Natural History of Retinitis Pigmentosa Associated With the C.4120c>t Eys Variant

Purpose Eyes shut homolog ( EYS ) is the gene most frequently associated with autosomal recessive retinitis pigmentosa (RP) in Portugal. This study describes the progression of RP associated with the EYS (NM_001142800.2):c.4120C>T(p.Arg1374*) variant by correlating functional and structural measures with patient-reported outcomes (PRO). Methods Study conducted at a Portuguese reference center for inherited retinal diseases. Patients with EYS-associated disease, with at least one c.4120C>T variant were identified using the IRD-PT registry (retina.com.pt). Other inclusion criteria were: at least 36 months of follow-up and baseline/last visit best-corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence phenotype and PRO (Michigan Retinal Degeneration Questionnaire (MRDQ); Michigan Vision-Related Anxiety Questionnaire (MVAQ)) data. Baseline and follow-up parameters were compared. Results Eleven patients (9 families; 72.7% men; mean age of 43.8 ± 11.29 years) were included. Among the 11 patients carrying the variant, 3 (27.3%) were homozygous and 8 (72.7%) compound heterozygous. Mean follow-up was 43.2 ± 1.2 months. In the better-seeing eye, BCVA deteriorated significantly ( p =0.007). There was a significant worsening in MRDQ (central vision, p =0.006; photopic peripheral function, p =0.033) and a significant increase in cone-related anxiety on the MVAQ ( p =0.008). Structural parameters, including EZ area, showed no statistically significant change ( p= 0.130). Changes in rod/cone anxiety correlated moderately ( r =0.692; p =0.018) and scotopic deterioration was strongly associated with mesopic peripheral limitation ( r= 0.873; p <0.001). Conclusion Disease progression was characterized by functional decline and increased psychosocial burden without significant structural deterioration. Integrating PRO with clinical and structural measures supports the design of therapeutic trials and clinical monitoring.