With advances in gene-based therapies for heritable retinal diseases, primary eye care clinicians should be informed on ocular genetics topics. This cross-sectional survey evaluated knowledge, attitudes, and concerns regarding genetic testing and gene therapy for retinal diseases among optometrists in Australia and New Zealand. Survey data included practitioner background, attitudes and practices towards genetic testing for monogenic inherited retinal disease (IRDs) and age-related macular degeneration, and knowledge of ocular genetics and gene therapy. Responses were received from 516 optometrists between 1 April and 31 December 2022. Key perceived barriers to accessing genetic testing were lack of clarity on referral pathways (81%), cost (65%), and lack of treatment options if a genetic cause is identified (50%). Almost all respondents (98%) believed that ophthalmologists should initiate genetic testing for IRDs and fewer understood the role of genetic counsellors and clinical geneticists. This study found that optometrists in Australia and New Zealand have a high level of interest in ocular genetics topics. However, knowledge gaps include referral pathways and awareness of genetic testing and gene therapy outcomes. Addressing perceived barriers to access and promoting sharing of knowledge between interdisciplinary networks can set the foundation for genetic education agendas in primary eye care.

Choroidal neovascularization (CNV) is usually considered to be a late-stage complication in Best vitelliform macular dystrophy (BVMD) and can be difficult to diagnose with fluorescein angiography. This study used swept-source (SS) OCT angiography (OCTA) to evaluate the prevalence of CNV in BVMD, identify structural features associated with CNV, and provide insight into the role of CNV in vitelliform lesion evolution.
Institutional review board-approved, retrospective, cross-sectional, and longitudinal study.
Patients with molecularly confirmed BVMD.
Charts from consecutive patients with BVMD imaged with SS-OCTA (PLEX Elite 9000, Carl-Zeiss Meditec Inc) at the University of Iowa from September 2017 to October 2021 were reviewed. Clinical data, including age, gender, best-corrected visual acuity (BCVA), and treatment with intravitreal anti-VEGF injections were recorded. The presence of CNV on SS-OCTA was determined by expert graders and correlated with structural features, such as interstitial fluid, subretinal fluid, nodular subretinal pillar, focal choroidal excavation (FCE), and subfoveal choroidal thickness, with a P value of < 0.05 considered statistically significant.
Presence of CNV on SS-OCTA and correlation with structural features on SS-OCT.
A total of 53 eyes from 27 patients (13 women; 48.1%) were included. The mean age was 45 years (range, 8-79 years), and the mean logarithm of the minimum angle of resolution BCVA was 0.38 (range, 0-1). Choroidal neovascularization was identified on SS-OCTA in 27 eyes (50.9%), of which 63.0% had a vitelliform (Gass stage 2) lesion. In 40.7% (11 of 27) of eyes, there was no prior clinical diagnosis of CNV. Other structural features associated with CNV included FCEs (15.1%, 8 of 53 eyes) and nodular pillars (15.1%, 8 of 53 eyes) (P < 0.01). Seven patients had available longitudinal imaging, and most of these patients had CNV visible on SS-OCTA (71.4%; 10 of 14 eyes).
Choroidal neovascularization is common in BVMD, including in the early stages of the disease. The presence of FCEs or nodular pillars should heighten the clinical suspicion of CNV, which may accelerate vitelliform lesion evolution.
Proprietary or commercial disclosure may be found after the references.

Background: Congenital Stationary Night Blindness (CSNB) is a clinically and genetically heterogenous inherited retinal disorder associated with nystagmus, myopia, strabismus, defective dark adaptation, and decreased vision. Pathogenic variants in at least 17 genes have been associated with CSNB, where a hemizygous variant of NYX causing an X-linked form of the disorder is among the commonest causes.Materials and Methods: A retrospective chart review of a single pedigree was performed. Three pediatric patients underwent ophthalmic examinations, visual electrophysiology, and ocular imaging. Molecular genetic testing for CSNB was pursued where clinically indicated.Results: Two male siblings demonstrated clinical and electroretinographic evidence of complete CSNB. Genetic testing identified a NYX pathogenic, in-frame deletion in both children. Targeted variant analysis of the mother failed to identify the variant in two independent samples, most consistent with mosaicism.Conclusions: Clinical and molecular analyses within the described family demonstrate the possibility of maternal mosaicism in NYX-related CSNB. The importance of cascade molecular testing is highlighted. The prospect of somatic or germline mosaicism in NYX-related CSNB informs genetic counseling, genetic testing decisions, and risk assessment in affected families.

Inherited retinal degenerations (IRD) are rare genetic disorders with > 300 known genetic loci, manifesting variably progressive visual dysfunction. IRDs were historically underserved due to lack of effective interventions. Many novel therapies will require accurate diagnosis (phenotype and genotype), thus an efficient and effective pathway for assessment and management is required.
Using surveys of existing practice patterns and advice from international experts, an all-Ireland IRD service (Target 5000) was designed. Detailed phenotyping was followed by next generation genetic sequencing in both a research and accredited laboratory. Unresolved pedigrees underwent further studies (whole gene/whole exome/whole genome sequencing). Novel variants were interrogated for pathogenicity (cascade screening, in silico analysis, functional studies). A multidisciplinary team (MDT; ophthalmologists, physicians, geneticists, genetic counsellors) reconciled phenotype with genotype. A bespoke care plan was created for each patient comprising supports, existing interventions, and novel therapies/clinical trials.
Prior to Target 5000, a significant cohort of patients were not engaged with healthcare/support services due to lack of effective interventions. Pathogenic or likely pathogenic variants in IRD-associated genes were detected in 62.3%, with 11.6% having variants of unknown significance. The genotyping arm of Target 5000 allowed a 42.73% cost saving over independent testing, plus the value of MDT expertise/processing. Partial funding has transferred from charitable sources to government resources.
Target 5000 demonstrates efficacious and efficient clinical/genetic diagnosis, while discovering novel IRD-implicated genes/variants and investigating mechanisms of disease and avenues of intervention. This model could be used to develop similar IRD programmes in small/medium-sized nations.

Ocular Genetics at Wills Eye Hospital sees a wide range of rare disorders for accurate diagnosis. To demonstrate how focused consultation and genetic testing results in precise diagnoses, we investigated false diagnosis rates for patients referred with a diagnosis of Stargardt disease. This is a retrospective review of patients over a 3 year period referred to our Ocular Genetics clinic for possible Stargardt disease, or already holding a diagnosis of Stargardt disease. Results of diagnostic and genetic testing were compared to standard definition of Stargardt. Of 40 patients, 14 (35%) had been misdiagnosed. Four had non-Stargardt phenotype of which three had ABCA4 pathogenic variants with phenotypes inconsistent with Stargardt disease. Two of those with pathogenic ABCA4 variants were related. Nine had pathogenic variants in other different genes with overlapping features of Stargardt disease. One had Thioridazine maculopathy. Our study highlights the essential role of the subspecialty field of ocular genetics in obtaining accurate diagnoses for the delivery of correct counseling and interventional trial eligibility assessment.

The aim of this review is to reveal Turkey\'s current status of medical practice in inherited eye diseases and the necessary steps to improve healthcare services and research activities in this area. Since consanguinity rate is high, disease burden is estimated to be high in Turkey. Universal health insurance system, easily accessible medical specialists, increasing genetic test, and counseling opportunities are the key advantages of Turkey\'s healthcare system. However, specialized clinics for inherited eye diseases, low-vision rehabilitation services, training of ophthalmologists about the recent developments in ocular genetics, and multidisciplinary translational research are the main headlines needed to be focused for better health services and successful research in Turkey.

Clinical genetics has evolved significantly to become an efficient and effective means of diagnosing disease. Genetic treatments are now being developed which are showing promising results. However, ophthalmic patients are not utilizing genetic testing as part of their diagnostic workups. This paper explores the patient experience at the Ocular Genetics Clinic (OGC) at the University of Arkansas for Medical Sciences (UAMS) Jones Eye Institute and discusses reasons why patients continue to not pursue genetic testing.
We performed a retrospective chart review to understand the main reasons why patients were referred to the OGC between 2009 and 2018, with a detailed analysis of why patients did not pursue genetic testing.
Patients mainly did not undergo testing due to the cost of testing. However, patient availability, patient interest, and diagnostic workup also drove a significant amount of this lack of testing.
Ocular genetic testing is becoming an increasingly beneficial tool for diagnosing ocular disease. However, to date, patients do not utilize this service fully. At the OGC, there are several main drivers for this lack of testing, namely finances, interest/availability, and diagnostic workup. As more ocular genetics clinics are established, it will be imperative to address reasons for forgoing genetic testing and to develop strategies to encourage patients to pursue this testing.

Alström syndrome is a multi-system recessive disorder caused by mutations in ALMS1 gene. The aim of this study was to characterize morphological retinal changes in Alström patients using spectral-domain optical coherence tomography.
We studied volunteer patients attending the conference of Alström Syndrome International, a support group for affected families, using hand-held spectral-domain optical coherence tomography (SD-OCT) in an office setting. Patients had a clinical dilated retinal examination. Past medical records were reviewed.
Twenty-two Alström patients (mean age 17 years, range 2-38 years, 12 males) were studied. OCT imaging demonstrated that central macular OCT changes are often mild during the first decade of life and gradually progress, demonstrating disruption of normal retinal architecture, and progressive loss of photoreceptors and retinal pigment epithelium. Other changes found included hyperreflectivities in all retinal layers, severe retinal wrinkling, optic nerve drusen, and vitreoretinal separation. Vision correlated with severity of OCT macular changes (r = 0.89, p = 0.002).
This study reports on OCT findings in a large group of patients with Alström syndrome. We document a panretinal gradual progression of retinal changes, which are often mild during the first years of life. Previously unreported observations include intraretinal opacities, optic nerve drusen, and foveal contour abnormalities. Morphological retinal changes demonstrated by SD-OCT may help in understanding the pathophysiology of the disease and defining strategies for treatment such as gene therapy.

Prostaglandins are small pro-inflammatory molecules derived from arachidonic acid that play roles in a multitude of biological processes including, but not limited to, inflammation, pain modulation, allergies, and bone formation. Prostaglandin analogues are the front-line medications for the treatment of glaucoma, a condition resulting in blindness due to the death of retinal ganglion cells. These drugs act by lowering intraocular pressure (IOP), a major risk factor for glaucoma. The currently used prostaglandin analogues (latanoprost, bimatoprost, tafluprost, and travoprost) mimic PGF2 and target one of the prostaglandin receptors (FP), though research into harnessing the other receptors using compounds like Sulprostone (EP3 receptor), or Iloprost (IP receptor) are currently ongoing. In this review, we summarize the research into each of the prostaglandin molecules (PGD2, PGE2, PGF2, PGI2, TXA2) and their respective receptors (DP, EP1, 2, 3, 4, FP, IP). We examine the modes of action of each of these receptors, their expression, their role in aqueous humour production and outflow within the eye, as well as their roles as medications for the treatment of glaucoma.

OBJECTIVE: To investigate the clinical findings and outcomes of rhegmatogenous retinal detachment (RRD) in Stickler syndrome on affected and fellow eyes that underwent prophylactic retinopexy.
METHODS: Chart review of 70 eyes (62 patients). Incidence of RRD, postoperative visual acuity, and risk factors were evaluated.
RESULTS: Twenty-two patients (35%) had RRD in the fellow eye, 37% of the eyes had cataract, 93% had macular detachment, 50% had proliferative vitreoretinopathy, and 41% had posterior vitreous detachment. Success rates were: 60% of patients after scleral buckling; 57.1% after pars plana vitrectomy; and 75% after combined scleral buckling and pars plana vitrectomy. Sixty-one (93.8%) of patients had successful surgery (including second surgery). Silicone oil tamponade was significantly associated with final anatomic outcome, with a protective odds ratio of 0.11 (P=0.027). Visual acuity improved in 54% of eyes and decreased in 5%. Statistically significant associations were present for eyes with final visual acuity ≥20/200, and total retinal detachment (P<0.001); preoperative cataract (P=0.023); and proliferative vitreoretinopathy (P<0.001). RRD developed in 16/44 eyes despite laser prophylaxis.
CONCLUSIONS: Prophylactic retinopexy was not beneficial for Stickler syndrome patients. Success of primary surgery for RRD remains low. The primary surgery should be vitrectomy combined with scleral buckling and silicone oil tamponade.