An Australian study has warned eye health professionals about the potential for dystrophies to mimic age-related macular degeneration (AMD). The study was led by medical student Demi Markakis, supported by Dr Ceecee Britten-Jones, Professor Lauren Ayton and Associate Professor Heather Mack from Centre for Eye Research Australia and was an audit of medical records of Eye Surgery Associates in Melbourne.
While the potential misdiagnosis rate of 1.9% for geographic atrophy (GA) is low, the investigators warned that with treatment options becoming available for both GA and inherited retinal diseases (IRDs) – and diagnosis complicated by the phenotypical similarities – ensuring patients receive an accurate diagnosis is more important than ever.
“Misdiagnosis may lead to inappropriate treatment strategies and missed opportunities for disease-specific interventions,” the researchers said.
“We sought to determine the possible frequency of misdiagnosis when considering people with a diagnosis of GA secondary to AMD by performing an audit of real-world clinical records from a large ophthalmology practice in Australia.”
To conduct the study, a retrospective medical record assessment was undertaken of patient records at Eye Surgery Associates (ESA), a large multidisciplinary ophthalmic practice in Melbourne, for patients diagnosed with AMD, over almost 30 years, from January 1995 to May 2023.
Those diagnosed with GA without drusen were further assessed for a potentially missed IRD with macular atrophy. Experts in AMD and IRD then reviewed the identified cases to establish a most-likely diagnosis.
A total of 1,136 cases were flagged and reviewed. The authors reported a possible rate of misdiagnosis of 1.9%, with 1.0% representing potentially missed IRDs, most commonly pattern dystrophy (0.5%).
The Challenges of Distinguishing between Macular Diseases
The authors, most of whom are associated with the Centre for Eye Research Australia and University of Melbourne, suggest a multi-modal approach, including clinical features and patient history, is important to limit the possibility of misdiagnosis of GA, and identify a subset of patients who might benefit from genetic testing prior to considering possible treatments.
“In the context of emerging treatments for both GA and IRD, this retrospective clinical study of a private, tertiary ophthalmology clinic in Australia has identified a low potential rate of misdiagnosis rate of 1.9% of patients previously diagnosed with AMD with GA.
“Our finding was based on review of clinical imaging of patients with macular atrophy and without obvious drusen present. Genetic testing was not undertaken. Nonetheless, these findings highlight the challenges of distinguishing between macular diseases based solely on phenotypes in a real-world clinical setting, especially in situations where genetic testing might not be readily accessible.”
The authors said the low potential misdiagnosis rate for IRD compares well with other ophthalmic conditions and there was no statistical difference in diagnostic accuracy between retinal and non-retinal ophthalmologists.
“In the future it is hoped that making genetic testing available for selected patients could serve as a valuable tool for screening for potential IRDs. Genetic sequencing technology has progressed significantly, including development of effective sequencing strategies for genetic diagnosis of macular dystrophies.
“Despite progress, IRD genetic screening remains unsustainable to offer to patients routinely in suspected AMD. Additionally, studies screening AMD patients for macular dystrophy-associated genes have demonstrated that there is a degree of genetic overlap between these two cohorts. Patients may also have both an IRD and AMD. Therefore, even with genetic testing targeted for selected patients, in many cases diagnosis will be based on clinical judgement, carrying a low inherent risk of misdiagnosis.”
The authors noted other learnings for eye care professions, including confirmation bias, where the original diagnosis of AMD was not changed over the subsequent years despite new fundus autofluorescence (FAF) data emerging suggestive of an IRD.
This article was updated on 19 May 2025.
Reference
- Markakis D, Britten-Jones AC, Mack HG, et al. Retrospective audit reviewing accuracy of clinical diagnosis of geographic atrophy in a single centre private tertiary retinal practice in Australia. Sci Rep. 2025;15:8528. doi: 10.1038/s41598-025-90516-z.
