A multidisciplinary approach to inherited retinal dystrophies from diagnosis to initial care: a narrative review with inputs from clinical practice

Abstract

Background Non-syndromic inherited retinal dystrophies (IRDs) such as retinitis pigmentosa or Leber congenital amaurosis generally manifest between early childhood and late adolescence, imposing profound long-term impacts as a result of vision impairment or blindness. IRDs are highly heterogeneous, with often overlapping symptoms among different IRDs, and achieving a definite diagnosis is challenging. This narrative review provides a clinical overview of the non-syndromic generalized photoreceptor dystrophies, particularly retinitis pigmentosa and Leber congenital amaurosis. The clinical investigations and genetic testing needed to establish a diagnosis are outlined, and current management approaches are discussed, focusing on the importance of the involvement of an interdisciplinary team from diagnosis and initial care to long-term follow-up and support. Results The effective management of IRDs requires a multidisciplinary, and ideally interdisciplinary, team of experts knowledgeable about IRDs, with experienced professionals from fields as diverse as ophthalmology, neuropsychiatry, psychology, neurology, genetics, orthoptics, developmental therapy, typhlology, occupational therapy, otolaryngology, and orientation and mobility specialties. Accurate clinical diagnosis encompasses a range of objective and subjective assessments as a prerequisite for the genetic testing essential in establishing an accurate diagnosis necessary for the effective management of IRDs, particularly in the era of gene therapies. Improvements in genome sequencing techniques, such as next-generation sequencing, have greatly facilitated the complex process of determining IRD-causing gene variants and establishing a molecular diagnosis. Genetic counseling is essential to help the individual and their family understand the condition, the potential risk for offspring, and the implications of a diagnosis on visual prognosis and treatment options. Psychological support for patients and caregivers is important at all stages of diagnosis, care, and rehabilitation and is an essential part of the multidisciplinary approach to managing IRDs. Effective communication throughout is essential, and the patient and caregivers’ needs and expectations must be acknowledged and discussed. Conclusion As IRDs can present at an early age, clinicians need to be aware of the clinical signs suggesting visual impairment and follow up with multidisciplinary support for timely diagnoses to facilitate appropriate therapeutic or rehabilitation intervention to minimize vision loss.

Clinical and analytical validation of an 82-gene comprehensive genome-profiling panel for identifying and interpreting variants responsible for inherited retinal dystrophies

“…IRDs are high heterogeneous in both phenotypes and genotypes [ 1 , 2 ]. Because of their heterogeneous nature and the overlapping of clinical phenotypes among the different types of IRDs, a definitive diagnosis is challenging.…”

“…Inherited retinal dystrophies (IRDs) comprise a large family of rare eye diseases characterized by the progressive dysfunction and loss of photoreceptors and retinal pigment epithelium (RPE) [ 1 – 3 ]. These degenerative events lead to the gradual impairment of color and night vision, peripheral visual defects, and ultimately, blindness [ 1 , 2 ].…”

“…Inherited retinal dystrophies (IRDs) comprise a large family of rare eye diseases characterized by the progressive dysfunction and loss of photoreceptors and retinal pigment epithelium (RPE) [ 1 – 3 ]. These degenerative events lead to the gradual impairment of color and night vision, peripheral visual defects, and ultimately, blindness [ 1 , 2 ]. The prevalence of IRDs ranges from approximately 1 in 2,000 to 1 in 3,000 individuals [ 4 , 5 ] and is thought to involve nearly 300 different genes, each of which plays a crucial role in the survival, function, and metabolism of retinal cells [ 3 ].…”

Age-dependent changes on fractalkine forms and their contribution to neurodegenerative diseases

“…Retinitis pigmentosa is the more common non-syndromic inherited retinal dystrophy that include several heterogeneous retinal neurodegenerative conditions in which mutations in photoreceptor or retinal pigment epithelium genes result in progressive degeneration of photoreceptors (Hartong et al, 2006;Murro et al, 2023). Retinitis pigmentosa is characterized by a primary degeneration of rod photoreceptors that progresses to the loss of cone photoreceptors, followed by an aberrant remodeling of retina resulting in disconnection of neural retina from photoreceptors, associated with changes from the molecular to tissue levels (Hartong et al, 2006;Zieger et al, 2014;Murro et al, 2023). Retinal degeneration 10 (rd10) is a mouse model of autosomal recessive retinitis pigmentosa, consisting in the spontaneous mutation of the rod-phosphodiesterase-6b (Pde6b) gene, that leads to rod degeneration and later to cone degeneration (Chang et al, 2002).…”