Longitudinal Assessment of Female Carriers of Choroideremia Using Multimodal Retinal Imaging

Overview

Journal Br J Ophthalmol

Specialty Ophthalmology

Date 2024 Aug 9

PMID 39122355

Authors

Sena A Gocuk

Lauren N Ayton

Thomas L Edwards

Myra B McGuinness

Robert E MacLaren

Laura J Taylor

Jasleen K Jolly

Affiliations

Soon will be listed here.

Abstract

Background/aims: Female choroideremia carriers present with a spectrum of disease severity. Unlike in men, the rate of disease progression has not been well characterised in carriers. This longitudinal study aimed to determine the rate of retinal degeneration in choroideremia carriers, using multimodal imaging and microperimetry.

Methods: Choroideremia carriers previously seen at Oxford Eye Hospital (United Kingdom) between 2012 and 2017 returned for testing between 2015 and 2023, providing up to 11 years' follow-up data. Participants had optical coherence tomography, fundus-tracked microperimetry and fundus autofluorescence (FAF) imaging performed.

Results: Thirty-four eyes of 17 choroideremia carriers were examined using multimodal imaging. Median age was 44 (range: 15-73) years at baseline and median follow-up duration was 7 (range: 1-11) years. At baseline, phenotype was classified as fine (n=5 eyes), coarse (n=13 eyes), geographic (n=12 eyes) or male pattern (n=4 eyes). Thirteen patients showed no change in phenotype classification, four showed slight changes associated with choroideremia-related retinal degeneration. Despite this, carriers with severe retinal phenotypes had a statistically significant decline in average retinal sensitivity (-0.7 dB and -0.8 dB per year, respectively, p<0.001), area of geographic loss defined by FAF (+2.5 mm and +3.7 mm per year, respectively, p<0.001) and thinning of the photoreceptor complex (up to -2.8 microns and -10.3 microns per year, p<0.001).

Conclusion: Choroideremia carriers, particularly those with severe retinal phenotypes, exhibit progressive retinal degeneration, as evident by multimodal imaging biomarkers and functional testing. Clinicians should not rely on retinal severity classification alone to assess disease progression.

References

Josan A, Buckley T, Wood L, Jolly J, Cehajic-Kapetanovic J, MacLaren R . Microperimetry Hill of Vision and Volumetric Measures of Retinal Sensitivity. Transl Vis Sci Technol. 2021; 10(7):12. PMC: 8196404. DOI: 10.1167/tvst.10.7.12. View

Wood L, Jolly J, Josan A, Buckley T, MacLaren R . Low Luminance Visual Acuity and Low Luminance Deficit in Choroideremia and RPGR-Associated Retinitis Pigmentosa. Transl Vis Sci Technol. 2021; 10(2):28. PMC: 7900861. DOI: 10.1167/tvst.10.2.28. View

Wu Z, Ayton L, Luu C, Guymer R . Longitudinal changes in microperimetry and low luminance visual acuity in age-related macular degeneration. JAMA Ophthalmol. 2015; 133(4):442-8. DOI: 10.1001/jamaophthalmol.2014.5963. View

Shen L, Ahluwalia A, Sun M, Young B, Grossetta Nardini H, Del Priore L . Long-term Natural History of Atrophy in Eyes with Choroideremia-A Systematic Review and Meta-analysis of Individual-Level Data. Ophthalmol Retina. 2020; 4(8):840-852. PMC: 7415675. DOI: 10.1016/j.oret.2020.03.003. View

Coussa R, Kim J, Traboulsi E . Choroideremia: effect of age on visual acuity in patients and female carriers. Ophthalmic Genet. 2011; 33(2):66-73. DOI: 10.3109/13816810.2011.623261. View

Schmitz-Valckenberg S, Pfau M, Fleckenstein M, Staurenghi G, Sparrow J, Bindewald-Wittich A . Fundus autofluorescence imaging. Prog Retin Eye Res. 2020; 81:100893. DOI: 10.1016/j.preteyeres.2020.100893. View

Gocuk S, Jolly J, Edwards T, Ayton L . Female carriers of X-linked inherited retinal diseases - Genetics, diagnosis, and potential therapies. Prog Retin Eye Res. 2023; 96:101190. DOI: 10.1016/j.preteyeres.2023.101190. View

S Dimopoulos I, Hoang S, Radziwon A, Binczyk N, Seabra M, MacLaren R . Two-Year Results After AAV2-Mediated Gene Therapy for Choroideremia: The Alberta Experience. Am J Ophthalmol. 2018; 193:130-142. DOI: 10.1016/j.ajo.2018.06.011. View

Bellmann C, Rubin G, Kabanarou S, Bird A, Fitzke F . Fundus autofluorescence imaging compared with different confocal scanning laser ophthalmoscopes. Br J Ophthalmol. 2003; 87(11):1381-6. PMC: 1771908. DOI: 10.1136/bjo.87.11.1381. View

10.

Aleman T, Han G, Serrano L, Fuerst N, Charlson E, Pearson D . Natural History of the Central Structural Abnormalities in Choroideremia: A Prospective Cross-Sectional Study. Ophthalmology. 2016; 124(3):359-373. PMC: 5319901. DOI: 10.1016/j.ophtha.2016.10.022. View

11.

Spaide R . Fundus autofluorescence and age-related macular degeneration. Ophthalmology. 2003; 110(2):392-9. DOI: 10.1016/S0161-6420(02)01756-6. View

12.

Renner A, Kellner U, Cropp E, Preising M, MacDonald I, van den Hurk J . Choroideremia: variability of clinical and electrophysiological characteristics and first report of a negative electroretinogram. Ophthalmology. 2006; 113(11):2066.e1-10. DOI: 10.1016/j.ophtha.2006.05.045. View

13.

Syed N, Smith J, John S, Seabra M, Aguirre G, Milam A . Evaluation of retinal photoreceptors and pigment epithelium in a female carrier of choroideremia. Ophthalmology. 2001; 108(4):711-20. DOI: 10.1016/s0161-6420(00)00643-6. View

14.

Jolly J, Xue K, Edwards T, Groppe M, MacLaren R . Characterizing the Natural History of Visual Function in Choroideremia Using Microperimetry and Multimodal Retinal Imaging. Invest Ophthalmol Vis Sci. 2017; 58(12):5575-5583. PMC: 5850987. DOI: 10.1167/iovs.17-22486. View

15.

Schachar I, Zahid S, Comer G, Stem M, Schachar A, Saxe S . Quantification of fundus autofluorescence to detect disease severity in nonexudative age-related macular degeneration. JAMA Ophthalmol. 2013; 131(8):1009-15. DOI: 10.1001/jamaophthalmol.2013.4014. View

16.

Karna J . Choroideremia. A clinical and genetic study of 84 Finnish patients and 126 female carriers. Acta Ophthalmol Suppl (1985). 1986; 176:1-68. View

17.

Jolly J, Menghini M, Johal P, Buckley T, Bridge H, MacLaren R . Inner retinal thickening affects microperimetry thresholds in the presence of photoreceptor thinning in patients with retinitis pigmentosa. Br J Ophthalmol. 2020; 106(2):256-261. DOI: 10.1136/bjophthalmol-2020-317692. View

18.

Jauregui R, Park K, Tanaka A, Cho A, Paavo M, Zernant J . Spectrum of Disease Severity and Phenotype in Choroideremia Carriers. Am J Ophthalmol. 2019; 207:77-86. PMC: 7579725. DOI: 10.1016/j.ajo.2019.06.002. View

19.

Gochfeld M . Sex-gender research sensitivity and healthcare disparities. J Womens Health (Larchmt). 2010; 19(2):189-94. DOI: 10.1089/jwh.2009.1632. View

20.

Pfau M, Jolly J, Wu Z, Denniss J, Lad E, Guymer R . Fundus-controlled perimetry (microperimetry): Application as outcome measure in clinical trials. Prog Retin Eye Res. 2020; 82:100907. DOI: 10.1016/j.preteyeres.2020.100907. View