Publications by authors named "Melissa Kasilian"

10 Publications

  • Page 1 of 1

Longitudinal Assessment of Remnant Foveal Cone Structure in a Case Series of Early Macular Telangiectasia Type 2.

Transl Vis Sci Technol 2020 03 30;9(4):27. Epub 2020 Mar 30.

Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Purpose: To determine the extent of remnant cone structure within early foveal ellipsoid zone (EZ) lesions in macular telangiectasia type 2 longitudinally using both confocal and split detector adaptive optics scanning light ophthalmoscopy (AOSLO).

Methods: Spectral domain optical coherence tomography (SDOCT), confocal and split detector AOSLO were acquired from seven patients (10 eyes) with small (early) EZ lesions on SDOCT secondary to macular telangiectasia type 2 at baseline, 6 months, and 12 months. The presence of cone structure on AOSLO in areas of EZ loss as well as cones at 1° eccentricity, and their change over time were quantified.

Results: By split detector AOSLO, remnant cone structure was identified within and on the borders of all foveal EZ lesions. Within the extent of these lesions, cone spacing ranged from 4.97 to 9.95 µm at baseline, 5.30 to 6.10 µm at 6 months, and 4.99 to 7.12 µm at 12 months. Four eyes with significantly smaller EZ lesions showed evidence of recovery of EZ reflectivity on SDOCT B-scans. Remnant cone structure was identified in some areas where EZ reflectivity recovered at the following time point. Eyes that showed recovery of EZ reflectivity had a continuous external limiting membrane.

Conclusions: Remnant cone structure can persist within small SDOCT-defined EZ lesions, which can wax and wane in appearance over time. AOSLO can help to inform the interpretation of SDOCT imaging.

Translational Relevance: The absence of EZ in early macular telangiectasia type 2 and other retinal conditions needs careful interpretation because it does not always indicate an absence of underlying cone structure. The integrity of the external limiting membrane may better predict the presence of remnant cone structure and recovery of EZ reflectivity.
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http://dx.doi.org/10.1167/tvst.9.4.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396184PMC
March 2020

Residual Cone Structure in Patients With X-Linked Cone Opsin Mutations.

Invest Ophthalmol Vis Sci 2018 08;59(10):4238-4248

University College London Institute of Ophthalmology, London, United Kingdom.

Purpose: To assess residual cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW opsin.

Methods: Thirteen males had their OPN1LW/OPN1MW opsin genes characterized. The cone mosaic was imaged using both confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO), and retinal thickness was evaluated using optical coherence tomography (OCT). Six subjects completed serial imaging over a maximum period of 18 months and cone density was measured across imaging sessions.

Results: Ten subjects had an OPN1LW/OPN1MW "interchange" opsin mutation designated as LIAVA or LVAVA, which both introduce exon 3 splicing defects leading to a lack of functional photopigment in cones expressing LIAVA and greatly reduced functional photopigment in cones expressing LVAVA. Despite disrupted cone reflectivity and reduced numerosity, residual inner segments could be visualized. Similar patterns were observed in individuals with an exon 2 insertion, or an exon 4 splice defect, both of which are also expected to produce cones that are devoid of functional opsin protein. OCT revealed variably reduced retinal thickness. A significant inverse relationship was found between the proportion of waveguiding cones and axial length.

Conclusions: Split-detection imaging revealed that the altered appearance of the cone mosaic in confocal images for subjects with exon 2, 3, and 4 mutations was generally due to disrupted waveguiding, rather than structural loss, making them possible candidates for gene therapy to restore cone function. The relative fraction of waveguiding cones was highly variable across subjects, which appears to influence emmetropization in these subjects.
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http://dx.doi.org/10.1167/iovs.18-24699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103386PMC
August 2018

Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy.

Ophthalmology 2018 05 6;125(5):735-746. Epub 2018 Jan 6.

Department of Genetics, University College London Institute of Ophthalmology, University College London, London, United Kingdom; Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom. Electronic address:

Purpose: To describe the earliest features of ABCA4-associated retinopathy.

Design: Case series.

Participants: Children with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy.

Methods: The retinal phenotype was characterized by color fundus photography, OCT, fundus autofluorescence (FAF) imaging, electroretinography, and in 2 patients, adaptive optics scanning laser ophthalmoscopy (AOSLO). Sequencing of the ABCA4 gene was performed in all patients.

Main Outcome Measures: Visual acuity, OCT, FAF, electroretinography, and AOSLO results.

Results: Eight children with ABCA4-associated retinopathy without macular atrophy were identified. Biallelic variants in ABCA4 were identified in all patients. Four children were asymptomatic, and 4 reported loss of VA. Patients were young (median age, 8.5 years; interquartile range, 6.8 years) with good visual acuity (median, 0.155 logarithm of the minimum angle of resolution [logMAR]; interquartile range, 0.29 logMAR). At presentation, the macula appeared normal (n = 3), had a subtly altered foveal reflex (n = 4), or demonstrated manifest fine yellow dots (n = 1). Fundus autofluorescence identified hyperautofluorescent dots in the central macula in 3 patients, 2 of whom showed a normal fundus appearance. Only 1 child had widespread hyperautofluorescent retinal flecks at presentation. OCT imaging identified hyperreflectivity at the base of the outer nuclear layer in all 8 patients. Where loss of outer nuclear volume was evident, this appeared to occur preferentially at a perifoveal locus. Longitudinal split-detector AOSLO imaging in 2 individuals confirmed that the greatest change in cone spacing occurred in the perifoveal, and not foveolar, photoreceptors. Electroretinography showed a reduced B-wave-to-A-wave ratio in 3 of 5 patients tested; in 2 children, recordings clearly showed electronegative results.

Conclusions: In childhood-onset ABCA4-associated retinopathy, the earliest stages of macular atrophy involve the parafovea and spare the foveola. In some cases, these changes are predated by tiny, foveal, yellow, hyperautofluorescent dots. Hyperreflectivity at the base of the outer nuclear layer, previously described as thickening of the external limiting membrane, is likely to represent a structural change at the level of the foveal cone nuclei. Electroretinography suggests that the initial site of retinal dysfunction may occur after phototransduction.
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http://dx.doi.org/10.1016/j.ophtha.2017.11.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5917070PMC
May 2018

CELLULAR IMAGING OF THE TAPETAL-LIKE REFLEX IN CARRIERS OF RPGR-ASSOCIATED RETINOPATHY.

Retina 2019 Mar;39(3):570-580

Moorfields Eye Hospital, London, United Kingdom.

Purpose: To examine the features of the tapetal-like reflex (TLR) in female carriers of RPGR-associated retinopathy by means of adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography.

Methods: Nine molecularly confirmed RPGR carriers and three healthy controls underwent ocular examination and the following retinal imaging modalities: color photography, near-infrared reflectance, fundus autofluorescence, spectral domain optical coherence tomography, and AOSLO. After identifying TLR areas across all imaging modalities, normalized local contrast of outer retinal bands on spectral domain optical coherence tomography was calculated and AOSLO-acquired photoreceptor mosaic analysis was performed.

Results: Seven carriers had TLR areas, which colocalized with increased rod photoreceptor reflectivity on confocal AOSLO and reduced cone photoreceptor densities. Parafoveal TLR areas also exhibited reduced local contrast (i.e., increased reflectivity) of the outer retinal bands on spectral domain optical coherence tomography (inner segment ellipsoid zone and outer segment interdigitation zone). Healthy controls did not show TLR.

Conclusion: The cellular resolution provided by AOSLO affords the characterization of the photoreceptor mosaic in RPGR carriers with a TLR. Features revealed include reduced cone density, increased cone inner segment diameter, and increased rod outer segment reflectivity.
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http://dx.doi.org/10.1097/IAE.0000000000001965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963958PMC
March 2019

Reliability and Repeatability of Cone Density Measurements in Patients With Stargardt Disease and RPGR-Associated Retinopathy.

Invest Ophthalmol Vis Sci 2017 07;58(9):3608-3615

UCL Institute of Ophthalmology, University College London, London, United Kingdom 2Moorfields Eye Hospital, London, United Kingdom.

Purpose: To assess reliability and repeatability of cone density measurements by using confocal and (nonconfocal) split-detector adaptive optics scanning light ophthalmoscopy (AOSLO) imaging. It will be determined whether cone density values are significantly different between modalities in Stargardt disease (STGD) and retinitis pigmentosa GTPase regulator (RPGR)-associated retinopathy.

Methods: Twelve patients with STGD (aged 9-52 years) and eight with RPGR-associated retinopathy (aged 11-31 years) were imaged using both confocal and split-detector AOSLO simultaneously. Four graders manually identified cone locations in each image that were used to calculate local densities. Each imaging modality was evaluated independently. The data set consisted of 1584 assessments of 99 STGD images (each image in two modalities and four graders who graded each image twice) and 928 RPGR assessments of 58 images (each image in two modalities and four graders who graded each image twice).

Results: For STGD assessments the reliability for confocal and split-detector AOSLO was 67.9% and 95.9%, respectively, and the repeatability was 71.2% and 97.3%, respectively. The differences in the measured cone density values between modalities were statistically significant for one grader. For RPGR assessments the reliability for confocal and split-detector AOSLO was 22.1% and 88.5%, respectively, and repeatability was 63.2% and 94.5%, respectively. The differences in cone density between modalities were statistically significant for all graders.

Conclusions: Split-detector AOSLO greatly improved the reliability and repeatability of cone density measurements in both disorders and will be valuable for natural history studies and clinical trials using AOSLO. However, it appears that these indices may be disease dependent, implying the need for similar investigations in other conditions.
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http://dx.doi.org/10.1167/iovs.17-21904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525557PMC
July 2017

Unsupervised identification of cone photoreceptors in non-confocal adaptive optics scanning light ophthalmoscope images.

Biomed Opt Express 2017 Jun 26;8(6):3081-3094. Epub 2017 May 26.

Translational Imaging Group, Centre for Medical Image Computing, UCL, Gower Street, WC1E 6BT, UK.

Precise measurements of photoreceptor numerosity and spatial arrangement are promising biomarkers for the early detection of retinal pathologies and may be valuable in the evaluation of retinal therapies. Adaptive optics scanning light ophthalmoscopy (AOSLO) is a method of imaging that corrects for aberrations of the eye to acquire high-resolution images that reveal the photoreceptor mosaic. These images are typically graded manually by experienced observers, obviating the robust, large-scale use of the technology. This paper addresses unsupervised automated detection of cones in non-confocal, split-detection AOSLO images. Our algorithm leverages the appearance of split-detection images to create a cone model that is used for classification. Results show that it compares favorably to the state-of-the-art, both for images of healthy retinas and for images from patients affected by Stargardt disease. The algorithm presented also compares well to manual annotation while excelling in speed.
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http://dx.doi.org/10.1364/BOE.8.003081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480451PMC
June 2017

OCT angiography in the management of choroidal neovascular membrane secondary to Sorsby fundus dystrophy.

BMJ Case Rep 2016 Sep 1;2016. Epub 2016 Sep 1.

Moorfields Eye Hospital NHS Foundation Trust, London, UK UCL Institute of Ophthalmology, London, UK.

We describe the management of a woman aged 52 years with molecularly confirmed Sorsby fundus dystrophy, who presented with acute visual deterioration in her right eye. Fundus examination identified a right macular lesion suggestive of a choroidal neovascular membrane (CNVM). Optical coherence tomography angiography (OCTA) confirmed the presence of a CNVM. She was treated with 2 monthly intravitreal injections of bevacizumab, associated with OCTA evidence of regression of the CNVM and improvement in her visual acuity. OCTA is a novel, non-invasive method of imaging the retinal vasculature. Images are acquired rapidly, with no associated side effects, offering advantages over the current gold standard technique-fundus fluorescein angiography.
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http://dx.doi.org/10.1136/bcr-2016-216453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020863PMC
September 2016

Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency.

Invest Ophthalmol Vis Sci 2016 07;57(8):3853-63

Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 9Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 10Department of Cell Biology, Neurobiology, & Anatomy, Medical Coll.

Purpose: Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction.

Methods: We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family.

Results: There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array.

Conclusions: Our findings provide a direct link between disruption of the cone mosaic and L/M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.
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http://dx.doi.org/10.1167/iovs.16-19608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968428PMC
July 2016

Comparison of Short-Wavelength Reduced-Illuminance and Conventional Autofluorescence Imaging in Stargardt Macular Dystrophy.

Am J Ophthalmol 2016 08 11;168:269-278. Epub 2016 Jun 11.

Moorfields Eye Hospital, London, United Kingdom; University College London, Institute of Ophthalmology, London, United Kingdom. Electronic address:

Purpose: To compare grading results between short-wavelength reduced-illuminance and conventional autofluorescence imaging in Stargardt macular dystrophy.

Design: Reliability study.

Methods: setting: Moorfields Eye Hospital, London (United Kingdom).

Patients: Eighteen patients (18 eyes) with Stargardt macular dystrophy.

Observation Procedures: A series of 3 fundus autofluorescence images using 3 different acquisition parameters on a custom-patched device were obtained: (1) 25% laser power and total sensitivity 87; (2) 25% laser power and freely adjusted sensitivity; and (3) 100% laser power and freely adjusted total sensitivity (conventional). The total area of 2 hypoautofluorescent lesion types (definitely decreased autofluorescence and poorly demarcated questionably decreased autofluorescence) was measured.

Main Outcome Measures: Agreement in grading between the 3 imaging methods was assessed by kappa coefficients (κ) and intraclass correlation coefficients.

Results: The mean ± standard deviation area for images acquired with 25% laser power and freely adjusted total sensitivity was 2.04 ± 1.87 mm(2) for definitely decreased autofluorescence (n = 15) and 1.86 ± 2.14 mm(2) for poorly demarcated questionably decreased autofluorescence (n = 12). The intraclass correlation coefficient (95% confidence interval) was 0.964 (0.929, 0.999) for definitely decreased autofluorescence and 0.268 (0.000, 0.730) for poorly demarcated questionably decreased autofluorescence.

Conclusions: Short-wavelength reduced-illuminance and conventional fundus autofluorescence imaging showed good concordance in assessing areas of definitely decreased autofluorescence. However, there was significantly higher variability between imaging modalities for assessing areas of poorly demarcated questionably decreased autofluorescence.
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http://dx.doi.org/10.1016/j.ajo.2016.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977015PMC
August 2016

Unilateral BEST1-Associated Retinopathy.

Am J Ophthalmol 2016 Sep 7;169:24-32. Epub 2016 Jun 7.

Moorfields Eye Hospital, London, United Kingdom; University College London Institute of Ophthalmology, London, United Kingdom. Electronic address:

Purpose: To describe a series of patients with molecularly confirmed mutation in BEST1 causing Best disease but with unilateral clinical manifestation.

Design: Retrospective observational case series.

Methods:

Setting: Moorfields Eye Hospital and Great Ormond Street Hospital, London (United Kingdom).

Patients: Five patients (10 eyes) with uniocular manifestation of BEST1 mutation causing Best disease were ascertained retrospectively from the clinical and genetic databases.

Main Outcome Measures: Patients had full ophthalmologic examination, color fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography, and detailed electrophysiological assessment. Genetic testing was performed.

Results: All cases had a clinical appearance typical of and consistent with Best disease at various stages, except that the presentation was unilateral. The reduced electrooculogram light rise was bilateral and in the context of normal electroretinograms therefore indicates generalized dysfunction at the level of the retinal pigment epithelium.

Conclusions: Mutation in BEST1 has variable penetrance and expressivity, and can be uniocular. The clinical and electrophysiological features described assist targeted mutational screening and alert to the potential diagnosis even when there is an atypical unilateral presentation.
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http://dx.doi.org/10.1016/j.ajo.2016.05.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016077PMC
September 2016
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