Development of Anti-VEGF Therapies for Intraocular Use: A Guide for Clinicians

Angiogenesis is the process by which new blood vessels form from existing vessel networks. In the past three decades, significant progress has been made in our understanding of angiogenesis; progress driven in large part by the increasing realization that blood vessel growth can promote or facilitate disease. By the early 1990s, it had become clear that the recently discovered “vascular endothelial growth factor” (VEGF) was a powerful mediator of angiogenesis. As a result, several groups targeted this molecule as a potential mediator of retinal ischemia-induced neovascularization in disorders such as diabetic retinopathy and retinal vein occlusion. Around this time, it also became clear that increased intraocular VEGF production was not limited to ischemic retinal diseases but was also a feature of choroidal vascular diseases such as neovascular age-related macular degeneration (AMD). Thus, a new therapeutic era emerged, utilizing VEGF blockade for the management of chorioretinal diseases characterized by vascular hyperpermeability and/or neovascularization. In this review, we provide a guide for clinicians on the development of anti-VEGF therapies for intraocular use

Retinal vein occlusion and macular edema – critical evaluation of the clinical value of ranibizumab

Retinal vein occlusions (RVOs) constitute the second most common cause of retinal vascular disease after diabetic retinopathy, with a prevalence of between 1% and 2% in persons older than 40 years of age. Despite the existence of numerous potential therapeutic options, none is entirely satisfactory, and many patients with RVO suffer irreversible visual loss. Fortunately however, the recent introduction of antivascular endothelial growth factor (VEGF) agents, such as ranibizumab (Lucentis®, Genentech, South San Francisco, CA) and bevacizumab (Avastin®, Genentech), offers a potentially new treatment approach for clinicians managing this disorder. The results of the BRAVO and CRUISE trials have provided the first definitive evidence for the efficacy and safety of ranibizumab in the treatment of RVO. As a result, ranibizumab has recently been approved by the US Food and Drug Administration for the treatment of RVO-associated macular edema. In this review, we provide a critical evaluation of clinical trial data for the safety and efficacy of ranibizumab, and address unresolved issues in the management of this disorder

Management of Neovascular Age-Related Macular Degeneration in Clinical Practice: Initiation, Maintenance, and Discontinuation of Therapy

Neovascular age-related macular degeneration (AMD) is a leading cause of irreversible visual loss in elderly populations. In recent years, pharmacological inhibition of vascular endothelial growth factor (VEGF), via intravitreal injection of ranibizumab (Lucentis) or bevacizumab (Avastin), has offered the first opportunity to improve visual outcomes in patients diagnosed with this disorder. In this paper, we provide recommendations on how bevacizumab and ranibizumab may be best applied in current clinical practice, with an emphasis on their underlying pharmacology and efficacy. In addition, we review current guidelines for the initiation, maintenance, and discontinuation of anti-VEGF therapies, as well as emerging treatment strategies and future directions in the field

New meaning for NLP: the trials and tribulations of natural language processing with GPT-3 in ophthalmology

Natural language processing (NLP) is a subfield of machine intelligence focused on the interaction of human language with computer systems. NLP has recently been discussed in the mainstream media and the literature with the advent of Generative Pre-trained Transformer 3 (GPT-3), a language model capable of producing human-like text. The release of GPT-3 has also sparked renewed interest on the applicability of NLP to contemporary healthcare problems. This article provides an overview of NLP models, with a focus on GPT-3, as well as discussion of applications specific to ophthalmology. We also outline the limitations of GPT-3 and the challenges with its integration into routine ophthalmic care

Investigating the impact of OCT imaging of the crystalline lens on the accuracy and precision of cataract assessment

Purpose: To determine if supplementing standard clinical assessments with Optical Coherence Tomography (OCT) imaging of the crystalline lens improves the accuracy and precision of lens opacity assessment and associated clinical management decisions by optometrists. Methods: Fifty optometrists registered in the UK or Éire undertook a clinical vignette study where participants graded lens opacities and made associated clinical management decisions based on the image(s)/information displayed. Three forms of vignettes were presented: (1) Slit‐lamp (SL) images of the lens, (2) SL and OCT images and (3) SL, OCT and visual function measures. Vignettes were constructed using anonymised data from 50 patients with varying cataract severity, each vignette being presented twice in a randomised order (total vignette presentations = 300). The accuracy of opacity and management decisions were evaluated using descriptive statistics and non‐parametric Bland–Altman analysis where assessments from experienced clinicians were the reference. The precision of assessments was examined for each vignette form using non‐parametric Bland–Altman analysis. Results: All (n = 50) participants completed the study, with 36 working in primary eyecare (primary eyecare) settings and 14 in hospital eyecare services (HES). Agreement was highest where vignettes contained all clinical data (i.e., SL, OCT and visual function data—grading: 51.0%, management: 50.5%), and systematically reduced with decreasing vignette content (p < 0.001). A larger number of vignettes containing imaging and visual function measures exhibited below reference (i.e., less conservative) grading compared with vignettes containing imaging data alone (all p < 0.05). HES‐based optometrists were more likely to grade lens opacities lower than clinicians working in primary eyecare (p < 0.001). Good measurement precision was evident for all vignettes, with a mean bias close to zero and limits of agreement below one grading step for all conditions. Conclusions: The addition of anterior segment OCT to SL images improved the accuracy of lens opacity grading. Structural assessment alone yielded more conservative decision making, which reversed once visual functional data was available

Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration

Treatment of the neovascular form of age-related macular degeneration (AMD) has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and "real-world" outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography

Human Factor and Usability Testing of a Binocular Optical Coherence Tomography System

PURPOSE: To perform usability testing of a binocular optical coherence tomography (OCT) prototype to predict its function in a clinical setting, and to identify any potential user errors, especially in an elderly and visually impaired population. METHODS: Forty-five participants with chronic eye disease (mean age 62.7 years) and 15 healthy controls (mean age 53 years) underwent automated eye examination using the prototype. Examination included 'whole-eye' OCT, ocular motility, visual acuity measurement, perimetry, and pupillometry. Interviews were conducted to assess the subjective appeal and ease of use for this cohort of first-time users. RESULTS: All participants completed the full suite of tests. Eighty-one percent of the chronic eye disease group, and 79% of healthy controls, found the prototype easier to use than common technologies, such as smartphones. Overall, 86% described the device to be appealing for use in a clinical setting. There was no statistically significant difference in the total time taken to complete the examination between participants with chronic eye disease (median 702 seconds) and healthy volunteers (median 637 seconds) (P = 0.81). CONCLUSION: On their first use, elderly and visually impaired users completed the automated examination without assistance. Binocular OCT has the potential to perform a comprehensive eye examination in an automated manner, and thus improve the efficiency and quality of eye care. TRANSLATIONAL RELEVANCE: A usable binocular OCT system has been developed that can be administered in an automated manner. We have identified areas that would benefit from further development to guide the translation of this technology into clinical practice