Imaging and Diagnostics

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Diaz DJ, Wang JC, Oellers P, Lains I, Sobrin L, Husain D, Miller JW, Vavvas DG, Miller JB. Imaging the Deep Choroidal Vasculature Using Spectral Domain and Swept Source Optical Coherence Tomography Angiography. J Vitreoretin Dis 2018;2(3):146-154.Abstract
Purpose: To evaluate the deeper choroidal vasculature in eyes with various ocular disorders using spectral domain (SD) optical coherence tomography angiography (OCTA) and swept source (SS) OCTA. Methods: Patients underwent OCTA imaging with either SD-OCTA (Zeiss Cirrus Angioplex or Optovue AngioVue) or SS-OCTA (Topcon Triton). Retinal pigment epithelium (RPE) integrity, structural visualization of deep choroidal vessels on en face imaging, and OCTA of deep choroidal blood flow signal were analyzed. Choroidal blood flow was deemed present if deeper choroidal vessels appeared bright after appropriate segmentation. Results: Structural visualization of choroidal vessels was feasible in all eyes by en face imaging. In both SD-OCTA and SS-OCTA, choroidal blood flow signal was present in all eyes with overlying RPE atrophy (100% of eyes with RPE atrophy, 28.6% of all imaged eyes, P < .001). Conclusions: While choroidal vessels can be visualized anatomically in all eyes by en face imaging, choroidal blood flow detection in deep choroidal vessel is largely restricted to areas with overlying RPE atrophy. Intact RPE acts as a barrier for reliable detection of choroidal flow using current OCTA technology, inhibiting evaluation of flow in deeper choroidal vessels in most eyes.
Douglas VP, Douglas KA, Torun N. Optical coherence tomography angiography in neuro-ophthalmology. Curr Opin Ophthalmol 2023;34(4):354-360.Abstract
PURPOSE OF REVIEW: Optical coherence tomography angiography (OCTA) is a novel, noninvasive imaging technique, which provides depth resolved visualization of microvasculature of the retina and choroid. Although OCTA has been widely used for the evaluation of a number of retinal diseases, its use in the field of neuro-ophthalmology has been less studied. In this review, we provide an update on the utility of OCTA in neuro-ophthalmic conditions. RECENT FINDINGS: Peripapillary and macular microvasculature analyses have indicated that OCTA can be a promising tool for early detection of a number of neuro-ophthalmic diseases, differential diagnosis, and monitoring of disease progression. Recent studies have demonstrated that structural and functional impairment can develop at early stages in some conditions such as in multiple sclerosis and Alzheimer's disease even in the absence of overt clinical symptoms. Furthermore, this dye-less technique can be a valuable adjunct tool in the detection of complications commonly seen in some congenital entities such optic disc drusen. SUMMARY: Since its introduction, OCTA has emerged as an important imaging approach shedding light on unrevealed pathophysiological mechanisms of several ocular diseases. The use of OCTA as a biomarker in the field of neuro-ophthalmology has recently gained considerable attention with studies supporting its role in clinical setting while larger studies are warranted for correlating these findings with traditional diagnostic procedures and clinical features and outcomes.
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Evans KK, Haygood TM, Cooper J, Culpan A-M, Wolfe JM. A half-second glimpse often lets radiologists identify breast cancer cases even when viewing the mammogram of the opposite breast. Proc Natl Acad Sci U S A 2016;113(37):10292-7.Abstract

Humans are very adept at extracting the "gist" of a scene in a fraction of a second. We have found that radiologists can discriminate normal from abnormal mammograms at above-chance levels after a half-second viewing (d' ∼ 1) but are at chance in localizing the abnormality. This pattern of results suggests that they are detecting a global signal of abnormality. What are the stimulus properties that might support this ability? We investigated the nature of the gist signal in four experiments by asking radiologists to make detection and localization responses about briefly presented mammograms in which the spatial frequency, symmetry, and/or size of the images was manipulated. We show that the signal is stronger in the higher spatial frequencies. Performance does not depend on detection of breaks in the normal symmetry of left and right breasts. Moreover, above-chance classification is possible using images from the normal breast of a patient with overt signs of cancer only in the other breast. Some signal is present in the portions of the parenchyma (breast tissue) that do not contain a lesion or that are in the contralateral breast. This signal does not appear to be a simple assessment of breast density but rather the detection of the abnormal gist may be based on a widely distributed image statistic, learned by experts. The finding that a global signal, related to disease, can be detected in parenchyma that does not contain a lesion has implications for improving breast cancer detection.

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Ferry JA, Klepeis V, Sohani AR, Harris NL, Preffer FI, Stone JH, Grove A, Deshpande V. IgG4-related Orbital Disease and Its Mimics in a Western Population. Am J Surg Pathol 2015;Abstract

Although chronic inflammatory disorders of the ocular adnexa are relatively common, their pathogenesis is in many cases poorly understood. Recent investigation suggests that many cases of sclerosing orbital inflammation are a manifestation of IgG4-related disease; however, most patients reported have been Asian, and it is not clear whether the results of studies from the Far East can be reliably extrapolated to draw conclusions about Western patients. We evaluated 38 cases previously diagnosed as orbital inflammatory pseudotumor or chronic dacryoadenitis to determine whether our cases fulfill the criteria for IgG4-RD (IgG4-related dacryoadenitis when involving the lacrimal gland, and IgG4-related sclerosing orbital inflammation when involving orbital soft tissue). Fifteen patients had IgG4-related dacryoadenitis or orbital inflammation. These patients included 9 men and 6 women, aged 24 to 77 years (median, 64 y). Lesions involved orbital soft tissue (8 cases), lacrimal gland (6 cases), and canthus (1 case). In 1 case, focal in situ follicular neoplasia was seen in a background of IgG4-RD. In another case, a clonal IGH gene rearrangement was detected. Four patients with IgG4-RD had evidence of IgG4-RD in other anatomic sites. Five patients, 1 man and 4 women, aged 26 to 74 years (median 50 y) had orbital lesions (2 involving lacrimal gland, 3 involving soft tissue) suspicious for, but not diagnostic of, IgG4-RD. Of 16 patients with IgG4-RD or probable IgG4-RD with information available regarding the course of their disease, 11 patients experienced recurrent or persistent orbital disease. However, no patient developed lymphoma, and no patient died of complications of IgG4-RD. Eighteen patients had lesions not representing IgG4-RD. They included 6 male and 12 female individuals aged 6 to 77 years (median, 47 y). These patients had a variety of diseases, including granulomatosis with polyangiitis (3 cases), Rosai-Dorfman disease (1 case), nonspecific chronic inflammation and fibrosis involving lacrimal gland or soft tissue (12 cases), and others. Clinical and pathologic findings among our patients with IgG4-RD involving the orbit are similar to those previously described in Asian patients. Careful evaluation of histologic and immunophenotypic features and clinical correlation are required to distinguish orbital IgG4-RD from other sclerosing inflammatory lesions in the orbit.

Fonda SJ, Bursell S-E, Lewis DG, Clary D, Shahon D, Silva PS. Prevalence of Diabetic Eye Diseases in American Indians and Alaska Natives (AI/AN) as Identified by the Indian Health Service's National Teleophthalmology Program Using Ultrawide Field Imaging (UWFI). Ophthalmic Epidemiol 2022;29(6):672-680.Abstract
PURPOSE: Estimates of diabetic eye disease in American Indian and Alaska Natives (AI/AN) vary over time, region, and methods. This article reports recent prevalence of diabetic retinopathy (DR) and diabetic macular edema (DME) in AI/AN served by the Indian Health Services' (IHS) teleophthalmology program, as identified using ultrawide field imaging (UWFI). METHODS: This was a retrospective analysis of 2016-2019 clinical data (n = 53,900). UWF images were acquired by certified imagers using a validated protocol, and graded by licensed, certified optometrists supervised by an ophthalmologist. Graders evaluated the extent/severity of retinal lesions in comparison to standard photographs. DR lesions predominantly in any peripheral field were considered "predominantly peripheral lesions" (PPL). The analyses calculated prevalence of any DR, any DME, DR and DME severity, sight-threatening disease, and PPL. RESULTS: Patients averaged 56 years of age with a 68 mmol/mol A1c and 55% had had diabetes for 5+ years. Prevalence of any DR, any DME, and sight-threatening disease was 28.6%, 3.0%, and 3.0%. In patients with mild nonproliferative DR, PPL was seen in 25.3%. PPL suggested a more severe level of DR in 8.7% of patients. DR increased with age. DME decreased with age. Males and patients in the Nashville IHS area had more diabetic eye disease. CONCLUSION: AI/AN have a high burden of diabetes and its complications. The IHS is resource-constrained, making accurate disease estimates necessary for resource allocation and budget justifications to Congress. These data update the estimates of diabetic eye disease in Indian Country and suggest that UWFI identifies early DR.
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Gaier ED, Wang M, Gilbert AL, Rizzo JF, Cestari DM, Miller JB. Quantitative analysis of optical coherence tomographic angiography (OCT-A) in patients with non-arteritic anterior ischemic optic neuropathy (NAION) corresponds to visual function. PLoS One 2018;13(6):e0199793.Abstract
PURPOSE: Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common cause of non-glaucomatous optic neuropathy in older adults. Optical coherence tomographic angiography (OCT-A) is an emerging, non-invasive method to study the microvasculature of the posterior pole, including the optic nerve head. The goal of this study was to assess the vascular changes in the optic nerve head and peripapillary area associated with NAION using OCT-A. DESIGN: Retrospective comparative case series. METHODS: We performed OCT-A in 25 eyes (7 acute and 18 non-acute) in 19 patients with NAION. Fellow, unaffected eyes were analyzed for comparison. Patent macro- and microvascular densities were quantified in the papillary and peripapillary regions of unaffected, acutely affected, and non-acutely affected eyes and compared across these groups according to laminar segment and capillary sampling region, and with respect to performance on automated visual field testing. RESULTS: In acutely affected eyes, OCT-A revealed a reduction in the signal from the major retinal vessels and dilation of patent superficial capillaries in the peripapillary area. By contrast, non-acutely affected eyes showed attenuation of patent capillaries. The peripapillary choriocapillaris was obscured by edema in acute cases, but was similar between non-acute and unaffected eyes. The degree of dilation of the superficial microvasculature in the acute phase and attenuation in the non-acute phase each correlated inversely with visual field performance. The region of reduced patent capillary density correlated with the location of visual field defects in 80% of acute cases and 80% of non-acute cases. CONCLUSIONS: OCT-A reveals a dynamic shift in the superficial capillary network of the optic nerve head with strong functional correlates in both the acute and non-acute phases of NAION. Further study may validate OCT-A as a useful adjunctive diagnostic tool in the evaluation of ischemic optic neuropathy.
García-Posadas L, Contreras-Ruiz L, Soriano-Romaní L, Dartt DA, Diebold Y. Conjunctival Goblet Cell Function: Effect of Contact Lens Wear and Cytokines. Eye Contact Lens 2016;42(2):83-90.Abstract

This review focuses on conjunctival goblet cells and their essential function in the maintenance of eye health. The main function of goblet cells is to produce and secrete mucins that lubricate the ocular surface. An excess or a defect in those mucins leads to several alterations that makes goblet cells central players in maintaining the proper mucin balance and ensuring the correct function of ocular surface tissues. A typical pathology that occurs with mucous deficiency is dry eye disease, whereas the classical example of mucous hyperproduction is allergic conjunctivitis. In this review, we analyze how goblet cell number and function can be altered in these diseases and in contact lens (CL) wearers. We found that most published studies focused exclusively on the goblet cell number. However, recent advances have demonstrated that, along with mucin secretion, goblet cells are also able to secrete cytokines and respond to them. We describe the effect of different cytokines on goblet cell proliferation and secretion. We conclude that it is important to further explore the effect of CL wear and cytokines on conjunctival goblet cell function.

Garg I, Uwakwe C, Le R, Lu ES, Cui Y, Wai KM, Katz R, Zhu Y, Moon JY, Li CY, Laíns I, Eliott D, Elze T, Kim LA, Wu DM, Miller JW, Husain D, Vavvas DG, Miller JB. Nonperfusion Area and Other Vascular Metrics by Wider Field Swept-Source OCT Angiography as Biomarkers of Diabetic Retinopathy Severity. Ophthalmol Sci 2022;2(2)Abstract
Purpose: To study the wider field swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, especially non-perfusion area (NPA), in the diagnosing and staging of DR. Design: Cross-sectional observational study (November 2018-September 2020). Participants: 473 eyes of 286 patients (69 eyes of 49 control patients and 404 eyes of 237 diabetic patients). Methods: We imaged using 6mm×6mm and 12mm×12mm angiograms on WF SS-OCTA. Images were analyzed using the ARI Network and FIJI ImageJ. Mixed effects multiple regression models and receiver operator characteristic analysis was used for statistical analyses. Main Outcome Measures: Quantitative metrics such as vessel density (VD); vessel skeletonized density (VSD); foveal avascular zone (FAZ) area, circularity, and perimeter; and NPA in DR and their relative performance for its diagnosis and grading. Results: Among patients with diabetes (median age 59 years), 51 eyes had no DR, 185 eyes (88 mild, 97 moderate-severe) had non-proliferative DR (NPDR); and 168 eyes had proliferative DR (PDR). Trend analysis revealed a progressive decline in superficial capillary plexus (SCP) VD and VSD, and increased NPA with increasing DR severity. Additionally, there was a significant reduction in deep capillary plexus (DCP) VD and VSD in early DR (mild NPDR), but the progressive reduction in advanced DR stages was not significant. NPA was the best parameter to diagnose DR (AUC:0.96), whereas all parameters combined on both angiograms efficiently diagnosed (AUC:0.97) and differentiated between DR stages (AUC range:0.83-0.97). The presence of diabetic macular edema was associated with reduced SCP and DCP VD and VSD within mild NPDR eyes, whereas an increased VD and VSD in SCP among moderate-severe NPDR group. Conclusions: Our work highlights the importance of NPA, which can be more readily and easily measured with WF SS-OCTA compared to fluorescein angiography. It is additionally quick and non-invasive, and hence can be an important adjunct for DR diagnosis and management. In our study, a combination of all OCTA metrics on both 6mm×6mm and 12mm×12mm angiograms had the best diagnostic accuracy for DR and its severity. Further longitudinal studies are needed to assess NPA as a biomarker for progression or regression of DR severity.
Garg I, Miller JB. Semi-automated algorithm using directional filter for the precise quantification of non-perfusion area on widefield swept-source optical coherence tomography angiograms. Quant Imaging Med Surg 2023;13(6):3688-3702.Abstract
BACKGROUND: The clinical application of optical coherence tomography angiography (OCTA) has been well documented in literature with its promising potential in dye-less evaluation of various retinal vascular pathologies. Recent advances in OCTA help us gather wider field of view with 12 mm × 12 mm and montage compared to the standard dye-based scans, which has a higher accuracy and sensitivity in detection of peripheral pathologies. The aim of this study is to build a semi-automated algorithm to precisely quantify the non-perfusion areas (NPAs) on widefield swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: All subjects underwent imaging on 100 kHz SS-OCTA device acquiring 12 mm × 12 mm angiograms centered on fovea and optic disc. After a comprehensive literature review, a novel algorithm using FIJI (ImageJ) was designed to calculate the NPAs (mm2) after excluding the threshold and segmentation artifact areas from the total field of view. Segmentation and threshold artifacts were first removed from enface structure images using the spatial variance and mean filter respectively. Vessel enhancement was achieved by using 'Subtract Background' followed by directional filter. The cut off for Huang's fuzzy black and white thresholding was defined from the pixel values based of the foveal avascular zone. Then, the NPAs were calculated using the 'Analyze Particles' command with a minimum size of ~0.15 mm2. Finally, the artifact area was subtracted from to give the corrected NPAs. RESULTS: Our cohort had 44 eyes of 30 control patients and 107 eyes of 73 patients with diabetes mellitus (both median age 55 years, P=0.89). Of 107 eyes, 21 eyes had no evidence of diabetic retinopathy (DR), 50 eyes had non-proliferative DR and 36 eyes had proliferative DR. The median NPA was 0.20 (0.07-0.40) in controls, 0.28 (0.12-0.72) in no DR, 5.54 (3.12-9.10) in non-proliferative DR and 13.38 (8.73-26.32) in proliferative DR eyes. Using mixed effects-multiple linear regression analysis adjusting for age, there was significant progressive increase in NPA with increasing DR severity. CONCLUSIONS: This is one of the first study to use the directional filter for WFSS-OCTA image processing which is known to be superior to other Hessian based multiscale, linear, and non-linear filters especially for vascular analysis. Our method could greatly refine and streamline the calculation of signal void area proportion, while being much quicker and accurate than manual delineation of NPAs and subsequent estimation. This combined with the wide field of view can have a great prognostic and diagnostic clinical impact for future applications in DR and other ischemic retinal pathologies.
Gupta MP, Dow E, Jeng-Miller KW, Mukai S, Orlin A, Xu K, Yonekawa Y, Chan PRV. SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN COATS DISEASE. Retina 2019;39(6):1177-1185.Abstract
PURPOSE: To evaluate microstructural retinal abnormalities on spectral domain optical coherence tomography (SD-OCT) imaging of eyes with Coats disease. METHODS: This is a multicenter, retrospective study in which SD-OCT images of patients with treatment-naive Coats disease were correlated with clinical examination and visual acuity and, when available, followed longitudinally over time. RESULTS: Macular SD-OCT of 27 eyes with Coats disease revealed intraretinal edema (59%), intraretinal exudates (67%), subretinal fluid (37%), subretinal exudate (48%), ellipsoid zone disruption (52%), external limiting membrane disruption (41%), and subfoveal nodule (26%). All these microstructural abnormalities correlated with worse baseline and final visual acuities (P < 0.05) on univariate analysis, except for intraretinal edema which exhibited a nonstatistically significant trend toward worse baseline visual acuity (P = 0.16). Within stage 2b eyes, external limiting membrane disruption and subretinal nodule on SD-OCT were associated with worse baseline visual acuity (P = 0.02 for both), and there was a trend toward worse final visual acuity with external limiting membrane disruption and subretinal nodule (P = 0.17 for both) and worse baseline (P = 0.08) and final (P = 0.13) visual acuities with ellipsoid zone disruption. No microstructural abnormalities were noted on OCT of fellow eyes. CONCLUSION: Spectral domain OCT can identify microstructural abnormalities in Coats disease that are associated on univariate analysis with worse baseline visual acuity and visual prognosis. Further larger studies are necessary.
Gutierrez A, Chen TC. Artificial intelligence in glaucoma: posterior segment optical coherence tomography. Curr Opin Ophthalmol 2023;34(3):245-254.Abstract
PURPOSE OF REVIEW: To summarize the recent literature on deep learning (DL) model applications in glaucoma detection and surveillance using posterior segment optical coherence tomography (OCT) imaging. RECENT FINDINGS: DL models use OCT derived parameters including retinal nerve fiber layer (RNFL) scans, macular scans, and optic nerve head (ONH) scans, as well as a combination of these parameters, to achieve high diagnostic accuracy in detecting glaucomatous optic neuropathy (GON). Although RNFL segmentation is the most widely used OCT parameter for glaucoma detection by ophthalmologists, newer DL models most commonly use a combination of parameters, which provide a more comprehensive approach. Compared to DL models for diagnosing glaucoma, DL models predicting glaucoma progression are less commonly studied but have also been developed. SUMMARY: DL models offer time-efficient, objective, and potential options in the management of glaucoma. Although artificial intelligence models have already been commercially accepted as diagnostic tools for other ophthalmic diseases, there is no commercially approved DL tool for the diagnosis of glaucoma, most likely in part due to the lack of a universal definition of glaucoma defined by OCT derived parameters alone (see Supplemental Digital Content 1 for video abstract, http://links.lww.com/COOP/A54 ).
Guzman Aparicio MA, Chen TC. New views on three-dimensional imaging technologies for glaucoma: an overview. Curr Opin Ophthalmol 2022;33(2):103-111.Abstract
PURPOSE OF REVIEW: To summarize the literature on three-dimensional (3D) technological advances in ophthalmology, the quantitative methods associated with this, and their improved ability to help detect glaucoma disease progression. RECENT FINDINGS: Improvements in measuring glaucomatous structural changes are the result of dual innovations in optical coherence tomography (OCT) imaging technology and in associated quantitative software. SUMMARY: Compared with two-dimensional (2D) OCT parameters, newer 3D parameters provide more data and fewer artifacts.
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Hanumunthadu D, Lescrauwaet B, Jaffe M, Sadda SV, Wiecek E, Hubschman JP, Patel PJ. Clinical Update on Metamorphopsia: Epidemiology, Diagnosis and Imaging. Curr Eye Res 2021;46(12):1777-1791.Abstract
Purpose: To discuss the pathophysiology of metamorphopsia, its characterisation using retinal imaging and methods of assessment of patient symptoms and visual function.Methods: A literature search of electronic databases was performedResults: Metamorphopsia has commonly been associated with vitreomacular interface disorders (such as epiretinal membrane) and has also regularly been noted in diseases of the retina and choroid, particularly age-related macular degeneration and central serous chorioretinopathy. Developments in optical coherence tomography retinal imaging have enabled improved imaging of the foveal microstructure and have led to the localisation of the pathophysiology of metamorphopsia within the retinal layers of the macula. Alteration of alignment of inner and outer retinal layers at various retinal loci has been identified using multimodal imaging in patients with metamorphopsia in a range of conditions. Although the Amsler Grid assessment of metamorphopsia is a useful clinical indicator, new emerging methods of metamorphopsia assessment with psychophysical tests such as M-CHARTS and preferential hyperacuity perimetry, have been developed.Conclusions: It appears that there is a complex relationship between visual acuity and metamorphopsia symptoms that vary between retinal conditions. Although metamorphopsia has traditionally been challenging to measure in the clinic, advances in technology promise more robust, easy-to-use tests. It is possible that home assessment of metamorphopsia, particularly in conditions such as age-related macular degeneration, may help to guide the need for further clinic evaluation and consideration of treatment.
Houston KE, Paschalis EI. Feasibility of Magnetic Levator Prosthesis Frame Customization Using Craniofacial Scans and 3-D Printing. Transl Vis Sci Technol 2022;11(10):34.Abstract
Purpose: To determine the feasibility of a custom frame generation approach for nonsurgical management of severe blepharoptosis with the magnetic levator prosthesis (MLP). Methods: Participants (n = 8) with severe blepharoptosis (obscuring the visual axis) in one or both eyes who had previously been using a non-custom MLP had a craniofacial scan with a smartphone app to generate a custom MLP frame. A magnetic adhesive was attached to the affected eyelid. The custom MLP frame held a cylindrical magnet near the eyebrow above the affected eyelid, suspending it in the magnetic field while still allowing blinking. The spectacle magnet could be rotated manually, providing adjustable force via angular translation of the magnetic field. Fitting success and comfort were recorded, and interpalpebral fissure (IPF) was measured from video frames after 20 minutes in-office and one-week at-home use. Preference was documented, custom versus non-custom. Results: Overall, 88% of patients (7/8) were successfully fitted with a median 9/10 comfort (interquartile 7-10) and median ptosis improvement of 2.3 mm (1.3-5.0); P = 0.01). Exact binomial testing suggested, with 80% power, that the true population success rate was significantly greater than 45% (P = 0.05). Five participants took the custom MLP home for one week, with only one case of mild conjunctival redness which resolved without treatment. Highest to lowest force modulation resulted in a marginally significant median IPF adjustment of 1.5 mm (0.8 to 2.7; P = 0.06). All preferred the custom frame. Conclusions: The three-dimensional custom MLP frame generation approach using a smartphone app-based craniofacial scan is a feasible approach for clinical deployment of the MLP. Translational Relevance: First demonstration of customized frame generation for the MLP.
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Inomata T, Nakamura M, Sung J, Midorikawa-Inomata A, Iwagami M, Fujio K, Akasaki Y, Okumura Y, Fujimoto K, Eguchi A, Miura M, Nagino K, Shokirova H, Zhu J, Kuwahara M, Hirosawa K, Dana R, Murakami A. Smartphone-based digital phenotyping for dry eye toward P4 medicine: a crowdsourced cross-sectional study. NPJ Digit Med 2021;4(1):171.Abstract
Multidimensional integrative data analysis of digital phenotyping is crucial for elucidating the pathologies of multifactorial and heterogeneous diseases, such as the dry eye (DE). This crowdsourced cross-sectional study explored a novel smartphone-based digital phenotyping strategy to stratify and visualize the heterogenous DE symptoms into distinct subgroups. Multidimensional integrative data were collected from 3,593 participants between November 2016 and September 2019. Dimension reduction via Uniform Manifold Approximation and Projection stratified the collected data into seven clusters of symptomatic DE. Symptom profiles and risk factors in each cluster were identified by hierarchical heatmaps and multivariate logistic regressions. Stratified DE subgroups were visualized by chord diagrams, co-occurrence networks, and Circos plot analyses to improve interpretability. Maximum blink interval was reduced in clusters 1, 2, and 5 compared to non-symptomatic DE. Clusters 1 and 5 had severe DE symptoms. A data-driven multidimensional analysis with digital phenotyping may establish predictive, preventive, personalized, and participatory medicine.
Islam R, Jackson C, Eidet JR, Messelt EB, Corraya RM, Lyberg T, Griffith M, Dartt DA, Utheim TP. Effect of Storage Temperature on Structure and Function of Cultured Human Oral Keratinocytes. PLoS One 2015;10(6):e0128306.Abstract

PURPOSE/AIMS: To assess the effect of storage temperature on the viability, phenotype, metabolism, and morphology of cultured human oral keratinocytes (HOK). MATERIALS AND METHODS: Cultured HOK cells were stored in HEPES- and sodium bicarbonate-buffered Minimum Essential Medium (MEM) at nine temperatures in approximately 4°C increments from 4°C to 37°C for seven days. Cells were characterized for viability by calcein fluorescence, phenotype retention by immunocytochemistry, metabolic parameters (pH, glucose, lactate, and O2) within the storage medium by blood gas analysis, and morphology by scanning electron microscopy and light microscopy. RESULTS: Relative to the cultured, but non-stored control cells, a high percentage of viable cells were retained only in the 12°C and 16°C storage groups (85%±13% and 68%±10%, respectively). Expression of ABCG2, Bmi1, C/EBPδ, PCNA, cytokeratin 18, and caspase-3 were preserved after storage in the 5 groups between 4°C and 20°C, compared to the non-stored control. Glucose, pH and pO2 in the storage medium declined, whereas lactate increased with increasing storage temperature. Morphology was best preserved following storage of the three groups between 12°C, 16°C, and 20°C. CONCLUSION: We conclude that storage temperatures of 12°C and 16°C were optimal for maintenance of cell viability, phenotype, and morphology of cultured HOK. The storage method described in the present study may be applicable for other cell types and tissues; thus its significance may extend beyond HOK and the field of ophthalmology.

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Jabroun MN, AlWattar BK, Fulton AB. Optical Coherence Tomography Angiography in Prematurity. Semin Ophthalmol 2021;36(4):264-269.Abstract
Purpose: During normal foveal development there is a close interaction between the neurosensory and vascular elements of the fovea making it vulnerable to prematurity and retinopathy of prematurity (ROP). We aim to assess this potential effect on foveal development in preterms evaluated simultaneously with both optical coherence tomography (OCT) and OCT angiography (OCTA).Method: Unrestricted literature search in the PubMed and Cochrane library databases yielded 20 distinct citations. Fifteen were relevant and reviewed.Results: In preterms, OCTA demonstrated a significant decrease in the foveal avascular zone area and an increase in foveal vessel density. OCT showed a decrease in foveal pit depth and an increase in the thickness of the subfoveal retinal layers. Some studies correlated these changes with reduced vision.Conclusion: Changes in the vascular and neurosensory retina were found in premature children. It remains unclear whether this is related to prematurity alone or ROP and its treatment.
Jacoba CMP, Cavallerano JD, Tolston AM, Silva PS. Effect of Accessible Nonmydriatic Retinal Imaging on Diabetic Retinopathy Surveillance Rates. Telemed J E Health 2023;29(11):1667-1672.Abstract
Purpose: To evaluate the impact on surveillance rates for diabetic retinopathy (DR) by providing nonmydriatic retinal imaging as part of comprehensive diabetes care at no cost to patients or insurers. Methods: A retrospective comparative cohort study was designed. Patients were imaged from April 1, 2016 to March 31, 2017 at a tertiary diabetes-specific academic medical center. Retinal imaging was provided without additional cost beginning October 16, 2016. Images were evaluated for DR and diabetic macular edema using standard protocol at a centralized reading center. Diabetes surveillance rates before and after no-cost imaging were compared. Results: A total of 759 and 2,080 patients respectively were imaged before and after offering no-cost retinal imaging. The difference represents a 274% increase in the number of patients screened. Furthermore, there was a 292% and 261% increase in the number of eyes with mild DR and referable DR, respectively. In the comparative 6-month period, 92 additional cases of proliferative DR were identified, estimated to prevent 6.7 cases of severe visual loss with annual cost savings of $180,230 (estimated yearly cost of severe vision loss per person: $26,900). In patients with referable DR, self-awareness was low, with no significant difference in the before and after groups (39.4% vs. 43.8%, p = 0.3725). Conclusions: Providing retinal imaging as part of comprehensive diabetes care substantially increased the number of patients identified by nearly threefold. The data suggest that the removal of out-of-pocket costs substantially increased patient surveillance rates, which may translate to improved long-term patient outcomes.
Joseph S, Rajan RP, Sundar B, Venkatachalam S, Kempen JH, Kim R. Validation of diagnostic accuracy of retinal image grading by trained non-ophthalmologist grader for detecting diabetic retinopathy and diabetic macular edema. Eye (Lond) 2023;37(8):1577-1582.Abstract
PURPOSE: To validate the fundus image grading results by a trained grader (Non-ophthalmologist) and an ophthalmologist grader for detecting diabetic retinopathy (DR) and diabetic macular oedema (DMO) against fundus examination by a retina specialist (gold standard). METHODS: A prospective diagnostic accuracy study was conducted using 2002 non-mydriatic colour fundus images from 1001 patients aged ≥40 years. Using the Aravind Diabetic Retinopathy Evaluation Software (ADRES) images were graded by both a trained non-ophthalmologist grader (grader-1) and an ophthalmologist (grader-2). Sensitivity, specificity, positive predictive value and negative predictive value were calculated for grader-1 and grader-2 against the grading results by an independent retina specialist who performed dilated fundus examination for every study participant. RESULTS: Out of 1001 patients included, 42% were women and the mean ± (SD) age was 55.8 (8.39) years. For moderate or worse DR, the sensitivity and specificity for grading by grader-1 with respect to the gold standard was 66.9% and 91.0% respectively and the same for the ophthalmologist was 83.6% and 80.3% respectively. For referable DMO, grader-1 and grader-2 had a sensitivity of 74.6% and 85.6% respectively and a specificity of 83.7% and 79.8% respectively. CONCLUSIONS: Our results demonstrate good level of accuracy for the fundus image grading performed by a trained non-ophthalmologist which was comparable with the grading by an ophthalmologist. Engaging trained non-ophthalmologists potentially can enhance the efficiency of DR diagnosis using fundus images. Further study with multiple non-ophthalmologist graders is needed to verify the results and strategies to improve agreement for DMO diagnosis are needed.
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Kiely C, Douglas KA, Douglas VP, Miller JB, Lizano P. Overlap between ophthalmology and psychiatry - A narrative review focused on congenital and inherited conditions. Psychiatry Res 2024;331:115629.Abstract
A number of congenital and inherited diseases present with both ocular and psychiatric features. The genetic inheritance and phenotypic variants play a key role in disease severity. Early recognition of the signs and symptoms of those disorders is critical to earlier intervention and improved prognosis. Typically, the associations between these two medical subspecialties of ophthalmology and psychiatry are poorly understood by most practitioners so we hope to provide a narrative review to improve the identification and management of these disorders. We conducted a comprehensive review of the literature detailing the diseases with ophthalmic and psychiatric overlap that were more widely represented in the literature. Herein, we describe the clinical features, pathophysiology, molecular biology, diagnostic tests, and the most recent approaches for the treatment of these diseases. Recent studies have combined technologies for ocular and brain imaging such as optical coherence tomography (OCT) and functional imaging with genetic testing to identify the genetic basis for eye-brain connections. Additional work is needed to further explore these potential biomarkers. Overall, accurate, efficient, widely distributed and non-invasive tests that can help with early recognition of these diseases will improve the management of these patients using a multidisciplinary approach.

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