Papers by Denise Cunningham
Fundus Photography
CRC Press eBooks, Jun 24, 2024
Basic Photography
CRC Press eBooks, Jun 24, 2024
Digital Photography Assessment of Ocular Surface Vital Dye Staining
Investigative Ophthalmology & Visual Science, May 14, 2008

Detection of anomaly in human retina using Laplacian Eigenmaps and vectorized matched filtering
Proceedings of SPIE, Mar 20, 2015
We present a novel method for automated anomaly detection on auto fluorescent data provided by th... more We present a novel method for automated anomaly detection on auto fluorescent data provided by the National Institute of Health (NIH). This is motivated by the need for new tools to improve the capability of diagnosing macular degeneration in its early stages, track the progression over time, and test the effectiveness of new treatment methods. In previous work, macular anomalies have been detected automatically through multiscale analysis procedures such as wavelet analysis or dimensionality reduction algorithms followed by a classification algorithm, e.g., Support Vector Machine. The method that we propose is a Vectorized Matched Filtering (VMF) algorithm combined with Laplacian Eigenmaps (LE), a nonlinear dimensionality reduction algorithm with locality preserving properties. By applying LE, we are able to represent the data in the form of eigenimages, some of which accentuate the visibility of anomalies. We pick significant eigenimages and proceed with the VMF algorithm that classifies anomalies across all of these eigenimages simultaneously. To evaluate our performance, we compare our method to two other schemes: a matched filtering algorithm based on anomaly detection on single images and a combination of PCA and VMF. LE combined with VMF algorithm performs best, yielding a high rate of accurate anomaly detection. This shows the advantage of using a nonlinear approach to represent the data and the effectiveness of VMF, which operates on the images as a data cube rather than individual images.
Ophthalmic Plastic and Reconstructive Surgery, Sep 1, 1994

Quantitative analysis of longitudinal changes in multimodal imaging of Late-Onset Retinal Degeneration
Investigative Ophthalmology & Visual Science, Jun 10, 2020
PURPOSE To quantitatively analyze clinically relevant features on longitudinal multimodal imaging... more PURPOSE To quantitatively analyze clinically relevant features on longitudinal multimodal imaging of L-ORD (late-onset retinal degeneration) to characterize disease progression. METHODS Fundus autofluorescence (FAF), infrared reflectance (IR), and optical coherence tomography (OCT) imaging of 4 L-ORD patients were acquired over 3-15 years (20 visits total). Corresponding regions-of-interest were analyzed on FAF (reticular pseudodrusen (RPD), "speckled FAF", and chorioretinal atrophy) and IR (hyporeflective RPD and target RPD) using quantitative measurements including contour area, distance to fovea, contour overlap, retinal thickness, and texture features. RESULTS Cross-sectional analysis revealed moderate correlation (RPD FAF ∩ RPD IR = 63%) between contour area across modalities. Quantification of retina thickness and texture analysis of areas contoured on FAF objectively differentiated the contour types. Longitudinal analysis of aligned images demonstrates that the contoured region of atrophy both encroaches toward the fovea and grows monotonically with a rate of 0.531-1.969 mm/year (square root of area, n=5 eyes). A retrospective analysis of precursor lesions of atrophy reveals quantifiable progression from RPD to speckled FAF to atrophy. CONCLUSIONS Image analysis of timepoints prior to the development of atrophy reveals consistent patterns over time and space in L-ORD that may provide useful outcomes for L-ORD and other degenerative retinal diseases.
Clinical Ocular Photography
... Marge rarely missed a vein during fluorescein angiography, Mary rarely missed an opportunity ... more ... Marge rarely missed a vein during fluorescein angiography, Mary rarely missed an opportunity to be kind, and Jean rarely missed an interesting ... When Maureen Hargaden, VMD, ACLAM, a doctor of veterinary medicine, and I worked together for a few months on her research ...

American Journal of Ophthalmology, Sep 1, 2013
Purpose-To investigate the association of spontaneous drusen regression in intermediate agerelate... more Purpose-To investigate the association of spontaneous drusen regression in intermediate agerelated macular degeneration (AMD) with changes on fundus photography and fundus autofluorescence (FAF) imaging. Methods-Fundus images from 58 eyes (in 58 patients) with intermediate AMD and large drusen were assessed over 2 years for areas of drusen regression which exceeded the area of circle C1 (diameter 125μm; Age-Related Eye Disease Study grading protocol). Manual segmentation and computer-based image analysis were used to detect and delineate areas of drusen regression. Delineated regions were graded as to their appearance on fundus photographs and FAF images, and changes in FAF signals were graded manually and quantitated using automated image analysis. Results-Drusen regression was detected in approximately half of study eyes using manual (48%) and computer-assisted (50%) techniques. At year 2, the clinical appearance of areas of drusen regression on fundus photography was mostly unremarkable, with a majority of eyes (71%) demonstrating no detectable clinical abnormalities, and the remainder (29%) showing minor pigmentary changes. However, drusen regression areas were associated with local changes in FAF

Retina-the Journal of Retinal and Vitreous Diseases, Dec 1, 2016
Purpose-To characterize longitudinal structural changes in early stages of late-onset retinal deg... more Purpose-To characterize longitudinal structural changes in early stages of late-onset retinal degeneration (L-ORD) to investigate pathogenic mechanisms. Methods-Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence (FAF) images, near infrared reflectance (NIR-R) fundus images, and spectral domain optical coherence tomography (SD-OCT) scans were acquired during follow-up. Results-Both patients, aged 45 and 50 years, had good visual acuities (> 20/20 OU) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellowwhite, punctate lesions in the temporal macula that correlated with a reticular pattern on FAF and NIR-R imaging. Baseline SD-OCT imaging revealed subretinal deposits that resemble reticular pseudodrusen (RPD) described in age-related macular degeneration (AMD). During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial (RPE) layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt RPE and outer retinal atrophy. Conclusions-Structural changes in early stage L-ORD revealed by multimodal imaging resemble those of RPD observed in AMD and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.

American journal of ophthalmology, Jan 16, 2015
To identify factors associated with best-corrected visual acuity (BCVA) presentation and two-year... more To identify factors associated with best-corrected visual acuity (BCVA) presentation and two-year outcome in 479 intermediate, posterior, and panuveitic eyes. Cohort study using randomized controlled trial data METHODS: Multicenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and 2 years' follow-up used gold standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and two-year change in BCVA. Baseline factors significantly associated with reduced BCVA included: age≥50 vs. <50 years; posterior vs. intermediate uveitis; uveitis duration>10 vs. <6 years; anterior chamber (AC) flare>grade 0; cataract; macular thickening; and exudative retinal detachment. Over two years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (p=0.52) and 10 letters (p<0.001) respectively. Both treatment groups and all sit...

Detection of anomaly in human retina using Laplacian Eigenmaps and vectorized matched filtering
SPIE Proceedings, 2015
We present a novel method for automated anomaly detection on auto fluorescent data provided by th... more We present a novel method for automated anomaly detection on auto fluorescent data provided by the National Institute of Health (NIH). This is motivated by the need for new tools to improve the capability of diagnosing macular degeneration in its early stages, track the progression over time, and test the effectiveness of new treatment methods. In previous work, macular anomalies have been detected automatically through multiscale analysis procedures such as wavelet analysis or dimensionality reduction algorithms followed by a classification algorithm, e.g., Support Vector Machine. The method that we propose is a Vectorized Matched Filtering (VMF) algorithm combined with Laplacian Eigenmaps (LE), a nonlinear dimensionality reduction algorithm with locality preserving properties. By applying LE, we are able to represent the data in the form of eigenimages, some of which accentuate the visibility of anomalies. We pick significant eigenimages and proceed with the VMF algorithm that classifies anomalies across all of these eigenimages simultaneously. To evaluate our performance, we compare our method to two other schemes: a matched filtering algorithm based on anomaly detection on single images and a combination of PCA and VMF. LE combined with VMF algorithm performs best, yielding a high rate of accurate anomaly detection. This shows the advantage of using a nonlinear approach to represent the data and the effectiveness of VMF, which operates on the images as a data cube rather than individual images.

American journal of ophthalmology, Jan 31, 2015
To describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treat... more To describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treatment (MUST) Trial. Randomized clinical trial with extended follow-up. Review of data collected on the first implant in the eye(s) of participants. Dissociation was defined as the drug pellet no longer being affixed to the strut and categorized as spontaneous or surgically-related. 250 eyes (146 patients) had at least one implant placed. Median time follow-up time after implant placement was 6 years (range 0.5 to 9.2). Thirty-four dissociations were reported in 30 participants. There were 22 spontaneous events in 22 participants; 6-year cumulative risk of a spontaneous dissociation was 4.8% (95% confidence interval (CI): 2.4%-9.1%). The earliest event occurred 4.8 years after placement. Nine of 22 eyes with data had a decline in visual acuity >5 letters temporally related to the dissociation. 39 implant removal surgeries were performed, 33 with replacement. Twelve dissociations were no...

Progression of Pseudovitelliform Macular Dystrophy
Archives of Ophthalmology, Mar 1, 1984
Pseudovitelliform macular dystrophy is a dominantly inherited macular disorder. It is characteriz... more Pseudovitelliform macular dystrophy is a dominantly inherited macular disorder. It is characterized by the presence of horizontally oval yellowish deposits within the maculas that are approximately one-third disc diameter in size. As classically described, progression of the lesions over a follow-up period of as long as six years has not been described and the prognosis for retention of good visual function is excellent. We report the ophthalmoscopic appearance of six eyes of three patients from a very subtle alteration of macular pigmentation to severe disruption of macular architecture, and demonstrate in one of our patients drastic deterioration in both ophthalmoscopic appearance and visual function over a three-year period of follow-up. The prognosis for retention of good vision in this disorder must include the possibility of the eventual development of severe visual impairment.
American Journal of Ophthalmology, Jul 1, 1994
Ophthalmic Plastic and Reconstructive Surgery, Dec 1, 1996

Archives of Ophthalmology, Feb 1, 2012
Objective-Changing lipofuscin and melanin content in RPE cells has been hypothesized to contribut... more Objective-Changing lipofuscin and melanin content in RPE cells has been hypothesized to contribute to Stargardt disease pathogenesis. Longitudinal study of autofluorescence in Stargardt disease which reflect changing fluorophore compositions can reveal aspects of disease progression not previously evident. Method-We examined the temporal-spatial patterns of fundus autofluorescence with excitation at both 488 nm (standard fundus autofluorescence, FAF) and 795nm (near infrared autofluorescence, NIA) in a longitudinal case series involving 8 eyes of 4 patients (range of follow-up = 11 to 57 months; mean = 39 months). Image processing was performed to analyze spatial and temporal cross-modality associations. Results-Longitudinal FAF imaging of fleck lesions revealed hyperautofluorescent lesions that extended in a centrifugal direction from the fovea with time. Patterns of spread were non-random and followed a radial path that leaves behind a trail of diminishing autofluorescence. Longitudinal NIA imaging also demonstrated centrifugal lesion spread, but with fewer hyperautofluorescent lesions, suggestive of more transient hyperautofluorescence and more rapid decay at longer wavelengths. FAF and NIA abnormalities were spatially correlated to each other, and together reflect systematic progressions in fleck distribution and fluorophore composition occurring during the natural history of the disease. Conclusion-Stargardt disease fleck lesions do not evolve randomly in location but instead follow consistent patterns of radial expansion and a systematic decay of autofluorescence that reflect changing lipofuscin and melanin compositions in RPE cells. These progressive foveal-toperipheral changes are helpful in elucidating molecular and cellular mechanisms underlying Stargardt disease and may constitute potential outcome measures in clinical trials.
A Novel Imaging Analysis Method to Quantify Fleck Area in ABCA4 Retinopathy
Investigative Ophthalmology & Visual Science, Jul 22, 2019
The National Eye Institute Prospective ABCA4 Retinopathy Natural History Study: Two Year Imaging Analysis
Investigative Ophthalmology & Visual Science, Jun 23, 2017
Validation study for an image-based standardized grading system for scleritis
Investigative Ophthalmology & Visual Science, Sep 26, 2016
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Papers by Denise Cunningham