RESUMEN
BACKGROUND: Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus and is often used for other inflammatory conditions, but a critical long-term adverse effect is vision-threatening retinopathy. OBJECTIVE: To characterize the long-term risk for incident hydroxychloroquine retinopathy and examine the degree to which average hydroxychloroquine dose within the first 5 years of treatment predicts this risk. DESIGN: Cohort study. SETTING: U.S. integrated health network. PARTICIPANTS: All patients aged 18 years or older who received hydroxychloroquine for 5 or more years between 2004 and 2020 and had guideline-recommended serial retinopathy screening. MEASUREMENTS: Hydroxychloroquine dose was assessed from pharmacy dispensing records. Incident hydroxychloroquine retinopathy was assessed by central adjudication of spectral domain optical coherence tomography with severity assessment (mild, moderate, or severe). Risk for hydroxychloroquine retinopathy was estimated over 15 years of use according to hydroxychloroquine weight-based dose (>6, 5 to 6, or ≤5 mg/kg per day) using the Kaplan-Meier estimator. RESULTS: Among 3325 patients in the primary study population, 81 developed hydroxychloroquine retinopathy (56 mild, 17 moderate, and 8 severe), with overall cumulative incidences of 2.5% and 8.6% at 10 and 15 years, respectively. The cumulative incidences of retinopathy at 15 years were 21.6% for higher than 6 mg/kg per day, 11.4% for 5 to 6 mg/kg per day, and 2.7% for 5 mg/kg per day or lower. The corresponding risks for moderate to severe retinopathy at 15 years were 5.9%, 2.4%, and 1.1%, respectively. LIMITATION: Possible misclassifications of dose due to nonadherence to filled prescriptions. CONCLUSION: In this large, contemporary cohort with active surveillance retinopathy screening, the overall risk for hydroxychloroquine retinopathy was 8.6% after 15 years, and most cases were mild. Higher hydroxychloroquine dose was associated with progressively greater risk for incident retinopathy. PRIMARY FUNDING SOURCE: National Institutes of Health.
Asunto(s)
Antirreumáticos , Lupus Eritematoso Sistémico , Enfermedades de la Retina , Humanos , Hidroxicloroquina/efectos adversos , Antirreumáticos/efectos adversos , Estudios de Cohortes , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/tratamiento farmacológico , Lupus Eritematoso Sistémico/tratamiento farmacológicoRESUMEN
PURPOSE: To demonstrate rapid macular thinning as an early and objective sign of hydroxychloroquine retinopathy. DESIGN: Retrospective case cohort. PARTICIPANTS: Cohort of 301 patients receiving long-term hydroxychloroquine therapy at Kaiser Permanente Northern California who underwent a minimum of 4 OCT studies that included Early Treatment Diabetic Retinopathy Study (ETDRS) retinal thickness values over a minimum of 4 years. METHODS: Creation of sequential retinal thickness plots to show the rate of change in macular thickness within ETDRS regions. MAIN OUTCOME MEASURES: Identification of rapid macular thinning, comparison of patients with rapid thinning to those with stable macular thickness, and comparison of rapid thinning patients with and without conventional OCT or 10-2 visual field signs of hydroxychloroquine toxicity. RESULTS: Retina thinning in 219 stable patients receiving long-term hydroxychloroquine therapy averaged (mean ± standard deviation) 0.62 ± 0.45 µm/year, whereas 82 patients showed a period of relatively linear rapid thinning with a loss of 3.75 ± 1.34 µm/year. Of the patients with rapid thinning, 38 eventually demonstrated conventional OCT or 10-2 visual field signs of hydroxychloroquine retinal toxicity. The cumulative retinal thinning in these patients was 25.1 ± 6.2 µm compared with 15.7 ± 4.0 µm in those without conventional toxicity (P < 0.01). CONCLUSIONS: Retinal thickness remains stable for many years in most patients receiving long-term hydroxychloroquine therapy, but after a critical point, the retina may begin to thin rapidly. Sequential plots of inner and outer ETDRS ring macular thickness provide objective evidence of this early structural change several years before conventional signs appear. This approach can alert patients and prescribing physicians to potential retinal damage and uses readily available OCT measurements that could be automated by manufacturers for use in comprehensive eye care settings.
Asunto(s)
Antirreumáticos , Retinopatía Diabética , Degeneración Retiniana , Antirreumáticos/efectos adversos , Humanos , Hidroxicloroquina/efectos adversos , Retina , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: The photopic negative response (PhNR) correlates with ganglion cell function and has previously been examined as an indicator of glaucomatous optic nerve damage. However, it is a prolonged response that is measured against baseline, and its clinical utility has been limited by extensive variability, poor repeatability, and baseline instability. We have observed a distinct brief negative wave ("N-wave") commonly present within the slow PhNR trough, which may provide practical and analytic advantages as a clinical measure. METHODS: We reviewed data from an interventional trial of 59 glaucoma patients who had 4 exams over an 8-month period. The PhNR was recorded with standard ISCEV stimuli (1 Hz and in some cases 4 Hz stimulation), and N-waves were measured manually, relative to return to baseline. RESULTS: N-waves, when present, could be measured easily despite shifting baselines and a degree of background noise. The PhNR median amplitude centered around 18 µV, while the N-wave median centered around 7 µV, with a distribution of responses skewed toward low or zero amplitudes. CONCLUSIONS: The N-wave appears to be a component of the longer PhNR, though its exact origin and significance remain unclear. As a rapid waveform that is independent of baseline, the N-wave is in many ways easier to measure accurately than the slower PhNR, which is highly dependent on baseline stability. The N-wave may prove useful clinically if further studies can optimize its stimulation, show its behavior in normal individuals and find correlation with markers of optic nerve disease.
Asunto(s)
Visión de Colores/fisiología , Glaucoma/fisiopatología , Enfermedades del Nervio Óptico/fisiopatología , Retina/fisiopatología , Células Ganglionares de la Retina/fisiología , Administración Oftálmica , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Electrorretinografía , Femenino , Glaucoma/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Factor de Crecimiento Nervioso/uso terapéutico , Soluciones Oftálmicas , Enfermedades del Nervio Óptico/tratamiento farmacológico , Estimulación Luminosa , Estudios Prospectivos , Proteínas Recombinantes , Adulto JovenRESUMEN
PURPOSE: To characterize the stability or progression of different stages of hydroxychloroquine (HCQ) retinopathy up to 20 years after stopping the drug. METHODS: We reviewed findings from 13 patients with initial HCQ retinopathy classified as early (patchy photoreceptor damage), moderate (ring of photoreceptor thinning or scotoma), or severe (retinal pigment epithelial [RPE] damage). Patients had been off HCQ for as many as 14 years at initial examination and were subsequently followed for 5 years to 8 years with repeated fundus autofluorescence and spectral domain optical coherence tomography. RESULTS: Early and moderate cases stabilized in fundus autofluorescence appearance, foveal thickness, ellipsoid zone line length, and visual acuity for up to 9 years after stopping HCQ. By contrast, severe cases demonstrated a continual loss of these parameters for up to 20 years off the drug. The presence of RPE damage at initial examination predicted progressive retinopathy over many years. CONCLUSION: The steady progression of severe HCQ retinopathy in eyes showing RPE damage after drug cessation suggests a metabolic insult that chronically destabilizes rather than destroys cellular function, with a clinical course resembling that of genetic dystrophies. Our findings stress the importance of early detection to minimize progression and visual loss.
Asunto(s)
Antirreumáticos/efectos adversos , Inhibidores Enzimáticos/efectos adversos , Hidroxicloroquina/efectos adversos , Enfermedades de la Retina , Progresión de la Enfermedad , Femenino , Angiografía con Fluoresceína , Fóvea Central/patología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/patología , Enfermedades de la Retina/fisiopatología , Epitelio Pigmentado de la Retina/patología , Escotoma/inducido químicamente , Escotoma/patología , Tomografía de Coherencia Óptica , Trastornos de la Visión/inducido químicamente , Agudeza Visual/fisiología , Pruebas del Campo Visual , Campos Visuales/fisiologíaRESUMEN
PURPOSE: Complete congenital stationary night blindness (CSNB) is most often x-linked or recessive, and associated with a transmission defect from photoreceptors to bipolar cells. This produces a characteristic "negative" Schubert-Bornschein type of scotopic rod-cone electroretinogram (ERG) with a large a-wave and minimal b-wave. CSNB from abnormalities in phototransduction can be recessive or dominant and is much less common. This produces a Riggs type of ERG with loss of the rod a-wave as well as the b-wave. We report the clinical and ERG findings from a family with autosomal dominant CSNB that was shown previously to have a new GNAT1 mutation with a novel mechanism of action. They provide a classic demonstration of the Riggs-type ERG and have an unusual systemic association. METHODS: Clinical case report of a father and daughter. RESULTS: A Chinese father and daughter presented with good visual acuity, moderate myopia, and lifelong night blindness. Both show normal fundi except for mild myopia, and fundus autofluorescence and OCT images are normal. Their ERGs illustrate the typical Riggs-type ERG with no rod a-wave (they have only a small cone-dominated combined response). They also have postural orthostatic tachycardia syndrome (POST), which is an autonomic dysfunction disorder thought usually to be sporadic. The retinal gene analyses revealed no abnormalities that might account for POST. CONCLUSIONS: Our family's ERG showed essentially no rod response, consistent with a Danish GNAT1 pedigree but different from the Nougaret GNAT1 pedigree that shows partial preservation of rod signal. A genetic connection between CSNB and POST would be intriguing, but we found no evidence for this.
Asunto(s)
Electrorretinografía , Enfermedades Hereditarias del Ojo/genética , Enfermedades Hereditarias del Ojo/fisiopatología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Proteínas de Unión al GTP Heterotriméricas/genética , Mutación , Miopía/genética , Miopía/fisiopatología , Ceguera Nocturna/genética , Ceguera Nocturna/fisiopatología , Síndrome de Taquicardia Postural Ortostática/genética , Células Fotorreceptoras Retinianas Bastones/fisiología , Adulto , Femenino , Humanos , Masculino , Síndrome de Taquicardia Postural Ortostática/fisiopatología , Tomografía de Coherencia Óptica , Transducina , Adulto JovenRESUMEN
PURPOSE: Many mfERG displays show normal responses that are larger at the center than peripherally, and the typical linear display of signals is inaccurate with respect to the retinal location of the signals. Printouts do not always indicate retinal or field view, they sometimes emphasize 3-D topographic plots which are not always representative of physiologic signals, and they show ring response densities which are different in every ring and hard to interpret without norms. These problems limit the clinical usefulness of the mfERG and limit communication in the literature. We share our Stanford Display to illustrate possible solutions to these problems. METHODS: We have changed the scaling factor for our mfERG unit to produce a trace array with near equal signals everywhere. We display responses is a spatially scaled array, in a retinal view, so that signals appear in their correct anatomic locations relative to a fundus image. The 3-D display is minimized on the page of signal analysis, and we emphasize ring response averages rather than ring response densities. RESULTS: The new scaling and trace array display greatly facilitate the analysis of retinal disease. Regions of loss are easily recognized in their fundus location. Ring ratios based upon response amplitudes all have a normal value of 1.0 which simplifies analysis. A case of early hydroxychloroquine retinopathy demonstrates the use of this Stanford display. CONCLUSIONS: Recognition of these recording and display options may help mfERG users to maximize the value of the test. Proper scaling of the mfERG stimulus array facilitates localization of retinal disease and simplifies ring response analysis. Different laboratories will have different priorities for signal analysis, but mfERG displays should always indicate the eccentricity of responses, and the use of a retina or field view.
Asunto(s)
Antirreumáticos/toxicidad , Presentación de Datos , Electrorretinografía/efectos de los fármacos , Hidroxicloroquina/toxicidad , Retina/fisiopatología , Enfermedades de la Retina/fisiopatología , Electrorretinografía/métodos , Femenino , Fondo de Ojo , Humanos , Persona de Mediana Edad , Valores de Referencia , Retina/efectos de los fármacos , Enfermedades de la Retina/inducido químicamenteRESUMEN
PURPOSE: To study whether the ERG and other clinical findings help to distinguish between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse retinitis pigmentosa (RP) with similar fundus appearance. METHODS: We conducted a retrospective analysis of patients with advanced HCQ retinopathy (n = 11), pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as having limited fundus damage and relatively normal flicker ERG time-to-peak. Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients showed reduced amplitude of the ISCEV responses in the full-field electroretinogram (ERG). Aspects of history, visual field results, fundus appearance, fundus autofluorescence and ocular coherence tomography were also compared. RESULTS: Relative to pericentral RP, patients with HCQ toxicity showed delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined rod-cone responses. Relative to diffuse RP, most HCQ toxicity patients had some preserved rod ERG response, and there was no obvious predilection for rod over cone damage. In addition, patients with HCQ toxicity usually lacked markers of long-standing degeneration such as bone spicule figures or severe loss of peripheral field. History of familial disease and long-standing night blindness were specific to RP. CONCLUSIONS: While the early signs of HCQ damage are typically regional in the posterior pole, advanced disease is characteristically diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is the finding that rods and cones were both affected in the ERG to a similar degree (unlike genetic rod-cone dystrophies). For patients with severe HCQ exposure and some of our discriminatory findings, and no family history or prior night blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare disease (Occam's razor).
Asunto(s)
Electrorretinografía , Inhibidores Enzimáticos/efectos adversos , Hidroxicloroquina/efectos adversos , Enfermedades de la Retina/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Células Fotorreceptoras de Vertebrados/fisiología , Retinitis Pigmentosa/diagnóstico , Estudios Retrospectivos , Campos VisualesRESUMEN
BACKGROUND: The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools. PATTERN OF RETINOPATHY: Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. DOSE: We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight. RISK OF TOXICITY: The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year. MAJOR RISK FACTORS: High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen. SCREENING SCHEDULE: A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors. SCREENING TESTS: The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus. TOXICITY: Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication. COUNSELING: Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening.
Asunto(s)
Antirreumáticos/toxicidad , Cloroquina/toxicidad , Hidroxicloroquina/toxicidad , Enfermedades de la Retina/diagnóstico , Trastornos de la Visión/diagnóstico , Academias e Institutos , Adulto , Antirreumáticos/administración & dosificación , Pueblo Asiatico/etnología , Cloroquina/administración & dosificación , Electrorretinografía/efectos de los fármacos , Femenino , Angiografía con Fluoresceína , Humanos , Hidroxicloroquina/administración & dosificación , Concentración Máxima Admisible , Persona de Mediana Edad , Oftalmología/organización & administración , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/etnología , Factores de Riesgo , Tomografía de Coherencia Óptica , Estados Unidos , Trastornos de la Visión/inducido químicamente , Trastornos de la Visión/etnología , Agudeza Visual/efectos de los fármacos , Agudeza Visual/fisiología , Pruebas del Campo Visual , Campos Visuales/efectos de los fármacos , Campos Visuales/fisiologíaRESUMEN
PURPOSE: To describe patterns of hydroxychloroquine retinopathy distinct from the classic parafoveal (bull's eye) maculopathy. DESIGN: Retrospective case series. PARTICIPANTS: Patients from a large multi-provider group practice and a smaller university referral practice diagnosed with hydroxychloroquine retinopathy. Patients with widespread or "end-stage" retinopathy were excluded. METHODS: Review of ophthalmic studies (fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, multifocal electroretinography, visual fields) and classification of retinopathy into 1 of 3 patterns: parafoveal (retinal changes 2°-6° from the fovea), pericentral (retinal changes ≥ 8° from the fovea), or mixed (retinal changes in both parafoveal and pericentral areas). MAIN OUTCOME MEASURES: Relative frequency of different patterns of hydroxychloroquine retinopathy and comparison of risk factors. RESULTS: Of 201 total patients (18% Asian) with hydroxychloroquine retinopathy, 153 (76%) had typical parafoveal changes, 24 (12%) also had a zone of pericentral damage, and 24 (12%) had pericentral retinopathy without any parafoveal damage. Pericentral retinopathy alone was seen in 50% of Asian patients but only in 2% of white patients. Patients with the pericentral pattern were taking hydroxychloroquine for a somewhat longer duration (19.5 vs. 15.0 years, P < 0.01) and took a larger cumulative dose (2186 vs. 1813 g, P = 0.02) than patients with the parafoveal pattern, but they were diagnosed at a more severe stage of toxicity. CONCLUSIONS: Hydroxychloroquine retinopathy does not always develop in a parafoveal (bull's eye) pattern, and a pericentral pattern of damage is especially prevalent among Asian patients. Screening practices may need to be adjusted to recognize pericentral and parafoveal hydroxychloroquine retinopathy.
Asunto(s)
Antirreumáticos/toxicidad , Pueblo Asiatico/etnología , Hidroxicloroquina/toxicidad , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/etnología , Población Blanca/etnología , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Fóvea Central , Fondo de Ojo , Humanos , Persona de Mediana Edad , Enfermedades de la Retina/diagnóstico , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tomografía de Coherencia Óptica , Agudeza Visual , Pruebas del Campo Visual , Campos VisualesRESUMEN
PURPOSE: A pericentral pattern of hydroxychloroquine (HCQ) retinopathy recently has been recognized in the United States in patients of Asian heritage. We report on an investigation of this pericentral retinopathy within a Korean population. DESIGN: Retrospective, observational study. PARTICIPANTS: Patients taking HCQ who were referred to ophthalmology for screening of HCQ retinopathy. METHODS: The medical records of patients were reviewed, including spectral domain optical coherence tomography, fundus autofluorescence, and visual fields. MAIN OUTCOME MEASURES: Frequency of pericentral pattern of HCQ retinopathy and features of progression. RESULTS: Among 218 patients referred, 9 (4.1%) were diagnosed with toxicity. Of these, 8 had a predominantly pericentral pattern of retinal change, whereas only 1 had the classic parafoveal distribution of retinal damage. Progression of retinopathy was documented in 3 patients followed more than 12 months while taking HCQ. No progression was seen in 2 patients without retinal pigment epithelial (RPE) damage who were followed for at least 12 months after discontinuation of HCQ. CONCLUSIONS: We found that a pericentral pattern of HCQ retinopathy was predominant among Korean patients, rather than the traditional (bull's eye) parafoveal pattern of damage. Retinopathy progressed while on the drug, but the progression stopped in patients with toxicity detected before RPE damage. These observations suggest the need for new approaches when screening for HCQ toxicity in Asian patients.
Asunto(s)
Antirreumáticos/efectos adversos , Hidroxicloroquina/efectos adversos , Enfermedades de la Retina/inducido químicamente , Adulto , Anciano , Pueblo Asiatico/etnología , Progresión de la Enfermedad , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/etnología , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Tomografía de Coherencia Óptica , Selección Visual , Pruebas del Campo Visual , Campos Visuales/fisiologíaRESUMEN
This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for full-field clinical electroretinography (ffERG or simply ERG). The parameters for Standard flash stimuli have been revised to accommodate a variety of light sources including gas discharge lamps and light emitting diodes. This ISCEV Standard for clinical ERGs specifies six responses based on the adaptation state of the eye and the flash strength: (1) Dark-adapted 0.01 ERG (rod ERG); (2) Dark-adapted 3 ERG (combined rod-cone standard flash ERG); (3) Dark-adapted 3 oscillatory potentials; (4) Dark-adapted 10 ERG (strong flash ERG); (5) Light-adapted 3 ERG (standard flash "cone" ERG); and (6) Light-adapted 30 Hz flicker ERG. ISCEV encourages the use of additional ERG protocols for testing beyond this minimum standard for clinical ERGs.
Asunto(s)
Electrorretinografía/normas , Oftalmología/organización & administración , Células Fotorreceptoras de Vertebrados/fisiología , Sociedades Médicas/normas , Acomodación Ocular/fisiología , Adaptación a la Oscuridad/fisiología , Electrodos , Electrorretinografía/instrumentación , Humanos , Estimulación Luminosa/métodos , Neuronas Retinianas/fisiologíaRESUMEN
This article considers the impact of vision and hearing loss on great painters and musical composers. The visual work of Mary Cassatt, Georgia O'Keeffe, Edgar Degas, and Claude Monet all showed alterations as their vision failed. In contrast, Gabriel Fauré, Bedrich Smetana, and Ludwig von Beethoven wrote many of their best compositions while totally deaf, and Georg Friedrich Handel and Frederick Delius struggled to compose late in life when they lost their vision (although their hearing remained excellent). There are 2 major distinctions between the role of vision and hearing for these artistic disciplines. First, there is a surrogate means of "hearing" music, through the musical score, which allows composers to write and edit music while totally deaf. The greatest problem with deafness for a skilled composer is interference from internal noise (tinnitus). There is no surrogate for vision to allow a painter to work when the subject is a blur or the colors on the canvas cannot be distinguished. Second, although the appreciation of art is visual and that of music is auditory, the transcription of both art and musical composition is visual. Thus, visual loss does pose a problem for a composer accustomed to working with good sight, because it disrupts habitual methods of writing and editing music.
Asunto(s)
Personajes , Pérdida Auditiva/historia , Música/historia , Pinturas/historia , Personas con Deficiencia Auditiva/historia , Baja Visión/historia , Personas con Daño Visual/historia , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , HumanosRESUMEN
PURPOSE: American Academy of Ophthalmology recommendations for screening for hydroxychloroquine (HCQ) retinopathy advise objective measures, such as spectral-domain optical coherence tomography (SD-OCT) and multifocal electroretinography (mfERG) along with visual fields. However, the relative sensitivity and specificity of screening tests have not been fully resolved. We characterize a subset of patients with toxicity who show unusual disparity between fields and SD-OCT and thus have implications for screening practice. DESIGN: Review of charts and clinical data. PARTICIPANTS: Patients at Stanford and Kaiser Permanente who had used HCQ with greater than 1000 g cumulative exposure. There were more than 2000 such individuals, among whom 150 had clear evidence of toxicity. METHODS: Patients were evaluated by visual fields (10-2 white Swedish Interactive Threshold Algorithm pattern deviation plots), SD-OCT, and sometimes mfERG or fundus autofluorescence. MAIN OUTCOME MEASURES: Relative findings on visual fields in comparison with SD-OCT. RESULTS: There were 11 patients among those with HCQ toxicity who had parafoveal ring scotomas but a normal-appearing SD-OCT. None had a history of macular disease or evidence for any other cause of bull's eye maculopathy. Conversely, all cases with a clear degree of parafoveal damage on SD-OCT showed at least some focal spots of parafoveal field loss. CONCLUSIONS: Approximately 10% of patients with early HCQ toxicity showed prominent ring scotomas on field testing without obvious SD-OCT abnormality. This should encourage the inclusion of visual fields as a key screening tool, even when SD-OCT (a more specific and objective test) also is performed. The combination of visual fields and SD-OCT gives both sensitivity and specificity while avoiding unnecessary stoppage of the drug.
Asunto(s)
Antirreumáticos/efectos adversos , Hidroxicloroquina/efectos adversos , Enfermedades de la Retina/diagnóstico , Escotoma/diagnóstico , Tomografía de Coherencia Óptica , Trastornos de la Visión/diagnóstico , Campos Visuales/efectos de los fármacos , Anciano , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Enfermedades de la Retina/inducido químicamente , Estudios Retrospectivos , Escotoma/inducido químicamente , Sensibilidad y Especificidad , Trastornos de la Visión/inducido químicamente , Pruebas del Campo VisualRESUMEN
PURPOSE: To review reported retinal side effects from current cancer therapy drugs. METHODS: Retinal toxicities from ophthalmologic or oncologic case reports, case series, and clinical trials were identified by a systematic literature search using Lexicomp and PubMed. RESULTS: Four biologics, 8 small molecule inhibitors, and 17 traditional chemotherapy agents had reported retinal side effects. For biologics, interferon alpha 2b was associated with retinopathy, denileukin diftitiox with pigmentary retinopathy, ipilimumab with a Vogt-Koyanagi-Harada-like syndrome, and trastuzumab with retinal ischemia. For small molecule inhibitors, v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors were associated with uveitis, mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitors with pigment epithelium detachments, and tyrosine kinase inhibitors with macular edema. Steroid antagonists were associated with crystalline retinopathy and macular edema. Nitrosoureas, platinum analogs, and cytosine arabinoside were associated with retinal vascular occlusions. Antimicrotubular agents were associated with cystoid macular edema but without fluorescein leakage. Retinoic acid derivatives were associated with impaired night vision, and mitotane was associated with a pigmentary retinopathy and papilledema. CONCLUSION: Certain agents used in the treatment of systemic cancer are associated with ocular complications. Awareness of these complications will allow early detections and maybe reversal of some of the ocular problems.
Asunto(s)
Anticuerpos Monoclonales/toxicidad , Antineoplásicos/toxicidad , Inhibidores Enzimáticos/toxicidad , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Retina/efectos de los fármacos , Enfermedades de la Retina/inducido químicamente , HumanosRESUMEN
Importance: The major toxic effect of hydroxychloroquine is retinopathy. Thus, current guidelines recommend limiting the dose and screening annually for retinopathy among all long-term users, but individual patient factors may be associated with retinopathy risk. Objective: To identify risk factors beyond hydroxychloroquine dose and duration of use for hydroxychloroquine retinopathy. Design, Setting, and Participants: This cohort study of 4677 patients in the Kaiser Permanente Northern California integrated health network who initiated hydroxychloroquine, continued treatment, and underwent retinopathy screening after 5 years of use was conducted from July 1, 1997, to December 31, 2020, with up to 15 years of follow-up. Statistical analysis was performed in August 2023. Exposure: Candidate risk factors included age at hydroxychloroquine initiation, sex, race and ethnicity, indications, chronic kidney disease (CKD), liver disease, diabetes, tamoxifen use, and medications that interact with hydroxychloroquine metabolism. Hydroxychloroquine dose was assessed from pharmacy dispensing records. Main Outcome and Measures: Incident hydroxychloroquine retinopathy was adjudicated from masked review of guideline-recommended screening studies and classified as parafoveal or pericentral pattern. Multivariable Cox proportional hazards regression was used to assess potential risk factors for hydroxychloroquine retinopathy within 15 years of initiation. Results: Of 4677 long-term hydroxychloroquine users (mean [SD] age at initiation, 52.4 [14.1] years; 3877 women [82.9%]), 125 patients developed hydroxychloroquine retinopathy within 15 years (102 parafoveal, 23 pericentral). Older age at time of hydroxychloroquine initiation was associated with retinopathy risk, with adjusted hazard ratios (HRs) of 2.48 (95% CI, 1.28-4.78) for those aged 45 to 54 years, 3.82 (95% CI, 2.05-7.14) for those aged 55 to 64 years, and 5.68 (95% CI, 2.99-10.79) for those aged 65 years or older compared with those younger than 45 years. The risk of retinopathy was higher among females than males (HR, 3.83 [95% CI, 1.86-7.89]), among patients with CKD stage 3 or greater (HR, 1.95 [95% CI, 1.25-3.04]), and among individuals with tamoxifen use (HR, 3.43 [95% CI, 1.08-10.89]). The likelihood of pericentral retinopathy was higher among Asian patients (HR, 15.02 [95% CI, 4.82-46.87]) and Black patients (HR, 5.51 [95% CI, 1.22-24.97]) compared with non-Hispanic White patients. Conclusions and Relevance: This study suggests that increasing age, female sex, CKD stage 3 or greater, and tamoxifen use were associated with a higher risk of hydroxychloroquine retinopathy, whereas being younger than 45 years at hydroxychloroquine initiation and male sex were associated with a lower risk. Race and ethnicity were also associated with the pattern of retinopathy. These factors should be incorporated into hydroxychloroquine dosing decisions.