Research Detects Fast-Progressing Subtype of Terrien’s Marginal Degeneration

While this study was unable to uncover a unifying genetic cause of Terrien marginal degeneration, it was able to identify various progression markers that could help guide clinical interventions and potentially aid in the future development of targeted therapies. These markers included younger age at diagnosis, unilaterality, cavities, crab claw topographic pattern, increasing topographic astigmatism, thinning of the corneal periphery below 450μm and sectoral hyperemia. Photo: Christine Sindt, OD. Click image to enlarge. A recent study aimed to explore the immunological and genetic risk factors of a commonly overlooked corneal disease, Terrien’s marginal degeneration (TMD), as well as monitor its long-term progression. While it found no shared genetic cause among affected patients, the authors did identify various clinical characteristics that suggest more progressive disease.The hospital-based longitudinal study involved a combined retrospective and partially prospective follow-up of 32 eyes from 16 Finnish patients with a median follow-up duration of 7.3 years (range: 0.3 to 15.2 years). The analysis included clinical symptoms, BCVA, axial power map patterns, astigmatism, corneal thickness, higher-order irregularity, presence of corneal cavities, disease progression and human leukocyte antigen genotypes. Additionally, exome sequencing was performed on 13 blood samples to investigate 483 genes associated with corneal and inflammatory diseases.The median age at initial examination was 61 years (range: 13 to 89). Of the 16 patients, 11 (69%) were male, and 13 (81%) had bilateral involvement. The median annual progression rates were 0.03D for topographic astigmatism (range: -1.50D to 3.60D) and 12.9μm for new corneal thinning (range: -107.8μm to 93.0μm).Among patients with faster disease progression (six individuals, 38%), which the researchers defined as “an accelerated peripheral thinning or >1D increase in topographic astigmatism,” the median annual changes were 0.15D (range: -1.50D to 1.17D) and 21.6μm (range: 1.3μm to 93.0μm). In contrast, those with slower progression (10 individuals, 72%) showed smaller annual changes: 0.02D (range: -0.06D to 3.60D) and 4.1μm (range: -107.8μm to 24.7μm). The researchers identified various features associated with rapid progression, including distinct topographic patterns, unilateral disease, presence of corneal cavities, sectoral hyperaemia, poor response to medical therapy and postoperative thinning. Patients diagnosed at a younger age were also more likely to be faster progressors. Corneal thickness at the point of maximal thinning dropped below 450μm only in cases of fast progression. Additionally, five eyes exhibited a change in topographic pattern during follow-up, and one patient was diagnosed with coexisting keratitis fugax hereditaria.The sequence analysis of gene variants associated with corneal and immune-related disorders revealed that the 13 Finnish patients with TMD shared no monogenic germline cause, despite two previous familial occurrences of Terrien’s being reported in the literature. This study is limited by its partially retrospective design, small sample size and subjective visual pattern grading. Also, variable ocular comorbidities and differences in analysis methods between fast and slow progressors may have biased results. Uneven follow-up times and disease asymmetry, particularly in fast-progressing cases, may also have influenced progression assessments. A future study with a larger number of patients will be needed to corroborate the findings of this analysis.Despite its limitations, this study marks the first to describe the long-term course of fast- and slow-progressing TMD. The researchers conclude by noting that “the identification of the disease type enables us to study new efficient treatments while curbing the need to expose patients to ineffective or even harmful ones.”Click here for the journal source. Ruutila M, Repo P, Immonen AT, et al. Progression and topographic subtypes of Terrien marginal degeneration. Acta Ophthalmologica. May 6, 2025. [Epub ahead of print].