AMD and low vision awareness month: Using the MTII to evaluate progression of GA

A new study¹ of the natural history of preservation of the central macula in patients with geographic atrophy (GA) showed that using the macular tissue integrity index (MTII) may paint a better picture of the remaining tissue function with disease progression. First author Sairi Zhang, MD, and colleagues described their study in Ophthalmology Science. She is from the Department of Ophthalmology and Visual Sciences, Wisconsin Reading Center, University of Wisconsin-Madison.

The investigators explained that the “most common primary endpoint in GA clinical trials is the change in the total GA area measured on fundus autofluorescence.².⁸ However, this has not been shown to correlate with change in visual functions, especially visual acuity (VA).^3-5 This discrepancy can be attributed to the fact that the location of GA and its direction of growth are not reflected in the total area.⁶”

However, the bottom line is that the total area of GA does not reflect the relation between the visual function and progression of the lesion.

They explained that the MTII was proposed as “a potential marker of GA progression with a modest structure-function relationship that is stronger than that of GA area”⁷ in that it measures the area of retinal tissue with GA lesions in the central 1-mm and 3-mm diameter circles around the fovea.

That pilot study⁷ reported a significant cross-sectional association between the MTII at baseline in the 1-mm circle and the BCVA.⁷ But they pointed out that over time, the changes in the MTII and the BCVA remain unclear and require further investigation. In light of that, they believed that further investigation was warranted in a larger and longer study.

The goal of their study was to investigate the natural history of macular tissue preservation in GA by evaluating the relationship between the MTII and BCVA over time.

MTII study methods

The study under discussion was a post hoc analysis of Age-Related Eye Disease Study 2, a randomized clinical trial that included patients with GA lesions that were not under the fovea.

The authors defined the MTII as “the percentage of the macula without GA within the central 1-mm and 3-mm circles. They assessed the baseline associations with the BCVA; the analyses over time evaluated GA progression, MTII loss, and BCVA decline. The main outcomes were the GA area, the MTII, and the BCVA, the authors recounted.

What did the MTII study show?

A total of 194 patients (243 eyes) were included. The patients were followed for a median of 2 years.

Zhang and colleagues reported, “At baseline, the mean GA area was 1.8 mm² (standard deviation 2.7), and the growth rate was 1.3 mm²/year. The baseline mean MTII in the 1-mm zone was 95.2% (standard deviation 9.1) with a decrease of 5.4%/year, and 87.3% (standard deviation 14.5) in the 3-mm zone with a decrease of 6.7%/year. The baseline mean BCVA was 76.4 letters (standard deviation 11.8; Snellen equivalent 20/30) with a 1.5-letter loss/year. The baseline MTII showed significant correlations with the BCVA (1 mm: r = 0.17, P = 0.01; 3 mm: r = 0.14, P = 0.03), while the GA area was not significantly associated with the BCVA (r = –0.02, P = 0.71).”

The analysis showed that visual loss was associated with the MTII in the 1-mm and 3-mm zones (P < 0.0001 for both comparisons). When they stratified the eyes by the decline of the MTII based on three degrees (stable/moderate/rapid), those with rapid decline had numerically greater vision loss and GA growth.

The study concluded, “This longitudinal study supports MTII as a clinically meaningful biomarker of central retinal preservation that correlates with VA and captures GA progression over time. Additional studies incorporating multimodal imaging, particularly photoreceptor integrity with OCT imaging, and more comprehensive functional endpoints will be needed to establish the relevance of macular integrity as a complementary clinical trial endpoint.”

References

1. Zhang S, Saunders TF, Csaky KG, et al. Longitudinal study of macular preservation and geographic atrophy progression in Age-Related Eye Disease Study 2. Ophthalmol. Sci. 2026;6: 101028; https://www.ophthalmologyscience.org/article/S2666-9145(25)00326-4/fulltext

2. Sadda SR, Chakravarthy U, Birch DG, et al. Clinical endpoints for the study of geographic atrophy secondary to age-related macular degeneration. Retina. 2016;36:1806-1822.

3. Bagheri S, Lains I, Silverman RF, et al. Percentage of foveal vs total macular geographic atrophy as a predictor of visual acuity in age-related macular degeneration. J Vitreoretin Dis. 2019;3:278-282.

4. Lindner M, Nadal J, Mauschitz MM, et al. Combined fundus autofluorescence and near infrared reflectance as prognostic biomarkers for visual acuity in foveal-sparing geographic atrophy. Invest Ophthalmol Vis Sci. 2017;58:BIO61-BIO67.

5. Heier JS, Pieramici D, Chakravarthy U, et al. Visual function decline resulting from geographic atrophy: results from the Chroma and Spectri phase 3 trials. Ophthalmol Retina. 2020;4:673-688.

6. Csaky KG, Miller JML, Martin DF, et al. Drug approval for the treatment of geographic atrophy: how we got here and where we need to go. Am J Ophthalmol. 2024;263:231-239.

7. Erb BM, Botros E, Saunders TF, et al. Investigating macular tissue integrity index as a novel biomarker in geographic atrophy. Ophthalmol Sci. 2025;5:100871.