Recent Submissions

  • Treatment of age-related macular degeneration with aflibercept using a treat, extend and fixed protocol; A 4-year study of treatment outcomes, durability, safety and quality of life (An extension to the MATE randomised controlled trial)

    Dhar-Munshi, Sushma
    Purpose: Data are limited pertaining to the long-term benefits of aflibercept treatment for neovascular age-related macular degeneration (nAMD). The aim of this study was to provide outcomes, safety, durability and quality-of-life data with aflibercept using a modified treat, extend and fixed regime over 4 years. Methods: Prospective, multicentre, single cohort observational study of treatment-naïve nAMD participants treated with aflibercept as 2-year extension of the MATE-trial that compared early and late Treat-and-Extend for 2 years. Refracted ETDRS best corrected visual acuity (BCVA), central retinal thickness (CRT), treatment interval and adverse events were assessed. Quality-of-life was measured using the Macular Disease Dependent Quality of Life (MacDQoL) and Macular Disease Treatment Satisfaction Questionnaires (MacTSQ). Results: Twenty-six of 40 participants completing the MATE-trial were enrolled with 20 completing the total 4-year study. Mean BCVA was 60.7 at Month 0 and 64.8 ETDRS letters at Month 48 while CRT decreased from 423.7 μm to 292.2 μm. Five participants discontinued treatment due to inactivity. The mean number of treatments and visits for the remaining participants was 27 and 30.0, respectively, with treatment intervals extended to 12 weeks in four participants at Month 48. Both AMD-specific QoL and treatment satisfaction remained stable between Months 0 and 48 and mean BCVA significantly correlated with AMD-specific QoL scores at Months 12, 24 and 48. Conclusions: Results suggest that BCVA can be maintained over 48 months when following a treat-extend-and-fix regimen of aflibercept with intervals out to 12 weeks, while maintaining AMD-specific QoL and treatment satisfaction.
  • TANDEM TRIAL: a factorial randomised controlled trial of dose and review schedule of bevacizumab (Avastin) for neovascular macular degeneration in the East Midlands

    Dhar-Munshi, Sushma (BMJ Open Ophthalmology, 2020-12)
    Objective: Neovascular age-related macular degeneration (nAMD) causes damage to the macula and severe vision loss. Bevacizumab is the most cost-effective nAMD treatment. The TANDEM trial was designed to determine whether, in patients with nAMD, low-dose bevacizumab is non-inferior to the standard dose in terms of visual deterioration and whether a bimonthly regimen is non-inferior to monthly, treatment as required, regimens. Methods: This was a multicentre, 2×2 factorial, double-masked, non-inferiority randomised trial with patients considered eligible if they met the National Institute for Health and Care Excellence criteria for nAMD treatment with ranibizumab. Participants were randomly assigned to standard (1.25 mg) or low (0.625 mg) dose bevacizumab and either monthly or bimonthly review regimen. The primary outcome was time to vision deterioration, defined as reduction of ≥15 letters (three lines) during the loading phase (visual acuity scores at visits B and C compared with the initial visit A), or ≥6 letters (one line) during the maintenance phase (visual acuity scores at subsequent visits compared with mean vision at visits A-C). Results: In total 812 participants (918 eyes) were randomised into the trial. The low dose showed some evidence of being non-inferior to standard dose (HR 1.07; 95% CI 0.80 to 1.42), however, there was no strong evidence of bimonthly review being non-inferior to monthly review (HR 1.45; 95% CI 1.09 to 1.94). There was no difference in visual acuity when assessed at 9 months and no major differences in the frequency of serious adverse events or reactions between the groups. Conclusion: The standard dose of bevacizumab can be halved without compromising efficacy. Bimonthly review cannot be considered to be no worse than monthly review.
  • Preseptal cellulitis and infraorbital abscess as a complication of a routine COVID-19 swab

    Fazekas, Balazs; Fazekas, Bence; Jayakumar, Delicia (2021-05)
    This case report describes a significant complication of a routine COVID-19 swab in a previously fit and well young patient who developed preseptal cellulitis and an infraorbital abscess as a consequence of the mentioned nasal swabbing. Other authors have previously reported various complications in connection with the use of nasal swabs, including retained swab fragments, epistaxis and cerebrospinal fluid leakage. To our knowledge, to date, this is the first reported case of an abscess as a consequence of COVID-19 swabbing. There has been a clear growth in the use of nasal swabbing worldwide over the last 9 months and many healthcare workers involved in COVID-19 prevention may not be aware of the potential risks of nasopharyngeal swabbing. The presented case highlights the need for better awareness of the complications of these routine tests and we hope that it will also lead to their safer implementation.
  • Ophthalmological Aspects of von-Hippel-Lindau Syndrome

    Ali, Wajahat (2021)
    Background: von Hippel-Lindau (VHL) syndrome is a multisystem neoplastic disorder involving eyes, central nervous system, kidneys, spine, and other tissues. A retinal capillary hemangioma (RCH) is the earliest manifestation of the VHL disease in most cases.Areas covered:This paper aims to provide an up-to-date review of the current literature about von Hippel-Lindau syndrome. Molecular background, systemic and ocular features of the diseases as well as the utility of newer imaging modalities in diagnosis and monitoring of ocular VHL disease have been described. Besides, we have discussed newer treatment modalities and therapeutic targets.Conclusion: Modern imaging technologies like optical coherence tomography and optical coherence tomography angiography are tools of the trade, in making an appropriate diagnosis and monitoring disease activity and response to treatment. Peripheral RCH may be treated using laser photocoagulation in tumors up to 3000 µm. Vascular endothelial growth factor suppression can help in reducing tumor activity and stabilize the tumor size; however, it does not regress the RCH.
  • Comparing different dosing regimens of bevacizumab in the treatment of neovascular macular degeneration: study protocol for a randomised controlled trial.

    Dhar-Munshi, Sushma (2015-03)
    Background: Bevacizumab (Avastin®) is as effective as ranibizumab (Lucentis®) in the treatment of neovascular age-related macular degeneration (nAMD). However it has two important structural differences. First, it has two active sites instead of one; second, it retains the Fc portion of the antibody which would be expected to confer a significantly longer half-life. These agents have been associated with systemic complications including strokes, so it is desirable to use the smallest effective dose. Furthermore, the standard dosing regimen requires monthly hospital visits, which present a significant challenge both to the hospital services and to the patients (who are elderly). Methods/design: Patients ≥50 years who are eligible for anti-vascular endothelial growth factor (VEGF) treatment of nAMD in the NHS, who are either newly referred for treatment or have reactivation of nAMD and who have not received treatment to either eye for the previous six months. We have designed a factorial multi-centre masked randomised controlled trial using bevacizumab as the intervention, with patients randomised to one of four arms: to standard or low dose and to monthly or two-monthly patient review. The aim is to recruit sufficient patients (around 1,000) to obtain 304 patients meeting the endpoint over a four-year period. The primary endpoint is time to treatment failure to be analysed using Cox regression. Discussion: This randomised control trial will show if half dose and two monthly as required is as effective as full dose and monthly regimes. A two monthly as required regimen of Bevacizumab would significantly reduce both the cost and the service delivery burden for the treatment of nAMD while a reduced dose would be expected to enhance the safety profile of this treatment regime.
  • The diagnostic accuracy of spectral-domain optical coherence tomography for neovascular age-related macular degeneration: A comparison with fundus fluorescein angiography.

    Lakshmanan, A.; Dhar-Munshi, Sushma; Amankwah, Ruby (2015-05)
    Purpose: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) for neovascular age-related macular degeneration (nAMD): a comparison against fundus fluorescein angiography (FFA). Methods: A retrospective review of SD-OCT, colour fundus photographs (FP), and FFA of 411 consecutive patients referred to a rapid access Macular Clinic over a 4-year period was performed. FFA images were reviewed non-stereoscopically. SD-OCT images were acquired using the Topcon 3D OCT-1000 instrument. All FFA and OCT images were graded by at least two ophthalmologists independently. Side-by-side grading took place with immediate open discussion and adjudication. If there was disagreement between the two grading ophthalmologists or they were not 90% confident of their assigned grade, then adjudication by a third ophthalmologist was performed. Results: A total of 278 eyes were graded as having choroidal neovascularisation (CNV) with SD-OCT and 231 diagnosed with FFA. The main diagnostic CNV classifications on FFA were: classic no occult in 27 eyes, predominantly classic in 16, minimally classic in 50, occult in 129, and 9 peripapillary membranes. There were a total of 47 false positives with SD-OCT: a rate of 16.9%. The sensitivity and specificity of SD-OCT alone for detecting CNV was 100 and 80.8%, respectively. Conclusion: Our study confirms SD-OCT in comparison to the reference standard of non-stereoscopic FFA is highly sensitive at detecting newly presenting nAMD in the setting of a specialist AMD clinic where the investigations are interpreted by trained specialists. However, it does not seem accurate enough to replace FFA in the diagnosis on nAMD in current practice.
  • Computer vision syndrome-A common cause of unexplained visual symptoms in the modern era.

    Dhar-Munshi, Sushma (2017-07)
    Objectives: The aim of this study was to assess the evidence and available literature on the clinical, pathogenetic, prognostic and therapeutic aspects of Computer vision syndrome.Methods: Information was collected from Medline, Embase & National Library of Medicine over the last 30 years up to March 2016. The bibliographies of relevant articles were searched for additional references.Findings: Patients with Computer vision syndrome present to a variety of different specialists, including General Practitioners, Neurologists, Stroke physicians and Ophthalmologists. While the condition is common, there is a poor awareness in the public and among health professionals.Interpretations and Implications: Recognising this condition in the clinic or in emergency situations like the TIA clinic is crucial. The implications are potentially huge in view of the extensive and widespread use of computers and visual display units. Greater public awareness of Computer vision syndrome and education of health professionals is vital. Preventive strategies should form part of work place ergonomics routinely. Prompt and correct recognition is important to allow management and avoid unnecessary treatments.
  • Prevalence of reticular pseudodrusen in eyes with newly presenting neovascular age-related macular degeneration.

    Dhar-Munshi, Sushma (2016-03)
    Purpose: To use multimodal imaging to evaluate the prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting neovascular age-related macular degeneration (nAMD) in a UK population and explore associations with RPD and angiographic subtypes of nAMD. Methods: A retrospective review of all spectral-domain optical coherence tomography, color fundus photographs, red-free and blue channel images, and fundus fluorescein angiograms of 202 consecutive patients who presented to a rapid access macular clinic over a 4-year period was performed. All images were graded by at least 2 ophthalmologists for the presence of RPD and choroidal neovascular membrane (CNV) subtypes. Results: A total of 231 consecutive eyes were studied, of which 131 (56.7%) were in women. Of these, 51 eyes with CNV (22.1%) had identifiable RPD, with one or more imaging methods in that eye. A total of 30.3% of patients with newly presenting CNV in either or both eyes had identifiable RPD. The RPD were bilateral in 85.4% of patients and were identified more commonly in women than men (72.5% vs 27.5%), a difference that reached statistical significance (p = 0.011). No association between RPD and any particular CNV subtype was demonstrated, including for retinal angiomatous proliferations (RAP). Conclusions: Reticular pseudodrusen have a high prevalence in eyes presenting with nAMD (22.1%), although at rates much lower than that of conventional drusen. They are largely a bilateral finding, occurring more frequently in women. Unlike other previous reports, we found no difference in their occurrence between the different subtypes of CNV including RAPs.
  • Prevalence of reticular pseudodrusen in newly presenting adult onset foveomacular vitelliform dystrophy.

    Dhar-Munshi, Sushma (2016-06)
    Purpose To report the association and prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting adult onset foveomacular vitelliform dystrophy (AFVD). To compare the strength of association with other pathologies resulting from dysfunction of the choroid-Bruch's membrane-retinal pigment epithelium (RPE) complex, including eyes with geographic atrophy (GA) and angioid streaks. Methods Retrospective single-centre review of all consecutive newly presenting AFVD. Multimodal imaging with spectral domain optical coherence tomography, fundus photographs, red-free/blue light images, and fundus fluorescein angiograms were graded for the presence of RPD. For comparison, all consecutive newly presenting cases of GA and eyes with angioid streaks were studied. Results Fifteen (15) patients were identified with AFVD (mean age of 77.3 years; 73.3% female). Mean age of patients with AFVD and RPD was 80.5 years (SD 3.7), whereas that of patients with AFVD without RPD was 75.1 years (SD 7.0). This age difference did not reach statistical significance, P=0.1. Six (40%) had identifiable RPD; being a bilateral finding in 100% of patients. No males with AFVD and RPD were identified. A total of 92 eyes presented with GA. Twenty-three (23) of these (25.0%) had RPD. Twelve (12) patients presented with identifiable angioid streaks, with 4 (36.4%) having RPD. Conclusion RPD are a frequent finding in eyes with newly presenting AFVD; not being restricted to AMD, but a finding common among diseases where pathophysiological mechanisms involve damage to Bruch's membrane and the RPE, whether genetic or degenerative. Our study supports the concept that they occur with high but variable frequencies in eyes with various pathologies.