Autofluorescence of choroidal vessels in Bietti’s crystalline dystrophy

ObjectiveTo describe the pattern of fundus autofluorescence (FAF) in Bietti’s crystalline dystrophy (BCD).Methods and analysisFrom the National Institutes of Health EyeGene database of 2769 patients with known pathogenic mutations, 5 patients with BCD-causing CYP4V2 mutations who had FAF images were selected. Demographic and genetic information and imaging files were obtained. From the FAF imaging files, unique autofluorescence (AF) patterns and correlation with retinal structures were assessed by three investigators for clinical significance.ResultsFive patients (four males, one female; mean age 56 years, range 42–76 years) were included, all with different CYP4V2 mutations. All patients displayed varying degrees of hypo-AF in the posterior pole. In four out of five patients, there was a relative hyper-AF of choroidal vessels within the hypo-AF area; this feature was limited to sclerotic vessels only. A transitional zone of speckled AF was visible around the hypo-AF area. This zone corresponded to the area containing retinal crystals on colour fundus photography; however, retinal crystals did not demonstrate hyper or hypo-AF.ConclusionsThis study presents a previously unreported characteristic finding in patients with BCD with CYP4V2 mutations. AF of choroidal vessels may aid in differentiating BCD from other retinal dystrophies.

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Choroidal congestion mouse model: Could it serve as a pachychoroid model?

PLoS ONE ◽

10.1371/journal.pone.0246115 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0246115

Author(s):

Hidetaka Matsumoto ◽

Ryo Mukai ◽

Junki Hoshino ◽

Mai Oda ◽

Toshiyuki Matsuzaki ◽

...

Keyword(s):

Mouse Model ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Posterior Pole ◽

Fundus Photography ◽

Control Group ◽

Choroidal Thickening ◽

Tissue Sections ◽

Vortex Vein ◽

Choroidal Vessels

Pachychoroid spectrum diseases have been described as a new clinical entity within the spectrum of macular disorders. “Pachychoroid” is defined as choroidal thickening associated with dilated outer choroidal vessels often showing retinal pigment epithelium (RPE) degeneration. Although various clinical studies on the pachychoroid spectrum diseases have been conducted, the pathophysiology of pachychoroid has yet to be fully elucidated. In this study, we attempted to establish a mouse model of pachychoroid. We sutured vortex veins in eyes of wild type mice to imitate the vortex vein congestion in pachychoroid spectrum diseases. Fundus photography and ultra-widefield indocyanine green angiography showed dilated vortex veins from the posterior pole to the ampulla in eyes after induction of choroidal congestion. Optical coherence tomography and tissue sections presented choroidal thickening with dilatation of choroidal vessels. The RPE-choroid/retina thickness ratios on the tissue sections in the treated day 1 and day 7 groups were significantly greater than that in the control group (0.19±0.03 and 0.16±0.01 vs. 0.12±0.02, P<0.05 each). Moreover, immunohistochemistry using RPE flatmount revealed focal RPE degeneration in the treated eyes. Furthermore, inflammatory response-related genes were upregulated in eyes with choroidal congestion induction, and macrophages migrated into the thickened choroid. These results indicated that vortex vein congestion triggered some pachychoroid features. Thus, we have established a choroidal congestion mouse model by suturing vortex veins, which would potentially be useful for investigating the pathophysiology of pachychoroid spectrum diseases.

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Genotypes Predispose Phenotypes—Clinical Features and Genetic Spectrum of ABCA4-Associated Retinal Dystrophies

Genes ◽

10.3390/genes11121421 ◽

2020 ◽

Vol 11 (12) ◽

pp. 1421

Author(s):

Yu-Chi Sung ◽

Chang-Hao Yang ◽

Chung-May Yang ◽

Chao-Wen Lin ◽

Ding-Siang Huang ◽

...

Keyword(s):

Visual Acuity ◽

Retinal Degeneration ◽

Medical Center ◽

Fundus Autofluorescence ◽

Genetic Diagnosis ◽

Common Disease ◽

Genetic Characteristics ◽

Retinal Dystrophies ◽

High Prevalence ◽

Abca4 Gene

The ABCA4 gene is one of the most common disease-causing genes of inherited retinal degeneration. In this study, we report different phenotypes of ABCA4-associated retinal dystrophies in the Taiwanese population, its clinical progression, and its relationship with genetic characteristics. Thirty-seven subjects were recruited and all patients underwent serial ophthalmic examinations at a single medical center. Fundus autofluorescence (FAF) images were quantified for clinical evaluation, and panel-based next-generation sequencing testing was performed for genetic diagnosis. Visual preservation, disease progression, and genotype–phenotype correlation were analyzed. In this cohort, ABCA4-associated retinal degeneration presented as Stargardt disease 1 (STGD1, 62.16%), retinitis pigmentosa (32.43%), and cone-rod dystrophy (5.41%). STGD1 could be further divided into central and dispersed types. In each phenotype, the lesion areas quantified by FAF increased with age (p < 0.01) and correlated with poorer visual acuity. However, three patients had the foveal sparing phenotype and had relatively preserved visual acuity. Forty-two ABCA4 variants were identified as disease-causing, with c.1804C>T (p.Arg602Trp) the most frequent (37.84%). Patients with a combination of severe/null variants could have more extensive phenotypes, such as arRP and dispersed STGD1. This is the first cohort study of ABCA4-associated retinal degeneration in Taiwan with wide spectrums of both genotypic and phenotypic characteristics. An extremely high prevalence of c.1804C>T, which has not been reported in East Asia before, was noted. The extensiveness of retinal involvement might be regarded as a spectrum of ABCA4-associated retinal dystrophies. Different types of genetic variations could lead to distinctive phenotypes, according to the coding impact of variants.

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Structural evaluation in inherited retinal diseases

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319228 ◽

2021 ◽

pp. bjophthalmol-2021-319228

Author(s):

Malena Daich Varela ◽

Burak Esener ◽

Shaima A Hashem ◽

Thales Antonio Cabral de Guimaraes ◽

Michalis Georgiou ◽

...

Keyword(s):

Adaptive Optics ◽

Fundus Autofluorescence ◽

Standard Of Care ◽

Laser Speckle ◽

Fundus Photography ◽

Laser Speckle Flowgraphy ◽

Retinal Diseases ◽

Autofluorescence Imaging ◽

Structural Evaluation ◽

Fundus Imaging

Ophthalmic genetics is a field that has been rapidly evolving over the last decade, mainly due to the flourishing of translational medicine for inherited retinal diseases (IRD). In this review, we will address the different methods by which retinal structure can be objectively and accurately assessed in IRD. We review standard-of-care imaging for these patients: colour fundus photography, fundus autofluorescence imaging and optical coherence tomography (OCT), as well as higher-resolution and/or newer technologies including OCT angiography, adaptive optics imaging, fundus imaging using a range of wavelengths, magnetic resonance imaging, laser speckle flowgraphy and retinal oximetry, illustrating their utility using paradigm genotypes with on-going therapeutic efforts/trials.

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Establishing the Diagnosis

Retinal Detachment ◽

10.1093/oso/9780195330823.003.0009 ◽

2009 ◽

Author(s):

Daniel A. Brinton ◽

Charles P. Wilkinson

Keyword(s):

Retinal Detachment ◽

Posterior Pole ◽

Peripheral Retina ◽

Retinal Breaks ◽

Yellow Color ◽

Red Color ◽

The Central Nervous System ◽

Retinal Artery ◽

Ciliary Artery ◽

Choroidal Vessels

The differential diagnosis of rhegmatogenous retinal detachment includes secondary (nonrhegmatogenous) retinal detachment and other entities that may simulate a retinal detachment. Nonrhegmatogenous detachments are categorized as exudative (serous) and tractional detachments. Conditions that may be mistaken for retinal detachment include retinoschisis, choroidal detachment or tumors, and vitreous membranes. Sometimes benign findings in the peripheral retina are mistaken for retinal breaks. The most prominent feature of the fundus is the optic nerve head or disc, the only place in the human body that affords a direct view of a tract of the central nervous system. The foveola, the functional center of the fundus, is located in the center of the fovea, which has a diameter of about 5°. The macula is centered on the fovea and has a diameter of about 17°. The multiple branches of the central retinal artery are readily identifi ed by their bright red color and relatively narrow caliber. The multiple tributaries of the central retinal vein are recognized by their dark red color and relatively wider caliber. In a darkly pigmented fundus, the choroidal vessels in the posterior pole can be obscured from view, but in an eye with minimal pigment, they are readily visible. The venous tributaries of the choroid that make up the vortex veins are usually easily seen. The most prominent features of the choroidal venous system are the vortex ampullae, of which there are usually four (but sometimes more). They are located approximately in the 1-, 5-, 7-, and 11-o’clock meridians, just posterior to the equator. The horizontal meridians are usually identifiable by their radially oriented, long posterior ciliary nerves, and infrequently the long posterior ciliary artery can be seen adjacent to the nerve. The nerve is relatively broad and has a yellow color, and the artery is identifiable by its red color. The artery is usually inferior to the nerve temporally, and superior to it nasally (Figure 5–1).

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Tele-glaucoma versus clinical evaluation: The New Jersey Health Foundation Prospective Clinical Study

Journal of Telemedicine and Telecare ◽

10.1177/1357633x19845273 ◽

2019 ◽

Vol 26 (9) ◽

pp. 536-544 ◽

Cited By ~ 1

Author(s):

Subhashini Chandrasekaran ◽

William Kass ◽

Loka Thangamathesvaran ◽

Nicole Mendez ◽

Peter Khouri ◽

...

Keyword(s):

Pearson Correlation ◽

Corneal Thickness ◽

Correlation Coefficients ◽

Retinal Nerve Fibre Layer ◽

Posterior Pole ◽

Fundus Photography ◽

Prospective Clinical Study ◽

Ganglion Cell Complex ◽

Complex Data ◽

A Prospective Study

Introduction Glaucoma, the second most common cause of blindness, is normally detected in clinic. With technological improvements, tele-glaucoma exams can identify these changes off-site. The quality of tele-glaucoma exams needs to be compared with that of traditional exams. This study’s purpose was to validate the tele-glaucoma programme, which allows a physician comprehensive access to patients’ data, by comparing results to clinical examinations. Methods A prospective study of 107 subjects evaluated in clinic and then tele-glaucoma stations, which consisted of non-mydriatic fundus photography, puff-tonometry, auto-refraction and Optical Coherence Tomography (OCT). The OCT captured central corneal thickness, angle anatomy, cup-to-disc ratio (CDR), retinal nerve fibre layer distribution and posterior-pole ganglion cell complex data. Results Intraocular pressure (IOP) comparisons between clinical and tele-glaucoma exams had strong positive Pearson correlation coefficients (0.8248 OD, 0.8672 OS). Strong positive correlations were seen for CDR (0.7835 OD, 0.8082 OS) as well as diagnosis (glaucoma, no glaucoma or glaucoma suspect). A moderate positive correlation was seen for return to clinic time (RTC). Tele-glaucoma had an average lower RTC (2.7 vs 3.9 months). Tele-glaucoma was more likely to elicit a non-glaucomatous diagnosis not found in clinic vs a diagnosis found only in clinic (18% vs 5% of subjects). Discussion Tele-glaucoma allows for detecting glaucoma remotely. These advancements alleviate patient difficulties with obtaining adequate glaucoma screenings and helps ophthalmologists triage patients with more severe pathology. Our study indicates that our tele-glaucoma protocol is comparable to a clinical exam in its ability to detect glaucoma. Further studies will be needed for off-site testing and transferring data separately for analysis.

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Idiopathic Acute Exudative Polymorphous Vitelliform Maculopathy: Insight into Imaging Features and Outcomes

Case Reports in Ophthalmological Medicine ◽

10.1155/2020/7254038 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Sónia Torres-Costa ◽

Susana Penas ◽

Ângela Carneiro ◽

Renato Santos-Silva ◽

Rodolfo Moura ◽

...

Keyword(s):

Complete Resolution ◽

Indocyanine Green Angiography ◽

Fundus Autofluorescence ◽

Correct Diagnosis ◽

Posterior Pole ◽

Imaging Features ◽

Corrected Visual Acuity ◽

Blurry Vision ◽

One Year ◽

Insight Into

The authors describe imagiological findings in idiopathic exudative polymorphous vitelliform maculopathy. A 41-year-old woman complained of bilateral blurry vision. Best-corrected visual acuity was 20/20 bilaterally. Bilateral small serous neurosensory detachments in the fovea were seen at fundoscopy and confirmed by spectral-domain optical coherence tomography. Fluorescein angiography was unremarkable. Indocyanine green angiography presented discrete hyperfluorescent spots on the posterior pole. Later, more bleb-like lesions with a vitelliform appearance and hyperautofluorescent on blue fundus autofluorescence were detected. One year later, a complete resolution of the fluid was observed. To conclude, multimodal evaluation of patients with idiopathic exudative polymorphous vitelliform maculopathy is essential for the correct diagnosis of this disease.

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Microglia dynamics in retinitis pigmentosa model: formation of fundus whitening and autofluorescence as an indicator of activity of retinal degeneration

Scientific Reports ◽

10.1038/s41598-020-71626-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Kenichi Makabe ◽

Sunao Sugita ◽

Michiko Mandai ◽

Yoko Futatsugi ◽

Masayo Takahashi

Keyword(s):

Retinitis Pigmentosa ◽

Retinal Degeneration ◽

Outer Nuclear Layer ◽

Fundus Autofluorescence ◽

Fundus Photography ◽

Photoreceptor Outer Segments ◽

Diagnostic Interpretation ◽

Model Formation ◽

Thinning Rate

Abstract In patients with retinitis pigmentosa (RP), color fundus photography and fundus autofluorescence (FAF) have been used to estimate the disease progression. To understand the origin and the diagnostic interpretation of the fundus color and FAF, we performed in vivo imaging of fundus color and FAF together with histological analyses of the retinal degeneration process using the RP model mice, rd10. FAF partly represented the accumulation of microglia in the photoreceptor outer segments. Fundus whitening suggested the presence of apoptotic cells, which spatiotemporally preceded increase in FAF. We observed two patterns of FAF localization, arcuate and diffuse, each indicating different pattern of apoptosis, wavy and diffuse, respectively. Diffuse pattern of apoptosis was suppressed in dark-raised rd10 mice, in which outer nuclear layer (ONL) loss was significantly suppressed. The occupancy of FAF correlated with the thinning rate of the ONL. Fractalkine, a microglia chemotactic factor, was detected in apoptotic photoreceptors, suggesting chemokine-induced recruitment of microglia into the ONL, which paralleled with accelerated ONL loss and increased FAF occupancy. Thus, we propose that the degree of photoreceptor apoptosis and the rate of ONL thinning in RP patients might be read from the fundus color and the FAF.

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Multimodal imaging of chorioretinal folds induced by orbital vascular malformation in two cases

European Journal of Ophthalmology ◽

10.1177/1120672120957582 ◽

2020 ◽

pp. 112067212095758

Author(s):

Ahmet Kaan Gündüz ◽

Carol L Shields ◽

Şükran Bekdemir ◽

Jerry A Shields

Keyword(s):

Functional Status ◽

Multimodal Imaging ◽

Pigment Epithelium ◽

Fundus Autofluorescence ◽

Retinal Pigment ◽

Late Phase ◽

Vascular Tumor ◽

Fundus Photography ◽

Swept Source ◽

Chorioretinal Folds

Purpose: To investigate the alterations in the retinal pigment epithelium (RPE) in the crest and trough portions of chorioretinal folds (CRFs) induced by an orbital vascular tumor. Methods: Review of multimodal imaging in two eyes of two patients with globe compression and CRFs from an orbital vascular tumor. Results: Fundus photography demonstrated obliquely extending CRFs with alternating hyperpigmented and hypopigmented linear alterations in both eyes. Fundus autofluorescence (AF) imaging showed obliquely oriented hypoAF lines, incompletely alternating with hyperAF lines. In Case 1, the hyperAF lines had interspersed hypoAF segments and Case 2 had peripapillary mottling of AF. Fluorescein angiography (FA) showed alternating hyper and hypofluorescent lines in the late phase in Case 1. Optical coherence tomography (OCT) documented relative thinning of RPE at the folded crests in Case 1 and preservation of RPE in Case 2. Swept-source OCT angiography (SS-OCTA) demonstrated oblique hyporeflective lines in the outer retina and choriocapillaris layers in Case 2. These findings suggest that the crest of a CRF represents thinned or rarified RPE with hypoAF, transmission hyperfluorescence (FA), partially attenuated RPE layer (OCT), and isoreflectivity (SS-OCTA) while the trough represents compressed RPE with irregular hyperAF, transmission hypofluorescence (FA), thickened RPE layer (OCT), and hyporeflectivity (SS-OCTA). Conclusion: The anatomic and functional status of the RPE in CRFs based on multimodal imaging reveals normal to attenuated RPE with hypofunctionality at the fold crest and compacted, thickened RPE at the trough with segmental functional impairment on AF imaging. Anatomic information regarding CRFs is evident on OCT, FA, and SS-OCTA while the functional status is depicted on AF.

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Novel mutations in the 3-box motif of the BACK domain of KLHL7 associated with nonsyndromic autosomal dominant retinitis pigmentosa

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1275-2 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Jin Kyun Oh ◽

Jose Ronaldo Lima de Carvalho ◽

Young Joo Sun ◽

Sara Ragi ◽

Jing Yang ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Autosomal Dominant ◽

Fundus Autofluorescence ◽

Retinal Dystrophy ◽

Protein Modeling ◽

Fundus Photography ◽

Imaging Biomarkers ◽

Loss Of Function ◽

Gene Panel Testing ◽

Sd Oct

Abstract Background Mutations in the Kelch-like protein 7 (KLHL7) represent a recently described and, to date, poorly characterized etiology of inherited retinal dystrophy. Dominant mutations in KLHL7 are a cause of isolated, non-syndromic retinitis pigmentosa (RP). In contrast, recessive loss-of-function mutations are known to cause Crisponi or Bohring-Opitz like cold induced sweating syndrome-3 (BOS-3). In this study, the phenotype and progression of five unrelated patients with KLHL7 mediated autosomal dominant RP (adRP) are characterized. Clinical evaluation of these patients involved a complete ophthalmic exam, full-field electroretinography (ffERG), and imaging, including fundus photography, spectral domain optical coherence tomography (SD-OCT), short wavelength fundus autofluorescence (SW-AF), and near-infrared fundus autofluorescence (NIR-AF). Molecular diagnoses were performed using whole-exome sequencing or gene panel testing. Disease progression was monitored in three patients with available data for a mean follow up time of 4.5 ± 2.9 years. Protein modeling was performed for all variants found in this study in addition to those documented in the literature for recessive loss-of-function alleles causing Crisponi or Bohring-Opitz like cold-induced sweating syndrome. Results Genetic testing in three patients identified two novel variants within the 3-box motif of the BACK domain: c.472 T > C:p.(Cys158Arg) and c.433A > T:p.(Asn145Tyr). Clinical imaging demonstrated hyperautofluorescent ring formation on both SW-AF and NIR-AF in three patients, with diffuse peripheral and peripapillary atrophy seen in all but one case. SD-OCT demonstrated a phenotypic spectrum, from parafoveal atrophy of the outer retina with foveal sparing to widespread retinal thinning and loss of photoreceptors. Incidence of cystoid macular edema was high with four of five patients affected. Protein modeling of dominant alleles versus recessive loss-of-function alleles showed dominant alleles localized to the BTB and BACK domains while recessive alleles were found in the Kelch domain. Conclusions We report the phenotype in five patients with KLHL7 mediated adRP, two novel coding variants, and imaging biomarkers using SW-AF and NIR-AF. These findings may influence future gene-based therapies for adRP and pave the way for mechanistic studies that elucidate the pathogenesis of KLHL7-mediated RP.

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Differential distribution of manifest lesions in diabetic retinopathy by fundus fluorescein angiography and fundus photography

BMC Ophthalmology ◽

10.1186/s12886-020-01740-2 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Xiaoli Li ◽

Jie Xie ◽

Liang Zhang ◽

Ying Cui ◽

Guanrong Zhang ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Fluorescein Angiography ◽

Posterior Pole ◽

Chinese Patients ◽

Fundus Photography ◽

Peripheral Retina ◽

Multiple Logistic Regression ◽

Fundus Fluorescein Angiography ◽

Differential Distribution ◽

Nonproliferative Diabetic Retinopathy

Abstract Background To analyze the distribution of manifest lesions of diabetic retinopathy (DR) by fundus fluorescein angiography (FFA) and color fundus photography (FP). Methods A total of 566 eyes of 324 Chinese patients diagnosed with DR were included in this retrospective study. DR severity was graded by the international grading criterion. The distributions of microaneurysms (MA), intraretinal hemorrhages/exudates (He/Ex), intraretinal microvascular abnormality (IRMA), capillary nonperfusion areas (NPA), and neovascularization (NV) were estimated by multiple logistic regression analyse based on nine-field FFA and FP images. Results In mild nonproliferative diabetic retinopathy (NPDR), the highest frequency of MA was found in the posterior pole (67.7%), followed by the inferior nasal (59.4%), and the nasal (55.4%) fields. In moderate NPDR, MA frequently distributed in the posterior pole (98.0%), nasal (97.0%), superior (96.0%), inferior nasal (94.9%), and inferior (92.9%) fields, whereas He/Ex were most prevalent in the posterior pole (69.7%). In severe NPDR and proliferative DR, IRMA, NPA, and NV were more frequent in the nasal field, particularly in the inferior nasal field (60.3, 38.7, and 76.0%, respectively). All lesions were more observed in the combined posterior pole, nasal, and inferior nasal fields than in the posterior pole or combined two fields in the early and severe stages of DR (P < 0.05). Conclusions The manifest lesions of DR were common in the nasal field besides the posterior pole in Chinese patients. A combined examination of the posterior pole, nasal, and inferior nasal mid-peripheral retina would help to detect different retinal lesions of DR. Trial registration ClinicalTrial. gov, NCT03528720. Registered 18 May 2018 - Retrospectively registered.

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