Avenell L. Chew

Semi-automated identification of cones in the human retina using circle Hough transform

A large number of human retinal diseases are characterized by a progressive loss of cones, the photoreceptors critical for visual acuity and color perception. Adaptive Optics (AO) imaging presents a potential method to study these cells in vivo. However, AO imaging in ophthalmology is a relatively new phenomenon and quantitative analysis of these images remains difficult and tedious using manual methods. This paper illustrates a novel semi-automated quantitative technique enabling registration of AO images to macular landmarks, cone counting and its radius quantification at specified distances from the foveal center. The new cone counting approach employs the circle Hough transform (cHT) and is compared to automated counting methods, as well as arbitrated manual cone identification. We explore the impact of varying the circle detection parameter on the validity of cHT cone counting and discuss the potential role of using this algorithm in detecting both cones and rods separately.

The use of microperimetry to detect functional progression in non-neovascular age-related macular degeneration: A systematic review

Abstract: We reviewed the current literature on the ability of microperimetry to detect non‐neovascular age‐related macular degeneration (AMD) disease progression. The index test was retinal sensitivity measurement assessed by microperimetry and comparators were other functional measures (best‐corrected and low‐luminance visual acuities, and fixation stability) and structural parameters [retinal thickness, choroidal thickness, and area of geographic atrophy (GA) determined by color fundus photographs, short‐wave or near‐infrared fundus autofluorescence]. The reference standard was area of GA. The literature search was conducted in January 2016 and included MEDLINE, EMBASE, the Cochrane Library, Biosis, Science Citation Index, ProQuest Health and Medicine, CINAHL, and Highwire Press. We included 6 studies that enrolled 41 eyes with intermediate AMD (from a single study) and 80 eyes with GA secondary to AMD. Retinal sensitivity measured by microperimetry was the only functional measure that consistently detected progression in each cohort. Insufficient reported data precluded meta‐analysis. Various microperimetry parameters were used to assess cohort‐level change in retinal sensitivity, but the methods of analysis have yet to mature in complexity in comparison with established glaucoma field progression analysis. Microperimetry‐assessed retinal sensitivity measurement may be more sensitive in detecting progression than other functional measures in non‐neovascular AMD. However, the lack of standardized testing protocol and methods of progression analysis hindered comparison. Harmonization of testing protocol and development of more robust methods of analyzing raw microperimetric data will facilitate clinical implementation of this valuable retinal assessment tool.

Enhanced visualization of subtle outer retinal pathology by en face optical coherence tomography and correlation with multi-modal imaging

Purpose To present en face optical coherence tomography (OCT) images generated by graph-search theory algorithm-based custom software and examine correlation with other imaging modalities. Methods En face OCT images derived from high density OCT volumetric scans of 3 healthy subjects and 4 patients using a custom algorithm (graph-search theory) and commercial software (Heidelberg Eye Explorer software (Heidelberg Engineering)) were compared and correlated with near infrared reflectance, fundus autofluorescence, adaptive optics flood-illumination ophthalmoscopy (AO-FIO) and microperimetry. Results Commercial software was unable to generate accurate en face OCT images in eyes with retinal pigment epithelium (RPE) pathology due to segmentation error at the level of Bruch’s membrane (BM). Accurate segmentation of the basal RPE and BM was achieved using custom software. The en face OCT images from eyes with isolated interdigitation or ellipsoid zone pathology were of similar quality between custom software and Heidelberg Eye Explorer software in the absence of any other significant outer retinal pathology. En face OCT images demonstrated angioid streaks, lesions of acute macular neuroretinopathy, hydroxychloroquine toxicity and Bietti crystalline deposits that correlated with other imaging modalities. Conclusions Graph-search theory algorithm helps to overcome the limitations of outer retinal segmentation inaccuracies in commercial software. En face OCT images can provide detailed topography of the reflectivity within a specific layer of the retina which correlates with other forms of fundus imaging. Our results highlight the need for standardization of image reflectivity to facilitate quantification of en face OCT images and longitudinal analysis.

Fundus autofluorescence in rubella retinopathy: Correlation with photoreceptor structure and function

Purpose: To illustrate altered fundus autofluorescence in rubella retinopathy and to investigate their relationships with photoreceptor structure and function using multimodal imaging. Methods: The authors report four cases of rubella retinopathy aged 8, 33, 42, and 50 years. All patients had dilated clinical fundus examination; wide-field color photography; blue, green, and near-infrared autofluorescence imaging and spectral domain optical coherence tomography. Two patients also underwent microperimetry and adaptive optics imaging. En face optical coherence tomography, cone mosaic, and microperimetry were coregistered with autofluorescence images. The authors explored the structure–function correlation. Results: All four patients had a “salt-and-pepper” appearance on dilated fundus examination and wide-field color photography. There were variable-sized patches of hypoautofluorescence on both blue and near-infrared excitation in all four patients. Wave-guiding cones were visible and retinal sensitivity was intact over these regions. There was no correlation between hypoautofluorescence and regions of attenuated ellipsoid and interdigitation zones. Hyperautofluorescent lesions were also noted and some of these were pseudo-vitelliform lesions. Conclusion: Patchy hypoautofluorescence on near-infrared excitation can be a feature of rubella retinopathy. This may be due to abnormal melanin production or loss of melanin within retinal pigment epithelium cells harboring persistent rubella virus infection. Preservation of the ellipsoid zone, wave-guiding cones, and retinal sensitivity within hypoautofluorescent lesions suggest that these retinal pigment epithelium changes have only mild impact on photoreceptor cell function.

Agreement in Cone Density Derived from Gaze-Directed Single Images Versus Wide-Field Montage Using Adaptive Optics Flood Illumination Ophthalmoscopy

Purpose We compared cone density measurements derived from the center of gaze-directed single images with reconstructed wide-field montages using the rtx1 adaptive optics (AO) retinal camera. Methods A total of 29 eyes from 29 healthy subjects were imaged with the rtx1 camera. Of 20 overlapping AO images acquired, 12 (at 3.2°, 5°, and 7°) were used for calculating gaze-directed cone densities. Wide-field AO montages were reconstructed and cone densities were measured at the corresponding 12 loci as determined by field projection relative to the foveal center aligned to the foveal dip on optical coherence tomography. Limits of agreement in cone density measurement between single AO images and wide-field AO montages were calculated. Results Cone density measurements failed in 1 or more gaze directions or retinal loci in up to 58% and 33% of the subjects using single AO images or wide-field AO montage, respectively. Although there were no significant overall differences between cone densities derived from single AO images and wide-field AO montages at any of the 12 gazes and locations (P = 0.01–0.65), the limits of agreement between the two methods ranged from as narrow as −2200 to +2600, to as wide as −4200 to +3800 cones/mm2. Conclusions Cone density measurement using the rtx1 AO camera is feasible using both methods. Local variation in image quality and altered visibility of cones after generating montages may contribute to the discrepancies. Translational Relevance Cone densities from single AO images are not interchangeable with wide-field montage derived–measurements.

Acute progressive paravascular placoid neuroretinopathy with negative-type electroretinography in paraneoplastic retinopathy

PurposeParaneoplastic retinopathy can be the first manifestation of systemic malignancy. A subset of paraneoplastic retinopathy is characterized by negative-type electroretinography (ERG) without fundus abnormality. Here we describe the multimodal imaging and clinico-pathological correlation of a unique case of acute progressive paravascular placoid neuroretinopathy with suspected retinal depolarizing bipolar cell dysfunction preceding the diagnosis of metastatic small cell carcinoma of the prostate.MethodsERG was performed according to the International Society for Clinical Electrophysiology of Vision standards. Imaging modalities included near-infrared reflectance, blue-light autofluorescence, fluorescein and indocyanine green angiographies, spectral domain optical coherence tomography, ultra-widefield colour and green-light autofluorescence imaging, microperimetry and adaptive optics imaging. Patient serum was screened for anti-retinal antibodies using western blotting. Immunostaining and histological analyses were performed on sections from human retinal tissues and a patient prostate biopsy.ResultsSerial multimodal retinal imaging, microperimetry and adaptive optics photography demonstrated a paravascular distribution of placoid lesions characterized by hyper-reflectivity within the outer nuclear layer resembling type 2 acute macular neuroretinopathy. There was no visible lesion within the inner nuclear layer despite electronegative-type ERG. Six months later, the patient presented with metastatic small cell carcinoma of the prostate. Tumour cells were immunopositive for glyceraldehyde-3-phosphate dehydrogenase, enolase and recoverin as well as neuroendocrine markers. The patient’s serum reacted to cytoplasmic and nuclear antigens in the prostate biopsy and in human retina. Anti-retinal antibodies against several antigens were detected by both commercial and in-house western blots.ConclusionsA spectrum of autoreactive anti-retinal antibodies is associated with a unique phenotype of acute progressive paravascular placoid neuroretinopathy resulting in degeneration of photoreceptor cells, inner retinal dysfunction and classic electronegative ERG in paraneoplastic retinopathy. Detailed clinical, functional and immunological phenotyping of paraneoplastic retinopathy illustrated the complex mechanism of paraneoplastic syndrome.

Structure-function correlation and natural history of accidental juxtafoveal injury from a 250 milliwatt recreational hand-held green laser device.

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