Real-world experience of using stereotactic radiotherapy combined with anti-vascular endothelial growth factor to treat neovascular AMD.

INTRODUCTION: Adjunctive treatment or longer-acting drugs are required to treat nAMD to help ease burdens for patients and hospital clinics alike. Stereotactic therapy is one such option, providing a reduction in the number of injections over time. OBJECTIVE: To determine the clinical outcomes in a cohort of patients with nAMD receiving a combination therapy of stereotactic radiotherapy (SRT) with intravitreal anti-VEGF injections (IVI). METHOD: A retrospective analysis of 74 patients with nAMD, who had received IVI and SRT (16 Gray maximum dose to the macula) at a large tertiary university eye hospital, between March 2018 and September 2019 was performed. The number of IVIs, visual acuity (VA), and central retinal thickness (CRT) were evaluated at 12, 24, and 36 months after patients received SRT and compared to the same time interval prior to SRT. RESULTS: Follow-up data at 12, 24, and 36 months following and prior to SRT was available for 74, 48, and 22 patients respectively. Overall there was a significant reduction in the number of injections post-SRT. Twelve months following SRT, the median number of IVI was reduced by 1 (p < 0.05). The reduction in the median number of IVI was significantly reduced by 3 and 6 injections at 24- and 36-month follow-up respectively (p < 0.05). The CRT was significantly reduced post-SRT compared to the baseline values at all time periods. There was no statistically significant difference in VA at 12-month follow-up compared to baseline. The VA, however, significantly decreased at 24- and 36-month follow-up (p < 0.05). CONCLUSION: A therapy combining SRT with IVI has shown an overall reduction in the number of injections required in nAMD patients at 12, 24, and 36 months following SRT compared to IVI treatment alone. These real-world outcomes are comparable to other studies while also confirming the maintenance of the reduced frequency of required IVI for patients with nAMD.

Comparison of 3-year outcomes of photodynamic therapy combined with intravitreal ranibizumab or aflibercept for polypoidal choroidal vasculopathy in a European cohort.

PURPOSE: Combined use of photodynamic therapy (PDT) with intravitreal anti-vascular endothelial growth factors (anti-VEGF) agents, such as ranibizumab (IVR) or aflibercept (IVA), has been shown to be effective for treating polypoidal choroidal vasculopathy (PCV). However, it is currently not well established which anti-VEGF agent provides superior outcomes for performing combination therapy. The present study compares the visual outcomes and re-treatment burden of combination therapy of PDT with either IVR or IVA in a European cohort of patients with PCV. METHODS: A retrospective analysis was done on PCV patients who had received combination therapy of PDT with either IVR or IVA. The demographic characteristics, visual outcome, and anti-VEGF re-treatment exposures were analysed and compared. RESULTS: A total of forty-four eyes (n = 11 male, 25%) were included in the analysis: 7 patients received IVR, 19 started with IVR but switched to IVA (IVS), and 18 received IVA, in combination with PDT. The BCVA improved in all three groups at 6-, 12-, 18-, 24-, 30-, and 36-month follow-ups after PDT, although the improvement was not statistically significant in the IVR group. The number of intravitreal anti-VEGF injections required/year after PDT was significantly fewer than before PDT. Significantly less eyes in the IVS group attained a good visual acuity of more than 70 ETDRS letters at the final visit. CONCLUSION: Both IVR and IVA combined with PDT were effective treatments for the European cohort of patients with PCV. In eyes refractory to IVR, performing PDT promptly may be more beneficial than switching to IVA.

IMAGE ANALYSIS OF OPTICAL COHERENCE TOMOGRAPHY SCANS TO EXPLORE ESTABLISHED AND NOVEL CHOROIDAL FEATURES IN PATIENTS WITH CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To explore the characteristics of choroidal tissue in patients with and without central serous chorioretinopathy (CSC) using an automated system of image analysis to determine known and novel metrics. METHODS: This was a retrospective case-control analysis of optical coherence tomography scans of patients seen at Manchester Royal Eye Hospital, UK, comparing patients with active CSC to an age-matched and gender-matched group with no CSC using a purpose-built automated system of image analysis. The expert system segments and measures established and novel features of choroid using a combination of thresholding, noise removal, and morphological techniques. RESULTS: A total of 72 patients were included in this study, with 40 included in the group with CSC and 32 patient controls with no CSC. There were significant increases from normal to CSC of median choroidal vascularity index, 54.7(median absolute deviation = 9.8) to 61.2(4.3), and all choroidal thickness indices including maximum depth, from 249.0(90.1) µm to 372.3(80.3) µm. For novel measures, there was a significant increase in tissue entropy from 6.68(0.28) to 6.95(0.17) and area of the largest five vessels from 6.28(3.04) mm2 to 9.10(3.49) mm2. The ratio of vessel lumen to stromal tissue intensity was conversely significantly reduced from 0.674(0.11) in normal patients to 0.59(0.06) in CSC. CONCLUSION: The automated system of choroidal analysis expands on the utility of known measures and introduces novel metrics. These findings contribute pathophysiological insights and metrics for further assessment and research on conditions affecting choroidal tissue.

Intra and inter-rater agreement of inflammatory choroidal neovascular membrane measurements using optical coherence tomography angiography.

PURPOSE: Automated measurement algorithm software is not routinely available in optical coherence tomography angiography (OCTA) devices and manual measurement of choroidal neovascular membrane (CNVM) size is necessary. Our aim was to determine intra- and inter-rater agreement of inflammatory CNVM manual measurements obtained with OCTA. METHODS: OCTA (Triton® Topcon Corporation) images in patients with inflammatory CNVM were imported into ImageJ software v1.50 (NIH image). Two experienced observers performed manual area and perimeter measurements independently, and one of the observers performed the same measurements twice. Agreement was evaluated with intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC). Bland-Altman plots were plotted to graphically assess concordance. Statistical analysis was performed using STATA v13.0. RESULTS: Sixteen eyes of 16 subjects, with a mean age of 39.0 ± 16.6 years (range 13-71), were included. Mean CNVM area and perimeter was 124.83 ± 117.80 and 4.20 ± 2.00 mm, respectively. Intra-rater ICC for both area and perimeter measured was 0.99 (95% confidence interval (CI) 0.99-0.99). Inter-rater ICC for area and perimeter measured was 0.95 (95%CI 0.87-0.98) and 0.81 (95%CI 0.17-0.94), respectively. Intra-rater CCC for both area and perimeter measured was 0.99 (95%CI 0.99-0.99). Inter-rater CCC for both area and perimeter measured was 0.91 (95%CI 0.81-0.99) and 0.66 (95%CI 0.44-0.88), respectively. CONCLUSIONS: Inflammatory CNVM manual measurement showed high intra-rater agreement and moderate inter-rater agreement. Repeatability and reproducibility studies are essential in manual analysis to establish thresholds that can distinguish measurements variation from true clinical change. An automatic algorithm may be helpful to accurately grade lesions and monitor disease activity and response to treatment.

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.

An unusual case report of primary vitreoretinal lymphoma.

BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is a rare ocular condition and its diagnosis remains a challenge. The clinical presentation is variable and it can masquerade as chronic intermediate or posterior uveitis. We report an unusual case of primary central nervous system lymphoma (PCNSL) presenting as migrating retinal lesions with unique shapes. The diagnostic challenges are described and the clinical features of intraocular lymphoma are reviewed. CASE PRESENTATION: A 53 year-old gentleman presented with unilateral visual disturbance and a wide area of retinal whitening with sharp borders temporal to the macula, corresponding to hyper-reflective subretinal changes on optical coherence tomography (OCT). The lesion resolved spontaneously after 6 weeks but was replaced by multiple punctate sub-retinal and sub-retinal pigment epithelial lesions. The second eye was involved 4 months later and there were new areas of hyper-reflective changes in both eyes, which migrated nasally within a week, with no evidence of scarring in the previous sites. The diagnosis of diffuse B-cell lymphoma was made on brain biopsy when the patient subsequently presented with acute confusion and magnetic resonance imaging brain scan showed a frontal lesion. Following systemic chemotherapy, the sub-retinal changes resolved with complete restoration of retinal architecture and improvement in visual acuity. CONCLUSION: We report an unusual case of PVRL presenting as migrating retinal lesions with unique shapes. PVRL is a great imitator and a high index of clinical suspicion is required in unexplained ocular lesions to prevent a delay in diagnosis.

Intravitreal Fluocinolone 0.19mg Implant in the Management of Chronic Non-Infectious Uveitis: 12-Month Outcomes from a Single Tertiary Centre.

AIM: To present efficacy and safety of 0.19 mg fluocinolone acetonide insert (FAi) to treat chronic noninfectious uveitis (NIU) in a single referral center. METHODS: A retrospective observational clinical study of 11 eyes with NIU complicated by chronic cystoid macular edema (CMO). RESULTS: The main indication for treatment was chronic CMO in all 11 eyes. The mean central retinal thickness (CRT) at baseline was 435 µm ± 176, improving to 296 µm ± 67 at 12 months. Raised intraocular pressure (IOP) was the commonest adverse event. An IOP >21 mmHg was observed in three eyes, and >30 mmHg in one eye, managed with topical therapy. The mean best corrected visual acuity (BCVA) was stable at 12 months. There were no observed recurrences of uveitis. Two eyes received adjunctive treatment for worsening CRT. CONCLUSIONS: Our results suggest FAi is an effective maintenance treatment for NIU with favorable functional and anatomical outcomes.

Real-world outcomes of combined therapy of photodynamic therapy with anti-vascular endothelial growth factor for polypoidal choroidal vasculopathy.

OBJECTIVES: To describe the real-world outcomes of photodynamic therapy (PDT) as a rescue therapy in eyes with polypoidal choroidal vasculopathy (PCV) refractory to anti-vascular endothelial growth factor (VEGF) monotherapy in a British cohort of patients. METHODS: This is a retrospective chart review of 53 eyes with PCV. Based on the timing of PDT, the eyes were stratified into two groups (9 in the Initial-PDT group, 44 in the Deferred group). The number of anti-VEGF injections/year and the best corrected visual acuity (BCVA) before and after PDT were analysed. Multivariate regression model was created to identify factors predictive of visual outcome and treatment burden after PDT. RESULTS: The Deferred group received a mean of 9.4 injections/year but significantly reduced to 7.2 after PDT (p < 0.001). The Initial-PDT group required significantly fewer injections after PDT compared to the Deferred group (p = 0.004). The Deferred group experienced improvement in BCVA from 58.7 letters at baseline to 63.8 at 18-months follow-up (p < 0.001), but no significant increase was observed in the Initial-PDT group (p = 0.310). Better baseline BCVA is associated with higher likelihood of achieving good BCVA ≥ 70 letters after PDT (Odd Ratio=1.12, 95% CI: 1.03-1.21, p = 0.006), while increased number of anti-VEGF injections/year before PDT reduces the likelihood of easing treatment burden to ≥12 weeks apart between each injection after PDT (Odd Ratio=0.724, 95% CI: 0.58-0.91, p = 0.006). CONCLUSIONS: PDT as a rescue therapy is beneficial in the long-term management of PCV, particularly in eyes that had experienced a significant period of prior exposure to anti-VEGF monotherapy.

Impact of COVID-19-associated anxiety on the adherence to intravitreal injection in patients with macular diseases a year after the initial outbreak.

BACKGROUND: As the primary burden of treating COVID-19 patients began to ease in the United Kingdom, ophthalmology clinic volume within the National Health Service has since recovered. Alarmingly, the rate of non-attendance remains higher than the pre-pandemic level. PURPOSE: The purpose was to assess how the perceived risk of contracting coronavirus disease 2019 (COVID-19) influences the willingness of individuals with sight-threatening macular conditions to attend intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection appointments during the second wave of the pandemic. METHODS: This prospective cross-sectional survey was conducted at the Macular Treatment Centre, Manchester Royal Eye Hospital. Patients who missed their appointment in January 2021 were invited to complete an anonymous survey over the telephone. The survey consisted of two parts: (1) a 23-item questionnaire aiming to assess fear of contracting COVID-19 in different hospital-related settings; and (2) the validated COVID-19 Anxiety Syndrome Scale (C-19ASS) to evaluate COVID-19-related anxiety. RESULTS: A total of 104 patients agreed to participate in the survey. Only a small proportion of patients believed COVID-19 vaccination (23 out of 88, 26.1%) had influenced their willingness to attend injection appointments. Majority of patients felt concerned about contracting COVID-19 during hospital appointments (n = 63, 60.6%). Only a minority of patients (n = 36, 34.6%) agreed with the hospital guidance on minimising clinical examinations during clinic visit. The C-19ASS was significantly higher in female patients, those older than 70 years and those with mobility issues. Higher C-19ASS, older age and living alone were predictors of clinic nonattendance. CONCLUSION: COVID-19 anxiety and fear of viral exposure could adversely affect patient adherence to clinic appointments during the pandemic. Particular attention should be provided to older patients, those who live alone and patients with impaired mobility. This is particularly relevant as hospital eye services across the world are in the process of restarting.

Visual and anatomical outcomes of central serous chorioretinopathy patients presenting to a tertiary unit: a prospective analysis.

AIM: The aim of this study was to prospectively define the characteristics and outcomes of a cohort of central serous chorioretinopathy patients using optical coherence tomography imaging to determine anatomical disease resolution. Much of the literature available on the characteristics of central serous chorioretinopathy patients pre date the advent of OCT imaging, with conclusive epidemiological evidence being scarce. We describe a cohort of patients presenting to a large centre over the course of a year. METHODS: Prospective data collection was undertaken for all patients diagnosed with central serous chorioretinopathy at our unit over the course of 1 year. All patients underwent thorough history taking and optical coherence tomography imaging. RESULTS: In total, 59 eyes from 51 patients were diagnosed with central serous chorioretinopathy between April 2017 and April 2018; 23 (45.1%) patients had optical coherence tomography evidence of complete anatomical resolution within a year, with three (5.88%) patients suffering a worse visual acuity compared with that at presentation at 1-year end point; and three patients developed secondary choroidal neovascular membranes. CONCLUSION: Our study reports much-needed prospective outcomes of patients with central serous chorioretinopathy, which helps to guide clinicians when deciding treatment strategies, as well as better informing patients of their prognosis for visual improvement.

Long-Term Outcomes and Complications of Baerveldt Glaucoma Drainage Implants in Adults with Glaucoma Secondary to Uveitis.

Purpose: This study investigated the efficacy and safety of Baerveldt glaucoma implants (BGI) in adults with uveitic glaucoma (UG) at the Manchester Uveitis Clinic.Methods: This was a retrospective study of 42 patients with UG who underwent BGI implantation between 2006 and 2015. Primary outcome measures were intraocular pressure (IOP) reduction and number of medications at 5-year follow-up. Three IOP success criteria were chosen: 1.IOP ≤21 mmHg and ≥20% reduction from baseline 2.IOP ≤17 mmHg and ≥20% reduction from baseline and 3.IOP ≤14 mmHg.Results: The mean pre-operative IOP was 29.5 ± 9.5 mmHg on 3.9 antiglaucoma drops. At 5-year follow-up, IOP reduced to 14.4 ± 7.0 mmHg (p < 0.005) on 1.4 drops. The cumulative probability of failure at 5 years based on criteria 1, 2, and 3 was 24.3%, 39.6%, and 56.3%, respectively.Conclusion: This study demonstrated that BGI are safe and effective in refractory UG, especially in younger adults with complex uveitis.

Polymerase chain reaction testing of vitreous in atypical ocular syphilis.

PURPOSE: To illustrate the diagnostic importance of syphilis PCR testing on intraocular fluid for atypical presentations. METHODS: Retrospective case series. RESULTS: Two cases of atypical intraocular inflammation were confirmed by PCR testing of vitreous for Treponema pallidum DNA. CONCLUSIONS: Ocular syphilis may be present in atypical fashion, and delayed treatment may lead to irreversible visual loss. Sampling of intraocular fluid for PCR testing may confirm diagnosis and lead to appropriate treatment.