Characterising the diagnosis of genetic maculopathies in a real-world private tertiary retinal practice in Australia: protocol for a retrospective clinical audit

Abstract

Purpose

Accurate diagnosis of macular atrophy is paramount to enable appropriate treatment when novel treatments for geographic atrophy and macular dystrophies become available. Genetic testing is useful in distinguishing between the two conditions but is not feasible for the majority of patients in real-world clinical practice. Therefore, we aimed to investigate the potential misdiagnosis of inherited macular dystrophy as age-related macular degeneration (AMD) in real-world ophthalmic practice to assist in the development of guidelines to improve diagnostic accuracy while minimizing genetic testing for targeted patients.

Methods

Retrospective review of the medical records of patients diagnosed with AMD, which included imaging, between 1995 and 2023 from a large multidisciplinary private ophthalmic practice in Australia. We will use a stepwise method to screen for probable cases of macular dystrophy, followed by a consensus review by an expert panel. The outcomes are (1) to determine the potential misdiagnosis rate of macular dystrophy as atrophic AMD by retinal specialists and general ophthalmologists; (2) to identify clinical imaging modalities that are most useful for differentiating macular dystrophy from atrophic AMD; and (3) to establish preliminary guidance for clinicians to improve the diagnosis of macular atrophy from AMD in practice, and thereby target cost-efficient genetic testing.

Discussion

Improving the diagnostic accuracy of both AMD and macular dystrophy, while ensuring cost-efficient genetic testing, will improve the targeted treatment of macular diseases when emerging treatments become available.

Keywords:

• Age-related macular degeneration
• inherited retinal disease
• inherited macular disease
• macular dystrophy
• fundus autofluorescence
• retrospective clinical review

Acknowledgements

The IT and orthoptic staff of ESA and ophthalmologists: Helen Chan, Ben Connell, Trevor Gin, Anthony JH Hall, Nathan Kerr, Lyndell Lim, Ming-Lee Lin, Weng Ng, Salmaan Qureshi, Simon Skalicky, Richard Stawell, RCAndrew Symons, and Wilson Heriot for allowing review of their patients.

Authors contributions

The study concept and design were conceived by H.G.M., A.C.B.-J., R.H.G. and L.N.A. Data collection and screening will be performed by D.M. and H.G.M. The expert panel for the final clinical review includes A.C.B.-J., R.H.G., M.-L.L., L.N.A. and H.G.M. Data analysis will be performed by A.C.B.-J. H.G.M., A.C.B.-J. and D.M. drafted the manuscript with edits and critical revisions from R.H.G. and L.N.A. A.C.B.-J. prepared the figure and tables. All authors reviewed the final manuscript, gave approval for it to be published and agreed to be accountable for all aspects of the work.

Disclosure statement

H.G.M. declares that she has received funding from Novartis regarding the introduction of voretigene neparvovec-rzyl in Australia. R.H.G. is a member of the advisory boards of Bayer, Novartis, Apellis Pharmaceuticals, and Roche-Genentech, and reports honoraria from Apellis Pharmaceuticals, Bayer, and Novartis, consulting fees from Roche-Genentech, and receipt of loaned equipment from Zeiss. LNA is a consultant for Novartis and Apellis Pharmaceuticals. The remaining authors declare that they have no conflicts of interest.

Data availability statement

De-identified data will be available from the principal investigator (H.G.M.) upon reasonable request.

Additional information

Funding

D.M. was awarded a Cabrini Medical Staff Scholarship for this study. Researchers were supported by an Australian National Health and Medical Research Council Fellowship (grant No. 1195713 to L.N.A.), a University of Melbourne Driving Research Momentum Fellowship (L.N.A.) and a University of Melbourne Postdoctoral Fellowship (A.C.B.-J.). Centre for Eye Research Australia receives support from the Victorian Government through its Operational Infrastructure Support Program. ESA will provide in-kind funding for data extraction.