An OTX2 Gene Mutation Causing a More Severe Retinal Phenotype in a Female RPGR Mutation Carrier.

This study describes the clinical features of a pedigree with a novel retinitis pigmentosa GTPase regulator gene mutation in whom one hemizygous man has a typical manifesting phenotype and three heterozygous women demonstrate a typical carrier phenotype. A fourth heterozygous woman is described with a strikingly severe retinal phenotype and also harbors an independent disease-causing mutation in the OTX2 gene and an associated systemic phenotype. This study hypothesizes that the OTX2 mutation in combination with the familial retinitis pigmentosa GTPase regulator gene variant results in a more severe ocular phenotype than is seen in the other heterozygous women in this pedigree due to a loss of OTX2-mediated photoreceptor protection. [Ophthalmic Surg Lasers Imaging Retina. 2022;53(4):216-220.].

The Natural History of Leber Congenital Amaurosis and Cone-Rod Dystrophy Associated with Variants in the GUCY2D Gene.

OBJECTIVE: To describe the spectrum of Leber congenital amaurosis (LCA) and cone-rod dystrophy (CORD) associated with the GUCY2D gene and to identify potential end points and optimal patient selection for future therapeutic trials. DESIGN: International, multicenter, retrospective cohort study. SUBJECTS: Eighty-two patients with GUCY2D-associated LCA or CORD from 54 families. METHODS: Medical records were reviewed for medical history, best-corrected visual acuity (BCVA), ophthalmoscopy, visual fields, full-field electroretinography, and retinal imaging (fundus photography, spectral-domain OCT [SD-OCT], fundus autofluorescence). MAIN OUTCOMES MEASURES: Age of onset, evolution of BCVA, genotype-phenotype correlations, anatomic characteristics on funduscopy, and multimodal imaging. RESULTS: Fourteen patients with autosomal recessive LCA and 68 with autosomal dominant CORD were included. The median follow-up times were 5.2 years (interquartile range [IQR] 2.6-8.8 years) for LCA and 7.2 years (IQR 2.2-14.2 years) for CORD. Generally, LCA presented in the first year of life. The BCVA in patients with LCA ranged from no light perception to 1.00 logarithm of the minimum angle of resolution (logMAR) and remained relatively stable during follow-up. Imaging for LCA was limited but showed little to no structural degeneration. In patients with CORD, progressive vision loss started around the second decade of life. The BCVA declined annually by 0.022 logMAR (P < 0.001) with no difference between patients with the c.2513G>A and the c.2512C>T GUCY2D variants (P = 0.798). At the age of 40 years, the probability of being blind or severely visually impaired was 32%. The integrity of the ellipsoid zone (EZ) and that of the external limiting membrane (ELM) on SD-OCT correlated significantly with BCVA (Spearman ρ = 0.744, P = 0.001, and ρ = 0.712, P < 0.001, respectively) in those with CORD. CONCLUSIONS: Leber congenital amaurosis associated with GUCY2D caused severe congenital visual impairment with relatively intact macular anatomy on funduscopy and available imaging, suggesting long preservation of photoreceptors. Despite large variability, GUCY2D-associated CORD generally presented during adolescence, with a progressive loss of vision, and culminated in severe visual impairment during mid-to-late adulthood. The integrity of the ELM and EZ may be suitable structural end points for therapeutic studies of GUCY2D-associated CORD.

PERIPAPILLARY MITOCHONDRIAL RETINOPATHY SECONDARY TO A NOVEL MITOCHONDRIAL DNA MUTATION.

PURPOSE: To report a case of pigmentary retinopathy associated with a novel mitochondrial DNA mutation. METHODS: Patient and Results: Patient presented with reduced vision. Visual acuity, ophthalmic examination, color photographs, spectral domain optical coherence tomography, autofluorescence, and genetic testing were performed. Pigmentary retinopathy together with perifoveal atrophy characteristic of mitochondrial retinopathy was identified. Genetic testing confirmed a novel mitochondrial mutation. CONCLUSION: We report bilateral symmetric retinopathy caused by a novel mitochondrial DNA mutation m.16021_16022delCT MTTP (tRNA pro).

Adaptive optics: principles and applications in ophthalmology.

This is a comprehensive review of the principles and applications of adaptive optics (AO) in ophthalmology. It has been combined with flood illumination ophthalmoscopy, scanning laser ophthalmoscopy, as well as optical coherence tomography to image photoreceptors, retinal pigment epithelium (RPE), retinal ganglion cells, lamina cribrosa and the retinal vasculature. In this review, we highlight the clinical studies that have utilised AO to understand disease mechanisms. However, there are some limitations to using AO in a clinical setting including the cost of running an AO imaging service, the time needed to scan patients, the lack of normative databases and the very small size of area imaged. However, it is undoubtedly an exceptional research tool that enables visualisation of the retina at a cellular level.

Gene, Cell and Antibody-Based Therapies for the Treatment of Age-Related Macular Degeneration.

Here we discuss antibody, cell and gene-based therapies that are currently available and under investigation for both wet and dry age-related macular degeneration (AMD). We initially discuss ocular anatomy, AMD modelling as well as the underlying pathophysiology of AMD. The antibody-based trials which have revolutionised the management of wet AMD are reviewed. The latest concepts in antibody therapy for wet AMD such as the port delivery systems, bispecific antibodies, designed ankyrin repeat protein (DARPINs) and brolucizumab are explored. Furthermore, the antibody-based trials targeting the complement pathway to reduce progression of geographic atrophy (GA) in dry AMD are discussed. Stem cell therapy and gene therapy are novel treatment modalities with no established clinical use in wet or dry AMD. Here, we discuss their efficacy so far in clinical trials. Their benefits and risk in the treatment of both wet and dry AMD are evaluated.

Use of stem cells and growth factors in rotator cuff tendon repair.

In this review, we analysed the role of stem cell and growth factor therapy on rotator cuff tendon repair. The injury to the rotator cuff tendons can be sustained in numerous ways and generally causes significant pain and disability to the affected individual. Following surgical repair of ruptured rotator cuff tendons re-rupture rates can be as high as 20-60%. In order to augment this repair process and to decrease the re-rupture rates tissue engineering methods can be used. These include the use of stem cells and growth factors. Mesenchymal stem cells are stem cells which can differentiate into a variety of connective tissue cell types and can therefore be utilised in repairing tendons. So far there has only been one human study using stem cells in rotator cuff tendon repair. This study has produced a positive result but consisted of only 14 patients and lacks a control group for comparison. Similar work has also been done using growth factors. Both individual and combination growth factor therapy have been used to improve rotator cuff tendon repair. However, the results so far have been disappointing with growth factors. For the purpose of future studies better techniques should be explored with regards to the delivery of stem cells and growth factors as well as the possibility of combining growth factor and stem cell therapy to improve repair rates.