In a large retrospective study, researchers from the University of Campania Luigi Vanvitelli in Naples, Italy identified significant associations between specific genetic mutations and the development of cystoid macular edema (CME) in patients with nonsyndromic retinitis pigmentosa (RP).

According to the findings, which were published recently in Investigative Ophthalmology & Visual Science, the cohort included 580 participants (59.3% male) who were a mean age of 38.1±17.6 years (range, 5 to 85). Patients underwent spectral-domain optical coherence tomography (SD-OCT) to assess retinal morphology. Overall, 179 patients (30.9%) developed CME during the disease course—124 bilaterally (21.4%) and 55 unilaterally (9.5%), for a total of 303 affected eyes.

CME prevalence differed significantly by inheritance pattern (P<.001):

• Autosomal dominant (AD): 51.4% (90/175)

• Autosomal recessive (AR): 28.1% (80/285)

• X-linked (XL): 7.5% (9/120)

A higher CME rate was initially observed in females (39.4% vs. 25% in males; P<.001), but this difference was not significant after adjusting for inheritance pattern.

Forty-five causative genes were identified across the cohort. CME prevalence varied widely by gene (P<.001):

• Highest CME prevalence:

  • PRPF3 – 75% (9/12)

  • PRPF8 – 72.7% (8/11)

  • RHO – 58.2% (39/67)

  • USH2A – 45.5% (35/77)

• Lowest CME prevalence:

  • RP2 – 3.4% (1/29)

  • RPGR – 8.8% (8/91)

Notably, autosomal dominant RP associated with RHO, PRPF8, and PRPF3 mutations showed the strongest CME correlation. Variants in RHO such as p.Arg135Trp and p.Pro347Leu were frequently linked to CME (61.5% and 66.6%, respectively). Conversely, X-linked forms caused by RP2 or RPGR mutations were rarely associated with CME.

Genes encoding splicing factors (PRPF3, PRPF8, PRPF31) collectively demonstrated a 57.7% CME prevalence (30/52 cases), which suggested that spliceosome dysregulation may play a role in CME pathogenesis, lead author Francesco Testa wrote with colleagues. Meanwhile, they added, genes with inflammatory involvement, such as RHO, PRPF, and USH2A, showed moderate-to-high CME frequencies.

The study authors noted that their analysis offered no information about leakage because fluorescein angiography was not consistently performed and, indeed, is not included in the routine diagnostic clinical pathway. Underdiagnosis was also possible because of inherent interscan variability and the minimum cystic changes that were included. Syndromic forms of RP were also not included in the study.

“Our results emphasize the importance of SD-OCT morphological assessments in RP patients both to improve disease management and to better explore genotype–phenotype correlations,” the researchers concluded. “Further research is needed to elucidate the underlying mechanisms and eventually lead to new therapeutic targets for the treatment of CME.” RP