Moorfields Eye Hospital Research Articles

Bilateral multifocal inner retinitis following a viral illness, likely Covid-19

Purpose: To describe a young female patient who presented with unilateral vision loss with multiple bilateral inner retinal lesions after a non-specific viral illness, likely Covid -19. Methods: Case Report: We reviewed the medical record, examined the retina, OCT images and fundus fluorescein angiogram of the patient along with the relevant medical literature. Results: The patient presented to our Emergency Department at Moorfields Eye Hospital with a two-week history of new onset floaters and blurred vision in her right eye. On examination she was found to have a low grade bilateral vitritis, mild right optic nerve head swelling and multiple white inner retinal lesions in both eyes. Conclusion: Retinitis can be due to multiple infectious and non-infectious aetiologies. In this case report we discuss a case of rare multifocal inner retinitis from a non-specific viral illness - likely COVID -19.

Quantification of Fundus Autofluorescence Features in a Molecularly Characterized Cohort of More Than 3500 Inherited Retinal Disease Patients from the United Kingdom

PurposeTo quantify relevant fundus autofluorescence (FAF) image features cross-sectionally and longitudinally in a large cohort of patients with inherited retinal diseases (IRDs). DesignRetrospective study of imaging data (55-degree blue-light FAF, Heidelberg Spectralis) . ParticipantsPatients with a clinical and molecularly confirmed diagnosis of IRD who have undergone 55-degree FAF imaging at Moorfields Eye Hospital (MEH) and the Royal Liverpool Hospital (RLH) between 2004 and 2019. MethodsFive FAF features of interest were defined: vessels, optic disc, perimacular ring of increased signal (ring), relative hypo-autofluorescence (hypo-AF) and hyper-autofluorescence (hyper-AF). Features were manually annotated by six graders in a subset of patients based on a defined grading protocol to produce segmentation masks to train an AI model, AIRDetect, which was then applied to the entire imaging dataset. Main Outcome MeasuresQuantitative FAF imaging features including area in mm2 and vessel metrics, were analysed cross-sectionally by gene and age, and longitudinally to determine rate of progression. AIRDetect feature segmentation and detection were validated with Dice score and precision/recall, respectively. ResultsA total of 45,749 FAF images from 3,606 IRD patients from MEH covering 170 genes were automatically segmented using AIRDetect. Model-grader Dice scores for disc, hypo-AF, hyper-AF, ring and vessels were respectively 0.86, 0.72, 0.69, 0.68 and 0.65. Across patients within our cohort at presentation, the five genes with the largest hypo-AF areas were CHM, ABCC6, RDH12, ABCA4, and RPE65, with mean per-patient areas of 43.72, 29.57, 20.07, 19.65, and 16.92 mm2. The five genes with the largest hyper-AF areas were BEST1, CDH23, NR2E3, MYO7A, and RDH12, with mean areas of 0.50, 047, 0.44, 0.38, and 0.33 mm2 respectively. The five genes with largest ring areas were NR2E3, CDH23, CRX, EYS and PDE6B, with mean areas of 3.60, 2.90, 2.89, 2.56, and 2.20 mm2. Vessel density was found to be highest in EFEMP1, BEST1, TIMP3, RS1, and PRPH2 (11.0%, 10.4%, 10.1%, 10.1%, 9.2%) and was lower in Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis genes. Longitudinal analysis of decreasing ring area in four RP genes (RPGR, USH2A, RHO, EYS) found EYS to be the fastest progressor at -0.18 mm2/year. ConclusionsWe have conducted the first large-scale cross-sectional and longitudinal quantitative analysis of FAF features across a diverse range of IRDs using a novel AI approach.

Posterior uveal biopsy and the trans-scleral Essen forceps biopsy technique.

Differentiating neoplastic and non-neoplastic uveal tumours can present a diagnostic challenge; intra-ocular biopsy may be necessary. The novel trans-scleral Essen Forceps biopsy (TSEB) technique can improve diagnostic yield compared to fine needle aspiration biopsy (FNAB). We present a case demonstrating the technique and its added value. We also review the success rate of TSEB performed at two tertiary eye centres. Retrospective case report and consecutive case series from August 2021 to March 2023. Inclusion criteria were patients who underwent TSEB of posterior uveal lesions from Moorfields Eye Hospital and Sheffield Teaching Hospitals in the United Kingdom. The outcomes were biopsy success rate and complication rate RESULTS: Eleven biopsies met the inclusion criteria. Eight (73%) were successful, which comprised six uveal melanomas, one melanocytoma and one extranodal marginal zone (ENMZ) lymphoma. One TSEB did not yield tissue for histological examination because of perioperative sample handling. Two (18%) biopsies were histologically inconclusive; both were treated as uveal melanoma on clinical grounds or repeat biopsy. The only complication was vitreous loss and retinal hole without retinal detachment in one eye with a very posterior, shallow choroidal lesion. TSEB is an effective alternative to established biopsy techniques, yielding larger tissue samples than FNAB with intact tissue architecture. We recommend adding TSEB to the armamentarium of the ocular oncologist.

Reactivation of stable neovascular age-related macular degeneration following treat-and-extend regimen discontinuation.

To describe the incidence and pattern of reactivation of neovascular age-related macular degeneration (nAMD) following successful treatment with treat-and-extend intravitreal anti-vascular endothelial growth factor therapy. Consecutive patients with treated nAMD who did not require further treatment over a 6-month period and who attended their 3-monthly optical coherence tomography monitoring clinic in Moorfields Eye Hospital from 1 November 2019 to 31 January 2020 were included. Patients with diagnoses of macular neovascularization other than AMD, and patients with incomplete data were excluded. Baseline demographics recorded were age, sex, race, laterality, cause of macular neovascularization, drug, number of injections, and duration of treatment. Date, setting, symptoms, and time to retreatment were collected among patients with disease reactivation. The medical records of 286 patients were included. Most patients were female (64.3%), white (68.18%), and were receiving aflibercept monotherapy (55.2%). Mean number of injections at baseline was 17.79 ± 11.74 (range 3-62) with a mean treatment duration of 39.47 ± 30.68 months (range 2-139). Reactivation of AMD was identified in 32.2% of cases with 87% of recurrences identified via scheduled visit. The most common symptom was blurring of vision in 44.6%, while 39.1% were asymptomatic. Mean time from baseline to retreatment was 29.37 ± 22.40 months (range 5-104), with 20.7%, 73.9% and 88.04% of these patients requiring retreatment within 1, 3, and 5 years, respectively. Despite prior treatment with no reactivation in 6 months, 32.2% reactivate, 73.9% of which within 3 years. A significant proportion, 39.1%, reactivated without symptoms necessitating regular monitoring in the first 5 years.

Bibliometric analysis of ophthalmic OCT and OCT angiography research trends over the past 20 years.

Optical coherence tomography (OCT) and OCT angiography (OCTA) are widely used in the diagnosis of ophthalmic diseases. This study aims to provide a comprehensive bibliometric analysis of ophthalmologic OCT and OCT angiography. We retrieved publications on ophthalmic OCT and OCTA from 2003 to 2022 from the Web of Science Core Collection and used bibliometric tools to analyze and visualize the distribution, trend, and hotspots. In total, 20,817 articles written by 48,160 authors from 106 countries were selected. The number of publications has significantly increased. In the last two decades, the USA was the most productive country and received the highest citations. The most productive journal was Investigative Ophthalmology and Visual Science and received the highest number of citations. Moorfields Eye Hospital was the most productive institution. Bandello F published the most papers, while Spaide RF was the highest cited author. SPAIDE RF, 2011, AM J Ophthalmology was the most cited document. "OCT", "glaucoma" and "OCTA" were three hotspots in the last two decades. "Vessel density" and "deep learning" would be research hotspots in the future. The bibliometric analysis of ophthalmic OCT and OCTA research over the past two decades on keywords, authors, citations, hotspots and trends will provide global researchers with valuable information for future research and cooperation.

Digital Exclusion, Social Deprivation, and Clinical Outcomes of Patients Undergoing Hyperacuity Home Monitoring.

Digital exclusion is a growing challenge when deploying digital patient care pathways and a potential barrier to widespread implementation, especially in the field of smartphone-based self-monitoring of vision. This retrospective case series seeks to examine the characteristics of individuals who adhere to a smartphone homemonitoring programme using the Alleye app for retinal disease, with a focus on digital exclusion, social deprivation and clinical outcomes. We conducted a retrospective analysis of 89 patients with retinal pathologies including diabetic retinopathy and retinal vein occlusions at Moorfields Eye Hospital participating in an Alleye homemonitoring programme between April 2020 and November 2022. Postcodes were used to determine the Digital Exclusion Risk Index (DERI) and the Index of Multiple Deprivation (IMD) rebased for London. Clinical information from the electronic patient record and Alleye app usage data were extracted for each patient. Associations between the DERI/IMD, clinical parameters and app use were examined using multivariable regression models. Mean DERI was 2.56 (standard deviation [SD] = 0.36), IMD was 6.25 (SD = 2.79), visual acuity (VA) in the better eye at study entry was 83.28 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (SD = 7.92), and mean follow-up was 344.46days (SD = 260.13). During the observation period, 36% received an intravitreal injection (IVI) and VA fell by at least ten letters in approximately one in four patients. In 87.5% of patients requiring IVI, the use of the app increased. We found no association between clinical parameters and programme adherence for DERI or IMD. We found no association between high digital exclusion risk and high social deprivation with monitoring adherence to smartphone-based self-monitoring of vision, contrary to the currently available evidence. This suggests that smartphone-based self-monitoring of vision is accessible to population groups of varying digital exclusion and social deprivation risk, and can be safely employed to monitor clinical progression.

Paracentral Acute Middle Maculopathy and Risk of Cardiovascular Disease, Stroke, and Death: A Longitudinal Study

To evaluate the risk of acute cardiovascular events (CVE), including cardiovascular diseases, cerebrovascular diseases, and all-cause mortality in patients with paracentral acute middle maculopathy (PAMM). Retrospective cohort study METHODS: We studied 43 individuals with optical coherence tomography -documented PAMM attending Moorfields Eye Hospital between January 2014 and June 2021. We excluded patients with preceding (< 2 years) major adverse cardiac events. We stratified patients by age (<50 years & ≥50 years) and whether associated with retinal vascular diseases (RVD) or isolated (iPAMM). We assessed risk factors, clinical characteristics, and visual prognosis of the patients. CVE risk was estimated using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards regression. In young patients with iPAMM patients (n=12), underlying predisposing factors included six (50%) sickle cell disease and five (41.6%) others, including breakthrough bleeding in pregnancy, migraine, genetic cardiomyopathy, amphetamine use; among those with PAMM+RVD (n=12) one (9%) had a vascular disorder, and four (44.4%) oral contraceptive use. In the older group of 20 patients, 15 (75%) had at least one coronary risk factor. During a median follow-up of 14 months (range 12-54), older subjects with iPAMM had a higher risk of developing CVE than those with PAMM+RVD (p<0.001). Notably, iPAMM displayed a significantly earlier peak in peri-PAMM CVE risk compared to PAMM+RVD (median: 1 month, range 1-40 months vs. 36 months, range 12-54 months). Relative to those with PAMM+RVD, risk of CVE was significantly higher in patients with iPAMM, adjusted for age and sex (hazard ratio: 6.37, 95% Confidence Interval 1.68-24.14, p=0.017). No young patients experienced adverse CVE. At baseline, older iPAMM patients mean best corrected visual acuity of 0.7 (0-1.8) LogMAR, which improved significantly to 0.2 (0-1.30) LogMAR at the latest visit (p=0.033). Young individuals with iPAMM have a higher prevalence of predisposing factors compared to those presenting with combined PAMM+RVD. Older patients with iPAMM had a higher risk of CVE than those with PAMM+RVD, especially in the peri-onset timeframe. This suggests the need for a prompt cardiovascular assessment to rule out systemic etiologies and optimize cardiovascular risk factors, in addition to ongoing ophthalmology input.

Quantification of Fundus Autofluorescence Features in a Molecularly Characterized Cohort of More Than 3500 Inherited Retinal Disease Patients from the United Kingdom.

To quantify relevant fundus autofluorescence (FAF) image features cross-sectionally and longitudinally in a large cohort of inherited retinal diseases (IRDs) patients. Retrospective study of imaging data (55-degree blue-FAF on Heidelberg Spectralis) from patients. Patients with a clinical and molecularly confirmed diagnosis of IRD who have undergone FAF 55-degree imaging at Moorfields Eye Hospital (MEH) and the Royal Liverpool Hospital (RLH) between 2004 and 2019. Five FAF features of interest were defined: vessels, optic disc, perimacular ring of increased signal (ring), relative hypo-autofluorescence (hypo-AF) and hyper-autofluorescence (hyper-AF). Features were manually annotated by six graders in a subset of patients based on a defined grading protocol to produce segmentation masks to train an AI model, AIRDetect, which was then applied to the entire MEH imaging dataset. Quantitative FAF imaging features including area in mm 2 and vessel metrics, were analysed cross-sectionally by gene and age, and longitudinally to determine rate of progression. AIRDetect feature segmentation and detection were validated with Dice score and precision/recall, respectively. A total of 45,749 FAF images from 3,606 IRD patients from MEH covering 170 genes were automatically segmented using AIRDetect. Model-grader Dice scores for disc, hypo-AF, hyper-AF, ring and vessels were respectively 0.86, 0.72, 0.69, 0.68 and 0.65. The five genes with the largest hypo-AF areas were CHM , ABCC6 , ABCA4 , RDH12 , and RPE65 , with mean per-patient areas of 41.5, 30.0, 21.9, 21.4, and 15.1 mm 2 . The five genes with the largest hyper-AF areas were BEST1 , CDH23 , RDH12 , MYO7A , and NR2E3 , with mean areas of 0.49, 0.45, 0.44, 0.39, and 0.34 mm 2 respectively. The five genes with largest ring areas were CDH23 , NR2E3 , CRX , EYS and MYO7A, with mean areas of 3.63, 3.32, 2.84, 2.39, and 2.16 mm 2 . Vessel density was found to be highest in EFEMP1 , BEST1 , TIMP3 , RS1 , and PRPH2 (10.6%, 10.3%, 9.8%, 9.7%, 8.9%) and was lower in Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis genes. Longitudinal analysis of decreasing ring area in four RP genes ( RPGR, USH2A, RHO, EYS ) found EYS to be the fastest progressor at -0.18 mm 2 /year. We have conducted the first large-scale cross-sectional and longitudinal quantitative analysis of FAF features across a diverse range of IRDs using a novel AI approach.

Incidence and outcomes of post-operative endophthalmitis following elective phacoemulsification cataract surgery, between 2015 and 2022.

Cataract surgery remains the commonest ophthalmic surgical procedure in the UK. Post-operative endophthalmitis (POE) is a sight-threatening complication. This study presents the incidence and outcomes of POE within Moorfields Eye Hospital NHS Foundation Trust (MEH) in London, UK. We conducted a retrospective, tertiary-centre study of the incidence and outcomes of POE following elective phacoemulsification cataract surgery between 2015 and 2022. We report a rate of 18 out of 154 826 (0.012%) cases of POE within seven weeks of cataract surgery. The age range was 43-87 years (mean age 67.1 years), and the male-to-female ratio was 1:1. Two cases were associated with intraoperative vitreous loss, one with anterior capsular tear extending to posterior capsular tear and the other with posterior capsular tear and dropped fragment. Two cases had a concomitant intravitreal injection, one of Triamcinolone Acetonide and the other of Dexamethasone implant (Ozurdex®), to manage chronic uveitic macular oedema. The majority of samples (89.9%) resulted in Gram-positive species. A final best corrected visual acuity (BCVA) of Snellen 6/36 or better was achieved in 12/18 (66.67%). The time from cataract surgery to suspicion of POE ranged from 3 to 44 days (mean 15.8 days). Eight cases (44.4%) required pars plana vitrectomy (PPV). We demonstrate an incidence of POE of 0.012% following phacoemulsification at MEH from January 2015 to December 2022. Such results are a testament to high-quality surgery, training supervision and post-operative care whilst adhering to local and international standards.

Real-World Experience of Fluocinolone Acetonide 0.19 mg in the Management of Non-Infectious Uveitis

ABSTRACT Purpose This study aims to evaluate the real-world efficacy and safety profile of fluocinolone acetonide (FAc) implants for the treatment of non-infectious uveitis (NIU). Methods A retrospective, observational study was conducted at Moorfields Eye Hospital, London, involving patients who received FAc 0.19 mg implants (Iluvien®) for NIU. 2-year follow-up data on baseline characteristics, indications, and outcomes was collected. The primary indicator for treatment failure was defined as the need for rescue treatment with dexamethasone (DEX) implants, while secondary indicators included changes in steroid and systemic immunosuppression requirements, or the need for a second FAc implant before 3 years. The occurrence of complications was collected. Results Of the 146 eyes treated with FAc implants, 24.0% experienced treatment failure requiring DEX implant within 2 years. About 42.9% required this within the first 6 months. There was an increase in the number of patients requiring steroids and/or systemic immunosuppression. Within the first 2 years post-FAc implant, only 13.7% experienced an IOP rise, with 4.1% requiring IOP-lowering surgery. About 57.9% of the phakic eyes developed cataracts. Conclusion This study provides valuable real-world evidence supporting the efficacy of FAc implant in NIU. It demonstrates a good safety profile at 2 years, with a significant reduction in uveitis recurrence rate and treatment burden. Our results are especially pertinent to the treatment of uveitic cystoid macular oedema (CMO), which was the primary indication in over 75% of our patients. Furthermore, it suggests that while FAc implant controls retinal inflammation effectively, choroidal inflammation would require alternative treatment.

Real-World 1-Year Outcomes of Treatment-Intensive Neovascular Age-Related Macular Degeneration Switched to Faricimab

PurposeTo report one-year anatomical and functional real-world outcomes of treatment intensive neovascular age related macular degeneration (nAMD) patients switched to faricimab DesignRetrospective multi-centre cohort study SubjectsConsecutive nAMD patients on 4-weekly treatment interval with either ranibizumab or aflibercept 2mg in the last three visits within a treat and extend protocol (high treatment burden) prior to switch to faricimab at Moorfields Eye Hospital between 5/9/2022- 5/12/2022. MethodsTotal number of nAMD patients switched to faricimab were identified from electronic medical records and those who met criteria of high treatment burden were included. Data collected included pre and post-switch visual acuity (VA), treatment intervals, length of follow-up, baseline macular morphology, changes in central subfield thickness (CST), macular fluid status and adverse events. Main outcome measuresVA, CST, presence of intraretinal fluid (IRF), subretinal fluid (SRF) and injection intervals over one-year following switch to faricimab. ResultsA total of 130/ 286 (45.5%) eyes met inclusion criteria of being switched due to high treatment burden and 117 were included in analysis. Prior to switch to faricimab, these eyes received mean total number of injections of 33.4±19.6 over mean of 51.3±34.9 months. Mean number of injections in 12 months preceding switch was 10.1±1.6 and mean interval of the preceding three injections was 4.2±0.3 weeks. Mean VA, CST and percentage of patients with dry macula prior to switch were 66.0±11.9 ETDRS letters, 259.6±76.0μm and 18.3% respectively. Following switch, there was no statistical difference in mean VA after each visit and at 12 months. Mean CST statistically significantly reduced following the 3rd faricimab injection and at 12 months by 20.0μm (p=0.035) and 22.1μm (p=0.041) respectively. Mean treatment intervals increased to 6.9±2.3 weeks (p<0.005) at 12 months with 42.9% and 11.4% of patients being on ≥8 weekly and ≥12 weekly treatment intervals respectively. ConclusionAt 12 months, patients with nAMD with previous record of high treatment burden when switched to faricimab maintained visual acuities and improved anatomical outcomes on extended treatment intervals. Physician bias is inherent in these types of observational studies so a prospective randomised controlled trial is recommended to validate these findings.

Quantifying Changes on OCT in Eyes Receiving Treatment for Neovascular Age-Related Macular Degeneration

PurposeApplication of artificial intelligence (AI) to macular optical coherence tomography (OCT) scans to segment and quantify volumetric change of anatomical and pathological features during intravitreal treatment for neovascular age-related macular degeneration (AMD). DesignRetrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. Participants2115 eyes from 1883 patients that started anti-vascular endothelial growth factor (anti-VEGF) treatment between 1st June 2012 and 30th June 2017. MethodsThe Moorfields Eye Hospital neovascular AMD database was queried for first and second eyes that received anti-VEGF treatment and had an OCT scan at baseline and at 12 months. Follow-up scans were input into the AI system to derive volumetric outputs for the following variables: intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), subretinal hyperreflective material (SHRM), hyperreflective foci (HRF), neurosensory retina (NSR) and retinal pigment epithelium (RPE). Volumes were studied at different time points and comparisons made with respect to baseline volume groups. Cross-sectional comparisons between time points were conducted using Mann-Whitney U test. ResultsMean volumes of analysed features decreased significantly from baseline to both four and 12 months, in both first and second-treated eyes. Pathological features that reflect exudation, including pure fluid components (IRF and SRF) and those with a mixture of fluid and fibrovascular tissue (PED and SHRM), displayed similar response to treatment over 12 months. Mean PED and SHRM volumes showed less pronounced but also substantial decreases over the first two months, reaching a plateau post loading phase, and minimal change to 12 months. Both NSR and RPE volumes showed gradual reductions over time, and not as substantial as exudative features. Conclusion:We report the results of a quantitative analysis of change in retinal segmented features over time, enabled by an AI segmentation system. Cross-sectional analysis at multiple time points demonstrated significant associations between baseline OCT-derived segmented features and the volume of biomarkers at follow-up. Demonstrating how certain OCT biomarkers progress with treatment and the impact of pre-treatment retinal morphology on different structural volumes may provide novel insights into disease mechanisms and aid personalization of care. Data will be made public for future studies.

Artificial Intelligence to Facilitate Clinical Trial Recruitment in Age-Related Macular Degeneration

ObjectiveRecent developments in artificial intelligence (AI) have positioned it to transform several stages of the clinical trial process. In this study, we explore the role of AI in clinical trial recruitment of individuals with geographic atrophy (GA), an advanced stage of age-related macular degeneration, amidst numerous ongoing clinical trials for this condition. DesignCross-sectional study.Subjects, Participants, and/or Controls: Retrospective dataset from the INSIGHT Health Data Research Hub at Moorfields Eye Hospital in London, United Kingdom, including 306,651 patients (602,826 eyes) with suspected retinal disease who underwent optical coherence tomography (OCT) imaging between 1 January 2008 and 10 April 2023. Methods, Intervention, or TestingA deep learning model was trained on OCT scans to identify patients potentially eligible for GA trials, using AI-generated segmentations of retinal tissue. This method's efficacy was compared against a traditional keyword-based electronic health record (EHR) search. A clinical validation with fundus autofluorescence (FAF) images was performed to calculate the positive predictive value (PPV) of this approach, by comparing AI predictions to expert assessments. Main Outcome MeasuresThe primary outcomes included the PPV of AI in identifying trial-eligible patients, and the secondary outcome was the intraclass correlation between GA areas segmented on FAF by experts and AI-segmented OCT scans. ResultsThe AI system shortlisted a larger number of eligible patients with greater precision (1,139, PPV: 63%; 95% CI: 54–71%) compared to the EHR search (693, PPV: 40%; 95% CI: 39–42%). A combined AI-EHR approach identified 604 eligible patients with a PPV of 86% (95% CI: 79–92%). Intraclass correlation of GA area segmented on FAF versus AI-segmented area on OCT was 0.77 (95% CI: 0.68–0.84) for cases meeting trial criteria. The AI also adjusts to the distinct imaging criteria from several clinical trials, generating tailored shortlists ranging from 438 to 1,817 patients. ConclusionsThis study demonstrates the potential for AI in facilitating automated pre-screening for clinical trials in GA, enabling site feasibility assessments, data-driven protocol design, and cost reduction. Once treatments are available, similar AI systems could also be used to identify individuals who may benefit from treatment.

Long-term outcomes after acute primary angle closure: case series from Moorfields Eye Hospital, UK

BackgroundThere is limited data regarding the morbidity and progression to primary angle closure glaucoma in those presenting with acute primary angle closure (APAC) in the UK. We aim to report...

Retinal morphological differences in atypical Parkinsonism: A cross-sectional analysis of the AlzEye cohort

ObjectiveAtypical Parkinsonian syndrome (APS) describes a heterogeneous group of disorders mimicking the clinical presentation of Parkinson disease (PD) but with disparate natural history and pathophysiology. While retinal markers of PD are increasingly described, APS has been afforded less attention possibly owing to its lower prevalence. Here, we investigate retinal morphological differences in individuals with APS in a large real world cohort. MethodsWe conducted a cross-sectional analysis of the AlzEye study, a retrospective cohort where ophthalmic data of individuals attending Moorfields Eye Hospital between January 2008 and March 31st 2018 (inclusive) has been linked with systemic disease data through national hospital admissions. Retinal features were extracted from macula-centered color fundus photography (CFP) and optical coherence tomography (OCT) and compared between individuals with APS and those unaffected. Individuals with idiopathic PD were excluded. Retinal neural and vascular features were measured using automated segmentation and analyzed with multivariable-adjusted regression models. ResultsAmong a cohort of 91,170 patients, there were 51 patients with APS and 91,119 controls. Individuals with APS were older and more likely to have hypertension and diabetes mellitus. After adjusting for age, sex, hypertension and diabetes melitus, individuals with APS had a thinner ganglion cell-inner plexiform layer (-3.95 microns, 95% CI: −7.53, −0.37, p = 0.031) but no difference in other retinoneural or retinovascular indices. Optic nerve cup-to-disc ratio was similar between groups. ConclusionOur cross-sectional analysis of the AlzEye cohort reveals distinct retinal morphological characteristics in APS compared to healthy controls. The study notably identifies a thinner ganglion cell-inner plexiform layer in APS patients, without accompanying changes in the inner nuclear layer or significant alterations in retinovascular indices and optic nerve cup-disc ratio. These changes are distinct from those observed in PD, where thinning of the inner nuclear layer (INL) is a characteristic feature. SignificanceThese findings demonstrate a retinal phenotype in APS, markedly different from both healthy controls and idiopathic Parkinson's disease, highlighting the potential of retinal imaging in differentiating neurodegenerative disorders. By establishing a distinct retinal phenotype for APS, our findings underscore the potential of retinal imaging as a valuable, non-invasive diagnostic tool. This advancement is particularly significant for enhancing diagnostic accuracy, facilitating early detection, and offering a window into the underlying disease mechanisms in APS, thereby aiding in the development of targeted therapeutic interventions and personalized patient care strategies.

Optometrist-delivered selective laser trabeculoplasty in the HES – a training protocol and early service evaluation

Over the last decade, the delivery of glaucoma care in the UK has changed dramatically, with more non-medical ophthalmic practitioners involved in the care of glaucoma patients. Optometrists and other non-medical professionals are now involved in the delivery of laser treatments in the Hospital Eye Service (HES), but there is currently no standardised national training framework for non-medical clinicians. Moorfields Eye Hospital and UCL’s Institute of Ophthalmology have developed and delivered an education and training programme for the delivery of lasers, including Selective Laser Trabeculoplasty (SLT) by non-medical ophthalmic practitioners. The training programme is based on medical education principles, is informed by previous qualitative research into the role of ophthalmic practitioners in the delivery of laser treatments and is expected to have multidisciplinary benefits for ophthalmic healthcare. Clinical audit data indicate that optometrists can deliver safe SLT treatments, adhering to local protocols.

Congenital Stationary Night Blindness: Structure, Function and Genotype–Phenotype Correlations in a Cohort of 122 Patients

To examine the molecular causes of Schubert-Bornschein (S-B) congenital stationary night blindness (CSNB), clinically characterize in detail, and assess genotype-phenotype correlations for retinal function and structure. Retrospective, longitudinal, single-center case series. One hundred twenty-two patients with S-B CSNB attending Moorfields Eye Hospital, United Kingdom. All case notes, results of molecular genetic testing, and OCT were reviewed. Molecular genetics, presenting complaints, rates of nystagmus, nyctalopia, photophobia, strabismus, color vision defects and spherical equivalent refraction (SER). Retinal thickness, outer nuclear layer (ONL) thickness, and ganglion cell layer+ inner plexiform layer (GCL+IPL) thickness from OCT imaging. X-linked (CACNA1F and NYX) and autosomal recessive (TRPM1, GRM6, GPR179 and CABP4) genotypes were identified. The mean (± standard deviation) reported age of onset was 4.94 ± 8.99 years. Over the follow-up period, 95.9% of patients reported reduced visual acuity (VA), half had nystagmus, and 64.7% reported nyctalopia. Incomplete CSNB (iCSNB) patients more frequently had nystagmus and photophobia. Nyctalopia was similar for iCSNB and complete CSNB (cCSNB). Color vision data were limited but more defects were found in iCSNB. None of these clinical differences met statistical significance. There was no significant difference between groups in VA, with a mean of 0.46 logarithm of the minimum angle of resolution, and VA remained stable over the course of follow-up. Complete congenital stationary night blindness patients, specifically those with NYX and TRPM1 variants, were more myopic. CACNA1F patients showed the largest refractive variability, and the CABP4 patient was hyperopic. No significant differences were found in OCT structural analysis during the follow-up period. Retinal structure in CSNB is stationary and no specific genotype-structure correlates were identified. Visual acuity seems to be relatively stable, with rare instances of progression. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Adaptive Optics Retinal Imaging in RDH12-Associated Early Onset Severe Retinal Dystrophy.

RDH12 is among the most common genes found in individuals with early-onset severe retinal (EOSRD). Adaptive optics scanning light ophthalmoscopy (AOSLO) enables resolution of individual rod and cone photoreceptors in the retina. This study presents the first AOSLO imaging of individuals with RDH12-associated EOSRD. Case series of patients who attended Moorfields Eye Hospital (London, UK). Spectral-domain optical coherence tomography, near-infrared reflectance (NIR), and blue autofluorescence imaging were analyzed. En face image sequences of photoreceptors were recorded using either of two AOSLO modalities. Cross-sectional analysis was undertaken for seven patients and longitudinal analysis for one patient. Nine eyes from eight patients are presented in this case series. The mean age at the time of the assessment was 11.2 ± 6.5years of age (range 7-29). A subfoveal continuous ellipsoid zone (EZ) line was present in eight eyes. Posterior pole AOSLO revealed patches of cone mosaics. Average cone densities at regions of interest 0.5° to the fovea ranged from 12,620 to 23,660 cells/mm2, whereas intercell spacing ranged from 7.0 to 9.7µm. This study demonstrates that AOSLO can provide useful high-quality images in patients with EOSRD, even during childhood, with nystagmus, and early macular atrophy. Cones at the posterior pole can appear as scattered islands or, possibly later in life, as a single subfoveal conglomerate. Detailed image analysis suggests that retinal pigment epithelial stress and dysfunction may be the initial step toward degeneration, with NIR being a useful tool to assess retinal well-being in RDH12-associated EOSRD.

Sight threatening diabetic retinopathy in patients with macular telangiectasia type 2

PurposeAlthough diabetes is highly prevalent in patients with macular telangiectasia type 2 (MacTel), progression to severe non-proliferative (NPDR) and proliferative diabetic retinopathy (PDR) is rarely reported. We report multimodal imaging features of sight-threatening diabetic retinopathy (STDR) in eyes with MacTel.MethodsRetrospective case series of seven participants of the MacTel Study at the Moorfields Eye Hospital NHS Foundation Trust study site and one patient from the Institute of Retina and Vitreous of Londrina, Brazil. Sight threatening diabetic retinopathy was defined as severe NPDR, PDR or diabetic macular edema.ResultsWe report imaging features of 16 eyes of eight patients (7/8, 87.5% female) with diagnoses of MacTel and type 2 diabetes mellitus with STDR. Mean (SD) age was 56 (8.3) years. Patients were followed-up for a mean time of 9.1 (4.7) years. A total of 10/16 (62.5%) eyes showed PDR and 2/16 (12.5%) eyes presented a macular epiretinal neovascularization.ConclusionsPeople with diabetes mellitus and MacTel may not be protected from STDR as previously reported. Although the two diseases rarely co-exist, regular monitoring for diabetic retinopathy progression is recommended according to baseline retinopathy severity grades in line with established international guidelines. The presence of MacTel may not modify extended screening intervals, but there is no current evidence. The limited case series in the literature support treatment for complications and should follow the standard of care for either condition. Due to dual pathology, reactivation may be difficult to diagnose on standard imaging and multimodal imaging is recommended.

PHYH c.678+5G>T Leads to In-Frame Exon Skipping and Is Associated With Attenuated Refsum Disease.

To investigate the molecular effect of the variant PHYH:c.678+5G>T. This variant has conflicting interpretations in the ClinVar database and a maximum allele frequency of 0.0045 in the South Asian population in gnomAD. We recruited patients from Moorfields Eye Hospital (London, UK) and Buenos Aires, Argentina, who were diagnosed with retinitis pigmentosa and found to have biallelic variants in PHYH, with at least one being c.678+5G>T. Total RNA was purified from PaxGene RNA-stabilized whole-blood samples, followed by reverse transcription to cDNA, PCR amplification of the canonical PHYH transcript, Oxford Nanopore Technologies library preparation, and single-molecule amplicon sequencing. Four patients provided a blood sample. One patient had isolated retinitis pigmentosa and three had mild extraocular findings. Blood phytanic acid levels were normal in two patients, mildly elevated in one, and markedly high in the fourth. Retinal evaluation showed an intact ellipsoid zone as well as preserved autofluorescence in the macular region in three of the four patients. In all patients, we observed in-frame skipping of exons 5 and 6 in 31.1% to 88.4% of the amplicons and a smaller proportion (0% to 11.3% of amplicons) skipping exon 6 only. We demonstrate a significant effect of PHYH:c.678+5G>T on splicing of the canonical transcript. The in-frame nature of this may be in keeping with a mild presentation and higher prevalence in the general population. These data support the classification of the variant as pathogenic, and patients harboring a biallelic genotype should undergo phytanic acid testing.