub 2022 Jun 16.

Moorfields and UCL Institute of Ophthalmology BMRC, Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Background: Thyroid-associated ophthalmopathy (TAO) is the most frequent extrathyroidal manifestation of Graves' disease, affecting up to 50% of patients. It has a great impact on quality of life. Rituximab (RTX) is a human/murine chimeric monoclonal antibody that targets the CD20 receptor on B-lymphocytes. Preliminary work has shown that blocking this CD20 receptor with RTX may affect the clinical course of TAO by reducing inflammation and the degree of proptosis.  OBJECTIVES: This review update, originally published in 2013, assesses the efficacy and safety of using RTX for the treatment of TAO.

Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 2), which contains the Cochrane Eyes and Vision Trials Register, Ovid MEDLINE, Ovid Embase, Latin American and Caribbean Health Science Information database (LILACS), the ISRCTN registry, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform (WHO ICTRP). There were no language restrictions in the electronic search for trials. We last searched the electronic databases on 22 February 2022.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) of RTX administered by intravenous infusion using any dosage regimen for the treatment of active TAO in adults, compared to placebo or glucocorticoids treatment.  DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently scanned titles and abstracts, and screened full-text reports of potentially relevant studies. The outcomes of interest in this review were: clinical activity score (CAS), NOSPECS severity scale, proptosis (mm), palpebral aperture (mm), extraocular motility (degrees or diplopia rating scale), quality of life and adverse effects.

Main Results: We identified two studies that met the inclusion criteria in this updated review. Across both studies, the mean age of participants was 55 years and 77% were women. RTX compared to intravenous methylprednisolone (IVMP) One study, conducted in Italy, compared RTX (n = 15 after one participant withdrew) with IVMP (n = 16) for active TAO (CAS ≥ 3 out of 7 or 4 out of 10). We judged this study to be at low risk of bias in most domains, but it was stopped early because of disease reactivation in the comparator group (5/16 participants). This study provided low-certainty evidence that RTX may result in CAS improvement at 24 weeks compared to IVMP (15/15 versus 12/16 improved by ≥ 2 points; risk ratio (RR) 1.32, 95% confidence interval (CI) 0.98 to 1.78). Only very low-certainty evidence was available for the other outcomes: NOSPECS improvement by 2 or more classes (3/15 versus 3/16; RR 1.07, 95% CI 0.25 to 4.49); proptosis improvement by 2 mm or more (0/15 versus 1/16; RR 0.35, 95% CI 0.02 to 8.08); palpebral aperture improvement by 3 mm or more (2/15 versus 0/16; RR 5.31, 95% CI 0.28 to 102.38); motility improvement by 1 class or more (3/15 versus 3/16; RR 1.07, 95% CI 0.25 to 4.49); and improvement on the Graves' ophthalmopathy QoL scale by at least 6 points for "functioning" (5/14 versus 8/13; RR 0.58, 95% CI 0.25 to 1.32), and "appearance" (9/14 versus 6/13; RR 1.39, 95% CI 0.69 to 2.82). Adverse events were more common in the RTX group (RR 1.39, 95% CI 0.90 to 2.13; low-certainty evidence). Minor adverse effects (mild infusion reactions) were observed in most people receiving RTX at first infusion. Two participants experienced a major infusion reaction, likely cytokine release syndrome. RTX compared to placebo One study, conducted in the USA, enrolled 25 participants with active TAO (CAS ≥ 4 out of 7), comparing RTX (13 participants) to placebo. We judged this study to be at low risk of bias in most domains, but it was stopped early due to recruitment issues. It provided very low-certainty evidence on the following outcomes at 24 weeks: CAS improvement by 2 or more points (4/13 RTX versus 3/12 placebo; RR 1.23, 95% CI 0.34 to 4.40); NOSPECS improvement by 2 or more classes (2/13 versus 2/12; RR 0.92, 95% CI 0.15 to 5.56); proptosis improvement by 2 mm or more (2/13 versus 4/12; RR 0.46, 95% CI 0.10 to 2.08); palpebral aperture median change (0 mm in RTX group, in both eyes separately, versus -0.5 mm and 0.5 mm in placebo group right and left eye, respectively); motility median diplopia score (3 versus 2.5); SF-12 physical component median score (45.9 versus 40.3) and mental component median score (52.8 versus 46.1). More participants in the RTX group experienced adverse effects (8/13 versus 3/12; RR 2.46, 95% CI 0.84 to 7.18).  AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support the use of RTX in people with TAO. Future studies investigating RTX in people with active TAO may need to be multi-centre in order to recruit enough participants to make an adequate judgement on the efficacy and safety of this novel therapy.
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http://dx.doi.org/10.1002/14651858.CD009226.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202994PMC
June 2022

A patient-initiated treatment model for blepharospasm and hemifacial spasm: a randomized controlled trial.

BMC Neurol 2022 Mar 17;22(1):99. Epub 2022 Mar 17.

Moorfields Eye Hospital NHS Foundation Trust, Adnexal Department, London, UK.

Background: To test, in a two-arm, single center, superiority, randomized controlled trial, the effectiveness of and costs associated with a patient-initiated treatment model for people with hemifacial spasm (HFS) and blepharospasm (BEB) in comparison to usual care.

Methods: One hundred and thirty patients with HFS or BEB, aged 18 years or over, were recruited from a nurse-led botulinum toxin type A clinic at an eye hospital in the United Kingdom (UK), completed baseline measures and were randomized (1:1). The intervention group determined their own botulinum toxin type A (BoNT/A) treatment schedule during the trial period (9 months) and received an information leaflet with a "hotline" number to book an appointment. Usual care appointments were scheduled by treating clinicians. Data analysts were blind to study group. The primary outcomes were disease severity and functional disability, as measured by the Jankovic Rating Scale and Blepharospasm Disability Index, respectively. Secondary outcomes included quality of life, anxiety and depression, satisfaction with care, confidence in the service, economic costs and employment days lost.

Results: Sixty-five patients were randomized to each group. The intervention demonstrated no statistically significant difference to usual care for any of primary outcomes. On secondary outcomes the levels of anxiety differed significantly (F = 1.65, p = 0.02), with the intervention arm exhibiting a decrease and the control arm an increase (Hedges' g = - 0.26 [99% CI -0.83, 0.32]). No other statistically significant differences were found for secondary outcomes. Overall healthcare costs and costs to the patient were on average £198.95 less (95% CI -£256.76, £654.67; p = 0.10) per participant for those in the intervention compared to usual care, although this finding was not significant.

Conclusions: We did not observe differences between the patient-initiated treatment model and usual care for people with BEB or HFS, on any primary outcome measure, quality of life, or depression. The patient-initiated treatment model may, however, have the potential to save healthcare costs and reduce anxiety. Patients using this new model were also equally as satisfied in the service and confident in their care as those receiving treatment as usual.

Trial Registration: Clinicaltrials.gov ID NCT02577224 , 16th October 2015.
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http://dx.doi.org/10.1186/s12883-022-02603-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928587PMC
March 2022

Telemedicine in oculoplastic and adnexal surgery: clinicians' perspectives in the UK.

Br J Ophthalmol 2021 Apr 28. Epub 2021 Apr 28.

Adnexal Department, Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Background/aims: The COVID-19 has facilitated a paradigm shift in the sphere of ophthalmic telemedicine: its utility is no longer limited to providing care to remote regions, rather it is expeditiously being adopted as the new standard of care. The aim of our paper is to explore the current attitudes of oculoplastic surgeons towards telemedicine and its utility in the present landscape and its prospects in the future.

Methods: A 39-item questionnaire was distributed to consultant oculoplastic surgeons practising across the UK and anonymised responses were collected and analysed.

Results: The COVID-19 pandemic has allowed rapid implementation of telemedicine services in oculoplastic departments across the UK with 86.6% of the respondents incorporating telemedicine into the routine clinical practice. Clinicians reported a statistically significant increase in utility of telemedicine, confidence in using telemedicine and quality of infrastructure available to employ telemedicine following the COVID-19 outbreak. The greatest utility of telemedicine is in triaging, postoperative assessment and eyelid lesion assessment. Main barriers to implementation of telemedicine included difficulties in conducting clinical examinations, lack of administrative support and poor access to digital technologies for patients. Overall, most clinicians were satisfied with the impact of telemedicine services and almost all experts foresee themselves continuing to use telemedicine in the future.

Conclusions: Telemedicine has become an integral part of the oculoplastic service delivery since the COVID-19 pandemic its use is likely to continue. Further development of digital infrastructure and improvement of clinical examination capabilities are required to enable its wider adoption.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318696DOI Listing
April 2021

Recurrent epiphora after dacryocystorhinostomy surgery: Structural abnormalities identified with dacryocystography and long term outcomes of revision surgery : Success rates of further surgery following failed dacryocystorhinostomy surgery.

BMC Ophthalmol 2021 Mar 5;21(1):117. Epub 2021 Mar 5.

Moorfields Eye Hospital NHS Trust, 162 City Road, London, EC1V2PD, UK.

Background: To investigate the aetiopathology of recurrent epiphora or stickiness after dacryocystorhinostomy (DCR) surgery, identifiable on dacryocystography (DCG), and to assess the success rates of secondary corrective surgeries.

Methods: Consecutive post-DCR DCG images from patients with recurrent symptoms were reviewed between 2012 and 2015.

Results: One hundred fifty-nine eyes of 137 patients were evaluated. Fifty-eight DCGs showed normal postoperative findings, 4 an upper/lower canalicular block, 13 a common canalicular block, 31 a completely closed anastomosis, 50 a narrow anastomosis, and 3 an anastomosis draining into a nasal sinus. The most successful corrective procedures for each failure category were: Lester Jones Tube (LJT) for a normal post-operative DCG (17/18 success), Sisler trephination with tubes for upper/lower canalicular block (1/2 success), redo-DCR with tube for common canalicular blockage (5/6 success), redo-DCR +/- tube for completely closed anastomosis (12/16 success), LJT followed by redo-DCR +/- tube for narrow surgical anastomosis (1/1 and 17/27 success respectively), and redo-external-DCR with tube for anastomosis into a nasal sinus (1/1 success). Redo-DCR was ineffective in patients who had good post-DCR anatomical patency (22% success).

Conclusion: This is the first study to report success rates of redo-DCR surgery according to anatomical findings confirmed by DCG. The outcome flow diagram help clinicians recommend procedures that are most likely to be successful for their patient's specific anatomical abnormality. It also provides a visual tool for the shared decision-making process. Notably, symptomatic patients with a normal DCG post DCR are unlikely to benefit from redo-DCR, with a LJT being the recommended next step.
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http://dx.doi.org/10.1186/s12886-021-01869-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934262PMC
March 2021

Quantitative Assessment of Orbital Decompression Surgery Using Photogrammetric Stereoimaging.

Ophthalmic Plast Reconstr Surg 2021 Sep-Oct 01;37(5):420-423

Adnexal Service, Moorfields Eye Hospital.

Purpose: To evaluate periorbital volume changes, using quantitative photogrammetric stereoimaging, after bony orbital decompression for thyroid eye disease (TED) and compare this to changes in Hertel exophthalmometry. Tissue volumes of the upper and lower eyelids were also assessed independently.

Design: Prospective, nonrandomized, nonconsecutive series of patients.

Subjects: Adults with inactive TED who had elected to undergo bony orbital decompression at Moorfields Eye Hospital between 2015 and 2017.

Methods: With their eyes gently closed, patients with inactive TED underwent imaging using the VECTRA M3 system (Canfields Imaging, Fairfield, NJ), both before and at least 3 months after orbital decompression. Proptosis was assessed by Hertel exophthalmometry. Using the manufacturer's software, changes in periorbital volumes between the preoperative and postoperative images were calculated for the upper and lower eyelids. The Pearson product-moment correlation coefficient was used to assess the linear relationship between changes in periorbital volume and exophthalmometry.

Main Outcome Measures: Change in stereoimaging volumes of the upper and lower eyelids, and clinical proptosis as measured with Hertel exophthalmometry.

Results: Thirty-three patients (11 males; 33%) underwent lateral decompression (39 orbits in 26 patients), lateral decompression with complete ethmoidectomy (3 orbits in 3 patients), combined decompression of lateral wall, medial wall, and medial half of floor (10 orbits in 6 patients), or bilateral lateral, medial, and complete floor decompression (1 patient). The corresponding average volumetric changes were 1.74 ml (median 1.64; range 0.39-3.73 ml), 3.38 ml (median 3.38, range 1.89-4.88 ml), 4.05 ml (median 3.53, range 1.72-6.43 ml), and 4.52 ml (range 4.36-4.68 ml), respectively. Similarly, the average reduction in proptosis was 3.6 mm (median 3; range 1.5-7 mm), 5.3 mm (median 5; range 5-6 mm), 7.4 mm (7.5; range 6-9 mm), and 9 mm (range 8-10 mm). Periorbital volume changes were related to the reduction in exophthalmometry (r = 0.713, p < 0.0001), and reduction of lower eyelid volume did not increase further with more than two-wall decompression.

Conclusion: Graded orbital decompression reduces both proptosis and the upper and lower eyelid tissue volumes, the eyelid changes being likely to influence decisions about future restorative eyelid surgery. The significant changes in eyelid profiles underlines the established principle of thyroid periocular rehabilitation, namely decompression, then strabismus surgery, and finally eyelid surgery.
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http://dx.doi.org/10.1097/IOP.0000000000001885DOI Listing
October 2021

A Tenon's capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery.

PLoS One 2020 3;15(11):e0241569. Epub 2020 Nov 3.

UCL Institute of Ophthalmology, UCL, London, United Kingdom.

Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but the most common cause of failure is scarring at the incision site. This occurs in the conjunctiva/Tenon's capsule layer overlying the scleral coat of the eye. Currently used antimetabolite treatments to prevent post-surgical scarring are non-selective and are associated with potentially blinding side effects. Developing new treatments to target scarring requires both a better understanding of wound healing and scarring in the conjunctiva, and new means of delivering anti-scarring drugs locally and sustainably. By combining plastic compression of collagen gels with a soft collagen-based layer, we have developed a physiologically relevant model of the sub-epithelial bulbar conjunctiva/Tenon's capsule interface, which allows a more holistic approach to the understanding of subconjunctival tissue behaviour and local drug delivery. The biomimetic tissue hosts both primary human conjunctival fibroblasts and an immune component in the form of macrophages, morphologically and structurally mimicking the mechanical proprieties and contraction kinetics of ex vivo porcine conjunctiva. We show that our model is suitable for the screening of drugs targeting scarring and/or inflammation, and amenable to the study of local drug delivery devices that can be inserted in between the two layers of the biomimetic. We propose that this multicellular-bilayer engineered tissue will be useful to study complex biological aspects of scarring and fibrosis, including the role of inflammation, with potentially significant implications for the management of scarring following glaucoma filtration surgery and other anterior ocular segment scarring conditions. Crucially, it uniquely allows the evaluation of new means of local drug delivery within a physiologically relevant tissue mimetic, mimicking intraoperative drug delivery in vivo.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241569PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608904PMC
December 2020

Videographic Analysis of Blink Dynamics following Upper Eyelid Blepharoplasty and Its Association with Dry Eye.

Plast Reconstr Surg Glob Open 2020 Jul 21;8(7):e2991. Epub 2020 Jul 21.

Moorfields Eye Hospital, UCL Institute of Ophthalmology NIHR Biomedical Research Centre for Ophthalmology, London, United Kingdom.

This study was undertaken to characterize the effects of upper eyelid blepharoplasty on blink dynamics and to evaluate the hypothesis that changes in blink dynamics following blepharoplasty are associated with postoperative dry eye.

Methods: The voluntary blink of 14 eyes of 7 patients with dermatochalasis undergoing upper eyelid blepharoplasty was recorded with a high-speed camera preoperatively and 6-8 months postoperatively, alongside a group of 11 controls. The images were analyzed for palpebral aperture, blink duration, and maximum velocity during opening and closing phases. Patients undergoing blepharoplasty were assessed for dry eye symptoms pre- and postoperatively at 6-8 months using the ocular surface disease index score.

Results: Despite intraoperative orbicularis oculi resection, there was no significant compromise of blink duration or maximum velocity of eyelid opening or closure post-blepharoplasty. Postoperatively, patients had an increase in palpebral aperture compared with both preoperatively (8.71 versus 7.85 mm; = 0.013) and control groups (8.71 versus 7.87 mm; = 0.04). Postoperatively at 6-8 months, there was an increase in dry eye symptoms in 6 of 7 patients compared with preoperatively (ocular surface disease index, 16.6 versus 12.5; < 0.05). There was no positive correlation between the increase in palpebral aperture and the increase in dry eye symptoms ( = -0.4; = 0.30).

Conclusions: Using modern videographic technology, this study demonstrates that upper eyelid blepharoplasty results in an increase in resting palpebral aperture but has no effect on dynamic blink parameters. Changes in palpebral aperture or blink dynamics are unlikely to be the cause of dry eye syndrome following blepharoplasty.
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http://dx.doi.org/10.1097/GOX.0000000000002991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413808PMC
July 2020

Topical anaesthesia plus intracameral lidocaine versus topical anaesthesia alone for phacoemulsification cataract surgery in adults.

Cochrane Database Syst Rev 2020 Jul 28;7:CD005276. Epub 2020 Jul 28.

External Disease Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Background: Phacoemulsification cataract surgery is usually performed in adults under local anaesthesia. Topical anaesthesia, which involves instilling anaesthetic drops to the ocular surface prior to and during surgery, has found large acceptance internationally. It is safe and allows for rapid patient turnover and visual recovery. Some surgeons have supplemented topical anaesthesia with intracameral lidocaine, reasoning that this may further reduce intraoperative pain, particularly during surgical stages involving manipulation of intraocular structures and rapid changes in fluid dynamics. This review, originally published in 2006 and updated in 2020, explores the efficacy and safety of using supplementary intracameral lidocaine in phacoemulsification cataract surgery.

Objectives: To assess whether supplementing topical anaesthesia with intracameral lidocaine for phacoemulsification cataract surgery in adults reduces intraoperative and postoperative pain, and to assess differences in participant satisfaction, need for additional intraoperative anaesthesia, surgeon satisfaction, measures of intraocular toxicity, and adverse effects attributable to choice of anaesthesia.

Search Methods: We searched CENTRAL, MEDLINE, Embase, LILACS BIREME iAH, and six trial registries on 4 February 2020. We also searched the reference lists of identified studies. There were no language restrictions.

Selection Criteria: We included only randomized controlled trials (RCTs) where participants underwent phacoemulsification for age-related cataract under topical anaesthesia with or without intracameral lidocaine either in two eyes of the same participant, or in different participants. We also included studies that used oral or intravenous sedation in addition to local anaesthesia.

Data Collection And Analysis: Two review authors independently extracted data and assessed trial methodological quality using standard Cochrane procedures.

Main Results: We identified five new RCTs in this updated review. We included a total of 13 trials in the review, conducted in the UK, the USA, Australia, Italy, Canada, Taiwan, Singapore, India, and Pakistan, and comprising 2388 eyes of 2355 participants (one study was a paired-eye study with each participant acting as their own control). The age range of participants was 34 to 95 years. We excluded studies that only included low-risk participants and excluded more difficult operative cases, for example hard lens nuclei or small pupils. We excluded studies assessing only participants with Fuchs' endothelial dystrophy. We judged one study as at high risk for selection bias. We assessed five studies as having an unclear risk of bias for random sequence generation and seven studies an unclear risk of bias for allocation concealment. We judged three studies as at high risk of performance bias, as the surgeon was not blinded, and two studies as at unclear risk of bias for this domain. No studies were judged as at high risk for detection bias, but five studies were judged to have an unclear risk of bias for this domain. We judged all 13 included studies to have a low risk of attrition bias and an unclear risk of reporting bias. Data from eight RCTs favoured topical anaesthesia plus intracameral lidocaine 0.5% to 1% over topical anaesthesia alone for reducing intraoperative pain when measured using a 10-point visual analogue scale, analysed as a continuous outcome. Mean pain score was 0.26 lower in the supplemental intracameral lidocaine group (95% confidence interval (CI) -0.39 to -0.13, 1692 eyes, moderate-quality evidence). Data from seven RCTs favoured supplemental intracameral lidocaine for reducing intraoperative pain when measured as a dichotomous outcome. The odds ratio of experiencing any pain was 0.40 versus the topical anaesthesia-only group (95% CI 0.29 to 0.57, 1268 eyes, moderate-quality evidence). Data from four RCTs did not show any additional benefit on postoperative pain when measured using a 10-point visual analogue scale (mean difference 0.12 points, 95% CI -0.29 to 0.05, 751 eyes, moderate-quality evidence). The impact on participant satisfaction was uncertain as only one small study investigated this outcome. The study suggested no difference between groups (mean difference 0.1 points, 95% CI -0.47 to 0.27, 60 eyes, low-quality evidence). Data from seven RCTs did not demonstrate a difference between groups in the need for additional intraoperative anaesthesia (odds ratio 0.88, 95% CI 0.56 to 1.39, 1194 eyes of 1161 participants; low-quality evidence), although this result is uncertain. A variety of measures were reported relating to possible intraocular toxicity. Data from four RCTs did not demonstrate a difference between groups in mean percentage corneal endothelial cell count change from pre- to postoperatively (mean difference 0.89%, 95% CI -1.12% to 2.9%, 254 eyes of 221 participants, moderate-quality evidence). Synthesis of the evidence from eight RCTs identified no difference in intraoperative adverse events between groups (odds ratio 1.00, 95% CI 0.32 to 3.16, 1726 eyes, low-quality evidence). This result should be interpreted with caution, mainly due to a lack of clear definitions of adverse events, low numbers of events, heterogeneity between studies, and large confidence intervals. Large observational studies may have been more appropriate for looking at this outcome.

Authors' Conclusions: There is moderate-quality evidence that supplementation of topical anaesthesia with intracameral lidocaine 0.5% to 1% for phacoemulsification cataract surgery in adults reduces participant perception of intraoperative pain. The odds of experiencing any pain (as opposed to no pain) were 60% less for the topical anaesthesia plus intracameral lidocaine group versus the topical anaesthesia-only group. However, the numerical amplitude of the effect may not be of great clinical significance on the continuous pain score scale. Generally, the pain scores were consistently low for both techniques. We found moderate-quality evidence that there is no additional benefit of intracameral lidocaine on postoperative pain. There is insufficient evidence to determine the impact on participant satisfaction and need for additional intraoperative anaesthesia due to low-quality evidence. There is moderate-quality evidence that intracameral lidocaine supplementation does not increase measures of intraocular toxicity, specifically loss of corneal endothelial cells. There is low-quality evidence that the incidence of intraoperative adverse events is unchanged with intracameral lidocaine supplementation, but as RCTs are not the optimum medium for looking at this, this result should be interpreted with caution. Further research specifically investigating the adverse effects of intracameral anaesthesia might help to better determine its safety profile. Economic evaluations would also be useful for detailing cost implications.
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http://dx.doi.org/10.1002/14651858.CD005276.pub4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190979PMC
July 2020

Teprotumumab: a disease modifying treatment for graves' orbitopathy.

Thyroid Res 2020 4;13:12. Epub 2020 Jul 4.

Adnexal Department, Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London, EC1V 2PD UK.

Background: On 21st January 2020, the FDA approved Tepezza (teprotumumab-trbw) for the treatment of active Graves' orbitopathy (GO) in adults. This approval was based on positive results from two multinational randomised double-blind placebo-controlled clinical trials.

Discussion: This article discusses the outcomes of those trials and the potential role of teprotumumab in altering current treatment paradigms in Graves' orbitopathy. Future challenges are explored, including the need to confirm its disease-modifying effect, to establish its optimal position in the treatment pathway, and to define the appropriate subset of patients who would benefit from its use.

Conclusions: The results from these two large clinical trials have shown teprotumumab to have remarkable effects on multiple clinical outcomes in GO, particularly in its ability to reverse proptosis. It may herald a new era in the treatment of thyroid eye disease and could offer an alternative to surgery and its associated complications. Additional studies will continue to shape the treatment of GO and define the role of teprotumumab within the treatment paradigm.
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http://dx.doi.org/10.1186/s13044-020-00086-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334856PMC
July 2020

Which factors impact on quality of life for adults with blepharospasm and hemifacial spasm?

Orbit 2021 Apr 1;40(2):110-119. Epub 2020 Mar 1.

Moorfields Eye Hospital NHS Foundation Trust , London, UK.

: Benign essential blepharospasm (BEB) and hemifacial spasm (HFS) are debilitating conditions causing spasms to the eyes and/or face and can significantly impact on quality of life (QoL). Initial research has highlighted potential factors impacting on QoL in BEB, but there remains a wealth of demographic, clinical, and psychosocial factors that may contribute to QoL but have not received attention. : Cross-sectional baseline data were collected before a single-masked randomised controlled trial from 130 adults with BEB and HFS recruited from botulinum toxin clinics at Moorfields Eye Hospital, London. QoL was measured using the 24-item Craniocervical Dystonia Questionnaire (CDQ24), which provides a total score and five subscale scores relating to , and . Treating clinicians provided clinical data. Hierarchical multiple regressions were performed on this baseline data to identify significant predictors of QoL. : and were the areas most impacted upon whilst patients experienced better adjustment in relation to , and scores were explained by the model (80% variance) and were significantly associated with appearance concerns, emotional representations, perceived negative consequences of the condition, mood, and dose of botulinum toxin. : Patients with BEB and HFS report a detrimental impact on ADL and perceived stigma in relation to their condition. Predominantly, individual perceptions and mood are associated with QoL in this population, rather than demographic and clinical factors, signifying areas to target in the design of future healthcare services or interventions.
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http://dx.doi.org/10.1080/01676830.2020.1733028DOI Listing
April 2021

Validating three-dimensional imaging for volumetric assessment of periorbital soft tissue.

Orbit 2021 Feb 14;40(1):9-17. Epub 2020 Jan 14.

Adnexal Department, Moorfields Eye Hospital , London, UK.

: To evaluate the accuracy and interobserver variability of three-dimensional (3D) stereophotogrammetric imaging for volumetric assessment in the periorbital region and to propose a protocol for measurement. : A cross-sectional study was performed. Fifty-eight normal adult subjects had photographs taken using the VECTRA M3 imaging system on two separate occasions at a single center teaching hospital. The primary study outcome measurement was mean volume change in the periorbital region, using different methods of image analysis with the following variables: registration method, eyes open or closed, eyelids measured separately or together, extension of area measured to include mid-face. Accuracy was defined as the agreement between paired images with no measured change in volume (0 mL). The agreement between two independent observers was assessed using Bland-Altman plots. : There was a statistically significant difference ( < .0001) between the different methods of measurement, with registration of images having the most effect (partial eta squared 0.229). A mean change in volume of 0.11 ± 0.13 mL was reported for the most accurate method. Agreement between observers was confirmed (highest Intraclass Correlation Coefficient 0.63). : Assessment of volumetric change in the periorbital region using 3D image reconstruction is accurate with good interobserver repeatability and is suitable for clinical use. A protocol for data acquisition using the VECTRA M3 is proposed. 3D image reconstruction holds promise to enable diagnosis, treatment monitoring, and surgical outcome evaluation in ocular adnexal disease.
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http://dx.doi.org/10.1080/01676830.2020.1711780DOI Listing
February 2021

New insights into the pathogenesis and nonsurgical management of Graves orbitopathy.

Nat Rev Endocrinol 2020 02 30;16(2):104-116. Epub 2019 Dec 30.

Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK.

Graves orbitopathy, also known as thyroid eye disease or thyroid-associated orbitopathy, is visually disabling, cosmetically disfiguring and has a substantial negative impact on a patient's quality of life. There is increasing awareness of the need for early diagnosis and rapid specialist input from endocrinologists and ophthalmologists. Glucocorticoids are the mainstay of treatment; however, recurrence occurs frequently once these are withdrawn. Furthermore, in >60% of cases, normal orbital anatomy is not restored, and skilled rehabilitative surgery is required. Clinical trials have shown that considerable benefit can be derived from the addition of antiproliferative agents (such as mycophenolate or azathioprine) in preventing deterioration after steroid cessation. In addition, targeted biologic therapies have shown promise, including teprotumumab, which reduces proptosis, rituximab (anti-CD20), which reduces inflammation, and tocilizumab, which potentially benefits both of these parameters. Other strategies such as orbital radiotherapy have had their widespread role in combination therapy called into question. The pathophysiology of Graves orbitopathy has also been revised with identification of new potential therapeutic targets. In this Review we provide an up-to-date overview of the field, outline the optimal management of Graves orbitopathy and summarize the research developments in this area to highlight future research questions and direct future clinical trials.
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http://dx.doi.org/10.1038/s41574-019-0305-4DOI Listing
February 2020

Long-Term Outcomes of StopLoss Jones Tubes for Epiphora in Patients With Early or Multiple Loss of Lester Jones Tubes.

Ophthalmic Plast Reconstr Surg 2020 Mar/Apr;36(2):127-131

Lacrimal Clinic, Moorfields Eye Hospital.

Purpose: Extrusion is the most common cause of failure in conventional Lester Jones tubes (LJTs). StopLoss Jones tubes (SLJTs) with distal flange are designed to reduce this complication. This study compared the survival of SLJTs with their prior LJTs and control patients with LJTs-only.

Methods: Retrospective review of consecutive LJT or SLJT insertion between January 2014 and December 2016.

Results: Twenty-eight eyes of 23 patients had 31 SLJTs. Before their SLJTs, these patients had 116 cumulative failed LJTs. Forty-seven eyes of 34 patients had 59 LJTs only. Fifty-two percent of SLJT group and 18% of LJT-only group had complex medial canthal conditions (p = 0.003). Compared to their previous LJTs, the SLJTs were less likely to extrude (3% SLJT vs. 64% prior LJT, p < 0.0001); there was no statistical difference in rates of sinking in (26% SLJT vs. 13% prior LJT, p = 0.0964). The median survival of LJTs in those who went on to have a SLJT was 3.5 months. SLJT insertion significantly lengthened the median survival to 26 months (p < 0.0001), comparable to the LJT-only group (25.5 months, p = 0.45). While extrusion was also the most common complication in the LJT-only group, this occurred only in 20% of eyes; tube failure from sink-in occurred in 14% of eyes.

Conclusions: SLJTs, in patients prone to multiple or early prior LJT losses, can be used to rescue this group and allow them to regain a similar survival curve to the less complicated LJT-only group. Rates of tube extrusion are significantly reduced with the use of SLJT.
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http://dx.doi.org/10.1097/IOP.0000000000001479DOI Listing
March 2021

The first UK national blepharospasm patient and public involvement day; identifying priorities.

Orbit 2020 Aug 30;39(4):233-240. Epub 2019 Aug 30.

Moorfields Eye Hospital NHS Foundation Trust , London, UK.

Purpose: We describe the planning and outcomes of the first 'Blepharospasm Day' in the UK. Blepharospasm is a distressing condition for patients and carers. Our 'patient and public involvement' event aimed to: cultivate a more informed patient group via active dialogue, help clinicians more effectively prioritise research and to facilitate peer-to-peer support for affected patients and public.

Design: A national one-day event was organised by the oculoplastics department at Moorfields Eye Hospital. The event was divided into informative lectures delivered by professionals and a patient panel, during which patients shared their experiences and expectations.

Methods: Data were collected from a variety of sources including: an interactive voting "LiveWall" poster, a pre-event questionnaire; "living with Blepharospasm", transcripts from patient panel discussions; and a feedback questionnaire.

Results: The event was well-received with 100% of respondents rating it good or excellent. Four research themes were identified: "aetiology", "alternative treatments", "faster, more accurate diagnosis", and "symptom control". Delegates' self-reported knowledge of blepharospasm increased significantly after the event. Limitations of the BdSI severity-assessment tool were noted with 22% of respondents failing to utilise it appropriately.

Conclusion: Through our innovative "Blepharospasm Day", patient's priorities for research were identified, delegates understanding of blepharospasm increased and an independent blepharospasm patients-representatives' group was established; a first in the UK. Furthermore, short-fallings identified in the BdSI tool highlight the need for better severity-assessment tools. We demonstrate the benefits of the 'patient and public involvement' approach in the management of complex conditions such as blepharospasm.

Abbreviations: PPI: Patient and public involvement; SLV-PSP: sight loss and vision sector - priority setting partnership; BRC: Biomedical Research Centre; NIHR: National Institute for Health Research; BsDI: Blepharospasm Disability Index.
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http://dx.doi.org/10.1080/01676830.2019.1657469DOI Listing
August 2020

Macrophages promote a profibrotic phenotype in orbital fibroblasts through increased hyaluronic acid production and cell contractility.

Sci Rep 2019 07 3;9(1):9622. Epub 2019 Jul 3.

UCL Institute of Ophthalmology, London, EC1V 9EL, UK.

Graves' orbitopathy (GO) is an autoimmune inflammatory disease affecting the orbit. Orbital fibroblasts are a key component in GO pathogenesis, which includes inflammation, adipogenesis, hyaluronic acid (HA) secretion, and fibrosis. Macrophages are thought to participate in the immunological stage of GO, but whether they can directly affect the fibroblasts phenotype and modulate disease progression is unknown. We previously showed that GO adipogenic and fibrotic phenotypes could be modelled in a pseudo-physiological 3D environment in vitro. Here, we introduced macrophages in this 3D culture model to investigate role for macrophages in modulating adipogenesis, HA production, and contractility in orbital fibroblasts. Macrophages had a minimal effect on lipid droplet formation in fibroblasts, but significantly increased HA production and cell contractility, suggesting that they may promote the fibrotic phenotype. This effect was found to be mediated at least in part through phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) activation and linked to an increase in actin polymerization and protrusive activity in fibroblasts. Overall our work shows for the first time a direct role for macrophages in modulating the fibroblasts' phenotype in GO, supporting a role for macrophages in the progression of the fibrotic phenotype through induction of HA production and stimulation of the contractile phenotype in orbital fibroblasts.
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http://dx.doi.org/10.1038/s41598-019-46075-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610127PMC
July 2019

Characterizing Congenital Double Punctum Anomalies: Clinical, Endoscopic, and Imaging Findings.

Ophthalmic Plast Reconstr Surg 2019 Nov/Dec;35(6):549-552

Lacrimal Clinic, Moorfields Eye Hospital, London, United Kingdom.

Purpose: To characterize the anatomical anomaly of congenital double puncta, identify factors contributing to epiphora and its treatment.

Methods: Retrospective review of patients presenting with epiphora and a double lacrimal punctum over a 6-month period.

Results: Five consecutive patients (3 female) were identified. The median age was 50 years (range 34-76). Investigations included punctum optical coherence tomography, dacryocystography, and canalicular endoscopy. The medial punctum was more morphologically abnormal when compared with healthy puncta, with optical coherence tomography showing no vertical canalicular component in 80% (4/5) of patients, and a more superficial than usual horizontal canaliculus in 80% (4/5). Dacryocystography and canalicular endoscopy showed the junction of the 2 inferior canaliculi, which was very proximal in 1, mid canalicular in 2, and at the level of the common canaliculus in 2. In 1 patient, the only abnormality identified was the double lower punctum, with a high tear meniscus and delayed fluorescence dye disappearance test. They underwent endonasal dacryocystorhinostomy with improvement of epiphora. In the other 4 patients, causes of epiphora were nasolacrimal duct stenosis with mucocoele, punctal stenosis, common canalicular stenosis with nasolacrimal duct stenosis, upper canaliculitis, and blepharitis. Their treatments included endonasal dacryocystorhinostomy, punctoplasty, canaliculotomy, and blepharitis treatment. All had improvement of epiphora following treatment.

Conclusions: These findings suggest that the underlying canalicular anomalies are varied and that the clinical manifestation is also heterogenous. Optical coherence tomography imaging suggests that the medial of the 2 puncta is the more morphologically abnormal one, with dacryocystography and canalicular endoscopy demonstrating different accessory canaliculi lengths.Double puncta coexist with a range of other nasolacrimal pathologies. OCT suggests that the medial of the 2 double puncta is the abnormal one, with DCG and endoscopy demonstrating a range of accessory canaliculus lengths.
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http://dx.doi.org/10.1097/IOP.0000000000001368DOI Listing
January 2020

Sensory Trick Frames: A New Device for Blepharospasm Patients.

J Mov Disord 2019 01 16;12(1):22-26. Epub 2019 Jan 16.

Adnexal Service, Moorfields Eye Hospital, London, UK.

Objective: To determine whether the use of unique customized spectacles provided with modified side arms may be helpful in reducing benign essential blepharospasm (BEB) in patients describing periocular sensory tricks (ST).

Methods: A prospective descriptive study of patients with BEB with positive periocular or temporal region ST phenomenon response under the care of the Botox Clinic at Moorfields Eye Hospital, London, UK. Nine consecutive patients with BEB describing ST were recruited, and the disease frequency and severity were assessed with the Jankovic Rating Scale (JRS) and the Blepharospasm Disability Index (BSDI) before and after the use of the sensory trick frames (STF).

Results: A reduction in the score was noted in both severity (p = 0.0115) and frequency patterns (p = 0.0117) in the JRS in patients using the STF. A significant reduction of the BSDI score was also observed (p = 0.0314).

Conclusion: All the patients selected and fitted with the STF had a reduction in spasms and related symptoms. This new device may be helpful in some selected BEB patients who previously responded positively to periocular pressure alleviating maneuvers.
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http://dx.doi.org/10.14802/jmd.18010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369377PMC
January 2019

Tocilizumab for thyroid eye disease.

Cochrane Database Syst Rev 2018 11 27;11:CD012984. Epub 2018 Nov 27.

Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London, UK, EC1V 2PD.

Background: Thyroid eye disease (TED) is an autoimmune disorder that constitutes a major clinical and therapeutic challenge. Current treatment options for moderate-to-severe TED include immunotherapy, orbital radiotherapy and decompression surgery. Limited drugs of proven efficacy are available for the treatment of people with TED. Given the role in the pathogenesis of TED of interleukin (IL)-6 expression in adipocytes, fibroblasts and macrophages, the proposed theory is that inhibition of IL-6 by tocilizumab may be an effective treatment in TED by directly reducing the inflammatory response. In addition, there is an unmet need for a new treatment that can modify the natural course of the disease and reduce the incidence of late complications that can occur as a result of fibrosis following inflammation.

Objectives: To investigate the efficacy and harms of tocilizumab for the treatment of people with TED.

Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); MEDLINE Ovid; Embase Ovid; LILACS BIREME; OpenGrey; the ISRCTN registry; ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the EU Clinical Trials Register. The date of the search was 31 July 2018.

Selection Criteria: We searched for trials of tocilizumab administered by intravenous infusion using any dosage regimen, compared with placebo or intravenous glucocorticoid therapy for people with TED.

Data Collection And Analysis: We planned to use standard methods recommended by Cochrane. The primary outcome was change in TED score (as defined by investigators). Secondary outcomes included measurement of the following parameters: change in proptosis, change in extraocular motility, change in palpebral aperture measurements, number of relapses, development of optic neuropathy and change in quality of life score. We planned to measure these outcomes at three months (range two to six months) and 12 months (range six to 18 months) post-treatment. Adverse outcomes included any adverse effects identified in the trials at any time point.

Main Results: No studies met the inclusion criteria of this review. We found one randomised, placebo-controlled, double masked study (NCT01297699). This study plans to evaluate the efficacy and harms of tocilizumab administration in people with moderate-to-severe or sight-threatening graves' ophthalmopathy (GO), that had not responded adequately to treatment with intravenous corticosteroid pulses. It was completed in December 2015 and will be assessed for inclusion in the review when data become available.

Authors' Conclusions: There is currently no evidence from randomised controlled trials evaluating the efficacy and harms of tocilizumab for the treatment of people with TED.
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http://dx.doi.org/10.1002/14651858.CD012984.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517231PMC
November 2018

MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma.

Sci Rep 2018 05 14;8(1):7531. Epub 2018 May 14.

Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, London, UK.

Sebaceous gland carcinoma (SGC) is a rare, but life-threatening condition with a predilection for the periocular region. Eyelid SGC can be broadly categorised into two subtypes, namely either nodular or pagetoid with the latter being more aggressive and requiring radical excision to save life. We have identified key altered microRNAs (miRNA) involved in SGC shared by both subtypes, hsa-miR-34a-5p and hsa-miR-16-5p. However, their gene targets BCL2 and MYC were differentially expressed with both overexpressed in pagetoid but unchanged in nodular suggesting different modes of action of these two miRNAs on BCL/MYC expression. Hsa-miR-150p is nodular-specifically overexpressed, and its target ZEB1 was significantly downregulated in nodular SGC suggesting a tumour suppressor role. Invasive pagetoid subtype demonstrated specific overexpression of hsa-miR-205 and downregulation of hsa-miR-199a. Correspondingly, miRNA gene targets, EZH2 (by hsa-miR-205) and CD44 (by hsa-miR-199a), were both overexpressed in pagetoid SGC. CD44 has been identified as a potential cancer stem cell marker in head and neck squamous cell carcinoma and its overexpression in pagetoid cells represents a novel treatment target. Aberrant miRNAs and their gene targets have been identified in both SGC subtypes, paving the way for better molecular understanding of these tumours and identifying new treatment targets.
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http://dx.doi.org/10.1038/s41598-018-25900-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951834PMC
May 2018

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

Lancet Diabetes Endocrinol 2018 04 31;6(4):299-309. Epub 2018 Jan 31.

Moorfields Eye Hospital NHS Foundation Trust, London, UK.

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 (p=0·86). The adjusted odds ratio (OR) 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 OR 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.
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http://dx.doi.org/10.1016/S2213-8587(18)30021-4DOI Listing
April 2018

Patients' expectations for the functional and psychosocial outcomes of orbital decompression surgery for thyroid eye disease: a qualitative study.

Psychol Health Med 2018 04 25;23(4):475-484. Epub 2017 Jul 25.

a School of Health Sciences, City, University of London , London , UK.

Patients with appearance-altering conditions may be dissatisfied with the outcomes of reconstructive surgery due to unmet expectations. This study explored patients' expectations of orbital decompression surgery for thyroid eye disease (TED) and whether these were met. Semi-structured interviews were conducted at two times: (1) in the weeks after patients were listed for decompression surgery and before surgery; (2) up to 12 months after surgery. Thematic analysis was performed for each time point, to identify themes within the data. Fourteen adults with TED were interviewed prior to surgery and five were followed up after surgery. Thematic analyses found: (1) Prior to surgery, patients had formed expectations through online information about the procedure, consultations with physicians, the impact TED had on their lives, and speaking to relevant others. Patients had specific expectations about the procedure, the recovery, post-operative appearance and post-operative vision. (2) After surgery, patients generally felt their appearance and well-being had improved. However, dissatisfaction was linked to unanticipated specific aspects of surgical care, recovery, or appearance. Dissatisfaction can arise from unmet expectations for the outcomes of reconstructive surgery. Physicians should be aware of the processes by which patients form expectations, for example different types and quality of online information. Ensuring that preoperative expectations are realistic could enhance satisfaction after surgery.
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http://dx.doi.org/10.1080/13548506.2017.1356930DOI Listing
April 2018

Teprotumumab for Thyroid-Associated Ophthalmopathy.

N Engl J Med 2017 05;376(18):1748-1761

From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine (T.J.S.), University of Michigan Medical School, Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial Plastic Surgery Division, Oregon Health and Science University, Portland (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.); the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee (G.J.H.); the Department of Clinical and Experimental Medicine, University of Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital, Washington University, St. Louis (S.M.C.); the Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision Development, New York (R.M.W., K.G., G.M.).

Background: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy.

Methods: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed.

Results: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes.

Conclusions: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).
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http://dx.doi.org/10.1056/NEJMoa1614949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718164PMC
May 2017

The Application of Infrared Imaging and Optical Coherence Tomography of the Lacrimal Punctum in Patients Undergoing Punctoplasty for Epiphora.

Ophthalmology 2017 06 17;124(6):910-917. Epub 2017 Mar 17.

Lacrimal Clinic, Moorfields Eye Hospital, London, United Kingdom; NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom. Electronic address:

Purpose: To determine the application of imaging the stenotic lacrimal punctum with infrared photographs and optical coherence tomography (OCT) and to identify characteristics of the lacrimal punctum in patients who benefit from punctoplasty.

Design: Case-control study.

Participants: Twenty patients with epiphora who were listed for punctoplasty and 20 healthy controls.

Methods: Prospectively, 20 patients listed for punctoplasty were asked to rate their epiphora, using the Munk score, before and after punctoplasty. They also underwent preoperative OCT and infrared imaging of the affected punctum. They were divided into 2 groups, depending on whether the epiphora improved, and were compared with 20 healthy controls.

Main Outcome Measures: Measurements of puncta from infrared and OCT images were obtained along with Munk scores of patient epiphora.

Results: The infrared image measurements were significantly smaller in those patients whose epiphora improved compared with those whose did not in both the area of the punctal aperture and in the maximum punctal diameter. Additionally, those patients with improvement in epiphora had a significantly smaller preoperative punctal diameter at 100 μm depth on OCT compared with healthy controls; this was not observed in patients whose epiphora failed to improve. There was no significant difference in the punctum diameter among the 3 groups at the punctum surface entrance or at 500 μm depth. Patients with epiphora had a higher tear meniscus within the punctum compared with healthy controls.

Conclusions: Lacrimal punctum infrared and OCT imaging may be helpful in predicting patients more likely to benefit symptomatically from punctoplasty, with patients with smaller puncta having greater symptomatic improvement. However, the results suggest that inner punctum diameter (not readily measurable by slit-lamp examination), rather than the surface diameter, is correlated with outcome. Additionally, OCT measurements of the tear meniscus height within the punctum may be related to the degree of epiphora.
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http://dx.doi.org/10.1016/j.ophtha.2017.01.054DOI Listing
June 2017

Characterizing the Occluded Lacrimal Punctum Using Anterior Segment Optical Coherence Tomography.

Ophthalmic Plast Reconstr Surg 2018 Jan/Feb;34(1):26-30

Lacrimal Clinic, Moorfields Eye Hospital, and NIHR Biomedical Research Centre for Ophthalmology, UCL Institute of Ophthalmology, London, United Kingdom.

Purpose: Epiphora is sometimes associated with an absent or occluded lacrimal drainage punctum (or puncta). This study uses noninvasive "enhanced depth" anterior segment optical coherence tomography (OCT) to give improved characterization and understanding of absent or fully occluded puncta and the underlying canaliculus.

Methods: Anterior segment spectral domain OCT images were collected prospectively from 9 lower puncta of 6 patients with epiphora and absent or fully occluded puncta, not amenable to dilation in clinic, to see if a canaliculus was visible on OCT imaging below the occluded punctum.

Results: An epithelial lined canalicular lumen was visible on OCT in 4 lower eyelid puncta from 2 patients and OCT identified 80% (4/5) of the canaliculi that were located on microscope-assisted punctal exploration. These lumens were seen within 580 μm depth from the eyelid margin surface. A half of the eyes in which a canaliculus was identified on OCT (the 2 eyes in a single patient) had resolution of epiphora following punctoplasty, and the other patient was found to have coexisting nasolacrimal duct stenosis and required later dacryocystorhinostomy. The positive predictive value for identifying a canaliculus on lower eyelid punctal exploration in acquired complete punctal occlusion (excluding the congenital case) was 1, with a negative predictive value of 1.

Conclusions: This study demonstrates that canaliculi can be imaged with OCT where formal access is precluded by an occluded punctum. This noninvasive investigation might help predict the likelihood of successful retrieval of a canaliculus at surgical exploration.
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http://dx.doi.org/10.1097/IOP.0000000000000840DOI Listing
February 2018

Is strabismus the only problem? Psychological issues surrounding strabismus surgery.

J AAPOS 2016 10 17;20(5):383-386. Epub 2016 Sep 17.

City University, London, United Kingdom.

Background: Strabismus, which has been estimated to occur in 4% of the adult population, can have a negative psychosocial effect on an individual's quality of life. While correction of strabismus may improve quality of life, this is not always the case, even if realignment surgery is clinically successful. Surgeons need to understand patients' expectations of postsurgical outcomes and the impact surgery has on their psychosocial well-being.

Methods: This was a prospective cross-sectional study of 220 adult patients undergoing strabismus surgery at Moorfields Eye Hospital NHS Foundation Trust. Clinical assessments were performed before surgery and again 2 weeks and 3 months after surgery. Standardized psychological questionnaires were completed preoperatively and 3 and 6 months postoperatively.

Results: Of 220 patients included in the study (mean age, 45 years), 54% were female, 81% were white, and 58.6% had a concomitant deviation. Prior to surgery, 24% of study participants were experiencing clinical levels of anxiety; 11% were suffering clinical levels of depression. Quality of life improved and anxiety and depression were reduced after surgery. Approximately 6% of the sample regretted having undergone surgery either at 3 or 6 months after treatment.

Conclusions: It is important to identify patients who are experiencing significant psychosocial distress and to assess their postsurgical expectations in order to improve the outcomes of strabismus surgery. Presurgical psychosocial support should be considered for these patients.
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http://dx.doi.org/10.1016/j.jaapos.2016.07.221DOI Listing
October 2016

Fibroblasts profiling in scarring trachoma identifies IL-6 as a functional component of a fibroblast-macrophage pro-fibrotic and pro-inflammatory feedback loop.

Sci Rep 2016 06 20;6:28261. Epub 2016 Jun 20.

Department of Cell Biology, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK.

Trachoma is a conjunctiva scarring disease, which is the leading infectious cause of blindness worldwide. Yet, the molecular mechanisms underlying progressive fibrosis in trachoma are unknown. To investigate the contribution of local resident fibroblasts to disease progression, we isolated conjunctival fibroblasts from patients with scarring trachoma and matching control individuals, and compared their gene expression profiles and functional properties in vitro. We show that scarring trachoma fibroblasts substantially differ from control counterparts, displaying pro-fibrotic and pro-inflammatory features matched by an altered gene expression profile. This pro-inflammatory signature was exemplified by increased IL-6 expression and secretion, and a stronger response to macrophage-mediated stimulation of contraction. We further demonstrate that scarring trachoma fibroblasts can promote Akt phosphorylation in macrophages in an IL-6 -dependent manner. Overall this work has uncovered a distinctive molecular fingerprint for scarring trachoma fibroblasts, and identified IL-6- as a potential contributor to the chronic conjunctival fibrosis, mediating reciprocal pro-fibrotic/pro-inflammatory interactions between macrophages and fibroblasts.
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http://dx.doi.org/10.1038/srep28261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913315PMC
June 2016

Psychosocial interventions for improving quality of life outcomes in adults undergoing strabismus surgery.

Cochrane Database Syst Rev 2016 May 12(5):CD010092. Epub 2016 May 12.

Paediatrics and Strabismus, Moorfields Eye Hospital NHS Foundation Trust, City Road, London, UK, EC1V 2PD.

Background: Strabismus, also known as squint, can have a debilitating effect on a person's self-esteem, quality of life and mood, as well as increase their feelings of social anxiety and avoidance behaviour. Strabismus surgery can improve both the alignment of a person's eyes and, in appropriate cases, relieve symptoms such as double vision. However, evidence indicates that not all patients experience a meaningful improvement in their quality of life postsurgery. Pre-surgical psychosocial interventions have been found to improve patient reported outcomes in other long-term conditions.

Objectives: To assess the effects of psychosocial interventions versus no intervention on quality of life and psychosocial outcomes in adults undergoing strabismus surgery.

Search Methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2016, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2016), EMBASE (January 1980 to February 2016), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to February 2016), PsycINFO (January 1967 to February 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 February 2016.We also manually searched the British Orthoptic Journal, proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and published transactions from the meetings of European Strabismus Association (ESA) and American Association for Pediatric Ophthalmology and Strabismus (AAPOS). These were searched from 1980 to present. We also carried out handsearches of Psychology and Health, British Journal of Health Psychology, Health Psychology and Annals of Behavioral Medicine.

Selection Criteria: We planned to include randomised controlled trials (RCTs), including cluster-RCTs, in which effectiveness of a psychosocial intervention had been evaluated in patients due to undergo strabismus surgery.

Data Collection And Analysis: Two review authors independently reviewed the search results for eligibility.

Main Results: None of the 88 studies we identified met the inclusion criteria of this Cochrane review.

Authors' Conclusions: We found no evidence that evaluated the impact of psychosocial interventions on patients undergoing squint surgery. We believe future research should focus on developing and evaluating the use of targeted psychosocial interventions to improve a patient's quality of life after strabismus surgery.
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http://dx.doi.org/10.1002/14651858.CD010092.pub4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250695PMC
May 2016
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