Search

Age-related macular degeneration (AMD) is a growing public health concern given the aging population and it is the leading cause of blindness in developed countries, affecting individuals over the age of 55 years. AMD affects the retinal pigment epithelium (RPE) and Bruch's membrane in the macula, leading to secondary photoreceptor degeneration and eventual loss of central vision. Late AMD is divided into two forms: neovascular AMD and geographic atrophy (GA). GA accounts for around 60% of late AMD and has been the most challenging subtype to treat. Recent advances include approval of new intravitreally administered therapeutics, pegcetacoplan (Syfovre) and avacincaptad pegol (Iveric Bio), which target complement factors C3 and C5, respectively, which slow down the rate of enlargement of the area of atrophy. However, there is currently no treatment to reverse the central vision loss associated with GA. Optogenetics may provide a strategy for rescuing visual function in GA by imparting lightsensitivity to the surviving inner retina (i.e., retinal ganglion cells or bipolar cells). It takes advantage of residual inner retinal architecture to transmit visual stimuli along the visual pathway, while a wide range of photosensitive proteins are available for consideration. Herein, we review the anatomical changes in GA, discuss the suitability of optogenetic therapeutic sensors in different target cells in pre-clinical models, and consider the advantages and disadvantages of different routes of administration of therapeutic vectors. [ABSTRACT FROM AUTHOR]

BACKGROUND. Deep learning has been widely used for glaucoma diagnosis. However, there is no clinically validated algorithm for glaucoma incidence and progression prediction. This study aims to develop a clinically feasible deep-learning system for predicting and stratifying the risk of glaucoma onset and progression based on color fundus photographs (CFPs), with clinical validation of performance in external population cohorts. METHODS. We established data sets of CFPs and visual fields collected from longitudinal cohorts. The mean follow-up duration was 3 to 5 years across the data sets. Artificial intelligence (AI) models were developed to predict future glaucoma incidence and progression based on the CFPs of 17,497 eyes in 9346 patients. The area under the receiver operating characteristic (AUROC) curve, sensitivity, and specificity of the AI models were calculated with reference to the labels provided by experienced ophthalmologists. Incidence and progression of glaucoma were determined based on longitudinal CFP images or visual fields, respectively. RESULTS. The AI model to predict glaucoma incidence achieved an AUROC of 0.90 (0.81-0.99) in the validation set and demonstrated good generalizability, with AUROCs of 0.89 (0.83-0.95) and 0.88 (0.79-0.97) in external test sets 1 and 2, respectively. The AI model to predict glaucoma progression achieved an AUROC of 0.91 (0.88-0.94) in the validation set, and also demonstrated outstanding predictive performance with AUROCs of 0.87 (0.81-0.92) and 0.88 (0.83-0.94) in external test sets 1 and 2, respectively. CONCLUSION. Our study demonstrates the feasibility of deep-learning algorithms in the early detection and prediction of glaucoma progression. FUNDING. National Natural Science Foundation of China (NSFC); the High-level Hospital Construction Project, Zhongshan Ophthalmic Center, Sun Yat-sen University; the Science and Technology Program of Guangzhou, China (2021), the Science and Technology Development Fund (FDCT) of Macau, and FDCT-NSFC., Introduction Glaucoma is a major chronic eye disease characterized by optic nerve damage and visual field defects (1, 2). Its onset is often insidious, with a risk of irreversible visual [...]

Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up ((https://clinicaltrials.gov/): NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients. Early results from a first-in-human retinal gene therapy trial for X-linked retinitis pigmentosa indicate that, at an intermediate dose, AAV8-RPGR is safe and in a subset of patients can lead to gains in visual function., Author(s): Jasmina Cehajic-Kapetanovic [sup.1] [sup.2] , Kanmin Xue [sup.1] [sup.2] , Cristina Martinez-Fernandez de la Camara [sup.1] [sup.2] , Anika Nanda [sup.1] [sup.2] , Alexandra Davies [sup.1] [sup.2] , Laura [...]

Retinal gene therapy is increasingly recognized as a novel molecular intervention that has huge potential in treating common causes of blindness, the majority of which have a genetic aetiology.sup.1-5. Choroideremia is a chronic X-linked retinal degeneration that was first described in 1872.sup.6. It leads to progressive blindness due to deficiency of Rab-escort protein 1 (REP1). We designed an adeno-associated viral vector to express REP1 and assessed it in a gene therapy clinical trial by subretinal injection in 14 patients with choroideremia. The primary endpoint was vision change in treated eyes 2 years after surgery compared to unoperated fellow eyes. Despite complications in two patients, visual acuity improved in the 14 treated eyes over controls (median 4.5 letter gain, versus 1.5 letter loss, P = 0.04), with 6 treated eyes gaining more than one line of vision (>5 letters). The results suggest that retinal gene therapy can sustain and improve visual acuity in a cohort of predominantly late-stage choroideremia patients in whom rapid visual acuity loss would ordinarily be predicted. The long-term follow-up results of a phase 1/2 retinal gene therapy clinical trial for choroideremia ((https://clinicaltrials.gov/ct2/show/NCT01461213)) support the safety and efficacy of the treatment., Author(s): Kanmin Xue [sup.1] [sup.2] , Jasleen K Jolly [sup.1] [sup.2] , Alun R. Barnard [sup.1] [sup.2] , Anna Rudenko [sup.2] , Anna P. Salvetti [sup.1] [sup.2] , Maria I. [...]

Purpose: To report the use of flying baby spectral domain optical coherence tomography (SD‐OCT) on infants with advanced retinopathy of prematurity (ROP), where clinical findings alone failed to differentiate between retinoschisis and retinal detachment. Methods: Prospective, non‐interventional case‐series study of three premature infants with advanced ROP of clinically uncertain stage, after examination by indirect ophthalmoscopy. To confirm the diagnosis, table‐mounted SD‐OCT retinal imaging was performed with the infant held in the flying baby position under topical ocular anaesthesia only. Spectral domain optical coherence tomography (SD‐OCT) findings were correlated with clinical examination and ultra‐widefield scanning laser ophthalmoscopy to determine disease stage and appropriate management. Results: The flying baby position was well tolerated, and SD‐OCT images of central and peripheral retina were successfully obtained in all three cases. Additional information provided by the SD‐OCT changed the ROP staging from 3 to 4 in one case, which subsequently required surgical treatment. In two other cases, clinical suspicion of stage 4 ROP was overruled as SD‐OCT revealed tractional retinoschisis rather than full‐thickness retinal detachment, thereby avoiding the need for immediate surgical intervention. Conclusions: In this case‐series study, flying baby SD‐OCT provided a rapid and widely accessible imaging approach that overruled clinical findings and altered classification and management of infants with advanced ROP. The methodology was suitable for outpatient settings with no risks associated with systemic anaesthesia. The increased use of OCT imaging will make apparent how structural information is useful in management of ROP and may influence future classification of the disease. [ABSTRACT FROM AUTHOR]