Retinal Flecks Research Articles

Characterization of kjellin syndrome using spectral-domain optical coherence tomography and fundus autofluorescence.

The purpose of this study was to describe the characteristic funduscopic appearance of Kjellin syndrome, to report unique spectral-domain optical coherence tomography (Carl Zeiss Meditec, Dublin, CA) and fundus autofluorescence findings, and to provide long-term follow-up observations about this patient. A 43-year-old man presented for an ophthalmologic examination with a known diagnosis of hereditary spastic paraplegia and no visual complaints. Retinal flecks were present throughout the macula in both eyes of the patient. Fluorescein angiography showed flecks with central hypofluorescence and peripheral hyperfluorescence. Fundus autofluorescence showed hyperautofluorescence in the center of the visible flecks and a surrounding halo of hypoautofluorescence. An abnormal latticelike network of hyperautofluorescence was present in the nasal retina of both eyes. Spectral domain-optical coherence tomography showed hyperreflective material, accounting for the flecks located at the level of the retinal pigment epithelium. At the 6-year follow-up, this patient had not developed any subjective visual changes, and the appearance of his fundus remained relatively unchanged. The presence of hyperautofluorescent material outside the posterior pole in patients with Kjellin syndrome has not been previously reported and suggests that retinal pigment epithelium involvement in this condition is not limited to the macula. Spectral domain-optical coherence tomography of this patient showed that the accumulation of hyperreflective material accounting for the flecks was located at the level of the retinal pigment epithelium. The 6-year follow-up findings suggest that this condition is either stationary or slowly progressive.

Analysis of Retinal Flecks in Fundus Flavimaculatus Using High-Definition Spectral-Domain Optical Coherence Tomography

To assess morphologic changes associated with retinal flecks in fundus flavimaculatus using spectral-domain optical coherence tomography (SD-OCT). Observational case series. Simultaneous recordings of SD-OCT and confocal scanning laser ophthalmoscope (cSLO) fundus autofluorescence images were obtained in fundus flavimaculatus patients. Morphologic aspects of the retinal flecks were analyzed and classified. Thirty-one eyes of 17 consecutive patients (8 male, 9 female; mean age 47.9 +/- 17.1 years) were included for analysis. SD-OCT revealed 5 distinct types of lesions. Group A lesions were limited to the outer segment (OS) of the photoreceptors, the retinal pigment epithelium (RPE) interdigitations, and the RPE/Bruch membrane complex. Group B showed a protrusion of the hyper-reflective material through the interface of inner segment (IS)/OS of the photoreceptors up to the external limiting membrane. A further protrusion of the hyper-reflective material into the outer nuclear layer was seen in group C lesions. Group D lesions were characterized by an accumulation of the hyper-reflective material limited to the outer nuclear layer. Type E lesions can be described as drusen-like retinal pigment detachments. No significant correlation between the different types of flecks and visual acuity was observed (P > .05). SD-OCT allows one to distinguish at least 5 different types of lesions associated with retinal flecks in fundus flavimaculatus. The ability to characterize the different types of flecks and to analyze the photoreceptor layers surrounding these lesions suggests that SD-OCT might have a potential clinical role in the evaluation and follow-up of the structural changes in fundus flavimaculatus.

Intravitreal avastin for choroidal neovascularization associated with stargardt-like retinal abnormalities in pseudoxanthoma elasticum

The aim of the study was to describe a patient with pseudoxanthoma elasticum (PXE), showing Stargardt-like retinal abnormalities, who underwent treatment with intravitreal bevacizumab for subfoveal choroidal neovascularization (CNV) of the right eye (RE). A 57-year-old woman with diagnosis of angioid streaks, retinal flecks, and chorioretinal Stargardt-like atrophy due to PXE was referred to our department for sudden decreased vision in her RE (20/160). Upon a complete ophthalmologic examination, including fluorescein angiography (FA), and optical coherence tomography (OCT), the patient was diagnosed with subfoveal CNV of the RE. Owing to the subfoveal localization of the CNV, the patient was submitted to intravitreal bevacizumab injection. At the 1-month follow-up, visual acuity (VA) improved (20/40), and FA and OCT revealed the CNV closure. Twelve months after the treatment, the patient’s VA remained stable with no recurrence of active CNV. On the basis of our findings, a single intravitreal bevacizumab injection seems to induce total regression of CNV complicating PXE, in a patient showing Stargardt-like retinal abnormalities. Further investigations are required to confirm our results.

Bilateral Serous Retinal Detachment Associated With Alport's Syndrome

Purpose: To report a case of bilateral serous retinal detachment associated with Alport's syndrome that resolved following intensive blood pressure control and electrolyte imbalance correction. Case summary: A 50-year-old male patient presented with bilateral lenticonus and bilateral serous retinal detachment. Bilateral serous retinal detachment with retinal flecks characteristic of Alport's syndrome appeared along with the development of chronic renal failure and hypertension. The following kidney biopsy revealed Alport's syndrome. After 14 days, the serous detachment resolved and vision recovered following intensive blood pressure control and electrolyte imbalance correction fundus and FA results were nearly normal. Conclusions: In this case, bilateral serous retinal detachment in Alport's syndrome resolved with intensive blood pressure control and electrolyte imbalance correction. To the author’s knowledge, this is the first case in South Korea with documentation of the onset and resolution of bilateral serous retinal detachment in Alport'syndrome.

Autofluorescence and Infrared Retinal Imaging in patients and obligate carriers with Neuronal Ceroid Lipofuscinosis

Purpose: To measure fundus autofluorescence (FAF) in patients and obligate carriers with Neuronal Ceroid Lipofuscinosis (NCL) and document fundus abnormalities in NCL patients using standard retinal photography and confocal infra-red (IR) imaging.Methods: Twenty-seven patients with NCL, 50 obligate carriers of NCL, and 19 controls were imaged in IR and FAF modes by a confocal scanning laser opthalmoscope (HRA II, Heidelberg-Engineering, Inc). FAF intensities were referenced to the mean and standard deviation at the optic disk to remove inter-subject variance and then quantified along the horizontal and vertical meridians.Results: For NCL subjects, FAF images were successfully obtained in 16 eyes (9 of 27 subjects). Of these, 11 eyes had severely reduced or extinguished FAF and 5 eyes (3 subjects) could be analyzed along the meridians. An NCL subject with bilateral bull’s eye maculopathy showed overall increased FAF, the remaining 3 eyes had advanced retinal degeneration and showed reduced FAF. Four patterns of macular disease were observed: 1) bull’s eye atrophy 2) retinal pigment epithelium (RPE) dropout without pigmentary alterations, 3) RPE dropout with pigmentary alterations, 4) RPE dropout with pigmentary alterations and retinal flecks. Standard photography revealed focal retinal flecks in addition to severe retinal atrophy, RPE dropout, pigmentary clumping, and constricted vessels. Linear striations near the optic disc were highlighted by IR imaging. Topographical comparison of images demonstrated the focal flecks were not hyperfluorescent while the linear striations showed slight increases in FAF. For obligate carriers, FAF profiles were similar to controls with a mild increase in mean FAF intensity.Conclusions: Patients with NCL show increases in retinal fluorophores in early stages and decreases in FAF in late stages of the disease. Obligate carriers of NCL have mildly elevated FAF but this finding is not a specific measure of the carrier state.

High-Definition Optical Coherence Tomographic Visualization of Photoreceptor Layer and Retinal Flecks in Fundus Albipunctatus Associated With Cone Dystrophy

High-Definition Optical Coherence Tomographic Visualization of Photoreceptor Layer and Retinal Flecks in Fundus Albipunctatus Associated With Cone Dystrophy

G1961E mutant allele in the Stargardt disease gene ABCA4 causes bull's eye maculopathy

The aim of this study was to characterize the pathological and functional consequences of the G1961E mutant allele in the Stargardt disease gene ABCA4. Data from 15 patients were retrospectively reviewed and all the patients had at least one G1961E mutation. Comprehensive ophthalmic examination, full-field and pattern electroretinograms, and fundus autofluorescence (FAF) imaging were performed on all patients. Microperimetry, spectral-domain optical coherence tomography (OCT), and fluorescein angiography were performed in selected cases. Genetic screening was performed using the ABCR400 micro-array that currently detects 496 distinct ABCA4 variants. All patients had normal full-field scotopic and photopic electroretinograms (ERGs) and abnormal pattern electroretinograms (PERGs) performed on both eyes, and all the fundi had bull's eye maculopathy without retinal flecks on FAF. On OCT, 1 patient had disorganization of photoreceptor outer segment, 2 had outer nuclear layer (ONL) thinning likely due to photoreceptor atrophy proximal to the foveal center, and 3 had additional retinal pigment epithelium (RPE) atrophy. On microperimetry, 6 patients had eccentric superior fixation and amongst this group, 5 had an absolute scotoma in the foveal area. DNA analysis revealed that 3 patients were homozygous G1961E/G1961E and the rest were compound heterozygotes for G1961E and other ABCA4 mutations. The G1961E allele in either homozygosity or heterozygosity is associated with anatomical and functional pathologies limited to the parafoveal region and a trend to delayed onset of symptoms, relative to other manifestations of ABCA4 mutations. Our observations support the hypothesis that the G1961E allele contributes to localized macular changes rather than generalized retinal dysfunction, and is a cause of bull's eye maculopathy in either the homozygosity or heterozygosity state. In addition, genetic testing provides precise diagnosis of the underlying maculopathy, and current non-invasive imaging techniques could be used to detect photoreceptor damage at the earliest clinical onset of the disease.

The dot-and-fleck retinopathy of X linked Alport syndrome is independent of complement factor H (CFH) gene polymorphisms

Background and aims:X linked Alport syndrome is characterised by renal failure, hearing loss, lenticonus, and a central and peripheral dot-and-fleck retinopathy. complement factor H (CFH) gene variants are strongly associated...

Atteinte oculaire au cours du syndrome d’Alport. À propos de 32 cas

Alport syndrome is an inherited disease resulting in kidney failure, hearing loss, and ocular abnormalities. The purpose of this study was to describe the incidence and type of ocular abnormalities and to determine inheritance of this syndrome in our population. A total of 32 patients, from ten different families in South Tunisia, underwent a complete ocular examination. Inheritance was determined using pedigrees and genotyping. The best corrected visual acuity was 7.6/10. Biomicroscopy showed polymorphous dystrophy in 3%, anterior lenticonus in 28%, lens opacities in 3%, cataract in 19%, and retinal flecks in 37%. The genetic survey found five families with X-linked Alport syndrome, four families with recessive autosomal disease, and one family with dominant autosomal disease. Ocular abnormalities have been reported in 9%-82% of Alport syndrome patients. They are rare in childhood and increase in frequency and severity with age. The types of ocular defects described mostly involve the lens, the retina and more rarely the cornea. The most common changes are anterior lenticonus and perimacular retinal flecks. In approximately 85%, Alport syndrome is X-linked. In the remaining 15%, the transmission is autosomal recessive and exceptionally autosomal dominant. Ocular examination is a precious help for Alport syndrome diagnosis. It can also determine the prognosis of nephropathy.

Functional and clinical findings in 3 female siblings with crystalline retinopathy

To present functional and clinical findings in three female siblings with crystalline retinopathy. Functional and clinical examinations, including full-field and multi-focal electroretinograms (ERG), visual field, dark adaptation and fundus fluorescein angiography (FFA) were performed in three female siblings of a nonconsanguineous Chinese family, who exhibited characteristic retinal crystalline flecks of Bietti crystalline retinopathy. Ophthalmological examination revealed similar findings in the first and second daughter of the family. Best-corrected visual acuity was hand movement and finger counting respectively and funduscopic examination showed RPE clumping and relatively fewer yellow-white deposits in the posterior pole and mid-peripheral retina. FFA revealed massive RPE and choriocapillaris destruction. Ganzfeld ERG was undetectable or reduced markedly and multifocal ERG showed all responses were markedly depressed. Ophthalmological examination showed relative preservation of retinal function in the third daughter of the family (the proband). Best-corrected visual acuity was 0.5 in the right eye and 0.4 in the left eye. Funduscopic examination showed numerous crystal deposits scattered throughout the posterior pole. Dark adaptation revealed rod thresholds elevated dramatically and visual field examination demonstrated paracentral scotomas in both eyes. Full-field ERG was decreased slightly and multifocal ERG showed the central responses were markedly depressed. The present study describes typical crystalline retinopathy affecting three female siblings in a family.

A previously undescribed autosomal recessive retinal dystrophy

Abstract Purpose: To report a previously undescribed autosomal recessive retinal dystrophy Methods: Seven patients from five families in two countries were ascertained with progressive visual loss and punctate retinal flecks. All patients received full ophthalmic examination, ERGs, PERG, EOG and fundus autofluorescence imaging, and gave DNA for mutational screening. They had previously received a variety of diagnoses, including “Goldmann‐Favre syndrome”, “fundus flavimaculatus” and “unrecognised dystrophy”. Results: All patients had reduced visual acuity, were hyperopic and had irregularity of the RPE reflex with widespread subretinal deposits. A maculopathy was associated with intra‐retinal or subretinal fluid in four cases. Autofluorescence imaging was particularly useful in demonstrating these signs. Angle‐closure glaucoma was present in two cases. All patients had abnormality of both rod and cone full‐field ERG responses, with delay in the cone flicker ERG. All had abnormal EOG light‐rise. Progression in ERG abnormality was documented in three families. The results of genetic analysis will be discussed. Conclusions: A novel retinal disorder is described. The distinctive clinical and electrophysiological features enable directed mutational screening.

Kjellin syndrome: First case with retinal changes in carriers

A 32-year-old woman presented with dysarthria, spastic paraplegia, and dementia. Fundus examination revealed yellow retinal lesions (figure, A). Fluorescein angiography demonstrated characteristic features of retinal flecks (see the figure, B). Isolated flecks were found in the fundi of her …

Kjellin’s syndrome: Fundus autofluorescence, angiographic, and electrophysiologic findings

ObjectiveSyndromes with genetically determined retinal diseases and concurrent multiple neurologic abnormalities are rare. Kjellin described an autosomal recessive entity with spastic paraplegia, mental retardation, amyotrophia, and macular dystrophy. We sought to further characterize the retinal phenotype and to contrast fundus changes and the genotype to Stargardt’s disease in a young patient with progressive Kjellin’s syndrome. DesignObservational case report and family genetic study. PatientsOne affected and 11 unaffected members of a family with Kjellin’s syndrome were investigated. MethodsComplete ophthalmologic and neurologic examinations were performed, including electrophysiologic evaluation, color vision assessment, fundus autofluorescence, and fluorescence angiography. To investigate a possible role of the ABCA4 gene in the etiology of the macular changes, the entire 50 coding exons, including flanking intronic sequences of the patient, were analyzed by direct sequencing. Main outcome measuresThe patient was evaluated for her symptoms, retinal function, fundus autofluorescence, angiography, and mutations in the ABCA4 gene. ResultsA 27-year-old female patient initially was seen with trembling of her right hand. Subsequently, progressive paraspasticity occurred, and a diagnostic workup revealed mild mental retardation. Biomicroscopy disclosed symmetric multiple round yellowish flecks at the level of the retinal pigment epithelium scattered at the posterior pole, which showed increased intrinsic fluorescence in the center, with a halo of reduced autofluorescence. Multifocal electroretinography elicited abnormal responses in the macular area in the presence of normal Ganzfeld electroretinography recordings. In gene mapping, several common variants were identified, although none seem to be associated with the disease features. ConclusionsMacular changes in Kjellin’s syndrome share phenotypic characteristics with Stargardt’s disease, although there are differences with regard to appearance, distribution, angiographic, and autofluorescence behavior of the retinal flecks. Ophthalmologic examination is prudent in patients with similar neurologic deficits, because it is essential for the diagnosis and because visual symptoms may be absent even in the presence of obvious and widespread retinal manifestations. The abnormal gene product in Kjellin’s syndrome seems to cause progressive dysfunction in various neuronal tissues but seems to be distinct from the major defect underlying the Stargardt’s disease phenotype.

Ponctuations rétiniennes et syndrome d’Alport

Alport’s syndrome is a familial disorder characterized by progressive renal failure, sensorineural hearing loss and ocular manifestations. Case report. – The authors report a case of a 13-year-old child with Alport’s syndrome associated with retinal flecks. Conclusion. – Retinal flecks are the most frequent ocular manifestation in Alport’s syndrome and are a considerable help to diagnosis. They are often associated with severe renal failure.

Ocular findings in 34 patients with Alport syndrome: correlation of the findings to mutations in COL4A5 gene.

To describe the incidence and type of ocular findings of 34 patients with Alport syndrome and to analyze the association of gene defect in COL4A5 gene to ocular abnormalities found. A nationwide search of Alport syndrome patients was performed in Finland, and patients were invited to take part in a thorough ophthalmologic investigation. A total of 34 Alport syndrome patients from 14 different pedigrees were examined, and ocular abnormalities were found in 32% of them. The visual acuities were normal except in 4 of the 34 patients. Six individuals had retinal flecks and 4 men had anterior lenticonus. In 57% of the pedigrees the defect in COL4A5 gene was known. Ocular abnormalities were rare in childhood and increased with age. There was no correlation between the type of mutation and the type of ocular changes. In addition, the penetrance of the ocular findings varied considerably within most families.

Recurrent corneal erosion associated with Alport's Syndrome Rapid Communication

Ocular defects associated with Alport syndrome (AS) include anterior lenticonus and retinal flecks. We report on recurrent corneal erosion (RCE) as another ocular manifestation of the disease. Three brothers with AS reported a history of spontaneous attacks of RCE (2 episodes over 1 to 3 years in 2 of them and about 60 episodes in one brother over the last 10 years) characterized by acute ocular pain, lacrimation and photophobia lasting two to five days. The absence of RCE in the two other non-affected brothers from the same kindred suggested an association between AS and RCE, and prompted us to assess its prevalence. Forty-one patients with AS and renal failure and 67 control transplanted patients (with another original nephropathy) were evaluated. Seven AS patients had a history of RCE (first manifested between the ages of 12 and 21) versus only one control patient (P = 0.003). In conclusion, a history of RCE is found in about 20% of patients with AS and renal failure. RCE is likely to result from an inherent structural weakness of the corneal epithelial basement membrane (containing type IV collagen). A history of RCE should be sought when evaluating a patient for AS. Ophthalmologists should also be aware of this association, when confronted with a patient suffering from non-traumatic RCE.

Alport's syndrome with bilateral macular hole.

In this study 8 patients with Alport's syndrome are presented. The ocular manifestations of these patients were retinal flecks, macular depigmentation, microspherophakia and anterior lenticonus. One patient revealed bilateral macular hole which was an unusual feature. Four patients had renal biopsies with the characteristic electron microscopic changes of the disease. According to these findings our conclusion is that Alport's syndrome is a disorder of selected basement membranes.

Indocyanine Green Angiography in Stargardt's Flavimaculatus

We studied the indocyanine green videoangiographic characteristics of eyes in patients with Stargardt's flavimaculatus and fluorescein angiographic evidence of a dark choroid. Affected individuals underwent ophthalmic examination and fluorescein angiographic examination. Indocyanine green videoangiography was performed on eight patients with classic Stargardt's flavimaculatus. Two additional asymptomatic patients with mild manifestations of Stargardt's flavimaculatus, both of whom were related to one patient with the classic phenotype, were also examined with indocyanine green videoangiography. Choroidal detail was evident in all patients examined with indocyanine green videoangiography, and varying degrees of choroidal vascular closure were documented in the maculas of eight patients. Retinal pigment epithelial flecks were found to block indocyanine green videoangiographic fluoresence progressively. Late indocyanine green videoangiographic imaes frequently showed retinal pigment epithelial involvement in areas of retina thought to be uninvolved clinically and by fluorescein angiography. Peripapillary crescents of hypofluorescence, which in some patients were not noted clinically or by fluorescein angiography, were observed in all ten patients examined with indocyanine green videoangiography. In one asymptomatic patient, retinal pigment epithelial flecks could be identified only with indocyanine green videoangiography. Indocyanine green videoangiography in conjunction with fluorescein angiography can be a valuable tool in the recognition and further understanding of Stargardt's flavimaculatus.

CLINICAL FEATURES AND PATHOGENESIS OF ALPORT RETINOPATHY

Alport syndrome refers to the clinical triad of hereditary nephritis, sensorineural deafness, and ocular abnormalities. Ultrastructural findings in the lens capsule and in the renal glomeruli have provided evidence that abnormal basement membranes are elaborated in affected tissues of patients with this disorder. Recently, the results of several linkage studies have allowed the genetic defect in Alport syndrome to be mapped to a locus that codes for a subtype of type IV collagen (alpha 5) known to be present in glomerular basement membranes. In spite of these advances, the nature of the retinal flecks in Alport syndrome and the visual consequences of the flecks remain controversial. Detailed psychophysical and electrophysiologic testing was performed in a young man with Alport syndrome. The concurrence of an unusually extensive fleck retinopathy and unilateral pseudophakia afforded a unique opportunity to assess the effect of the flecks on retinal function. No sensory deficits were present in the eye with clear media. Macular flecks in Alport syndrome are not associated with demonstrable retinal dysfunction. The authors address questions about the nature and pathogenesis of the flecks in light of new clinical and genetic information.

An electrophysiological study on children and young adults with Alport's syndrome.

Alport's syndrome is characterised by progressive haematuric nephritis and high tone sensorineural hearing loss. Ocular signs are variable, the most consistent findings being anterior lenticonus and retinal flecks in the macula and mid peripheral areas. Previous electrophysiological studies on patients with Alport's syndrome have mostly been on adult patients undergoing haemodialysis, or after renal transplantation. A group of young patients with Alport's syndrome were studied to assess if early electrophysiological changes were detectable. A total of 20 patients (15 males and five females) between the ages of 3.5 and 22 years (mean 12.7 (years) were examined and compared with control subjects. Visual evoked potentials and electroretinograms were obtained following flash and pattern reversal stimulation. Electro-oculograms were also recorded. No significant electrophysiological changes were found in any of the 20 patients, including four who had visible fundus changes.