Characterizing the Preferred Retinal Locus and Fixation Stability in Diabetic Macular Ischemia: A One-Year Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Participants
2.3. Visual Acuity Measurement
2.4. Microperimetry
2.5. Optical Coherence Tomography
2.6. Optical Coherence Tomography Angiography
2.7. Statistical Analysis
3. Results
3.1. Demographic and Ocular Characteristics
3.2. Baseline Fixation Stability
3.3. Fixation Stability Between Eyes at Baseline
3.4. Fixation Stability Between Eyes at One Year
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Steinmetz, J.D.; Bourne, R.R.A.; Briant, P.S.; Flaxman, S.R.; Taylor, H.R.B.; Jonas, J.B.; Abdoli, A.A.; Abrha, W.A.; Abualhasan, A.; Abu-Gharbieh, E.G.; et al. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: The Right to Sight: An analysis for the Global Burden of Disease Study. Lancet Glob. Health 2021, 9, e144–e160. [Google Scholar] [CrossRef] [PubMed]
- Lee, R.; Wong, T.Y.; Sabanayagam, C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis. 2015, 2, 17. [Google Scholar] [CrossRef]
- Chong, V.; Nguyen, Q.D.; Sepah, Y.; Giani, A.; Pearce, E. HORNBILL: A phase I/IIa trial examining the safety, tolerability and early response of BI 764524 in patients with diabetic retinopathy and diabetic macular ischaemia-rationale, study design and protocol. Trials 2022, 23, 669. [Google Scholar] [CrossRef] [PubMed]
- Yang, D.; Tang, Z.; Ran, A.; Nguyen, T.X.; Szeto, S.; Chan, J.; Wong, C.Y.K.; Hui, V.; Tsang, K.; Chan, C.K.M.; et al. Assessment of Parafoveal Diabetic Macular Ischemia on Optical Coherence Tomography Angiography Images to Predict Diabetic Retinal Disease Progression and Visual Acuity Deterioration. JAMA Ophthalmol. 2023, 141, 641–649. [Google Scholar] [CrossRef]
- Tombolini, B.; Borrelli, E.; Sacconi, R.; Bandello, F.; Querques, G. Diabetic macular ischemia. Acta Diabetol. 2022, 59, 751–759. [Google Scholar] [CrossRef] [PubMed]
- Tsai, A.S.H.; Jordan-Yu, J.M.; Gan, A.T.L.; Teo, K.Y.C.; Tan, G.S.W.; Lee, S.Y.; Chong, V.; Cheung, C.M.G. Diabetic Macular Ischemia: Influence of Optical Coherence Tomography Angiography Parameters on Changes in Functional Outcomes Over One Year. Investig. Ophthalmol. Vis. Sci. 2021, 62, 9. [Google Scholar] [CrossRef]
- Liew, G.; Sim, D.A.; Keane, P.A.; Tan, A.G.; Mitchell, P.; Wang, J.J.; Wong, T.Y.; Fruttiger, M.; Tufail, A.; Egan, C.A. Diabetic macular ischaemia is associated with narrower retinal arterioles in patients with type 2 diabetes. Acta Ophthalmol. 2015, 93, e45–e51. [Google Scholar] [CrossRef]
- Tarita-Nistor, L.; Sverdlichenko, I.; Mandelcorn, M.S. What Is a Preferred Retinal Locus? Annu. Rev. Vis. Sci. 2023, 9, 201–220. [Google Scholar] [CrossRef]
- Cheung, C.M.G.; Pearce, E.; Fenner, B.; Sen, P.; Chong, V.; Sivaprasad, S. Looking Ahead: Visual and Anatomical Endpoints in Future Trials of Diabetic Macular Ischemia. Ophthalmologica 2021, 244, 451–464. [Google Scholar] [CrossRef]
- Levine, E.S.; Moult, E.M.; Greig, E.C.; Zhao, Y.; Pramil, V.; Gendelman, I.; Alibhai, A.Y.; Baumal, C.R.; Witkin, A.J.; Duker, J.S.; et al. Multiscale correlation of microvascular changes on optical coherence tomography angiography with retinal sensitivity in diabetic retinopathy. Retina 2022, 42, 357–368. [Google Scholar] [CrossRef]
- Datlinger, F.; Wassermann, L.; Reumueller, A.; Hajdu, D.; Steiner, I.; Salas, M.; Drexler, W.; Pircher, M.; Schmidt-Erfurth, U.; Pollreisz, A. Assessment of Detailed Photoreceptor Structure and Retinal Sensitivity in Diabetic Macular Ischemia Using Adaptive Optics-OCT and Microperimetry. Investig. Ophthalmol. Vis. Sci. 2021, 62, 1. [Google Scholar] [CrossRef] [PubMed]
- Molina-Martín, A.; Pérez-Cambrodí, R.J.; Piñero, D.P. Current Clinical Application of Microperimetry: A Review. Semin. Ophthalmol. 2018, 33, 620–628. [Google Scholar] [CrossRef]
- Morales, M.; Saker, S.; Wilde, C.; Pellizzari, C.; Pallikaris, A.; Notaroberto, N.; Rubinstein, M.; Rui, C.; Limoli, P.; Smolek, M.; et al. Reference Clinical Database for Fixation Stability Metrics in Normal Subjects Measured with the MAIA Microperimeter. Transl. Vis. Sci. Technol. 2016, 5, 6. [Google Scholar] [CrossRef]
- Mukherjee, D.; Lad, E.M.; Vann, R.R.; Jaffe, S.J.; Clemons, T.E.; Friedlander, M.; Chew, E.Y.; Jaffe, G.J.; Farsiu, S. Correlation Between Macular Integrity Assessment and Optical Coherence Tomography Imaging of Ellipsoid Zone in Macular Telangiectasia Type 2. Investig. Ophthalmol. Vis. Sci. 2017, 58, Bio291–Bio299. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Dunbar, H. Clinical Perspectives and Trends: Microperimetry as a Trial Endpoint in Retinal Disease. Ophthalmologica 2021, 244, 418–450. [Google Scholar] [CrossRef] [PubMed]
- Altinbay, D.; Sahli, E.; Bingol Kiziltunc, P.; Atilla, H. Evaluation of fixation characteristics in amblyopia using microperimetry. Int. Ophthalmol. 2023, 43, 3403–3412. [Google Scholar] [CrossRef]
- Kisilevsky, E.; Tarita-Nistor, L.; González, E.G.; Mandelcorn, M.S.; Brent, M.H.; Markowitz, S.N.; Steinbach, M.J. Characteristics of the preferred retinal loci of better and worse seeing eyes of patients with a central scotoma. Can. J. Ophthalmol. 2016, 51, 362–367. [Google Scholar] [CrossRef]
- Tarita-Nistor, L.; Mandelcorn, M.S.; Mandelcorn, E.D.; Markowitz, S.N. Effect of Disease Progression on the PRL Location in Patients with Bilateral Central Vision Loss. Transl. Vis. Sci. Technol. 2020, 9, 47. [Google Scholar] [CrossRef]
- Coulibaly, L.M.; Birner, K.; Zarghami, A.; Gumpinger, M.; Schürer-Waldheim, S.; Fuchs, P.; Bogunović, H.; Schmidt-Erfurth, U.; Reiter, G.S. Repeatability of Microperimetry in Areas of Retinal Pigment Epithelium and Photoreceptor Loss in Geographic Atrophy Supported by Artificial Intelligence—Based Optical Coherence Tomography Biomarker Quantification. Am. J. Ophthalmol. 2025, 271, 347–359. [Google Scholar] [CrossRef]
- Fujii, G.Y.; de Juan, E.; Sunness, J.; Humayun, M.S.; Pieramici, D.J.; Chang, T.S. Patient selection for macular translocation surgery using the scanning laser ophthalmoscope. Ophthalmology 2002, 109, 1737–1744. [Google Scholar] [CrossRef]
- Crossland, M.D.; Dunbar, H.M.P.; Rubin, G.S. Fixation stability measurement using the MP1 microperimeter. Retina 2009, 29, 651–656. [Google Scholar] [CrossRef]
- Zhou, Y.; Yu, W.; Ye, Q.; Xu, Z.; He, Y.; Yao, Y.; Pang, Y.; Zhong, Y.; Li, Q.; Feng, L.; et al. Fixation Stability Deficits in Anisometropic Amblyopia. Investig. Ophthalmol. Vis. Sci. 2025, 66, 14. [Google Scholar] [CrossRef] [PubMed]
- Humphreys, J.D.; Sivaprasad, S. Living Without a Diagnosis: A Patient’s Perspective on Diabetic Macular Ischemia. Ophthalmol. Ther. 2022, 11, 1617–1628. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, Q.D.; Sivaprasad, S.; Jhaveri, C.; Habib, M.; Giani, A.; Gliem, M.; Pearce, E. The Phase I/IIa HORNBILL study: Investigating BI 764524 in patients with diabetic macular ischemia. Investig. Ophthalmol. Vis. Sci. 2023, 64, 3752. [Google Scholar]
- Luo, C.; Sivaprasad, S.; Nguyen, Q.D.; Pearlman, J.; Jhaveri, C.; Giani, A.; Gliem, M.; Pearce, E. The Phase I/IIa PARTRIDGE study: Investigating BI 765128 in patients with diabetic macular ischemia. Investig. Ophthalmol. Vis. Sci. 2023, 64, 2667. [Google Scholar]
- Thottarath, S.; Tsai, W.-S.; Gurudas, S.; Pearce, E.; Cheung, C.M.G.; Yamaguchi, T.C.N.; Sivaprasad, S. Macular Capillary Nonperfusion in Eyes With Stable Laser-Treated Proliferative Diabetic Retinopathy. JAMA Ophthalmol. 2025, 143, 45–52. [Google Scholar] [CrossRef]
- Tsai, W.-S.; Thottarath, S.; Gurudas, S.; Sen, P.; Pearce, E.; Giani, A.; Chong, V.; Cheung, C.M.G.; Sivaprasad, S. Correlation of Optical Coherence Tomography Angiography Characteristics with Visual Function to Define Vision-Threatening Diabetic Macular Ischemia. Diagnostics 2022, 12, 1050. [Google Scholar] [CrossRef]
- Bianco, L.; Arrigo, A.; Marchese, A.; Antropoli, A.; Aragona, E.; La Franca, L.; Mauro, L.; Pina, A.; Hassan Farah, R.; Basile, G.; et al. Fixation Location and Stability in Best Vitelliform Macular Dystrophy. Ophthalmol. Sci. 2023, 3, 100329. [Google Scholar] [CrossRef]
- Altınbay, D.; İdil Ş, A. Fixation Stability and Preferred Retinal Locus in Advanced Age-Related Macular Degeneration. Turk. J. Ophthalmol. 2022, 52, 23–29. [Google Scholar] [CrossRef]
- CenterVue. MAIA Operating Manual; CenterVue: Padova, Italy, 2020. [Google Scholar]
- Holmen, I.C.; Konda, S.M.; Pak, J.W.; McDaniel, K.W.; Blodi, B.; Stepien, K.E.; Domalpally, A. Prevalence and Severity of Artifacts in Optical Coherence Tomographic Angiograms. JAMA Ophthalmol. 2020, 138, 119–126. [Google Scholar] [CrossRef]
- Karatsai, E.; Sen, P.; Gurudas, S.; Sivaprasad, S. Low Luminance Visual Acuity and Low Luminance Deficit in Proliferative Diabetic Retinopathy. J. Clin. Med. 2021, 10, 358. [Google Scholar] [CrossRef] [PubMed]
- Duffy, B.V.; Castellanos-Canales, D.; Decker, N.L.; Lee, H.J.-A.; Yamaguchi, T.C.; Pearce, E.; Fawzi, A.A. Foveal Avascular Zone Enlargement Correlates with Visual Acuity Decline in Patients with Diabetic Retinopathy. Ophthalmol. Retin. 2024. [Google Scholar] [CrossRef]
- Tarita-Nistor, L.; González, E.G.; Markowitz, S.N.; Steinbach, M.J. Fixation characteristics of patients with macular degeneration recorded with the mp-1 microperimeter. Retina 2008, 28, 125–133. [Google Scholar] [CrossRef] [PubMed]
- Pearce, E.; Sivaprasad, S.; Chong, N.V. Factors affecting reading speed in patients with diabetic macular edema treated with laser photocoagulation. PLoS ONE 2014, 9, e105696. [Google Scholar] [CrossRef] [PubMed]
- Baffour-Awuah, K.A.; Taylor, L.J.; Josan, A.S.; Jolly, J.K.; MacLaren, R.E. Investigating the impact of asymmetric macular sensitivity on visual acuity chart reading in choroideremia. Ophthalmic Physiol. Opt. 2024, 44, 1188–1201. [Google Scholar] [CrossRef]
- Tsai, W.S.; Thottarath, S.; Gurudas, S.; Pearce, E.; Giani, A.; Sivaprasad, S. Topographic Correlation of Microperimetry with Structural Characteristics in Diabetic Macular Ischemia. Am. J. Ophthalmol. 2023, 257, 25–33. [Google Scholar] [CrossRef]
Patients | All Participants (n = 79) |
---|---|
Age, mean (SD), years | 57.8 (11.7) |
Sex | |
Male, n (%) | 49 (62%) |
Female, n (%) | 30 (38%) |
Diabetes | |
Type 1, n (%) | 33 (42%) |
Type 2, n (%) | 46 (58%) |
Diabetes duration, mean (SD), years | 28.3 (13.6) |
Bilateral recruitment, n (%) | 66 (84%) |
Ocular characteristics | All eligible eyes (n = 145) |
Diabetic retinopathy severity | |
Active PDR, n (%) | 4 (3%) |
Stable-treated PDR, n (%) | 126 (87%) |
Severe NPDR, n (%) | 7 (5%) |
Moderate NPDR, n (%) | 6 (4%) |
Mild NPDR, n (%) | 2 (1%) |
Examinations | |
Intraocular pressure, mean (SD), mmHg | 15 (4) |
Spherical equivalent, mean (SD), diopter | −0.32 (2.09) |
Past ocular history | |
Cataract surgery, n (%) | 53 (37%) |
Pars plana vitrectomy, n (%) | 26 (18%) |
Diabetic macular edema, n (%) | 24 (17%) |
Macular Laser, n (%) | 31 (21%) |
Microperimetry | |
Fixation loss > 30%, n (%) | 13 (9%) |
Microperimetry | Eyes (n = 132) |
---|---|
Vision | |
BCVA, mean (SD), letters | 78 (9) |
LLVA, mean (SD), letters | 69 (10) |
Fixation loss, median, (Q1, Q3), % | 0 (0.0) |
PRL | |
PRL distance (i, f), mean (SD), ° | 0.29 (0.19) |
Eccentric distance (PRLf, EFL), mean (SD), ° | 0.18 (0.14) |
Superior, n (%) | 3 (2%) |
Superotemporal, n (%) | 30 (23%) |
Temporal, n (%) | 3 (2%) |
Inferotemporal, n (%) | 36 (27%) |
Inferior, n (%) | 1 (1%) |
Inferonasal, n (%) | 37 (28%) |
Nasal, n (%) | 2 (2%) |
Superonasal, n (%) | 20 (15%) |
BCEA@63%, mean (SD), deg2 | 0.97 (0.81) |
Abnormal (>0.8 deg2), n (%) | 69 (52%) |
BCEA@95%, mean (SD), deg2 | 2.91 (2.44) |
Abnormal (>2.4 deg2), n (%) | 64 (48%) |
P1, mean (SD), % | 92.9 (6.5) |
Abnormal (<95%), n (%) | 66 (50%) |
P2, mean (SD), % | 98.8 (2.1%) |
Abnormal (<99%), n (%) | 99 (75%) |
Fixation stability | |
Stable, n (%) | 131 (99%) |
Relative unstable, n (%) | 1 (1%) |
Unstable, n (%) | 0 (0%) |
Retinal sensitivity | |
oRS (macula), mean (SD), dB | 23.7 (4.1) |
MS1 (fovea), mean (SD), dB | 22.5 (4.8) |
RS1 (foveola), mean (SD), dB | 22.2 (4.5) |
Bilateral Recruitment (n = 55) | BSE | WSE | p-Value |
---|---|---|---|
Vision | Mean (SD) | Mean (SD) | |
BCVA (letters) | 81 (7) | 75 (10) | <0.001 |
LLVA (letters) | 71 (9) | 66 (11) | <0.001 |
Microperimetry | |||
PRL distance (i, f) (°) | 0.25 (0.15) | 0.32 (0.22) | 0.046 |
Eccentric distance (PRLf, EFL) (°) | 0.17 (0.15) | 0.19 (0.15) | 0.53 |
BCEA@63% (deg2) | 0.76 (0.55) | 0.99 (0.90) | 0.03 |
BCEA@95% (deg2) | 2.29 (1.68) | 2.97 (2.70) | 0.03 |
P1 (%) | 94.4 (5.4) | 93.0 (6.6) | 0.07 |
P2 (%) | 99.5 (1.2) | 98.7 (2.3) | 0.001 |
oRS (macula) (dB) | 24.1 (4.2) | 23.8 (3.9) | 0.45 |
MS1 (fovea) (dB) | 22.8 (5.0) | 22.8 (4.3) | 0.96 |
RS1 (foveola) (dB) | 22.6 (4.0) | 22.4 (4.2) | 0.77 |
OCT | |||
CST (µm) | 259 (29) | 265 (43) | 0.22 |
DRIL (µm) | 3153 (1800) | 3458 (1919) | 0.06 |
OCTA a | |||
FAZ (mm2) | 0.56 (0.39) | 0.62 (0.37) | 0.29 |
SVD (%) | 37.2 (4.8) | 36.8 (5.1) | 0.49 |
DVD (%) | 43.0 (4.8) | 42.7 (4.4) | 0.66 |
At One Year (n = 40) | BSE at Baseline | WSE at Baseline | p-Value |
---|---|---|---|
Vision | Mean (SD) | Mean (SD) | |
BCVA (letters) | 82 (8) | 78 (9) | <0.001 |
BCVA changes (letters) | 0 (3) | 2 (5) | 0.07 |
LLVA (letters) | 73 (8) | 69 (9) | <0.001 |
LLVA changes (letters) | 1 (5) | 2 (7) | 0.16 |
Microperimetry | |||
PRL distance (i, f) (°) | 0.28 (0.17) | 0.31 (0.17) | 0.22 |
PRL distance (i, f) changes (°) | 0.01 (0.20) | 0.01 (0.20) | 0.95 |
Eccentric distance (PRLf, EFL) (°) | 0.20 (0.25) | 0.22 (0.20) | 0.69 |
Eccentric distance (PRLf, EFL) changes (°) | 0.01 (0.27) | 0.04 (0.17) | 0.55 |
BCEA@63% (deg2) | 0.85 (0.67) | 0.93 (0.76) | 0.45 |
BCEA@63% changes (deg2) | 0.06 (0.63) | −0.08 (0.72) | 0.19 |
BCEA@95% (deg2) | 2.53 (2.01) | 2.80 (2.29) | 0.43 |
BCEA@95% changes (deg2) | 0.16 (1.89) | −0.22 (2.14) | 0.19 |
P1 (%) | 93.4 (6.4) | 93.5 (6.5) | 0.89 |
P1 changes (%) | −0.6 (5.5) | 0.2 (5.7) | 0.38 |
P2 (%) | 99.2 (1.8) | 98.9 (1.9) | 0.36 |
P2 changes (%) | −0.2 (2.1) | 0.4 (2.2) | 0.11 |
oRS (dB) | 24.6 (4.1) | 23.8 (4.1) | 0.19 |
oRS changes (dB) | 0.4 (2.8) | −0.1 (2.2) | 0.19 |
MS1 (dB) | 23.2 (5.5) | 22.9 (4.5) | 0.63 |
MS1 changes (dB) | 0.5 (3.2) | −0.2 (2.7) | 0.23 |
RS1 (dB) | 23.6 (3.9) | 22.0 (4.3) | 0.04 |
RS1 changes (dB) | 0.7 (5.0) | −0.4 (5.1) | 0.31 |
OCT | |||
CST (µm) | 255.8 (29.1) | 259.2 (40.0) | 0.46 |
CST changes (µm) | −3.4 (11.7) | −2.9 (22.0) | 0.90 |
DRIL (µm) | 3765 (1889) | 4226 (1945) | 0.049 |
DRIL (µm) | 530 (1083) | 595 (976) | 0.73 |
OCTA a | |||
FAZ (mm2) | 0.533 (0.292) | 0.631 (0.390) | 0.15 |
FAZ changes (mm2) | 0.013 (0.021) | 0.026 (0.053) | 0.21 |
SVD (%) | 37.6 (3.7) | 37.1 (5.4) | 0.59 |
SVD changes (%) | 0.0 (3.9) | −0.2 (3.5) | 0.75 |
DVD (%) | 43.1 (4.1) | 43.0 (4.9) | 0.91 |
DVD changes (%) | −0.5 (4.2) | −0.3 (3.2) | 0.83 |
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Lim, A.; Tsai, W.-S.; Thottarath, S.; Gurudas, S.; Yamaguchi, T.C.N.; Pearce, E.; Sivaprasad, S. Characterizing the Preferred Retinal Locus and Fixation Stability in Diabetic Macular Ischemia: A One-Year Study. Vision 2025, 9, 20. https://doi.org/10.3390/vision9010020
Lim A, Tsai W-S, Thottarath S, Gurudas S, Yamaguchi TCN, Pearce E, Sivaprasad S. Characterizing the Preferred Retinal Locus and Fixation Stability in Diabetic Macular Ischemia: A One-Year Study. Vision. 2025; 9(1):20. https://doi.org/10.3390/vision9010020
Chicago/Turabian StyleLim, Alicia, Wei-Shan Tsai, Sridevi Thottarath, Sarega Gurudas, Taffeta Ching Ning Yamaguchi, Elizabeth Pearce, and Sobha Sivaprasad. 2025. "Characterizing the Preferred Retinal Locus and Fixation Stability in Diabetic Macular Ischemia: A One-Year Study" Vision 9, no. 1: 20. https://doi.org/10.3390/vision9010020
APA StyleLim, A., Tsai, W.-S., Thottarath, S., Gurudas, S., Yamaguchi, T. C. N., Pearce, E., & Sivaprasad, S. (2025). Characterizing the Preferred Retinal Locus and Fixation Stability in Diabetic Macular Ischemia: A One-Year Study. Vision, 9(1), 20. https://doi.org/10.3390/vision9010020