Inherited retinal diseases

Inherited retinal diseases affect approximately 1 in 3,000 individuals, or more than two million people worldwide, and are the commonest cause of blindness in working-age people. They are caused by abnormality of photoreceptor (PR) cells, and retinal pigment epithelial (RPE) cells.

We work in ocular genomics and disease mechanisms has been translated to NATA-accredited (National Association of Testing Authorities, Australia), genomic testing at The Children’s Hospital at Westmead (CHW), Sydney, available for all Australian patients with ocular diseases. This is very productive, with a mutation detection rate for patients with retinal dystrophies of approximately 65-75%, allowing reproductive information for these patients and families, access to emerging clinical trials and the research towards therapies required for these conditions.

Our focus is on the diagnosis and treatment of inherited retinal disorders using a wide range of capabilities. By understanding the varying clinical presentations (phenotypes) that can occur with inherited retinal diseases (IRD) is crucial preparation for interpreting genetic analysis and preparing for therapeutic trials.

Multimodal imaging combined with functional visual assessment is one of the strengths of the unit. The group overseas the visual electrophysiology services at the Save Sight Institute – Sydney Eye Hospital campus and the Children’s Hospital at Westmead Sydney.

Visual electrophysiology is one of the clinical strengths of the unit with international reputation in functional assessment of patients with IRD. The visual electrophysiology service has been enhanced with collaboration with Professor Graham Holder, electrophysiologist, formerly of Moorfields Eye Hospital, London and now Singapore. Professor Holder has a visiting appointment at Save Sight Institute.

An example of the effectiveness of our approach was the publication of a paper demonstrating the value of detailed electrophysiological investigation and identification of complete loss of the KCNV2 gene in a child with poor vision and nystagmus.

Critically, there is a partially solved rate of an additional 25% of patients, where variants of uncertain significance (VUS) in known disease genes are identified. VUS leave patients and families frustratingly close to a genetic diagnosis, but the information cannot be used for family planning, access to clinical trials, or suitability for research studies towards novel therapies. The human retina is an inaccessible tissue for functional biological assays. We have introduced human induced pluripotent stem cell (iPSC)-derived retinal organoids which provide a tremendous resource for use in development of improved diagnosis and therapies in these conditions.

Our goal has been to develop therapies for these currently blinding conditions. The group conducted the first randomised trial in Australia for an inherited retinal disorder – X-linked retinoschisis examining the effectiveness of acetazolamide in improving visual acuity and reducing macular oedema.