Our data support the item fit, internal consistency, unidimensionality and construct validity of the NEI VFQ in a heterogeneous cohort of uveitis patients. This supports that Rasch scoring of the NEI VFQ-25 should be implemented in future uveitis trials, given validity in the investigated sub-populations (e.g. by anatomic location, inflammatory activity, complications).

This study confirms the psychometric findings obtained by methods from classical test theory [13]. Traditional sum scoring indicated a Cronbach’s alpha between 0.87 to 0.94 [13], while alpha was > 0.9 in our study. While previous assessments of psychometric properties (test–retest reliability, reproducibility, convergent validity) of the NEI VFQ in uveitis relied on conventional sum scoring [13], our current study delves further into psychometric dimensions such as item fit, targeting, and DIF, aspects that are not ascertainable through classical test theory methods. Additionally, the analyses reveal adjustments that may further optimize the assessment of VR-QoL in uveitis cohorts, which pends further evaluation.

Our study findings reveal relative mistargeting of the NEI VFQ-VF subscale in a heterogeneous population of uveitis patients, suggesting that the instrument may not effectively capture the full spectrum of VR-QoL issues experienced by uveitis patients. This may relate to the high levels of visual acuity observed in our cohort (mean visual acuity was 0.17 ± 0.28 logMAR units in the better eye). Clinical trials in uveitis often include participants with lower visual acuity levels than those in our study, while visual acuity levels in our cohort were at the upper end of the spectrum expected in uveitis trial populations [2, 11, 12]. Thus, we expect the NEI VFQ-25 to be better targeted at lower visual acuity populations. However, this needs to be further validated in an independent cohort.

Since the analyses were focused on the psychometric properties of scoring method based on Rasch models, our results do not allow commenting on the content validity of the NEI VFQ-25 in uveitis. The development of content domains and validation included 17/246 (7%) individuals with CMV retinitis, an infectious posterior uveitis [7]. The initial validation study of the NEI VFQ (51-item version) also included a proportion of individuals with CMV retinitis (37/598, 6%) [8]. This supports the content validity of the NEI VFQ in a specific uveitis entity but does not allow making assumptions about its validity in other types of uveitis (e.g. non-infectious forms, anterior uveitis), where more research is needed. However, the recent development of the Rasch model-scored version of the NEI VFQ (NEI VFQ-25C [15]), did not report inclusion of any uveitis patients and therefore, our results strengthen the use of an model-based scoring system of the NEI VFQ in instances where the use context justifies including NEI VFQ items to assess of VR-QoL in uveitis.

We have conducted an analysis of psychometric properties of a commonly used PROM in uveitis trials. While our findings suggest overall sound psychometric properties, it is important to acknowledge several limitations. Our sample was recruited via an online survey from patient organizations where only self-reported acuity data and no further clinical data were available, and a reporting bias cannot be fully excluded. As no information on the anatomic classification uveitis or level of inflammation were available, the external validity of our findings may be limited and further research is needed to validate the model-based scoring approach in clinical sub-populations. The performance on the NEI VFQ-25 may vary across different uveitis subtypes as uveitis is a largely heterogeneous condition with diverse clinical presentations and treatment responses. One of the NEI VFQ-25C sub-items (item 16a) could not be included in the analysis but has high content similarity with one item included (item 16), thus we do not expect this to impact the validity of the results. Moreover, the focus group discussions conducted during the development of the NEI VFQ involved only a limited number of uveitis patients. Despite the NEI VFQ-25 being commonly used in uveitis trials, further research is needed to investigate the content validity and patient-reported dimensions that are additionally relevant. Our study sample was recruited form uveitis patient organizations in Germany, possibly limiting its representativeness of uveitis patients internationally.

To address these limitations, future research should incorporate larger, more diverse uveitis populations with verified diagnoses and detailed subtype information, while also considering comprehensive validity assessments (concurrent, convergent, discriminant and known group) to confirm and extend our findings. A broader range of items with varying levels of difficulty and covering different aspects relevant to uveitis patients may be required to fully capture VR-QoL in uveitis.

Overall, the data from our exploratory study support the use of a Rasch model-based scoring algorithm in uveitis patients in the future, which can make PROM assessments more precise. Our study endorses the further use of patient-relevant endpoints in clinical studies in uveitis. Nevertheless, addressing the constraints identified in our research warrants further inquiry in future studies.