Showing papers in "Eye in 2021"

Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance.

Abstract: Corneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for 1.5–2.0 million new cases of monocular blindness per year, highlighting an ongoing uncurbed burden on human health. Among all aetiologies such as infection, trauma, inflammation, degeneration and nutritional deficiency, infectious keratitis (IK) represents the leading cause of corneal blindness in both developed and developing countries, with an estimated incidence ranging from 2.5 to 799 per 100,000 population-year. IK can be caused by a wide range of microorganisms, including bacteria, fungi, virus, parasites and polymicrobial infection. Subject to the geographical and temporal variations, bacteria and fungi have been shown to be the most common causative microorganisms for corneal infection. Although viral and Acanthamoeba keratitis are less common, they represent important causes for corneal blindness in the developed countries. Contact lens wear, trauma, ocular surface diseases, lid diseases, and post-ocular surgery have been shown to be the major risk factors for IK. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though its effectiveness is being challenged by the emergence of antimicrobial resistance, including multidrug resistance, in some parts of the world. In this review, we aim to provide an updated review on IK, encompassing the epidemiology, causative microorganisms, major risk factors and the impact of antimicrobial resistance.

Factors affecting anatomical and visual outcome after macular hole surgery: findings from a large prospective UK cohort

Abstract: To reassess the definition of a large macular hole, factors predicting hole closure and post-surgery visual recovery. Database study of 1483 primary macular hole operations. Eligible operations were primary MH operations treated with a vitrectomy and a gas or air tamponade. Excluded were eyes with a history of retinal detachment, high myopia, previous vitrectomy or trauma. A higher proportion of operations were performed in eyes from females (71.1%) who were ‘on average’ younger (p < 0.001), with slightly larger holes (p < 0.001) than male patients. Sulfur hexafluoride gas was generally used for smaller holes (p < 0.001). From 1253 operations with a known surgical outcome, successful hole closure was achieved in 1199 (96%) and influenced by smaller holes and complete ILM peeling (p < 0.001), but not post-surgery positioning (p = 0.072). A minimum linear diameter of ~500 μm marked the threshold where the success rate started to decline. From the 1056 successfully closed operations eligible for visual outcome analysis, visual success (defined as visual acuity of 0.30 or better logMAR) was achieved in 488 (46.2%) eyes. At the multivariate level, the factors predicting visual success were better pre-operative VA, smaller hole size, shorter duration of symptoms and the absence of AMD. Females undergoing primary macular hole surgery tend to be younger and have larger holes than male patients. The definition of a large hole should be changed to around 500 μm, and patients should be operated on early to help achieve a good post-operative VA.

Transforming ophthalmic education into virtual learning during COVID-19 pandemic: a global perspective.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has imposed measures of social distancing and barriers in delivery of “in person” education. Institutions, involved in training the next generation of ophthalmologists, are using alternative teaching methods to maintain the standard of education. We conducted a worldwide survey among physicians, who are actively involved in Ophthalmology-related education, between 3 and 14 April 2020. The expert survey, developed on the basis of literature search and focus group discussions, comprised 23 questions addressing the use of e-learning in Ophthalmology during the COVID-19 pandemic. A total of 321 participants from both academic and non-academic institutions worldwide, with variable practice experience and expertise, completed the survey. Before the pandemic, the majority of participants used traditional training modalities, including lectures, grand rounds and journal clubs, and 48% did not use any e-learning. There was a statistically significant increase in the use of all e-learning alternatives during the pandemic (p < 0.001), associated mainly with the availability of e-learning facilities (p < 0.001) and the academic character of institutions (p < 0.001). Zoom® was recognized as the mostly used platform for virtual teaching. Although theoretical teaching may take place, the surgical training of residents/fellows was dramatically reduced. The latter was significantly associated with participants’ perspectives about teaching practices (p < 0.001). COVID-19 pandemic imposed great challenges in the educational field of Ophthalmology. The experience related to virtual training in Ophthalmology, gained during the pandemic, may change the traditional teaching practices in the world and provide new educational opportunities.

Optical coherence tomography angiography in diabetic retinopathy: an updated review.

Abstract: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Optical coherence tomography angiography (OCTA) has been developed to visualize the retinal microvasculature and choriocapillaris based on the motion contrast of circulating blood cells. Depth-resolved ability and non-invasive nature of OCTA allow for repeated examinations and visualization of microvasculature at the retinal capillary plexuses and choriocapillaris. OCTA enables quantification of microvascular alterations in the retinal capillary network, in addition to the detection of classical features associated with DR, including microaneurysms, intraretinal microvascular abnormalities, and neovascularization. OCTA has a promising role as an objective tool for quantifying extent of microvascular damage and identify eyes with diabetic macular ischaemia contributed to visual loss. Furthermore, OCTA can identify preclinical microvascular abnormalities preceding the onset of clinically detectable DR. In this review, we focused on the applications of OCTA derived quantitative metrics that are relevant to early detection, staging and progression of DR. Advancement of OCTA technology in clinical research will ultimately lead to enhancement of individualised management of DR and prevention of visual impairment in patients with diabetes.

Refractive surgery beyond 2020.

Abstract: Refractive surgery refers to any procedure that corrects or minimizes refractive errors. Today, refractive surgery has evolved beyond the traditional laser refractive surgery, embodied by the popular laser in situ keratomileusis or 'LASIK'. New keratorefractive techniques such as small incision lenticule extraction (SMILE) avoids corneal flap creation and uses a single laser device, while advances in surface ablation techniques have seen a resurgence in its popularity. Presbyopic treatment options have also expanded to include new ablation profiles, intracorneal implants, and phakic intraocular implants. With the improved safety and efficacy of refractive lens exchange, a wider variety of intraocular lens implants with advanced optics provide more options for refractive correction in carefully selected patients. In this review, we also discuss possible developments in refractive surgery beyond 2020, such as preoperative evaluation of refractive patients using machine learning and artificial intelligence, potential use of stromal lenticules harvested from SMILE for presbyopic treatments, and various advances in intraocular lens implants that may provide a closer to 'physiological correction' of refractive errors.

Deep learning in glaucoma with optical coherence tomography: a review.

Abstract: Deep learning (DL), a subset of artificial intelligence (AI) based on deep neural networks, has made significant breakthroughs in medical imaging, particularly for image classification and pattern recognition. In ophthalmology, applying DL for glaucoma assessment with optical coherence tomography (OCT), including OCT traditional reports, two-dimensional (2D) B-scans, and three-dimensional (3D) volumetric scans, has increasingly raised research interests. Studies have demonstrated that using DL for interpreting OCT is efficient, accurate, and with good performance for discriminating glaucomatous eyes from normal eyes, suggesting that incorporation of DL technology in OCT for glaucoma assessment could potentially address some gaps in the current practice and clinical workflow. However, further research is crucial in tackling some existing challenges, such as annotation standardization (i.e., setting a standard for ground truth labelling among different studies), development of DL-powered IT infrastructure for real-world implementation, prospective validation in unseen datasets for further evaluation of generalizability, cost-effectiveness analysis after integration of DL, the AI "black box" explanation problem. This review summarizes recent studies on the application of DL on OCT for glaucoma assessment, identifies the potential clinical impact arising from the development and deployment of the DL models, and discusses future research directions.

Brolucizumab-early real-world experience: BREW study.

Abstract: Brolucizumab (Beovu, Novartis, Basel, Switzerland) is the newest anti-vascular endothelial growth factor (anti-VEGF) drug. It was approved for the treatment of neovascular agerelated macular degeneration (nAMD) by the US-FDA on October 7, 2019, followed by the European Commission’s approval for use in the European Union on February 17, 2020. Brolucizumab received marketing approval based on the two pivotal phase 3 clinical trials—HAWK and HARRIER, with a q8/q12 week dosing regimen [1]. To the best of our knowledge, real-world clinical data of consecutive patients who have undergone this therapy has not yet been reported. Here, we report the early clinical outcomes regarding safety and efficacy after brolucizumab administration. A retrospective, consecutive, interventional, uncontrolled, multicenter study was conducted incorporating data from four centers in the United States of America (USA). Institutional Review Board approval was obtained at each participating center and the investigators adhered to the tenets of the Declaration of Helsinki. All patients were treated with at least one intravitreal injection of brolucizumab 6 mg between December 2019 and February 2020. A minimum of 4-weeks follow-up was required to be included in the study. Eyes with structural changes other than nAMD and patients with vitreoretinal interface diseases were excluded. Each patient underwent bestcorrected visual acuity (BCVA) measurement with a Snellen chart (converted to LogMAR for analysis), central subfield thickness (CST) with spectral-domain optical coherence tomography and intraocular pressure measurement along with complete ophthalmic examination at baseline and the last follow-up after brolucizumab injection. Descriptive statistics including mean, standard deviation, median, and range were calculated for continuous variables. A paired sample t-test was used to measure the mean differences between preinjection and postinjection values. Forty-two eyes of 42 patients were included in this study. The patients received a total of 60 injections. The mean age was 79.2 ± 7.0 years and 57.2% were females. The mean follow-up period was 7.2 ± 3.6 weeks after the first injection of brolucizumab. Twenty-nine eyes received a single injection of brolucizumab, nine eyes received two injections, three eyes had three injections, and one eye had four injections. All the eyes were previously treated with single or a combination of other intravitreal anti-VEGFs (bevacizumab, ranibizumab, and aflibercept). The median number of previous anti-VEGF injections was 19 (range 3–107). Fifteen eyes received aflibercept and one eye received ranibizumab during the follow-up after brolucizumab injection. Immediate data prior to the first brolucizumab injection was considered as the baseline, and the subsequent data after brolucizumab injection were included in the analysis.

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data.

Abstract: The angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) pathway is an emerging key regulator in vascular development and maintenance Its relevance to clinicians and basic scientists as a potential therapeutic target in retinal and choroidal vascular diseases is highlighted by recent preclinical and clinical evidence The Ang/Tie pathway plays an important role in the regulation of vascular stability, in angiogenesis under physiological and pathological conditions, as well as in inflammation Under physiological conditions, angiopoietin-1 (Ang-1) binds to and phosphorylates the Tie2 receptor, leading to downstream signalling that promotes cell survival and vascular stability Angiopoietin-2 (Ang-2) is upregulated under pathological conditions and acts as a context-dependent agonist/antagonist of the Ang-1/Tie2 axis, causing vascular destabilisation and sensitising blood vessels to the effects of vascular endothelial growth factor-A (VEGF-A) Ang-2 and VEGF-A synergistically drive vascular leakage, neovascularisation and inflammation, key components of retinal vascular diseases Preclinical evidence suggests that modulating the Ang/Tie pathway restores vascular stabilisation and reduces inflammation This review discusses how targeting the Ang/Tie pathway or applying Ang-2/VEGF-A combination therapy may be a valuable therapeutic strategy for restoring vascular stability and reducing inflammation in the treatment of retinal and choroidal vascular diseases

Impact of macular fluid volume fluctuations on visual acuity during anti-VEGF therapy in eyes with nAMD

Abstract: Objectives To study the effect of repeated retinal thickness fluctuations during the anti-VEGF therapy maintenance phase in neovascular age-related macular degeneration (nAMD). Methods Data were extracted from electronic medical records of 381 nAMD patients, aged ≥50 years; baseline VA ≥33 and ≤73 letters; ≥24 months' follow-up and ≥2 optical coherence tomography (OCT) measurements. OCT scans were analysed using an artificial intelligence algorithm that quantified the volumes of intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED) and central subfield thickness (CSFT). IRF, SRF and PED were summed to obtain total fluid (TF). The standard deviation (SD) of IRF, SRF, PED, CSFT and TF was computed and categorised into quartiles (SD-Q). Relationships between SD-Qs for each OCT feature and VA change was tested using generalised estimating equations and linear regression. Results By Month 24, compared to SD-Q1, eyes in SD-Q2, SD-Q3, and SD-Q4 for IRF, SRF, PED, CSFT and TF showed greater VA losses. Eyes in SD-Q4 of TF were 9.4 letters worse compared to eyes in Q1 (95% Confidence Interval: -12.9 to -6.0). The frequency of clinic visits with IRF and SRF present on OCT scans by quartiles of CSFT was lower in eyes with least fluctuation (Q1) compared to eyes with the most fluid fluctuation (Q4) (median [IQR] IRF: 0.3 [0.0-0.7] versus 0.8 [0.5-1.0]; SRF: 0.0 [0.0-0.5] versus 0.6 [0.3-1.0]). Conclusions Greater fluctuations in retinal fluid volumes during the maintenance phase of anti-VEGF treatment in nAMD is associated with worse VA by 2 years.

Review of retinal cameras for global coverage of diabetic retinopathy screening

Abstract: The global burden of diabetes has resulted in an increase in the prevalence of diabetic retinopathy (DR), a microvascular complication of diabetes. Lifelong repetitive screening for DR is essential for early detection and timely management to prevent visual impairment due to the silent sight-threatening disorder. Colour fundus photography (CFP) is helpful for documentation of the retinopathy as well as for counselling the patient. CFP has established roles in DR screening, detection, progression and monitoring of treatment response. DR screening programmes use validated mydriatic or non-mydriatic fundus cameras for retinal imaging and trained image graders identify referable DR. Smartphone-based fundus cameras and handheld fundus cameras that are cost-effective, portable and easy to handle in remote places are gaining popularity in recent years. The images captured with these low-cost devices can be immediately sent to trained ophthalmologists for grading of DR. Recent increase in numbers of telemedicine programmes based on imaging with digital fundus cameras and remote interpretation has facilitated larger population coverage of DR screening and timely referral of those with sight-threatening DR to ophthalmologists. Good-quality retinal imaging and accurate diagnosis are essential to reduce inappropriate referrals. Advances in digital imaging such as ultra-wide field imaging and multi-modal imaging have opened new avenues for assessing DR. Fundus cameras with integrated artificial intelligence (AI)-based automated algorithms can also provide instant DR diagnosis and reduce the burden of healthcare systems. We review the different types of fundus cameras currently used in DR screening and management around the world.

Ocular benzalkonium chloride exposure: problems and solutions.

Abstract: Preservatives in multidose formulations of topical ophthalmic medications are crucial for maintaining sterility but can be toxic to the ocular surface. Benzalkonium chloride (BAK)-used in approximately 70% of ophthalmic formulations-is well known to cause cytotoxic damage to conjunctival and corneal epithelial cells, resulting in signs and symptoms of ocular surface disease (OSD) including ocular surface staining, increased tear break-up time, and higher OSD symptom scores. These adverse effects are more problematic with chronic exposure, as in lifetime therapy for glaucoma, but can also manifest after exposure as brief as seven days. Multiple strategies are available to minimize or eliminate BAK exposure, among them alternative preservatives, preservative-free formulations including sustained release drug delivery platforms, and non-pharmacological therapies for common eye diseases and conditions. In this paper, we review the cytotoxic and clinical effects of BAK on the ocular surface and discuss existing and emerging options for ocular disease management that can minimize or eliminate BAK exposure.

Psychosocial impact of COVID-19 pandemic lockdown on people living with eye diseases in the UK.

Abstract: In response to the Coronavirus disease 2019 (or COVID-19) pandemic, many countries across the world, including the UK, had imposed nationwide lockdown. Ophthalmology represents one of the busiest outpatient-based specialties, and cancellation of routine services meant that thousands of eye patients had been affected. Several studies have previously shown that COVID-19 lockdown and quarantine in general could negatively impact on the mental health of adults, children, and healthcare workers [1–3], but the impact of people with eye diseases has not been evaluated. In this survey, we aimed to evaluate the psychosocial impact of COVID-19 lockdown on people living with eye diseases in the UK. In May 2020, a 27-item online questionnaire-based survey was administered to individuals (≥18 years old) with eye diseases (Supplementary Table 1). Participants were identified through various eye support charities or support groups. The level of visual impairment (VI) was categorised into normal/mild, moderate, and severely sight impaired/ blind. Statistical analysis was performed using IBM SPSS Statistics v26. Multivariable logistic regression analysis was conducted to determine the predictive factors for worsened mental health, loneliness, and fear of further sight loss during lockdown. Ethical approval of this survey was waived as no medical assessment/intervention was performed. Informed consent for publication was obtained from all participants. Of all 325 respondents, 64.3% were ≥65 years and 71.1% were female (Supplementary Table 2). The level of VI was none/mild (34.8%), moderate (38.2%), severe/blind (24.9%), and unmentioned (8.3%). The lockdown negatively impacted on the mental health (45.9%), loneliness (46.0%), social life (85.3%), anxiety related to hospital visits (55.1%), and fear of further sight loss due to delayed review/treatment (45.9%), amongst others (Fig. 1). In addition, 39.2% respondents mentioned that their eye diseases had made it more difficult to cope with the lockdown. Logistic regression analyses demonstrated that the lockdown had significantly affected the mental health of people who were of 18–64 years (OR 3.16; p < 0.001), and with moderate (OR 2.61; p= 0.001) or severe VI (OR 2.07; p= 0.044; Table 1). People with moderate or severe VI were three times more likely to experience increased loneliness than those with mild/no VI (p < 0.001 and p= 0.002, respectively). Fear of further sight loss was similar across all age groups, gender, and extent of VI (all p > 0.05). The open comments reflected anxiety, stress, and fear impacting on mental health, compounded by the limitations posed by their VI on undertaking routine activities or providing care to other family members. Sight loss is a big health concern, and delay in follow-up and care could result in significant and/or permanent harm to vision [4]. We highlighted that COVID-19 lockdown could pose a significant negative psychosocial impact on people with VI. It is therefore important to recognise and provide additional psychosocial support to this vulnerable group of people during the pandemic [3]. COVID-19 pandemic has posed challenges but also presented new opportunities. In view of the significant backlog of work and ongoing social distancing measures, adoption of telemedicine in ophthalmology will likely become the new “norm” of ophthalmology during and after the pandemic [5]. * Darren Shu Jeng Ting ting.darren@gmail.com

Drusen and pachydrusen: the definition, pathogenesis, and clinical significance.

Abstract: The pachychoroid disease spectrum encompasses seven major retinal conditions including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and pachychoroid neovasculopathy or type I macular neovascularisation (MNV) secondary to chronic persistent thickening and dysfunction of the choroidal vasculature. Drusen are focal yellow-white deposits of extracellular debris, which consist of complement proteins, esterified and nonesterified cholesterol, apolipoproteins, carbohydrates, and trace elements, above the retinal pigment epithelium (RPE) or between the RPE and Bruch's membrane. Although drusen are an essential disease precursor of advanced age-related macular degeneration (AMD), a new entity "pachydrusen" has been identified to be associated with some of the enitites that constitute the pachychoroid spectrum. It remains to be determined what the exact differences are between soft drusen, pseudodrusen, and pachydrusen in terms of phenotype, genotype, and pathogenesis. Improving our knowledge in these areas will inevitably improve our understanding of their clinical significance especially as in disease prediction in AMD and the pachychroid spectrum disorders. It remains controversial whether PCV is a subtype of AMD. Understanding the pathogenesis of different types of drusen may also help in addressing if phenotype and/or genotype of type 1 MNV associated with pachychoroid are similar to type 1 MNV related to AMD. Furthermore, because pachydrusen links two pachychoroid diseases, CSC and PCV, it is also of great interest to investigate if CSC is an early stage or a predictor of PCV in future research. In this review, we share our experience in clinical practice and the latest published evidence-based literature to emphasize the differences and similarities in morphology, pathogenesis, and clinical significance of drusen and pachydrusen, a new member of the pachychoroid spectrum disorders.

Neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein associated disorder-optic neuritis: a comprehensive review of diagnosis and treatment.

Abstract: Optic neuritis (ON) is the most common cause of acute optic neuropathy in patients younger than 50 years of age and is most frequently idiopathic or associated with multiple sclerosis. However, the discovery of aquaporin-4 immunoglobulin G (IgG) and myelin oligodendrocyte glycoprotein (MOG)-IgG as biomarkers for two separate central nervous system inflammatory demyelinating diseases has revealed that neuromyelitis optica spectrum disorder (NMSOD) and MOG-IgG-associated disease (MOGAD) are responsible for clinically distinct subsets of ON. NMOSD-ON and MOGAD-ON both demonstrate tendencies for bilateral optic nerve involvement and often exhibit a relapsing course with the potential for devastating long-term visual outcomes. Early and accurate diagnosis is therefore essential. This review will summarize the current understanding of the clinical spectra of NMOSD and MOGAD, the radiographic and serological findings which support their diagnoses, and the current evidence behind various acute and long-term therapeutic strategies for ON related to these conditions. A particular emphasis is placed on a number of recent multi-centre randomized placebo-controlled trials, which provide the first level I evidence for long-term treatment of NMOSD.

Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae.

Abstract: Objectives To determine the presenting features of ocular surface disease in patients with atopic dermatitis (AD) treated with dupilumab at a tertiary, university hospital. To establish the need for treatment of dupilumab-associated ocular surface disease and report any long-term effects on the ocular surface. Methods A retrospective analysis of consecutive patients treated with dupilumab for AD between January 2017 and August 2019 was undertaken. Data were collected on demographics, incidence and type of ocular disease features, natural history and treatment. Results A total of 50% (14/28) patients developed ocular symptoms with a mean time of onset of 6.75 (±6.1) weeks from starting dupilumab. Of these, 69% (9/13) were diagnosed with conjunctivitis associated with cicatrisation in two patients and periorbital skin changes in four. Of these nine, four had prior history of atopic keratoconjunctivitis. All were treated with topical steroids; two required additional ciclosporin drops. In all, 67% (6/9) patients went on to have on-going ocular inflammation requiring maintenance drops at a mean of 16 (±6.9) months of follow-up. All patients had improvement in their AD severity; only one patient discontinued dupilumab due to ocular side effects. Conclusion The rate of dupilumab-associated ocular surface disease was 32%. Periorbital skin changes and conjunctival cicatrisation were noted in association with conjunctivitis. Ocular surface disease improved on topical steroids and ciclosporin but 67% of patients needed on-going treatment. Close liaison with an ophthalmologist should be considered in those patients who develop conjunctivitis or have a past history of severe ocular surface disease.

Adaptive optics: principles and applications in ophthalmology.

Abstract: This is a comprehensive review of the principles and applications of adaptive optics (AO) in ophthalmology. It has been combined with flood illumination ophthalmoscopy, scanning laser ophthalmoscopy, as well as optical coherence tomography to image photoreceptors, retinal pigment epithelium (RPE), retinal ganglion cells, lamina cribrosa and the retinal vasculature. In this review, we highlight the clinical studies that have utilised AO to understand disease mechanisms. However, there are some limitations to using AO in a clinical setting including the cost of running an AO imaging service, the time needed to scan patients, the lack of normative databases and the very small size of area imaged. However, it is undoubtedly an exceptional research tool that enables visualisation of the retina at a cellular level.

Conventional glaucoma implants and the new MIGS devices : a comprehensive review of current options and future directions

Abstract: Glaucoma is a progressive optic neuropathy that is the second leading cause of preventable blindness worldwide, after cataract formation. A rise in the intraocular pressure (IOP) is considered to be a major risk factor for glaucoma and is associated with an abnormal increase of resistance to aqueous humour outflow from the anterior chamber. Glaucoma drainage devices have been developed to provide an alternative pathway through which aqueous humour can effectively exit the anterior chamber, thereby reducing IOP. These devices include the traditional aqueous shunts with tube-plate design, as well as more recent implants, such as the trabeculectomy-modifying EX-PRESS® implant and the new minimally invasive glaucoma surgery (MIGS) devices. In this review, we will describe each implant in detail, focusing on their efficacy in reducing IOP and safety profile. Additionally, a critical and evidence-based comparison between these implants will be provided. Finally, we will propose potential developments that may help to improve the performance of current devices.

Deep learning-based automated detection for diabetic retinopathy and diabetic macular oedema in retinal fundus photographs.

Abstract: Objectives To present and validate a deep ensemble algorithm to detect diabetic retinopathy (DR) and diabetic macular oedema (DMO) using retinal fundus images. Methods A total of 8739 retinal fundus images were collected from a retrospective cohort of 3285 patients. For detecting DR and DMO, a multiple improved Inception-v4 ensembling approach was developed. We measured the algorithm's performance and made a comparison with that of human experts on our primary dataset, while its generalization was assessed on the publicly available Messidor-2 dataset. Also, we investigated systematically the impact of the size and number of input images used in training on model's performance, respectively. Further, the time budget of training/inference versus model performance was analyzed. Results On our primary test dataset, the model achieved an 0.992 (95% CI, 0.989-0.995) AUC corresponding to 0.925 (95% CI, 0.916-0.936) sensitivity and 0.961 (95% CI, 0.950-0.972) specificity for referable DR, while the sensitivity and specificity for ophthalmologists ranged from 0.845 to 0.936, and from 0.912 to 0.971, respectively. For referable DMO, our model generated an AUC of 0.994 (95% CI, 0.992-0.996) with a 0.930 (95% CI, 0.919-0.941) sensitivity and 0.971 (95% CI, 0.965-0.978) specificity, whereas ophthalmologists obtained sensitivities ranging between 0.852 and 0.946, and specificities ranging between 0.926 and 0.985. Conclusion This study showed that the deep ensemble model exhibited excellent performance in detecting DR and DMO, and had good robustness and generalization, which could potentially help support and expand DR/DMO screening programs.

Optical coherence tomography in the 2020s-outside the eye clinic.

Abstract: Optical coherence tomography (OCT) is a paragon of success in the translation of biophotonics science to clinical practice. OCT systems have become ubiquitous in eye clinics but access beyond this is limited by their cost, size and the skill required to operate the devices. Remarkable progress has been made in the development of OCT technology to improve the speed of acquisition, the quality of images and into functional extensions of OCT such as OCT angiography. However, more needs to be done to radically improve the access to OCT by addressing its limitations and enable penetration outside of typical clinical settings and into underserved populations. Beyond high-income countries, there are 6.5 billion people with similar eye-care needs, which cannot be met by the current generation of bulky, expensive and complex OCT systems. In addition, advancing the portability of this technology to address opportunities in point-of-care diagnostics, telemedicine and remote monitoring may aid development of personalised medicine. In this review, we discuss the major milestones in OCT hardware development to reach those beyond the eye clinic.

Teprotumumab for non-inflammatory thyroid eye disease (TED): evidence for increased IGF-1R expression

Abstract: Purpose Teprotumumab, a blocking antibody to the insulin like growth factor 1 receptor (IGF-1R) has been shown to significantly reduce proptosis in recent phase 2 and 3 trials in patients with inflammatory thyroid eye disease (TED). Herein, we investigate the impact of teprotumumab on patients with non-inflammatory TED. We also investigate the expression of the IGF-1R on orbital tissues from patients with inflammatory and non-inflammatory TED compared to controls. Methods Consecutive patients with non-inflammatory TED (clinical activity score, CAS ≤ 1, for at least 4 months, were treated with teprotumumab. They received a complete course (total eight infusions) of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for subsequent infusions every 3 weeks). The primary outcome was a proptosis response at week 24. Further, IGF-1R α and β expression was evaluated on orbital tissue from patients with inflammatory and non-inflammatory TED, as well as healthy controls. Non-biased histological analysis of IGF-1R expression was performed using ImageJ. Results Four patients met eligibility criteria for the clinical study, with a mean (SD) CAS of 0 (0). Following teprotumumab treatment, there was a mean (SD) reduction in proptosis of 2.6 mm (1.2). Five patients were included for each group of the histological study; inflammatory TED, non-inflammatory TED and controls. IGF-1Rα and IGF-1Rβ expression was significantly greater in the orbital tissues of patients with inflammatory TED and non-inflammatory TED, when compared to controls. Conclusion Our findings demonstrate for the first time, that teprotumumab, a blocking antibody to the IGF-1R reduces proptosis in a series of patients with non-inflammatory TED. Overexpression of the IGF-1R in orbital tissue from patients with non-inflammatory disease compared to controls may be an important consideration for effect.

The effect of home education on myopia progression in children during the COVID-19 pandemic.

Abstract: OBJECTIVES: To evaluate the effect of the COVID-19 pandemic restrictions on myopia progression (MP) in school age children. METHODS: A total of 115 children aged 8-17 years with a diagnosis of myopia who had been followed-up for at least three years, were included in this study with a retrospective and single-centre design. The subjects' age, the history of myopia in the family, the time spent in front of a screen, the digital devices used during home education (computer, tablet, smartphone, television), the time spent in open air (hours/day), the refractive error (RE) (spherical equivalent value) detected before the home education period and the changes in the myopia over the years, were recorded. RESULTS: The mean age was 12.06 (±2.29) years. Only the right eyes were included. The glasses use duration was 3.57 (±0.74) years. The annual MP amount 0.49 (±0.26), 0.41 (±0.36) and 0.54 (±0.43) dioptres (D) for the 2017, 2018 and 2019 years before home education, respectively, (p > 0.05), and 0.71 (±0.46) D in 2020, during home education. The increase in MP amount in 2020 compared to the 2019 and 2018 years was statistically significant (p < 0.003). MP was statistically significantly less in children who participated in open-air activities for 2 h a day and those who lived in detached houses (p = 0.004, p = 0.006, respectively). CONCLUSION: During home confinement, education programmes of school children should be designed while taking into account preventive measures for MP, in particular for allowing children to spend at least 2 h of outdoor time per day.

Optical coherence tomography (OCT) in neuro-ophthalmology.

Abstract: Optical coherence tomography (OCT) is a non-invasive medical imaging technology that is playing an increasing role in the routine assessment and management of patients with neuro-ophthalmic conditions. Its ability to characterise the optic nerve head, peripapillary retinal nerve fibre layer and cellular layers of the macula including the ganglion cell layer enables qualitative and quantitative assessment of optic nerve disease. In this review, we discuss technical features of OCT and OCT-based imaging techniques in the neuro-ophthalmic context, potential pitfalls to be aware of, and specific applications in more common neuro-ophthalmic conditions including demyelinating, inflammatory, ischaemic and compressive optic neuropathies, optic disc drusen and raised intracranial pressure. We also review emerging applications of OCT angiography within neuro-ophthalmology.

Addressing post-operative Mask-Associated Dry Eye (MADE).

Abstract: COVID-19 has resulted in public health legislation in the UK mandating the wearing of facemasks in all healthcare settings by both patients and hospital staff to try and reduce viral spread [1]. This recommendation has particular relevance to a ‘close proximity’ specialty like ophthalmology [1–3]. Previous publications have discussed the uncertain clinical significance from the potential reduction in microbiological particles onto the surgical field when ophthalmic surgeons wear surgical masks intraoperatively, yet COVID19 advice has now extended those principles to patients [3]. As the general population adjusts to widespread facemask use, there is an increasing awareness of Mask-Associated Dry Eye (MADE), due in part to ill-fitting designs and leakage of air [4]. We wish to report a recent case of acute post-operative MADE and discuss the implications of this public health recommendation on ocular surgery. A 66-year-old female with previous LASIK for high myopia attended for cataract surgery under topical anaesthesia. Following application of topical proxymetacaine and 5% povidone-iodine to the ocular surface, she underwent routine left phaco-emulsification surgery which lasted less than 10 min in total. At the end of the operation, the cornea looked clear and a clear plastic shield was placed as standard and her facemask replaced. On leaving the theatre environment, she expressed delight at her “clear vision”. A few hours later, she returned with distress, reporting increasingly blurred vision and discomfort. Unaided visual acuity was Counting Fingers, which improved to 6/9 Snellen with pinhole. She had widespread corneal haze and superficial staining with topical fluorescein but no epithelial defect or wound leak, normal IOP and no evidence of intraocular inflammation (Toxic Anterior Segment Syndrome; TASS). The LASIK flap was undisturbed. It was notable that the operated left eye was extremely dry compared to the right, and the patient’s facemask was very loose around her nose (Fig. 1). The clear shield was exchanged for a paraffin gauze dressing and pad for 24 h; she was advised to use her post-operative steroid and antibiotic drops as planned, and minimise facemask use where possible. She reported complete restoration of good vision within 2 days, confirmed as 6/7.5 Unaided Snellen at clinic review 1 week later with clear cornea and no evidence of dry eye (Fig. 2). Painful visual loss within a few hours following routine cataract surgery is concerning, and the ophthalmologist must rule out intra-ocular conditions such as TASS or raised pressure (due to retained viscoelastic, capsule distension syndrome or aqueous misdirection). Surface problems such as traumatic corneal abrasions can present in a similar way. We believe this to be the first reported case of visual loss due to acute post-operative MADE following routine topical cataract surgery. It is likely that the poorly fitting facemask was causing the patient’s breath to be directed onto the anaesthetised post-operative ocular surface and causing a variant of exposure keratopathy. Exposure keratopathy due to inappropriate airflow has been reported in the Intensive Care Unit and in patients using ventilation machines for sleep apnoea [5, 6]. Forced airflow has also been associated with dry eye, bacterial conjunctivitis and even

Repeatability of total Keratometry and standard Keratometry by the IOLMaster 700 and comparison to total corneal astigmatism by Scheimpflug imaging.

Abstract: Objectives We aimed (1) to assess the repeatability of Total Keratometry (TK) and standard keratometry (K) measurements, as provided by the IOLMaster 700 (Carl Zeiss Meditec), and (2) to compare the corneal astigmatism measured by TK to the total corneal astigmatism (TCA) measured by a Scheimpflug camera (Pentacam AXL, Oculus). Methods Two groups of patients were prospectively enrolled: Group A included previously unoperated eyes undergoing cataract surgery, and Group B eyes with previous myopic corneal excimer laser surgery. TK and K were measured three times by the same examiner. Repeatability was assessed based on the within-subject standard deviation (Sw), test-retest variability, coefficient of variation and intraclass correlation coefficient (ICC). In Group A, TCA was measured once and compared to TK astigmatism. Vector analysis was performed according to Naeser. Results In Group A (69 eyes) the mean K and TK were, respectively, 43.14 ± 1.37 D and 43.18 ± 1.37 D. In Group B (51 eyes) the mean K and TK were, respectively, 40.14 ± 2.20 D and 39.71 ± 2.35 D. The repeatability of the average K and TK was high (Sw 0.9. For most measurements the variance of K and TK did not show any statistically significant difference either within groups or between groups. Vectors KP(45) were significantly different between TK astigmatism and TCA. Conclusions TK measurements offer high repeatability in unoperated and post-excimer laser surgery eyes. TK astigmatism and TCA measurements could not be considered interchangeable.

Factors affecting visual recovery after successful repair of macula-off retinal detachments: findings from a large prospective UK cohort study

Abstract: Objective To identify risk factors affecting visual outcomes in successfully re-attached macula-off rhegmatogenous retinal detachment (RD) surgery. Design A prospective study, using online databases, of visual outcomes for 2074 macula-off retinal detachments that were successfully re-attached by vitrectomy and internal tamponade. The database included detailed retinal diagrams of each detachment. Main outcome measure The probability of achieving a post-operative visual acuity (VA) of ≤0.30 LogMAR (Snellen 6/12 or better). Results Male patients accounted for 64.9% of the sample and the median age was 63 years old. The median pre-operative VA was counting fingers (LogMAR 1.98); this improved to 0.41 LogMAR post-operatively. A post-operative VA of ≤0.30 LogMAR was achieved for 1012 (48.8%) eyes and the factors affecting this were the patient age and gender, pre-operative VA, duration of central vision loss, PVR grade, lens status, total RD and the presence of any ocular co-pathology where the model area under the receiver operator curve was 71.6%. Conclusions From the identified risk factors that decrease the probability of achieving a post-operative visual acuity of ≤0.30 LogMAR, the most important modifiable risk factor was the duration of central vision loss. Recent macula-off retinal detachments should be repaired within 72 h of the loss of central vision.

Advances and potential new developments in imaging techniques for posterior uveitis Part 2: invasive imaging methods.

Abstract: The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that have become available since the 1990s, some 30 years after fluorescein angiography had revolutionised imaging of posterior uveitis in particular imaging of the retinal vascular structures in the 1960s. We have focussed our review on precise imaging methods that have been standardised and validated and can be used universally thanks to commercially produced and available instruments for the diagnosis and follow-up of posterior uveitis. The second part of this imaging review will deal with invasive imaging methods and in particular ocular angiography.

Fluid as a critical biomarker in neovascular age-related macular degeneration management: literature review and consensus recommendations

Abstract: Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD A total of 654 publications were screened for relevance and 66 publications were included for review Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAMD However, few guidelines distinguished between types of fluid when providing recommendations A total of 52 publications reported primary evidence from clinical trials, studies, and chart reviews Observations from these were sometimes inconsistent, but trends were observed with regard to features reported as being predictive of visual outcomes Based on these findings, diagnostic recommendations and a treatment algorithm based on a treat-and-extend (T&E) regimen were developed These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the T&E regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity

Evaluation of the inner choroid using OCT angiography.

Abstract: The advent of optical coherence tomography angiography (OCTA) has allowed a qualitative and quantitative analysis of the retinal vasculature and the choriocapillaris. With the use of OCTA, several studies evaluated the changes in the choriocapillaris showing how this vascular structure plays a significant role in the pathogenesis of different conditions. This article reviews the current methods of analysis of the choriocapillaris and the relevant findings in different chorioretinal diseases.