Home-Monitoring Vision Tests to Detect Active Neovascular Age-Related Macular Degeneration.

Importance: Most neovascular age-related macular degeneration (nAMD) treatments involve long-term follow-up of disease activity. Home-monitoring would reduce the burden on patients and their caregivers and release clinic capacity. Objective: To evaluate 3 vision home-monitoring tests for patients to use to detect active nAMD compared with diagnosing active nAMD at hospital follow-up during the after-treatment monitoring phase. Design, Setting, and Participants: This was a diagnostic test accuracy study wherein the reference standard was detection of active nAMD by an ophthalmologist at hospital follow-up. The 3 home-monitoring tests evaluated included the following: (1) the KeepSight Journal (KSJ [International Macular and Retinal Foundation]), which contains paper-based near-vision tests presented as word puzzles, (2) the MyVisionTrack (mVT [Genentech]) vision-monitoring mobile app, viewed on an Apple mobile operating system-based device, and (3) the MultiBit (MBT [Visumetrics]) app, viewed on an Apple mobile operating system-based device. Participants were asked to test weekly; mVT and MBT scores were transmitted automatically, and KSJ scores were returned to the research office every 6 months. Raw scores between hospital follow-ups were summarized as averages. Patients were recruited from 6 UK hospital eye clinics and were 50 years and older with at least 1 eye first treated for active nAMD for at least 6 months or longer to a maximum of 42 months before approach. Participants were stratified by time since starting treatment. Study data were analyzed from May to September 2021. Exposures: The KSJ, mVT, and MBT were compared with the reference standard (in-hospital ophthalmologist examination). Main Outcomes and Measures: Estimated area under receiver operating characteristic curve (AUROC). The study had 90% power to detect a difference of 0.06, or 80% power to detect a difference of 0.05, if the AUROC for 2 tests was 0.75. Results: A total of 297 patients (mean [SD] age, 74.9 [6.6] years; 174 female [58.6%]) were included in the study. At least 1 hospital follow-up was available for 312 study eyes in 259 participants (1549 complete visits). Median (IQR) home-monitoring testing frequency was 3 (1-4) times per month. Estimated AUROC was less than 0.6 for all home-monitoring tests, and only the KSJ summary score was associated with lesion activity (odds ratio, 3.48; 95% CI, 1.09-11.13; P = .04). Conclusions and Relevance: Results suggest that no home-monitoring vision test evaluated provided satisfactory diagnostic accuracy to identify active nAMD diagnosed in hospital eye service follow-up clinics. Implementing any of these evaluated tests, with ophthalmologists only reviewing test positives, would mean most active lesions were missed, risking unnecessary sight loss.

Descriptive study of the challenges when implementing an app for patients with neovascular age-related macular degeneration to monitor their vision at home.

OBJECTIVES: Remote monitoring of health has the potential to reduce the burden to patients of face-to-face appointments and make healthcare more efficient. Apps are available for patients to self-monitor vision at home, for example, to detect reactivation of age-related macular degeneration (AMD). Describing the challenges when implementing apps for self-monitoring of vision at home was an objective of the MONARCH study to evaluate two vision-monitoring apps on an iPod Touch (Multibit and MyVisionTrack). DESIGN: Diagnostic Test Accuracy study. SETTING: Six UK hospitals. METHODS: The study provides an example of the real-world implementation of such apps across health sectors in an older population. Challenges described include the following: (1) frequency and reason for incoming calls made to a helpline and outgoing calls made to participants; (2) frequency and duration of events responsible for the tests being unavailable; and (3) other technical and logistical challenges. RESULTS: Patients (n=297) in the study were familiar with technology; 252/296 (85%) had internet at home and 197/296 (67%) had used a smartphone. Nevertheless, 141 (46%) called the study helpline, more often than anticipated. Of 435 reasons for calling, all but 42 (10%) related to testing with the apps or hardware, which contributed to reduced adherence. The team made at least one call to 133 patients (44%) to investigate why data had not been transmitted. Multibit and MyVisionTrack apps were unavailable for 15 and 30 of 1318 testing days for reasons which were the responsibility of the app providers. Researchers also experienced technical challenges with a multiple device management system. Logistical challenges included regulations for transporting lithium-ion batteries and malfunctioning chargers. CONCLUSIONS: Implementation of similar technologies should incorporate a well-resourced helpline and build in additional training time for participants and troubleshooting time for staff. There should also be robust evidence that chosen technologies are fit for the intended purpose. TRIAL REGISTRATION NUMBER: ISRCTN79058224.

A protocol paper for the MOTION Study-A longitudinal study in a cohort aged 60 years and older to obtain mechanistic knowledge of the role of the gut microbiome during normal healthy ageing in order to develop strategies that will improve lifelong health and wellbeing.

BACKGROUND: Advances in medicine and public health mean that people are living longer; however, a significant proportion of that increased lifespan is spent in a prolonged state of declining health and wellbeing which places increasing pressure on medical, health and social services. There is a social and economic need to develop strategies to prevent or delay age-related disease and maintain lifelong health. Several studies have suggested links between the gut microbiome and age-related disease, which if confirmed would present a modifiable target for intervention development. The MOTION study aims to determine whether and how changes in the gut microbiome are associated with physical and mental capacity. A comprehensive longitudinal multiparameter study such as this has not been previously undertaken. METHODS: MOTION is a longitudinal prospective cohort study with a focus on gut health and cognitive function. 360 healthy individuals aged 60 years and older, living in East Anglia, UK will be recruited to the study, stratified into one of three risk groups (cohorts) for developing dementia based on their cognitive function. Participants will attend study appointments every six months over four years, providing stool and blood samples and a health questionnaire. Participants will also undergo physical measurements and cognitive tests at alternating appointments, and undergo Optical Coherence Tomography scans at 3 timepoints. Two subgroups of participants in the study will provide colonic tissue biopsies (n = ≥30 from each cohort), and brain imaging (n = 30) at two timepoints. DISCUSSION: This study will provide new insights into the gut-(microbiota)-brain axis and the relationship between age-associated changes in gut microbe populations and cognitive health. Such insights could help develop new microbe-based strategies to improve lifelong health and wellbeing. TRIAL REGISTRATION: This study is registered in the ClinicalTrials.gov Database with ID: NCT04199195 Registered: May 14, 2019.

Erdheim-Chester Disease: Two cases from an ophthalmic perspective.

PURPOSE: We report two patients who presented initially to ophthalmology clinics with symptoms and signs of orbital inflammation that led to a diagnosis of Erdheim-Chester Disease (ECD). OBSERVATIONS: ECD is a rare form of non-Langerhans cell histiocytosis (LCH) which is characterised by multi-system organ involvement and poor prognosis with standard therapies. Both patients were positive for the BRAF V600E mutation on genetic testing and were treated with the BRAF inhibitors Vemurafenib and Dabrafenib respectively. These cases highlight the variable clinical presentation and course of ECD, the classical radiological and histopathological findings, and the high degree of clinical suspicion necessary to reach this diagnosis. CONCLUSIONS AND IMPORTANCE: The combination of xanthelasma and bilateral, diffuse intraconal orbital masses must suggest to the clinician the possibility of ECD; and consideration to arrange further investigation with a full body CT or FDG PET/CT scan should be given, even in the absence of wider systemic symptoms or signs. With the advent of targeted therapies such as BRAF inhibitors, it is of even more importance that a diagnosis of ECD is established in a timely manner in order to give these patients the best chance of reduced morbidity and increased survival.

Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study.

BACKGROUND/AIMS: Prospective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect of switching from aflibercept to ranibizumab on anatomical and functional outcomes in patients with persistent/recurrent disease activity. METHODS: SAFARI (NCT02161575) was a 6-month, prospective, single-arm study conducted in the UK and Germany. Patients, meeting strict eligibility criteria for one of two subgroups (primary treatment failure or suboptimal treatment response), received 3 monthly intravitreal ranibizumab injections (0.5 mg). Thereafter, ranibizumab was administered pro re nata at monthly visits. The primary endpoint was change from baseline (CfB) to day 90 in central subfield retinal thickness (CSRT). Best-corrected visual acuity (BCVA) and retinal morphology parameters were assessed. RESULTS: One hundred patients were enrolled (primary treatment failure, 1; suboptimal treatment response, 99). In the overall population, there was a significant CfB in median CSRT of -30.75 µm (95% CI -59.50,-20.50; p<0.0001) to day 90. Improvements were also observed in other quantitative and qualitative optical coherence tomography parameters. In Early Treatment Diabetic Retinopathy Study letters assessed by category, 55% and 59% of patients gained 0-≥15 letters versus baseline at day 90 and day 180, respectively. However, mean improvements in BCVA (CfB) to each time point were small (≤2 letters). No new safety signals were identified. CONCLUSION: Switching from aflibercept to ranibizumab led to a significant improvement in CSRT, with ~60% experiencing stabilised/improved BCVA. Therefore, patients with nAMD who have shown a suboptimal response to aflibercept may benefit from switching to ranibizumab.

Acute Macular Neuroretinopathy following Oral Intake of Adrenergic Flu Treatments.

PURPOSE: The purpose of this study was to report a case series of patients with acute macular neureretinopathy in which patients concomitantly used ephedrine or pseudo-ephedrine. METHODS: This is a retrospective case review. RESULTS: Two patients with retinal findings consistent with acute macular neuroretinopathy are presented. CONCLUSION: Acute macular neuroretinopathy should be considered in any young patient with unexplained loss of vision and exposed to direct or indirect adrenergic stimulation.

Optic neuropathy associated with systemic sarcoidosis.

OBJECTIVE: To identify and follow a series of 52 patients with optic neuropathy related to sarcoidosis. METHODS: Prospective observational cohort study. RESULTS: The disorder was more common in women and affected a wide age range. It was proportionately more common in African and Caribbean ethnic groups. Two clinical subtypes were identified: the more common was a subacute optic neuropathy resembling optic neuritis; a more slowly progressive optic neuropathy arose in the remaining 17%. Sixteen (31%) were bilateral. Concurrent intraocular inflammation was seen in 36%. Pain arose in only 27% of cases. An optic perineuritis was seen in 2 cases, and predominate involvement of the chiasm in one. MRI findings showed optic nerve involvement in 75% of cases, with adjacent and more widespread inflammation in 31%. Treatment with corticosteroids was helpful in those with an inflammatory optic neuropathy, but not those with mass lesions. Relapse of visual signs arose in 25% of cases, necessitating an increase or escalation of treatment, but relapse was not a poor prognostic factor. CONCLUSIONS: This is a large prospective study of the clinical characteristics and outcome of treatment in optic neuropathy associated with sarcoidosis. Patients who experience an inflammatory optic neuropathy respond to treatment but may relapse. Those with infiltrative or progressive optic neuropathies improve less well even though the inflammatory disorder responds to therapy.

Treatment satisfaction of patients undergoing ranibizumab therapy for neovascular age-related macular degeneration in a real-life setting.

CONTEXT: Treatment satisfaction with a loading phase of monthly injections for 3 months followed by a pro-re-nata regimen of ranibizumab in neovascular age-related macular degeneration (nAMD) remains unclear. AIMS: The aim was to evaluate the treatment satisfaction of persons with nAMD treated with ranibizumab in a real-life setting. SETTINGS AND DESIGN: A cross-sectional study was conducted across three eye clinics within the National Health Service in the UK, where treatment is provided free at point of contact. MATERIALS AND METHODS: A total of 250 patients were selected randomly for the study. Treatment satisfaction was assessed using the Macular Treatment Satisfaction Questionnaire. Data were collected on satisfaction of the service provided (Client Service Questionnaire-8) and the patients' demographic and quality of life and treatment history. Factors governing treatment questionnaire were determined. RESULTS: The most important factors that determined the satisfaction were the service provided at the clinic (Client Service Questionnaire-8), health-related quality of life (EQ-5D-3L), and duration of AMD. Visual acuity changes were rated as less important than one would have expected. CONCLUSION: The study result suggested that treatment satisfaction for nAMD was governed by the perception of being reviewed and injected regularly over a long period of time than the actual change in visual acuity from the treatment.

Ranibizumab 0.5 mg for Diabetic Macular Edema with Bimonthly Monitoring after a Phase of Initial Treatment: 18-Month, Multicenter, Phase IIIB RELIGHT Study.

PURPOSE: To evaluate ranibizumab 0.5 mg using bimonthly monitoring and individualized re-treatment after monthly follow-up for 6 months in patients with visual impairment due to diabetic macular edema (DME). DESIGN: A phase IIIb, 18-month, prospective, open-label, multicenter, single-arm study in the United Kingdom. PARTICIPANTS: Participants (N = 109) with visual impairment due to DME. METHODS: Participants received 3 initial monthly ranibizumab 0.5 mg injections (day 0 to month 2), followed by individualized best-corrected visual acuity (BCVA) and optical coherence tomography-guided re-treatment with monthly (months 3-5) and subsequent bimonthly follow-up (months 6-18). Laser was allowed after month 6. MAIN OUTCOME MEASURES: Mean change in BCVA from baseline to month 12 (primary end point), mean change in BCVA and central retinal thickness (CRT) from baseline to month 18, gain of ≥10 and ≥15 letters, treatment exposure, and incidence of adverse events over 18 months. RESULTS: Of 109 participants, 100 (91.7%) and 99 (90.8%) completed the 12 and 18 months of the study, respectively. The mean age was 63.7 years, the mean duration of DME was 40 months, and 77.1% of the participants had received prior laser treatment (study eye). At baseline, mean BCVA was 62.9 letters, 20% of patients had a baseline BCVA of >73 letters, and mean baseline CRT was 418.1 µm, with 32% of patients having a baseline CRT <300 µm. The mean change in BCVA from baseline to month 6 was +6.6 letters (95% confidence interval [CI], 4.9-8.3), and after institution of bimonthly treatment the mean change in BCVA at month 12 was +4.8 letters (95% CI, 2.9-6.7; P < 0.001) and +6.5 letters (95% CI, 4.2-8.8) at month 18. The proportion of participants gaining ≥10 and ≥15 letters was 24.8% and 13.8% at month 12 and 34.9% and 19.3% at month 18, respectively. Participants received a mean of 6.8 and 8.5 injections over 12 and 18 months, respectively. No new ocular or nonocular safety findings were observed during the study. CONCLUSIONS: The BCVA gain achieved in the initial 6-month treatment period was maintained with an additional 12 months of bimonthly ranibizumab PRN treatment.

Choroidal thinning and "stair-case" foveal sign in a patient with Alport syndrome.

PURPOSE: To quantitatively describe choroidal thickness in a patient with Alport syndrome and to qualitatively describe an unusual "stair-case" foveal sign. METHODS: Retrospective case report. RESULTS: This is the first case, to our knowledge, of the stair-case foveal sign. This is also the first case where choroidal thickness in a patient with Alport rsyndrome has been quantitatively described using enhanced depth imaging optical coherence tomography. CONCLUSION: Stair-case foveal sign and choroidal thinning are two new signs that clinicians can expect to encounter on optical coherence tomography imaging of patients with Alport syndrome.

Amitriptyline for pain control in scleritis may help to avoid excessive steroid use in selected cases: a case report.

INTRODUCTION: Pain in scleritis may be difficult to control with conventional immuno-suppressive regimes. Amitriptyline may be an effective option in those circumstances. CASE PRESENTATION: A 41-year-old woman presented with scleritis and eye pain that was refractory to treatment with steroid and immunosuppressive agents. Effective pain relief and reduction of steroid dose was only achieved after starting amitriptyline. CONCLUSION: Amitriptyline may be an effective option for pain control in case with scleritis which might otherwise require unnecessarily large doses of immunosuppression.

Raising the benchmark for the 21st century--the 1000 cataract operations audit and survey: outcomes, consultant-supervised training and sourcing NHS choice.

PURPOSE: Clinical outcomes for phacoemulsification surgery are still compared with the almost 10-year-old benchmark of the 1997-98 National Cataract Surgery Survey (NCSS) published in this journal. Extraneous to the peer-reviewed research literature, more recent databases suggest much better results may be being obtained. This offered the rare opportunity to perform an audit as research investigating if this was indeed the case and a new benchmark is needed, with the additional standard of rigorous study peer review by independent senior ophthalmologists. At this pilot centre for Patient Choice provision, all cataract surgery was performed on Consultant-supervised training lists, a novel extension in-sourcing care using public resources rather than to an independent sector that may not be supervised by NHS Consultants. Patient satisfaction was also surveyed. We asked whether the NCSS is out-of-date, and whether good outcomes on Choice schemes are compatible with Consultant-led training within the National Health Service? METHODS: An audit of 1000 consecutive patients undergoing cataract surgery on Patient Choice at the Western Eye Hospital between October 2002 and September 2004. All subjects were scheduled for phacoemulsification. A novel policy was extending "choice" onto training list slots for this period. A validated questionnaire assessed patient satisfaction. RESULTS: A best corrected visual acuity of 6/12 or better was obtained in 93% of cases. Over 80% of cases were +/-1 D of target refraction (65.7% within 0.5 D). The total incidence of complications was 8.7%. Overall incidence of major complications was 2.4%. Incidence of vitreous loss was 1.1% and that of endophthalmitis 0.1%. Complications rates were lowest for consultants (less than 1%). User satisfaction with having cataract surgery on "patient choice" was high. CONCLUSIONS: Cataract surgery under patient choice on supervised training lists is associated with a visual outcome and an incidence of complications at least as good as the published national average. User satisfaction is high. Cataract surgery under patient choice is compatible with training activity in receiving hospitals. The improvement in outcomes since the 1997-98 NCSS suggest that the accepted standards for complication rates should be updated to reflect the fact that phacoemulsification has become an established procedure.

Orbital varices, cranial defects, and encephaloceles: an unrecognized association.

PURPOSE: To highlight an apparently unreported association between orbital varices and malformations of the cranial skeleton with or without abnormalities of the underlying cerebral parenchyma. DESIGN: Retrospective, noncomparative review of case notes and radiologic imaging. PARTICIPANTS: Three hundred ten patients attending the Orbital Clinic at Moorfields Eye Hospital, London, with a diagnosis of low-pressure, low-flow orbital venous anomalies. METHODS: All available orbital imaging for patients with orbital venous anomalies was examined. For those with defects of the cranial base, the radiologic characteristics were noted and the clinical details were reviewed. MAIN OUTCOME MEASURES: The presence and type of orbital roof or medial wall defects and associated nasal or other cranial anomalies. RESULTS: Imaging was adequate for review in 222 of 310 patients (72%), and anomalies of the neighboring cranium or cerebral structure were found in 10 of 222 patients (4.5%). In the group with cranial anomalies, the proportion of men (7/10; 70%) did not significantly differ from that in the group with varices but without cranial anomalies (93/212; 44%; P = 0.19, Fisher exact test). Orbital varices were associated with 3 types of cranial anomaly: major midline encephaloceles (type I anomaly; 4 cases), large superomedial defects of the orbital wall (type II; 3 cases), or defects of the greater wing of the sphenoid (type III; 3 cases). CONCLUSIONS: Clinicians should be aware of the possibility of significant cranio-orbital or cranionasal anomalies in patients with orbital venous anomalies; these anomalies can vary from minor defects in the cranial base to large encephalomeningoceles. This rare association should not be overlooked when orbital varices become markedly inflamed, because intranasal encephaloceles are a known predisposition to recurrent meningitis.