Outcomes of switching treatment to aflibercept in patients with macular oedema secondary to central retinal vein occlusion refractory to ranibizumab.

PURPOSE: To assess the treatment outcome of switching from ranibizumab to aflibercept intravitreal injections in patients with macular oedema secondary to central retinal vein occlusion (CRVO). METHODS: A prospective interventional study was conducted in a tertiary retina service in Leicester Royal Infirmary, UK, where patients with CRVO and associated macular oedema were recruited. First-line treatment involved three monthly ranibizumab injections. Non-responders were defined as patients who despite a minimum of three consecutive injections had persistent intraretinal fluid one month after the last injection. In these cases, a treatment change to aflibercept injections on a per-needed basis was decided. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before and after switching of treatment. Follow-up period lasted for a minimum of 24 weeks after switching. RESULTS: Twenty-nine eyes of 29 patients with refractory macular oedema secondary to CRVO were included. All eyes had an average of 4.5 ranibizumab intravitreal injections in a mean period of 6 months without reduction in intraretinal fluid and/or no visual acuity gain. A significant decrease in mean CRT from 633.67 ± 242.42 to 234.62 ± 78.28 µm and improvement in mean BCVA from 1.34 ± 0.66 log MAR to 0.91 ± 0.73 log MAR were noticed after switching treatment to aflibercept. The average number of aflibercept injections needed for oedema resolution was 2.19. CONCLUSIONS: Aflibercept is an effective alternative treatment for macular oedema secondary to CRVO refractory to ranibizumab. Good anatomical and functional result can be achieved with few injections. The maintenance of these results after 6 months is yet to be investigated.

A review of fitness to practise referrals and investigations of ophthalmologists by the General Medical Council in the United Kingdom.

BACKGROUND: The General Medical Council (GMC) is a public body which regulates doctors in the United Kingdom (UK). One of its main roles is to investigate any concerns raised regarding a doctor. We aimed to study the current trends in referrals of ophthalmologists to the GMC. METHODS: A request was made to the GMC under the Freedom of Information Act 2000 for all complaints of ophthalmologists received by the GMC between 2007 and 2019, their outcomes and types of allegations. We have also calculated the annual incidences of suspension and erasure. RESULTS: There were 1032 complaints received by the GMC against ophthalmologists in 2007-2019. No actions were taken in 569 cases (55%). GMC investigations were carried out in 347 cases (34%). Sixty cases were referred to the Medical Practitioners Tribunal Service tribunal (6%), some of which cases resulted in suspension (28, 3%) and erasure (11, 1%). The commonest allegation types were Clinical Care, Knowledge, Skills and Performance, Maintaining Trust, Communication, Partnership and Teamwork and Probity. Annual incidences of complaints and serious outcomes between 2009 and 2017 were 30.54 (range 18.7-42.4) and 1.1 (range 0.8-2.0) per 1000 ophthalmologists respectively. CONCLUSION: There is an overall increase in the number of complaints to the GMC for ophthalmologists from 2007 to 2015 but since then there has been a gradual reduction. The annual incidences of complaints and serious outcomes have remained stable.

Impact of COVID-19 pandemic and lockdown on eye emergencies.

BACKGROUND: To characterise and compare ocular pathologies presenting to an emergency eye department (EED) during the COVID-19 pandemic in 2020 against an equivalent period in 2019. METHODS: Electronic patient records of 852 patients in 2020 and 1818 patients in 2019, attending the EED at a tertiary eye centre (University Hospitals of Leicester, UK) were analysed. Data was extracted over a 31-day period during: (study period 1 (SP1)) COVID-19 pandemic lockdown in UK (24th March 2020-23rd April 2020) and (study period 2 (SP2)) the equivalent 2019 period (24th March 2019-23rd April 2019). RESULTS: A 53% reduction in EED attendance was noted during lockdown. The top three pathologies accounting for >30% of the caseload were trauma-related, keratitis and uveitis in SP1 in comparison to conjunctivitis, trauma-related and blepharitis in SP2. The overall number of retinal tears and retinal detachments (RD) were lower in SP1, the proportion of macula-off RD's (84.6%) was significantly (p = 0.0099) higher in SP1 (vs 42.9% in SP2). CONCLUSION: COVID-19 pandemic related lockdown has had a significant impact on the range of presenting conditions to the EED. Measures to stop spread of COVID-19 such as awareness of hand hygiene practices, social distancing measures and school closures could have an indirect role in reducing spread of infective conjunctivitis. The higher proportion of macula-off RD and lower number of retinal tears raises possibility of delayed presentation in these cases. Going forward, we anticipate additional pressures on EED and other subspecialty services due to complications and associated morbidity from delayed presentations.

A comparative study of lens management in the United Kingdom and India with regard to rhegmatogenous retinal detachment surgery.

INTRODUCTION: Lens management in phakic patients with rhegmatogenous retinal detachments undergoing para plana vitrectomy surgery remains controversial among vitreoretinal surgeons. When combined phacovitrectomy is performed, the biometry decisions can be challenging both in the face of macula-off rhegmatogenous retinal detachments and previous refractive surgery. This study analyses current trends in practise. METHODS: A scenario-related survey was sent to all members of the British and Eire Association of Vitreoretinal Surgeons and to vitreoretinal surgeons in the northern Indian state of Punjab. RESULTS: In post-laser-assisted in situ keratomileusis patients with a visually significant cataract and a macula-on rhegmatogenous retinal detachment, the majority of British and Eire Association of Vitreoretinal Surgeons members (67.3%) and surgeons in Punjab (91.4%) would perform a stand-alone para plana vitrectomy and defer cataract surgery. When a combined phacovitrectomy is performed in this scenario, the majority of British and Eire Association of Vitreoretinal Surgeons (68%) would implant an intraocular lens (using either Haigis-L or European Society of Cataract and Refractive Surgeons/American Society of Cataract and Refractive Surgeons calculators), whereas the majority of Punjab surgeons (79.3%) would leave the patient aphakic. In a patient with a cataract and macula-off rhegmatogenous retinal detachment undergoing combined phacovitrectomy surgery, without any previous refractive surgery, the majority of British and Eire Association of Vitreoretinal Surgeons members (47.3%) would use the opposite eye biometry, whereas most Punjab surgeons (62.7%) would leave the patient aphakic. DISCUSSION: Vitreoretinal surgeons in both the United Kingdom and Punjab predominantly avoid combined surgery in rhegmatogenous retinal detachment cases, even when faced with a visually significant cataract. When combined phacovitrectomy is performed, most vitreoretinal surgeons preference using the opposite eye biometry for macula-off cases and Haigis-L (myope) or online calculators for post-laser-assisted in situ keratomileusis cases.

Correction: Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group.

.

Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group.

The management of diabetic retinopathy (DR) has evolved considerably over the past decade, with the availability of new technologies (diagnostic and therapeutic). As such, the existing Royal College of Ophthalmologists DR Guidelines (2013) are outdated, and to the best of our knowledge are not under revision at present. Furthermore, there are no other UK guidelines covering all available treatments, and there seems to be significant variation around the UK in the management of diabetic macular oedema (DMO). This manuscript provides a summary of reviews the pathogenesis of DR and DMO, including role of vascular endothelial growth factor (VEGF) and non-VEGF cytokines, clinical grading/classification of DMO vis a vis current terminology (of centre-involving [CI-DMO], or non-centre involving [nCI-DMO], systemic risks and their management). The excellent UK DR Screening (DRS) service has continued to evolve and remains world-leading. However, challenges remain, as there are significant variations in equipment used, and reproducible standards of DMO screening nationally. The interphase between DRS and the hospital eye service can only be strengthened with further improvements. The role of modern technology including optical coherence tomography (OCT) and wide-field imaging, and working practices including virtual clinics and their potential in increasing clinic capacity and improving patient experiences and outcomes are discussed. Similarly, potential roles of home monitoring in diabetic eyes in the future are explored. The role of pharmacological (intravitreal injections [IVT] of anti-VEGFs and steroids) and laser therapies are summarised. Generally, IVT anti-VEGF are offered as first line pharmacologic therapy. As requirements of diabetic patients in particular patient groups may vary, including pregnant women, children, and persons with learning difficulties, it is important that DR management is personalised in such particular patient groups. First choice therapy needs to be individualised in these cases and may be intravitreal steroids rather than the standard choice of anti-VEGF agents. Some of these, but not all, are discussed in this document.

Metabolomic analysis of human vitreous humor differentiates ocular inflammatory disease.

PURPOSE: Vitreoretinal disorders lack specific biomarkers that define either disease type or response to treatment. We have used NMR-based metabolomic analysis of human vitreous humor to assess the applicability of this approach to the study of ocular disease. METHODS: Vitreous samples from patients with a range of vitreoretinal disorders were subjected to high-resolution (1)H-nuclear magnetic resonance spectroscopy (NMR). Good quality spectra were derived from the vitreous samples, and the profiles were analyzed by three different methods. RESULTS: Principal component analysis (PCA) showed a wide dispersal of the different clinical conditions. Partial least squares discriminant analysis (PLS-DA) was used to define differences between lens-induced uveitis (LIU) and chronic uveitis (CU) and could distinguish between these conditions with a sensitivity of 78% and specificity of 85%. A genetic algorithm coupled with multivariate classification identified a small number of spectral components that showed clear discrimination between LIU and CU samples with sensitivity and specificity >90%. Assignment of specific resonances indicated that some metabolites involved in the arginase pathway were significantly more abundant in LIU than CU. CONCLUSION: The discrimination we observed based on PCA, PLS-DA, and multivariate variable selection analysis of the NMR spectra suggests that a complex mix of metabolites are present in vitreous fluid of different uveitic conditions as a result of the disease process. Collectively the data demonstrates the efficacy of metabolomic analysis to distinguish between ocular inflammatory diseases.

Probing the Aggregation and Signaling Behavior of Some Twisted 9,9'-Bianthryl Derivatives: Observation of Aggregation-Induced Blue-Shifted Emission.

With an aim to understand the photophysical behavior of twisted organic fluorescent molecules in their aggregated state, two twisted biaryl molecules, namely, 9,9'-bianthryl and 10,10'-dicyano-9,9'-bianthryl, have been synthesized and characterized by conventional spectroscopic methods. To understand the role of C-C bond twisting on the photophysical response of biaryl aggregates, monoaryl counterparts (anthracene and 9-anthracenecarbonitrile) of the biaryl systems are also investigated. Photophysical behaviors of these systems along with their monoaryl counterpart are investigated in both solution and aggregated state. Investigations reveal that fluorescence spectra of the biaryl compounds show blue-shifted emission upon aggregation. Interestingly, no blue shift of the emission has been observed for monoaryl aggregates. Photophysical data of biaryl systems compared to monoaryl unit reveal that change in geometry, during self-assembly process, disfavors the formation of charge-transfer state, which eventually causes blue shift in the emission upon aggregation. In addition to this, potential of these systems toward signaling of nitroaromatic explosive has also been explored. Among all of the nitroaromatics, the highest fluorescence quenching is observed for nitrophenols (say picric acid (PA)). The investigation also reveals that compared to monoaryl systems, biaryl systems are more responsive to fluorescence quenching by nitroaromatics. Perrin's model of quenching sphere action has been attributed to nitrophenol (PA) selective signaling behavior of biaryl systems.

A Case Report of Conservative Management for a Roller-Coaster-Related Vitreous Haemorrhage.

The purpose of this report is to describe the case and management of an unexplained vitreous haemorrhage that occurred after repeated roller-coaster riding. The authors inadvertently demonstrate the value of observation over immediate surgery in certain situations and review the literature on vitreoretinal and other ocular complications after roller-coaster riding. A 26-year-old male presented 12 h after riding high-velocity roller-coasters with a left vitreous haemorrhage. A hazy view of the retina and B-scan revealed a bullous area of superior-temporal retinal lifting. A diagnosis of a presumed macula-on retinal detachment was made and the patient was listed for a pars plana vitrectomy retinal detachment repair. An abnormal clotting result, which was subsequently found out to be erroneous, ultimately delayed the procedure. During this delay the vision and retinal view improved to an extent whereby the diagnosis of a retinoschisis with an intraretinal cyst was made and surgery was avoided. The patient regained 6/6 vision, without the need to undergo surgery. Historically the management of an unexplained vitreous haemorrhage was observation with serial B-scans. The current evidence and practice for treating unexplained vitreous haemorrhage have since moved towards early surgical intervention. The authors highlight that despite the current trend, a place remains for conservative management for selected cases.

Real-World Cost Savings Demonstrated by Switching Patients with Refractory Diabetic Macular Edema to Intravitreal Fluocinolone Acetonide (Iluvien): A Retrospective Cost Analysis Study.

INTRODUCTION: It is hypothesized that using fluocinolone acetonide (FAc) implants such as Iluvien for the treatment of diabetic macular edema (DME) may reduce the total number of intravitreal injections and clinic visits, resulting in an overall treatment cost reduction. The primary aim of this study is to identify the real-world cost savings achievable in a tertiary National Health Service (NHS) hospital. METHODS: A retrospective cost analysis study was conducted. The inclusion criteria were patients with refractory DME who were switched to Iluvien. The average yearly costs were calculated both before and after the switch to Iluvien. All costs including medicines, investigations, clinics, and management of raised intraocular pressure (IOP) were calculated. The cost differences over the 3 years' worth of Iluvien treatment were calculated and analyzed. To ensure non-inferiority of this treatment intervention, the best corrected visual acuity (BCVA) and central retinal thickness (CRT) were also analyzed. Statistical analysis was conducted with a Student t test where appropriate and statistical significance is identified where p < 0.05. RESULTS: Fourteen eyes of 13 patients met the inclusion criteria. Switching patients to Iluvien achieved on average a saving of £2606.17 per patient (p = 0.33) over the 3 years. However, seven cases (50%) had a rise in IOP after Iluvien that warranted medical treatment and two cases (14.3%) required glaucoma surgery. Incorporating the costs of glaucoma management reduced the overall savings over 3 years to £1064.66 per patient. The BCVA and CRT analysis showed a non-inferiority relationship between Iluvien and any previous treatment. CONCLUSIONS: The use of Iluvien in refractory DME patients represents a cost- and time-saving procedure, while showing non-inferiority in terms of efficacy.

Multiplex bead analysis of vitreous humor of patients with vitreoretinal disorders.

PURPOSE: Vitreoretinal disorders are frequently characterized by increased vitreous levels of cellular mediators, including cytokines, chemokines, and growth factors. The study was conducted to investigate whether multiplex bead analysis could identify disease-specific profiles of these mediators in a variety of vitreoretinal diseases. METHODS: Levels of 19 mediators were measured: the cytokines IL-6, IL-10, IL-12, IL-13, IL-15, IL-17, TNF, IFN-gamma, granulocyte-macrophage-colony-stimulating factor (GM-CSF), and granulocyte-stimulating factor (G-CSF); the chemokines CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL8; and the growth factors epidermal growth factor (EGF), FGF, and VEGF, by using multiplex bead analysis of vitreous humor of 58 eyes undergoing vitrectomy for a variety of vitreoretinal disorders. RESULTS: The predominant mediators detected were IL-6, CXCL8, and CCL2. The most complex pattern of mediators was seen in patients with proliferative vitreoretinopathy (PVR) and included a mixture of cytokines, chemokines, and growth factors. Patients with chronic uveitis showed a limited mediator pattern that did not suggest either a Th1 or Th2 response. By comparison, patients with lens-induced uveitis (LIU) showed significantly greater levels of cytokines than did patients with chronic uveitis, including IFN-gamma and IL-12, with a trend toward an acute Th1 inflammatory response. Moreover, in samples from patients with LIU, CXCL8 inversely correlated with time after initial surgery and duration of treatment. CONCLUSIONS: Multiplex bead analysis allows the measurement of multiple mediators from a single vitreous sample. The data confirm patterns of mediators previously described in different vitreoretinal conditions. In addition, LIU mediator levels correlate with duration of treatment and time after cataract surgery.

Giant macular hole in Alport syndrome.

CASE REPORT: A 29-year-old woman with Alport syndrome presented with unilateral visual deterioration over an 8-year period. She had the rare ocular complication of a giant macular hole. She developed a small macular hole in the other eye. COMMENTS: The ocular features of Alport syndrome are described, including proposed mechanisms for hole formation.

Scotopic measurement of normal pupil size with the Colvard pupillometer and the Nidek auto-refractor.

PURPOSE: To compare prospectively, pupil size with the Nidek AR700A auto-refractor and the Colvard pupillometer. METHODS: Pupil diameter was measured in 46 eyes at 2 min intervals in a low mesopic and under photopic light conditions. RESULTS: The mean pupil diameter was 4.8+/-1.0mm with the Colvard pupillometer and 4.8+/-0.9mm with the Nidek auto-refractor in low mesopic light conditions. The mean photopic pupil diameter was 3.3+/-0.8mm with the Colvard pupillometer and 3.9+/-0.8mm with the Nidek auto-refractor. CONCLUSION: The pupil sizes are very similar with both instruments.

The danger of wearing an anorak.

Campaigns to reduce road traffic accidents have paid little attention to the way headgear could interfere with vision. Binocular visual field measurement was undertaken in six healthy volunteers wearing four different types of anorak. All four anoraks greatly reduced the horizontal and superior field of vision. The anorak producing the worst reduction resulted in a width of vision of 99 degrees and only 15 degrees of vision above eye level, versus 167 degrees and 52 degrees respectively without an anorak. Anorak wearers should turn their heads to look sideways before crossing the road.

Cytomegalovirus retinitis: an unusual presentation as vitreous hemorrhage.

PURPOSE: The purpose of this report is to describe an unusual presentation of vitreous hemorrhage (VH) in a patient with an immunosuppressive condition. METHODS: Retrospective case report. RESULTS: A 72-year-old woman with known T-cell prolymphocytic leukemia treated with a course of alemtuzumab presented to our department with a VH in her left eye after a fall. An initial diagnosis of hemorrhagic posterior vitreous detachment was made. However, as the VH was resolving, she was found to have underlying vitritis, occlusive vasculitis, and a pale optic nerve head. Vitreous biopsy confirmed cytomegalovirus retinitis. Despite treatment with intravenous foscarnet and oral valganciclovir, her vision continued to remain poor because of the severe damage from the retinal vasculitis and residual VH. CONCLUSION: As indications for immunosuppression increase, the incidence of cytomegalovirus retinitis in non-HIV-immunosuppressed patients is expected to rise. Therefore, in this subgroup of patients, we should be aware of any underlying retinitis especially in cases with an unusual presentation of VH.

Diagnosis and Monitoring of Choroidal Osteoma through Multimodal Imaging.

A 16-year-old Caucasian female with a 6-month history of decreased visual acuity and metamorphopsia in the left eye is reported. The fundus of the left eye revealed a well defined lesion in the macula region. Diagnosis of choroidal osteoma was established using spectral domain optical coherence tomography (OCT), fundus fluorescein angiography (FFA), indocyanine green angiography (ICG), and B-scan ultrasonography. Subretinal fluid (SRF) and retinal pigment epithelium (RPE) detachment were noted in the absence of obvious classic choroidal neovascularisation (CNV). The patient was followed up for over 13 months without any treatment in the interim and the lesion was noted to have enlarged but visual acuity and SRF had remained stable. We report an interesting case where subretinal fluid was noted in the absence of evident choroidal neovascularisation and provide an example of the imaging modalities application in the era of "optical biopsy."

Dexamethasone intravitreal implant for idiopathic retinal vasculitis, aneurysms, and neuroretinitis.

PURPOSE: To present the short-term favorable clinical results with the dexamethasone intravitreal implant in a patient with florid idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome (IRVAN).
 METHODS: A 26-year-old man presented with significant bilateral deterioration of vision due to vitreous hemorrhage and neuroretinitis with a background of vasculitis and neovascularization. The patient was initially treated with high doses of oral steroids (80 mg prednisolone), which were gradually tapered, and also received extensive argon laser photocoagulation in ischemic areas in both eyes. Despite vigorous treatment and an initial positive response to treatment, pars plana vitrectomy was eventually needed to address the recurrent vitreous hemorrhages in the left eye. Consequently, visual acuity improved from 0.1 to 0.2 (Snellen) and there was no relapse of vitreous hemorrhage. Persistent macular edema was noted, however, and it was decided to treat with a dexamethasone 0.7 mg intravitreal implant.
 RESULTS: Following the dexamethasone implant OS, visual acuity improved significantly from 0.2 to 0.5 (Snellen), the patient reported much less distortion, and there was marked reduction in central retinal thickness from 467 to 234 microns. The patient remains in remission without any exudation in the macula at 4 months follow-up.
 CONCLUSION: Dexamethasone 0.7 mg intravitreal implant appears to be a safe and effective solution in the treatment of macular edema in patients with IRVAN syndrome and could possibly be a treatment option for other cases of inflammatory induced macular edema.