Research Shows Pseudoexfoliation May Accurately Predict Glaucoma

A recent cross-sectional study conducted in Portugal revealed that pseudoexfoliation (PEX) syndrome and the ensuing thickness reduction of ganglion cell layer (GCL) and inner plexiform layer (IPL) could be used to predict glaucoma.

PEX is a known risk of contracting open-angle glaucoma (OAG), but its impact on retinal structure without glaucoma is relatively unstudied. What little research has been conducted indicates that glaucoma conversion is twice as high in patients with pseudoexfoliation as without.2

“In our study, we aimed to evaluate macular, GCL, IPL, cRFL, BMO-MRW, and choroid thickness in patients with PEX syndrome without OAG, compared to healthy controls,” wrote Ana Faria Pereira, Department of Ophthalmology, Unidade Local de Saúde de São João, and colleagues. “By focusing on these parameters, we seek to elucidate the structural changes associated with PEX and their potential implications for ocular health in the absence of glaucomatous damage.”1

The study included 60 eyes, 38 with PEX and 22 without. Participants in the PEX group had exfoliative material on the pupil margin or lens capture: if both eyes met the inclusion criteria, both were included; in the control group, one eye per subject was randomly selected if both eyes met the criteria. Exclusion criteria included ocular hypertension, opaque media, age-related macular degeneration, and diabetic retinopathy, among others.1

Investigators noted that the PEX group exhibited a thinner nasal-inferior circumpapillary retinal nerve fiber layer (cRNFL) compared to control (P <.05), as well as reduced thickness in superior, inferior, nasal-inferior, nasal-superior, and total ganglion cell layer (GCL), as well as nasal-inferior, nasal-superior, and total inner plexiform layer (IPL) compared to control (P <.05).1

Additionally, Bruch’s membrane opening-minimum rim width (BMO-MRW) thickness was generally thinner in all sectors for the PEX group, though no significant differences were found between the two groups. (P >.05).1

Faria Pereira and colleagues indicated that these results can be interpreted in two ways. First, it suggests that GCL and IPL analysis can be more sensitive early in glaucoma detection. The macula is a key area for early cell loss detection due to high cell density. Second, it could reflect retinal neurodegeneration associated with neurodegenerative diseases.1

Investigators pointed out that cRNFL thickness often decreases in conditions marked by the loss of ganglion cells, such as glaucoma. RNFL measurement is therefore critical for early diagnosis and monitoring. Faria Pereira and colleagues found that cRNFL thickness was largely reduced across all sectors in the PEX group, aligning with reports from other studies. Additionally, previous research suggests that BMO-MRW could be used to detect glaucomatous damage, typically when combined with cRNFL analysis.3

The choroid is also critical to maintaining circulation for the outer retinal layer and retinal pigment epithelium. Choroidal circulation also removes ocular waste and regulates temperature, both of which can be inhibited by intra- and extraocular inflammatory and vascular disorders. A reduction in vessel caliber usually manifests as decreased thickness, such as that discovered by Faria Pereira and colleagues.1

The team discovered a significant association between PEX and GCL and IPL thickness, measured by spectral domain optical coherence tomography. The nasal sectors of the macula may be the ideal location for early glaucoma screening.1

“However, this hypothesis needs to be tested through sequential studies involving larger populations to assess its clinical utility,” wrote Faria Pereira and colleagues. “Future research should include larger sample sizes and prospectively analyze spatiotemporal changes in OCT measurements to enhance the diagnostic capabilities of retinal imaging in early glaucoma detection and/or the diagnosis of preclinical neurodegenerative diseases.”1

References

1. Faria Pereira A, Mota Moreira P, Coelho-Costa I, Teixeira-Martins R, Estrela Silva S, Oliveira-Ferreira C. Retinal neurodegeneration, neuroretinal rim analysis and choroid thickness in pseudoexfoliation syndrome with spectral domain optical coherence tomography. Sci Rep. 2025;15(1):11576. Published 2025 Apr 4. doi:10.1038/s41598-025-95082-y

2. Grødum K, Heijl A, Bengtsson B. Risk of glaucoma in ocular hypertension with and without pseudoexfoliation. Ophthalmology. 2004;112(3):386-390. doi:10.1016/j.ophtha.2004.09.024

3. La Bruna S, Tsamis E, Zemborain ZZ, et al. A Topographic Comparison of OCT Minimum Rim Width (BMO-MRW) and Circumpapillary Retinal Nerve Fiber Layer (cRNFL) Thickness Measures in Eyes With or Suspected Glaucoma. J Glaucoma. 2020;29(8):671-680. doi:10.1097/IJG.0000000000001571