Study Confirms Retinal Structural Associations Between Retinitis Pigmentosa, Macular Edema

A study published in Scientific Reports confirmed previously identified retinal structural associations between macular edema (ME) and retinitis pigmentosa (RP) in addition to identifying potential new genetic associations with ME.

ME is most often the consequence of hyper-permeable retinal blood vessels that case the extraversion of fluid into the retinal interstitium, although a number of pathological ophthalmic diseases have been associated with ME. RP is made up of a group of inherited diseases that have a similar phenotype, with more than 60 genes known to cause RP.

Prevalence of ME in RP has ranged from 8% to 58% in previous literature, and this study aimed to gain insight into whether there are clinical features or genetic associations of ME in RP in a large cohort of RP cases in which most patients had genetic testing.

Colored Genetic Code DNA Molecule Structure | Image credit: ktsdesign - stock.adobe.com

The inherited retinal disease (IRD) database from UC San Diego was used to identify patients. Patients who were seen by attending retinal physicians between June 2008 and July 2021 were included in the database, and diagnoses of RP were confirmed by a history of progressive peripheral vision loss or nyctalopia and through ocular examination findings of RP. All eyes were imaged and all included patients had genetic testing performed using blood or saliva samples.

There were 571 patients in the database who had suspected IRD, with 287 eyes from 145 patients having RP and imaging available. The cohort had a mean (SD) age of 49.73 (19.75) years. ME was found to be more prevalent in the younger age group compared with the older age group (68.9% vs 60.3%).

A validation study was conducted to find agreement between 2 independent retinal specialists in grading ME, epiretinal membrane (ERM), posterior vitreous detachment (PVD), and vitreo-macular traction (VMT). There was an agreement of 92.5% with a Cohen’s Kappa of 0.850. Both graders combined had an agreement of 88.80% and a Cohen’s Kappa score of 0.77.

There were 186 eyes, or 73.1% of all included eyes in 106 patients, that had ME, with ERM, PVD, and VMT frequently identified. Intraretinal fluid and foveal thickness were both found to be significantly associated with ME in a c2 test; better visual acuity was associated with less ME. Autosomal-dominant variants (mean, 6.3%) had an increased prevalence of ME as well.

ERM presence (mean, 12.4%) and ME were found to have an association when using the Fisher’s test for analysis; VMT also showed a significant association with ME (mean, 4.9%). X-linked inheritance (mean, 6.3%) was found to have an association with ME presence when analyzing associations in genetic inheritance. No association between prior cataract surgery and ME was found. When analyzing other genetic associations, only RPI and EYS were found to have a significant association with ME.

There were some limitations to this study. The retrospective nature meant that some patients were excluded due to missing imaging. Molecular causes of RP were also likely underreported due to the type of genetic testing done. Genetic associations with features of RP are likely underreported due to only being able to identify the molecular cause of IRDs in 60%-70% of cases. The sample sizes were relatively small for each individual gene. There were 7 families included, which could be a confounding factor. Types of ME were also not noted, and there was a lack of angiography testing in the population.

The researchers concluded that the “present study confirms the retinal structural associations identified in previous studies and adds to the literature regarding associations of ME in RP.” Genetic associations with ME were also suggested and require future research.

Reference

Arias JD, Kalaw FGP, Alex V, et al. Investigating the associations of macular edema in retinitis pigmentosa. Sci Rep. 2023;13:14187. doi:10.1038/s41598-41464-z