Clinical utility of ultra-widefield fluorescein angiography and optical coherence tomography angiography for retinal vein occlusions

Retinal vein occlusions (RVOs) are the second most common retinal vascular disease after diabetic retinopathy, and are a significant cause of visual impairment, especially in the elderly population. RVOs result in visual loss due to macular ischemia, cystoid macular edema (CME), and complications related to neovascularization. Vascular assessment in RVOs traditionally relies on standard fluorescein angiography (FA) for assessment of macular and retinal ischemia, which aids in prognostication and guides intervention. Standard FA has significant limitations—it is time-consuming, requires invasive dye administration, allows for limited assessment of the peripheral retina, and is usually evaluated semi-qualitatively, by ophthalmologists with tertiary expertise. More recently, the introduction of ultra-widefield FA (UWF FA) and optical coherence tomography angiography (OCTA) into clinical practice has changed the tools available for vascular evaluation in RVOs. UWF FA allows for evaluation of peripheral retinal perfusion, and OCTA is non-invasive, rapidly-acquired, and provides more information on capillary perfusion. Both modalities can be used to provide more quantitative parameters related to retinal perfusion. In this article, we review the clinical utility and impact of UWF FA and OCTA in the evaluation and management of patients with RVOs

Using Real-World Observations to Individualise the Management of Age-Related Macular Degeneration: Data from the Fight Retinal Blindness! Registry

A significant shortcoming in the management of neovascular age related macular degeneration (nAMD) is the high treatment burden if clinical trial regimens are to be adhered to strictly. There is an unmet need for personalized treatment which considers the use of real-world evidence (RWE). This thesis critically reviewed current literature to ascertain the best way of analysing and reporting real world data and outcomes and provided key principles for the conduct, analysis and reporting of RWE in nAMD. Four principles are proposed: 1)Any RWE analysis should be designed with a clinical question and hypothesis. 2)The data source must be robust or evaluated critically for any limitations which may contribute to bias in outcomes. 3) Appropriate statistical techniques should be applied and predefined in a statistical analysis plan based on the clinical question and hypothesis. 4)The results should address the initial clinical question and acknowledge the limitations of the data and analysis. Next, data from the Fight Retinal Blindness! International AMD registry was used to showcase the application of this framework and establish important insights in the personalisation of nAMD treatment. These analyses are presented to mimic a patient’s treatment journey in clinical practice highlighting the importance of differentiating nAMD subtypes, the impact of long treatment patterns, consequences of nonadherence or non-persistence of treatment and lastly disease response and subsequent end stage phenotypes nAMD. These findings can be translated to feasible and practical recommendations that are immediately applicable to patients undergoing treatment for nAMD

The Use of Vascular Endothelial Growth Factor Inhibitors and Complementary Treatment Options in Polypoidal Choroidal Vasculopathy: A Subtype of Neovascular Age-Related Macular Degeneration

Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration (AMD; nAMD) which occurs more commonly in Asian populations as compared to Caucasians. PCV and nAMD share pathological mechanisms, including pathological expression of vascular endothelial growth factor (VEGF). The advent of anti-vascular endothelial growth factor (VEGF) revolutionized the treatment of nAMD. Despite being a subtype of nAMD, PCV responds less well to VEGF inhibitors; thus, photodynamic therapy (PDT) in combination with anti-VEGF treatment may be considered. This review aims to summarize the current evidence for the treatment of PCV, especially whether VEGF inhibitors should be used alone or in combination with PDT

The Use of Vascular Endothelial Growth Factor Inhibitors and Complementary Treatment Options in Polypoidal Choroidal Vasculopathy: A Subtype of Neovascular Age-Related Macular Degeneration

Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration (AMD; nAMD) which occurs more commonly in Asian populations as compared to Caucasians. PCV and nAMD share pathological mechanisms, including pathological expression of vascular endothelial growth factor (VEGF). The advent of anti-vascular endothelial growth factor (VEGF) revolutionized the treatment of nAMD. Despite being a subtype of nAMD, PCV responds less well to VEGF inhibitors; thus, photodynamic therapy (PDT) in combination with anti-VEGF treatment may be considered. This review aims to summarize the current evidence for the treatment of PCV, especially whether VEGF inhibitors should be used alone or in combination with PDT

Keeping our eyecare providers and patients safe during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the defining event of this generation. To date, there are over 2 million cases including more than 145,000 deaths with this number constantly rises day by day. The lack of a cure or a viable vaccine has resulted in the implementation of extreme social distancing measures with lockdowns declared in many countries to minimise person-to-person interactions to prevent the transmission of the virus. These measures have a profound impact on health care provision. A few sub-specialities such as ENT, anaesthesia and ophthalmology are considered to be at higher risk than others due to the close proximity to patients and the nature of procedures associated with higher transmission risk

Extended intervals for wet AMD patients with high retreatment needs: informing the risk during COVID-19, data from real-world evidence

BACKGROUND/OBJECTIVE Some clinicians may be forced to temporarily extend treatment intervals in neovascular age-related macular degeneration (nAMD) eyes with frequent retreatments to reduce the number of visits during the COVID-19 pandemic. To provide an indication of what these outcomes may be, we studied eyes with active lesions with unplanned treatment interval extensions before the pandemic occurred. METHODS We compared eyes with active disease despite ≤6 weekly injections whose next injection was extended to ≥7 weeks and those whose intervals were not extended. We identified 1559 (16%) of 9602 eyes from the Fight Retinal Blindness! (FRB!) registry (2013 and 2018) that fit this criteria. Eyes were further stratified into four groups by the mean interval over the following 6 months: (1) ≤6 weeks (81%), (2) 7-9 weeks (9%), (3) 10-12 weeks (5%) and (4) >12 weeks (5%). RESULTS There was a significant loss in VA in eyes extended to >12 weeks compared to the non-extended group (adjusted VA change, mean (95% CI): ≤6 weeks, 0.4 (-1.5 to 2.2), versus >12 weeks, -4.7 (-7.4 to -2.1), letters, p = 0.03 and a threefold increase in relative risk of losing ≥15 letters (absolute risk (14% versus 4%, p < 0.01)). CONCLUSION Mean VA remained stable for 6 months in eyes requiring frequent treatment despite retreatment interval extension up to 10-12 weeks. There was a significant short-term risk to vision when retreatment interval was extended beyond 12 weeks, hence extensions to this level should be considered cautiously. These data may be useful for physicians who are considering reducing visits to mitigate the risk of COVID-19

Prevalence and risk factors for the development of physician-graded subretinal fibrosis in eyes treated for neovascular age-related macular degeneration

PURPOSE To assess the prevalence and incidence of and risk factors for subretinal fibrosis (SRFi) in eyes with neovascular age-related macular degeneration (nAMD) that underwent vascular endothelial growth factor inhibitor treatment for up to 10 years. METHODS A cross-sectional and longitudinal analysis was performed on data from a neovascular age-related macular degeneration registry. The presence and location of SRFi were graded by the treating practitioner. Visual acuity, lesion characteristics (type, morphology, and activity), and treatment administered at each visit was recorded. RESULTS The prevalence of SRFi in 2,914 eyes rose from 20.4% at year interval 0-1 to 40.7% at year interval 9 to 10. The incidence in 1,950 eyes was 14.3% at baseline and 26.3% at 24 months. Independent characteristics associated with SRFi included poorer baseline vision (adjusted odds ratio 5.33 [95% confidence interval 4.66-7.61] for visual acuity ≤35 letters vs. visual acuity ≥70 letters, P < 0.01), baseline lesion size (adjusted odds ratio 1.08 [95% confidence interval 1.08-1.14] per 1000 µm, P = 0.03), lesion type (adjusted odds ratio 1.42 [95% confidence interval 1.17-1.72] for predominantly classic vs. occult lesions, P = 0.02), and proportion of active visits (adjusted odds ratio 1.58 [95% confidence interval 1.25-2.01] for the group with the highest level of activity vs. the lowest level of activity, P < 0.01). CONCLUSION Subretinal fibrosis was found in 40% of eyes after 10 years of treatment. High rates of lesion activity, predominantly classic lesions, poor baseline vision, and larger lesion size seem to be independent risk factors for SRFi

Optical Coherence Tomography Angiography in Retinal Vascular Disorders

Traditionally, abnormalities of the retinal vasculature and perfusion in retinal vascular disorders, such as diabetic retinopathy and retinal vascular occlusions, have been visualized with dye-based fluorescein angiography (FA). Optical coherence tomography angiography (OCTA) is a newer, alternative modality for imaging the retinal vasculature, which has some advantages over FA, such as its dye-free, non-invasive nature, and depth resolution. The depth resolution of OCTA allows for characterization of the retinal microvasculature in distinct anatomic layers, and commercial OCTA platforms also provide automated quantitative vascular and perfusion metrics. Quantitative and qualitative OCTA analysis in various retinal vascular disorders has facilitated the detection of pre-clinical vascular changes, greater understanding of known clinical signs, and the development of imaging biomarkers to prognosticate and guide treatment. With further technological improvements, such as a greater field of view and better image quality processing algorithms, it is likely that OCTA will play an integral role in the study and management of retinal vascular disorders. Artificial intelligence methods—in particular, deep learning—show promise in refining the insights to be gained from the use of OCTA in retinal vascular disorders. This review aims to summarize the current literature on this imaging modality in relation to common retinal vascular disorders

The Impact of Disease Activity on 5 year Outcomes in patients undergoing treatment for Neovascular Age Related Macular Degeneration

PURPOSE To assess the impact of disease activity on clinical outcomes in a "real-world" cohort with neovascular age related macular degeneration (nAMD) over 5 years. METHODS Data were obtained from the prospectively-defined Fight Retinal Blindness! registry. Eyes were divided into tertiles based on the proportion of visits where choroidal neovascular lesion was active (low, moderate and high) up until 5 years. RESULTS Data from 2109 eyes were included. The adjusted mean (95% CI) VA change was -0.5 letters (-1.8, 1.1), 1.8 letters (0.2, 3.4) and -2.5 letters (-4.2, -1.3) in the low, moderate and high activity groups respectively, p<0.001. Eyes in the low activity group were more likely to develop macular atrophy (56%, 47% and 26% in the low, moderate and high activity groups respectively, p<0.001) but less likely to develop subretinal fibrosis (27%, 35% and 42% in the low, moderate and high activity groups respectively, p<0.001). CONCLUSIONS Eyes with higher and lower levels of disease activity had poorer outcomes than eyes with moderate activity over 5 years, apparently due to the development of subretinal fibrosis or macular atrophy