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An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using Salmonella strains and E. coli, with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis. PolySia-NPs were administered intravenously in CD-1 mice and Sprague Dawley rats and assessed for survival and toxicity. Intravitreal (IVT) administration in Dutch Belted rabbits and non-human primates was assessed for ocular or systemic toxicity. In vitro results indicate that PolySia-NPs did not induce mutagenicity or cytotoxicity. Intravenous administration did not show clastogenic activity, effects on survival, or toxicity. A single intravitreal (IVT) injection and two elevated repeat IVT doses of PolySia-NPs separated by 7 days in rabbits showed no signs of systemic or ocular toxicity. A single IVT inoculation of PolySia-NPs in non-human primates demonstrated no adverse clinical or ophthalmological effects. The demonstration of systemic and ocular safety of PolySia-NPs supports its advancement into human clinical trials as a promising therapeutic approach for systemic and retinal degenerative diseases caused by chronic immune activation.
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The alternative pathway of the complement system is implicated in the etiology of age-related macular degeneration (AMD). Complement depletion with pegcetacoplan and avacincaptad pegol are FDA-approved treatments for geographic atrophy in AMD that, while effective, have clinically observed risks of choroidal neovascular (CNV) conversion, optic neuritis, and retinal vasculitis, leaving room for other equally efficacious but safer therapeutics, including Poly Sialic acid (PSA) nanoparticle (PolySia-NP)-actuated complement factor H (CFH) alternative pathway inhibition. Our previous paper demonstrated that PolySia-NP inhibits pro-inflammatory polarization and cytokine release. Here, we extend these findings by investigating the therapeutic potential of PolySia-NP to attenuate the alternative complement pathway. First, we show that PolySia-NP binds CFH and enhances affinity to C3b. Next, we demonstrate that PolySia-NP treatment of human serum suppresses alternative pathway hemolytic activity and C3b deposition. Further, we show that treating human macrophages with PolySia-NP is non-toxic and reduces markers of complement activity. Finally, we describe PolySia-NP-treatment-induced decreases in neovascularization and inflammatory response in a laser-induced CNV mouse model of neovascular AMD. In conclusion, PolySia-NP suppresses alternative pathway complement activity in human serum, human macrophage, and mouse CNV without increasing neovascularization.
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Age-related macular degeneration (AMD), a leading cause of visual loss and dysfunction worldwide, is a disease initiated by genetic polymorphisms that impair the negative regulation of complement. Proteomic investigation points to altered glycosylation and loss of Siglec-mediated glyco-immune checkpoint parainflammatory and inflammatory homeostasis as the main determinant for the vision impairing complications of macular degeneration. The effect of altered glycosylation on microglial maintained retinal para-inflammatory homeostasis and eventual recruitment and polarization of peripheral blood monocyte-derived macrophages (PBMDMs) into the retina can explain the phenotypic variability seen in this clinically heterogenous disease. Restoring glyco-immune checkpoint control with a sialic acid mimetic agonist targeting microglial/macrophage Siglecs to regain retinal para-inflammatory and inflammatory homeostasis is a promising therapeutic that could halt the progression of and improve visual function in all stages of macular degeneration.
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BACKGROUND: To determine the prevalence of macular cysts in patients with clinical cone-rod dystrophy (CORD) using spectral-domain optical coherence tomography (SD-OCT). If macular cysts could be demonstrated in such patients, they might benefit from treatment with a carbonic anhydrase inhibitor that has been shown to be effective for treating macular cysts in various night-blinding disorders. MATERIAL AND METHODS: Thirty-six CORD patients underwent a complete ophthalmic examination and an SD-OCT examination using two different systems. The presence of hypo-reflective lacunae was used to determine the presence of macular cysts. RESULTS: The patients' mean age was 42.9 ± 19.5 years (range 6-71 years). Mean BCVA was 1.09 ± 0.64 logMAR (range no light perception to 20/25 + 2 in the better-seeing eye). All the 72 eyes studied showed a variable degree of retinal thinning, disruption of what has been referred to as the inner segment ellipsoid and outer nuclear layer (ONL) thinning of the macula. None showed evidence of macular cysts on OCT testing. CONCLUSIONS: Although macular cysts are a common feature of various hereditary night-blinding retinal dystrophies, these were not identified in our cohort of CORD patients.
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Quistes/epidemiología , Retinitis Pigmentosa/epidemiología , Adolescente , Adulto , Anciano , Niño , Quistes/diagnóstico , Electrorretinografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Retinitis Pigmentosa/diagnóstico , Tomografía de Coherencia Óptica , Trastornos de la Visión/diagnóstico , Agudeza Visual/fisiología , Campos Visuales/fisiología , Adulto JovenAsunto(s)
Inhibidores de Anhidrasa Carbónica/uso terapéutico , Quistes/tratamiento farmacológico , Enfermedades de la Retina/tratamiento farmacológico , Retinosquisis/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Tiofenos/uso terapéutico , Adulto , Quistes/diagnóstico , Quistes/etiología , Electrorretinografía , Proteínas del Ojo/genética , Humanos , Masculino , Mutación Missense , Reacción en Cadena de la Polimerasa , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/etiología , Retinosquisis/complicaciones , Retinosquisis/diagnóstico , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To evaluate dark-adapted retinal sensitivity in patients with Stargardt disease (STGD1) using a modified MP-1 microperimeter and to compare the sensitivity loss with structural changes observed using spectral domain optical coherence tomography and confocal scanning laser ophthalmoscope infrared imaging. METHODS: Twelve STGD1 patients and 10 normally sighted controls participated. Dark-adapted mean sensitivity (MS) was obtained using a MP-1 microperimeter. Additionally, MS percent difference between the patients and the controls was obtained. Sensitivity results were superimposed on confocal scanning laser ophthalmoscope infrared images and compared with corresponding spectral domain optical coherence tomography scans. RESULTS: Dark-adapted MS ± standard deviation was 8.34 ± 1.54 dB for the controls and 3.68 ± 1.74 dB for STGD1 patients (P < 0.001). There was a significant reduction in MS of 24.0% in these patients. Sensitivity reductions were observed in areas that showed changes on confocal scanning laser ophthalmoscope infrared images and on spectral domain optical coherence tomography, including disorganizational loss of the retinal pigment epithelium, and abnormal photoreceptor inner segment ellipsoid and external limiting membrane reflectance bands. CONCLUSION: With topographical accuracy, dark-adapted MS measurements can be made in STGD1 patients and controls using the MP-1 microperimeter. Sensitivity loss is associated with structural changes. This finding can be useful for the determination of optimal areas for potential improvement of retinal function in patients with Stargardt disease.
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Adaptación a la Oscuridad/fisiología , Degeneración Macular/congénito , Retina/patología , Agudeza Visual/fisiología , Campos Visuales/fisiología , Adulto , Femenino , Humanos , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Oftalmoscopía , Enfermedad de Stargardt , Tomografía de Coherencia Óptica , Pruebas del Campo Visual , Adulto JovenRESUMEN
Cystic macular lesions frequently contribute to impaired visual acuity in hereditary retinal dystrophies. Their pathogenesis varies and is not entirely understood. Carbonic anhydrase inhibitors have proven to be potentially efficacious, although not in all cases. We discuss the various factors and mechanisms implicated in the etiology of cystic macular lesions (anatomical abnormalities, impairment of the blood-retinal barrier, tangential vitreous traction, and mutations in retinoschin, etc.) and the various treatments that have been proposed.
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Coroideremia/complicaciones , Enfermedades Hereditarias del Ojo/complicaciones , Atrofia Girata/complicaciones , Edema Macular/tratamiento farmacológico , Degeneración Retiniana/complicaciones , Retinitis Pigmentosa/complicaciones , Retinosquisis/complicaciones , Trastornos de la Visión/complicaciones , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Humanos , Edema Macular/diagnóstico , Edema Macular/etiologíaRESUMEN
PURPOSE: To determine the relationships among equivalent intrinsic noise (Neq), sampling efficiency, and contrast sensitivity (CS) in patients with retinitis pigmentosa (RP), where Neq is an estimate of the amount of noise within the visual pathway and sampling efficiency represents the subject's ability to use stimulus information optimally. METHODS: Participants included 10 patients with RP aged 10 to 54 years, who had visual acuities of 20/40 or better, and 10 visually normal control subjects aged 22 to 65 years. CS was measured for 2-cycles-per-degree Gabor patch targets presented in the absence of noise (CS0) and in five levels of noise spectral density. Data were fit with a standard linear amplifier model, which provided estimates of Neq and sampling efficiency. RESULTS: CS0 for the patients ranged from normal to as much as a factor of 3 below the lower limit of normal. All 10 patients had abnormally high Neq, including two patients with normal CS0. In comparison, only two patients had lower-than-normal sampling efficiency, and these two patients also had below-normal CS0. Log CS0 for the patients was correlated significantly with log Neq (r = -0.80, P < 0.05), but not with log efficiency (r = 0.54, P = 0.11). CONCLUSIONS: Low CS was associated with elevated intrinsic noise in this group of RP patients, but even patients with normal CS had elevated noise levels. The results suggest that CS measurement in both the presence and absence of luminance noise can provide important information about visual dysfunction in RP patients.
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Sensibilidad de Contraste/fisiología , Retinitis Pigmentosa/fisiopatología , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enmascaramiento Perceptual/fisiología , Estimulación Luminosa/métodos , Umbral Sensorial/fisiología , Adulto JovenRESUMEN
OBJECTIVE: To evaluate changes in visual acuity (VA) over time in patients with Leber congenital amaurosis (LCA) and mutations in the CEP290 gene. METHODS: Visual acuity was determined at the initial and most recent visits of 43 patients with LCA and CEP290 mutations. The main outcome measures included the best-corrected VA at the initial and most recent visits, as well as the correlation between age and VA. RESULTS: At the initial visit, 14 patients had measurable chart VA in the better-seeing eye, 25 patients had nonmeasurable chart VA, and 4 young patients did not have VA assessed. At the most recent visit, 15 patients had measurable chart VA and 28 had nonmeasurable chart VA. The average interval between the 2 visits was 10.4 years (range, 2-47 years). For patients with measurable chart VA, the median logMAR value at the initial visit (0.75; range, 0.10-2.30) and at the most recent visit (0.70; range, 0.10-2.00) did not differ significantly (P> .05). There was no significant relationship between VA and age. CONCLUSIONS: Patients with LCA and CEP290 mutations had a wide spectrum of VA that was not related to age or length of follow-up. Severe VA loss was observed in most, but not all, patients in the first decade. These data will help clinicians provide counseling on VA changes in patients with CEP290 mutations and could be of value for future treatment trials.
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Antígenos de Neoplasias/genética , Amaurosis Congénita de Leber/genética , Amaurosis Congénita de Leber/fisiopatología , Mutación , Proteínas de Neoplasias/genética , Agudeza Visual/fisiología , Adolescente , Adulto , Proteínas de Ciclo Celular , Niño , Preescolar , Proteínas del Citoesqueleto , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: This study aimed to determine whether the properties of the late negative responses (LNRs) of the electroretinogram (ERG) elicited by sawtooth flicker are consistent with the characteristics of the photopic negative response generated by a light pulse (PhNRpulse). METHODS: ERG recordings were obtained from 10 visually normal individuals and from 6 patients with optic atrophy (OA) in response to 8-Hz rapid-on and rapid-off sawtooth flicker and to brief (4 ms) light pulses. All stimuli were either long wavelength (R), middle wavelength (G), or a combination of equal luminances of long and middle wavelengths (Y) presented on a short-wavelength, rod-saturating adapting field. Amplitudes of LNRs were obtained in response to rapid-on (LNRon) and rapid-off (LNRoff) sawtooth flicker and were also derived from the sum of the ERG waveforms to the two sawtooth phases (LNRadd). RESULTS: For the control subjects, PhNRpulse amplitude varied with stimulus wavelength, being largest in response to a long-wavelength pulse, as expected. However, the amplitudes of LNRon, LNRoff, and LNRadd were not significantly different for R, Y, and G sawtooth flicker. Despite the absence of a chromatic effect, LNRoff and LNRadd amplitudes were significantly smaller in the OA patients than in the controls, similar to the results for the PhNRpulse, implying an inner retinal origin for the LNRoff and LNRadd. However, LNRon amplitudes did not differ significantly between the OA patients and controls, although there was a significant correlation between the LNRon and PhNRpulse for R stimuli. CONCLUSION: We conclude that LNRoff and LNRadd but not LNRon can be useful measures to assess the integrity of the inner retina that can complement the PhNRpulse.
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Adaptación Ocular , Visión de Colores/fisiología , Electrorretinografía/métodos , Atrofia Óptica/fisiopatología , Células Fotorreceptoras Retinianas Conos/fisiología , Adulto , Femenino , Humanos , Interneuronas/fisiología , Luz , Masculino , Persona de Mediana Edad , Atrofia Óptica/diagnóstico , Estimulación Luminosa , Adulto JovenRESUMEN
PURPOSE: To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. DESIGN: Prospective, observational case series. METHODS: We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. RESULTS: Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. CONCLUSIONS: The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus.
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Enfermedades Hereditarias del Ojo/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Miopía/diagnóstico , Ceguera Nocturna/diagnóstico , Células Fotorreceptoras de Vertebrados/patología , Células Bipolares de la Retina/patología , Células Ganglionares de la Retina/patología , Adolescente , Adulto , Adaptación a la Oscuridad/fisiología , Enfermedades Hereditarias del Ojo/genética , Femenino , Quinasa 1 del Receptor Acoplado a Proteína-G/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Miopía/genética , Ceguera Nocturna/genética , Oftalmoscopía , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Receptores de Glutamato/genética , Tomografía de Coherencia Óptica , Visión Ocular , Agudeza Visual/fisiología , Adulto JovenRESUMEN
PURPOSE: To measure the peripapillary retinal nerve fiber layer (RNFL) thickness using spectral-domain optical coherence tomography in patients with retinitis pigmentosa. METHODS: Fifty eyes of 30 patients with retinitis pigmentosa underwent a complete ocular examination, including best-corrected visual acuity using a Snellen chart, slit-lamp biomicroscopic examination, and Goldmann applanation intraocular pressure measurement. Dilated fundus examination was performed using both direct and indirect ophthalmoscopy. In addition, all patients underwent peripapillary RNFL thickness measurements using an OPKO spectral-domain optical coherence tomography (OPKO Instrumentations, Miami, FL). RESULTS: The mean (± SD) age of the study cohort was 45.8 (± 16.3) years. Of the 50 eyes, 18 (36%) showed a thinning of the peripapillary RNFL in 1 or more quadrants and 21 (42%) showed a thickening of the peripapillary RNFL in 1 or more quadrants. Four eyes (8%) showed both thinning and thickening of the peripapillary RNFL thickness. The overall circumferential RNFL thickness of the 14 eyes that showed only thinning in at least 1 quadrant was 78.78 µm. For the 17 eyes that showed only thickening in at least 1 quadrant, the RNFL thickness was 119.69 µm. The values of the eyes with thinning and the eyes with thickening were significantly different from normal (t = 6.31 and P < 0.01 for thickening; t = 3.62 and P < 0.01 for thinning). CONCLUSION: Using spectral-domain optical coherence tomography testing, we demonstrated in the current study that the peripapillary RNFL thickness in patients with RP can be decreased, increased, or maintained within normal limits. Assessment of the RNFL thickness seems prudent in these patients, particularly for identifying notable degrees of RNFL thinning in those being considered for future therapeutic trials.
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Axones/patología , Disco Óptico/patología , Células Ganglionares de la Retina/patología , Retinitis Pigmentosa/diagnóstico , Tomografía de Coherencia Óptica , Adolescente , Adulto , Anciano , Femenino , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Tonometría Ocular , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: : To determine the value of a topical carbonic anhydrase inhibitor on the macular thickness and function in choroideremia patients with cystoid macular edema. METHODS: : Two choroideremia patients with cystoid macular edema, observed by spectral-domain optical coherence tomography, were treated with a topical form of carbonic anhydrase inhibitor. Examinations performed before and during treatment included best-corrected visual acuity by using the Early Treatment Diabetic Retinopathy Study charts and contrast sensitivity measured with briefly presented grating targets and the Pelli-Robson letter contrast sensitivity chart, microperimetry, and spectral-domain optical coherence tomography. RESULTS: : The 2 choroideremia patients treated with dorzolamide 2% formulation had a noticeable reduction in macular thickness by spectral-domain optical coherence tomography. This reduction was found in both eyes after 2 months of treatment. After an additional 3 months of the same treatment regimen, a more noticeable reduction in macular thickness was observed. The two study patients had improvement of their visual acuity, in at least one eye, on Early Treatment Diabetic Retinopathy Study charts, but no clinically significant changes for the other measures of visual function. CONCLUSION: : The present study shows the potential efficacy of topical dorzolamide for treating choroideremia patients with cystoid macular edema.
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Inhibidores de Anhidrasa Carbónica/administración & dosificación , Coroideremia/complicaciones , Edema Macular/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Tiofenos/administración & dosificación , Sensibilidad de Contraste/fisiología , Humanos , Edema Macular/fisiopatología , Masculino , Persona de Mediana Edad , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Agudeza Visual/fisiología , Pruebas del Campo VisualRESUMEN
A 46-year-old woman with a vitelliform macular lesion secondary to desferrioxamine retinal toxicity in the right eye was treated with brinzolamide 1% ophthalmic drops three times a day. A spectral-domain optical coherence tomography (SD-OCT) unit was used to monitor any changes in the macular lesion. Two months after starting the eye drops, the SD-OCT showed a notable improvement in the vitelliform macular lesion's thickness. Six months later, further improvement was noted in the macular lesion thickness on SD-OCT testing in the right eye. Best-corrected visual acuity was initially 1.00 logarithm of the minimum angle of resolution (20/200 on a Snellen acuity chart) in the right eye and 0.14 logarithm of the minimum angle of resolution (20/25(-2)) in the left eye. After 6 months of treatment, visual acuity was 0.92 (20/200(+1)) in the right eye and 0.08 (20/25(+1)) in the left eye. The use of brinzolamide 1% was associated with a marked reduction in a vitelliform macular lesion on SD-OCT testing secondary to desferrioxamine retinal toxicity.
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Inhibidores de Anhidrasa Carbónica/uso terapéutico , Enfermedades de la Retina/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Tiazinas/uso terapéutico , Deferoxamina/efectos adversos , Femenino , Humanos , Mácula Lútea/efectos de los fármacos , Persona de Mediana Edad , Soluciones Oftálmicas/uso terapéutico , Enfermedades de la Retina/inducido químicamente , Sideróforos/efectos adversos , Tomografía de Coherencia Óptica/métodos , Resultado del Tratamiento , Agudeza VisualRESUMEN
PURPOSE: To assess photoreceptor structure and function in patients with congenital achromatopsia. METHODS: Twelve patients were enrolled. All patients underwent a complete ocular examination, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinographic (ERG), and color vision testing. Macular microperimetry (MP; in four patients) and adaptive optics (AO) imaging (in nine patients) were also performed. Blood was drawn for screening of disease-causing genetic mutations. RESULTS: Mean (± SD) age was 30.8 (± 16.6) years. Mean best-corrected visual acuity was 0.85 (± 0.14) logarithm of the minimal angle of resolution (logMAR) units. Seven patients (58.3%) showed either an absent foveal reflex or nonspecific retinal pigment epithelium mottling to mild hypopigmentary changes on fundus examination. Two patients showed an atrophic-appearing macular lesion. On anomaloscopy, only 5 patients matched over the entire range from 0 to 73. SD-OCT examination showed a disruption or loss of the macular inner/outer segments (IS/OS) junction of the photoreceptors in 10 patients (83.3%). Seven of these patients showed an optically empty space at the level of the photoreceptors in the fovea. AO images of the photoreceptor mosaic were highly variable but significantly disrupted from normal. On ERG testing, 10 patients (83.3%) showed evidence of residual cone responses to a single-flash stimulus response. The macular MP testing showed that the overall mean retinal sensitivity was significantly lower than normal (12.0 vs. 16.9 dB, P < 0.0001). CONCLUSIONS: The current approach of using high-resolution techniques to assess photoreceptor structure and function in patients with achromatopsia should be useful in guiding selection of patients for future therapeutic trials as well as monitoring therapeutic response in these trials.
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Defectos de la Visión Cromática/fisiopatología , Células Fotorreceptoras de Vertebrados/patología , Adolescente , Adulto , Pruebas de Percepción de Colores , Defectos de la Visión Cromática/congénito , Defectos de la Visión Cromática/genética , Canales Catiónicos Regulados por Nucleótidos Cíclicos/genética , Análisis Mutacional de ADN , Electrorretinografía , Exones/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Estimulación Luminosa , Reacción en Cadena de la Polimerasa , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Pruebas del Campo VisualRESUMEN
PURPOSE: To correlate macular structural changes by spectral-domain optical coherence tomography (SD-OCT) with functional changes by scanning laser ophthalmoscope (SLO) microperimetry testing in patients with sickle cell hemoglobinopathies. DESIGN: Prospective, investigational study. METHODS: Patients with electrophoretic confirmation of sickle cell hemoglobinopathies and normal subjects underwent SD-OCT and microperimetry testing with the OPKO Spectral OCT/SLO instrument. Based on SD-OCT findings, patients were grouped into those with focal macular thinning (Group A) and those without (Group B). Main outcome measure were mean retinal sensitivities measured by microperimetry and mean macular thicknesses in the 9 Early Treatment Diabetic Retinopathy Study (ETDRS)-like subfields. RESULTS: Thirty-seven eyes of 19 patients with sickle cell hemoglobinopathies (SS, SC, and S-thalassemia) and 34 eyes of 34 age-similar normal controls were included. Mean age and mean logMAR best-corrected visual acuity between Groups A and B were not statistically different (39.7 years vs 36.5 years, P = .64 and 0.015 vs 0.016, P = .93, respectively). Group A had significantly thinner retinas compared to Group B in the parafoveal superior (P = .019), parafoveal temporal (P < .004), parafoveal inferior (P = .003), perifoveal superior (P = .04), perifoveal temporal (P = .0005), and perifoveal inferior (P = .045) subfields. The overall mean microperimetry retinal sensitivities of Group A were significantly less than those of Group B (14.2 dB vs 16.5 dB, P = .00005). However, there was no statistical difference between Group B and controls (16.5 dB vs 16.7 dB, P = .63). CONCLUSION: Sickle cell patients with focal macular thinning present on SD-OCT have significantly decreased retinal sensitivities compared to those without focal thinning or normal controls based on mean microperimetry sensitivities, despite similar age and visual acuity. Microperimetry is a sensitive measurement of macular function in patients with sickle cell hemoglobinopathies.
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Anemia de Células Falciformes/fisiopatología , Retina/fisiopatología , Enfermedades de la Retina/fisiopatología , Tomografía de Coherencia Óptica , Adulto , Anciano , Humanos , Rayos Láser , Persona de Mediana Edad , Oftalmoscopios , Estudios Prospectivos , Agudeza Visual/fisiología , Pruebas del Campo Visual , Campos Visuales/fisiología , Adulto JovenRESUMEN
PURPOSE: To correlate the degree of functional loss with structural changes in patients with Stargardt disease. METHODS: Eighteen eyes of 10 patients with Stargardt disease were studied. Scanning laser ophthalmoscope infrared images were compared with corresponding spectral-domain optical coherence tomography scans. Additionally, scanning laser ophthalmoscope microperimetry was performed, and results were superimposed on scanning laser ophthalmoscope infrared images and in selected cases on fundus autofluorescence images. RESULTS: Seventeen of 18 eyes showed a distinct hyporeflective foveal and/or perifoveal area with distinct borders on scanning laser ophthalmoscope infrared images, which was less evident on funduscopy and incompletely depicted in fundus autofluorescence images. This hyporeflective zone corresponded to areas of significantly elevated psychophysical thresholds on microperimetry testing, in addition to thinning of the retinal pigment epithelium and disorganization or loss of the photoreceptor cell inner segment-outer segment junction and external-limiting membrane on spectral-domain optical coherence tomography. CONCLUSION: Scanning laser ophthalmoscope infrared fundus images are useful for depicting retinal structural changes in patients with Stargardt disease. A spectral-domain optical coherence tomography/scanning laser ophthalmoscope microperimetry device allows for a direct correlation of structural abnormalities with functional defects that will likely be applicable for the determination of retinal areas for potential improvement of retinal function in these patients during future clinical trials and for the monitoring of the diseases' natural history.
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Mácula Lútea/fisiopatología , Degeneración Macular/fisiopatología , Oftalmoscopios , Pruebas del Campo Visual , Transportadoras de Casetes de Unión a ATP/genética , Adolescente , Adulto , Femenino , Humanos , Rayos Infrarrojos , Rayos Láser , Degeneración Macular/congénito , Degeneración Macular/genética , Masculino , Persona de Mediana Edad , Epitelio Pigmentado de la Retina/patología , Enfermedad de Stargardt , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Adulto JovenRESUMEN
PURPOSE: To evaluate the presence of peripapillary retinal nerve fiber layer (RNFL) defects in patients with choroideremia by using spectral-domain optical coherence tomography (SD-OCT). METHODS: Twenty-nine eyes of 16 patients with choroideremia underwent peripapillary RNFL thickness measurements by using SD-OCT. RESULTS: The mean (±SD) age of the study population was 44.0 ± 16.0 years (range, 13-63 years). Thirteen eyes (45%) showed a thinning of the peripapillary RNFL in at least 1 quadrant in either 1 or both eyes. Thinning was most commonly found in the superior (13 eyes) and inferior (10 eyes) quadrants. Twenty-one eyes (72%) showed a thickening of the peripapillary RNFL in at least 1 quadrant in either 1 or both eyes. Of these 21 eyes, all had thickening in the temporal quadrant. Additionally, 2 eyes in each of the other 3 quadrants were found to be abnormally thick. CONCLUSION: Our study demonstrated the presence of defects in the peripapillary RNFL thickness in patients with choroideremia by using SD-OCT. It would be clinically prudent that choroideremia patients considered for various treatment options be considered for RNFL thickness measurements.
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Coroideremia/diagnóstico , Fibras Nerviosas/patología , Enfermedades del Nervio Óptico/diagnóstico , Nervio Óptico/patología , Células Ganglionares de la Retina/patología , Adolescente , Adulto , Coroideremia/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Estudios Prospectivos , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
AIMS: To evaluate the presence of peripapillary retinal nerve fibre layer (RNFL) defects in patients with Stargardt disease by using spectral-domain optical coherence tomography (SD-OCT). METHODS: Fifty-two eyes of 27 patients with Stargardt disease underwent peripapillary RNFL thickness measurements using SD-OCT. RESULTS: Twenty-seven patients with Stargardt disease were enrolled. Their mean (±SD) age was 38.3 (14.7) years. Fourteen patients (51.9%) showed a thinning of the peripapillary RNFL in one or more quadrants in at least one eye, and four patients (14.8%) in both eyes. Five patients (18.5%) showed a thickening of the peripapillary RNFL in at least one eye, and four patients (14.8%) in both eyes. CONCLUSION: This study demonstrated the presence of defects in the peripapillary RNFL thickness in patients with Stargardt disease by using SD-OCT. It would be clinically prudent that Stargardt patients considered for various treatment options be considered for RNFL thickness measurements.
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Mácula Lútea/patología , Fibras Nerviosas/patología , Retina/patología , Agudeza Visual/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Degeneración Macular/congénito , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad de Stargardt , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
The purpose of this study was to evaluate the efficacy of topical dorzolamide 2% eye drops on macular function and thickness in a case of enhanced S-cone syndrome (ESCS). A 24-year-old Asian man with enhanced S-cone syndrome treated with topical dorzolamide in the left eye participated in the study. Examinations performed before and during treatment were included visual acuity (VA), contrast sensitivity measured with briefly presented grating targets (grating CS) and the Pelli-Robson chart (P-R CS), microperimetry (MP), and spectral-domain optical coherence tomography (SD-OCT). Following 4 months of treatment, the mean thickness of the central 1-mm foveal subfield of the left eye, as measured by SD-OCT, decreased from 551 to 242 µm. Mean MP sensitivity within the central 12 degrees (28 points) increased from 9.4 dB at baseline to 11.2 dB. Although Pelli-Robson contrast sensitivity improved only minimally in the left eye, grating contrast sensitivity improved by more than a factor of two. Mean log MAR VA was 0.22 OD and 1.00 OS (at baseline), which improved to 0.10 OD and 0.66 OS after 4 months of treatment. The results indicate that in our patient with enhanced S-cone syndrome, treatment with topical dorzolamide was effective in improving macular thickness, VA, microperimetry sensitivity, and grating contrast sensitivity. These measures of retinal structure and function are sensitive tools for evaluating the effects of treatment in enhanced S-cone syndrome patients with cystoid macular edema. Further investigation is warranted to assess the relationships among visual performance for daily activities, visual sensitivity, and macular thickness.