A foundation model for generalizable disease detection from retinal images

Medical artificial intelligence (AI) offers great potential for recognizing signs of health conditions in retinal images and expediting the diagnosis of eye diseases and systemic disorders 1. However, the development of AI models requires substantial annotation and models are usually task-specific with limited generalizability to different clinical applications 2. Here, we present RETFound, a foundation model for retinal images that learns generalizable representations from unlabelled retinal images and provides a basis for label-efficient model adaptation in several applications. Specifically, RETFound is trained on 1.6 million unlabelled retinal images by means of self-supervised learning and then adapted to disease detection tasks with explicit labels. We show that adapted RETFound consistently outperforms several comparison models in the diagnosis and prognosis of sight-threatening eye diseases, as well as incident prediction of complex systemic disorders such as heart failure and myocardial infarction with fewer labelled data. RETFound provides a generalizable solution to improve model performance and alleviate the annotation workload of experts to enable broad clinical AI applications from retinal imaging.</p

A foundation model for generalizable disease detection from retinal images

Medical artificial intelligence (AI) offers great potential for recognizing signs of health conditions in retinal images and expediting the diagnosis of eye diseases and systemic disorders1. However, the development of AI models requires substantial annotation and models are usually task-specific with limited generalizability to different clinical applications2. Here, we present RETFound, a foundation model for retinal images that learns generalizable representations from unlabelled retinal images and provides a basis for label-efficient model adaptation in several applications. Specifically, RETFound is trained on 1.6 million unlabelled retinal images by means of self-supervised learning and then adapted to disease detection tasks with explicit labels. We show that adapted RETFound consistently outperforms several comparison models in the diagnosis and prognosis of sight-threatening eye diseases, as well as incident prediction of complex systemic disorders such as heart failure and myocardial infarction with fewer labelled data. RETFound provides a generalizable solution to improve model performance and alleviate the annotation workload of experts to enable broad clinical AI applications from retinal imaging

Periodontitis and outer retinal thickness:A cross-sectional analysis of the UK Biobank cohort

PurposePeriodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration, in individuals with no eye disease.DesignCross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank.ParticipantsSixty-seven thousand three hundred eleven UK residents aged 40-70 years recruited between 2006-2010 underwent retinal imaging.MethodsMacular-centered optical coherence tomography images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery.Main Outcome MeasuresPhotoreceptor layer (PRL) and retinal pigment epithelium-Bruch’s membrane (RPE-BM) thicknesses.ResultsAmong 36,897 participants included in the analysis, 1,571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation and were more likely to be hypertensive, diabetic and current smokers (all p&lt;0.001). On average, those with very severe periodontitis were myopic (-0.29 ± 2.40 diopters) while those unaffected were hyperopic (0.05 ± 2.27 diopters, p&lt;0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (-0.55 μm, 95% CI: -0.97, -0.12, p=0.022) but there was no difference in RPE-BM thickness (0.00 μm, 95% CI: -0.12, 0.13, p=0.97). The association between PRL thickness and very severe periodontitis was modified by age (p&lt;0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60-69 years with disease (-1.19 μm, 95% CI: -1.85, -0.53, p&lt;0.001) but not among those under 60 years.ConclusionsAmong those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient age-related macular degeneration. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease

Association Between Retinal Features From Multimodal Imaging and Schizophrenia

Importance: The potential association of schizophrenia with distinct retinal changes is of clinical interest but has been challenging to investigate because of a lack of sufficiently large and detailed cohorts./ Objective: To investigate the association between retinal biomarkers from multimodal imaging (oculomics) and schizophrenia in a large real-world population./ Design, Setting, and Participants: This cross-sectional analysis used data from a retrospective cohort of 154 830 patients 40 years and older from the AlzEye study, which linked ophthalmic data with hospital admission data across England. Patients attended Moorfields Eye Hospital, a secondary care ophthalmic hospital with a principal central site, 4 district hubs, and 5 satellite clinics in and around London, United Kingdom, and had retinal imaging during the study period (January 2008 and April 2018). Data were analyzed from January 2022 to July 2022./ Main Outcomes and Measures: Retinovascular and optic nerve indices were computed from color fundus photography. Macular retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer (mGC-IPL) thicknesses were extracted from optical coherence tomography. Linear mixed-effects models were used to examine the association between schizophrenia and retinal biomarkers./ Results: A total of 485 individuals (747 eyes) with schizophrenia (mean [SD] age, 64.9 years [12.2]; 258 [53.2%] female) and 100 931 individuals (165 400 eyes) without schizophrenia (mean age, 65.9 years [13.7]; 53 253 [52.8%] female) were included after images underwent quality control and potentially confounding conditions were excluded. Individuals with schizophrenia were more likely to have hypertension (407 [83.9%] vs 49 971 [48.0%]) and diabetes (364 [75.1%] vs 28 762 [27.6%]). The schizophrenia group had thinner mGC-IPL (−4.05 μm, 95% CI, −5.40 to −2.69; P = 5.4 × 10−9), which persisted when investigating only patients without diabetes (−3.99 μm; 95% CI, −6.67 to −1.30; P = .004) or just those 55 years and younger (−2.90 μm; 95% CI, −5.55 to −0.24; P = .03). On adjusted analysis, retinal fractal dimension among vascular variables was reduced in individuals with schizophrenia (−0.14 units; 95% CI, −0.22 to −0.05; P = .001), although this was not present when excluding patients with diabetes./ Conclusions and Relevance: In this study, patients with schizophrenia had measurable differences in neural and vascular integrity of the retina. Differences in retinal vasculature were mostly secondary to the higher prevalence of diabetes and hypertension in patients with schizophrenia. The role of retinal features as adjunct outcomes in patients with schizophrenia warrants further investigation.

Retinal Optical Coherence Tomography Features Associated With Incident and Prevalent Parkinson Disease

Background and objectives: Cadaveric studies have shown disease-related neurodegeneration and other morphological abnormalities in the retina of individuals with Parkinson disease (PD), however it remains unclear whether this can be reliably detected with in vivo imaging. We investigated inner retinal anatomy, measured using optical coherence tomography (OCT), in prevalent PD and subsequently assessed the association of these markers with the development of PD using a prospective research cohort.// Methods: This cross-sectional analysis used data from two studies. For the detection of retinal markers in prevalent PD, we used data from AlzEye, a retrospective cohort of 154,830 patients aged 40 years and over attending secondary care ophthalmic hospitals in London, UK between 2008 and 2018. For the evaluation of retinal markers in incident PD, we used data from UK Biobank, a prospective population-based cohort where 67,311 volunteers aged 40-69 years were recruited between 2006 and 2010 and underwent retinal imaging. Macular retinal nerve fibre layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layer (INL) thicknesses were extracted from fovea--centred OCT. Linear mixed effects models were fitted to examine the association between prevalent PD and retinal thicknesses. Hazard ratios for the association between time to PD diagnosis and retinal thicknesses were estimated using frailty models.// Results: Within the AlzEye cohort, there were 700 individuals with prevalent PD and 105,770 controls (mean age 65.5 ± 13.5 years, 51.7% female). Individuals with prevalent PD had thinner GCIPL (-2.12 μm, 95% confidence interval: -3.17, -1.07, p = 8.2 × 10⁻⁵) and INL (-0.99 μm, 95% confidence interval: -1.52, -0.47, p = 2.1 × 10⁻⁴). The UK Biobank included 50,405 participants (mean age 56.1 ± 8.2 years, 54.7% female), of whom 53 developed PD at a mean of 2653 ± 851 days. Thinner GCIPL (hazard ratio: 0.62 per standard deviation increase, 95% confidence interval: 0.46, 0.84, p=0.002) and thinner INL (hazard ratio: 0.70, 95% confidence interval: 0.51, 0.96, p=0.026) were also associated with incident PD.// Discussion: Individuals with PD have reduced thickness of the INL and GCIPL of the retina. Involvement of these layers several years before clinical presentation highlight a potential role for retinal imaging for at-risk stratification of PD

Retinal optical coherence tomography features associated with incident and prevalent parkinson disease

Background and Objectives: Cadaveric studies have shown disease-related neurodegeneration and other morphological abnormalities in the retina of individuals with Parkinson disease (PD); however, it remains unclear whether this can be reliably detected with in vivo imaging. We investigated inner retinal anatomy, measured using optical coherence tomography (OCT), in prevalent PD and subsequently assessed the association of these markers with the development of PD using a prospective research cohort. Methods: This cross-sectional analysis used data from 2 studies. For the detection of retinal markers in prevalent PD, we used data from AlzEye, a retrospective cohort of 154,830 patients aged 40 years and older attending secondary care ophthalmic hospitals in London, United Kingdom, between 2008 and 2018. For the evaluation of retinal markers in incident PD, we used data from UK Biobank, a prospective population-based cohort where 67,311 volunteers aged 40–69 years were recruited between 2006 and 2010 and underwent retinal imaging. Macular retinal nerve fiber layer (mRNFL), ganglion cell–inner plexiform layer (GCIPL), and inner nuclear layer (INL) thicknesses were extracted from fovea-centered OCT. Linear mixed-effects models were fitted to examine the association between prevalent PD and retinal thicknesses. Hazard ratios for the association between time to PD diagnosis and retinal thicknesses were estimated using frailty models. Results: Within the AlzEye cohort, there were 700 individuals with prevalent PD and 105,770 controls (mean age 65.5 ± 13.5 years, 51.7% female). Individuals with prevalent PD had thinner GCIPL (−2.12 μm, 95% CI −3.17 to −1.07, p = 8.2 × 10−5) and INL (−0.99 μm, 95% CI −1.52 to −0.47, p = 2.1 × 10−4). The UK Biobank included 50,405 participants (mean age 56.1 ± 8.2 years, 54.7% female), of whom 53 developed PD at a mean of 2,653 ± 851 days. Thinner GCIPL (hazard ratio [HR] 0.62 per SD increase, 95% CI 0.46–0.84, p = 0.002) and thinner INL (HR 0.70, 95% CI 0.51–0.96, p = 0.026) were also associated with incident PD. Discussion: Individuals with PD have reduced thickness of the INL and GCIPL of the retina. Involvement of these layers several years before clinical presentation highlight a potential role for retinal imaging for at-risk stratification of PD

Association Between Retinal Features From Multimodal Imaging and Schizophrenia

IMPORTANCE The potential association of schizophrenia with distinct retinal changes is of clinical interest but has been challenging to investigate because of a lack of sufficiently large and detailed cohorts. OBJECTIVE To investigate the association between retinal biomarkers from multimodal imaging (oculomics) and schizophrenia in a large real-world population. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional analysis used data from a retrospective cohort of 154 830 patients 40 years and older from the AlzEye study, which linked ophthalmic data with hospital admission data across England. Patients attended Moorfields Eye Hospital, a secondary care ophthalmic hospital with a principal central site, 4 district hubs, and 5 satellite clinics in and around London, United Kingdom, and had retinal imaging during the study period (January 2008 and April 2018). Data were analyzed from January 2022 to July 2022. MAIN OUTCOMES AND MEASURES Retinovascular and optic nerve indices were computed from color fundus photography. Macular retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (mGC-IPL) thicknesses were extracted from optical coherence tomography. Linear mixed-effects models were used to examine the association between schizophrenia and retinal biomarkers. RESULTS A total of 485 individuals (747 eyes) with schizophrenia (mean [SD] age, 64.9 years [12.2]; 258 [53.2%] female) and 100 931 individuals (165 400 eyes) without schizophrenia (mean age, 65.9 years [13.7]; 53 253 [52.8%] female) were included after images underwent quality control and potentially confounding conditions were excluded. Individuals with schizophrenia were more likely to have hypertension (407 [83.9%] vs 49 971 [48.0%]) and diabetes (364 [75.1%] vs 28 762 [27.6%]). The schizophrenia group had thinner mGC-IPL (-4.05 μm, 95% CI, -5.40 to -2.69; P = 5.4 × 10-9), which persisted when investigating only patients without diabetes (-3.99 μm; 95% CI, -6.67 to -1.30; P = .004) or just those 55 years and younger (-2.90 μm; 95% CI, -5.55 to -0.24; P = .03). On adjusted analysis, retinal fractal dimension among vascular variables was reduced in individuals with schizophrenia (-0.14 units; 95% CI, -0.22 to -0.05; P = .001), although this was not present when excluding patients with diabetes. CONCLUSIONS AND RELEVANCE In this study, patients with schizophrenia had measurable differences in neural and vascular integrity of the retina. Differences in retinal vasculature were mostly secondary to the higher prevalence of diabetes and hypertension in patients with schizophrenia. The role of retinal features as adjunct outcomes in patients with schizophrenia warrants further investigation

Periodontitis and outer retinal thickness:A cross-sectional analysis of the UK Biobank cohort

PURPOSE: Periodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone, can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration (AMD), in individuals with no eye disease.DESIGN: Cross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank.PARTICIPANTS: Sixty-seven thousand three hundred eleven UK residents aged 40 to 70 years recruited between 2006 and 2010 underwent retinal imaging.METHODS: Macular-centered OCT images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses, adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery.MAIN OUTCOME MEASURES: Photoreceptor layer (PRL) and retinal pigment epithelium-Bruch's membrane (RPE-BM) thicknesses.RESULTS: Among 36 897 participants included in the analysis, 1571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation, and were more likely to be hypertensive, diabetic, and current smokers (all P &lt; 0.001). On average, those with very severe periodontitis were hyperopic (0.05 ± 2.27 diopters) while those unaffected were myopic (-0.29 ± 2.40 diopters, P &lt; 0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (-0.55 μm, 95% confidence interval [CI], -0.97 to -0.12; P = 0.022) but there was no difference in RPE-BM thickness (0.00 μm, 95% CI, -0.12 to 0.13; P = 0.97). The association between PRL thickness and very severe periodontitis was modified by age (P &lt; 0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60 to 69 years with disease (-1.19 μm, 95% CI, -1.85 to -0.53; P &lt; 0.001) but not among those aged &lt; 60 years.CONCLUSIONS: Among those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient AMD. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease.FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p

Periodontitis and outer retinal thickness:A cross-sectional analysis of the UK Biobank cohort

PURPOSE: Periodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone, can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration (AMD), in individuals with no eye disease.DESIGN: Cross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank.PARTICIPANTS: Sixty-seven thousand three hundred eleven UK residents aged 40 to 70 years recruited between 2006 and 2010 underwent retinal imaging.METHODS: Macular-centered OCT images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses, adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery.MAIN OUTCOME MEASURES: Photoreceptor layer (PRL) and retinal pigment epithelium-Bruch's membrane (RPE-BM) thicknesses.RESULTS: Among 36 897 participants included in the analysis, 1571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation, and were more likely to be hypertensive, diabetic, and current smokers (all P &lt; 0.001). On average, those with very severe periodontitis were hyperopic (0.05 ± 2.27 diopters) while those unaffected were myopic (-0.29 ± 2.40 diopters, P &lt; 0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (-0.55 μm, 95% confidence interval [CI], -0.97 to -0.12; P = 0.022) but there was no difference in RPE-BM thickness (0.00 μm, 95% CI, -0.12 to 0.13; P = 0.97). The association between PRL thickness and very severe periodontitis was modified by age (P &lt; 0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60 to 69 years with disease (-1.19 μm, 95% CI, -1.85 to -0.53; P &lt; 0.001) but not among those aged &lt; 60 years.CONCLUSIONS: Among those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient AMD. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease.FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p