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

Quantitative analysis of vitreous inflammation using optical coherence tomography in patients receiving sub-Tenon's triamcinolone acetonide for uveitic cystoid macular oedema

Background/aims: To evaluate the vitreous signals obtained on spectral domain optical coherence tomography (SD-OCT) in patients with uveitic cystoid macular oedema (CMO) and compare these signals before and after sub-Tenon's triamcinolone acetonide injection. Methods: Retrospective study with standardised longitudinal imaging preintervention and postintervention. The study cohort comprises 22 patients (22 eyes) with uveitic CMO receiving a sub-Tenon's triamcinolone acetonide (STTA) injection. Post hoc analysis of SD-OCT images using custom software provided an ‘absolute’ measurement of vitreous signal intensity, which was expressed as a ratio to the retinal pigment epithelium intensity (‘VIT/RPE-relative intensity’) in arbitrary units. Main outcome measure: Difference in VIT/RPE-relative intensity before and after treatment. Results: Treatment with STTA resulted in a significant reduction in VIT/RPE-relative intensity, which was associated with both a reduction in central retinal thickness (CRT) and improvement in visual acuity. Mean (SD) VIT/RPE-relative intensity pretreatment was 0.139 (0.074) versus 0.053 (0.028) post-treatment (p=3×10−5). Mean (SD) CRT was 581 μm (119 μm) pretreatment versus 333 μm (95 μm) post-treatment (p=2×10−8); the mean reduction in CRT was 248 (95% CI 189 to 306). The correlation coefficient between VIT/RPE-relative intensity and CRT was 0.534 (p=0.011) and between VIT/RPE-relative intensity and visual acuity was 0.702 (p=0.0001). Conclusions: This study provides evidence that the OCT-derived VIT/RPE-relative intensity may be useful as a quantitative and objective marker of disease activity and treatment response in uveitis complicated by CMO. This first longitudinal study of this novel OCT parameter is an encouraging step in the development of sensitive objective OCT-based endpoints for trials of efficacy in uveitis