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PURPOSE: To test the hypothesis that Müller cell dysfunction in macular telangiectasia type 2 (MacTel) results in delayed cone adaptation kinetics and to assess absolute cone and rod thresholds in this condition. METHODS: Adaptation after an approximate 63.5% full-field cone photopigment bleach was assessed for Goldmann size V (1.7° diameter) 640 nm (red) and 480 nm (blue) targets presented at a retinal locus corresponding to 2° temporal to fixation. The cone time constant of adaptation and absolute cone and rod thresholds were calculated from exponential functions fitted to the resultant dark adaptation curves. RESULTS: Eighteen eyes with MacTel (from 11 patients) were compared with 19 control eyes (from 16 normal subjects). Cone adaptation kinetics were significantly impaired in MacTel, as was the absolute cone threshold. Final thresholds for blue targets were also significantly elevated in MacTel, consistent with impaired rod absolute threshold. Losses in sensitivity observed in MacTel were consistent with a so-called d1/2 mechanism (i.e., receptoral) site of sensitivity loss. CONCLUSION: In addition to previously documented impairments in rod dark adaptation, MacTel results in a significant elevation in cone thresholds because of pathology at the level of the photoreceptors. The delays in cone adaptation that we found in eyes with MacTel may reflect impairment of the Müller cell-mediated cone-specific visual cycle.
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Regeneración/fisiología , Células Fotorreceptoras Retinianas Conos/fisiología , Pigmentos Retinianos/fisiología , Telangiectasia Retiniana/fisiopatología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Adaptación a la Oscuridad/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Agudeza Visual/fisiología , Campos Visuales/fisiologíaRESUMEN
PURPOSE: The aim of the study was to quantify choriocapillaris (CC) flow alterations in early Sorsby fundus dystrophy (SFD) and to investigate the relationship of the CC flow deficits with the choroidal and outer retinal microstructure. METHODS: In this prospective case-control study, 18 eyes of 11 patients with early SFD and 31 eyes of 31 controls without ocular pathology underwent multimodal imaging, including spectral-domain optical coherence tomography (OCT), followed by deep-learning-based layer segmentation. OCT angiography (OCTA) was performed to quantify CC flow signal deficits (FDs). Differences in CC FD density between SFD patients and controls were determined, and the relationships with choroidal thickness, retinal pigment epithelium-drusen complex (RPEDC) thickness and outer retinal layer thicknesses were analyzed using mixed-model analysis. RESULTS: SFD patients exhibited a significantly greater CC FD density than controls (estimate [95% CI]: +20.0%FD [13.3; 26.7], p < 0.001 for SFD patients), even when adjusted for age. Square-root transformed choroidal thickness was a structural OCT surrogate of the CC FD density (-2.1%FD per âµm, p < 0.001), whereas RPEDC thickness was not informative regarding CC FD (p = 0.061). The CC FD density was associated with an altered microstructure of the overlying photoreceptors (outer segments, inner segments, and outer nuclear layer thinning of -0.19 µm, -0.08 µm and -0.30 µm per %FD, respectively, all p < 0.001). CONCLUSIONS: Patients with early SFD exhibit pronounced abnormalities of CC flow signal on OCTA, which are not limited to areas of sub-RPE deposits seen on OCT imaging. Thus, analysis of the CC flow may enable clinical trials at earlier disease stages in SFD.
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Coroides , Tomografía de Coherencia Óptica , Estudios de Casos y Controles , Angiografía con Fluoresceína/métodos , Humanos , Degeneración Macular , Tomografía de Coherencia Óptica/métodosRESUMEN
PURPOSE: To investigate multimodal retinal imaging characteristics including the retinal nerve fiber layer (RNFL) thickness in patients with RPGR-associated retinitis pigmentosa (RP). METHODS: This cross-sectional case-control study included 17 consecutive patients (median age, 21 years) with RPGR-associated RP who underwent retinal imaging including optical coherence tomography (OCT), short-wavelength fundus autofluorescence (AF) imaging, and RNFL scans centered on the optic disc. RNFL thickness was manually segmented and compared to clinical and imaging parameters including the transfoveal ellipsoid zone (EZ) width, the horizontal diameter of the macular hyperautofluorescent ring. RNFL thickness was compared to 17 age- and sex-matched controls. RESULTS: In patients with RPGR-associated RP, the EZ width (R2 = 0.65), the central hyperautofluorescent ring on AF images (R2 = 0.72), and visual acuity (R2 = 0.68) were negatively correlated with age. In comparison to controls, a significantly (p < 0.0001) increased global RNFL thickness was identified in RPGR-associated RP, which was, however, less pronounced in progressed disease as indicated by the EZ width or the diameter of the central hyperautofluorescent ring. CONCLUSIONS: This study describes retinal characteristics in patients with RPGR-associated RP including a pronounced peripapillary RNFL thickness compared to healthy controls. These results contribute to the knowledge about imaging biomarkers in RP, which might be of interest for therapeutic approaches such as gene replacement therapies.
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Retinitis Pigmentosa , Adulto , Biomarcadores , Estudios de Casos y Controles , Estudios Transversales , Proteínas del Ojo , Humanos , Fibras Nerviosas , Retinitis Pigmentosa/diagnóstico , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
PURPOSE: To define, characterize, and classify hyperreflectivity on optical coherence tomography and report its prevalence in macular telangiectasia Type 2. METHODS: In a primary cross-sectional analysis, multimodal imaging data were retrospectively analyzed. The definition of hyperreflectivity and neovascularization on optical coherence tomography followed optical coherence tomography angiography-based criteria. Eyes were graded for the presence of hyperreflectivity and neovascularization and further categorized into three classes based on position and extent of hyperreflectivity. In a secondary analysis, eyes were reviewed for ≥24 months using optical coherence tomography imaging. RESULTS: Three hundred and twenty-two eyes from 161 patients were analyzed in the cross-sectional analysis. Hyperreflectivity was found in 177 (55%) and neovascular membranes in 49 (15%) eyes. Hyperreflectivity correlated significantly with parameters indicative of disease progression. In the longitudinal analysis, 206 eyes from 103 patients were reviewed over a mean of 35.6 months. 17/86 eyes (20%) showed a de novo development of hyperreflectivity. 8/29 eyes (28%) with preexistent intraretinal hyperreflectivity developed outer retinal hyperreflectivity. A high proportion of eyes with outer retinal hyperreflectivity (17/52 [33%]) developed neovascular membranes. CONCLUSION: Hyperreflectivity represents a common finding in macular telangiectasia Type 2 but lacks a uniform definition. We propose a hyperreflectivity grading scale that may help to estimate disease progression and identify eyes at risk for developing neovascular membranes.
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Epitelio Pigmentado de la Retina/diagnóstico por imagen , Telangiectasia Retiniana/diagnóstico , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Anciano , Estudios Transversales , Progresión de la Enfermedad , Femenino , Angiografía con Fluoresceína/métodos , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Telangiectasia Retiniana/fisiopatología , Estudios RetrospectivosRESUMEN
PURPOSE: Two-colour computerised perimetry is a technique developed for assessing cone- and rod-function at fixed background luminances in retinal disease. However, the state of adaptation during testing is unknown but crucial in the interpretation of results. We therefore aimed to determine the adaptational state of rod- and cone-mechanisms in two-colour perimetry. METHODS: Sensitivity to 480 nm (blue) and 640 nm (red) Goldmann size V targets was determined for 10 normal subjects aged 16 to 46 years at 17 locations in the central 60 degrees of the visual field under scotopic conditions and then from -1.5 log cd m-2 to 2 log cd m-2 (white background) in 0.5 log unit steps. Data were fitted with threshold versus intensity (tvi) functions of the form logT = logT0 + log ((A + A0 )/A0 )n . RESULTS: No clear rod-cone break was observed for 640 nm stimuli. For 480 nm stimuli, transition from rod-detection to cone-detection occurred at mesopic illumination levels, where rod adaptation approached Weber behaviour. Cone detection mechanisms did not display Weber-like adaptation until the background luminance approached 1 log cd.m-2 . Diseases resulting in a "filter effect" - including disorders of the photoreceptors - are therefore predicted to affect sensitivity when rod function is probed with short-wavelength targets under scotopic conditions, but less so under mesopic conditions. Filter effects are similarly anticipated to affect cone function measured using long-wavelength targets under mesopic conditions (e.g., during microperimetry), but less so under photopic conditions. CONCLUSIONS: Asymmetries in adaptation in automated two-colour perimetry are predicted to artefactually favour the detection of losses in rod sensitivity under scotopic conditions and cones under mesopic conditions.
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Células Fotorreceptoras de Vertebrados/fisiología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/fisiopatología , Pruebas del Campo Visual/métodos , Campos Visuales/fisiología , Adolescente , Adulto , Visión de Colores/fisiología , Adaptación a la Oscuridad/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Umbral Sensorial/fisiología , Agudeza Visual/fisiología , Adulto JovenRESUMEN
PURPOSE: To systematically and longitudinally investigate the characteristics of flecks in ABCA4-related retinopathy under different fundus autofluorescence (AF) excitation and emission spectra. METHODS: A total of 132 eyes of 66 patients with ABCA4-related retinopathy were investigated using multimodal AF imaging and spectral domain optical coherence tomography. Autofluorescence imaging with blue (BAF), green (GAF), and near-infrared (NIR-AF) excitation wavelengths obtained by a confocal scanning laser ophthalmoscope was compared with AF imaging obtained by an innovative confocal light-emitting diode-based retinal imaging system (Color-AF) that allows for separation of short (green emission fluorescent component) and long (red emission fluorescent component) autofluorescence emission components. RESULTS: Color-AF, BAF, and GAF, overall, revealed similar presentation of hyperautofluorescent flecks. Flecks that showed predominantly red emission fluorescent component matched with hyperautofluorescent flecks in NIR-AF. Over the observation time of 5 to 14 months, flecks showed a transition in the AF emission spectrum to shorter wavelengths (red emission fluorescent component to green emission fluorescent component), associated with a progressed disruption of overlaying outer retinal bands in optical coherence tomography. Newer hyperautofluorescent flecks usually revealed predominantly red emission fluorescent component. CONCLUSION: By separation of the AF spectra, the remodeling of fluorophores and associated structural changes can be monitored over time indicating a novel and susceptible surrogate marker for disease progression and potential therapeutic effects.
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Transportadoras de Casetes de Unión a ATP/genética , Lipofuscina/metabolismo , Imagen Óptica , Distrofias Retinianas/diagnóstico por imagen , Distrofias Retinianas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios Transversales , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Oftalmoscopía , Distrofias Retinianas/genética , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
Ahead of Print article withdrawn by publisher.
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PURPOSE: To evaluate dark adaptation (DA) in patients with macular telangiectasia Type 2 (MacTel). METHODS: After a local photobleach (4 × 4° size, 83% bleach), DA was measured using a test stimulus (2° diameter) projected at 5° eccentricity horizontal from the foveal center within the temporal parafovea. Cone plateau, rod intercept time, and rod recovery rate (S2) were calculated from the resulting DA curves. Findings were correlated with disease stages (according to Gass and Blodi), the area of ellipsoid zone loss in optical coherence tomography, and macular pigment loss ("MP-Classes 1-3"). RESULTS: Fifty-nine eyes of 59 patients were compared with 18 eyes of 18 healthy controls. Dark adaptation was significantly impaired in patients with MacTel. Although differences were most pronounced for parameters indicating rod-mediated recovery, cone-mediated recovery was also decreased, yet to a lesser extent. Dark adaptation parameters were only weakly associated with disease stages and ellipsoid zone loss. A better association was found between rod-mediated recovery (S2 and rod intercept time) and macular pigment loss (Kendall's tau for rod intercept time: 0.69 and S2: -0.51; both P < 0.0001). CONCLUSION: Dark adaptation is significantly impaired in patients with MacTel. Our results indicate an association of reduced macular pigment and rod dysfunction in MacTel.
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Adaptación a la Oscuridad/fisiología , Telangiectasia Hemorrágica Hereditaria/fisiopatología , Anciano , Estudios Transversales , Femenino , Humanos , Pigmento Macular/metabolismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Células Fotorreceptoras Retinianas Conos/fisiología , Células Fotorreceptoras Retinianas Bastones/fisiología , Telangiectasia Hemorrágica Hereditaria/diagnóstico por imagen , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To characterize dark adaptation in patients with pseudoxanthoma elasticum, a systemic disease leading to calcification of elastic tissue including the Bruch membrane. METHODS: In this prospective case-control study, dark adaptation thresholds were measured using a Goldmann-Weekers dark adaptometer. Additional assessments included best-corrected visual acuity testing, contrast sensitivity, low luminance deficit, and vision-related quality of life. RESULTS: Dark adaptation thresholds were significantly higher, and adaptation periods were prolonged in patients with pseudoxanthoma elasticum (n = 35; 33 with 2 ABCC6 mutations) compared with controls (n = 35). The time to adapt 4 log units (20.6 ± 8.6 vs. 8.0 ± 1.3 minutes) and the mean dark adaptation threshold after 15 minutes (3.5 ± 1.1 vs. 1.8 ± 0.2 log units) were significantly different between patients and controls (both P < 0.001). Low luminance deficits (12.3 ± 6.4 vs. 6.1 ± 4.3 ETDRS letters), contrast sensitivity (1.4 ± 0.3 vs. 1.9 ± 0.1), and low luminance-related quality of life (LLQ score: 1,286 ± 355 vs. 2,167 ± 68) were also significantly worse in patients with pseudoxanthoma elasticum (all, P < 0.001). Two patients were treated with high-dose vitamin A which partially reversed impaired dark adaptation. CONCLUSION: Patients with pseudoxanthoma elasticum often have impaired dark adaptation. Positive effects of vitamin A supplementation may indicate restricted retinal access of vitamin A through the Bruch membrane as one possible underlying pathogenic factor.
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Lámina Basal de la Coroides/patología , Adaptación a la Oscuridad/fisiología , Seudoxantoma Elástico/fisiopatología , Enfermedades de la Retina/fisiopatología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Sensibilidad de Contraste/fisiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Seudoxantoma Elástico/tratamiento farmacológico , Calidad de Vida , Enfermedades de la Retina/tratamiento farmacológico , Agudeza Visual/fisiología , Vitamina A/administración & dosificación , Adulto JovenRESUMEN
PURPOSE: To investigate foveal photoreceptor configuration in Alport syndrome, a rare inherited disease characterized by Collagen IV dysfunction. METHODS: Adaptive optics scanning laser ophthalmoscope (AOSLO) in vivo imaging of the foveal center and quantitative analysis of cone photoreceptor topography in a 17-year-old male patient with Alport syndrome presenting absence of a foveal avascular zone (FAZ) and foveal hypoplasia in both eyes. RESULTS: Cone density analysis based on AOSLO images revealed an unusual linear cone topography profile displaying supernormal densities within the fovea (z-scores up to + 3.57 and + 2.97 in right and left eyes, respectively). CONCLUSION: Foveal hypoplasia has previously been associated with normal or reduced cone density. Our observation is the first case of disease-related supernormal cone density within the foveola, shedding light upon the role of Collagen IV in foveal maturation.
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Nefritis Hereditaria , Masculino , Humanos , Adolescente , Nefritis Hereditaria/diagnóstico , Tomografía de Coherencia Óptica/métodos , Fóvea Central/irrigación sanguínea , Retina , Colágeno Tipo IV/genética , Oftalmoscopía/métodosRESUMEN
BACKGROUND/AIMS: To determine the association of age, presence of optic nerve head drusen (ONHD) and number of previous intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections with inner retinal layer thicknesses in patients with pseudoxanthoma elasticum (PXE). METHODS: In this retrospective case-control study, longitudinal spectral-domain optical coherence tomography imaging data from patients with PXE were compared with controls. A custom deep-learning-based segmentation algorithm was trained and validated to quantify the retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL). The association of age, number of anti-VEGF injections and ONHD with the RNFL and GCL thickness in the outer ETDRS subfields as dependent variables was investigated using mixed model regression. RESULTS: Fourty-eight eyes of 30 patients with PXE were compared with 100 healthy eyes. The mean age was 52.5±12.9 years (range 21.3-68.2) for patients and 54.2±18.7 years (range 18.0-84.5) for controls. In patients, ONHD were visible in 15 eyes from 13 patients and 31 eyes had received anti-VEGF injections. In the multivariable analysis, age (-0.10 µm/year, p<0.001), the diagnosis of PXE (-2.03 µm, p=0.005) and an interaction term between age and the presence of ONHD (-0.20 µm/year, p=0.001) were significantly associated with the GCL thickness. Including the number of intravitreal injections did not improve the model fit. The RNFL thickness was not significantly associated with any of these parameters. CONCLUSIONS: This study demonstrates a significant association of ageing and ONHD with GCL thinning in patients with PXE, but not with the number of anti-VEGF injections. Given the severity of inner retinal degeneration in PXE, a clinical trial investigating neuroprotective therapy warrants consideration.
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Drusas del Disco Óptico , Disco Óptico , Seudoxantoma Elástico , Degeneración Retiniana , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Células Ganglionares de la Retina , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/diagnóstico , Degeneración Retiniana/complicaciones , Estudios Retrospectivos , Estudios de Casos y Controles , Fibras Nerviosas , Drusas del Disco Óptico/complicaciones , Drusas del Disco Óptico/diagnóstico , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: Tamoxifen-induced retinopathy (TR) and macular telangiectasia type 2 (MacTel) share a highly similar retinal phenotype. In this study, we aimed to evaluate differences and similarities that may point toward underlying mechanisms linking both disease entities. DESIGN: Retrospective, cross sectional study. SUBJECTS: Patients diagnosed with MacTel or TR. METHODS: Patients underwent multimodal retinal imaging, including color fundus photography, spectral-domain OCT, fundus autofluorescence, fluorescein angiography, and OCT angiography (if available). Age, age of onset, best-corrected visual acuity, and bilaterality of changes were evaluated. Patients' eyes were graded for different morphologic characteristics by 4 experienced graders. MAIN OUTCOME MEASURES: Phenotypical characterization and comparison of frequencies of retinal characteristics of TR and MacTel on multimodal imaging. RESULTS: Twenty-eight eyes of 14 patients with TR and 118 eyes of 59 patients with MacTel were included. Age, age of onset, and best-corrected visual acuity were similar in both cohorts. All but 1 patient showed bilateral changes. In patients with MacTel, neurodegenerative changes and vascular alterations were equally present, whereas in patients with TR, neurodegenerative changes usually prevailed. Predilection sites within the central retina differed between the 2 diseases: most findings in patients with TR were limited to the foveal center, whereas changes in patients with MacTel were present throughout a slightly larger region ("MacTel area"), with an epicenter temporal to the foveal center. Distinct morphologic features included the distribution of retinal crystals, the size and position of ellipsoid zone breaks, and the presence of hyperreflective changes on OCT images. Focal hyperpigmentation and neovascular membranes were only present in eyes with MacTel. CONCLUSIONS: Macular telangiectasia and TR share a highly similar retinal phenotype, especially in early disease stages. Subtle differences on multimodal retinal images may help distinguish between these 2 disease entities. Our findings indicate the involvement of Müller cells in both diseases, which may explain the observed phenotypic characteristics and similarities.
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Telangiectasia Retiniana , Tomografía de Coherencia Óptica , Humanos , Estudios Retrospectivos , Estudios Transversales , Tomografía de Coherencia Óptica/métodos , Telangiectasia Retiniana/diagnóstico , Retina , Tamoxifeno/efectos adversosRESUMEN
PURPOSE: Convergence spasm (CS, spasm of near reflex) is characterized by transient attacks of convergence, miosis and accommodation, often associated with functional neurological disorders. To date, no simple and efficient treatment option is available for CS. This study investigates whether periorbital botulinum toxin injections as used in essential blepharospasm are also a treatment option in these patients. METHODS: All patients with convergence spasm having been treated with periorbital BoNTA injections in the department of neuro-ophthalmology were identified. Data were extracted from patient files concerning details and subjective effectiveness of botulinum toxin injections and relation to psychiatric or neurological disorders. Patients reporting with a history of closed-head trauma or organic neurologic pathologies possibly causing CS were excluded. A telephone assessment with a standardized questionnaire was performed to evaluate mental health issues as a trigger, as well as the long-term effect and satisfaction with periorbital injections. RESULTS: Of 16 patients treated with periorbital botulinum toxin injections for convergence spasm, 9 patients reported depression and/or anxiety disorders ongoing or in the past. A median number of 3 injections (range 1-13) was administered with a variable effect (relief of symptoms) between no effect and effect of up to more than 12 weeks. A longitudinal follow-up revealed ongoing symptoms in five patients. CONCLUSIONS: Periorbital botulinum toxin injections are less invasive than injections in the medial rectus muscle and can be a bridging therapeutic option in patients with CS. Mental health exploration is important due to psychiatric comorbidity.
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Blefaroespasmo , Toxinas Botulínicas Tipo A , Espasmo Hemifacial , Blefaroespasmo/tratamiento farmacológico , Toxinas Botulínicas Tipo A/uso terapéutico , Músculos Faciales , Espasmo Hemifacial/tratamiento farmacológico , Humanos , Inyecciones , Músculos Oculomotores , Espasmo/tratamiento farmacológicoRESUMEN
AIMS: To identify morphological characteristics preceding the development of exudative neovascularisation secondary to Macular Telangiectasia type 2 (MacTel) using multimodal retinal imaging. METHODS: In this retrospective study, eyes with a minimum observation period of 6 months prior to the de novo diagnosis of an exudative neovascularisation secondary to MacTel were analysed. Morphological changes preceding the formation of neovascularisation were evaluated using colour fundus photography, infrared imaging, fluorescein angiography, macular pigment measurement and optical coherence tomography (OCT). OCT-angiography (OCT-A) images were additionally available in a subset of patients. RESULTS: Twenty eyes from 20 patients were examined over a median period of 17 months (range: 6-100 months). Eyes were characterised by an accelerated progression of ellipsoid zone loss (median of 0.013 mm2/month), increased thickness of the temporal parafovea and hyper-reflective lesions on OCT. The latter underwent morphological changes preceding the development of exudative neovascularisation, including an increase in size and density, and expansion to outer retinal layers and the retinal pigment epithelium. All eyes showed a foveal depletion of macular pigment. On OCT-A, a focal increase in blood flow was observed at the level of the outer retina/choriocapillaris, and retinal-retinal and retinal-choroidal anastomoses preceded the formation of exudative neovascularisation. CONCLUSIONS: Multimodal imaging allows the identification of prognostic morphological features preceding the formation of exudative neovascularisation in MacTel. Eyes exhibiting these characteristics should be monitored closely and patients should be alert for emergent symptoms in order to detect and treat neovascularisation early and, thereby, prevent irreversible visual loss.
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Pigmento Macular , Telangiectasia Retiniana , Humanos , Estudios Retrospectivos , Telangiectasia Retiniana/diagnóstico , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodosRESUMEN
Dark adaptation (DA) refers to the slow recovery of visual sensitivity in darkness following exposure to intense or prolonged illumination, which bleaches a significant amount of the rhodopsin. This natural process also offers an opportunity to understand cellular function in the outer retina and evaluate for presence of disease. How our eyes adapt to darkness can be a key indicator of retinal health, which can be altered in the presence of certain diseases, such as age-related macular degeneration (AMD). A specific focus on clinical aspects of DA measurement and its significance to furthering our understanding of AMD has revealed essential findings underlying the pathobiology of the disease. The process of dark adaptation involves phototransduction taking place mainly between the photoreceptor outer segments and the retinal pigment epithelial (RPE) layer. DA occurs over a large range of luminance and is modulated by both cone and rod photoreceptors. In the photopic ranges, rods are saturated and cone cells adapt to the high luminance levels. However, under scotopic ranges, cones are unable to respond to the dim luminance and rods modulate the responses to lower levels of light as they can respond to even a single photon. Since the cone visual cycle is also based on the Muller cells, measuring the impairment in rod-based dark adaptation is thought to be particularly relevant to diseases such as AMD, which involves both photoreceptors and RPE. Dark adaptation parameters are metrics derived from curve-fitting dark adaptation sensitivities over time and can represent specific cellular function. Parameters such as the cone-rod break (CRB) and rod intercept time (RIT) are particularly sensitive to changes in the outer retina. There is some structural and functional continuum between normal aging and the AMD pathology. Many studies have shown an increase of the rod intercept time (RIT), i.e., delays in rod-mediated DA in AMD patients with increasing disease severity determined by increased drusen grade, pigment changes and the presence of subretinal drusenoid deposits (SDD) and association with certain morphological features in the peripheral retina. Specifications of spatial testing location, repeatability of the testing, ease and availability of the testing device in clinical settings, and test duration in elderly population are also important. We provide a detailed overview in light of all these factors.
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Purpose: To investigate potential associations between renal function and age-related macular degeneration (AMD) features as assessed with multimodal retinal imaging. Methods: A subset of participants included in a dark adaptation study with varying AMD severities had estimated glomerular filtration rate (eGFR) values (mL/min/1.73 m2) obtained from renal function laboratory testing of serum creatinine and cystatin C. Multimodal imaging from visit dates associated with serum samples was graded by the Wisconsin Reading Center for AMD features. Associations of eGFR with AMD features and severity grades, age, smoker status and rod-intercept time were investigated. Simple univariate analyses, age-corrected multivariate analyses, and a feature-selecting least absolute shrinkage and selection operator regression were performed for eGFR as a continuous dependent variable. Results: A total of 110 patients (mean age, 75.1 ± 9.4 years; mean eGFR, 70.7 ± 18.2 mL/min/1.73 m2) were included. In univariate analyses age (estimate, -1.16 units/year; 95% confidence interval [CI], -1.46 to -0.87; P < 0.0001), rod-intercept time (estimate, -0.54 units/minute; 95% CI, -0.81 to -0.27; P < 0.001) and subretinal drusenoid deposits (-11.12 units for subretinal drusenoid deposit presence in either eye; 95% CI, -20.23 to -2.01; P = 0.017) were associated with decreased renal function. However, in age-corrected multivariate models, age was the only significant variable associated with renal function, confirmed by least absolute shrinkage and selection operator regression. Conclusions: Accounting for age, renal function parameters did not show an association with AMD features. Translational Relevance: Bruch's membrane of the eye and the glomerular basement membrane of the kidney share physiologic similarities such that decreased renal function may demonstrate associations with AMD phenotypes.
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Degeneración Macular , Humanos , Degeneración Macular/diagnóstico , Lámina Basal de la Coroides , Tasa de Filtración Glomerular , Fenotipo , Riñón/diagnóstico por imagen , Riñón/fisiologíaRESUMEN
PURPOSE: To elucidate morphological determinants of rod and cone dysfunction in Sorsby fundus dystrophy (SFD), and to systematically compare visual function tests for interventional trials. DESIGN: Prospective cross-sectional study. METHODS: Patients with SFD (n = 16) and controls (n = 20) underwent visual function testing (best-corrected visual acuity [BCVA] and low luminance visual acuity [LLVA], contrast sensitivity, mesopic and dark-adapted (DA) fundus-controlled perimetry [FCP], rod-mediated dark adaptation [RMDA]), and multimodal imaging. Vision-related quality of life was evaluated. FCP and RMDA thresholds were analyzed using mixed models and structure-function correlation using machine learning (ML). Longitudinal data of 1 patient with high-dose vitamin A supplementation were available. RESULTS: Although photopic BCVA was normative in SFD, LLVA was impaired (0.30 LogMAR [0.20; 0.45] vs 0.20 LogMAR [0.03; 0.28], P < .05). Scotopic visual function exhibited a delayed rod-intercept time (21 minutes [12.15; 21] vs 4.05 minutes [3.22; 5.36], P < .001), and marked DA cyan mean sensitivity loss (-11.80 dB [-3.47; -19.85]), paralleled by a reduced vision-related quality of life. ML-based structure-function correlation allowed prediction of mesopic, DA cyan, and red sensitivity with high accuracy (cross-validated mean absolute error: 4.36, 7.77, and 5.31 dB, respectively), whereas RMDA could be slowed even in the absence of fundus alterations on multimodal imaging. After high-dose vitamin A supplementation, RMDA and DA thresholds improved markedly. CONCLUSIONS: Patients with SFD exhibit severely impaired scotopic visual function even in the absence of funduscopic alterations on multimodal imaging. In contrast to BCVA, scotopic visual function tests are suitable to quantify dysfunction in the early stages. Improvement of scotopic dysfunction after (off-label) high-dose vitamin A intake, as observed in one patient in our study, is compatible with the hypothesized local deficiency of vitamin A secondary to Bruch's membrane alterations.
Asunto(s)
Calidad de Vida , Campos Visuales , Estudios Transversales , Adaptación a la Oscuridad , Humanos , Estudios Prospectivos , Agudeza Visual , Pruebas del Campo Visual/métodosRESUMEN
PURPOSE: To investigate the suitability of 6 rod- or cone-mediated dark adaptation (DA) parameters as outcome measures for clinical trials in age-related macular degeneration (AMD), including their retest reliability, association with age and disease severity, and measurable longitudinal change over time. DESIGN: Prospective, longitudinal study (Clinicaltrials.gov: NCT01352975). PARTICIPANTS: A total of 191 patients with AMD and older participants followed longitudinally over 5 years. METHODS: Dark adaptation testing was performed using the AdaptDx dark adaptometer with a maximum test time of 40 minutes. A 2-part exponential-linear curve was fitted to obtain values for cone decay, cone plateau, time to rod-cone break, rod intercept time (RIT), rod adaptation rate (S2), and area under the curve. Intersession retest reliability was assessed in tests performed within 2 weeks using the Bland-Altman analysis. The relationship of DA parameters with age, AMD severity, and reticular pseudodrusen (RPD) presence was evaluated using linear mixed models. MAIN OUTCOME MEASURES: Retest reliability, association with disease severity, and longitudinal change of 6 DA parameters. RESULTS: A total of 1329 DA curves were analyzed. Rod intercept time was the parameter that showed the greatest reliability (intraclass correlation coefficient of 0.88) and greatest association with age, AMD severity, and RPD (marginal R2 of 0.38), followed by the rod-mediated parameters area under the curve and rod-cone break. Cone plateau appeared constant at lower RIT values but increased with progressive rod dysfunction (RIT > 22.8 minutes) with a slope of 0.07 log units per 10 minutes RIT prolongation. Therefore, it might provide additional information in the advanced stages of AMD. CONCLUSIONS: Age-related macular degeneration severity and RPD presence are each associated with large differences in multiple DA curve parameters. In addition, substantial differences in some parameters occur with age, even accounting for AMD severity and RPD status. This supports the 2-hit hypothesis of age and disease status on DA (and perhaps AMD pathophysiology itself). Of the DA parameters, RIT has the highest retest reliability, closest correlation with AMD severity and RPD, and largest longitudinal changes. This underscores the suitability of RIT as an outcome measure in clinical trials. The cone plateau increases only in advanced stages of kinetic rod dysfunction, indicating rod dysfunction preceding cone dysfunction and degeneration in the temporal sequence of pathology in AMD.