Nikolaos Tzoumas

Sunderland Eye Infirmary

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Co-Authors

David Steel

Newcastle University

Salman Naveed Sadiq

Sunderland Eye Infirmary

Alexander Mehta

Sunderland Eye Infirmary

Declan C. Murphy

Newcastle University

Islam Mostafa

Newcastle University

Mohaimen Al-Zubaidy

Imperial College London

Anna Song

Kyungsung University

Ali E. Ghareeb

The Francis Crick Institute

David Kavanagh

Newcastle University

Claire L. Harris

Novartis (Switzerland)

Cooperative Institutions

University of Birmingham

173

Institut de Virologie

Newcastle University

NIHR Birmingham Biomedical Research Centre

Collaborative Group (United States)

Laboratoire des Sciences de l'Ingénieur, de l'Informatique et de l'Imagerie

Yorkshire Cancer Research

Urology Foundation

Association for Cancer Surgery

AstraZeneca (Brazil)

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Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease

British Journal of Pharmacology (2019)

Nikolaos Tzoumas Tariq E. Farrah Neeraj Dhaun David J. Webb

PDE type 5 inhibitors (PDE5Is), such as sildenafil, tadalafil and vardenafil, are a class of drugs used to prolong the physiological effects of NO/cGMP signalling in tissues through the inhibition of cGMP degradation. Although these agents were originally developed for the treatment of hypertension and angina, unanticipated side effects led to advances in the treatment of erectile dysfunction and, later, pulmonary arterial hypertension. In the last decade, accumulating evidence suggests that PDE5Is may confer a wider range of clinical benefits than was previously recognised. This has led to a broader interest in the cardiovascular therapeutic potential of PDE5Is, in conditions such as hypertension, myocardial infarction, stroke, peripheral arterial disease, chronic kidney disease and diabetes mellitus. Here, we review the pharmacological properties and established licensed uses of this class of drug, along with emerging therapeutic developments and possible future indications.

Vardenafil

Drug class

10.1111/bph.14920

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Citations (92)

Improved Outcomes with Heavy Silicone Oil in Complex Primary Retinal Detachment

Ophthalmology (2023)

Nikolaos Tzoumas David Yorston D A H Laidlaw Tom H. Williamson David Steel

PurposeTo establish whether Densiron® 68, a heavier-than-water endotamponade agent, is an effective alternative to conventional light silicone oil in primary rhegmatogenous retinal detachment surgery for eyes with inferior breaks in the detached retina and severe proliferative vitreoretinopathy.DesignCohort study of routinely collected data from the European Society of Retina Specialists (EURETINA) and British and Eire Association of Vitreoretinal Surgeons (BEAVRS) vitreoretinal database between 2015 and 2022.ParticipantsAll consecutive eyes that underwent primary rhegmatogenous retinal detachment surgery using either Densiron® 68 or light silicone oil as an internal tamponade agent.MethodsTo minimize confounding bias, we undertook 2:1 nearest neighbor matching on inferior breaks, large inferior rhegmatogenous retinal detachments, proliferative vitreoretinopathy, and, for visual analyses, baseline visual acuity between treatment groups. We fit regression models including prognostically relevant covariates, treatment-covariate interactions, and matching weights. We used g-computation with cluster-robust methods to estimate marginal effects. For nonlinear models, we calculated confidence intervals using bias-corrected cluster bootstrapping with 9 999 replications.Main Outcome MeasuresPresence of a fully attached retina and visual acuity at least two months after oil removal.ResultsOf 1061 eyes enrolled, 426 and 239 were included in our matched samples for anatomical and visual outcome analyses, respectively. The primary success rate was higher in the Densiron® 68 group (113 of 142; 80%) compared to the light silicone oil group (180 of 284; 63%), with an adjusted odds ratio of 1.90 (95% CI 1.63 to 2.23, P < 0.001). We also observed a significant improvement favoring Densiron® 68 of -0.26 logMAR in postoperative visual acuity between the two groups (95% CI -0.43 to -0.10, P = 0.002). The anatomical benefit of using Densiron® 68 in eyes with inferior retinal breaks and large detachments was more pronounced among eyes with proliferative vitreoretinopathy Grade C. We found no evidence of visual effect moderation by anatomical outcome or foveal attachment.ConclusionsDensiron achieved higher anatomical success rates and improved visual outcomes compared to conventional light silicone oil in eyes with inferior retinal pathology and severe proliferative vitreoretinopathy.

Silicone oil

Primary (astronomy)

10.1016/j.ophtha.2023.12.016

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Citations (5)

Infographic: the Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT)

Eye (2021)

Declan C. Murphy Nikolaos Tzoumas Alexander Mehta Islam Mostafa Salman Naveed Sadiq

Infographic

10.1038/s41433-021-01597-9

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Citations (2)

Infographic: Slow-release dexamethasone in proliferative vitreoretinopathy (PVR)

Eye (2021)

Islam Mostafa Mohaimen Al-Zubaidy Ali E. Ghareeb Anna Song Alexander Mehta

Proliferative Vitreoretinopathy

Infographic

10.1038/s41433-021-01532-y

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Citations (1)

Comparative analysis of large language models in the Royal College of Ophthalmologists fellowship exams

Eye (2023)

Raffaele Raimondi Nikolaos Tzoumas Thomas Salisbury Sandro Di Simplicio Mario R. Romano

10.1038/s41433-023-02563-3

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Citations (59)

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

British journal of surgery (2022)

A Sgrò Ruth Blanco‐Colino WUR Ahmed Niall Brindl RR Gujjuri

Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice.COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement.Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001).Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk.

Colorectal Surgery

10.1093/bjs/znac069

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Citations (29)

Infographic: Positioning In Macular hole Surgery (PIMS) trial

Eye (2021)

Nikolaos Tzoumas Declan C. Murphy Alexander Mehta Islam Mostafa Salman Naveed Sadiq

Infographic

10.1038/s41433-021-01559-1

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Citations (0)

Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration

Journal of Clinical Medicine (2023)

Sarah Hammadi Nikolaos Tzoumas Mariantonia Ferrara Ingrid P. Meschede Katharina Lo

The complement system is crucial for immune surveillance, providing the body's first line of defence against pathogens. However, an imbalance in its regulators can lead to inappropriate overactivation, resulting in diseases such as age-related macular degeneration (AMD), a leading cause of irreversible blindness globally affecting around 200 million people. Complement activation in AMD is believed to begin in the choriocapillaris, but it also plays a critical role in the subretinal and retinal pigment epithelium (RPE) spaces. Bruch's membrane (BrM) acts as a barrier between the retina/RPE and choroid, hindering complement protein diffusion. This impediment increases with age and AMD, leading to compartmentalisation of complement activation. In this review, we comprehensively examine the structure and function of BrM, including its age-related changes visible through in vivo imaging, and the consequences of complement dysfunction on AMD pathogenesis. We also explore the potential and limitations of various delivery routes (systemic, intravitreal, subretinal, and suprachoroidal) for safe and effective delivery of conventional and gene therapy-based complement inhibitors to treat AMD. Further research is needed to understand the diffusion of complement proteins across BrM and optimise therapeutic delivery to the retina.

Bruch's membrane

Degeneration (medical)

10.3390/jcm12082870

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Citations (15)

The rareC9P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade

Human Molecular Genetics (2021)

Orla McMahon Thomas M Hallam Shrena Patel Claire L. Harris Anaïs Menny

Abstract Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway.

Complement

Component (thermodynamics)

Degeneration (medical)

10.1093/hmg/ddab086

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Citations (17)

Revisiting the role of factor H in age-related macular degeneration: Insights from complement-mediated renal disease and rare genetic variants

Survey of Ophthalmology (2020)

Nikolaos Tzoumas Dean Hallam Claire L. Harris Majlinda Lako David Kavanagh

Drusen

Pathogenesis

Complement factor B

10.1016/j.survophthal.2020.10.008

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Citations (25)