Artificial intelligence in retinal disease: clinical application, challenges, and future directions.

Retinal diseases are a leading cause of blindness in developed countries, accounting for the largest share of visually impaired children, working-age adults (inherited retinal disease), and elderly individuals (age-related macular degeneration). These conditions need specialised clinicians to interpret multimodal retinal imaging, with diagnosis and intervention potentially delayed. With an increasing and ageing population, this is becoming a global health priority. One solution is the development of artificial intelligence (AI) software to facilitate rapid data processing. Herein, we review research offering decision support for the diagnosis, classification, monitoring, and treatment of retinal disease using AI. We have prioritised diabetic retinopathy, age-related macular degeneration, inherited retinal disease, and retinopathy of prematurity. There is cautious optimism that these algorithms will be integrated into routine clinical practice to facilitate access to vision-saving treatments, improve efficiency of healthcare systems, and assist clinicians in processing the ever-increasing volume of multimodal data, thereby also liberating time for doctor-patient interaction and co-development of personalised management plans.

Biomarkers of macular neovascularisation activity using optical coherence tomography angiography in treated stable neovascular age related macular degeneration.

BACKGROUND: The aim of this study was to describe features of disease activity in patients with treated stable macular neovascularisation (MNV) in neovascular age related macular degeneration (nAMD) using optical coherence tomography angiography (OCTA). METHODS: Thirty-two eyes of 32 patients with nAMD were included in this prospective, observational study. These patients were undergoing treatment with aflibercept on a treat-and-extend regimen attending an extension to a 12-week treatment interval. RESULTS: All subjects had no macular haemorrhage and no structural OCT markers of active MNV activity at the index 12-week treatment extension visit. 31/32 OCTA images were gradeable without significant imaging artefact. The mean MNV size was 3.6mm2 ± 4.6mm2 and 27 (87.1%) had detectable MNV blood flow. 29/31 (93.5%) subjects had MNV with mature phenotypes including 10 non-specific, 10 tangle and 3 deadtree phenotypes. MNV halo and MNV central feeder vessel were noted in 18 (58.1%) and 19 (61.3%) of subjects respectively; only 1 (3.2%) subject was noted to have a MNV capillary fringe. CONCLUSIONS: MNV blood flow is still detectable using OCTA in the majority of subjects in this study with treated stable MNV. OCTA features associated included MNV mature phenotype, MNV feeder vessel, MNV halo and absence of capillary fringe.

The effectiveness of interventions for optometric referrals into the hospital eye service: A review.

PURPOSE: Ophthalmic services are currently under considerable stress; in the UK, ophthalmology departments have the highest number of outpatient appointments of any department within the National Health Service. Recognising the need for intervention, several approaches have been trialled to tackle the high numbers of false-positive referrals initiated in primary care and seen face to face within the hospital eye service (HES). In this mixed-methods narrative synthesis, we explored interventions based on their clinical impact, cost and acceptability to determine whether they are clinically effective, safe and sustainable. A systematic literature search of PubMed, MEDLINE and CINAHL, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), was used to identify appropriate studies published between December 2001 and December 2022. RECENT FINDINGS: A total of 55 studies were reviewed. Four main interventions were assessed, where two studies covered more than one type: training and guidelines (n = 8), referral filtering schemes (n = 32), asynchronous teleophthalmology (n = 13) and synchronous teleophthalmology (n = 5). All four approaches demonstrated effectiveness for reducing false-positive referrals to the HES. There was sufficient evidence for stakeholder acceptance and cost-effectiveness of referral filtering schemes; however, cost comparisons involved assumptions. Referral filtering and asynchronous teleophthalmology reported moderate levels of false-negative cases (2%-20%), defined as discharged patients requiring HES monitoring. SUMMARY: The effectiveness of interventions varied depending on which outcome and stakeholder was considered. More studies are required to explore stakeholder opinions around all interventions. In order to maximise clinical safety, it may be appropriate to combine more than one approach, such as referral filtering schemes with virtual review of discharged patients to assess the rate of false-negative cases. The implementation of a successful intervention is more complex than a 'one-size-fits-all' approach and there is potential space for newer types of interventions, such as artificial intelligence clinical support systems within the referral pathway.

Assessment of optometrists' referral accuracy and contributing factors: A review.

PURPOSE: In the UK, ophthalmology has the highest number of outpatient appointments within the National Health Service. False-positive referrals from primary care are one of the main factors contributing to the oversubscription of hospital eye services (HESs). We reviewed the accuracy of referrals originating from primary care optometrists and contributing factors, such as condition type and years since registration. RECENT FINDINGS: Of the 31 studies included in the review, 22 were retrospective analyses of referrals and appointments at the HES. Eight were prospective studies, and one used online clinical vignettes. Seven assessed the accuracy of referrals for all ocular conditions. The remaining studies focused on glaucoma (n = 11), cataracts (n = 7), emergency conditions (n = 4), neovascular age-related macular degeneration (n = 1) and paediatric binocular vision (n = 1). The diagnostic agreement for suspected emergency ocular conditions was the lowest, with only 21.1% of referrals considered to require urgent attention in one study. For glaucoma, the first-visit discharge rate was high (16.7%-48%). Optometrist referral accuracy was overall 18.6% higher than General Medical Practitioners'; however, the two mainly referred different ocular conditions. Female optometrists made more false-positive referrals than males (p = 0.008). The proportion of false positives decreased by 6.2% per year since registration (p < 0.001). SUMMARY: There was significant variation in referral accuracy across different ocular conditions, partly due to differences when defining accurate referrals. Optometrists working in primary care are generally more limited in their resources than the HES. Thus, choosing the cautious option of referral when they are unsure could be in the patients' best interests. The possible effect of increased use of advanced imaging on referrals requires evaluation. Although interventions such as refinement schemes have been put in place, these vary across regions, and their approaches such as virtual referral triaging may reduce unnecessary HES face-to-face appointments and promote communication between primary and secondary care.

Evaluating an automated machine learning model that predicts visual acuity outcomes in patients with neovascular age-related macular degeneration.

PURPOSE: Neovascular age-related macular degeneration (nAMD) is a major global cause of blindness. Whilst anti-vascular endothelial growth factor (anti-VEGF) treatment is effective, response varies considerably between individuals. Thus, patients face substantial uncertainty regarding their future ability to perform daily tasks. In this study, we evaluate the performance of an automated machine learning (AutoML) model which predicts visual acuity (VA) outcomes in patients receiving treatment for nAMD, in comparison to a manually coded model built using the same dataset. Furthermore, we evaluate model performance across ethnic groups and analyse how the models reach their predictions. METHODS: Binary classification models were trained to predict whether patients' VA would be 'Above' or 'Below' a score of 70 one year after initiating treatment, measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The AutoML model was built using the Google Cloud Platform, whilst the bespoke model was trained using an XGBoost framework. Models were compared and analysed using the What-if Tool (WIT), a novel model-agnostic interpretability tool. RESULTS: Our study included 1631 eyes from patients attending Moorfields Eye Hospital. The AutoML model (area under the curve [AUC], 0.849) achieved a highly similar performance to the XGBoost model (AUC, 0.847). Using the WIT, we found that the models over-predicted negative outcomes in Asian patients and performed worse in those with an ethnic category of Other. Baseline VA, age and ethnicity were the most important determinants of model predictions. Partial dependence plot analysis revealed a sigmoidal relationship between baseline VA and the probability of an outcome of 'Above'. CONCLUSION: We have described and validated an AutoML-WIT pipeline which enables clinicians with minimal coding skills to match the performance of a state-of-the-art algorithm and obtain explainable predictions.

Quantitative Analysis of OCT for Neovascular Age-Related Macular Degeneration Using Deep Learning.

PURPOSE: To apply a deep learning algorithm for automated, objective, and comprehensive quantification of OCT scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD) and make the raw segmentation output data openly available for further research. DESIGN: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. PARTICIPANTS: A total of 2473 first-treated eyes and 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017. METHODS: A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first- and second-treated eyes by visual acuity (VA) and race/ethnicity and correlations between volumes. MAIN OUTCOME MEASURES: Volumes of segmented features (mm3) and central subfield thickness (CST) (µm). RESULTS: In first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR, and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED, and SRF. Eyes from Black individuals had higher SRF, RPE, and serous PED volumes compared with other ethnic groups. Greater volumes of the majority of features were associated with worse VA. CONCLUSIONS: We report the results of large-scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first- and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community.

Evaluation of training, patient and practitioner perspectives on community-based monitoring of patients with stable age-related macular degeneration compared to hospital-based care: The FENETRE study report no. 1.

PURPOSE: Describe the development, delivery, acceptability and evaluation of a modular training programme for community-based, non-medical practitioners monitoring patients with quiescent neovascular age related macular degeneration (QnAMD). Also, report on a qualitative process evaluation conducted during the pilot phase of a randomised control trial (the FENETRE Study) exploring patient and practitioner acceptability of community-based QnAMD care relative to hospital-based care. METHODS: Learning outcomes from The College of Optometrists' Medical Retina higher qualifications and the Royal College of Ophthalmologists' Common Clinical Competency Framework were used to develop a competency framework for QnAMD care. Training was delivered online, comprising six asynchronous lectures followed by two synchronous case-based discussion webinars, with an accredited assessment of 24 case vignettes. An anonymous evaluation survey was conducted with the first two FENETRE cohorts (n = 38). Separately, we undertook a qualitative process evaluation, sampling purposively in four hospitals and five community-based practices, interviewing nine patients and eight practitioners. RESULTS: Survey responses (n = 26) showed community optometrists were very satisfied (n = 12; 46%) or satisfied (n = 14; 54%) with the training; feedback reflected by qualitative process evaluation data. Overall, optometrists also felt either confident (n = 15; 58%) or very confident (n = 8; 31%) in conducting AMD monitoring appointments following training, a finding also corroborated by interview data from optometrists participating in the initial pilot phase roll-out. Optometrists identified patient convenience and alleviating pressures in hospital care as the primary reasons for acceptability of community pathways. Data from patients entering community practices suggested they largely found this at least as safe and convenient as hospital care, although some patients randomised to hospital care perceived that as safer. CONCLUSION: This pilot study has shown the development and implementation of a collaborative community monitoring model is feasible, with satisfaction from community optometrists for training and accreditation, and broad acceptance for the pathway by both patients and practitioners.

Macular Telangiectasia Type 2: Visual Acuity, Disease End Stage, and the MacTel Area: MacTel Project Report Number 8.

PURPOSE: To report the visual acuity measures from the macular telangiectasia type 2 (MacTel) registry and to investigate and describe phenotypic findings in eyes with substantial vision loss resulting from MacTel. DESIGN: Cross-sectional multicenter study. PARTICIPANTS: Participants in the MacTel Natural History Observation Registration Study. METHODS: Best-corrected visual acuity (BCVA) data, retinal imaging data, and clinical data were accessed from the MacTel Study databases in May 2019. MAIN OUTCOME MEASURES: Frequency distribution of BCVA and its relationship to age; morphologic changes in eyes with very late disease stages, defined by a BCVA of 20/200 or worse; average retinal thickness of macular subfields on OCT; and dimensions of the area affected by MacTel (i.e., the MacTel area). RESULTS: Best-corrected visual acuity was 20/50 or worse in 37.3% and 20/200 or worse in 3.8% of 4449 eyes of 2248 patients; 18.4% and 0.7% of all patients showed bilateral BCVA of 20/50 or worse and 20/200 or worse, respectively. Asymmetry between right and left eyes was present (median BCVA, 71 letters vs. 74 letters), a finding supported by more advanced morphologic changes in right eyes. Participant age correlated with BCVA, but the effect size was small. If a neovascularization or macular hole were present, bilateral occurrence was frequent (33% or 17%, respectively), and BCVA was better than 20/200 (79% or 78%, respectively) or 20/50 or better (26% or 13%, respectively). Eyes with advanced disease (BCVA, ≤20/200) showed the following characteristics: (1) atrophy of the foveal photoreceptor layer with or without associated subretinal fibrosis; (2) an affected area, termed MacTel area, limited to a horizontal diameter not exceeding the distance between the temporal optic disc margin and foveal center, and the vertical diameter not exceeding approximately 0.8 times this distance (exceptions were eyes with large active or inactive neovascular membranes); (3) reduced retinal thickness measures within the MacTel area; and (4) less frequent retinal greying and more frequent hyperpigmentations compared with eyes that have better BCVA. CONCLUSIONS: Severe vision loss is rare in MacTel and is related to photoreceptor atrophy in most people. Results indicate disease asymmetry with slightly worse vision and more advanced disease manifestation in right eyes. MacTel-related neurodegeneration does not spread beyond the limits of the MacTel area.

Delivering personalized medicine in retinal care: from artificial intelligence algorithms to clinical application.

PURPOSE OF REVIEW: To review the current status of artificial intelligence systems in ophthalmology and highlight the steps required for clinical translation of artificial intelligence into personalized health care (PHC) in retinal disease. RECENT FINDINGS: Artificial intelligence systems for ophthalmological application have made rapid advances, but are yet to attain a state of technical maturity that allows their adoption into real-world settings. There remains an 'artificial intelligence chasm' in the spheres of validation, regulation, safe implementation, and demonstration of clinical impact that needs to be bridged before the full potential of artificial intelligence to deliver PHC can be realized. SUMMARY: Ophthalmology is currently in a stage between the demonstration of the potential of artificial intelligence and widespread deployment. Next stages include aggregating and curating datasets, training and validating artificial intelligence systems, establishing the regulatory framework, implementation and adoption with ongoing evaluation and model adjustment, and finally, meaningful human-artificial intelligence interaction with clinically validated tools that have demonstrated measurable impact on patient and healthcare system outcomes. Ophthalmologists should leverage the ability of artificial intelligence systems to glean insights from large volumes of multivariate data, and to interpret artificial intelligence recommendations in a clinical context. In doing so, the field will be well positioned to lead the transformation of health care in a personalized direction. VIDEO ABSTRACT: http://links.lww.com/COOP/A35.

Novel biomarker of sphericity and cylindricity indices in volume-rendering optical coherence tomography angiography in normal and diabetic eyes: a preliminary study.

PURPOSE: Preliminary to evaluate geometric indices (vessel sphericity and cylindricity) for volume-rendered optical coherence tomography angiography (OCTA) in healthy and diabetic eyes. METHODS: Twenty-six eyes of 13 healthy subjects and 12 eyes of patients with central ischemic, non-proliferative diabetic retinopathy were included. OCTA volume and surface area of the foveal vessels were measured and compared to determine OCTA sphericity and cylindricity indices and surface efficiency (SE). RESULTS: The overall average OCTA volume in healthy was 0.49 ± 0.09 mm3 (standard deviation [SD]), compared to 0.44 ± 0.07 mm3 (SD) in the diabetic eyes (difference in means 0.06 mm3, p = 0.054). The overall average OCTA surface area in the healthy eyes was 87.731 ± 9.51 mm2 (SD), compared to 76.65 ± 13.67 mm2 (SD) in the diabetic eyes (difference in means 11.08 mm2, p = 0.021). In relation to total foveolar tissue volume, the proportion of blood vessels was 22% in healthy individuals and only 20% in diabetics. The difference between the groups was more pronounced with respect to the total OCTA surface area, with a decrease of 13% in diabetics. A diabetic eye was most likely using geometric vessel indices analysis if the sphericity value was ≥ 0.190, with a cylindricity factor of ≥ 0.001. Reproducibility of the method was good. CONCLUSIONS: A method for OCTA surface area and volume measurements was developed. The application of the novel OCTA sphericity and cylindricity indices could be suitable as temporal biomarker to characterize stable disease or disease progression and may contribute to a better understanding in the evolution of diabetic retinopathy.

Psychological and Psychosocial Interventions for Depression and Anxiety in Patients With Age-Related Macular Degeneration: A Systematic Review.

OBJECTIVE: To review the current literature on psychosocial and psychological interventions to prevent and treat depression and anxiety in patients with age-related macular degeneration (AMD). METHODS: The authors conducted a systematic review of literature evaluating psychosocial and psychological interventions for depression and anxiety in patients with AMD. Primary searches of PubMed, Cochrane library, EMBASE, Global Health, Web of Science, EBSCO, and Science Direct were conducted to include all articles published up to April 21, 2018. RESULTS: Of a total of 398 citations retrieved, the authors selected 12 eligible studies published between 2002 and 2016. The authors found nine randomized controlled trials (RCT), and three non-randomized intervention (NRI) studies. RCT studies suggested that interventions using group self-management techniques and individual behavioral activation plus low vision rehabilitation can be effective to treat and prevent depression in patients with AMD, and one study suggested that a stepped-care intervention using cognitive-behavioral techniques can be effective to manage anxiety and depression over time. NRI studies highlighted a positive effect of self-help and emotion-focused interventions to reduce depression. CONCLUSION: Clinical practice with patients with AMD can rely on some tailored cognitive-behavioral therapeutic protocols to improve patients' mental health, but further clinical trials will generate the necessary evidence-based knowledge to improve those therapeutic techniques and offer additional tailored interventions for patients with AMD.

Impact of optical coherence tomography on diagnostic decision-making by UK community optometrists: a clinical vignette study.

PURPOSE: In recent years, there has been widespread investment in imaging technologies by community optometrists in the UK, most notably optical coherence tomography (OCT). The aim of the current study was to determine the value of OCT in the diagnosis of posterior segment diseases in a representative sample of community optometrists using a clinical vignette methodology. METHODS: A group of community optometrists (n = 50) initially completed a standardised training package on OCT interpretation followed by a computer-based assessment featuring 52 clinical vignettes, containing images of healthy (n = 8) or glaucomatous (n = 18) discs or healthy (n = 8) or diseased (n = 18) fundi. Each vignette featured either a single fundus/disc photographic image, or a combination of a fundus/disc image with the corresponding OCT scan. An expert panel confirmed that the fundus images presented alone and those in combination with OCT data were of a similar level of difficulty and that the cases were typical of those seen in primary care. For each case, the optometrist selected their diagnosis from a pull-down list and reported their confidence in their decision using a 10-point Likert scale. Pairwise comparisons of the fundus image alone and fundus image/OCT combination were made for both diagnostic performance and confidence. RESULTS: The mean percentage of correct diagnoses using fundus imaging alone was 62% (95% CI 59-64%) and for the combination of fundus image/OCT was 80% (95% CI 77-82%). The mean false negative rate with fundus alone was 27% reducing to 13% with the OCT combination. Median confidence scores for fundus imaging alone was 8.0 (IQR 7.0-8.0) and 8.3 (IQR 8.0-9.0) for the combination. Improvements in performance and confidence were statistically significant (p < 0.001). CONCLUSION: The results from this vignette study suggests that OCT improves optometrists' diagnostic performance compared to fundus observation alone. These initial results suggest that OCT provides valuable additional data that could augment case-finding for glaucoma and retinal disease; however, further research is needed to assess its diagnostic performance in a routine clinical practice setting.

Treatment decisions of UK hospital optometrists and ophthalmologists in patients with nAMD: a vignette study.

PURPOSE: A vignette study to examine treatment decisions made by UK hospital optometrists in patients with neovascular age-related macular degeneration (nAMD) and the effect of optometrists' experience on agreement. METHODS: Patients with nAMD attending Manchester Royal Eye Hospital, Manchester, UK were identified as potential candidates for the case series of vignettes. The cases were chosen to reflect a varied case-mix with respect to difficulty as well as ensuring good quality of the images. Each vignette included a history summary consisting of the number of previous injections given and visual acuity measurements at baseline, the previous visit, and the current visit. Images were compiled to show baseline fundus photographs and ocular coherence tomography (OCT) images with the current visit images on which the treatment decision was to be made along with the images from the previous visit. Hospital optometrists were recruited and asked to complete the series of vignettes, deciding if treatment was required at that visit and how confident they felt with that decision. Their responses were compared to the reference standard created by a consensus of consultant ophthalmologists with a sub-speciality interest in medical retina. RESULTS: Regarding treatment decision for optometrists, the percentage correct value was 75% with the sensitivity being 75.6% (95% CI 70.1-80.3) and the specificity as 75.1% (95% CI 72.1-77.8). No statistically significant difference was found between differing levels of experience. However, there was a significant difference in confidence levels between groups. Potentially sight threatening decisions accounted for 6.4% of the optometrists' decisions, 3.5% were made with a high confidence rating suggesting no discussion with an ophthalmologist was required. CONCLUSIONS: Although the optometrists showed modest agreement with the reference standard in a series of cases that have higher than average complexity, the optometrists showed a similar amount of variability within their treatment decisions compared to the reference standard. The optometrists were therefore not inferior in their performance compared to the ophthalmologists and this can be seen as supporting evidence for their extended role within this clinical area. Experience did not have an effect on 'correct' treatment decisions although there was a statistically significant effect on increasing confidence of treatment decision.

Swept-source optical coherence tomography angiography features of sub-retinal fibrosis in neovascular age-related macular degeneration.

IMPORTANCE: The study highlights the role of optical coherence angiography in the management of patients with neovascular age-related macular degeneration (nAMD) who have developed sub-retinal fibrosis. BACKGROUND: Development of sub-retinal fibrosis in the context of nAMD is known to adversely affect visual function. The aim of this study is to assess structure and flow features obtained through swept-source optical coherence tomography angiography (OCTA) in patients with sub-retinal fibrosis and associate these with visual acuity (VA). DESIGN: Institutional retrospective cohort study. PARTICIPANTS: A total 39 eyes of 39 patients with nAMD with sub-retinal fibrosis imaged with OCTA were included in this study. METHODS: Patients underwent swept-source OCTA. Thickness of sub-retinal hyper-reflective material (SHRM) and presence and configuration of a choroidal neovascular membrane were recorded in each case. MAIN OUTCOME MEASURES: A univariate multiple regression was performed seeking associations between VA and structural and flow OCTA features. RESULTS: Average VA on the date of OCTA was 53 ± 22 ETDRS letters. Average thickness of centre-involving SHRM was 157 ± 73 µm. A choroidal neovascular membrane was detectable in 26 cases and not detectable in 13. VA was independently influenced by thickness of SHRM (P = 0.034) and presence of a detectable choroidal neovascular membrane (P = 0.02) on OCTA. CONCLUSIONS AND RELEVANCE: Poorer VA in patients with nAMD and sub-retinal fibrosis is associated with presence of a detectable neovascular membrane on OCTA. The role of OCTA to guide nuanced management decisions in this patient population may be significant.

Features of choroidal naevi on swept source optical coherence tomography angiography and structural reverse flow optical coherence tomography.

PURPOSE: The purpose of our study was to describe features of choroidal naevi as seen on swept source optical coherence tomography angiography (OCTA) and also on en face images derived from structural data from OCTA. METHODS: A prospective observational cohort study was carried out. Patients attending a specialised choroidal naevomelanocytic with known naevi were imaged with swept source OCTA. RESULTS: Seventy-one eyes of 70 patients were imaged. Forty-three patients and 44 eyes were included. Mean age was 57.7 years (SD 14.9), range 29-81 years. Male to female ratio was 20:23. On OCTA after manual segmentation, naevi could be seen in 47.6% of cases, whereas in the en face images, naevi could be clearly visualised in 79.5% of cases. In OCTA, the superficial and deep capillary plexuses appeared undisturbed as did the outer retinal layer appeared in all cases of flat naevi. In choroidal naevi with mild elevation, the outer retinal layer appeared more susceptible to projection artefacts from overlying retinal vasculature. The choriocapillaris layer showed a fading of the normal homogenous vascular mosaic corresponding to the area of the naevus. In the en face images, even the faintest and thinnest naevi could be visualised in striking detail, and naevi greater than 120 µm thickness appeared darker (p = 0.0034). CONCLUSIONS: OCTA presents characteristic changes in the choriocapillaris layers in cases of choroidal naevi. The association of naevus substance appearing darker with increasing thickness may offer a novel prognostic clue. En face structural OCT may allow accurate, detailed measurement of lateral dimensions which could be of value in the monitoring of suspicious naevi.

QUANTITATIVE ANALYSIS OF PIGMENT EPITHELIAL DETACHMENT RESPONSE TO DIFFERENT ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS IN WET AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess whether best-corrected visual acuity and pigment epithelial detachment (PED) height, volume, and reflectivity in patients with wet age-related macular degeneration are influenced by baseline anatomical and functional parameters, including quantifiable metrics of PED morphology and choice of treatment. METHODS: One hundred two consecutive, treatment-naive wet age-related macular degeneration patients with PED (>50 µm) treated with aflibercept (52) or ranibizumab (50) were retrospectively included. Pigment epithelial detachment height, horizontal and vertical dimensions, and volume were recorded at baseline, 3 months, and 1 year, respectively. Bespoke image analysis software provided a quantifiable measure of reflectivity. RESULTS: Best-corrected visual acuity at 3 months was influenced by baseline best-corrected visual acuity (P = 0.006). Pigment epithelial detachment height was influenced by baseline height (P = 0.009), subretinal fluid (P = 0.008), central macular thickness (P = 0.006), and use of aflibercept (P = 0.003) at 3 months and by baseline height (P = 0.018), volume (P = 0.017), vertical dimension (P = 0.0004), and aflibercept (P = 0.015) at 1 year. Pigment epithelial detachment reflectivity increased from 43.59 to 55.86 (3 months) and 57.35 (1 year) (P < 0.001) and was influenced by its baseline values and, interestingly, use of aflibercept at 3 months (P = 0.013). CONCLUSION: Quantifiable metrics of PED morphology improve with treatment, and PED content becomes hyperreflective, more so on aflibercept. Pigment epithelial detachments respond better in the context of more active disease. More hyporeflective PED content may predispose to better treatment response, especially with aflibercept.

Psychological impact of anti-VEGF treatments for wet macular degeneration-a review.

PURPOSE: To review the current literature on the psychological impact of anti-VEGF treatments for wet age-related macular degeneration (wAMD), in terms of patients' experiences of receiving these treatments, and the impact of these treatments for patients' mental health and quality of life. METHODS: We critically analyzed current literature evaluating psychological impact of anti-VEGF treatments for wAMD. Primary searches of PubMed, Science Direct, and Web of Science were conducted in July and August of 2015. We reviewed all papers on the topic published until August 5, 2015. RESULTS: Our literature search found 14 papers addressing the psychological impact of anti-VEGF treatments for wAMD. Results highlighted potential anxieties and experiences of pain caused by receiving regular intravitreal injections. A positive visual outcome of anti-VEGF therapy is associated with positive vision-related QOL outcomes, although such association seems to be dependent on improvements on visual acuity. In the literature reviewed, patients receiving anti-VEGF treatments showed a prevalence rate of depression between 20 and 26 %. CONCLUSIONS: Although anti-VEGF treatments can cause some anxiety and being experienced as a stressful event, especially in the beginning of the treatment, preliminary findings suggest a potential benefit for long-term vision-related quality of life. Further longitudinal and qualitative research should bring more evidence on the positive and negative effects of these treatments on patients' long-term mental health.

A cross-sectional study of submacular thickening in intermediate uveitis and determination of treatment threshold.

BACKGROUND: The aim of this work is to refine understanding of anatomical and functional alterations in eyes with Intermediate Uveitis (IU), their natural history in mild cases not necessitating treatment and their response to treatment in severely affected eyes with macular edema. METHODS: 61 consecutive patients with IU presenting over a 6-year period were prospectively recruited into the study. Two subgroups of patients with IU were identified on the basis of the need or not for systemic cortico-steroid treatment. A group of healthy volunteers was identified for determining normal average central foveal thickness (CFT) values. Statistical comparisons were sought between patient sub-groups and with the group of normal volunteers for CFT and Best Corrected Visual Acuity (BCVA) at baseline and after 6 months. In a post hoc analysis, a cut-off value of CFT for systemic treatment initiation in IU was statistically identified and its sensitivity and specificity determined. RESULTS: A statistically significant difference in mean CFT at baseline was observed between patients under systemic treatment and untreated patients (p = 0.0005) as well as between untreated patients and healthy volunteers. (p < 0.001) After six months difference in CFT between the two patients subgroups was no longer significant (p = 0.699). BCVA was worse for patients under systemic treatment. No statistically significant difference could be identified between the subgroup of untreated patients and the group of healthy volunteers either at baseline or after 6 months. Correlation between LogMAR visual acuity and central retinal thickness at baseline was strong (r = 0.7436, p < 0.0001, Pearson's correlation coefficient). The cut-off value of CFT for initiating systemic treatment was determined at 215.5 µm in a post hoc analysis (sensitivity 62.5 %, specificity 96.4 %). CONCLUSIONS: Subclinical retinal thickening of mildly inflamed eyes with IU can occur though bearing no functional clinical significance and spontaneously resolving within 6 months. A cut-off CFT value for treatment of macular edema in IU, in the presence of other relevant morphological features on Optical Coherence Tomography, seems to emerge from post hoc analysis of collected data demonstrating strong specificity and moderate sensitivity.

Repeatability of visual function measures in age-related macular degeneration.

PURPOSE: To assess repeatability of visual function measures in patients with early, intermediate or late age-related macular degeneration (AMD) without active neovascular disease in the study eye, but active neovascular AMD in the fellow eye. METHODS: One hundred subjects from an ongoing trial were screened for this study in which their LogMAR acuity, contrast sensitivity and reading performance were assessed using standardised protocols by trained optometrists. The same measures were repeated one month later and repeatability of the visual functions assessed. RESULTS: Data from 83 subjects satisfied inclusion criteria for analysis. Coefficient of repeatability was 14.9 letters for LogMAR visual acuity , 7.2 letters for Pelli Robson contrast sensitivity, 0.72 for LogMAR reading acuity, 110.4 words/ min for reading speed and 0.67 for LogMAR critical print size. Intraclass correlation coefficients allowed comparison between measures and were found to be 0.96 for LogMAR visual acuity, 0.93 for contrast sensitivity, 0.75 for LogMAR reading acuity, 0.79 for reading speed and 0.74 for LogMAR critical print size. Coefficients of variation were 9.4 %, 10.7 %, 48.4 %, 28.4 % and 31.8 % respectively. CONCLUSIONS: We found coefficients of repeatability that concurred with previous studies demonstrating variability of visual functions in patients with AMD. In addition, we found intraclass correlation coefficients to be better with visual acuity and contrast sensitivity than with measures of reading performance.