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Showing papers in "British Journal of Ophthalmology in 2019"


Journal ArticleDOI
TL;DR: There are also potential challenges with DL application in ophthalmology, including clinical and technical challenges, explainability of the algorithm results, medicolegal issues, and physician and patient acceptance of the AI ‘black-box’ algorithms.
Abstract: Artificial intelligence (AI) based on deep learning (DL) has sparked tremendous global interest in recent years. DL has been widely adopted in image recognition, speech recognition and natural language processing, but is only beginning to impact on healthcare. In ophthalmology, DL has been applied to fundus photographs, optical coherence tomography and visual fields, achieving robust classification performance in the detection of diabetic retinopathy and retinopathy of prematurity, the glaucoma-like disc, macular oedema and age-related macular degeneration. DL in ocular imaging may be used in conjunction with telemedicine as a possible solution to screen, diagnose and monitor major eye diseases for patients in primary care and community settings. Nonetheless, there are also potential challenges with DL application in ophthalmology, including clinical and technical challenges, explainability of the algorithm results, medicolegal issues, and physician and patient acceptance of the AI ‘black-box’ algorithms. DL could potentially revolutionise how ophthalmology is practised in the future. This review provides a summary of the state-of-the-art DL systems described for ophthalmic applications, potential challenges in clinical deployment and the path forward.

669 citations


Journal ArticleDOI
TL;DR: This manuscript was aimed at reporting the revised IWOS criteria, established in an international meeting, for the diagnosis of ocular sarcoidosis, which was proposed by a consensus workshop held on 27 April 2017 in Nusa Dua, Bali, Indonesia.
Abstract: Aims International criteria for the diagnosis of ocular sarcoidosis (OS) was established by the first International Workshop on Ocular Sarcoidosis (IWOS) and validations studies revealed certain limitations of the criteria. To overcome the limitations, revised IWOS criteria was established in an international meeting. This manuscript was aimed at reporting the revised IWOS criteria. Methods A consensus workshop was carried out to discuss and revise the IWOS criteria. The workshop was held on 27 April 2017, in Nusa Dua, Bali, Indonesia. Prior to the workshop, a questionnaire proposing revised criteria and consisting of one item for differential diagnosis, seven items for ocular clinical signs, 10 items for systemic investigations and three categories of diagnostic criteria was circulated to 30 uveitis specialists. Questionnaire items with over 75% support were taken as consensus agreement; items with below 50% support were taken as consensus disagreement and items with 50%–75% support were discussed at the workshop. Of the latter items, those supported by two-thirds majority in the workshop were taken as consensus agreement. Results The survey and subsequent workshop reached consensus agreements of the revised criteria for the diagnosis of OS as follows: (1) other causes of granulomatous uveitis must be ruled out; (2) seven intraocular clinical signs suggestive of OS; (3) eight results of systemic investigations in suspected OS and (4) three categories of diagnostic criteria depending on biopsy results and combination of intraocular signs and results of systemic investigations. Conclusions Revised IWOS criteria were proposed by a consensus workshop.

159 citations


Journal ArticleDOI
TL;DR: The genetics, and clinical, psychophysical, electrophysiological and retinal imaging characteristics of cone and cone-rod dystrophies are discussed, focusing particularly on four of the most common disease-associated genes: GUCA1A, PRPH2, ABCA4 and RPGR.
Abstract: Progressive cone and cone-rod dystrophies are a clinically and genetically heterogeneous group of inherited retinal diseases characterised by cone photoreceptor degeneration, which may be followed by subsequent rod photoreceptor loss. These disorders typically present with progressive loss of central vision, colour vision disturbance and photophobia. Considerable progress has been made in elucidating the molecular genetics and genotype-phenotype correlations associated with these dystrophies, with mutations in at least 30 genes implicated in this group of disorders. We discuss the genetics, and clinical, psychophysical, electrophysiological and retinal imaging characteristics of cone and cone-rod dystrophies, focusing particularly on four of the most common disease-associated genes: GUCA1A, PRPH2, ABCA4 and RPGR Additionally, we briefly review the current management of these disorders and the prospects for novel therapies.

116 citations


Journal ArticleDOI
TL;DR: The i-ROP DL system accurately identifies diagnostic categories and overall disease severity in an automated fashion, after being trained only on posterior pole vascular morphology, provides proof of concept that a deep learning screening platform could improve objectivity of ROP diagnosis and accessibility of screening.
Abstract: Background Prior work has demonstrated the near-perfect accuracy of a deep learning retinal image analysis system for diagnosing plus disease in retinopathy of prematurity (ROP). Here we assess the screening potential of this scoring system by determining its ability to detect all components of ROP diagnosis. Methods Clinical examination and fundus photography were performed at seven participating centres. A deep learning system was trained to detect plus disease, generating a quantitative assessment of retinal vascular abnormality (the i-ROP plus score) on a 1–9 scale. Overall ROP disease category was established using a consensus reference standard diagnosis combining clinical and image-based diagnosis. Experts then ranked ordered a second data set of 100 posterior images according to overall ROP severity. Results 4861 examinations from 870 infants were analysed. 155 examinations (3%) had a reference standard diagnosis of type 1 ROP. The i-ROP deep learning (DL) vascular severity score had an area under the receiver operating curve of 0.960 for detecting type 1 ROP. Establishing a threshold i-ROP DL score of 3 conferred 94% sensitivity, 79% specificity, 13% positive predictive value and 99.7% negative predictive value for type 1 ROP. There was strong correlation between expert rank ordering of overall ROP severity and the i-ROP DL vascular severity score (Spearman correlation coefficient=0.93; p Conclusion The i-ROP DL system accurately identifies diagnostic categories and overall disease severity in an automated fashion, after being trained only on posterior pole vascular morphology. These data provide proof of concept that a deep learning screening platform could improve objectivity of ROP diagnosis and accessibility of screening.

109 citations


Journal ArticleDOI
TL;DR: Functional and structural impairments have already started in diabetic retina even in the absence of visible retinal lesions, and Subtle microvascular abnormalities rather than ganglion cell loss might be associated with early functional changes in NDR patients.
Abstract: Aims To investigate the function and the corresponding neurovascular structures in patients with diabetes without clinically detectable retinopathy. Methods Sixty-six patients with type 2 diabetes without retinopathy (NDR) and 62 healthy controls were recruited. The 16 and 32 Tds flicker electroretinography (ERG) was performed using a mydriasis-free, full-field flicker ERG recording device (RETeval). The vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP), FD300 and ganglion cell complex (GCC) thickness in the macula were quantified using optical coherence tomography angiography (OCTA). The retinal nerve fibre layer (RNFL) thickness and the radial peripapillary capillary (RPC) density in the peripapillary area were also measured with OCTA. Results Parafoveal and perifoveal VD in both SCP and DCP decreased in NDR group in comparison to control group (all p Conclusion Functional and structural impairments have already started in diabetic retina even in the absence of visible retinal lesions. Subtle microvascular abnormalities rather than ganglion cell loss might be associated with early functional changes in NDR patients. Poor control of blood glucose was associated with delayed implicit time of flicker ERG in preclinical diabetic retinopathy.

91 citations


Journal ArticleDOI
TL;DR: Overall, PD, VLD and FD progressively decreased with worsening DR severity in segmented and non-segmented layers for all SS-OCTA scan sizes, and for detecting DR, 3×3 mm images best predicted DR for all evaluated quantitative parameters.
Abstract: Aims To evaluate quantitative metrics of the retinal microvasculature in eyes with diabetic retinopathy (DR) using various en face swept-source optical coherence tomography angiography (SS-OCTA) image sizes. Methods Non-segmented and segmented images were acquired using an SS-OCTA device (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, California, USA). The scanning protocols included the 3×3 mm, 6×6 mm and 12×12 mm fields of view. Quantitative analysis of the perfusion density (PD), vessel length density (VLD) and fractal dimension (FD) was performed. The area under the receiver operating characteristic curve was estimated to assess the ability of each image size to predict DR. Results This prospective, cross-sectional study included 60 eyes, (non-DR, 13 eyes; non-proliferative DR (NPDR), 24 eyes; proliferative DR (PDR), 23 eyes) of 46 patients with diabetes and 21 eyes of 16 healthy individuals. In the 12×12 mm images, the PD of healthy individuals was significantly greater than that of patients with NPDR or PDR for all layers (NPDR, p Conclusions Vascular changes in DR can be monitored in detail through quantitative evaluations that combine different SS-OCTA scan sizes and parameters.

81 citations


Journal ArticleDOI
TL;DR: A significant impairment of the CC flow is present in the zone immediately surrounding the GA lesions strengthening the hypothesis that CC alterations may be relevant to the progression of GA.
Abstract: Aims To evaluate the choriocapillaris (CC) flow alterations around geographic atrophy (GA) in eyes with dry age-related macular degeneration. Methods Using a swept-source optical coherence tomography angiography (SS-OCTA) device, two volume 6×6 mm scans were acquired in patients with GA presenting between June and December 2017 at the Doheny-UCLA Eye Centers. The area of GA was delineated on the en face structural OCT fundus images. For each eye, the en face OCTA slabs at the level of the CC from the two acquisitions were averaged and compensated for signal loss using the corresponding structural en face images. The resulting images were binarised and analysed for the percentage of flow voids in the para-atrophy zone (a 500 µm wide ring around the immediate edge of the atrophy) and in the peri-atrophy zone (a 500 µm wide ring around the para-atrophy zone edge), the latter considered as a reference in the comparative analysis. Results Thirty eyes of 20 patients were enrolled. The percentage of flow voids in the para-atrophy zone was 27.23%±6.29% and was significantly higher than in the surrounding peri-atrophy zone (23.4%±6.01%; p Conclusions A significant impairment of the CC flow is present in the zone immediately surrounding the GA lesions strengthening the hypothesis that CC alterations may be relevant to the progression of GA.

80 citations


Journal ArticleDOI
Li-min Chen1, Lijuan Wang1, Yang Hu1, Xiao-han Jiang1, Yu-zhi Wang1, Yingqi Xing1 
TL;DR: Ulasonic measurement of ONSD can reflect the relative real-time changes in ICP, and with a reduction in cerebrospinal fluid pressure, 80 subjects showed an immediate drop in ONSD.
Abstract: The current study aimed to identify whether ultrasonographic measurements of optic nerve sheath diameter (ONSD) could dynamically and sensitively evaluate real-time intracranial pressure (ICP). ONSD measurements were performed approximately 5 min prior to and after a lumbar puncture (LP). A total of 84 patients (mean±SD age, 43.5±14.7 years; 41 (49%) men; 18 patients with elevated ICP) were included in the study. The Spearman correlation coefficients between the two observers were 0.779 and 0.703 in the transverse section and 0.751 and 0.788 in the vertical section for the left and right eyes, respectively. The median (IQR) change in ONSD (ΔONSD) and change in ICP (ΔICP) were 0.11 (0.05–0.21) mm and 30 (20–40) mmH2O, respectively, for all participants. With a reduction in cerebrospinal fluid pressure, 80 subjects (95%) showed an immediate drop in ONSD; the median (IQR) decreased from 4.13 (4.02–4.38) mm to 4.02 (3.90–4.23) mm (p

74 citations


Journal ArticleDOI
TL;DR: In this paper, a universal artificial intelligence (AI) platform for collaborative management of cataracts involving multilevel clinical scenarios and explored an AI-based medical referral pattern to improve collaborative efficiency and resource coverage.
Abstract: Purpose To establish and validate a universal artificial intelligence (AI) platform for collaborative management of cataracts involving multilevel clinical scenarios and explored an AI-based medical referral pattern to improve collaborative efficiency and resource coverage. Methods The training and validation datasets were derived from the Chinese Medical Alliance for Artificial Intelligence, covering multilevel healthcare facilities and capture modes. The datasets were labelled using a three-step strategy: (1) capture mode recognition; (2) cataract diagnosis as a normal lens, cataract or a postoperative eye and (3) detection of referable cataracts with respect to aetiology and severity. Moreover, we integrated the cataract AI agent with a real-world multilevel referral pattern involving self-monitoring at home, primary healthcare and specialised hospital services. Results The universal AI platform and multilevel collaborative pattern showed robust diagnostic performance in three-step tasks: (1) capture mode recognition (area under the curve (AUC) 99.28%–99.71%), (2) cataract diagnosis (normal lens, cataract or postoperative eye with AUCs of 99.82%, 99.96% and 99.93% for mydriatic-slit lamp mode and AUCs >99% for other capture modes) and (3) detection of referable cataracts (AUCs >91% in all tests). In the real-world tertiary referral pattern, the agent suggested 30.3% of people be ‘referred’, substantially increasing the ophthalmologist-to-population service ratio by 10.2-fold compared with the traditional pattern. Conclusions The universal AI platform and multilevel collaborative pattern showed robust diagnostic performance and effective service for cataracts. The context of our AI-based medical referral pattern will be extended to other common disease conditions and resource-intensive situations.

74 citations


Journal ArticleDOI
TL;DR: The ILM insertion technique may be as effective as the inverted ILM flap technique for the closure of large MHs, however, the latter technique results in better recovery of photoreceptor layers and, consequently, better postoperative visual acuity.
Abstract: Background To determine whether the internal limiting membrane (ILM) insertion technique is as effective as the inverted ILM flap technique for the initial surgical treatment of eyes with large idiopathic macular holes (MHs). Methods This retrospective, non-randomised, comparative clinical study included 41 eyes with large MHs (minimum diameter >500 µm) that were treated using the ILM insertion technique or the inverted ILM flap technique. The hole closure rate, postoperative best corrected visual acuity (BCVA) and swept source optical coherence tomography findings were analysed at 6 months after surgery. Results There were 15 and 26 eyes in the insertion and inverted flap groups, respectively. Hole closure was achieved in all eyes. The mean final BCVA was better in the inverted flap group than in the insertion group (0.527 vs 0.773, p=0.006), although significant postoperative improvements were observed in both groups (p Conclusion The ILM insertion technique may be as effective as the inverted ILM flap technique for the closure of large MHs. However, the latter technique results in better recovery of photoreceptor layers and, consequently, better postoperative visual acuity.

69 citations


Journal ArticleDOI
TL;DR: The evaluation of glaucoma in myopia requires a multimodal approach, to allow correlation between structural and functional assessments, and an overview on how to navigate this diagnostic dilemma is provided.
Abstract: Myopic eyes have an increased risk of glaucoma. However, glaucomatous changes in a myopic eye are often difficult to detect. Classic structural and functional investigations to diagnose glaucoma may be confounded by myopia. Here, we identify some of the common pitfalls in interpreting these structural parameters, and the possible solutions that could be taken to overcome them. For instance, in myopic eyes, we discuss the limitations and potential sources of error when using neuroretinal rim parameters, and retinal nerve fibre layer and ganglion cell-inner plexiform layer thickness measurements. In addition, we also review new developments and potential adjuncts in structural imaging such as the assessment of the retinal nerve fibre layer texture, and the examination of the microcirculation of the optic nerve head using optical coherence tomography angiography. For the functional assessment of glaucoma, we discuss perimetric strategies that may aid in detecting characteristic visual field defects in myopic glaucoma. Ultimately, the evaluation of glaucoma in myopia requires a multimodal approach, to allow correlation between structural and functional assessments. This review provides overview on how to navigate this diagnostic dilemma.

Journal ArticleDOI
TL;DR: Choriocapillaris and retinal CPD are reduced in diabetic retinopathy, while FAZ area is increased in eyes with PDR, which can further characterise diabetic choroidopathy.
Abstract: Background/aims Split-spectrum amplitude decorrelation angiography for spectral-domain optical coherence tomography has enabled detailed, non-invasive assessment of vascular flow. This study evaluates choriocapillaris and retinal capillary perfusion density (CPD) in diabetic eyes using optical coherence tomography angiography (OCTA). Methods Records of 136 eyes that underwent OCTA imaging at a single institution were reviewed. Eyes were grouped as non-diabetic controls (37 eyes), patients with diabetes mellitus (DM) without diabetic retinopathy (DM without DR, 31 eyes), non-proliferative diabetic retinopathy (NPDR, 41 eyes) and proliferative diabetic retinopathy (PDR, 27 eyes). Quantitative CPD analyses were performed on OCTA images for assessing perfusion density of the choriocapillaris and retinal plexus for all patients and compared between groups. Results Eyes with NPDR and PDR showed significantly decreased choriocapillaris CPD compared with controls, while DM eyes without DR did not show significant change. Choriocapillaris whole-image CPD was decreased by 8.3% in eyes with NPDR (p Conclusions Choriocapillaris and retinal CPD are reduced in diabetic retinopathy, while FAZ area is increased in eyes with PDR. Vascular changes captured by new imaging modalities can further characterise diabetic choroidopathy.

Journal ArticleDOI
TL;DR: Long-term follow-up analysis suggested that both SMILE and FS-LASIK were safe and equally effective for myopic and astigmatic correction.
Abstract: Aims To compare long-term clinical outcomes following small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for myopia and myopic astigmatism correction. Methods In this retrospective study, we enrolled a total of 101 patients (101 eyes) who underwent SMILE or FS-LASIK 3 years prior. Measured parameters included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction and corneal wavefront aberrations. Results No significant differences in patient characteristics were found between the two groups. At the 3-year follow-up, UDVA was better than or equal to 20/20 in 90% and 85% (p=0.540) of the eyes; the efficacy indexes were 1.05±0.19 and 1.01±0.21 in the SMILE and FS-LASIK groups, respectively (p=0.352). Safety indexes were 1.19±0.17 and 1.15±0.20 in the SMILE and FS-LASIK groups, respectively (p=0.307). Eighty per cent and 65% of eyes were within ±0.50 D of the attempted spherical equivalent correction after SMILE and FS-LASIK, respectively (p=0.164). Vector analysis revealed no significant differences in astigmatic correction between the two groups (p>0.05). Surgically induced spherical aberration was higher in the FS-LASIK group than in the SMILE group (p Conclusion Long-term follow-up analysis suggested that both SMILE and FS-LASIK were safe and equally effective for myopic and astigmatic correction.

Journal ArticleDOI
TL;DR: This review presents the current imaging modalities available from the anterior to posterior segment of the myopic eye, including the optic nerve, and summarises the clinical indications, image interpretation and future developments that may overcome current technological limitations.
Abstract: Myopia is rapidly increasing in Asia and around the world, while it is recognised that complications from high myopia may cause significant visual impairment. Thus, imaging the myopic eye is important for the diagnosis of sight-threatening complications, monitoring of disease progression and evaluation of treatments. For example, recent advances in high-resolution imaging using optical coherence tomography may delineate early myopic macula pathology, optical coherence tomography angiography may aid early choroidal neovascularisation detection, while multimodal imaging is important for monitoring treatment response. However, imaging the eye with high myopia accurately has its challenges and limitations, which are important for clinicians to understand in order to choose the best imaging modality and interpret the images accurately. In this review, we present the current imaging modalities available from the anterior to posterior segment of the myopic eye, including the optic nerve. We summarise the clinical indications, image interpretation and future developments that may overcome current technological limitations. We also discuss potential biomarkers for myopic progression or development of complications, including basement membrane defects, and choroidal atrophy or choroidal thickness measurements. Finally, we present future developments in the field of myopia imaging, such as photoacoustic imaging and corneal or scleral biomechanics, which may lead to innovative treatment modalities for myopia.

Journal ArticleDOI
TL;DR: The prevalence of treatable RP complications is high and suggests it may be clinically beneficial to screen patients with RP to identify those who may benefit from current or future interventions.
Abstract: Background/Aims To report the prevalence of treatable complications (cystoid macular oedema, CME; epiretinal membrane, ERM and cataract) in patients with retinitis pigmentosa (RP). Methods Consecutive patients with RP attending a tertiary eye clinic in 2012. Spectral domain-optical coherence tomography was used to determine presence of CME and ERM. Clinic records were reviewed to identify cataract and pseudophakia. Multivariable analyses adjusted for age, gender and other confounders. Results Data are presented for 338 eyes from 169 patients. CME was present in 58.6% of patients and 50.9% of eyes and was bilateral in 73.7%. ERM, cataract and pseudophakia were present in 22.8%, 23.4% and 11.2% eyes, respectively. In multivariable analyses, CME was associated with younger age (OR 0.81, 95% CI 0.67 to 0.98) but not with gender. Patients with ERM and cataract/pseudophakia were less likely to also have CME (OR 0.19, 95% CI 0.09 to 0.40 and OR 0.37, 95% CI 0.16 to 0.84, respectively). CME was most prevalent in patients with autosomal-dominant inheritance (71.4%), followed by autosomal recessive/sporadic inheritance (58.9%) and least likely in persons with X linked inheritance (12.5%, p Conclusions The prevalence of treatable RP complications is high and suggests it may be clinically beneficial to screen patients with RP to identify those who may benefit from current or future interventions.

Journal ArticleDOI
TL;DR: Myopia prevalence is similar to comparable studies of white European children, but the levels of presenting visual impairment are markedly higher than those reported for children living in Northern Ireland, suggesting barriers exist in accessing eye care.
Abstract: Aim To report refractive error prevalence and visual impairment in Republic of Ireland (henceforth 9Ireland9) schoolchildren. Methods The Ireland Eye Study examined 1626 participants (881 boys, 745 girls) in two age groups, 6–7 years (728) and 12–13 years (898), in Ireland between June 2016 and January 2018. Participating schools were selected by stratified random sampling, representing a mix of school type (primary/postprimary), location (urban/rural) and socioeconomic status (disadvantaged/advantaged). Examination included monocular logarithm of the minimum angle of resolution (logMAR) presenting visual acuity (with spectacles if worn) and cycloplegic autorefraction (1% Cyclopentolate Hydrochloride). Parents completed a questionnaire to ascertain participants’ lifestyle. Results The prevalence of myopia (spherical equivalent refraction (SER): ≤−0.50 D), hyperopia (SER: ≥+2.00 D) and astigmatism (≤−1.00 DC) among participants aged 6–7 years old was 3.3%, 25% and 19.2%, respectively, and among participants aged 12–13 years old was 19.9%, 8.9% and 15.9%, respectively. Astigmatic axes were predominately with-the-rule. The prevalence of ‘better eye’ presenting visual impairment (≥0.3 logMAR, with spectacles, if worn) was 3.7% among younger and 3.4% among older participants. Participants in minority groups (Traveller and non-white) were significantly more likely to present with presenting visual impairment in the ‘better eye’. Conclusions The Ireland Eye Study is the first population-based study to report on refractive error prevalence and visual impairment in Ireland. Myopia prevalence is similar to comparable studies of white European children, but the levels of presenting visual impairment are markedly higher than those reported for children living in Northern Ireland, suggesting barriers exist in accessing eye care.

Journal ArticleDOI
TL;DR: Given the high rates of undiagnosed glaucoma coupled with a significant ageing of the Australian population, improvements in case detection and access to low vision rehabilitation services may be required to cope with the growing burden of glau coma.
Abstract: Aim To estimate the prevalence of glaucoma in Australia. Methods This was a population-based study of 3098 non-Indigenous Australians (50–98 years) and 1738 Indigenous Australians (40–92 years) stratified by remoteness. Each participant underwent a standard examination that included visual field assessment, tonometry and non-mydriatic fundus photography. Two fellowship-trained glaucoma specialists independently assessed relevant case notes (past ocular history, best-corrected visual acuity, frequency doubling technology visual fields, Van Herick grade, intraocular pressure and optic disc-centred photographs) and assigned a diagnosis ranked on a scale of certainty: none, possible, probable or definite glaucoma. Results A total of 4792 (99.1%, 3062 non-Indigenous and 1730 Indigenous) participants had retinal photographs in at least one eye that were gradable for glaucoma. The weighted prevalence of glaucoma (definite) in non-Indigenous Australians and Indigenous Australians was 1.5% (95% CI 1.0 to 2.2) and 0.6% (95% CI 0.4 to 1.1), respectively. When definite and probable cases of glaucoma were combined, rates were 3.4% (95% CI 2.7 to 4.3) among non-Indigenous and 1.6% (95% CI 1.1 to 2.3) in Indigenous Australians. Only 52.4% of non-Indigenous Australians and 28.0% of Indigenous Australians with glaucoma self-reported a known history of glaucoma. Conclusion We estimate that 198 923 non-Indigenous Australians aged 50 years and over and 2139 Indigenous Australians aged 40 years and over have glaucoma. Given the high rates of undiagnosed glaucoma coupled with a significant ageing of the Australian population, improvements in case detection and access to low vision rehabilitation services may be required to cope with the growing burden of glaucoma.

Journal ArticleDOI
TL;DR: The study reinforces the good safety and effectiveness profile of FAc, and demonstrates the benefit of early FAc treatment, according to patients treated according to the European label requirements.
Abstract: Aims The ILUVIEN Registry Safety Study is an ongoing, multicentre, open-label, observational study collecting real-world data on the safety and effectiveness of the 0.2 µg/day fluocinolone acetonide (FAc) implant in patients treated according to the European label requirements. Methods Patients included in this analysis were treated for the licensed indication of chronic diabetic macular oedema (cDMO; that is, DMO that persists or recurs despite treatment). Data presented in the current analysis were collected from patient records up to 6 March 2017. Visual acuity (VA) data, including mean change in VA over time and at last observation, intraocular pressure (IOP) over the course of the study, IOP events, use of IOP-lowering therapy and cup:disc ratio were analysed. Information on additional DMO treatments post-FAc implant was also captured. Results Five hundred and sixty-three patients (593 eyes) were enrolled on the study. Mean IOP for the overall population remained within the normal range throughout follow-up and 76.7% of patients did not require IOP-lowering therapy following treatment with the FAc implant. Sixty-nine per cent of eyes did not require additional DMO treatments. Mean VA in the overall population increased from 51.9 letters at baseline to 55.6 letters at month 12, with a significant increase of 2.9 letters at last observation. Patients with short-term cDMO experienced greater VA gains than those with long-term cDMO. Conclusions The results of this analysis are comparable with those of other studies, including the Fluocinolone Acetate for Macular Edema study. The study reinforces the good safety and effectiveness profile of FAc, and demonstrates the benefit of early FAc treatment.

Journal ArticleDOI
TL;DR: New information on baseline morphology of retinal microvasculature and its associated factors in school children is provided, which will be useful for interpreting OCT-A metrics and for identifying and characterising pathological changes in retinalmicrovasculatures.
Abstract: Aims To evaluate the distributions of quantitative optical coherence tomography angiography (OCT-A) metrics and its associated factors in children. Methods 1059 children aged 6–8 years were recruited from the Hong Kong Children Eye Study. All the participants underwent OCT-A with a swept-source OCT. Retinal microvasculature on superficial capillary plexus was assessed and quantified by a customised automated image analysis programme. Univariable and multiple linear regression analyses were performed to determine systemic (body mass index (BMI), waist circumference, head circumference and blood pressure), demographic and ocular (axial length (AL), macular thickness and volume, retinal nerve fibre layer (RNFL) thickness and visual acuity) variables (independent variables) associated with OCT-A metrics (dependent variables). Results In multiple linear regression analyses, enlarged foveal avascular zone area was associated with female gender (β=0.110, p 0.05). Conclusion Our findings provides new information on baseline morphology of retinal microvasculature and its associated factors in school children, which will be useful for interpreting OCT-A metrics and for identifying and characterising pathological changes in retinal microvasculature.

Journal ArticleDOI
TL;DR: The study confirmed inner choroidal vascular flow void as a possible pathogenetic mechanism of AMN and found a focal impairment of the DCP within the AMN lesions.
Abstract: Aim To describe the optical coherence tomography angiography (OCT-A) features of patients affected by acute macular neuroretinopathy (AMN). Methods This is a prospective, observational, cross-sectional study. Multimodal imaging, including spectral domain OCT (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany) and 6×6 mm swept source OCT-A (ZEISS PLEX Elite 9000; ZEISS, Dublin, California), was performed on all patients. The primary outcome measure was assessment of the vascular alterations of the superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris (CC). A segmentation of the AMN lesions using enface OCT images of photoreceptors-retinal pigment epithelium complex was used to discriminate intralesional and extralesional regions on the OCT-A enface slabs of the DCP and CC reconstructions. Each OCT-A slab was imported into ImageJ V.1.50 and digitally binarised for quantitative analyses. Results Overall, seven patients (mean age 19.4±3.2 years, six women) affected by AMN were included. The mean best-corrected visual acuity was 0.00±0.00 logarithm of the minimum angle of resolution. Twelve healthy age-matched subjects (mean age 22±3.4 years, 10 women) represented the control group. The quantitative analysis of global vessel densities showed that the CC vessel density was significantly lower in patients with AMN (0.495±0.03) compared with the age-matched controls (0.545±0.02) (corrected p=0.0003). The intralesional vessel density of the DCP was 0.349±0.04 in AMN and vs 0.497±0.02 in the controls (corrected p=0.0002). Conclusions Our study confirmed inner choroidal vascular flow void as a possible pathogenetic mechanism of AMN. We also found a focal impairment of the DCP within the AMN lesions. Future studies are needed to clarify which is the primary location of the vascular insult in this condition.

Journal ArticleDOI
TL;DR: Early excisional penetrating keratoplasty showed to be the treatment with the highest therapeutic efficacy, lowest rate of complications and greater visual outcomes, and injection of antifungals right at the graft–host interface, was reported successful in some cases.
Abstract: Interface infectious keratitis (IIK) is a novel corneal infection that may develop after any type of lamellar keratoplasty. Onset of infection occurs in the virtual space between the graft and the host where it may remain localised until spreading with possible risk of endophthalmitis. A literature review identified 42 cases of IIK. Thirty-one of them occurred after endothelial keratoplasty and 12 after deep anterior lamellar keratoplasty. Fungi in the form of Candida species were the most common microorganisms involved, with donor to host transmission of infection documented in the majority of cases. Donor rim cultures were useful to address the infectious microorganisms within few days after surgery. Due to the sequestered site of infection, medical treatment, using both topical and systemic antimicrobials drugs, was ineffective on halting the progression of the infection. Injection of antifungals, right at the graft–host interface, was reported successful in some cases. Spreading of the infection with development of endophthalmitis occurred in five cases after Descemet stripping automated endothelial keratoplasty with severe sight loss in three cases. Early excisional penetrating keratoplasty showed to be the treatment with the highest therapeutic efficacy, lowest rate of complications and greater visual outcomes.

Journal ArticleDOI
TL;DR: A strong negative correlation was found between PD and ageing in the CC of healthy subjects, and the age-related changes were higher in the central area compared with the perifoveal area.
Abstract: Aim To analyse quantitative optical coherence tomography angiography (OCTA) parameters of choriocapillaris (CC) at the foveal, perifoveal and parafoveal regions in healthy subjects of different age. Methods In this observational cross-sectional study, consecutive healthy subjects underwent swept source OCTA (PLEX Elite 9000, Carl Zeiss Meditec, USA). 3×3 mm and 6×6 mm scans centred on the fovea were acquired analysed and postprocessed with thresholding and binarisation processes. The main outcome measures included CC quantitative OCTA features (perfusion density (PD), vessel length density (VLD) and vessel diameter index (VDI)) at the foveal, perifoveal and parafoveal regions, and their relationship with age. Results Seventy-two eyes (72 patients, mean age 47.4±19.2 years, mean axial length 24.0±0.7 mm) were included. The mean PD was statistically lower in the foveal region compared with the parafoveal region in 3×3 mm scans (p=0.009). In subjects aged 70–80, PD of the foveal region was significantly reduced compared with the perifoveal region in 6×6 mm scans (p=0.008). A strong negative correlation was found between PD and ageing in the foveal, parafoveal and perifoveal regions (p Conclusions We reported in vivo a strong negative correlation between PD and ageing in the CC of healthy subjects. This reduction seems related to a reduced diameter, and not to a reduced number, of capillaries. The age-related changes were higher in the central area compared with the perifoveal area.

Journal ArticleDOI
TL;DR: The associations found between myopia prevalence in schoolchildren in Ireland and demographic and lifestyle factors suggest that longitudinal research investigating the associations between myopic prevalence and these factors may be beneficial in advising preventative public health programmes.
Abstract: Aim To examine the demographic and social factors associated with myopia in schoolchildren in Ireland. Methods Thirty-seven schools participated, representing a mix of urban and rural schools and schools in socioeconomically disadvantaged and non-disadvantaged areas in Ireland. Examination included cyclopleged autorefraction (1% cyclopentolate hydrochloride). Height and weight of participants were measured. Parents filled in a participant’s lifestyle questionnaire, including questions on daily screen time use and daylight exposure. Myopia was defined as spherical equivalent ≤−0.50 D. Results Data from 1626 participants (881 boys, 745 girls) in two age groups, 6–7 years (728) and 12–13 years (898), were examined. Myopia prevalence was significantly higher in children aged 12–13 years old (OR=7.7, 95%CI 5.1 to 11.6, p 3 hours per day (OR=3.7, 95% CI 2.1 to 6.3, p Conclusions The associations found between myopia prevalence in schoolchildren in Ireland and demographic and lifestyle factors suggest that longitudinal research investigating the associations between myopia prevalence and these factors may be beneficial in advising preventative public health programmes.

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TL;DR: By providing an alternative source of innervation in patients with neurotrophic keratopathy treated with minimally invasive corneal neurotisation (MICN), MICN improvesCorneal sensation and stabilises the corneals epithelium, permitting optical keratoplasty for patients with NK-related cornea opacity.
Abstract: Aim To report clinical outcomes and evidence of corneal innervation in patients with neurotrophic keratopathy (NK) treated with minimally invasive corneal neurotisation (MICN) using a sural nerve graft and donor sensory nerves from the face. Methods Patients undergoing MICN at The Hospital for Sick Children, Toronto, Canada were prospectively recruited. Data on central corneal sensation (CCS, measured with Cochet-Bonnet aesthesiometer), best-corrected visual acuity (BCVA) and corneal epithelial integrity were collected. In four patients who subsequently underwent keratoplasty, immunohistochemical analysis was performed on the corneal explants. One patient underwent magnetoencephalography (MEG) after MICN to characterise the neurophysiological pathways involved. Results Between November 2012 and February 2017, 19 eyes of 16 patients underwent MICN. Mean follow-up was 24.0±16.1 months (range, 6–53). Mean CCS significantly improved from 0.8±2.5 mm to 49.7±15.5 mm at final follow-up (p Conclusions By providing an alternative source of innervation, MICN improves corneal sensation and stabilises the corneal epithelium, permitting optical keratoplasty for patients with NK-related corneal opacity.

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TL;DR: Peripapillary vessel density might be a sensitive predictor of visual outcomes in NMOSD patients with ON and the decrease in retinal vessel density could occur before ON and retinal nerve fibre layer (RNFL) atrophy.
Abstract: Background/aims Current understanding of the alterations in the retinal vascular network in neuromyelitis optica spectrum disorders (NMOSDs) is limited. We aim to assess the peripapillary and parafoveal vessel density in aquaporin-4 antibody-positive NMOSD patients by optical coherence tomography (OCT) angiography. Methods A total of 55 aquaporin-4 antibody-positive NMOSD patients with or without a history of optic neuritis (ON) and 33 healthy controls underwent spectral domain OCT and OCT angiography. Clinical histories, Expanded Disability Status Scale score, visual functional system score (VFSS) and disease duration were collected. Results Peripapillary and parafoveal vessel density was significantly decreased in NMOSD eyes with or without a history of ON. The decrease in retinal vessel density could occur before ON and retinal nerve fibre layer (RNFL) atrophy. Peripapillary vessel density correlated well with the spectral domain OCT measurements and VFSS in NMOSD eyes with a history of ON. Conclusion Subclinical primary retinal vasculopathy may occur in NMOSD prior to ON and RNFL atrophy. Peripapillary vessel density might be a sensitive predictor of visual outcomes in NMOSD patients with ON.

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TL;DR: Steroid use, antidepressant or anxiolytic drug use, smoking, pregnancy and hyperopia were risk factors, and myopia was a protective factor for CSC.
Abstract: Aims To determine the demographic and morphological characteristics of patients with central serous chorioretinopathy (CSC) and describe risk factors for CSC. Methods We retrospectively reviewed medical records of 811 patients with CSC and 816 healthy controls referred from 2002 to 2018. Results The female/male ratio of patients with CSC was 1/2.7. Mean age of onset was 45.2 years. The peak prevalence for men occurred at 45–49 years. Women had two prevalence peaks, the higher at 55–59 years and the other at 45–49 years. Of these patients, 56.8% had unilateral disease, 42.1% had bilateral disease and 1.1% had only one eye. 671 (82.7%) patients had spectral domain optical coherence tomography (SD-OCT) images and 598 (73.7%) had enhanced depth choroidal images. Pigment epithelial detachment (PED) was detected in 763 (80.7%) of 945 eyes with SD-OCT images. Chronic cases were more likely to be bilateral and multifocal and to have PED (all p Conclusion This is the largest case-control study of CSC to evaluate demographic morphological characteristics and risk factors. Multiple factors are associated with CSC.

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TL;DR: Keratoconus progression should be defined by evaluating parameters that consider several corneal changes; the suggested D-index and KPI to detect progression are suggested.
Abstract: Aim To define variables for the evaluation of keratoconus progression and to determine cut-off values. Methods In this retrospective cohort study (2010–2016), 265 eyes of 165 patients diagnosed with keratoconus underwent two Scheimpflug measurements (Pentacam) that took place 1 year apart ±3 months. Variables used for keratoconus detection were evaluated for progression and a correlation analysis was performed. By logistic regression analysis, a keratoconus progression index (KPI) was defined. Receiver-operating characteristic curve (ROC) analysis was performed and Youden Index calculated to determine cut-off values. Results Variables used for keratoconus detection showed a weak correlation with each other (eg, correlation r=0.245 between RPImin and Kmax, p Conclusions Keratoconus progression should be defined by evaluating parameters that consider several corneal changes; we suggest D-index and KPI to detect progression.

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TL;DR: Retinal microaneurysms in DME could be classified topographically and morphologically by OCTA and this appeared to be dependent on leakage activity and retinal thickening.
Abstract: Aims To investigate retinal microaneurysms in patients with diabetic macular oedema (DME) by optical coherence tomography angiography (OCTA) according to their location and morphology in relationship to their clinical properties, leakage on fundus fluorescein angiography (FFA) and retinal thickening on structural OCT. Methods OCTA and FFA images of 31 eyes of 24 subjects were graded for the presence of microaneurysms. The topographical and morphological appearance of microaneurysms on OCTA was evaluated and classified. For each microaneurysm, the presence of focal leakage on FFA and associated retinal thickening on OCT was determined. Results Of all microaneurysms flagged on FFA, 295 out of 513 (58%) were also visible on OCTA. Microaneurysms with focal leakage and located in a thickened retinal area were more likely to be detected on OCTA than not leaking microaneurysms in non-thickened retinal areas (p=0.001). Most microaneurysms on OCTA were seen in the intermediate (23%) and deep capillary plexus (22%). Of all microaneurysms visualised on OCTA, saccular microaneurysms were detected most often (31%), as opposed to pedunculated microaneurysms (9%). Irregular, fusiform and mixed fusiform/saccular-shaped microaneurysms had the highest likeliness to leak and to be located in thickened retinal areas (p Conclusions Retinal microaneurysms in DME could be classified topographically and morphologically by OCTA. OCTA detected less microaneurysms than FFA, and this appeared to be dependent on leakage activity and retinal thickening. Morphological appearance of microaneurysms (irregular, fusiform and mixed saccular/fusiform) was associated with increased leakage activity and retinal thickening.

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TL;DR: The presence of tiny branching vessels and a peripheral anastomotic arcade appears to predict the lesion activity with a good accuracy and the model based on four criteria enables optimal decisions regarding retreatment in eAMD.
Abstract: Aims To evaluate on optical coherence tomography angiography (OCT-A), the predictive role of different qualitative findings of choroidal neovascularisations (CNV) in assessing the status of exudative age-related macular degeneration (eAMD) and to develop a potential model to predict the CNV activity. Methods Retrospective review of the multimodal imaging records of patients with eAMD obtained during treatment for type 1 or type 2 CNV. The qualitative analysis of CNVs on OCT angiograms assessed the presence or absence of tiny branching vessels, loops, peripheral anastomotic arcades and choriocapillaris hypointense halo. These findings were then correlated with those of structural OCT scans. A score forecast was built and validated. Results One hundred and twenty-six eAMD eyes were enrolled in the study. Exudation was observed in 90 eyes (71%) on structural OCT. The qualitative OCT-A analysis revealed: tiny branching vessels in 82.5% of the cases, vascular loops in 81.7%, peripheral anastomotic arcades in 66.7% and choriocapillaris hypointense halo in 54.8%. In the univariate analysis, each OCT-A parameter showed a statistically significant correlation with exudation on structural OCT (p Conclusions The presence of tiny branching vessels and a peripheral anastomotic arcade appears to predict the lesion activity with a good accuracy and the model based on four criteria enables optimal decisions regarding retreatment in eAMD.

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TL;DR: This work, for the first time, defines the disease burden of uveal melanoma in Canada and highlights important longitudinal, geographical and spatial differences in the distribution of this malignancy in Canada.
Abstract: Background In the developed countries, uveal melanoma is the most common primary intraocular malignancy in adults. Little is known about the epidemiological and geographical distribution of uveal melanoma in Canada. Methods To determine the incidence patterns and geographical distribution of uveal melanoma cases in Canada, we conducted the first comprehensive, population-based national study of this malignancy across all Canadian provinces and territories during 1992–2010 years. We examined two independent population-based registries: the Canadian Cancer Registry and Le Registre Quebecois du Cancer using corresponding International Classification of Diseases for Oncology-3rd edition codes for all histological subtypes of uveal melanoma. Results We report that 2215 patients were diagnosed with uveal melanoma, of which 52.1% were males. The average -annual incidence rate of uveal melanoma in Canada was 3.75 cases per million individuals per year (95% CI 3.60 to 3.91). Overall, we report a steady increase in uveal melanoma incidence with an annual increase of 0.074 cases per million individuals per year. Significant differences in the incidence rates of uveal melanoma between Canadian provinces and territories were noted, where the highest crude incidence was in British Columbia and Saskatchewan with rates of 6.38 and 5.47 cases per million individuals per year, respectively. Conclusions This work, for the first time, defines the disease burden of uveal melanoma in Canada and highlights important longitudinal, geographical and spatial differences in the distribution of uveal melanoma in Canada.