[Advances on gene therapy for USH2A exon 13 related inherited retinal dystrophy].

Biallelic pathogenic variants in the USH2A gene result in Usher syndrome type Ⅱ and non-syndromic retinitis pigmentosa, both of which entail the progressive loss of photoreceptors leading to blindness. The cDNA of the USH2A gene is extensive, consisting of 15 606 base pairs, rendering it impractical for delivery via adeno-associated virus vectors for gene replacement therapy. Notably, exon 13 has emerged as a focal point for therapeutic intervention, given its predilection for harboring the most pathogenic variants within USH2A. Recent intervention studies targeting USH2A exon 13 through the utilization of antisense oligonucleotides, genome editing, and RNA editing approaches have exhibited promising therapeutic potential. This paper provides a comprehensive overview of the molecular mechanisms, outcome data, and the challenges associated with the application of these interventions in this domain.

[Full-field stimulus threshold testing for evaluation of the retinal function in patients with inherited retinal dystrophy].

Objective: To analyze the characteristics of full-field stimulus thresholds (FST) in patients with middle-and late-stage inherited retinal dystrophy (IRD), and to explore the feasibility of the FST test in evaluating the retinal function for IRD patients. Methods: It was a retrospective case series study. Twenty-eight patients with IRD whose full-field electroretinogram (ERG) results showed no electrical activity (20 patients) or a serious decrease in electrical activity (8 patients) were enrolled, including 17 males and 11 females, with a median age of 32 years. Ten normal controls were also enrolled. All eyes had a measurement of best corrected visual acuity (BCVA) and an ERG test. FST stimulated by red, blue and white lights were examined with an electrophysiological instrument. The decimal value of BCVA was converted to logarithm of the minimum angle of resolution. Data of the better eye of each participant were used for statistical analysis. Independent sample t-test was used to analyze the difference in FST among patients. Linear regression was used to analyze the correlation between FST, visual acuity and ERG amplitudes. Results: The BCVA of all eyes was 0.7±0.6. Under the stimulation of red, blue and white lights, the FST were(-27.0±7.1), (-47.4±12.2) and(-41.7±11.5) dB in the 8 eyes with decreased electrical activity, (-16.3±7.0), (-27.2±13.7) and(-23.5±12.5) dB in the 20 eyes with no electrical activity, and(-39.9±4.0), (-65.8±4.0) and(-58.5±3.4) dB in the 10 control eyes, respectively. The FST of IRD patients were higher than the normal controls. The FST with red, blue and white lasers in eyes with no electrical activity were higher than those with severely reduced electrical activity (t=-3.472, -3.506, -3.433; all P=0.002). The BCVA was not correlated with the FST under the red, blue and white light stimulation in eyes with a serious reduction in electrical activity (r=0.134, 0.011, 0.010; P=0.055, 0.601, 0.611). There was a linear correlation between the red light stimulus FST and the b-wave amplitude of flicker ERG response (r=-0.591, P=0.026), but there was no significant correlation between other amplitudes and FST. Conclusions: The FST test is a supplementary method to evaluate the retinal function of patients with middle-and late-stage IRD. It can quantitatively reflect the function of rod and cone cell system. As the retinal function of IRD patients decreases, the FST gradually increase.

[Correctly interpret the genetic testing results of inherited optic neuropathy].

Inherited optic neuropathy (ION), which can be characterized by isolated optic atrophy or together with systemic manifestations, is a rare optic nerve dysfunction with multiple genetic patterns. Genetic testing plays the key roles in the diagnosis, genetic counseling and treatment of ION. Currently, most ophthalmologists are unfamiliar with how to interpret the genetic testing results correctly. This article describes the genetic characteristics of ION and explains the main points on genetic reports interpretation to help ophthalmologists getting familiar with this relatively rare field and to promote the clinical application of gene testing. (Chin J Ophthalmol, 2021, 57: 326-330).