Retinal Architecture in ​\u3cem\u3eRGS9-\u3c/em\u3e and ​\u3cem\u3eR9AP\u3c/em\u3e-Associated Retinal Dysfunction (Bradyopsia)

Purpose To characterize photoreceptor structure and mosaic integrity in subjects with RGS9- and R9AP-associated retinal dysfunction (bradyopsia) and compare to previous observations in other cone dysfunction disorders such as oligocone trichromacy. Design Observational case series. Methods setting: Moorfields Eye Hospital (United Kingdom) and Medical College Wisconsin (USA). study population: Six eyes of 3 subjects with disease-causing variants in RGS9 or R9AP. main outcome measures: Detailed retinal imaging using spectral-domain optical coherence tomography and confocal adaptive-optics scanning light ophthalmoscopy. Results Cone density at 100 μm from foveal center ranged from 123 132 cones/mm2to 140 013 cones/mm2. Cone density ranged from 30 573 to 34 876 cones/mm2 by 600 μm from center and from 15 987 to 16,253 cones/mm2 by 1400 μm from center, in keeping with data from normal subjects. Adaptive-optics imaging identified a small, focal hyporeflective lesion at the foveal center in both eyes of the subject with RGS9-associated disease, corresponding to a discrete outer retinal defect also observed on spectral-domain optical coherence tomography; however, the photoreceptor mosaic remained intact at all other observed eccentricities. Conclusions Bradyopsia and oligocone trichromacy share common clinical symptoms and cannot be discerned on standard clinical findings alone. Adaptive-optics imaging previously demonstrated a sparse mosaic of normal wave-guiding cones remaining at the fovea, with no visible structure outside the central fovea in oligocone trichromacy. In contrast, the subjects presented in this study with molecularly confirmed bradyopsia had a relatively intact and structurally normal photoreceptor mosaic, allowing the distinction between these disorders based on the cellular phenotype and suggesting different pathomechanisms

Occult macular dystrophy in an Italian family carrying a mutation in the RP1L1 gene.

Occult macular dystrophy (OMD) is an inherited macular disease characterized by progressive visual decline with the absence of visible retinal abnormalities. Typical alterations of the retinal structure are detectable by spectral domain optical coherence tomography (SD\u2011OCT). Mutations in the RP1L1 gene have been identified to be responsible for the disease in Asian subjects. The present study assessed the role of mutations in the RP1L1 gene in an Italian family with OMD. One patient with OMD and five related subjects (two male offspring affected by progressive visual decline and three asymptomatic siblings of the patient) were subjected to complete ophthalmological examination. SD\u2011OCT was also performed. All subjects were screened for OMD\u2011associated genetic mutations in the RP1L1 gene. The OMD patient and the two symptomatic offspring presented with a reduced best\u2011corrected visual acuity. Although no fundus abnormalities were observed, SD\u2011OCT examination showed that the external limiting membrane and the inner segment/outer segment band were not clearly identifiable and a focal disruption of the photoreceptor layer was present. The degree of photoreceptor alterations was correlated with the severity of visual impairment. Clinical and tomographic results in the three asymptomatic relatives were normal. A p.Arg45Trp mutation in the RP1L1 gene was identified in the OMD patient, in the two symptomatic offspring and also in two of the asymptomatic siblings of the patient. The identification of RP1L1 mutations in subjects with OMD may improve the accuracy of diagnosis of this rare condition and may aid in enhancing the efficacy of genetic counseling

Eletroretinograma de padrão reverso no diagnóstico e acompanhamento das afecções da via óptica anterior

The pattern electroretinogram is an electrophysiological test that assesses the function of inner retinal layers, particularly the ganglion cells layer of retina, using a reversing checkerboard or grating pattern that produces no change in average luminance over time. The normal pattern electroretinogram is composed of a proeminent positive component (P50) and a large later negative component (N95). Since structural damage that compromises the retinal ganglion cell layer can lead to pattern electroretinogram changes, particularly in the N95 amplitude, the test can be useful in the treatment of a number of anterior visual pathway diseases. In this article, we review the methods for recording pattern electroretinogram and its usefulness in the diagnosis and management of diseases including inflammatory, hereditary, ischemic and compressive lesions of the anterior visual pathway.O eletroretinograma de padrão reverso é um teste eletrofisiológico que avalia a função das camadas internas da retina, especialmente a camada de células ganglionares, através de um estímulo em xadrez ou em barras que não apresenta variação na luminância do estímulo. É composto de um componente positivo (P50) e um componente negativo (N95) tardio. Uma vez que lesões estruturais às células ganglionares da reitna podem levar a alterações no eletroretinograma de padrão reverso, especialmente na amplitude da onda N95, o teste pode ser útil no tratamento de várias doenças da via óptica anterior. Neste artigo revisamos os métodos de obtenção do eletroretinograma de padrão reverso e a sua utilidade no diagnóstico e acompanhamento de doenças incluindo lesões inflamatórias, hereditárias, isquemicas e compressivas na via óptica anterior

Detection of early age-related macular degeneration using novel functional parameters of the focal cone electroretinogram

The focal cone electroretinogram is a sensitive marker for macular disease, but have we unlocked its full potential? Typically assessment of waveform parameters is subjective and focuses on a small number of locations (e.g. the a-wave). This study evaluated the discriminatory and diagnostic potential of 4 conventional and 15 novel, objectively determined, parameters in patients with early Age-related Macular Degeneration. Focal cone electroretinograms were recorded in 54 participants with early Age-related Macular Degeneration (72.9±8.2 years) and 54 healthy controls (69±7.7 years). Conventional a and b wave amplitudes and implicit times were measured and compared to novel parameters derived from both the 1st and 2nd derivatives and the frequency-domain power spectrum of the electroretinogram.Statistically significant differences between groups were shown for all conventional parameters, the majority of 1st and 2nd derivative parameters and the power spectrum at 25 and 30 Hz. Receiver operating characteristics showed that both conventional and 1st and 2nd derivative implicit times had provided the best diagnostic potential. A regression model showed a small improvement over any individual parameter investigated. The non-conventional parameters enhanced the objective evaluation of the focal electroretinogram, especially when the amplitude was low. Furthermore, the novel parameters described here allow the implicit time of the electroretinogram to be probed at points other than the peaks of the a and b waves. Consequently these novel analysis techniques could prove valuable in future electrophysiological investigation, detection and monitoring of Age-related Macular Degeneration

Evaluating Retinal Function in Age-Related Maculopathy with the ERG Photostress Test

PURPOSE. To evaluate the diagnostic potential of the electroretinogram (ERG) photostress test and the focal cone ERG in age-related maculopathy (ARM). METHODS. The cohort comprised 31 patients with ARM and 27 age-matched control subjects. The ERG photostress test was used to monitor cone adaptation after intense light adaptation. Focal 41- and 5-Hz cone ERGs were recorded monocularly (central 20°) to assess steady state retinal function. Univariate analysis identified electrophysiological parameters that differed between groups, and receiver operating characteristic (ROC) curves were constructed to assess their diagnostic potential. Logistic regression analysis determined the diagnostic potential of a model incorporating several independent predictors of ARM. RESULTS. The rate of recovery of the ERG photostress test was reduced (recovery was slower) in subjects with ARM. The parameter exhibited good diagnostic potential (P = 0.002, area under ROC curve = 0.74). The implicit times of the 5-Hz (a-wave, P = 0.002; b-wave, P < 0.001) and the 41-Hz (P < 0.001) focal cone ERGs were increased, and the 41-Hz focal cone ERG amplitude (P = 0.003) and focal to full-field amplitude ratio (P = 0.001) were reduced in the ARM group. Logistic regression analysis identified three independent predictors of ARM, including the rate of recovery of the ERG photostress test. CONCLUSIONS. Early ARM has a marked effect on the kinetics of cone adaptation. The clinical application of the ERG photostress test increases the sensitivity and specificity of a model for the diagnosis of ARM. Improved assessment of the functional integrity of the central retina will facilitate early diagnosis and evaluation of therapeutic interventions

Bilateral cystoid macular edema following docetaxel chemotherapy in a patient with retinitis pigmentosa: a case report.

BACKGROUND: Docetaxel is a chemotherapeutic agent of the taxane class of drugs for the treatment of breast cancer. We present a female patient who noted decreased vision after docetaxel treatment. CASE PRESENTATION: A 45-year-old female patient received docetaxel treatment after resection of a breast carcinoma. Funduscopy and optical coherence tomography (OCT) showed cystoid macular edema on both eyes. Dilated funduscopy also showed bone spicule-like pigmented deposits, typical for retinitis pigmentosa. Besides the fundus appearance restricted peripheral vision and scotopic electroretinogram confirmed the diagnosis of retinitis pigmentosa. Chemotherapy was discontinued following a consulation with the oncologist of the patient. After five weeks, visual acuity improved significantly along with decrease of retinal thickness measured by OCT. CONCLUSION: Docetaxel may cause ocular adverse effects such as cystoid macular edema. Ophthalmological examination is warranted for patients with visual complaints during docetaxel chemotherapy

Optical coherence tomography in Alzheimer's disease. A meta-analysis

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder, which is likely to start as mild cognitive impairment (MCI) several years before the its full-blown clinical manifestation. Optical coherence tomography (OCT) has been used to detect a loss in peripapillary retina nerve fiber layer (RNFL) and a reduction in macular thickness and volume of people affected by MCI or AD. Here, we performed an aggregate meta-analysis combining results from different studies. METHODS AND FINDINGS: Data sources were case-control studies published between January 2001 and August 2014 (identified through PubMed and Google Scholar databases) that examined the RNFL thickness by means of OCT in AD and MCI patients compared with cognitively healthy controls. RESULTS: 11 studies were identified, including 380 patients with AD, 68 with MCI and 293 healthy controls (HC). The studies suggest that the mean RNFL thickness is reduced in MCI (weighted mean differences in μm, WMD = -13.39, 95% CI: -17.34 to -9.45, p = 0.031) and, even more so, in AD (WMD = -15.95, 95% CI: -21.65 to -10.21, p<0.0001) patients compared to HC. RNFL in the 4 quadrants were all significantly thinner in AD superior (superior WMD = -24.0, 95% CI: -34.9 to -13.1, p<0.0001; inferior WMD = -20.8, 95% CI: -32.0 to -9.7, p<0.0001; nasal WMD = -14.7, 95% CI: -23.9 to -5.5, p<0.0001; and temporal WMD = -10.7, 95% CI: -19.9 to -1.4, p<0.0001); the same significant reduction in quadrant RNFL was observed in MCI patients compared with HC (Inferior WMD = -20.22, 95% CI: -30.41 to -10.03, p = 0.0001; nasal WMD = -7.4, 95% CI: -10.08 to -4.7, p = 0.0000; and temporal WMD = -6.88, 95% CI: -12.62 to -1.13, p = 0.01), with the exception of superior quadrant (WMD = -19.45, 95% CI: -40.23 to 1.32, p = 0.06). CONCLUSION: Results from the meta-analysis support the important role of OCT for RNFL analysis in monitoring the progression of AD and in assessing the effectiveness of purported AD treatments

Reduction of foveal bulges and other anatomical changes in fellow eyes of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes

Purpose: To compare the foveal characteristics in fellow eyes (FE) of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes with eyes of healthy controls. Methods: Forty-seven FE and 52 eyes of 52 age- and sex-matched healthy controls were studied. Quantitative assessment of the dome-shaped appearance of the hyperreflective lines that represent external limiting membrane (ELM_bulge) and inner outer segment junctions (IS/OS_bulge) were made by optical coherence tomography (OCT) images. Inner retinal complex thickness (IRCT) was quantitatively assessed at 1000 and 2000 µm of the foveal center in nasal and temporal quadrants. Presence of alterations in the inner retinal outer layers and central foveal thickness (CFT) were also analyzed. Results: Significantly lower ELM_bulge (p < 0.0001; Mann-Whitney test) and IS/OS_bulge (p < 0.001; student t test) and higher cases with COST alterations, expressed as a diffuse line (p < 0.006; Chi2 test) were found in FE than control eyes. IRCT were significantly reduced in FE at all the studied locations when comparing to control eyes (p < 0.05; student t test), maintaining anatomical proportionality among locations. Conclusion: FE without pathologic vitreomacular interactions seems to present some central cone alterations that may be related to other causes than vitreomacular traction.Preprin