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Glaucoma is a leading cause of progressive blindness and visual impairment worldwide. Microstructural evidence of glaucomatous damage to the optic nerve head and associated tissues can be visualized using optical coherence tomography (OCT). In recent years, development of novel deep learning (DL) algorithms has led to innovative advances and improvements in automated detection of glaucomatous damage and progression on OCT imaging. DL algorithms have also been trained utilizing OCT data to improve detection of glaucomatous damage on fundus photography, thus improving the potential utility of color photos which can be more easily collected in a wider range of clinical and screening settings. This review highlights ten years of contributions to glaucoma detection through advances in deep learning models trained utilizing OCT structural data and posits future directions for translation of these discoveries into the field of aging and the basic sciences.

Ailin Song,1,* Nicholas Johnson,1,* Alexandria Ayala,1 Atalie C Thompson2 1Duke University School of Medicine, Durham, NC, USA; 2Department of Ophthalmology, Duke University, Durham, NC, USA*These authors contributed equally to this workCorrespondence: Atalie C ThompsonDepartment of Ophthalmology, Duke University, 2351 Erwin Road, DUMC 3802, Durham, NC 27710, USATel +1-919-681-3937Fax +1-919-681-8267Email ataliethompson@gmail.comPurpose: Although Alzheimer’s disease (AD) is a leading cause of dementia worldwide, its clinical diagnosis remains a challenge. Optical coherence tomography (OCT) and OCT with angiography (OCTA) are non-invasive ophthalmic imaging tools with the potential to detect retinal structural and microvascular changes in patients with AD, which may serve as biomarkers for the disease. In this systematic review, we evaluate whether certain OCT and OCTA parameters are significantly associated with AD and mild cognitive impairment (MCI).Methods: PubMed database was searched using a combination of MeSH terms to identify studies for review. Studies were organized by participant diagnostic groups, type of imaging modality, and OCT/OCTA parameters of interest. Participant demographic data was also collected and baseline descriptive statistics were calculated for the included studies.Results: Seventy-one studies were included for review, representing a total of 6757 patients (2350 AD, 793 MCI, 2902 healthy controls (HC), and 841 others with a range of other neurodegenerative diagnoses). The mean baseline ages were 72.78± 3.69, 71.52± 2.88, 70.55± 3.85 years for AD, MCI and HC groups, respectively. The majority of studies noted significant structural and functional decline in AD patients when compared to HC. Although analysis of MCI groups yielded more mixed results, a similar pattern of decline was often noted amongst patients with MCI relative to HC. OCT and OCTA measurements were also shown to correlate with established measures of AD such as neuropsychological testing or neuroimaging.Conclusion: OCT and OCTA show great potential as non-invasive technologies for the diagnosis of AD. However, further research is needed to determine whether there are AD-specific patterns of structural or microvascular change in the retina and optic nerve that distinguish AD from other neurodegenerative diseases. Development of sensitive and specific OCT/OCTA parameters will be necessary before they can be used to detect AD in clinical settings.Keywords: optical coherence tomography, optical coherence tomography angiography, Alzheimer’s disease, mild cognitive impairment, dementia

Samuel F Passi,1,2 Cassandra C Brooks,1 Atalie C Thompson,1 Preeya K Gupta1 1Department of Ophthalmology, Duke University, Durham, NC, USA; 2Minnesota Eye Consultants, Bloomington, MN, USACorrespondence: Preeya K Gupta Email preeya.gupta@duke.eduPurpose: To evaluate the optical quality and tear film quality in patients with dry eye syndrome (DES) before and after using an intranasal neurostimulation device to stimulate tear production.Methods: Cross-sectional review of 33 eyes in 21 patients with DES who underwent optical quality and tear film analysis as part of their routine dry eye evaluation pre- and post-neurostimulation trial in office. Optical quality was assessed by measuring the objective scattering index (OSI) and modulation transfer function (MTF). The time to blink and mean tear film OSI were used to analyze the tear film.Results: Optical quality after the use of the intranasal neurostimulator improved with an average decrease (improvement) in OSI of 0.30± 0.68 (P=0.015) and an average increase (improvement) in MTF of 2.12± 9.2 (P=0.15). Pre-intranasal neurostimulation OSI had a positive correlation with age (Spearman’s rho 0.60, p < 0.001), while MTF had a negative correlation (Spearman’s rho − 0.38, p = 0.03). Pre-intranasal neurostimulation OSI had a negative correlation with MTF (Spearman’s rho − 0.85, p < 0.001) and a positive correlation with tear film mean OSI (Spearman’s rho 0.85, p < 0.001).Conclusion: The optical quality of patients with DES is improved with the use of intranasal neurostimulation for tear production, and there was a trend towards improved MTF though not statistically significant. Future studies are needed to follow patients longitudinally.Keywords: neurostimulation, objective scatter index, modulation transfer function, dry eye syndrome

PURPOSE: To evaluate and compare the retinal microvasculature in the superficial capillary plexus (SCP) in persons with Alzheimer’s disease (AD), mild cognitive impairment (MCI), and cognitively intact controls using optical coherence tomography angiography (OCTA). Various OCT parameters were also compared. DESIGN: Cross-sectional study. PARTICIPANTS: 70 eyes from 39 AD subjects, 72 eyes from 37 MCI subjects, and 254 eyes from 133 control subjects were enrolled. METHODS: Subjects were imaged using the Zeiss Cirrus HD-5000 with AngioPlex. All subjects underwent cognitive evaluation with Mini Mental State Examination (MMSE). MAIN OUTCOME MEASURES: The vessel density (VD) and perfusion density (PD) in the SCP within the Early Treatment Diabetic Retinopathy Study (ETDRS) 6mm circle, 3mm circle, and 3mm ring were compared between groups. The foveal avascular zone (FAZ) area, central subfield thickness (CST), macular ganglion cell-inner plexiform layer (GC-IPL) thickness, and peripapillary retinal nerve fiber layer (RNFL) thickness were also compared. RESULTS: AD subjects had a significantly decreased SCP VD and PD in the 3mm ring (p=0.001 and 0.002 respectively) and 3mm circle (p=0.003 and 0.004 respectively) as well as VD in the 6mm circle (p=0.047) when compared to MCI and a significantly decreased SCP VD and PD in the 3mm ring (p=0.008 and 0.004 respectively) and 3mm circle (p=0.015 and 0.009 respectively) as well as PD in the 6mm circle (p=0.033) when compared to cognitively intact controls. However, there was no difference in SCP VD or PD between MCI and controls (p>0.05). The FAZ area and CST did not significantly differ between groups (p>0.05). AD subjects had significantly decreased GC-IPL thickness over the inferior (p=0.032) and inferonasal (p=0.025) sectors compared to MCI subjects and significantly decreased GC-IPL thickness over the whole (p=0.012), superonasal (p=0.041), inferior (p=0.004), and inferonasal (p=0.006) sectors when compared to controls. MCI subjects had significantly decreased temporal RNFL thickness (p=0.04) compared to controls. CONCLUSIONS: AD subjects had significantly reduced macular VD, PD, and GC-IPL thickness compared to MCI and control subjects. Changes in the retinal microvasculature may mirror small vessel cerebrovascular changes in AD. These parameters may serve as surrogate non-invasive biomarkers in the diagnosis of AD.

PURPOSE: To evaluate whether loss of ≥5 μm in global retinal nerve fiber layer (RNFL) thickness on spectral-domain optical coherence tomography (SDOCT) between two consecutive visits is specific for glaucoma progression. DESIGN: Prospective cohort. PARTICIPANTS: 92 eyes in 49 controls and 300 eyes in 210 glaucoma subjects. METHODS: Study subjects completed at least five standard automated perimetry and SDOCT examinations at 6-month intervals over at least 2 years. Eyes were categorized as progressing from glaucoma if the average RNFL declined by ≥5 μm between two consecutive visits. The false positive proportion was estimated by two methods: 1) ≥5 μm loss in controls and 2) ≥5 μm gain in glaucoma. The false positive proportion was subtracted from the cumulative proportion of eyes categorized with glaucoma progression in order to estimate the true progression prevalence. MAIN OUTCOME MEASURES: False positive and true progression prevalence of subjects with glaucoma detected as progressing on SDOCT. RESULTS: After five years of semi-annual testing, the cumulative proportion of false positives based on ≥5 μm RNFL losses between visits was 24.8% in the controls. While 40.6% of glaucoma eyes were diagnosed with progression at 5 years, only 15.8% would have been considered ‘true’ progression based on the expected false positive ratio from the controls (i.e. 40.6% – 24.8%). The cumulative proportion of an intervisit gain of ≥5 μm at 5 years was 27.4% in glaucoma eyes, suggesting that only 13.2% of eyes with glaucoma had truly progressed (i.e. 40.6% – 27.4%). CONCLUSION: Loss of ≥5 μm in average RNFL between consecutive SDOCT tests is not specific for glaucoma progression. Application of this intervisit “rule of 5” can result in a high cumulative proportion of false positives over time, which could lead to unnecessary interventions in patients whose disease is stable. More specific diagnostic criteria are needed to help clinicians determine whether patients are progressing from glaucoma so that therapy escalation is both timely and appropriate.