Monitoring Of Age-related Macular Degeneration Research Articles

Telehealth improves follow-up and monitoring of age-related macular degeneration during the COVID-19 pandemic.

To prevent vision loss, it is important to monitor patients with age-related macular degeneration (AMD) for the development of choroidal neovascularization. The coronavirus disease 2019 (COVID-19) pandemic caused many patients to miss or delay visits. To offset those gaps in care, providers utilized telehealth (TH) to evaluate patients for symptoms of disease progression and provide health education on the importance of continuous monitoring. This study evaluates the impact of TH encounters on the rate of return for recommended in-person examinations for 1103 patients with non-neovascular (dry) AMD seen in an outpatient ophthalmology clinic in 2019 and due for return evaluation after the outbreak of COVID-19 in 2020. Logistic regression analysis was used to identify demographic, clinical, and sociomedical factors associated with TH utilization and in-person return. 422 patients (38%) utilized TH during the study period. Patients who completed a TH encounter were more likely to return for an in-person examination as compared with those who did not receive TH (OR: 1.8, CI 95%: 1.4-2.3, P < 0.001). Completing a TH visit was associated with the detection of new wet AMD (OR: 3.3, 95% CI 1.04-10.6, P = 0.043), as well as with an earlier return for those patients who were found to have disease progression (62 ± 54days vs. 100 ± 57days, P = 0.049). Completing a TH visit increased the rate at which patients with dry AMD returned for recommended in-person eye examinations. In many cases, this permitted the earlier detection of wet AMD, which is linked with achieving better outcomes.

Novel Epigenetic Clock Biomarkers of Age-Related Macular Degeneration.

Age-Related Macular Degeneration (AMD) is a bilateral ocular condition resulting in irreversible vision impairment caused by the progressive loss of photoreceptors in the macula, a region at the center of the retina. The progressive loss of photoreceptor is a key feature of dry AMD but not always wet AMD, though both forms of AMD can lead to loss of vision. Regression-based biological age clocks are one of the most promising biomarkers of aging but have not yet been used in AMD. Here we conducted analyses to identify regression-based biological age clocks for the retina and explored their use in AMD using transcriptomic data consisting of a total of 453 retina samples including 105 Minnesota Grading System (MGS) level 1 samples, 175 MGS level 2, 112 MGS level 3 and 61 MGS level 4 samples, as well as 167 fibroblast samples. The clocks yielded good separation among AMD samples with increasing severity score viz., MGS1-4, regardless of whether clocks were trained in retina tissue, dermal fibroblasts, or in combined datasets. Clock application to cultured fibroblasts, embryonic stem cells, and induced Pluripotent Stem Cells (iPSCs) were consistent with age reprograming in iPSCs. Moreover, clock application to in vitro neuronal differentiation suggests broader applications. Interesting, many of the age clock genes identified include known targets mechanistically linked to AMD and aging, such as GDF11, C16ORF72, and FBN2. This study provides new observations for retina age clocks and suggests new applications for monitoring in vitro neuronal differentiation. These clocks could provide useful markers for AMD monitoring and possible intervention, as well as potential targets for in vitro screens.

Multispectral pattern recognition measures change in drusen area in age-related macular degeneration with high congruency to expert graders.

Drusen are a hallmark lesion of age-related macular degeneration (AMD) and changes in their area and/or volume are strongly associated with disease progression. Assessment of longitudinal change in drusen size in clinical practice however is limited to a single commercial tool or manual inspection by clinicians. In this study we analysed change in drusen area in 33 eyes with intermediate AMD across two separate visits using a novel technique known as multispectral pattern recognition for en face retinal images from various imaging modalities (infrared (815 nm), fundus autofluorescence (488 nm) and green (532 nm) scanning laser ophthalmoscopy). We found 91% (30/33 eyes) agreement in the direction of drusen change for multispectral pattern recognition relative to expert graders who graded eyes as having drusen progression, regression or being stable. Multispectral pattern recognition showed 100% sensitivity (22/22 eyes) and 73% specificity (8/11 eyes). In comparison, we found only 70% (23/33 eyes) agreement in the direction of drusen change with a commercially available change analysis software, the Cirrus Advanced RPE Analysis relative to expert graders, with a sensitivity 64% (14/22 eyes) and specificity of 82% (9/11 eyes). Total drusen area or amount of change between visits had no significant effect on agreement. This suggests multispectral pattern recognition can quantify longitudinal change in drusen area from multimodal imaging with greater congruency to expert graders than a commercially available platform based on a single imaging modality. Considering the association of drusen area and disease progression, this method could aid clinical assessment and monitoring of AMD.

Ophthalmic Telemedicine in the Pandemic–Endemic World: Present and Future Perspectives

COVID-19 restrictions have increased the need and use of telemedicine in ophthalmology but this approach requires remote data collection and reliable technologies to ensure accurate and safe examination and diagnosis. This article reviews the existing telemedicine technologies for age-related macular degeneration (AMD), diabetic retinopathy (DR) and paediatric ophthalmology, and discusses their applicability in the COVID-19 era. We conducted a literature search of PubMed using telemedicine keywords for all relevant pathologies (AMD, DR and paediatric ophthalmology) to identify English-language articles published between 2001 and 2021. We assessed whether existing telemedicine technologies would meet the needs of patients under COVID-19 restrictions. Our findings showed that there are reliable existing home-monitoring technologies. However, self-operated home optical coherence tomography is still an investigational technology for AMD monitoring and is not yet available for routine use. Computerized algorithms aimed at identifying DR pathology and or deterioration in relevant parameters under investigation have shown excellent results. In paediatric ophthalmology, parents can conduct basic testing of their child's ophthalmic parameters; improvements in parental testing will require the development of quick and reliable automatic instruments. In conclusion, current technologies lend themselves to remote use for ophthalmic examination by non-professional individuals, which is particularly relevant for ophthalmic care provision in the pandemic setting. Further investigative effort is needed in order to improve home monitoring and computerized data processing.

Automatic segmentation of retinal layers in OCT images with intermediate age-related macular degeneration using U-Net and DexiNed

Age-related macular degeneration (AMD) is an eye disease that can cause visual impairment and affects the elderly over 50 years of age. AMD is characterized by the presence of drusen, which causes changes in the physiological structure of the retinal pigment epithelium (RPE) and the boundaries of the Bruch’s membrane layer (BM). Optical coherence tomography is one of the main exams for the detection and monitoring of AMD, which seeks changes through the evaluation of successive sectional cuts in the search for morphological changes caused by drusen. The use of CAD (Computer-Aided Detection) systems has contributed to increasing the chances of correct detection, assisting specialists in diagnosing and monitoring disease. Thus, the objective of this work is to present a method for the segmentation of the inner limiting membrane (ILM), retinal pigment epithelium, and Bruch’s membrane in OCT images of healthy and Intermediate AMD patients. The method uses two deep neural networks, U-Net and DexiNed to perform the segmentation. The results were promising, reaching an average absolute error of 0.49 pixel for ILM, 0.57 for RPE, and 0.66 for BM.

Home Monitoring of Age-Related Macular Degeneration: Utility of the ForeseeHome Device for Detection of Neovascularization

PurposeTo evaluate the real-world utility of the ForeseeHome monitoring device (Notal Vision, Ltd., Tel Aviv, Israel) for the detection of conversion from intermediate age-related macular degeneration (iAMD) to neovascular AMD (nAMD) and to compare with results published by the Home Monitoring of the Eye (HOME) study.DesignRetrospective analysis of electronic health records.ParticipantsEyes prescribed use of the ForeseeHome device across 4 retinal practices in the United States.MethodsUsage information was collected from the online ForeseeHome portal for all eyes prescribed the device. For a predetermined subset of eyes, additional clinical information was collected through chart review and analyzed for clinical utility.Main Outcome MeasuresFrequency and length of use, number of eyes that used the device, number of eyes that established a baseline measurement, number of eyes that converted to nAMD, and number of alerts.ResultsSeven hundred seventy-five eyes of 448 patients were prescribed use of the ForeseeHome device. Six hundred forty-nine eyes (83.7%) used the device at least once; among this population, 478 (73.7%) established a baseline measurement. Patients who established a baseline measurement were significantly younger than those who did not (P < 0.001). Among eyes that established a baseline measurement, 126 (26.4%) had an overall inadequate frequency of use (≥2 tests per week), and 250 (52.3%) did not use the device as frequently as instructed by the manufacturer (≥3 tests per week); 24.7% of eyes discontinued use within 1 year. Of the 136 eyes that established a baseline measurement among 211 eyes prescribed the device at 1 clinical site, 52 alerts were recorded; 3 (6.8%) correctly identified conversion to nAMD and 47 (93.2%) represented false-positive alerts.ConclusionsCompared with the prospective HOME study, the utility of the ForeseeHome device in the current analysis of clinical practice application was limited. A meaningful proportion of eyes never used the device or could not establish a baseline measurement. Overall frequency of use was low, and continuous use of the device decreased over time. A need exists for improvement in home monitoring technology for eyes with iAMD at risk of conversion to nAMD.

High-Speed, Ultrahigh-Resolution Spectral-Domain OCT with Extended Imaging Range Using Reference Arm Length Matching.

PurposeTo develop high-speed, extended-range, ultrahigh-resolution spectral-domain optical coherence tomography (UHR SD-OCT) and demonstrate scan protocols for clinical retinal imaging.MethodsA UHR SD-OCT operating at 840-nm with 150-nm bandwidths was developed. The axial imaging range was extended by dynamically matching reference arm length to the retinal contour during acquisition. Two scan protocols were demonstrated for imaging healthy participants and patients with dry age-related macular degeneration. A high-definition raster protocol with intra–B-scan reference arm length matching (ReALM) was used for high-quality cross-sectional imaging. A cube volume scan using horizontal and vertical rasters with inter–B-scan ReALM and software motion correction was used for en face and cross-sectional imaging. Linear OCT signal display enhanced visualization of outer retinal features.ResultsUHR SD-OCT was demonstrated at 128- and 250-kHz A-scan rates with 2.7 µm axial resolution and a 1.2-mm, 6-dB imaging range in the eye. Dynamic ReALM was used to maintain the retina within the 6-dB imaging range over wider fields of view. Outer retinal features, including the rod and cone interdigitation zones, retinal pigment epithelium, and Bruch's membrane were visualized and alterations observed in age-related macular degeneration eyes.ConclusionsTechnological advances and dynamic ReALM improve the imaging performance and clinical usability of UHR SD-OCT.Translational RelevanceThese advances should simplify clinical imaging workflow, reduce imaging session times, and improve yield of high quality images. Improved visualization of photoreceptors, retinal pigment epithelium, and Bruch's membrane may facilitate diagnosis and monitoring of age-related macular degeneration and other retinal diseases.

Retinal volume change is a reliable OCT biomarker for disease activity in neovascular AMD.

Current algorithms for automated computer interpretation of optical coherence tomography (OCT) imaging of patients suffering from neovascular age-related macular degeneration (AMD) mostly rely on fluid detection. However, fluid detection itself and correct interpretation of the fluid currently limits diagnostic accuracy. We therefore performed a detailed analysis of the requirements that would have to be met for fluid detection approaches. We further investigated if monitoring retinal volume would be a viable alternative to detect disease activity. Retrospective analysis and manual grading of 764 OCT volume scans of 44 patients with exudative AMD treated with intravitreal anti-VEGF injections at a pro-re-nata (PRN) treatment regimen for at least 24months. Detection of subretinal fluid (SRF) or intraretinal fluid (IRF) alone is not sufficient for disease detection. A combination of SRF and IRF can detect disease activity with a sensitivity of 98.6% and a specificity of 82%. With further characterization of IRF into exudative and degenerative cysts, specificity can be increased to 100%. However, correct characterization is currently not achieved by published fluid detection approaches. Change of macular retinal volume (MRV) can depict disease activity with sensitivity of 88.4% and specificity of 89.6%. Combination with the detection of SRF can further improve diagnostic accuracy to a specificity of 93.3% and sensitivity of 93.9% without relying on IRF or IRF characterization. Fluid detection without further characterization is not sufficient for AMD monitoring. Either further distinction between exudative and degenerative cysts is necessary, or other activity markers have to be taken into account. MRV offers good potential to fill this diagnostic gap and might become an important monitoring marker.

Accuracy of a Self-monitoring Test for Identification and Monitoring of Age-related Macular Degeneration: A Diagnostic Case-control Study.

Objective:To evaluate diagnostic accuracy of a new self-monitoring device using a Vernier hyperacuity alignment task.Method:A total of 11 wet Age-Related Macular Degeneration (AMD) patients and 9 controls contributing 37 eyes were consecutively enrolled into this prospective diagnostic case-control study at the retina centre of the Cantonal Hospital Lucerne, Switzerland. Vernier acuity testing (index test) and Optical Coherence Tomography (OCT, reference test) were performed in all participants. OCT scans were evaluated and graded by a retinal specialist masked to diagnosis and index test results. Candidate parameters of the index test to be used as the diagnostic statistic were identified using a bootstrap procedure. Ten parameters remaining were further assessed in univariate analyses. The overall Standard Deviation (SD) of absolute distances across all four axes of the Vernier acuity test provided the highest area under the Receiver Operating Characteristics (ROC) curve and was therefore selected.Results:Mean age of patients with wet AMD was 81.2 years (SD 4.99), mean numbers of letters were 67.4 (SD 14.1). The proportion of women was similar in both groups (controls: 88%, wet AMD: 72%). The area under the ROC curve was 0.87 (95% confidence interval CI: 0.75- 0.99) indicating excellent discrimination. Best accuracy was reached at a cut-off value of 0.64 with a sensitivity of 75% and a specificity of 94%.Conclusion:This diagnostic case-control study of a new screening device for AMD shows acceptable diagnostic accuracy. The promising preliminary data of this study call for further upstream evaluations in reasonably sized clinical studies.

Wearable diagnostic system for age-related macular degeneration.

This paper presents a novel head-mounted point-of-care diagnostic system for detection and continuous monitoring of Age-related Macular Degeneration (AMD). This wearable embedded open-source platform enables accurate monitoring of AMD by taking advantage of multiple standard graphical interface techniques such as Amsler Grid, Threshold Amsler Grid, Macular Computerized Psychophysical Test and Preferential Hyperacuity Perimeter (PHP). Here, we describe the proposed multi-Grid or so-called NGRID software and elaborate on the hardware prototype. This prototype includes a commercially available Oculus HMD incorporated with a single board computer. As the first step towards a fully integrated wearable system, this paper successfully proves the functionality of head-mounted graphical interface device ready for a live demonstration. Participants can experience this device and take a 10-minute AMD eye-exam. Furthermore, NGRID has been approved and permitted for an in-hospital clinical trial.

Prospective evaluation of teleophthalmology in screening and recurrence monitoring of neovascular age-related macular degeneration: a randomized clinical trial.

Teleophthalmology has the potential to reduce costs and inconveniences associated with frequent patient visits. Evaluating teleophthalmology in the management of age-related macular degeneration (AMD) will allow for future implementation of this technology. To evaluate teleophthalmology as a tool for the screening and monitoring of neovascular AMD. Prospective, randomized clinical trial that included 106 referral eyes for suspected neovascular AMD and 63 eyes with stable neovascular AMD. New referrals for patients with suspected neovascular AMD and patients with stable neovascular AMD were randomized into either routine or teleophthalmologic groups. In the routine group, patients received clinical assessment and diagnostic imaging at a tertiary hospital-based retina clinic. In the teleophthalmologic group, patients received basic examination and diagnostic imaging at a stand-alone teleophthalmologic site, where patient information and imaging studies were acquired and electronically sent over to tertiary hospital-based retina specialists. Patients in the teleophthalmologic group were called back to the tertiary treatment center if the teleophthalmologic data set suggested pathology or was inconclusive for diagnosis. Patient wait times for diagnosis and/or treatment, referral accuracy, and visual outcome. For neovascular AMD screening, the average referral-to-diagnostic imaging time was 22.5 days for the teleophthalmologic group and 18.0 days for the routine group, for a difference of 4.5 days (95% CI, 11.8 to -2.8 days; P = .23). The average diagnostic imaging to treatment time was 16.4 days for the teleophthalmologic group and 11.6 days for the routine group, for a difference of 4.8 days (95% CI, 10.7 to -1.1 days; P = .11). For neovascular AMD monitoring, the average recurrence to treatment time was shorter for the routine group (0.04 days) compared with 13.6 days for the teleophthalmologic group, for a difference of -13.5 days (95% CI, -18.2 to -9.0 days; P < .01). There was no difference identified between end-of-study visual acuities in the 2 groups (P = .99). A delay of referral to treatment time could not be identified when comparing teleophthalmologic screening for suspected neovascular AMD with retinal specialist-based screening. Teleophthalmologic monitoring for neovascular AMD recurrence resulted in longer wait times for treatment reinitiation, but no adverse visual outcomes were identified. clinicaltrials.gov Identifier:NCT01581606.

Detection of early age-related macular degeneration using novel functional parameters of the focal cone electroretinogram.

The focal cone electroretinogram is a sensitive marker for macular disease, but have we unlocked its full potential? Typically assessment of waveform parameters is subjective and focuses on a small number of locations (e.g. the a-wave). This study evaluated the discriminatory and diagnostic potential of 4 conventional and 15 novel, objectively determined, parameters in patients with early Age-related Macular Degeneration. Focal cone electroretinograms were recorded in 54 participants with early Age-related Macular Degeneration (72.9±8.2 years) and 54 healthy controls (69±7.7 years). Conventional a and b wave amplitudes and implicit times were measured and compared to novel parameters derived from both the 1st and 2nd derivatives and the frequency-domain power spectrum of the electroretinogram.Statistically significant differences between groups were shown for all conventional parameters, the majority of 1st and 2nd derivative parameters and the power spectrum at 25 and 30 Hz. Receiver operating characteristics showed that both conventional and 1st and 2nd derivative implicit times had provided the best diagnostic potential. A regression model showed a small improvement over any individual parameter investigated. The non-conventional parameters enhanced the objective evaluation of the focal electroretinogram, especially when the amplitude was low. Furthermore, the novel parameters described here allow the implicit time of the electroretinogram to be probed at points other than the peaks of the a and b waves. Consequently these novel analysis techniques could prove valuable in future electrophysiological investigation, detection and monitoring of Age-related Macular Degeneration.

Handheld Shape Discrimination Hyperacuity Test on a Mobile Device for Remote Monitoring of Visual Function in Maculopathy

Frequency monitoring of age-related macular degeneration (AMD) and diabetic retinopathy (DR) is crucial for timely intervention. This study evaluated a handheld shape discrimination hyperacuity (hSDH) test iPhone app designed for visual function self-monitoring in patients with AMD and DR. One hundred subjects (27 visually normal, 37 with AMD, and 36 with DR) were included based on clinical documentation and visual acuity of 20/100 or better. The hSDH test was implemented on the iOS platform. A cross-sectional study was conducted to compare the hSDH test with a previously established desktop SDH (dSDH) test and to assess the effect of disease severity on the hSDH test. A user survey was also conducted to assess the usability of the hSDH test on the mobile device. The hSDH test and dSDH test were highly correlated (r = 0.88, P < 0.0001). Bland-Altman analysis indicated no significant difference in hSDH and dSDH measurements. One-way ANOVA indicated that the mean hSDH measurement of the eyes with advanced AMD (n = 16) or with severe to very severe nonproliferative DR (NPDR) (n = 12) was significantly worse than that of the eyes with intermediate AMD (n = 11) or with mild to moderate NPDR (n = 11) (P < 0.0001). Ninety-eight percent of 46 patients (10 with AMD and 36 with DR) who completed the usability survey reported that the hSDH test was easy to use. This study demonstrated that the hSDH test on a mobile device is comparable to PC-based testing methods. As a mobile app, it is intuitive to use, readily accessible, and sensitive to the severity of maculopathy. It has the potential to provide patients having maculopathy with a new tool to monitor their vision at home.

The importance of optical coherence tomography examination of normal fellow eyes in neovascular age-related macular degeneration monitoring clinics

Purpose: To demonstrate the importance of OCT examination of fellow, normal eyes in unilateral nAMD follow up clinics. Methods: The authors present three cases of unilateral nAMD who were undergoing treatment with ranibizumab, in whom OCT evaluation of the previously unaffected, asymptomatic fellow eye allowed early diagnosis, treatment and preservation of vision. Fundus examination had previously failed to demonstrate abnormality. Results: Intravitreal anti-VEGF treatment for nAMD has caused a sharp increase in the number of subjects attending macular clinics, frequently overburdening the system. It may sometimes be tempting for hospitals to reduce the workload by for example, concentrating only on OCT examination of the affected eye in cases of unilateral nAMD. The three reported cases demonstrate that OCT scanning of the fellow, previously unaffected eye is essential in detecting asymptomatic nAMD, which gives a better chance of preservation of vision. Conclusions: Patients with unilateral neovascular AMD undergoing review in macular clinics should always undergo OCT scanning of normal, fellow eyes, as otherwise asymptomatic, “invisible” choroidal neovascular membranes may be missed.

Long-Term Monitoring of Age-Related Macular Degeneration with Preferential Hyperacuity Perimetry

To estimate the efficacy and usability of preferential hyper-acuity perimetry (PHP) for monitoring patients with high-risk intermediate age-related macular degeneration (AMD). A long-term, observational, prospective case series of patients with intermediate AMD who underwent fluorescein angiography at recruitment. Eyes were examined every 3 months with PHP, visual acuity, and biomicroscopy. Optical coherence tomography (OCT) imaging was performed when PHP was outside normal limits. In case of suspected findings in OCT, fluorescein angiography was also performed. Patients diagnosed as having choroidal neovascularization (CNV) were offered anti-vascular endothelial growth factor therapy. Twenty-six eyes (25 patients) were monitored for a mean follow-up period of 600 days. Of the 172 PHP tests done by these 26 eyes with intermediate AMD, 158 were within normal limits yielding a false-positive rate of 8.1%. Three of 4 eyes that converted to CNV had PHP test results outside normal limits before or on the day of diagnosis. PHP is useful for detecting CNV in regularly monitored eyes with intermediate AMD while maintaining a low false-positive rate.

Better Monitoring of Age-related Macular Degeneration with Preferential Hyperacuity Perimetry

Better Monitoring of Age-related Macular Degeneration with Preferential Hyperacuity Perimetry