Topical Chloramphenicol in Ophthalmology: Old is Gold.

PURPOSE: Topical chloramphenicol is one of the most ubiquitous antibiotics used in ophthalmology and oculoplastic surgery globally. It shows broad-spectrum activity against a variety of different pathogenic organisms, is well tolerated on the ocular surface and displays excellent topical pharmacokinetics. Chloramphenicol has been available for purchase over the counter in the United Kingdom since 2005. Despite this, the largest health economy in the world, The United States has had a de-facto moratorium on its use for the past 30 years. In this review, we aim to evaluate topical chloramphenicol in ophthalmology and oculoplastic surgery and to determine whether its reputation within the US is warranted and justified. METHODS: We conducted a comprehensive literature review to evaluate the different facets of chloramphenicol, providing a detailed understanding of the drug, its historical context, the benefits and perceived risks, including safety concerns, and clinical perspectives of its use in clinical practice. RESULTS: The mechanism of chloramphenicol, the context around which the drug's use in the US declined, and the drug's evidence base and safety data, including published case reports of serious adverse events, were analysed. The perceived benefits of the drug, particularly in light of antimicrobial resistance and its economic impact, were reviewed. Finally, perspectives on its use in clinical practice in ophthalmology and associated allied specialities were presented. CONCLUSION: Chloramphenicol and its topical application have been misunderstood for many decades, particularly in the United States. Its demise across the Atlantic was due to an overzealous response to a dubious association with a weak evidence base. Numerous authors have since validated the safety profile of the and its safety has been borne out. The benefits of chloramphenicol, an effective broad-spectrum agent with a positive cost differential in the era of anti-microbial resistance and fiscal tightening, cannot be understated. Its likely effectiveness as a therapeutic topical agent in ophthalmic surgery makes it a valuable tool in the ophthalmic anti-microbial armoury. We would encourage the reinstatement of this valuable yet misunderstood drug as a first-line agent for simple ophthalmic infections.

Ophthalmic complication of pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP) is a rare dermatological condition which may present with ocular manifestations. We report a case of recurrent cicatricial ectropion (CE) with topical beta-blocker use in the rare dermatological condition PRP. The patient underwent release of scar tissue, lateral tarsal strip and full-thickness supraclavicular skin graft for CE following immunosuppression with methotrexate for 3 months. Postoperatively, CE recurred, with skin graft shrinkage and resumption of periocular disease activity, 8 weeks following the introduction of topical timolol. The patient was referred for further immunosuppression and substitution of timolol before consideration for further surgery. PRP has a variety of potential ocular complications. Surgery has a high risk of recurrence and should be performed when the overall disease is quiescent and drugs, which could trigger reactivation, have been discontinued and/or substituted. Skin grafts should be oversized to off-set shrinkage.

The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK.

OBJECTIVES: To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy. METHODS: Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them. RESULTS: In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases). CONCLUSIONS: A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease.

The changing landscape of thyroid eye disease: current clinical advances and future outlook.

AIMS: This review aims to provide an overview of the current understanding of TED and its pathophysiology. To describe the evidence base for current consensus treatment recommendations and newer biological therapies available as well as to present future therapeutic research. METHODS: We reviewed and assessed the peer-reviewed literature placing particular emphasis on recent studies evaluating the pathophysiology of TED, landmark trials forming the basis of current management and recent clinical trials informing future therapeutics. Searched were made in MEDLINE Ovid, Embase Ovid, US National Institutes of Health Ongoing Trials Register and EU Clinical Trials Register. Keywords included: "Thyroid Eye Disease", "Graves Orbitopathy", "Thyroid Orbitopathy" and "Graves' Ophthalmopathy". RESULTS AND CONCLUSIONS: The pathophysiology of TED involves a complex array of cellular and humoral based autoimmune dysfunction. Previous therapies have been broad-based acting as a blunt instrument on this mechanism with varying efficacy but often accompanied with a significant side effect profile. The recent development of targeted therapy, spearheaded by Teprotumumab has led to an array of treatments focusing on specific components of the molecular pathway optimising their impact whilst possibly minimising their side effect profile. Future challenges involve identifying the most effective target for each patient rather than any single agent being a panacea. Long-term safety profiles will require clarification as unintended immunological consequence downstream may become manifest as seen in other diseases. Finally, future novel therapeutics will entail significant expenditure and may lead to a divergence of available treatment modalities between healthcare systems due to funding disparities.

Lateral tarsal strip procedure: comparison of absorbable sutures and non-absorbable polypropylene suture. Does the suture type matter?

BACKGROUND/OBJECTIVES: To determine whether the success and complication rates of the Lateral Tarsal Strip (LTS) Procedure, when treating involutional ectropion/entropion, is influenced by the use of suture when attaching the tarsal strip to the periosteum. SUBJECTS/METHODS: Multi-centre retrospective comparative study of re-operation and complication rates (Recurrence, Dehiscence, Suture Infection, Granuloma, Haemorrhage, Residual-Lid Laxity, Suture Extrusion and Repeat Procedure) in LTS, between 01/01/2017 and 01/01/2022 who met the inclusion/exclusion criteria, for involutional ectropion/entropion using an absorbable polyglactin (vicryl) and non-absorbable polypropylene suture (prolene). RESULTS: 1079 operations in 891 patients (36% female, average age 81.4 years) were performed with an average follow-up of 1.785 years. 588 operations in 475 patients were performed using prolene whilst 491 procedures in 416 patients were performed using vicryl sutures. Of these, 61% were performed by a consultant surgeon in the prolene group compared to 49.7% in the vicryl group. Overall complication rates between prolene and vicryl were 24.7% and 29.7% (p = 0.061) respectively. Higher complication rates for post-operative residual lid laxity, granuloma and suture infection were greater in the vicryl group versus prolene (2.65% and 0.51% p = 0.004, 2.24% and 0.68% p = 0.03, 1.83% and 0.17% p = 0.007 respectively). Non-significant results for dehiscence or repeat procedures (2.24% and 2.21% p = 0.974, 6.72% and 9.01% p = 0.166 respectively). CONCLUSIONS: Both sutures are effective for the correction of involutional ectropion/entropion with LTS. Dehiscence and redo rates were not statistically significant. Nevertheless, the use of vicryl suture was found to be associated with a higher complication rate for: post-operative residual lid laxity, granuloma and suture infection.

High Astigmatism Secondary to Peripheral Ectasia Recurrence in Postpenetrating Keratoplasty Eyes Managed With Miniscleral Contact Lenses.

OBJECTIVES: After penetrating keratoplasty (PK) for keratoconus, vision can be impaired by high-degree astigmatism, particularly in those patients with recurrent peripheral ectasia. Scleral contact lenses (CLs) have long been used in the management of keratoconus both in treatment-naive corneas and those postcorneal transplants. We report the use of miniscleral CLs and their related visual and clinical outcomes in a series of patients with post-PK peripheral rim ectasia. METHODS: In this retrospective case series, 5 patients (7 eyes) presented because of reduced visual acuity with their spectacles/CLs and/or reduced comfort with their existing rigid gas-permeable lenses. All patients in this series underwent PK more than two decades ago for keratoconus (mean 28.7 years±7.2). All patients demonstrated characteristic thinning at the graft-host junction, with anterior chamber deepening. Central corneas had remained clear in all patients inferring high visual potential. Contact lenses used were No 7 Comfort 15 miniscleral and the Onefit MED scleral with 14.5 mm and 15.6 mm diameters, respectively. RESULTS: All eyes achieved a best-corrected visual acuity of 6/9 or greater. One case had difficulty with insertion and removal and has since discontinued wearing lens at this time. All others are successfully wearing the lenses regularly. CONCLUSION: Despite advances in CL design, surgical management is still required in some patients. Miniscleral CLs are effective in the refractive management of peripheral ectasia in keratoconic post-PK eyes and should be considered in such eyes before proceeding with repeat surgical intervention.

Thyrotropin Receptor Autoantibody Assessment in Thyroid Eye Disease: Does the Assay Type Matter?

PURPOSE: Thyroid receptor antibodies can quantify thyroid eye disease activity, predict outcomes and aid timing of interventions. The type and generation of assay is frequently unspecified, complicating meta-analyses. To determine the clinical and biochemical relationships between a second-generation thyrotropin receptor-binding inhibition antibody (TRAb) immunoassay, detecting stimulatory and blocking antibodies, with the thyroid stimulating immunoglobulin (TSI) bridging immunoassay detecting the stimulatory component only. METHODS: Retrospective review of 100 consecutive patients attending a regional specialist service. For each patient and visit, both a TRAb and TSI were performed, and a clinical activity score (CAS) recorded. RESULTS: A significant positive correlation between TRAb and TSI (rho = 0.828, p < 0.01) but a weaker correlation between the assays and CAS (TRAb: rho = 0.439, p < 0.01; TSI: r = 0.357, p < 0.01) were found. In 10% of the episodic data, patients had a TRAb level that was disproportionately high (39.41 ± 52.84 IU/L), compared to their TSI levels (9.53 ± 12.10 IU/L) with a higher-than-average CAS (2.47 ± 1.78; range, 0-5). Within 12 months of diagnosis, a significant positive correlation between CAS and TRAb (rho = 0.503, p < 0.01) as well as between CAS and TSI (rho = 0.329, p < 0.01) were found. In patients with a diagnosis over 12 months, the correlation with CAS for both TSI and TRAb were Spearman rank correlation coefficient of 0.347 (p < 0.01) and 0.327 (p < 0.01), respectively. CONCLUSIONS: TRAb and TSI correlate strongly and to a lesser extent with the CAS. For most patients, TRAb can be replaced with the more economical TSI. TRAb also correlates better with newly diagnosed, more active patients than TSI. In a subset of patients, blocking antibodies may play a significant pathogenic role, requiring different treatment and monitoring. Further studies are required to investigate this relationship.

Analysis of microbial keratitis incidence, isolates and in-vitro antimicrobial susceptibility in the East of England: a 6-year study.

BACKGROUND/OBJECTIVES: To report the incidence, microbiological profile and in-vitro antimicrobial susceptibilities of microbial keratitis (MK) in the East of England (EoE) over a 6-year period. SUBJECTS/METHODS: A retrospective study of patients diagnosed with MK who underwent corneal scraping at participating trusts, within the EoE, between 01/01/2015-01/07/2020. Analysis was performed on MK isolate profiles, in-vitro anti-microbial sensitivities and trends over time. RESULTS: The mean incidence of IK, in the EoE, was estimated at 6.96 per 100 000 population/year. 1071 corneal scrapes were analysed, 460 were culture positive (42.95%) of which 87.2% were bacteria (50.3% gram-positive and 49.7% gram-negative), 2.4% polymicrobial, 9.3% fungi and 1.1% acanthamoeba. The most common organisms were pseudomonas spp (29.57%). There was a non-statistically significant trend (NST) in increasing incidence of pseudomonas spp, staph aureus and serratia (p = 0.719, p = 0.615, and p = 0.099 respectively) and a declining NST in Fungi (p = 0.058). Susceptibilities in-vitro to, penicillin classes, fluoroquinolone and aminoglycosides were 76.7% and 89.4%, 79.2% and 97.2% and 95.4 and 96.1% to gram-positive and gram-negative bacteria respectively. Gram-negative organisms were increasingly resistant to cephalosporins with a 19.2% reduction in sensitivity over time. (p = 0.011). Ceftriaxone showed the greatest decrease in sensitivity of 41.67% (p = 0.006). CONCLUSION: In the EoE, MK is relatively prevalent though likely underestimated. Profiles are similar to other UK regions with the exception of a higher fungal and lower acanthamoeba incidence. Common first and second-line antimicrobial selection provides, on the whole, good coverage. Nevertheless, anti-microbial resistance, to cephalosporins, was observed so selection should be carefully considered when treating MK empirically.

Anterior segment ischemia following modified Nishida procedure.

Anterior segment ischemia (ASI) can occur following strabismus surgery on multiple muscles. Procedures such as modified Nishida procedure (MNP) have been developed to reduce the risk of ASI. We report the case of a 68-year-old patient presenting with traumatic bilateral abducens nerve palsies who required surgical intervention. We performed MNP with medial rectus recession. The patient presented with reduced vision, corneal edema, anterior chamber reaction, and pupillary dilation 24 hours after surgery. A diagnosis of ASI was made, and immediate reversal of the Nishida procedure was performed. Symptoms improved within 24 hours. In this case, ASI may have been caused by ligation and compression of ciliary arteries due to overstretching of the vertical rectus muscles during transposition.

The Genetic Architecture of Non-Syndromic Rhegmatogenous Retinal Detachment.

Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment (RD), affecting 1 in 10,000 patients per year. The condition has significant ocular morbidity, with a sizeable proportion of patients obtaining poor visual outcomes. Despite this, the genetics underpinning Idiopathic Retinal Detachment (IRD) remain poorly understood; this is likely due to small sample sizes in relevant studies. The majority of research pertains to the well-characterised Mende lian syndromes, such as Sticklers and Wagners, associated with RRD. Nevertheless, in recent years, there has been an increasing body of literature identifying the common genetic mutations and mechanisms associated with IRD. Several recent Genomic Wide Association Studies (GWAS) studies have identified a number of genetic loci related to the development of IRD. Our review aims to provide an up-to-date summary of the significant genetic mechanisms and associations of Idiopathic RRD.

Tectonic Mini-DSAEK Facilitates Closure of Corneal Perforation in Eyes With Healthy Endothelium.

PURPOSE: The purpose of this study was to report a surgical technique for closure of a traumatic corneal perforation in a patient with healthy endothelium. METHODS: A 69-year-old male patient presented to Southend University Hospital with a 2.5 mm round temporal corneal perforation caused by a metallic foreign body from an industrial accident. Best-corrected visual acuity at presentation was 6/36. The patient received a tectonic small diameter Descemet stripping automated endothelial keratoplasty (mini-DSAEK) to close the perforation. The patient subsequently developed traumatic cataract and underwent cataract surgery 8 months later. Clinical outcomes at 1 week, 1 month, 3 months, 6 months, and 9 months were evaluated. The primary outcomes of interest were successful sustained closure of the perforation and surgical complications, with secondary outcomes of best-spectacle corrected visual acuity (BSCVA, Snellen) and keratometric astigmatism (KA, Pentacam). RESULTS: The anterior chamber was reformed by the graft, restoring the globe's mechanical integrity. The bare stroma reepithelized by 1 week. Neither intraoperative nor postoperative surgical complications were reported. The anterior chamber remained deep and formed during subsequent follow-ups through 9 months. At the 9-month follow-up, final best spectacle-corrected visual acuity was 6/6-1 (Snellen fraction). Keratometric astigmatism was 1.1 diopters. CONCLUSIONS: Tectonic mini-Descemet stripping automated endothelial keratoplasty is a safe technique in the management of corneal perforations too large for tissue adhesives, with a low astigmatic profile and rapid visual recovery.

Discrediting microscopic pyuria and leucocyte esterase as diagnostic surrogates for infection in patients with lower urinary tract symptoms: results from a clinical and laboratory evaluation.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Microscopic pyuria is widely used as a surrogate marker of infection, although there is little data supporting its use in patients who present with non-acute LUTS. The effects of urinary storage, preservation, and the use of laboratory methods to enhance leucocyte detection, are also unclear. This large, prospective study highlights the poor performance of dipstick urine analysis, and direct microscopy, as surrogate markers of UTI in patients with LUTS. A series of laboratory analyses also examine the effects of urine handling and processing on test integrity, which have important implications for clinical practice. OBJECTIVE: To evaluate the diagnostic performance of pyuria as a surrogate marker of urinary tract infection (UTI) in patients with chronic lower urinary tract symptoms (LUTS), and determine the impact of sample storage, cytocentrifugation, and staining techniques, on test performance. PATIENTS AND METHODS: Between 2008 and 2011, we recruited 1223 patients (120 men; 1103 women; mean age 54 years) with one or more LUTS from a specialist urological outpatient service. We conducted a prospective observational study to determine the performance of microscopic pyuria ≥10 wbc/µL as a surrogate marker of UTI in patients with LUTS. All patients provided clean-catch midstream urine (MSU) samples for analysis, and routine microbiological cultures were used as our reference standard. We also scrutinised the performance of dipstick leucocyte esterase ≥ 'trace' in the detection of microscopic pyuria. The influence of sample handling and processing on test performance was examined in a series of laboratory studies. The effects of storage on leucocyte decay were determined using repeated microscopic assessments of individual urine samples, to plot temporal changes in leucocyte numbers. This study used varied storage conditions (≈20 °C and 4 °C), and boric acid preservation. Paired microscopic assessments were used to determine the effects of centrifugation on leucocyte salvage in spun/unspun samples (relative centrifugal force range 39-157 g). Similar methods were used to assess microscopic leucocyte quantification in stained/unstained urine (Sternheimer-Malbin protocol). RESULTS: The positive predictive value (PPV) and negative predictive value (NPV) of pyuria as a surrogate marker of UTI were 0.40 (95% confidence interval [CI] 0.37-0.43) and 0.75 (95% CI 0.73-0.76), respectively. The dipstick was unable to identify significant microscopic pyuria (≥10 wbc/µL) in 60% of the samples: PPV 0.51 (95% CI 0.48-0.55); NPV 0.75 (95% CI 0.73-0.76). Microscopic pyuria performed poorly as a surrogate of UTI defined by bacterial culture. Whilst refrigeration and preservation did retard leucocyte loss (F = 11; DF = 2; P < 0.001), 40% of cells were still lost by 4 h. Centrifugation had an unpredictable influence on cell salvage (coefficient of variation 5750%) and the use of staining to improve leucocyte detection proved ineffective (Z = -0.356; P = 0.72). CONCLUSIONS: Pyuria performs badly as a surrogate of UTI in patients with LUTS. This is exacerbated by cell loss during storage, and neither centrifugation, nor staining, appears to confer any diagnostic advantage. Clinicians should be alerted to the significant limitations of these tests.