Identifying Risk Factors for AMD Progression Could Improve Clinical Outcomes

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The analysis of AMD progression found significant associations between worse initial visual acuity, the presence of wet AMD subtype in fellow eyes, and thyroxine treatment with disease development.

Identifying risk factors for age-related macular degeneration (AMD) progression may help improve outcomes with earlier intervention, ultimately preventing the expansion of the late stage of the disease, according to new research.1

Baseline clinical characteristics were not related to AMD progression, but worse visual acuity and wet AMD subtype in one eye were significantly correlated with disease advancement in the data. Medication use showed a lack of association with disease advancement, save for thyroxine use, which was a significant predictor of AMD progression.

“Identifying modifiable risk factors for disease progression, such as thyroid hormone imbalance, is particularly valuable as a potential target of prevention and requires further study in a larger and more homogenous group of patients,” wrote the investigative team.

Inconsistencies among literature data on factors that may affect AMD progression led Anna Machalinska, First Department of Ophthalmology, Pomeranian Medical University and colleagues to examine the relationship between progression with clinical characteristics, demographic, and environmental risk factors over a 3-year period. The influence of 3 genetic AMD polymorphisms (CFH Y402H, ARMS2 A69S, and PRPH2 c.582-67T>A) on progression of AMD was additionally investigated.

The study initially selected 244 patients with clinically diagnosed early or intermediate AMD among patients of the outpatient clinic of the department in 2016-2017. Due to the COVID-19 pandemic disrupting follow-up examinations, only 94 (38.5%) of the original population were followed-up after 3 years.

Investigators collected data on medical history, current drug use, smoking status, and physical activity from the enrolled participants. Each participant underwent a detailed ophthalmologic examination, including initial visual outcomes, retinal imaging data, and choroidal imaging data. In order to identify the impact of specific systemic and ocular parameters on AMD deterioration, patients were assigned to one of two subgroups depending on disease progression status.

AMD progression was defined as the change in disease stage from early to intermediate AMD as well as the presence of late-stage disease features in the eyes previously classified as early or intermediate in at least one eye. No progression in AMD was established when none of the signs of a more advanced disease stage were observed by investigators.

Among the patients with AMD, 48 presented with AMD progression and 46 showed no disease worsening at 3 years. Investigators assessed the effects of systemic factors on AMD progression, finding no association between patient age, sex, iris color, and AMD family history with disease advancement.

There was additionally no association between medication use and disease development, except for thyroxine use. Thyroxine use was a significant predictor of disease deterioration, remaining significant in adjusted multivariable logistic regression analysis (odds ratio [OR], 4.77; 95% confidence interval [CI], 1.25 - 18.25; P = .002).

Genetic factors influencing AMD progression revealed the CC variant of CFH Y402H was significantly associated with AMD advancement compared to the TC + TT phenotype (OR, 2.76; 95% CI, 0.97 - 7.79; P = .05). Tested variants of the ARMS2 and PPH2 genes showed no significant association with the progression of AMD in multivariable logistic regression analysis.

Among clinical parameters, those with worse initial visual acuity scores were more likely to develop AMD progression after 3 years of observation (OR, 6.74; 95% CI, 1.24 - 36.79; P = .03). In addition, the presence of the wet AMD subtype in fellow eyes was an important predictor of disease deterioration (OR, 3.79; 95% CI, 0.94 - 15.2; P = .05). However, there was no association of disease progression with initial retinal thickness, drusen size, and type or AMD stage.

“Progression from early to late AMD is associated with severe and irreversible vision loss,” investigators wrote. “Therefore, deteriorating vision and its decreased acuity are important outcome measures for defining AMD progression in prospective clinical trials.”


  1. Krytkowska E, Ulańczyk Z, Grabowicz A, Safranow K, Kawa MP, Pałucha A, Wąsowska A, Matczyńska E, Boguszewska-Chachulska A, Machalińska A. Influence of Clinical and Genetic Factors on the Progression of Age-Related Macular Degeneration: A 3-Year Follow-Up. Journal of Clinical Medicine. 2023; 12(5):1963.